PRACTICAL

PAEDIATRICS


Commissioning Editor: Pauline Graham

Development Editor: Veronika Watkins/Clive Hewat
Project Manager: Vinod Kumar
Designer/Design Direction: Charles Gray/Miles Hitchen
Illustration Manager: Bruce Hogarth
Illustrator: Antbits
 

PRACTICAL
PAEDIATRICS
EDITED BY

Professor Mike South MBBS DCH MD MRCP FRACP FJFICM FCICM

Paediatrician & Intensivist,
Director, Department of General Medicine
Royal Children's Hospital;
Fellow, Murdoch Children's Research Institute,
Professor of Paediatric Medicine, Department of Paediatrics,
University of Melbourne
Australia

Professor David Isaacs MBBCHIR MD(Cantab) FRACP FRCPCH

Senior Staff Specialist
Department of Infectious Diseases & Microbiology
Clinical Professor in Paediatric Infectious Diseases,
University of Sydney
Australia

SEVENTH EDITION

ERRNVPHGLFRVRUJ

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Notices
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Preface

Welcome to the 7th edition of Practical Paediatrics. 120 authors (51 of them new for this edition). They
Practical Paediatrics is used by medical students, are all highly acknowledged experts in their field and
doctors training in paediatrics and other specialty prominent teachers in paediatrics in Australia and
areas of medicine, primary care practitioners, nurses New Zealand.
and allied health trainees and practitioners, and many Reading lists and up-to-date websites that give useful
other health professional groups. academic and parent and family information have been
Practical Paediatrics is intended to bridge the gap included as in the last two editions. These, along with
between some of the highly summarized handbooks a comprehensive set of Self Assessment Questions, are
of paediatrics and the bigger textbooks. It gives more now available on a website which is accessible to pur-
than the bare dot-points of paediatric learning with- chasers of the textbook. This allows easy searching
out going into highly advanced detail. It covers all of the reading lists, linkages to the websites, and also
of the common and important childhood conditions linkages to online sections of the textbook itself. There
seen in the more resource-rich countries, and also cov- are many new Self Assessment Questions, which have
ers many aspects of normal child development, family been a popular feature, providing a practical assess-
influences, and topics such as Indigenous child health. ment of learning by testing problem-solving skills. The
Practical Paediatrics was first published in 1986. answers to each question are accompanied by a ratio-
The concept was to provide a paediatric text for medi- nale explaining the reasons for the answers.
cal students that would be user-friendly, practical in its Many new Clinical Examples have been incorpo-
approach, relevant to curricula in Australia and New rated to assist the reader in placing information in
Zealand, the Asia–Pacific region and internationally, context and to aid the learning process. Highlighted
be up to date in its information, and available at a rea- Practical Points in each section serve to emphasize key
sonable price. Practical Paediatrics has more than met issues, and also function as an aid to revision.
all of these objectives. There has been a new edition We are grateful to all the contributing authors, and
approximately every 4 years and we are pleased that it to staff from Elsevier including Veronika Watkins,
remains so popular that we now to have the opportu- Clive Hewat and Vinod Kumar, who have made much
nity to publish the 7th edition. of our task easy and pain-free.
Max Robinson founded the book and was an ­editor We hope that you will find this edition of Practical
of all editions up to and including the 5th edition. Don Paediatrics useful, and that it assists in developing
Roberton joined Max for the 3rd edition and contin- an understanding and interest in the health needs of
ued until the 6th. The 6th edition was co-edited by children, their families and their communities.
Mike South, and he has been joined for the 7th edition
by David Isaacs. Mike South
In this edition, all content has been revised, often David Isaacs
extensively. There are now 78 chapters with a total of

v
 Contributors

Frances Abbott BScN MRCNA Louise A Baur AM MBBS(Hons) BSc(Med) PhD FRACP
Clinical Nurse Consultant – Culture, Professor, Discipline of Paediatrics & Child Health,
Royal Darwin Hospital, Sydney Medical School,
Darwin, Australia The Children's Hospital at Westmead,
Indigenous culture and health Sydney, New South Wales, Australia
Navid Adib MBBS FRACP PhD Obesity
Paediatric Rheumatologist, Spencer Beasley MBChB(Otago) MS(Melbourne) FRACS
Queensland Paediatric Rheumatology Services, Clinical Director, Department of Paediatric Surgery,
Brisbane, Queensland, Australia Christchurch Hospital,
Arthritis and connective tissue disorders Christchurch, New Zealand
George Alex MBBS MMed, MRCP FRACP PhD Abdominal pain and vomiting
Consultant Surgical conditions in the newborn
Gastroenterologist/Hepatologist, Surgical conditions in older children
Royal Children's Hospital, Sean Beggs MBBS MPH FRACP
Melbourne, Victoria, Australia Staff Specialist, Department of Paediatrics
Diarrhoea Royal Hobart Hospital,
Jane Alsweiler MBChB FRACP PhD Hobart, Australia
Senior Lecturer in Paediatrics, The clinical consultation
University of Auckland, Julie Bines MBBS MD FRACP
Auckland, New Zealand Victor and Loti Smorgon Professor of Paediatrics,
Low birth weight, prematurity and jaundice University of Melbourne, Melbourne, Victoria;
in infancy Department of Gastroenterology and Clinical
Antoinette Anazodo MBBS MSC Nutrition, Royal Children's Hospital,
Diploma Adolescent Cancer FRACP Melbourne, Victoria;
Director of Youth Cancer Services, Murdoch Childrens Research Institute,
Sydney Children's Hospital and Prince of Wales Melbourne, Australia
Hospital, Nutrition
Sydney, New South Wales, Australia Helen L M Bird MBChB, FRANZCR
Cancers Consultant Paediatric Radiologist,
Chris Barnes MBBS(Hons) FRACP FRCPA Royal Children's Hospital,
Haematologist, Royal Children's Hospital, Melbourne, Victoria, Australia
Melbourne, Victoria, Australia Imaging
Abnormal bleeding and clotting Robert Booy MBBS(Hons) MSc MD FRACP FRCPCH
Christopher Barnett MBBS FRACP FCCMG Head, Clinical Research, National Centre for
Consultant Clinical Geneticist, Immunisation Research & Surveillance,
SA Clinical Genetics Service, Discipline of Paediatrics and Child Health and School of
Women's and Children's Hospital, Public Health, The University of Sydney,
North Adelaide, South Australia, Sydney, Australia
Australia Meningitis and encephalitis
The dysmorphic child David Brewster BA(Hons) MD MPH FRACP PhD
Paul Bauert OAM FAMA BSc MBBS FRACP AM(Honorary)
Director of Paediatrics, Royal Darwin Hospital, Professor of Paediatrics, University of Botswana,
Darwin, Australia Gaborone, Botswana, South Africa
vi Indigenous culture and health Infections in tropical and developing countries
 CONTRIBUTORS

Justin Brown MA MBBChir MRCP MRCPCH FRACP Anne B Chang MBBS MPHTM FRACP PhD
Paediatric Endocrinologist, Professor, Child Health Division, Menzies School
Monash Children's Hospital, of Health Research,
Monash Medical Centre, Melbourne; Charles Darwin University, Darwin, North Territory;
Senior Lecturer, Monash University, Queensland Children's Respiratory Centre, Queensland
Melbourne, Victoria, Australia Medical Research Institute, Royal Children's
Thyroid disorders Hospital,
Brisbane, Queensland, Australia
Leo Buchanan MBChB FRACP
An approach to chronic cough and cystic
Taranaki and TeAtiawa
fibrosis
Senior Clinical Lecturer Paediatrics,
University of Otago, Wellington, New Zealand Michael Cheung BSc MBChB MD MRCP (UK) FRACP
Indigenous culture and health Director of Cardiology,
Royal Children's Hospital,
Mariam Buksh MBBS Dip. Paediatrics FRACP(Paediatrics)
Melbourne, Victoria, Australia
Neonatal Paediatrician,
Heart disease
Auckland City Hospital,
Suspected heart disease: assessment
Auckland, New Zealand
Low birth weight, prematurity and jaundice Kevin J Collins MBBS FRACP GDipArts(French)
Paediatric Neurologist, Departments of Neurology and
David Burgner BSc(Hons) MBChB MRCP MRCPCH
Developmental Medicine,
DTM&H FRACP PhD
Royal Children's Hospital,
Principal Research Fellow and Consultant in Paediatric
Melbourne, Victoria, Australia
Infectious Diseases,
Cerebral palsy and neurodegenerative disorders
Murdoch Children's Research Institute,
Royal Children's Hospital and Monash David Coman MBBS MPhil FRACP
Children's Hospital, Staff Specialist, Department of Metabolic Medicine,
Melbourne, Victoria, Australia University of Queensland,
Infectious disease Brisbane, Australia
Refugee health Inborn errors of metabolism
Fergus Cameron BMedSci MBBS DipRACOG FRACP MD Carolyn Cottier MBBS BA FRACP
Professor and Head, Diabetes Services and Deputy Staff Specialist, Sydney Children's Hospital,
Director, Randwick and Campbelltown Hospital,
Department of Endocrinology and Diabetes, and Centre Campbelltown, Sydney, Australia
for Hormone Research, Developmental surveillance and assessment
Royal Children's Hospital and Murdoch Children's
Jennifer Couper MBChB MD FRACP
Research Institute,
Head, Deptartment of Diabetes and
Melbourne, Victoria, Australia
Endocrinology,
Thyroid disorders
Women's and Children's Hospital Network,
Jonathan Rhys Carapetis, MBBS FRACP FAFPHM PhD Discipline of Paediatrics, University of Adelaide,
Professor and Director, Menzies School of Health Research, Adelaide, South Australia, Australia
Darwin, Northern Territory, Australia Diabetes
Bone and joint infections
Peter Cundy MBBS FRACS
Susan M Carden MBBS FRANZCO FRACS PhD Head of Orthopaedic Surgery,
Senior Lecturer, University of Melbourne; Women's & Children's Hospital,
Senior Ophthalmologist, Royal Children's Hospital, Adelaide, South Australia, Australia
Melbourne, Victoria, Australia Orthopaedic problems
Eye disorders
Brian A Darlow MA MBBChir MD FRCP FRACP
Daniel Cass MBBS FRACS FRCS PhD FRCPCH
William Dunlop Professor of Paediatric Surgery, CureKids Professor of Paediatric Research, University
Department of Surgery, Children’s Hospital at Westmead, of Otago,
Sydney, Australia Christchurch, New Zealand
Trauma Newborn infant: stabilization and examination vii
 
CONTRIBUTORS

Geoffrey Davidson MBBS MD FRACP Dawn Elder MBChB DCH FRACP PhD
Senior Gasroenterologist, Associate Professor,
Women's & Children's Hospital, Department of Paediatrics and Child Health,
Adelaide, South Australia, Australia University of Otago,
Gastro-oesophageal reflux and Helicobacter pylori Wellington, New Zealand
infection Sudden unexpected death in infancy

Mark William Davies MBBS DCH PhD FRACP James E Elder MBBS FRANZCO FRACS
Eminent Senior Staff Specialist in Neonatology Consultant Ophthalmologist, Department of
(Consultant Neonatologist), Ophthalmology,
Royal Brisbane & Women's Hospital; Royal Children's Hospital, Melbourne;
Associate Professor of Neonatology, Department of Paediatrics, University of Melbourne;
University of Queensland, Melbourne, Australia
Brisbane, Queensland, Australia Eye disorders
Breathing problems in the newborn Jan Fairchild MBBS FRACP
Andrew Day MBChB MD FRACP AGAF Senior Staff Specialist, Department of Endocrinology
Associated Professor and Head of Department, and Diabetes,
Paediatrics, Women's and Children's Hospital, Adelaide, South
University of Otago, Australia, Australia
Christchurch, New Zealand The child of uncertain sex
Abdominal pain and vomiting Peter Flett MBBS FRACP FACRM FAFRM(RACP)
Associate Professor and Paediatric
Martin Delatycki MBBS FRACP PhD
Rehabilitation Specialist,
Professor and Director,
State-wide Director, Paediatric Rehabilitation,
Clinical Genetics, Austin Health Heidelberg,
Royal Hobart Hospital,
Victoria, Australia
Tasmania, Australia
Genetic counselling
Neural tube defects, large heads and hydrocephalus
Terence Donald MBBS FRACP
Jeremy L Freeman MBBS FRACP
Senior Consultant, Child Protection Unit,
Staff Specialist, The Royal Children's Hospital,
Women's and Children's Hospital,
Melbourne, Victoria, Australia
Adelaide, South Australia, Australia
Seizures and epilepsies
Child abuse
Michael Gold, MBBChB DCH MD FCP FRACP
Trevor Duke, MD FRACP FCICM Senior Staff Specialist and Associate Professor,
Director, Centre for International Child HealthUniversity, Department of Allergy and Immunology & Discipline
Department of Paediatrics, of Paediatrics,
Royal Children's Hospital, University of Adelaide,
Melbourne, Victoria, Australia Adelaide, South Australia, Australia
Child health in a global context Atopy
Fluid replacement therapy
Brian Graetz PhD MPsych(Clin)
Shoma Dutt BMedSci MBBS PhD FRACP Program Director,
Staff Specialist, Department of Gastroenterology, beyondblue: The National Depression Initiative,
The Children’s Hospital at Westmead; Melbourne, Victoria, Australia
Lecturer, Discipline of Paediatrics & Child Health, Common mental health problems
Sydney Medical School, University of Sydney,
Stephen M Graham MBBS DTCH FRACP PhD
Sydney, Australia
Associate Professor of International Child Health,
Chronic diarrhoea and malabsorption
University of Melbourne Department of Paediatrics,
Daryl Efron MBBS FRACP MD The Royal Children's Hospital, Melbourne, Australia;
Consultant Paediatrician, Consultant in Child Lung Health,
Royal Children's Hospital, International Union Against Tuberculosis and Lung Disease,
Melbourne, Victoria, Australia Paris, France
viii Failure to thrive Infections in tropical and developing countries
 CONTRIBUTORS

Sonia Grover MBBS FRANZCOG MD Harriet Hiscock MD FRACP Grad Dip Epi
Head of Department, Paediatric and Adolescent Associate Professor and General
Gynaecology, Royal Children's Hospital; Paediatrician,
Honorary Principal fellow, Department of Paediatric, Centre for Community Child Health;
Melbourne University. (Consultant gynaecologist NHMRC Post-doctoral Research Fellow,
Mercy Hospital for Women; consultant gynaecologist Murdoch Children's Research Institute,
Austin Health.) The Royal Children's Hospital, Melbourne;
Deptartment of Paediatric and Adolescent Gynaecology, Principal Fellow, Department of Paediatrics,
Royal Children's Hospital, Melbourne, Australia University of Melbourne,
Gynaecology Melbourne, Victoria, Australia
Life events of normal children
Wolfram Haller MD MRCPCH (UK)
Fellow Paediatric Gastroenterology, Neil Hotham BPharm
Royal Children's Hospital, Melbourne, Senior Specialist Drug Information
Parkville, Victoria, Australia Pharmacist,
Liver diseases Women's and Children's Hospital,
Kerrod B Hallett MDSc MPH FRACDS FICD North Adelaide, South Australia, Australia
Director, Department of Dentistry, Birth defects, prenatal diagnosis and teratogens
Royal Children's Hospital,
David Isaacs, MBBChir MD(Cantab) FRACP FRCPCH
Melbourne, Australia
Senior Staff Specialist,
Teeth and oral cavity disorders
Department of Infectious Diseases & Microbiology,
Paul Hammond MBBS FRACP The Children's Hospital at Westmead;
Senior Staff Specialist, Gastroenterology Unit, Clinical Professor in Paediatric Infectious Diseases,
Women's and Children's Hospital, University of Sydney,
Adelaide, Australia Sydney, New South Wales, Australia
Gastro-oesophageal reflux and Helicobacter pylori Infectious disease
infection
Winita Hardikar MBBS FRACP PhD Adam Jaffé BSc(Hons) MBBS MD FRCP FRCPCH FRACP
Associate Professor and Head of Liver and Intestinal Consultant in Respiratory Medicine;
Transplantation, Head of Respiratory Department,
Department of Gastroenterology, Sydney Children's Hospital;
Royal Children's Hospital, Conjoint Professor, School of Women's and Children's
Melbourne, Victoria, Australia Health,
Liver diseases University of New South Wales,
Sydney, New South Wales, Australia
Jane Harding MBChB Dphil FRACP Asthma
Professor of Neonatology, Liggins Institute,
University of Auckland, Luke Anthony Jardine MBBS FRACP MClinEpid
Auckland, New Zealand Neonatologist, Mater Mother's Hospital,
Low birth weight, prematurity and jaundice in infancy South Brisbane;
Honorary Researcher, Mater Medical Research
A Simon Harvey MD FRACP
Institute;
Neurologist and Epileptologist,
Senior Lecturer, University of Queensland,
Department of Neurology,
Queensland, Australia
The Royal Children's Hospital,
Breathing problems in the newborn
Melbourne, Victoria, Australia
Seizures and epilepsies
Cheryl Jones MBBS (Hons) Phd FRACP
Helen S. Heussler MBBS FRACP MRCPCH PGCAP DM Clinical academic, Paediatric infectious diseases
Associate Professor and Senior Staff Specialist, specialist,
Developmental Paediatrics and Sleep Medicine, Deptartment of Infectious Diseases & Microbiology,
Mater Children's Hospital, University of Sydney,
Brisbane, Queensland, Australia Sydney, Australia
Sleep problems Meningitis and encephalitis ix
 
CONTRIBUTORS

Colin Jones MBBS FRACP PhD Jan Liebelt MBBS(Hons) FRACP(Clin Genet), MSc
Professor and Director, Department of Nephrology, Clinical Geneticist,
Royal Children's Hospital, South Australian Clinical Genetics Service,
Parkville, Victoria, Australia Adelaide, South Australia, Australia
Urinary tract infections and malformations Birth defects, prenatal diagnosis and teratogens
Bone mineral disorders Zoe McCallum MBBS FRACP
Timothy W Jones MD DCH FRACP Department of Gastroenterology and Clinical Nutrition,
Head of Department, Department of Endocrinology, Royal Children's Hospital,
Princess Margaret Hospital for Children and Telethon Melbourne, Australia
Institute for Child Health Research, Nutrition
Perth, Australia Brett McDermott, MBBS MD FRANZCP CertChildPsych
Diabetes Executive Director, Child and Youth Mental Health Service,
Mater Children's Hospital,
Nitin Kapur MBBS MD PhD Brisbane, Australia
Associate Lecturer, School of Medicine, Major psychiatric disorders
University of Queensland,
James McGill, MBBS(Hons) FRACP FRCPA HGSA Certified
Brisbane, Australia
Clinical Geneticist
An approach to chronic cough and cystic fibrosis
Director, Department of Metabolic Medicine,
Joshua Y Kausman MBBS FRACP Royal Children's Hospital,
Paediatric Nephrologist, Brisbane, Australia
Royal Children's Hospital, Inborn errors of metabolism
Melbourne, Victoria, Australia Sarah Kate McMahon MBBS(Hons) PhD FRACP
Urinary tract infections and malformations Staff Specialist, Department of Endocrinology and Diabetes,
Bone mineral disorders Royal Children's Hospital,
Andrew Kennedy MBBS, FRACP Brisbane, Queensland, Australia
General Paediatrician and Adolescent Physician, Growth and variations of growth
Princess Margaret Hospital, Sarah McNab MBBS FRACP
Perth, Western Australia, Australia General Paediatrician,
Care of the adolescent Royal Children's Hospital,
Melbourne, Victoria, Australia.
Nicky Kilpatrick BDS PhD
Fluid replacement therapy
Professor, Paediatric Dentistry,
University of Bristol, Steven McTaggart MBBS FRACP PhD
Bristol, UK Associate Professor and Director, Child & Adolescent
Teeth and oral cavity disorders Renal Service,
Royal Children's and Mater Children's Hospitals,
Sebastian King, BSc(Med) MBBS PhD Brisbane, Queensland, Australia
Paediatric Surgical Registrar, Glomerulonephritis, renal failure and hypertension
Christchurch Hospital,
Craig Mellis, MBBS MPH MD FRACP
Christchurch, New Zealand
Associate Dean and Head, Central Clinical School,
Surgical conditions in the newborn
University of Sydney,
Surgical conditions in older children
Sydney, New South Wales, Australia
Andrew J Kornberg MBBS(Hons) FRACP Acute upper respiratory infections
Associate Professor and Director of Neurology, Paul Monagle MBBS MSc MD FRACP FRCPA FCCP
Royal Children's Hospital, Stevenson chair, Head of Department,
Parkville, Victoria, Australia Department of Paediatrics, University of Melbourne,
Neuromuscular disorders Melbourne, Victoria, Australia
Peter Le Souëf MBBS MD FRACP Anaemia
Professor of Paediatrics, School of Paediatrics and Kevin J Murray MBBS FRACP
Child Health, Head of Department, Department of Rheumatology,
University of West Australia, Princess Margaret Hospital for Children,
x Perth, Western Australia, Australia Perth, Western Australia, Australia
Lower respiratory tract infections and abnormalities Arthritis and connective tissue disorders
 CONTRIBUTORS

Ed Oakley MBBS FACEM Dinah Reddihough MD BSc FRACP FAFRM

Director, Paediatric Emergency Medicine Paediatrician, Developmental Medicine,
Monash Children's, Southern Health, Royal Children's Hospital;
Melbourne, Victoria, Australia Clinical Professor, Department of Paediatrics,
Poisoning and envenomation University of Melbourne;
Resuscitation Group Leader, Developmental Disability and
Rehabilitation Research, Murdoch Childrens Research
Tracey O'Brien FRACP MBChB MHL BSc DCH Institute,
Head, Cord & Marrow Transplant Program, Senior Melbourne, Australia
Staff Specialist, Cerebral palsy and neurodegenerative disorders
Centre for Children's Cancer & Blood Disorders,
Sydney Children's Hospital, Peter Richmond MBBS MRCP(UK) FRACP
Sydney, Australia University of Western Australia School of Paediatrics and
Cancers Child Health;
Director, Vaccine Trials Group, Telethon Institute
Michael O'Callaghan MBBS MSc FRACP for Child Health Research;
Director, Child Development and Rehabilitation, Consultant Paediatric Immunologist and
Mater Children's Hospital, Paediatrician,
Brisbane, Queensland, Australia Princess Margaret Hospital for Children;
Developmental disability Director, Child Health Research Network, Children
and Adolescent Health Service,
Edward V O'Loughlin MD(Syd) FRACP Perth, Western Australia, Australia
Senior Staff Specialist, Imumunization
Department of Gastroenterology,
The Children's Hospital at Westmead,
Gehan Roberts MPH PhD FRACP
Sydney, New South Wales, Australia
Developmental-Behavioural Paediatrician,
Chronic diarrhoea and malabsorption
Centre for Community Child Health;
NHMRC Post-doctoral research fellow,
Georgia Paxton MBBS(hons) BMedSci MPH FRACP
Murdoch Children's Research Institute,
Paediatrician, Medical Coordinator, Immigrant
The Royal Children's Hospital,
Health Department of General Medicine,
Melbourne, Victoria, Australia
Royal Children's Hospital,
Life events of normal children
Parkville, Victoria, Australia
Refugee health
Maureen Rogers MBBS FACD
Emeritus Consultant Dermatologist,
Roderic J Phillips BSc MBBS FRACP PhD
Deptartment of Dermatology, The Children's
Paediatric Skin Specialist,
Hospital at Westmead,
Royal Children's Hospital,
Westmead, New South Wales, Australia
Melbourne, Australia
Skin disorders
Skin disorders

Nicola K Poplawski MBChB DipPaed FRACP MD Elizabeth Rose MBBS FRACS

Clinical Geneticist, Consultant Otolaryngologist,
Women's and Children's Hospital, North Adelaide; Royal Children's Hospital and Royal Victorian Eye
SA Pathology, University of Adelaide, Adelaide, and Ear Hospital,
South Australia, Australia Melbourne, Australia
Modern genetics Ear, nose and throat disorders

Jeremy Raftos MBBS(Hon) FRACP Jeremy Rosenbaum, MBBS(Hons) FRACP

Senior Staff Specialist, Paediatric Emergency Department of Gastroenterology, Hepatology
Department, and Nutrition,
Women's & Children's Hospital, Royal Children's Hospital,
North Adelaide, South Australia, Australia Melbourne, Victoria, Australia xi
Emergencies: causes and assessment Diarrhoea
 
CONTRIBUTORS

Remo (Ray) N Russo PhD MBBS FRACP Peter D Sly MBBS MD FRACP DSc
FAFRM (RACP) Professor and Deputy Director, Queensland
Director, Paediatric Rehabilitation Department, Children's Medical Research Institute,
Women's and Children's Health Network, University of Queensland,
Women's & Children's Hospital Campus, Brisbane, Queensland, Australia
Adelaide, South Australia, Australia Stridor
Neural tube defects, large heads and hydrocephalus
Mike South, MBBS DCH MRCP(UK) FRACP FJFICM
FCICM MD
Monique Ryan M Med BS, FRACP
Senior Staff Specialist, Children's Professor and Director, Department of
Neurosciences Centre, General Medicine,
Royal Children's Hospital, Royal Children's Hospital,
Melbourne, Australia Melbourne, Victoria, Australia
Neuromuscular disorders Resuscitation
The clinical consultation
Michael G Sawyer MBBS, PhD, Dip Child Psych
Zornitza Stark MA(Oxon) BM BCh FRACP
FRANZCP FRCPC
Clinical Geneticist, Genetic Health Services,
Head, Research and Evaluation Unit,
Melbourne, Victoria, Australia
Women's and Children's Hospital,
Genetic counselling
Adelaide;
Professor, Discipline of Paediatrics, Mike Starr, MBBS FRACP
University of Adelaide, Paediatrician; Infectious Diseases Physician; Consultant
Adelaide, South Australia, Australia in Emergency Medicine;
Common mental health problems Director of Paediatric Physician Training,
Susan M Sawyer MBBS MD FRACP FSAHM Royal Children's Hospital,
Director, Centre for Adolescent, Melbourne, Victoria, Australia
Royal Children's Hospital, Congenital and perinatal infections
Department of Paediatrics, David Starte MBBS MRCPCH FAFPHM FRACP
University of Melbourne; Senior Staff Specialist,
Murdoch Children's Research Institute Child Development Service,
Melbourne, Victoria, Australia Royal North Shore Hospital,
Care of the adolescent Sydney, New South Wales, Australia
An approach to chronic cough and cystic fibrosis Developmental surveillance and assessment
Ben Saxon MBBS FRACP FRCPA
Andrew Steer MBBS
Haematologist, Children, Youth and
Clinical and Public Health Research Fellow,
Women's Health Service,
Medical Coordinator, Fiji, Suva, Fiji Islands
North Adelaide, South Australia, Australia
Bone and joint infections
Abnormal bleeding and clotting
Hiran Selvadurai, MBBS FRACP PhD Gopinath Musuwadi Subramanian MD DNB(Paed) DM
Associate Professor and Paediatric Respiratory DNB(Neurology) FRACP
Physician; Staff Specialist in Paediatric Neurology,
Staff Specialist, John Hunter Children's Hospital,
The Children's Hospital at Westmead, Newcastle, New South Wales, Australia
Sydney, New South Wales, Australia Headache
Wheezing disorders other than asthma
Sadasivam Suresh MBBS, MRCPCH, FRACP
Jill Sewell MBBS FRACP RACP RCPCH(Hon) Staff Specialist, Paediatric Respiratory & Sleep Medicine,
Deputy Director centre for Community Child Health Mater Children's Hospital,
The Royal Children's Hospital, Brisbane, Queensland, Australia
Melbourne, Australia Stridor
Hyperactivity and inattention Sleep problems

xii
 CONTRIBUTORS

Barry Taylor MBChB FRACP Neil Wigg MBBS FRACP MPolAdmin

Head of the Department of Women's and Children's Health, Associate Professor and Director, Community
Dunedin School of Medicine and Consultant Child Health Services,
Paediatrician, Southern DHB, NZ, Fortitude Valley, Queensland, Australia
University of Otago, The child and the family
Dunedin, New Zealand
Sudden unexpected death in infancy Ian Wilkinson MBBS (University of Queensland) FRACP
Staff Paediatric Neurologist,
Rita L. Teele MD RANZCR John Hunter Children's Hospital,
Consultant Paediatric Radiologist and Honorary Newcastle, New South Wales, Australia
Professor of Radiology with Anatomy, Headache
Department of Radiology, Starship Children's Hospital
and Auckland School of Medicine, Ken Winkel MBBS BMedSci PhD FACTM
Auckland, New Zealand Director, Australian Venom Research Unit,
Imaging Department of Pharmacology,
University of Melbourne,
Elizabeth Mary Thompson MBBS MD FRACP Melbourne, Australia
SA Pathology at the Women's and Children's Poisoning and envenomation
Hospital,
Adelaide, South Australia, Australia Li-Chuen Wong MBBS(Hons) MM DCH FACD
The dysmorphic child Visiting Medical Officer (VMO), The Children's Hospital
at Westmead,
James Tibballs BMedSc(Hons) MBBS MEd MBA MD Sydney, New South Wales, Australia
MHlth&MedLaw DALF PGDipArts(Fr) FANZCA FCICM Skin disorders
FACLM
Associate Professor and Deputy Director; Paediatric Melanie Wong MBBS(Hons) PhD FRACP FRCPA
Intensive Care Unit & Resuscitation Officer, Senior Staff Specialist,
Royal Children's Hospital, Department of Allergy and Immunology,
Melbourne; The Children's Hospital at Westmead
Principal Fellow, Departments of Paediatrics and Sydney, New South Wales, Australia
Pharmacology (Australian Venom Research Unit), Immunodeficiency and its investigation
University of Melbourne,
Karen Zwi MBBCh MSc MMed MRCP FRACP
Melbourne, Victoria, Australia
Community Paediatrician and Head of Department
Poisoning and envenomation
of Community Child Health;
Graham Vimpani AM MBBS PhD FRACP FAFPHM Senior Lecturer, University of New South Wales,
Clinical Chair, Kaleidoscope Greater Newcastle, Sydney Children's Hospitals Network,
Newcastle, Australia Sydney, New South Wales, Australia
Child health and disease Child health and disease

xiii
 Contents

Preface v 3.4 Obesity 75

Contributors vi Louise A. Baur
3.5 Immunization 89
Peter Richmond
3.6 Trauma 97
Part 1 Danny Cass
Current paediatrics 3.7 Failure to thrive 102
1.1 Child health and disease 2 Daryl Efron
Karen Zwi, Graham Vimpani
3.8 Developmental disability 106
1.2 Child health in a global context 15 Michael O'Callaghan
Trevor Duke
3.9 Child abuse 113
Terence Donald
3.10 Sudden unexpected death in infancy 123
Part 2 Barry Taylor, Dawn Elder
Clinical assessment 3.11 Care of the adolescent 130
2.1 The clinical consultation 24 Susan Sawyer, Andrew Kennedy
Mike South, Sean A. Beggs 3.12 Gynaecology 141
2.2 Developmental surveillance and Sonia R. Grover
assessment 36 3.13 Sleep problems 149
David Starte, Carolyn Cottier Sadasivam Suresh, Helen Heussler
3.14 Refugee health 155
Georgia Paxton, David Burgner
Part 3
Social and preventative
paediatrics Part 4
3.1 The child and the family 44 Behaviour and mental health
Neil Wigg needs
3.2 Indigenous culture and health 50 4.1 Life events of normal children 166
Part 1: Aboriginal and Torres Strait Gehan Roberts, Harriett Hiscock
Islanders 50
Paul Bauert, Francis Abbott
4.2 Common mental health problems 172
Michael Sawyer, Brian Graetz
Part 2: Maori view of child health
and illness 56 4.3 Hyperactivity and inattention 179
Leo Buchanan Jill Sewell
3.3 Nutrition 61 4.4 Major psychiatric disorders 183
Zoe McCallum, Julie Bines Brett McDermott

xiv
 Contents

10.4 Genetic counselling 311

Part 5 Zornitza Stark, Martin Delatycki
Paediatric emergencies 10.5 Inborn errors of metabolism 318
5.1 Emergencies: causes and assessment 194 David Coman, Jim McGill
Jeremy Raftos
5.2 Resuscitation 200
Ed Oakley, Mike South
Part 11
5.3 Poisoning and envenomation 208 Neonatal problems
James Tibballs, Ed Oakley, Ken Winkel
11.1 The newborn infant: stabilization and
examination 328
Brian Darlow
Part 6
Fluid replacement 11.2 Low birth weight, prematurity and jaundice
in infancy 341
6.1 Fluid replacement therapy 222 Jane Harding, Jane Alsweiler, Mariam Buksh
Trevor Duke, Sarah McNab
11.3 Breathing problems in the newborn 352
Luke Jardine, Mark Davies

Part 7 11.4 Congenital and perinatal infections 363

Mike Starr
Principles of imaging
11.5 Surgical conditions in the newborn 375
7.1 Imaging 236
Sebastian K. King, Spencer W. Beasley
Rita L. Teele, Helen L.M. Bird

Part 8 Part 12
Common orthopaedic problems Infections
and fractures 12.1 Infectious disease 382
8.1 Orthopaedic problems 252 David Burgner, David Isaacs
Peter Cundy 12.2 Bone and joint infections 393
Jonathan Carapetis, Andrew Steer

Part 9 12.3 Meningitis and encephalitis 402

Robert Booy, Cheryl Jones
Common paediatric surgical problems
12.4 Infections in tropical and developing
9.1 Surgical conditions in older children 266 countries 413
Sebastian K. King, Spencer W. Beasley Stephen Graham, David Brewster

Part 10
Inherited and metabolic problems Part 13
10.1 Birth defects, prenatal diagnosis and
Allergy, immunity and inflammation
teratogens 276 13.1 Atopy 426
Jan Liebelt, Neil Hotham Mike Gold
10.2 Modern genetics 289 13.2 Immunodeficiency and its investigation 439
Nicola Poplawski Melanie Wong
10.3 The dysmorphic child 303 13.3 Arthritis and connective tissue disorders 453 xv
Elizabeth Thompson, Christopher Barnett Kevin Murray, Navid Adib
 Contents

17.2 Cerebral palsy and neurodegenerative

Part 14 disorders 593
Respiratory disorders Dinah Reddihough, Kevin Collins

14.1 Acute upper respiratory infections 468 17.3 Neuromuscular disorders 603
Craig Mellis Monique Ryan, Andrew Kornberg

14.2 Stridor 475 17.4 Neural tube defects, large heads and
Sadasivam Suresh, Peter Sly hydrocephalus 613
Peter Flett, Ray Russo
14.3 Asthma 482
Adam Jaffé 17.5 Headaches 625
Ian Wilkinson, Gopinath Musuwadi Subramanian
14.4 Wheezing disorders other than
asthma 491
Hiran Selvadurai Part 18
14.5 Lower respiratory tract infections and Urinary tract disorders and
abnormalities 498
Peter LeSouëf
hypertension
14.6 An approach to chronic cough and cystic
18.1 Urinary tract infections and malformations 638
Colin Jones, Joshua Kausman
fibrosis 507
Anne Chang, Nitin Kapur 18.2 Glomerulonephritis, renal failure and
hypertension 648
Steven McTaggart

Part 15
Cardiac disorders Part 19
15.1 Suspected heart disease: assessment 518 Endocrine disorders
Michael Cheung 19.1 Growth and variations of growth 658
15.2 Heart disease 526 Sarah McMahon
Michael Cheung 19.2 Thyroid disorders 672
Fergus Cameron, Justin Brown
19.3 The child of uncertain sex 680
Part 16 Jan Fairchild
Haematological disorders 19.4 Diabetes 687
and malignancies Jennifer Couper, Timothy W. Jones

16.1 Anaemia 540 19.5 Bone mineral disorders 696

Paul Monagle Colin Jones, Joshua Kausman

16.2 Abnormal bleeding and clotting 558

Ben Saxon, Chris Barnes Part 20
16.3 Cancers 568 Gastrointestinal tract and hepatic
Antoinette Anazodo, Tracey O'Brien disorders
20.1 Abdominal pain and vomiting 706
Spencer Beasley, Andrew Day
Part 17
20.2 Infective diarrhoea and inflammatory bowel
Seizure disorders and disorders disease 715
of the nervous system Jeremy Rosenbaum, George Alex
17.1 Seizures and epilepsies 582 20.3 Chronic diarrhoea and malabsorption 724
xvi
Jeremy Freeman, Simon Harvey Shoma Dutt, Edward O'Loughlin
 Contents

20.4 Gastro-oesophageal reflux and Helicobacter

pylori infection 735 Part 22
Paul Hammond, Geoffrey Davidson ENT, eye and dental disorders
20.5 Liver diseases 744 22.1 Ear, nose and throat disorders 780
Wolfram Haller, Winita Hardikar Elizabeth Rose
22.2 Eye disorders 790
Susan Carden, James Elder
Part 21 22.3 Teeth and oral cavity disorders 799
Skin disorders Nicky Kilpatrick, Kerrod Hallett
21.1 Skin disorders 756 Index 811
Maureen Rogers, Rod Phillips, Li-Chuen Wong

xvii
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 1
PART

CURRENT
PAEDIATRICS

1
 1.1 Child health and disease
Karen Zwi, Graham Vimpani

• 4.8% of Australian children are Indigenous and

Setting the scene 38% of the Indigenous population is aged less than
Globally deaths in children under the age of 5 years 14 years. This reflects the higher birth rate amongst
are at their lowest level ever. They fell by over three Indigenous women (2.1 births per 1000 compared
million to 10 million deaths annually in the 15 years with 1.8 per 1000 in the total population) and the
prior to 2006. Australian children are amongst the younger age structure of the Indigenous population
healthiest children in the world, generally have access due to shorter life expectancy.
to high-quality health care, and infant and child mor- • 5.9% of Australian children were born overseas in
tality rates halved between 1986 and 2006, which com- 2009 and 33% have at least one overseas-born parent.
pares favourably with other high-income countries. Sudan-born had the highest proportion (21%) of
However, there are significant groups of children in residents aged 0–14 years, followed by the USA (16%),
Australia that have relatively poor health and access Afghanistan (14%), South Africa, Singapore, Pakistan
to care. These include Aboriginal and Torres Strait and Zimbabwe (12–13% each). Most migrants enjoy
Islander children, refugee children, children living in health that is equal to or better than that of the
out-of-home care (foster or kinship care), children with Australian-born population, often with lower rates of
disabilities, children from socioeconomically disadvan- death, mental illness and disease risk factors.
taged backgrounds, and children living in rural and Almost 1% of all Australian children are ­refugees,
remote Australia. There are also new emerging mor- nearly a quarter of them from Sudan. These ­children
bidities, such as the rising rates of childhood obesity, have higher health needs on arrival than the local
diabetes, dental decay and emotional–behavioural dis- population due to their adverse environmental
­
orders. In addition, many of our childhood deaths are ­circumstances and restricted access to health care in
still preventable, especially those due to injuries such their countries of origin.
as motor vehicle incidents and drowning. Fortunately The number of children in out-of-home care has
children are living for longer with chronic diseases and more than doubled since 1997, from 11 600 to 26 700 in
as long-term survivors of cancer. Therefore, the role 2008, with the rate increasing from 3.0 placements per
of the health system in offering high-quality, child- 1000 children in 1997 to 6.5 per 1000 in 2008. Children
centred care close to home is becoming increasingly enter statutory care most often because of child abuse
important. This chapter discusses the key child health and neglect. Some of the risk factors include low
issues facing Australian children today and ways to ­family income, parental substance abuse, ­mental health
improve the health of our children. issues, and community and family v­ iolence. Across the
­country, Indigenous children are nine times more likely
to be placed in out-of-home care (foster care, kinship
care, ­residential care) than ­non-Indigenous children.
Australian surveys have shown that the majority of
What do we know about children these children have chronic physical, developmental
and young people in Australia or mental health conditions arising from their earlier
neglect and trauma.
today?
Children and young people (up to the age of 24 years)
comprise approximately one-third of the 22.5 million
population of Australia, but, as in most other devel- Where do Australian children live
oped countries, this proportion is falling.
• 19.4% of the Australian population is now aged
and why is this important?
0–14 years (4.1 million children), compared The majority (86%) of Australian children aged 0–14
with over 28% in 1971, although children in the years in 2007 live in the south-eastern mainland states:
Northern Territory comprise about 25% of the almost one-third in New South Wales, a quarter in
2
population. Victoria and one-fifth in Queensland.
 Child health and disease 1.1
Two-thirds of Australian children aged 0–14 years • Australia had the second highest proportion of
live in major cities. Three per cent of children live in working-age, jobless families with children aged
remote and very remote areas. Indigenous children 0–17 years of 24 OECD countries in 2000, largely
are eight times more likely to live in remote and very due to the relatively high rate of one-parent
remote areas, accounting for 38% of all children in households in Australia and the high rate of
these areas, despite accounting for less than 5% of joblessness (51%) among this group.
all children. Children comprise a larger proportion
of the total population living in rural and remote
Why does this matter?
areas. Access to high-quality health care is poorer in
these areas and children experience higher death rates, Members of jobless households report worse physi-
higher rates of neural tube defects and lower rates of cal and mental health and lower life satisfaction than
cancer survival than those in major cities. members of households where someone is employed.
There are causal relationships between parental job-
lessness and family conflict, family breakdown and
child abuse. Secure employment provides financial sta-
What are the circumstances bility, self-confidence and social contact for parents,
of Australian households? with positive effects flowing on to children.
Family composition
The type of family in which children live has changed
minimally in the decade to 2007. Some 83% live in
Childcare and early childhood
­couple families (including 10% in blended and step education
families) and around 17% in one-parent families, 87%
Why are early childhood education and care
with their mother.
important for health and wellbeing?
Most Australian children participate in child care or
Family income and work
early education prior to school entry. Early experi-
Poverty is well known to affect the health of c­ hildren. ences in a child's life strongly influence the ­biological­
Australia is ranked behind many developed c­ ountries, pathways that affect cognition, behaviour, ­ language
with 10 of 24 Organisation for Economic Co-operation development, capacity to learn, memory, stress re-
and Development (OECD) countries having a lower sponse, and physical and mental health and w ­ ellbeing
proportion of children living in relative income throughout life. Early childhood ­education is ­important
­poverty than Australia. for successful transition to formal ­schooling. It is also
• In 1999, 12% of Australian children aged 0–17 associated with a lower incidence of p­ ersonal and social
years lived in households with equivalent income problems in later life, such as school dropout, welfare
of less than 50% of the median household income dependency, unemployment and criminal behaviour.
(relative poverty). Preschool programmes may be especially positive in
• In 2005–2006, low-income households (those in the lives of children from ­disadvantaged backgrounds,
the second and third income deciles) with children where children may not be receiving the stimulation
aged 0–12 years accounted for 421 300 households they require from the home environment. An English
Australia-wide and received on average $347 a week study of over 3000 preschool children found that
($218 a week less than median-income households the increased risk of antisocial or worried behaviour
with children aged 0–12 years). among disadvantaged children at school entry can be
• Jobless families are disproportionately likely to reduced by high-­quality preschool care at 3 and 4 years
be reliant on welfare, to have low incomes and of age.
to experience financial stress. In 2006, 15% of
Australian children aged 0–14 years lived in jobless
Australian children's experiences of child care
families, a decline from 19% in 1996.
and early education
• Nearly half (42%) of Indigenous children aged 0–14
years live in jobless families, three times the proportion In 2008, 50.2% of Australian under 2-year-olds were
of all children. The higher proportion of Indigenous in formal or informal child care, compared with 41%
children living in one-parent families contributes to in care in 2002. Around half (47%) of children in
this higher rate, as 45% of Indigenous children live in child care spent less than 10 hours per week in care.
one-parent families compared with 20% of all children. A ­further 37% were in care for 10–29 hours, and 16%
68% of Indigenous children living in one-parent of children spent more than 30 hours per week in
3
families do not live with an employed parent. child care. It is within this latter group where British
 1.1 CURRENT PAEDIATRICS

and American studies have raised concerns about the ­opulation proportion (aged 0–14 years) will drop
p
increased ­prevalence of disruptive behaviour in later from almost 20% in 2010 to 12–15% in the year 2051.
childhood. Whilst it can be argued that expenditure on quality,
Overall, the most commonly used type of child care evidence-based services for children and young people
was informal care, used by 29% of all children aged is a c­ ost-beneficial investment likely to promote ­better
0–12 years. Care provided by grandparents was the health and wellbeing in the population generally, the
most common type of informal care and was used by ageing population is likely to create pressure on the allo-
19% of children. cation of resources for children's services in the future.
Social Trends 2010 reported that the use of child
care was highest (78%) for children in one-parent fam-
ilies where the parent was in full-time employment.
Around two-thirds (64%) of children attended care if Child health
their parent was employed part-time, whereas the pro-
What affects child health?
portion of children attending care dropped to 40% if
the parent was not employed. The health of a child reflects a complex interaction
The story was similar for couple families. When between biological susceptibility and the child's expe-
both parents were in full-time employment, 60% rience of the environment. The child's environment
of children usually attended child care. This fell to affects health in both immediate and long-term ways,
51% for children in families where one parent was with physical factors such as pollution or hunger due
employed full-time and the other part-time. The pro- to neglect having a short-term impact as well as pos-
portion of children in child care was lower when both sibly affecting the child's wellbeing and health in the
parents were employed part-time (41%) or if only one long term. Many factors previously thought to be
parent was employed full-time (25%) or part-time short-term problems (such as low birth weight) are
(26%). The proportion of children in child care was now known to produce adverse health effects well into
only 17% for couple families where neither parent adult life.
was employed. The context in which a child grows up plays a major
It is difficult to estimate the number of children who role in that child's lifetime health. A child's health can
participate in formal early childhood education pro- be deeply affected by the family circumstances, the
grammes in the years before the first year of primary community in which the child is raised, and the cul-
schooling owing to the varied nature of children's ser- tural and social factors operating in society. Factors
vices throughout Australia and differences in data col- such as the protection of children's rights in society,
lection between states and territories. According to the community support to new parents, how a society
Australian Bureau of Statistics (ABS) 2005 Child Care deals with poverty or discrimination, the availability
Survey, 68% of children aged 3–4 years attended pre- of maternity leave or welfare grants to unemployed
school or a long day-care centre. Nearly half (48%) of parents all affect the health of that society's children.
long day-care services offered a preschool (or struc- There is convincing evidence that home visiting to
tured educational) programme. high-risk, disadvantaged parents before and after the
In terms of children's participation in pre-primary birth of their child and good-quality early childhood
education, Australia is one of the worst performers in education can significantly affect the life trajectory of
the OECD, despite growing evidence that preschool those children, affecting their cognitive development
education has major long-term benefits for the child's and successful transition to formal schooling. These
educational and social trajectory. interventions are associated with lower incidence
of personal and social problems later in life, such as
school dropout, welfare dependency, unemployment
and criminal behaviour. These effects are more marked
Why is the proportion of children in children from disadvantaged backgrounds and
therefore may be particularly effective in closing the
in the population declining and gap between advantaged and disadvantaged children.
what does that mean for children Greater understanding of the role of gene–environment
interactions on child health outcomes (­epigenetics)
of the future? has demonstrated the combined impact of biological
Since the last century there has been a general decline susceptibility and adverse environmental factors. For
in fertility in Australia to the current level of 1.77 chil- example, a Canadian study has shown that adults who
dren per woman. In addition there has been a sig- have committed suicide and were abused as children
nificant increase in life expectancy leading to ageing have reduced NR3C1 gene expression (through methy­
4
of the population. Consequently, the projected child lation) and reduced total g­ lucocorticoid expression in
 Child health and disease 1.1
the hippocampus c­ ompared with those who c­ ommitted Individual and social determinants of health
suicide with no history of childhood maltreatment.
Levels of health and wellbeing depend on two broad
This ­combination leads to reduced ­feedback inhibi-
forces: determinants (factors that influence health)
tion and thus to higher cortisol levels in response to
and interventions (interventions to improve health).
stress, enhancing its effects in a­ dulthood, ­vulnerability
There are many determinants and they interact in
to mood ­disorders and increasing suicide risk.
complex ways. They range from individual behaviours
(such as smoking or drink-driving) to much broader
factors such as socioeconomic background. All of
How do we describe child health?
these interact with our genetic makeup to produce
We use rates of mortality and morbidity to eval- health outcomes, such as reduced life expectancy, and
uate the health status of a community. Mortality increased illness or disability. Interventions can range
is a very crude index of health and is of limited from personal services to treat the sick to broad pre-
value in assessing the health status and health ventive campaigns such as encouraging breastfeeding.
needs of a community. Morbidity is a measure of Protective factors promote positive health and
the presence or absence of medical diseases or con- development and include factors such as infant breast-
ditions. A widely accepted view is that to describe feeding, physical activity and sound nutrition. Factors
health adequately involves also measuring a broad that increase the risk of ill-health in children include
range of social and economic risk and protective overweight and obesity, exposure to tobacco smoke or
factors. In 1946, the World Health Organization alcohol use in pregnancy. From a practical point of
(WHO) defined health holistically as ‘a state of view, complete paediatric clinical assessment requires
complete physical, mental, and social wellbeing a consideration of all aspects of the child's life, such
and not merely the absence of disease or i­ nfirmity’. as the home circumstances, the access to health care,
A child's physical, mental and social wellbeing is the physical and mental health of the parents, and the
­inextricably linked to the environment and social quality of community support available. This applies
values surrounding that child. Furthermore, chil- equally to every child whether they present with
dren and adolescents are growing and developing ­leukaemia, cystic fibrosis, acute bacterial meningitis,
rapidly, and may be more susceptible than adults to developmental delay, child maltreatment, behaviour
adverse e­ nvironmental influences (Fig. 1.1.1). problems or even a well-child review (Fig. 1.1.2).

Determinants Resources

Biomedical and genetic factors

Health and wellbeing
Human
Life expectancy
Subjective health Material
Functioning, disability
Health behaviours Financial
Illness, disease, injury
Research

Evaluation
Interventions
Socioeconomic factors
Prevention and Monitoring
health promotion
Surveillance
Treatment and care

Environmental factors Rehabilitation Technology

Other information

Fig. 1.1.1 A conceptual framework for Australia's health. (From Australian Institute of Health and Welfare 2010 Australia's health 2010: 5
the twelfth biennial health report of the Australian Institute of Health and Welfare. AIHW, Canberra, p 4, with permission.)
 1.1 CURRENT PAEDIATRICS

Broad features Socioeconomic Health behaviours Biomedical factors

of society characteristics
Culture Education Tobacco use Body weight
Alcohol
Resources Blood pressure
Employment consumption
Systems Physical activity Blood cholesterol
Income and wealth
Policies Dietary behaviour Glucose regulation
Individual and
Affluence Family and Immune status population
Use of illicit drugs health and
neighbourhood
Social cohesion funtioning
Sexual behaviours
Access to services
Social inclusion Vaccination
behaviours
Media Housing

Environmental Knowledge, Psychological

factors attitudes and beliefs factors
Natural
Safety
Built factors

Individual physical and psychological makeup

(genetics, ageing, life course and intergenerational influences)

Fig. 1.1.2 A conceptual framework for determinants of health. (From Australian Institute of Health and Welfare 2010 Australia's health
2010: the twelfth biennial health report of the Australian Institute of Health and Welfare. AIHW, Canberra, p 65, with permission.)

• Death rates among children and young people have

Mortality halved in the last two decades, largely due to fewer
Death rates in children provide insights into the social transport-related deaths.
and environmental conditions in which Australia's chil- • Neonatal mortality has fallen below 3 per 1000 for
dren grow and develop. In 2007 there were 1709 deaths the first time, in association with better perinatal care.
among children, with 70% of these in infants (under • Post-neonatal mortality has improved due to the
1 year of age), a rate of 4.2 deaths per 1000 live births. declining rate of sudden unexplained deaths in infancy.
The number of deaths among 1–14-year-olds was consid- • The Indigenous infant mortality rate declined by
erably lower at 506 deaths (a rate of 13 per 100 000). Over 47% between 1991 and 2006 (Fig. 1.1.3).
the last two decades there has been a steady decline in the • Infectious disease mortality is declining as a result
death rate for those aged 1–14 years. In contrast, infant of improved socioeconomic circumstances and
mortality rates almost halved between 1986 and 2006. universal immunization programmes.

How is mortality in Australia changing?

• Australia's life expectancy at birth continues to rise
Spotlight on Indigenous children
and is among the highest in the world (79 years for In Australia, Indigenous mortality and morbidity
males and almost 84 years for females), although for rates are substantially higher than non-Indigenous
Indigenous people it remains about 20 years less. rates at all ages.
• Infant mortality has fallen from a rate of • The proportion of low birth weight infants is 5.9%
approximately 100 per 1000 live births at the turn of the overall, but 12.5% for Indigenous births.
6
20th century to the 2007 rate of 4.2 per 1000 live births. • The proportion of preterm infants is 7.9% overall,
Figure 1.1.3 shows the decline over the last two decades. but 13.7% for Indigenous births.
 Child health and disease 1.1
12
Males
Females
10

Infant deaths per 1,000 live births

Persons

0
86
87
88
89
90
91
92
93
94
95
96
97
98
99
00
01
02
03
04
05
06
19
19
19
19
19
19
19
19
19
19
19
19
19
19
20
20
20
20
20
20
20
Year

Fig. 1.1.3 Infant mortality rate, 1986–2006. (From Australian Institute of Health and Welfare 2010 A picture of Australia's children 2009.
AIHW, Canberra, with permission.)

• The Indigenous perinatal mortality rate is two times levels of ­education, employment and income, and results
higher than the non-Indigenous rate (20 per 1000 in greater exposure to factors such as smoking, poor
versus 10 per 1000). nutrition, alcohol misuse, overcrowded living conditions
• The Indigenous infant mortality rate is three times and violence. However, not all the health inequalities are
higher than the non-Indigenous rate (13 per 1000 explained by socioeconomic differences and there are com-
versus 4.2 per 1000), although the gap is closing. plex historical, cultural, access and political factors impact-
• The Indigenous 1–14 years mortality rate is three ing on Indigenous health. On the positive side, Indigenous
times higher than that of non-Indigenous Australians children are just as likely to be fully immunized at 2 years
(39 per 100 000 compared with 13 per 100 000). of age as non-Indigenous children, and Indigenous house-
• Some 70% of the ‘excess’ deaths in rural and remote holds with children aged 0–14 years are just as able to get
areas (observed deaths in rural and remote areas support during a time of crisis (reflecting extended fam-
compared with what would be expected if city death ily and community support structures – ‘social capital’) as
rates had applied) occur in Indigenous children. non-Indigenous households. The Council of Australian
• Injury (which is largely preventable) was the leading Governments has committed to halving the mortality gap
cause of death for Indigenous children, accounting for Indigenous children aged under 5 years within a decade.
for almost half of all deaths (46%). Improvements in Indigenous child mortality (Fig.1.1.4)
• Indigenous Australians have the highest recorded require better access to antenatal care, teenage reproductive
rates of acute rheumatic fever and rheumatic heart and sexual health services, child and maternal health ser-
disease in the world, almost exclusively restricted to vices, and integrated child and family services.
the Northern Territory and Central Australia, and
extremely rare in other Australians.
• The teenage birth rate is five times higher in
Indigenous women (80 births per 1000 compared Infant mortality
with 15 per 1000), and increases the risk of adverse
health outcomes. The rate increases with increasing Infant mortality rates are important indicators of
remoteness. child health, and refer to infant deaths within 1 year
of birth. The leading causes of death in this age group
in 2007 were:
How can we explain the health of Indigenous
children?
• Perinatal conditions (48%)
• Congenital anomalies (26%)
The health inequality of Indigenous Australians ­compared • Ill-defined conditions, mostly sudden infant death
with the rest of the population reflects disadvantage across syndrome (SIDS) (12%).
a range of socioeconomic f­actors that affect health and Part of infant mortality is neonatal mortality, which is
7
wellbeing. The low ­socioeconomic status arises from lower death within 28 days (ABS definition) of birth. Neonatal
 1.1 CURRENT PAEDIATRICS

30
Indigenous infants
Other infants
25

Infant deaths per 1,000 live births

20

15

10

0
91

92

93

94

95

96

97

98

99

00

01

02

03

04

05

06
19

19

19

19

19

19

19

19

19

20

20

20

20

20

20

20
Year

Fig. 1.1.4 Infant mortality by Indigenous status, 1991–2006. Deaths are based on year of registration and state of usual residence
(Western Australia, South Australia or Northern Territory). The average of births over 1993–1995 in Western Australia was used as the
denominator for infant mortality rates for 1991 and 1992 to correct for errors in births recorded for 1991 and 1992. (From Australian
Institute of Health and Welfare 2010 A picture of Australia's children 2009. AIHW, Canberra, with permission.)

mortality has reduced substantially since the 1920s in Iceland 1st

Australia. Some 60% of neonatal deaths occur on the Luxembourg 2nd
day of birth, with most being due to extreme prematurity, Japan 3rd
Ireland 12th
poor fetal growth, congenital ­malformations or preg- Australia 20th
nancy complications. With the advent of n ­ eonatal inten- United Kingdom 21st
sive care in the late 1960s, the n­ eonatal mortality rate OECD average
New Zealand 22nd
declined even f­urther. Other important factors contrib- 24th
Canada
uting to the decline have been the use of p
­ ericonceptional United States 28th
folate to prevent neural tube defects (anencephaly, spina Turkey 30th

bifida and encephalocele) and improved ­understanding 0 5 10 15 20 25

of the determinants of premature labour, intrauterine Deaths per 1,000 live births
growth restriction, and some developmental anomalies.
Fig. 1.1.5 Infant mortality rates among selected OECD countries,
Figure 1.1.5 shows Australia's Infant Mortality Rate as 2006. Data for Canada and the USA are for 2005. Based on
compared to other selected OECD countries. data from 30 OECD countries, using the most recent year of
available data. (From Australian Institute of Health and Welfare
2010 A picture of Australia's children 2009. AIHW, Canberra, with
Sudden infant death syndrome permission.)
A major contributor to the recent decline in post-neo-
natal mortality (children aged over 1 month and under remains higher than in non-Indigenous infants, probably
1 year) has been the decline in deaths from SIDS. SIDS because of a higher prevalence of the risk factors.
is the commonest cause of sudden unexplained death in
infancy (SUDi), for which strict diagnostic criteria must
Causes of death between 1 and 14 years
be satisfied. Between 1982 and 2002, the SIDS death rate
fell from 180 to 46 deaths per 100 000 live births. Public More than 98% of children survive from birth to 15 years
education campaigns during the 1990s, e­mphasizing of age (Fig. 1.1.6). The mortality rate for ­children aged
that babies should be placed on their back when placed 1–14 years declined by 52% between 1983 and 2003.
to sleep, contributed to the decline. Apart from sleep- The three main causes of death in 2007 were:
ing position, other risk factors have also been identified • injury (37%)
consistently from epidemiological studies. These include • cancer (17%)
maternal cigarette smoking, lack of breastfeeding, over- • diseases of the nervous system (10%). (Figure 1.1.7)
heating of the baby and a parental history of illicit drug The leading causes of injury death in this age group
8
use. Unfortunately, the rate of SIDS in Indigenous infants are road transport incidents (involving occupants,
 Child health and disease 1.1
60
1–4 years
5–9 years
50
10–14 years

Deaths per 100,000 children

40

30

20

10

0
86
87
88
89
90
91
92
93
94
95
96
97
98
99
00
01
02
03
04
05
06
19
19
19
19
19
19
19
19
19
19
19
19
19
19
20
20
20
20
20
20
20
Year

Fig. 1.1.6 Death rates for children aged 1–14 years, 1986–2006. (From Australian Institute of Health and Welfare 2010 A picture of
Australia's children 2009. AIHW, Canberra, with permission.)

Injuries
Male
1–4 years

All cancer

Female Diseases of the nervous system

Male Congenital anomalies

5–9 years
Age

Symptoms, signs and ill-defined conditions

Female
Circulatory conditions
10–14 years

Male Other causes

Female

0 5 10 15 20 25 30

Deaths per 100 000 live children

Fig. 1.1.7 Leading causes of death among children aged 1–14 years, 2004–2006. ‘Other causes’ accounted for 17% of child deaths
among 1–14-year-olds in 2004–2006. (From Australian Institute of Health and Welfare 2010 A picture of Australia's children 2009. AIHW,
Canberra, with permission.)

­edestrians and cyclists) and drowning (domestic

p Another important cause of preventable mortality in
swimming pools, bathtubs, dams and drains, rivers and children is bacterial meningitis. Introduction of uni-
sea, and domestic buckets). Swimming pool drowning versal immunization for Haemophilus influenzae type b
accounts for about half of all drownings in those aged (Hib), meningococcus C and pneumococcal infections
under 5 years, a proportion that has shown no signifi- has resulted in a significant decrease in invasive disease
cant change since the 1990s. due to these organisms.
The decline in injury mortality has been due to a
number of preventive actions, including:
Causes of death between 15 and 19 years
• child-resistant packaging of medication
• traffic control measures (such as infant and child Mortality rates in this age group are about five times
seat-restraint legislation, improved vehicle design, traffic higher than in children aged 5–14 years, although
control through speed cameras, random breath-testing, substantially lower than in the 0–4-year group. The
school speed zones and young driver regulations) principal causes of death in adolescents are injury
9
• domestic pool isolation fencing. (50%), suicide (20%) and cancer (10%). T
­ raffic-related
 1.1 CURRENT PAEDIATRICS

causes are the most important contributor and alco- births) during the last 25 years, largely due to the
hol use is the key risk factor. The mortality rate improved survival of these children.
for males is twice that of females in this age group. • Rates of sexually transmitted infections (chlamydia
The ­disturbing increase in adolescent male suicide and gonococcal infections) are increasing amongst
that occurred between 1979 and 1998, with the rate young people aged 15–24 years.
increasing by 40%, has begun to fall for reasons that
are unclear; in 2002 rates were at their lowest since
Which diseases are declining and why?
1984. The male rate is currently four times higher
than the female rate. Paediatrics has changed dramatically during the past
50 years, as the mortality rate for all life-threatening
conditions has declined. The most dramatic change
has been as a result of declines in infectious diseases
in particular. This has been the result of improved
Morbidity living conditions, higher levels of education, and the
Changes in disease patterns ­availability of immunization and antibiotics.
Of particular importance is the greatly reduced inci-
How is children's health changing?
dence of tuberculosis; chronic suppurative diseases of
• The prevalence of asthma in children and young the chest, bone and ear; rheumatic fever and rheumatic
people rose during the 1980s and 1990s (from heart disease; and streptococcal infections. It should
12.3% to 19.2%), but there has been no further be noted that the incidence of all infections was falling
increase since then. Currently, 12% of children well before the advent of antibiotic and chemothera-
report asthma as a long-term condition, one of the peutic drugs, which are often credited incorrectly for
highest rates in the world. Around 40% of children control of infection.
with asthma live with a person who smokes; higher
exposure rates occur among socioeconomically
Which diseases are increasing?
disadvantaged children.
• There has been increasing concern about problems In contrast to these improvements, some other child-
of developmental health and wellbeing, with 35% hood diseases have shown a rising prevalence, for
of new paediatric consultations for behaviour which the causes are unclear. The incidence of type
problems and 13% for learning problems. Around 1 diabetes has increased since 2000. The increase has
one in seven (14%) of Australian children aged been too rapid to be caused entirely by genetic factors
4–14 years had mental health problems in the latest and is more likely to be environmental factors causing
National Survey of Health and Wellbeing (1998). changes in the immune system that trigger the disease.
• One in four children (25%) aged 5–17 years are New challenges have also been posed by the emergence
overweight or obese. of problems of developmental health and ­wellbeing that
• The prevalence of disability has increased from are related to extensive changes in social and family life
5.3% in 1981 to 8.3% in 2003. Almost half of during the past 30 years. Examples are child maltreat-
these children had severe or profound core ment, behaviour and learning p ­ roblems, youth suicide,
activity limitations, so that they needed assistance obesity and other eating ­disorders, ­substance misuse and
with one or more of the core activities of daily early onset of c­ riminal behaviour.
living (self-care, mobility or communication
tasks). Some 75% of 5–19-year-olds with a
Burden of disease and long-term health
disability also experienced schooling restrictions
conditions
that resulted in them needing special assistance,
arrangements or equipment at school, attending Chronic and long-term conditions account for a large
special classes or a special school, needing proportion of the burden of disease among ­children,
frequent time off school or having difficulty with and can affect growth and physical, social and ­emotional
aspects of school work or the school environment. development. In 2003, almost a q ­ uarter of the burden
A quarter of those with a disability had asthma of disease in children was due to m ­ ental ­disorders such
and others had autism, disruptive behaviour as anxiety and d ­epression, ­ attention-deficit disorder
and intellectual impairment. More than 90% and autism spectrum d ­ isorders. A further 18% was due
of children with autism had severe or profound to chronic respiratory conditions (mainly asthma) and
core activity limitations, and all had schooling 16% to neonatal conditions (Table 1.1.1).
restrictions. Conditions such as cancer and diabetes are
10 • There has been a rising incidence of cerebral palsy ­uncommon in childhood but a considerable number
in births under 1500 g (from 10 to 70 per 1000 live of c­hildren are affected by them each year. Type 1
Table 1.1.1 Burden of disease and mortality in 0–14-year-olds in Australia

Parent-reported prevalence Burden of disease and injury

(2007–2008) Hospitalizations (2007–2008) Infant mortality (2007) Child (1–14 years) mortality (2007) (DALYs)* (2003)

% of % of all child % of all % of all child % of all child

Condition children Condition hospitalizations Condition infant deaths Condition deaths Condition DALYs

Respiratory 17.4 Respiratory 18.6 Perinatal 47.7 Injury and 36.8 Mental disorders 22.6
diseases conditions conditions poisoning

Eye and adnexa 10.1 Injury and 12.1 Congenital 25.8 Cancer 17.0 Chronic respiratory 18.1
disorders poisoning anomalies conditions

Ill-defined 6.7 Perinatal 10.3 Ill-defined 12.1 Diseases of the 9.9 Neonatal conditions 15.6
conditions† conditions conditions† nervous system

Mental and 5.3 Digestive 10.2 Injury and 3.0 Circulatory 6.3 Congenital 11.6
behavioural conditions poisoning conditions conditions
problems

Ear and mastoid 3.2 Ill-defined 6.9 Diseases of the 2.3 Ill-defined 6.3 Injuries 7.4
disorders‡ conditions† nervous system conditions†

*Disability-adjusted life-years.
†
Parent-reported prevalence, hospitalizations and deaths from ill-defined conditions include those for which a more specific diagnosis could not be made or where signs or symptoms
could not be determined.

Child health and disease

‡
Diseases of skin and subcutaneous tissue were in equal fifth position with ear and mastoid disorders.
Note: The conditions listed above are based on the International Classification of Diseases, tenth revision (ICD-10), chapter level headings, except for the burden of disease data, where
conditions are grouped using a different methodology.
Source: Australian Institute of Health and Welfare 2010 Australia's health 2010: the twelfth biennial health report of the Australian Institute of Health and Welfare. AIHW, Canberra, p 299.

1.1
11
 1.1 CURRENT PAEDIATRICS

­ iabetes most often appears during childhood or ado-

d cost-effective. Some key performance indicators are
lescence and requires ongoing management to control used to reflect how well the system is performing in
and reduce the risk of complications. The rate of new delivering quality health care to Australian children.
cases in 2007 (24 per 100 000 children) has increased These include the coverage of screening programmes
significantly since 2000 (19 per 100 000 children). such as the neonatal hearing screening programme,
For cancer, the rate of 14 per 100 000 children in the and preventive interventions such as childhood immu-
5-year period from 2002 to 2006 has not increased nization. In general, preventive activity is more cost-
since 1996–2000. The most common cancer types are effective than interventions designed to treat health
lymphoid leukaemia, cancer of the brain and myeloid problems that have already occurred. Nonetheless our
leukaemia. Overall survival from cancer and leukae- health-care expenditure is heavily weighted towards
mia in particular continues to improve. The 5-year treatment rather than preventive services. Health-care
survival rate for children with leukaemia increased costs are rising steadily in Australia and redirecting
from 64% to 83% between 1982–1986 and 1998–2004. more funding towards prevention of disease may help
to reduce this escalation.

Is birth weight important?

A key indicator of infant health is the proportion
of infants with low birth weight. ‘Low birth weight’
Why are children taken to a
is defined as less than 2500 g at birth; ‘very low birth health service?
weight’ is under 1500 g and ‘extremely low birth Hospitalizations
weight’ is under 1000 g. There has been little change in
the incidence of low birth weight in recent generations. Around 10% of hospital admissions in Australia
Indeed, there has been a slight rise in its incidence in are for children under 15 years. Respiratory condi-
the last decade (from 6.3% to 6.8%), which is explained tions were the most common reason for hospitaliza-
partly by a higher proportion of older mothers giving tion in 2007–2008, followed by injury and poisoning.
birth. In 1998, the birth rate in women over 35 years Boys were 1.6 times more likely to be hospitalized for
of age exceeded that in those less than 19 years for injury as girls, with falls accounting for 39% and land
the first time. Low birth weight babies have a greater ­transport incidents for 13%.
risk of poor health and dying, require longer periods
of hospitalization after birth and are more likely to Children and adolescents presenting to general
develop significant disabilities. practitioners
Low birth weight has been found to have endur-
ing effects on health and is associated in adulthood From an ongoing national survey of general practice
with type 2 diabetes, high blood pressure, meta- statistics, it is known that 15.8% of total general practice
bolic and cardiovascular disease, and possibly obe- encounters in Australia are for children aged 0–14 years,
sity. Many of the risk factors for low birth weight with a further 9.8% for young persons aged 15–24 years.
are modifiable by providing good antenatal care to The top reasons for consulting a ­doctor, including but
pregnant women, reducing smoking, and optimiz- not limited to general practitioners (GPs), in children
ing general health and nutrition before and during aged under 15 years were respiratory conditions (upper
pregnancy. respiratory infection, including tonsillitis, asthma and
acute bronchitis) and immunization. Rates of presen-
tation to GPs for asthma fell by almost one-third in
0–4-year-olds between 1998–1999 and 2001–2002.
Australian health services
Children and adolescents presenting to
• Health expenditure in 2007–2008 exceeded $100
specialized paediatric services
billion for the first time and equalled 9.1% of gross
domestic product (GDP). In the Australian health-care system, children may be
• In 2007–2008, just over 2% of total health referred to a consultant or specialist paediatrician by
expenditure was for preventive services or health a general (or primary care) practitioner for consulta-
promotion. tion on difficult problems, or for management of rare
In addition to the risk and protective factors discussed or difficult-to-treat chronic illnesses. Paediatricians
above, the capacity of the system to deliver a high- work in the community and/or in g­eneral ­hospitals
quality service plays a major role in improving the with paediatric facilities (secondary paediatric ­services)
health and wellbeing of children. Care should be or ­ children's hospitals with extensive subspecialty
12
accessible, responsive to the population it serves and­ ­services (tertiary hospitals). In addition, ­public and
 Child health and disease 1.1
some ­private hospitals provide accident and e­ mergency in developed countries is now arguably one of the
­services for children. The pattern of injuries and acute major determinants of public health, being implicated
and chronic illnesses seen in these settings v­aries in the high prevalence of academic failure, disruptive
according to the mix of private and public paediat- behaviour and other mental health problems, inten-
ric hospitals s­erving urban and rural communities. tional and unintentional injuries, substance misuse
The case mix (pattern of clinical problems) differs for and juvenile crime.
outpatient clinic attendances, emergency department Other health behaviours may also have benefits or
­presentations and ­hospital admissions. adverse effects; for example, high rates of breastfeed-
A 12-month survey of the practice profile of ing and immunization, use of child restraints in motor
­paediatricians in the Barwon region of Victoria in vehicles, sun exposure protection using clothing and
1996–1997 found that 10% of the childhood popula- sun-screen creams, healthy nutrition, active lifestyles,
tion had consulted a paediatrician practising in the pool fences and swimming competence, and bicycle
community during this period: 68.9% of ­consultations helmets all have a beneficial impact on disease and
concerned medical problems, with central nervous
­ injury prevention.
system/disability and the respiratory system each
­
accounting for 16%, and gastrointestinal problems
Smoking and sun exposure
a further 14%. Nearly 35% of children seen had
­behavioural problems, with 76% of these relating to The massive increase in the incidence of lung cancer
attention-deficit/hyperactivity disorder (ADHD), in men over the age of 50 years preceding the 1980s
which was the most common diagnosis overall. A and, in more recent years, the rise in women, along
further 14.5% of consultations concerned children
­ with the increase in melanoma in both sexes, stands
with epilepsy or disability, 13% were for children with in stark contrast to the relatively stable incidence of
learning problems and 10% were for asthma. Just over most other cancers. What have these outcomes to do
4% of all consultations involved children with signifi- with ­paediatrics? The answer is that the behaviours
cant social problems. At least 50% of these paediatric associated with an increased risk of these diseases
­
medical consultations involved children with a chronic commence in childhood and adolescence.
illness.
Attendances at an emergency department provide
Smoking-related disorders
a further component of the picture of child injury
and acute illness. Gastroenteritis, asthma and injuries The current patterns of lung cancer incidence and
dominate the mix of clinical conditions treated in this mortality in men (a 2% per year decline) and women
setting. Children aged 0–4 years with asthma attend (a 1.6% per year increase) probably reflect smoking
emergency departments relatively more often than behaviour patterns 20 years ago. Most smokers com-
people of other ages who have asthma. mence smoking in adolescence and this behaviour, once
established, may be difficult to change. In a­ ddition, the
number of pack-years of smoke exposure is directly
related to the risk of smoking-related cancers, cardio-
Health behaviours vascular disease and numerous other health problems.
The health status of children and young people is The relationship between media exposure to ciga-
changing as evidenced by health behaviour changes: rette promotion and the likelihood of young people
• Increased immunization uptake has followed becoming smokers is strong and well established. With
the establishment of the Australian Childhood increasing awareness of the profound and irrefutable
Immunisation Register (ACIR): 90.5% fully causal relationship between cigarette smoking and dis-
immunized at 1 year in 2002, 87.8% at 2 years and ease, and with new laws restricting the way in which cig-
80.6% at 6 years. arettes may be advertised, the prevalence of adolescent
• There has been a plateau in rates of adolescent smokers in Australia has finally started to decline dur-
smoking but with persisting higher rates among ing the past 15 years, although daily smoking rates are
girls (32% versus 28% for boys). higher in 16–17-year-old girls (14.5%) compared with
• Rates of obesity and overweight are rising: 25% boys (7.95%).
of 7–18-year-olds in Sydney and Melbourne are Furthermore, the recent widespread recognition of
overweight. the harmful effects of both prenatal and postnatal pas-
A number of factors that rely on public participa- sive smoke exposure in children (low birth weight and
tion have a profound impact on child health, and on prematurity, and all of their consequences, r­ espiratory
future good health as an adult. In traditional societies, infections, asthma, otitis media, impaired lung growth)
­parenting was a responsibility of the clan, not just the has led to rapid changes in public policy, laws and
13
biological parents. The quality of parenting p ­ rovided community practices aimed at reducing e­ nvironmental
 1.1 CURRENT PAEDIATRICS

tobacco smoke exposure, especially for children.

The clinician's role is to assist in the ­education of Future directions
young parents, to provide access to professional quit There is widespread recognition that social, environ­
­programmes and to encourage smokers in the mean- mental, family and technological changes during the
time to smoke only outside the family home and wear past half century have contributed to the changing
protective clothing while doing so, and never in the ­pattern of childhood mortality and morbidity. There
family vehicle or in the company of children. is also increasing awareness that exposures and
behaviours occurring in fetal life and childhood have
Melanoma lifelong implications for physical, developmental and
In the case of melanoma, the incidence rates have increased mental. The benefits of investing in children flow
markedly since 1983, especially for males. Australian mel- through to the entire population, with outcomes as
anoma rates are among the highest in the world, with a diverse as greater productivity, lower burden of dis-
10-fold difference in incidence between Australia and ease, stronger families, and safer and more con-
England and Wales. Melanoma risk is related to ultravio- nected communities. The health and wellbeing
let radiation exposure and the incidence is higher in indi- experience of children is thus increasingly being seen
viduals with many moles, those with fair, sun-sensitive as having wide ramifications for the competence,
skin, and those who have intermittent high recreational c oping and adaptability of human populations
­
exposure. It is thought that exposure in childhood may undergoing massive social changes associated with
be particularly important. It is therefore disconcerting to their transformation from industrial to globalized,
note that surveys have found that between 9% and 12% information-based economies. Child health, as it was
of children and young people in all age groups who have at the turn of the 20th century but for very different
been exposed to the sun have not used sun protection. reasons, is once more at centre stage in the grand
vision of improving the health and wellbeing of
Obesity and physical fitness human populations.

There has been growing concern about the increasing

levels of obesity and lack of physical fitness in children
and young people in Australia. In 1985, 4% of boys What are our ongoing challenges?
and 6% of girls were classified, according to their body
mass index (BMI – a measure of weight for height) • The health of Indigenous children remains significantly
as being overweight. More recent studies found that poorer on a range of indicators compared with the health
of all Australian children.
about 25% of children aged 7–18 years in Sydney and • Some 40% of deaths in 1–14-year-olds are due to
Melbourne were overweight, had sedentary lifestyles, unintentional injury, a preventable cause of death.
and consumed a diet high in fat and low in the intake of • Rates of severe disability and diabetes are rising in
fruit and vegetables. It is of some concern that around children.
one-third of children under 12 years of age do not eat • An ‘excess’ of deaths of young children (100 per year)
any fruit or fruit products, and more than 1 in 5 do not occurs in rural and remote areas.
• The teenage birth rate in Australia is higher than the OECD
eat any vegetables or vegetable ­products. Childhood
average, at 18 births per 1000 15–19-year-olds, 42% of
obesity is now being tackled as part of a national strat- whom smoke during pregnancy.
egy developed by the National Obesity Taskforce.

14
 Child health in a global 1.2
context
Trevor Duke

Inequity exists also within countries. For exam-

Introduction ple, in Papua New Guinea in 1999 the median child
In the 20th century there were dramatic reductions ­mortality rate was 89 per 1000 live births, but some
in child mortality and general improvements in child provinces had under-5 mortality rates as low as 49 and
health in Western countries. These resulted from eco- others as high as 164 per 1000 live births. Similarly in
nomic development, public health interventions, Cambodia, the child mortality rates in various prov-
urbanization, better nutrition, maternal health and inces ranged from 50 to 229 per 1000 live births. Urban
education, immunization and advances in health tech- child mortality is generally lower than rural mortality,
nology and curative care. Child mortality rates have for example: 43 versus 71 per 1000 live births respec-
fallen from over 100 per 1000 live births in the UK, tively in South Africa. The neonatal mortality rate in
North America, Australia, New Zealand, Japan, remote mountainous areas of Vietnam is three times
Scandinavian countries and western Europe at the end higher than in urban areas. In general, the rapid trend
of the 19th century, to around 4–5 per 1000 live births towards urbanization has contributed to lower child
at the beginning of the 21st century. The vast major- mortality, but some city slums in developing countries
ity of the world's people who live in developing coun- have rates of child disease and death that are higher
tries have not shared in this prosperity and progress. than their nation's average.
Although progress is being made in most countries, Income is a major determinant of child mor-
gross inequity exists, with sub-Saharan African and tality risk. In 2003, the average under-5 mortality
South Asian countries carrying the greatest burden of rate was 123 deaths per 1000 in low-income coun-
child deaths and morbidity. tries, 39 in lower-middle-income countries and 22 in
The World Health Organization (WHO) estimated ­upper-middle-income countries. In high-income coun-
in 2000 that 10.7 million children under the age of tries the rate was less than 7 per 1000. Within-country
5 years die annually and 99% of these deaths occur income inequity also has a great effect on child mor-
in developing countries. By 2008, the estimated num- tality risk. Among the poorest quintiles (the poorest
ber of deaths had fallen to 8.8 million. Figure 1.2.1 20%) of the populations of Cambodia and Vietnam,
shows the distribution of child mortality globally, child m ­ ortality rates are two to three times higher
the ­majority of under-5 deaths being concentrated than in the richest quintiles. Equity of income distri-
in sub-Saharan Africa and South Asia. In 2010, it is bution is also an important determinant: countries
estimated that 26 countries had child mortality rates with low gross domestic product (GDP) but a more
greater than 100 per 1000 live births, all in sub-Saharan even income distribution have much lower rates of
Africa except two, Afghanistan and Haiti. A ­further mortality than other countries with higher GDP but
30 ­countries had under-5 mortality rates above 50 per ­inequitable income distribution. Maternal education
1000 live births. and access to health services are also closely related to
child mortality risk.
Disparities exist in the financial, technical and
human resources available for child health, globally
and within countries, and this is closely related to mor-
Child health inequity tality risk. In 1973, Professor David Morley said of
Inequity is unfair distribution, and child health has Nigeria: ‘Three quarters of our population are rural,
many layers of inequity. Inequity between regions and yet three quarters of our medical resources are spent
countries is brought into sharp focus in the 21st cen- in the towns where three quarters of our d ­ octors live;
tury because of globalization and freedom to travel. three quarters of the people die from diseases which
Countries that are half a day's flying time away from could be prevented at low cost, and yet three quar-
capital cities in Australia, for example, have child ters of medical budgets are spent on curative s­ ervices.’
mortality rates 10 times higher than that of non-­
­ Unfortunately, the same is still true today of many
Indigenous children in Sydney or Melbourne. developing countries. The doctor : population ratios
15
 1.2 CURRENT PAEDIATRICS

The distribution of global child mortality

1 dot = 5000 annual deaths

Fig. 1.2.1 The distribution of global child mortality. 1 dot = 5000 annual deaths. (Source: Black RE, Morris SS, Bryce J 2003 Where and
why are 10 million children dying each year? Lancet 361: 2226–2234.)

of many countries are 20 times higher in cities than $8.40 is spent on research into HIV, malaria and tuber-
in rural areas. Differences in health service access culosis, only $0.51 per DALY is spent on research into
between rural and urban populations manifest in dis- acute respiratory infection and $0.30 per DALY on
parities of functional outcomes as well as mortality diarrhoea. Some 86% of scientific publications and
risk. For example, compared to urban children with 97% of patents are held by 16% of the world (the
epilepsy, children with epilepsy in rural Zimbabwe advanced economies), while the remaining 84% pub-
are less likely to receive treatment (63% rural versus lish a mere 14% of the world's scientific papers and
95% urban), have a greater seizure burden (2.3 versus hold 3% of the world's patents. Therefore, between
1 per month) and are more likely to have problems that countries and for all major diseases, capacities to deal
impair social and educational attainment. with child health problems are inversely proportional
Human resources in low-income countries are being to the magnitude of the problems.
further eroded by the drain of doctors and nurses
migrating to richer countries. Human immunodefi-
ciency virus/acquired immune deficiency syndrome
(HIV/AIDS) has exacerbated this human resources
Causes of global child mortality
crisis; to implement effective antiretroviral treatment The major causes of death in children aged under
programmes requires increased numbers of trained 5 years globally are listed in Table 1.2.1. The percent-
health workers. However, the cruel irony is that HIV/ ages vary widely across regions, with skewed distribu-
AIDS is claiming a major proportion of the young tion in the Africa region. For example, 94% and 89%
population of doctors and nurses in countries, particu- of the world's malaria and HIV/AIDS deaths occur in
larly in Africa, that most need effective prevention and Africa.
treatment programmes. More than one-third of children who die in devel-
Research in child health is also disproportionate to oping countries have moderate or severe ­malnutrition,
the burden of diseases and inequitably distributed. and malnutrition is implicated in deaths from diar-
While $73 is spent on health research per disability- rhoea (61%), malaria (57%), pneumonia (52%) and
adjusted life-year lost (DALY: an index that combines measles (45%). However, malnutrition is often under-
16
both mortality and disability) for diseases overall and reported in national statistics and under-recognized
 Child health in a global context 1.2
Table 1.2.1 Major causes of death in children under 5 years
of age globally, with estimates for 2000–2003 and 2008
Progress in child mortality
globally
No. of deaths, in thousands
Since 1990 there have been substantial reductions in
2000–2003 2008 deaths in children under 5 years of age. The child mor-
tality rate was 11.9 million in 1990, 10.6 million in 2000,
Deaths in children aged 6685 (63%) 5220 (59%)
1 month to 5 years and one modelled projection for 2010 was 7.7 million,
Acute respiratory infections 2027 (19%) 1189 (14%)* a 35% reduction over 20 years. Now no country has
Diarrhoeal diseases 1762 (17%) 1257 (14%) a rate of under-5 mortality more than 200 per 1000
Malaria 853 (8%) 732 (8%) live births, whereas in 2000 there were 10 such affected
Measles 395 (4%) 118 (1%) countries. The causes of this progress are many, but
HIV/AIDS 321 (3%) 201 (2%) include better coverage of health interventions includ-
Injuries 305 (3%) 279 (3%)
ing immunization, vitamin A, insecticide-treated nets,
Meningitis 164 (2%)
Pertussis 195 (2%) prevention of parent-to-child transmission of HIV, the
Congenital anomalies 104 (1%) beneficial effects of urbanization and improved educa-
Other 1022 (10%) 981 (11%) tion for girls. In several low-income countries in sub-
Saharan Africa there has been an accelerated decline
Neonatal deaths 3910 (37%) 3573 (41%) in child mortality since 2000. One factor behind this
Pre-term birth 1083 (10%) 1033 (12%) is resolution of civil wars, allowing health services to
Severe infection 1016 (10%)
re-establish and enabling basic health, education and
Sepsis 521 (6%)
Pneumonia 386 (4%) community interventions to be more widely accessible.
Birth asphyxia 894 (8%) 814 (9%) Understanding the broader determinants of child sur-
Congenital anomalies 294 (3%) 272 (3%) vival is crucial to understanding the potential impact
Neonatal tetanus 257 (2%) 59 (1%) of any intervention and the obstacles to reducing child
Diarrhoeal diseases 108 (1%) 79 (1%) mortality. A recent analysis of data from 152 countries
Other 258 (2%) 409 (5%) found that gross national income (GNI) per capita,
Total deaths in children 10 595 (100%) 8793 (100%)
female illiteracy and income equality predicted 92% of
under 5 years
the variance in child mortality. A recent study from the
Values in parentheses are percentages of total annual global Gambia showed that community and social networks,
deaths. personal support for caregivers in the home, and finan-
*The apparent dramatic reduction in pneumonia deaths in cial autonomy were more important d ­ eterminants of
2008 compared with 2000–2003 was highly dependent on
child mortality than access to health services. Several
data from China, the validity of which is uncertain. Note also
that deaths from pertussis and meningitis were reported
large prospective studies have shown that access to
separately in 2008, and neonatal pneumonia was not community mothers’ groups which support skills and
specifically reported in 2000–2003 data. care-seeking results in fewer neonatal deaths.
Data from: World Health Organization 2005 The World Health
Report 2005 – make every mother and child count. WHO,
Geneva, p 190 (http://www.who.int/whr/2005/en/) and
Black RE, Cousens S, Johnson HL et al. 2010 Global, regional, Child disability and development
and national causes of child mortality in 2008: a systematic
analysis. Lancet 375:1969–1987. Like mortality, the capacity of countries to prevent
and treat child disability is inversely proportional to
the burden of the problems. Child disability and devel-
opmental problems occur at high rates in poor coun-
tries because of the frequency of neurological disease
in clinical settings where childhood malnutrition is (including perinatal asphyxia, bacterial and tubercu-
so common as almost to be the norm. The s­ituation lous meningitis, cerebral malaria, viral encephalitis and
is even more complex than Table 1.2.1 suggests: neurocysticercosis), the contribution of undernutrition
although children often present with a single condi- to developmental retardation (maternal malnutrition,
tion (e.g. acute respiratory infection), those who are low birth weight, iron and iodine deficiency), high rates
most likely to die will often have experienced several of trauma and injury, in utero exposure to drugs and
other ­infections in recent months, have more than one alcohol, congenital syphilis and rubella syndromes, and
infection ­concurrently (e.g. pneumonia and diarrhoea, exposure to environmental toxins. Institutionalization
or pneumonia and malaria) and have malnutrition of orphans and disabled children in some countries
with micronutrient (such as iron, zinc or vitamin A) also contributes to severe ­developmental delay, because
17
deficiency. of emotional neglect and malnutrition. The lack of
 1.2 CURRENT PAEDIATRICS

­ rimary prevention, screening and rehabilitation ser-

p Four out of five people between 10 and 24 years of
vices that might mitigate the effect of disabilities on age live in d ­ eveloping countries. Although mortality
function also worsens the impact of these conditions rates for adolescents in developing countries are much
on individuals and the community. lower than for children under 5 years, the ­proportion
In some countries, community rehabilitation services of deaths occurring in adolescents is several times
have improved the lives of many disabled children, higher in developing countries than in industrialized
iodine and other micronutrient supplementation and ­countries. However, it is the future costs of current
fortification programmes are under way, programmes morbidity and the adoption of unhealthy behaviours
for the primary prevention of injuries are starting, and by young people that pose the greatest risk and pro-
increasingly developing countries are gaining access to vide the greatest opportunities for prevention. As
vaccines that will prevent meningitis. However, more countries pass through economic transition, as the
work in these areas is urgently needed. HIV/AIDS pandemic has developed and with increas-
ing urbanization, the health problems of young people
are increasingly on the global agenda. WHO estimates
that half of all HIV infections have occurred in ­people
Neonatal health less than 25 years old. There is high potential for
More than one-third of all under-5 deaths occur in ­prevention of many of the major diseases in adults by
the first month of life (see Table 1.2.1) and the major- interventions targeted at adolescents. Indeed, improv-
ity of neonatal deaths occur in the first few days after ing the health of young people may be a major key
birth, making the neonatal period the most hazard- to improving health at all ages: improving adolescent
ous time of life. The majority of the 3.5 million annual education, delaying reproductive age, improving nutri-
neonatal deaths occur in socioeconomic deprivation in tion and exercise, reducing smoking and drug and
developing countries. Programmes to improve neona- alcohol ­consumption, and preventing sexually trans-
tal survival are focusing on supervised clean d ­ eliveries, mitted infections will have beneficial effects on the
essential care of the newborn (early breastfeeding, young people themselves now and in decades to come,
skin-to-skin warmth), steroids for preterm labour, and reduce the burden of disease among newborns
antibiotics for premature rupture of membranes, and children in future generations.
maternal tetanus toxoid to prevent neonatal tetanus,
prevention of parent-to-child transmission of HIV
and identification of sick neonates requiring referral Children in complex emergencies
to hospital. Improving obstetric services is essential
to addressing neonatal mortality, especially that due Complex emergencies are identified as acute ­situations
to birth asphyxia. WHO has produced guidelines for in which there is excess mortality (more than 1 death
the management of seriously ill neonates in hospitals per 10 000 population per day). They may be due to nat-
in developing countries. Improving neonatal health, ural (e.g. flood, tsunami or earthquake) or unnatural
particularly the reduction in low birth weight through (war, famine) disasters, or both. With c­ limate change
improved maternal health, may reduce the risk of adult and population growth placing increasing demands on
diseases such as hypertension, coronary artery d ­ isease the environment, conflict over basic resources is likely
and non-insulin-dependent diabetes, which form a to increase. Complex emergencies are dynamic, with
large and increasing burden of non-communicable variable durations of emergency, recovery, resettle-
diseases in developing countries. As neonatal mortal- ment, rehabilitation and development phases. After
ity falls, resources need to be available to deal with the the initial disaster, high mortality rates are usually due
increased morbidity that will occur in survivors. Such to diarrhoeal disease, cholera and dysentery, measles,
morbidities include malnutrition, chronic lung disease malaria, meningococcal disease, tuberculosis, neonatal
and neurological disease among survivors of prema- causes, trauma, malnutrition and micronutrient defi-
turity. Mechanisms to follow up very low birth weight ciency. High rates of mental health problems, including
babies in low income countries are needed to optimize post-traumatic stress disorder, depression and anxiety,
outcomes. have been reported in many studies of children living
in refugee camps or exposed to ­violence or armed con-
flict. At the end of 2009, there were 10.4 million refu-
gees under the ­mandate of the United Nations High
Commission for Refugees (UNHCR), 4.6 million of
Adolescent health whom came from Afghanistan and Iraq. In addition,
The health of young people (defined by WHO as there were 27 ­ million conflict-­generated, internally
aged 10–24 years) in developing countries has rela- ­displaced persons, mostly in these two c­ ountries and
18
tively recently been recognized as a high priority. in Somalia.
 Child health in a global context 1.2
Many factors impede the delivery of health care in
such situations, including lack of human resources International conventions and
and referral services, security constraints, poor super- child health
vision and coordination, and failure of integration
with local health services or transition to a sustain- There have been several United Nations (UN) con-
able health system. In addition, lack of comprehensive ventions designed to improve global child health in
guidelines and approaches, especially for the manage- the last 30 years. The Declaration of Alma Ata in
ment of neonatal problems, HIV infection, mental 1978 was one of the first to identify primary health
health problems, and child and sexual abuse, limit the as being crucial to child survival, and stressed that
impact of health care in these situations. improvements in food security, clean water, sanita-
tion, ­appropriate housing and education were c­ rucial
to progress. In 1990, the UN Convention on the Rights
of the Child stated that all children have the right to
Climate change and child health the highest attainable standard of health, and access
Like poverty, climate change has a disproportionate to care and medicines when they are sick, and held
effect on the health of children, and is a major threat to governments responsible for providing comprehen-
progress in child survival. There is increasing evidence sive health services. The mantra of the Declaration of
that many of the main killers of children (malaria, diar- Alma Ata was ‘Health for all by the year 2000’. Sadly,
rhoea and malnutrition) are highly sensitive to climatic for many reasons – the emergence of the HIV/AIDS
conditions. The regions of the world affected by malaria pandemic, lack of political commitment, inadequate
and dengue are expected to extend. In many Asian coun- financing, a drastic human resources shortage and
tries cholera is no longer a seasonal disease but occurs inadequate attention to non-health-sector elements –
year round, likely because of increases in sea tempera- this ambitious aim did not come close to being real-
tures. Mass displacement because of rising sea levels in ized. In 2000, the UN developed the Millennium
low-lying Pacific island nations and food shortages in Development Goals (MDGs) plan, which was signed
other countries because of reduced arable land have their by all UN member states and set specific goals in eight
greatest effects on children in the poorest communities. areas (Box 1.2.1). The fourth MDG calls for a reduc-
tion in child mortality. Specifically, MDG-4 states that
countries should aim to reduce child mortality by two-
The effect of poor child health on thirds of what it was in 1990, by 2015. Some national
governments have signed up to a modified target for
communities MDG-4 to reflect what is feasible and realistic. Other
Childhood disease has major effects on the economy MDGs are crucial to child health and development
and lives of families, communities and developing including: to halve the proportion of the population
nations (see Clinical example). Poor health among living on less than US$1 per day; to ensure universal
children or a family member is a common reason for primary education; to eliminate gender disparity in all
families sliding into poverty. For affected families, the levels of education; to reduce by three-quarters the
cycle of poverty, poor nutrition, chronic ill-health and maternal mortality ratio; to reverse the rising incidence
low educational attainment is common. of HIV, malaria and other diseases; to halve the pro-
portion of people without sustainable access to safe
drinking water and sanitation; and targets in develop-
Clinical example ment aid, market access, debt relief, employment and
information access. Each of these goals has specific
Chinua is a 10-year-old Nigerian boy who has targets and indicators that can be used as benchmarks.
sickle cell disease (HbSS). He has had repeated
episodes of severe acute vaso-occlusive crises,
and recently had a stroke, which left him with
a mild left hemiparesis. Previously he had Salmonella
osteomyelitis of the right femoral head. He walks with a
Evidence for effective
crutch made by his father. He must take penicillin and interventions in reducing child
folic acid daily. A doctor suggested that he could also take
hydroxycarbamide (hydroxyurea) to reduce the frequency of mortality
crises, but Chinua's family cannot afford this. His mother, a In 2003, The Lancet published a series on child
weaver, can no longer trade because of Chinua's frequent
need for hospitalization and care at home, and his father
­survival, outlining the evidence for effectiveness of
has used all the spare cash they had for transportation to the interventions in reducing child mortality. Twenty-
district hospital, clinical care and medicines. three interventions (15 preventive and 8 curative)
19
aimed at the commonest causes of child m
­ ortality had
 1.2 CURRENT PAEDIATRICS

Box 1.2.1 The eight Millennium Development Goals and key indicators

1 Eradicate extreme poverty and hunger 5 Improve maternal health

• Population below $1 a day (%) • Maternal mortality ratio (modelled estimate, per 100 000
• Percentage share of income or consumption held by live births)
poorest 20% • Births attended by skilled health staff (% of total)
• Prevalence of child malnutrition (% of children under 5)
• Population below minimum level of dietary energy 6 Combat HIV/AIDS, malaria and other diseases
consumption (%) • Prevalence of HIV, female (% ages 15–24)
• Contraceptive prevalence rate (% of women ages 15–49)
2 Achieve universal primary education • Number of children orphaned by HIV/AIDS
• Net primary enrolment ratio (% of relevant age group) • Incidence of tuberculosis (per 100 000 people)
• Percentage of cohort reaching grade 5 (%)
• Youth literacy rate (% ages 15–24) 7 Ensure environmental sustainability
• Forest area (% of total land area)
3 Promote gender equality • Nationally protected areas (% of total land area)
• Ratio of girls to boys in primary and secondary education (%) • GDP per unit of energy use (PPP $ per kg oil equivalent)
• Ratio of young literate females to males (% ages 15–24) • Carbon dioxide emissions (metric tons per capita)
• Share of women employed in the non-agricultural • Access to an improved water source (% of population)
sector (%) • Access to improved sanitation (% of population)
• Proportion of seats held by women in national parliament (%)
8 Develop a Global Partnership for Development
4 Reduce child mortality • Youth unemployment rate (% of total labour force aged
• Under-5 mortality rate (per 1000) 15–24)
• Infant mortality rate (per 1000 live births) • Fixed line and mobile telephones (per 1000 people)
• Immunization, measles (% of children under 12 months) • Personal computers (per 1000 people)

high-grade evidence for effectiveness (i.e. large ran- In recognizing that primary health care will have
domized c­ ontrolled trials and/or systematic reviews). an optimal impact on child mortality only if there are
These interventions were selected for being low cost effective referral services, WHO has produced comple-
and having potential for implementation at near- mentary guidelines on paediatric care for district or
universal scale in low-income countries. Some inter- provincial hospitals. These guidelines emphasize that
ventions protect against deaths from many causes. For diagnosis and drug treatment are not sufficient for
example, breastfeeding protects against deaths from optimal care of the seriously ill child, and that triage,
diarrhoea, pneumonia and neonatal sepsis, whereas supportive care (including fluids, oxygen, nutrition),
insecticide-treated materials (bed-nets, sheets, etc.) monitoring, discharge planning and follow-up are also
protect against deaths from malaria and also reduce essential. These processes of care were found to be
deaths from p ­reterm delivery. However, with the deficient in audits of practice in many developing and
exception of breastfeeding (estimated global ­coverage transitional countries, and there is now good evidence
of 90%), global coverage of known effective inter- that mortality rates can fall substantially when these
ventions for reducing child deaths from common issues are addressed.
­conditions is low. To move closer to MDG-4 in all countries by 2015,
To promote a comprehensive model of care for the the focus will need to be on achieving universal access
sick child, in 1995 WHO developed the Integrated to health services and on improving equity. Limited
Management of Childhood Illness (IMCI). IMCI resources may need to target interventions towards
is a case management and training strategy that marginalized populations within low- and middle-
focuses on primary health workers managing the income countries. These populations include the poor,
most important causes of childhood illness, includ- refugees and internally displaced persons, families
ing identification and treatment of children with mul- ­living in remote rural areas and urban slums, d ­ isaster
tiple pathologies. Evaluation of IMCI in Bangladesh areas and war zones, ethnic minorities, Indigenous
and Tanzania showed improvements in the quality populations, new immigrants, AIDS orphans, child
of case management, and increased health-service workers, child soldiers and abandoned children. There
­utilization, increased rates of breastfeeding and nutri- is also a need for an ‘enabling environment’ for child
tion ­practices, and lower prevalence of stunting. Now, health and survival: political commitment, a­ dequate
more than 90 countries have adopted the strategy, funding, human resources, community awareness
20
albeit often in pilot projects with moderate coverage. and support, improvements in water, sanitation and
 Child health in a global context 1.2
the environment, and improvements in education
Box 1.2.2 Principles of global child health
and gender equality. The quality of care provided in
health facilities and the nature of interactions between 1. Focus on children who have least access to services
health systems, families and communities have major 2. Support simple, low-cost interventions that can achieve
­consequences for child health, human rights, poverty high coverage
alleviation and development. 3. Improvement in nutrition is vital
4. Support national and local services and institutions, and
deliver services where possible through existing local
structures
How can child health 5. Seek out, respect and support local human capacity; it is
often greater than you think
professionals in developed 6. Local ownership of ideas and strategies is essential for
sustainability
countries contribute to global 7. Support multidisciplinary and multisector collaboration
child health? 8. Use a framework that incorporates human rights and
equity
There are many pathways to meaningful contributions 9. Critical evaluation of programmes is crucial to the
to global child health. However, they all require expe- efficient and ethical use of resources
rience, technical expertise, perspective and cultural 10. Be patient – progress that incorporates these principles
may not be fast, but it may be longlasting
understanding. These prerequisites can best be gained
by an extended time living and working in a developing
country. This early experience, and the eventual expres-
sion of this work, can be immensely varied: working contributions to global child health, as part of their
as a medical officer, nurse, teacher or researcher in a core work. For others, financial contributions to child
government hospital, university, public health service, health programmes in developing countries may be
mission hospital, research institute, non-governmental a preferred option. Whatever the pathways, there are
organization working with children, UN organization several principles of international health collaboration
or collaborative institute for child health. A contribu- that should be followed (Box 1.2.2).
tion can be made from virtually any specialty, but clini- The highest priorities for paediatrics in the 21st
cians familiar with Western models of curative health century are located firmly in the poorest areas of
care need to appreciate the central importance of pub- the developing world. Solutions will be largely local,
lic health. Skills in teaching, epidemiology, research although regional and global support for local ini-
and infectious diseases are especially valuable. In the tiatives and priorities is essential. Increasingly this is
forthcoming decades, increasing numbers of doctors being recognized by individual health professionals,
and other health professionals from developed coun- education and research institutions, medical journals
tries will make substantial, ongoing and career-long and professional societies in developed countries.

21
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 2
PART

CLINICAL
ASSESSMENT

23
 2.1 The clinical consultation
Mike South, Sean A. Beggs

The clinical consultation is the central act of medicine, it comes to recording your notes. It facilitates recording
with its primary aim being to arrive at a diagnosis and them in a clear and concise manner that is easily under-
management plan that will assist the patient. For chil- stood by others involved in the care of the patient.
dren, as with adults, there are three main pillars for S – subjective: the history as given by the carers
arriving at a diagnosis, namely history, examination and child
and investigations. In most presentations, the majority O – objective: physical examination and results of
of the information required for a diagnosis comes from investigations
the history, with a smaller amount coming from the A – assessment: primary diagnosis and differential
physical examination. In many cases, no investigations diagnosis
are required. A common paediatric scenario is one in P – plan: immediate and long-term plan to manage
which a difficult diagnosis is able to be made by an expe- the patient.
rienced clinician who simply takes a thorough history. When planning your approach to a paediatric consul-
tation it is important to understand how children dif-
fer from adults. Consideration needs to be given to the
age and developmental stage of the child, the setting
Practical points and acuity of the presentation and how to best estab-
lish rapport with the child and family.
• Skills in history-taking and examination cannot be
acquired adequately by reading a textbook. Ensure you Age and developmental stage of the child
have lots of practice with children of all ages and in
different clinical settings. The approach to clinical history-taking and physi-
• Learn to appreciate what constitutes normal growth, cal examination of children differs from that used
development and physical findings on examination. Take for adults; it also differs with the age and develop-
every opportunity you can to observe normal children mental stage of the child. These differences relate to
(who might be visiting the hospital or community health the fact that children are growing and are acquiring
centre, in the cafeteria, or even travelling on public
transport). Try to guess their ages from your observations
new developing skills. There is also generally a third party
(based on size, development and behaviour) and then ask (parent or caregiver) present, providing a significant
how old they really are. component of the history. Therefore the description of
• Adapt the content and techniques of history-taking and symptoms may be modified by the parent's perceptions
examination to fit the age of the child and the urgency of or interpretations, and by factors such as anxiety. These
the medical problem. factors vary with age also. You will need to modify your
• Learn to be flexible in your approach – some patients will approach to establishing rapport with the patient and
need to be examined on the floor, while in a play area, or
from a distance.
how the examination is conducted according to the age
and developmental stage of the patient. There are dif-
ferences in the techniques of physical examination and
in expected findings at different ages. Different aspects
of the history will require emphasis at different ages.
Planning your approach For example, details of the pregnancy and birth are rel-
evant in infancy, whereas immunizations, growth and
To ensure you gain as much information as possible it is
developmental milestones are important in preschool-
important to have given consideration to how you will
aged children, and behaviour and schooling need to be
approach the consultation. The basic structure of the
explored in older children.
clinical consultation is to take an accurate history and
elicit all the relevant clinical signs in order to generate
Acuity of the presentation
a differential diagnosis list and management plan. The
use of a framework such as the SOAP note (below) is of The urgency of the presenting problem will impact
great assistance when planning your initial approach to significantly on how the consultation is conducted.
24
a consultation. This framework is also of great use when In an emergency presentation, urgent treatment will
 The clinical consultation 2.1
obviously take priority over obtaining a complete his- Ask what name the child likes to be called by. How
tory. It is, however, usually appropriate to return to much you should talk directly to the child at this
aspects of the history at another time. For example, a stage will vary with the age of the child and with your
complete past history and developmental assessment assessment of how relaxed the child is. Some chil-
would not be necessary in a 4-year-old presenting with dren respond well to questions and comments about
acute diarrhoea and vomiting, prior to commencing their favourite sports team, school or a toy they have
rehydration. However, it would be essential if the pre- brought with them, whereas others are shy and anxious
sentation was because of parental concern over the if you address them directly. Learn to read children's
child's speech. In other cases it may be appropriate to responses and adapt accordingly. Young children may
split the consultation into more than one session. This is initially be very shy and cautious, and become much
often appropriate for the assessment of more complex more confident and interactive later in the consultation.
problems. Young children often become bored, tired, Children's behaviour will often reflect how their par-
hungry or irritable if a consultation lasts more than ents are feeling. It is common for parents to be anx-
about 30 minutes. This can limit their ability to con- ious when attending a medical consultation. If you can
centrate or cooperate with the assessment. form a good relationship with the parents, they will
feel more at ease during the consultation and you will
also have a better relationship with the child.
Clinical example Sometimes it is appropriate to reassure the child at the
start that nothing unpleasant is going to happen during
Louise, a 4-month-old girl, was the first baby
in her family. She was taken to the general
the consultation (e.g. no blood tests or ‘needles’). The
practitioner by her mother, Mary, who was child may associate visits to the doctor with memories
very anxious because she felt that her baby of past uncomfortable experiences. Never hesitate to
was constipated, with a bowel action only once every explain why you are asking a certain question or why
3 days. Mary was worried that this was because she was you are performing a particular part of the examination.
not producing enough breast milk to meet Louise's needs.
Mary had been advised by a relative to give Louise laxative
drops and to switch to bottle-feeding. The setting
Careful history-taking revealed that Louise was feeding
well and was passing a partly formed stool every third The physical environment makes a big difference to
day without difficulty. There were no abnormalities on how children feel. An adult may tolerate undressing
examination. Her growth chart showed that she was gaining in a cold room to be examined, but a 2-year-old will
weight well and was tracking just above the 50th centile probably cry. A bright, colourful room with pictures
for her age. Mary was shown the chart to reassure her that on the wall and toys on the floor is much more condu-
her baby was thriving. It was explained that Louise's stool
cive than a ‘sterile’ clinical environment. A good range
frequency was within the normal range for breastfed babies.
Mary was encouraged to continue breastfeeding. of toys, drawing materials, puzzles and other activities
for all ages will be helpful.

Establishing rapport with the child and family Observation

Your success in obtaining valuable information from It is important to remember that you can gain a signifi-
the history and physical examination will depend on cant amount of information regarding a child's state of
establishing a good relationship with the child and health and development, prior to launching into the for-
family. The parents need to know who you are, and mal history and examination, simply by observation. It is
to understand the purpose and likely outcome of the important when planning your consultation to allow time
consultation. The child needs to feel comfortable in to sit back and observe the child's interaction with their
the environment and with you, particularly as you parent/carer and the environment. You should be able to
move on to the physical examination. Stranger anxiety, assess whether the child looks well or unwell, is appro-
especially in children from about 8 months to 5 years priately grown and ­developmentally appropriate for age.
of age, can be a significant obstacle. Experience and Your ability to do this will increase with experience.
understanding help to overcome this.
Introduce yourself to the parents and, for almost all
Referral information
ages, to the child. Explain who you are and your role
in the child's care. A common concern from parents You will often have referral information from another
of recently hospitalized children or children attending doctor in the form of either a referral letter from a
clinics is that they met many doctors and other health general practitioner or the notes from the emergency
professionals, not really knowing who they were or department doctor. You need to take this informa-
25
who was ‘in charge’. tion into consideration, but not trust it implicitly.
 2.1 CLINICAL ASSESSMENT

It is vital that you assess the child yourself and deter- iliac fossa in appendicitis). Parents know their children
mine what you believe is the cause of the problem. best and are generally good judges of when something is
Parents/patients often dislike having to repeat them- wrong. Their concerns should be taken seriously.
selves several times, so it is important to explain clearly You then need to explore the symptoms in more
why you are asking them to repeat the story again. detail; for example, if the presenting symptom is
cough, you will want to learn its character, whether it
is repetitive, whether it occurs under certain circum-
stances and whether it is moist or dry. When seeking
Taking the history extra detail or clarification, ensure your questions are
As mentioned above, the history is the most impor- open (e.g. ‘Can you tell me about his bowel actions?’)
tant component of the clinical consultation, as this is rather than closed (e.g. ‘So he has not had any diar-
where the majority of information for making a diag- rhoea?’). It is important to gain information from the
nosis comes from. The basic outline or structure of child as well as the carer. How you go about this will
paediatric history is the same as in adult medicine, but depend on the age of the child. For an infant it will be
with the need for some variation in the areas that are by observation alone, whereas an adolescent may well
focused on. This structure includes the following areas, be the primary provider of the history.
which are described in more detail below: Be sure that the parent understands the terminol-
• Presenting problem ogy you use and always avoid medical jargon. It is also
• Past history important that you ensure you and the parents have the
• Systems review same understanding of terms that are used in everyday
• Family history language but are also medical. For example, when a
• Social history parent uses the term diarrhoea they may mean loose,
• Developmental history but not frequent, stools. Or when they say, ‘He vom-
• Behaviour ited bile’, are they referring to yellow gastric juices,
• Sleep which is often the case, or do they mean true bright
• Immunizations green bile? You will want to enquire about appropriate
• Medications epidemiological features such as whether anyone else
• Reviewing your understanding of the history. in the family or other contacts has had similar symp-
It is worth remembering that a number of factors may toms, or whether anyone at home is a smoker.
impact on the taking of a paediatric history, such as how Summarize your understanding of the symptoms
distressed the child is, the level of parental anxiety and and discuss this with the child and their parents once
sleep deprivation, which is common when looking after you feel you have a complete picture of the present-
sick children. There will also be cases where the family ing problems and symptoms, to ensure that you have
do not speak English and it is vital to use an interpreter. understood the information correctly and also to allow
further information to be added if needed.

The presenting problem

Start by asking the parent (and/or child) about the cur-
Clinical example
rent problem or problems. It is important to find out what
they perceive to be wrong and why they have chosen to William, a 5-year-old boy, was brought by his
seek medical attention at this time, and to get this infor- parents for assessment because they noticed
mation in their own words. It is also useful to ask what that he was tired each day in the late afternoon.
they believe the cause of the problem may be. Remember He would lie on the sofa for up to an hour and
to use open-ended questions such as: ‘Why have you be uninterested in playing during that time. Following this, he
would seem to be his normal self.
come to see me today?’ Allow the parent/child to provide This had been going on for nearly a year, since he
the whole story before interrupting to clarify symptoms started school. The rest of the history and examination
as this will disrupt their flow and may result in the omis- were unremarkable. The parents’ concerns seemed out
sion of key information. Understanding the sequence of proportion to what is fairly common behaviour in early
and evolution of symptoms can be just as important as school-age children. When asked why they had chosen
otherwise listing the symptoms themselves. Ensure you to seek a medical opinion now, they revealed that a child
of one of the mother's work colleagues had recently been
get the story from the beginning. Questions such as:
diagnosed with leukaemia, and tiredness had been one of
‘When was she last completely well?’ can be very help- the features of her illness. The parents’ major concern was
ful. The pattern of evolution will often reveal the diagno- that William might have the same diagnosis.
sis (e.g. central abdominal pain, later moving to the right
26
 The clinical consultation 2.1
Questions should be relevant to the current p
­ roblem
Practical points and the age of the child, rather than a long list of
routine items. Ask about recent travel or potential
• To obtain the trust of a child, you also need to gain the environmental exposures if they are relevant to the
trust of the parent/s. presenting problem.
• Do not use abbreviations or medical jargon during
discussion with the family (say ‘blue’ rather than
‘cyanosed’ and ‘breathing difficulty’ rather than Family and social history
‘dyspnoea’).
• When the family use descriptions such as ‘wheezing’ or These are in fact separate but closely aligned, and
‘croupy’, make sure that these words mean the same to therefore are often enquired about at the same time.
them as they do to you. The young child's world is the family and it is impor-
tant to obtain an understanding of the family and
social contexts of the child's illness and management.
Past history Ask about the age and health of the child's parents
The initial enquiry about the past history seeks to gain and siblings. Who else lives in the same household,
information relevant to the current problem and age and who provides most of the child's care? Does the
of the child. It is important to ask whether the cur- child live in more than one household, as is often
rent problem has ever occurred in the past and about the case when parents are separated? Does the child
past illness that might relate to the current presenta- attend day care, kindergarten or school? Is there
tion (e.g. a past history of meningitis will be very rel- a family history relevant to the child's presenting
evant for a 2-year-old who now presents with a seizure problems?
disorder). Then move on to the child's general state of Find out about the family's housing and eco-
health. Are they usually active and healthy? Have they nomic situation. Are the parents employed? Do they
had any other significant illness, operations or hospital receive any financial allowances or community ser-
admissions in the past? vices? Look for factors that might adversely affect
For infants, it is important to obtain a history of the the child's health (e.g. smoking by household mem-
mother's pregnancy (her health, nutrition, use of med- bers), or that may influence management decisions
ications, alcohol intake and smoking during the preg- (e.g. if the family lives a long way from hospital and
nancy, etc.), details of the birth (gestation, problems has no car).
during labour, breech delivery, use of forceps or cae- It is usually useful to draw a brief family tree
sarean section) and the condition of the infant at birth (Fig. 2.1.1).
(including the Apgar score, if known, and the need for
any medical interventions such as oxygen therapy).
What were the birth weight and other measurements?
Ask about the infant's course in the first few weeks, Frank
including any illness and details of feeding and weight 78
Dementia
gain. Parents may have the child's health record, which Lives with family
will provide many of these details. Simple questions Smoker
such as, ‘Was the mother allowed to hold her baby
immediately after birth?’ and ‘How soon was the baby
discharged from hospital after birth?’ can probe for David Maria
problems. In young children, the early feeding history 38 36
Asthma Sciatica
is also important. Printer-night duty Post-natal depression
Details of the pregnancy, birth and early course of Part-time hairdressing
postnatal life are usually of less significance for an
older child presenting with an acute illness. They will
be important, however, for an older child if the pre-
senting problem is neurological or there is a concern
Dominic Claire John
about developmental progress. 9 3 15 months
Severe cerebral Moderate Patient
palsy eczema
Systems review
Fig. 2.1.1 This brief family tree reveals a lot about the genetic
A brief check for other symptoms should be under- and environmental factors that affect John, who now presents
taken, using the usual organ systems approach. with recurrent cough and wheeze.
27
 2.1 CLINICAL ASSESSMENT

language and special senses, and personal–social. This

Clinical example assessment has its greatest importance in the early
years of life to enable early detection of developmental
Mrs Baker brought her 10-year-old daughter, difficulties (e.g. hearing impairment, motor difficulties
Ruth, for assessment. Ruth had previously been
due to cerebral palsy) and allow early intervention.
an outgoing and active girl but recently had
seemed tired and listless, had lost her appetite
For older children, ask about progress at kinder-
and would often miss days of school because of headaches garten or school, including parents’ assessment as to
and abdominal pain. Mrs Baker was concerned that Ruth motor skills and cognitive abilities in comparison with
had an underlying illness such as glandular fever. Mrs Baker siblings and peers. For school-aged children, enquire
had had glandular fever herself when she was in her about special abilities that their child exhibits both in
teenage years. learning and in skills in sports or other activities. Ask
As part of the history-taking, enquiry was made about the
children what they enjoy most in their learning activi-
family's current circumstances. Ruth's parents had recently
separated, and Ruth, who had been close to her father, saw ties (‘What things are really fun to do?’) and in what
him only occasionally. Unfortunately, her parents were no activities they see themselves as having special abilities
longer on speaking terms. On examination, Ruth appeared (‘What are you really good at?’).
well although she was rather withdrawn. Blood tests did not If this screening raises concerns, a more detailed
suggest any evidence of glandular fever. Ruth's symptoms developmental assessment is required (see Chapter 2.2).
were due to the changes in her parents’ relationship and
she was assisted by counselling and support from a child
psychologist. Behaviour
A brief history of the child's general behaviour is
appropriate. Sometimes a perceived behavioural dif-
Growth and development
ficulty is the presenting problem and a more detailed
One of the aspects of childhood that clearly differentiates history is necessary (see Chapters 4.1–4.3).
it from adult life is that children are growing physically
and acquiring new developmental skills. The achieve-
Sleep
ment of a child's full growth and developmental potential
is a central component of childhood and it follows that Sleep issues can often be a major concern for parents
progress in this area requires careful assessment during of young children. Poor sleep has been shown to have
the clinical consultation. During the history you should significant impact on a child's behaviour and devel-
assess this via questions regarding the parents’ perception opment. It is important always to ask some screening
and later confirm during the examination phase. questions regarding sleep; if these raise any concern, a
In infancy, growth is assessed mainly by checking for more detailed history should be taken.
adequate weight gain, whereas in older children linear
growth and appropriate body weight are both assessed.
Medications
Where possible, birth measurements and any other pre-
vious growth measurement should be plotted on appro- Enquire about current and past medications, includ-
priate length/height, weight and head circumference ing any adverse reactions and suspected drug allergies.
centile charts (see Chapter 19.1). This provides two types Ask specifically about prescription medications and
of information: an estimate of growth achievement in over-the-counter items. Complementary or alternative
comparison with that expected for the ‘normal’ popula- therapies are now frequently used in children, but par-
tion, and also growth progression with time in relation ents often forget or are reluctant to mention their use.
to expected genetic potential by observing ‘tracking’
along centile channels. Measurements are recorded most
Immunization status
commonly in the parent-held child health record. An
appropriate nutritional intake is an obvious and impor- Full details of past immunizations should always be
tant prerequisite for normal growth: you should find out obtained. Don't just ask: ‘Is she up to date with immuni-
the usual daily pattern of food intake (breastfeeding in zations?’ or ‘Has he had all his needles?’ The answer you
early childhood, type of formula feeds and intake pat- get will often be ‘yes’ and may be incorrect. Take time
tern in later childhood) (see Chapter 3.3). to go through what has been administered and compare
You should also ask questions to ascertain whether this with the recommended schedule. Again, the child
developmental progress is within normal expectations. health record will be useful if available. Remember that,
This can be done for young children by asking specific unless there is a specific contraindication, every clinical
‘screening’ questions that determine developmental consultation should be seen as an opportunity to check
progress at hallmark ages for each of the four major immunization status and to offer immunizations that
28
areas of development: gross motor, fine motor/adaptive, are due or have been missed (see Chapter 3.5).
 The clinical consultation 2.1
Closing questions Privacy during physical examination is just as
important to children as to adults. You need to be
Complete the history-taking by providing the parent
friendly and relaxed, with a quiet and calm voice, and
and child with the opportunity to add extra informa-
use gentle, unhurried physical movements. In young
tion that may have been left out and to air their own
children you will often have to be opportunistic in your
concerns about causes of the presenting problem. The
examination and be prepared to vary the sequence of
following closing questions will sometimes bring out
the examination according to what the child is doing,
very important information:
examining them where they are most comfortable. For
• Is there anything else that is worrying you? example, if a 2-year-old is asleep on his father's shoul-
• Is there anything else I should know or anything der, take the opportunity to auscultate while they are
I have forgotten to ask you?
quiet. In young children, ask yourself what are the
• Do you have any ideas of your own about what may most important items that you need to examine and do
be causing your child's symptoms?
these first rather than adopting the more traditional
sequence of examination used in adults and older chil-
dren. Leave any potentially distressing components
Practical points until last (e.g. examination of ears and throat).You
may not be able to undertake all aspects of the exami-
• Always undertake a brief but accurate assessment of nation at one time because it is tiring or frightening for
growth and development at any consultation. the child. Do not push the child; be prepared to come
• Remember to ask about all types of therapy used. back at a later stage to continue. Undressing a young
Specifically enquire about complementary or alternative child completely will often upset him or her, and you
medications and other therapies. should consider what it is necessary to expose accord-
• Always take the opportunity to check that the child has ing to the clinical situation.
received all his/her immunizations at the appropriate ages.
• The closing questions will often be the ones to bring out
Hand hygiene is also very important. It is vital that
the parents’ deepest concerns regarding their child's you wash your hands, or use an alcohol-based hand
problem. Don't omit this important opportunity, and leave rub, before and after every patient contact. This is the
yourself enough time to ask. single most important measure to prevent hospital-
• Be observant of the child's physical activities and the acquired infections.
child–parent interactions during the history-taking. These
unstructured observations are an important part of the
information-gathering process.

Clinical example

Ravi, an 18-month-old boy, presented to hospital

The physical examination with a history of cough and noisy breathing. His
elder sibling had recently had a cold. Ravi was
Introduction obviously frightened and upset when placed on
The purpose of the physical examination is to pro- the couch for the physical examination. He cried and clung
to his mother's blouse when the emergency department
vide additional information to aid in the diagnosis,
resident tried to undress him.
assessment of the response to therapy, clues to co- David, the paediatric registrar, suggested that Ravi be
morbidities, and important screening data on growth placed on his mother's lap while he observed him from a
and development. By the time you are ready to move short distance. The nurse handed Ravi a brightly coloured toy.
to the examination you need to ensure you have gained He stopped crying and started to examine the toy. David was
as much information as possible from observation. able to note that Ravi was well grown, did not look seriously
This is a very important technique with young chil- unwell and was alert. He was pink in room air, there was a
clear nasal discharge, and he had an obvious barking cough
dren as they will not understand why they are being
and mild stridor when resting. David asked that Ravi's mother
approached and touched by a stranger. Shyness and lift his upper clothing to expose most of his chest. Ravi looked
stranger anxiety may limit their cooperation and some apprehensive but did not cry. David was able to observe good
will simply refuse any physical contact. This is par- symmetrical chest movements with a respiratory rate of 22 per
ticularly the case for children between approximately minute, and there was minimal indrawing of the intercostal soft
9 months and 3 years of age. Obtaining cooperation tissues. David approached with his stethoscope but again Ravi
looked as if he was about to cry. David knew that auscultation
and a successful examination requires skill, understand-
of the chest would not add much additional useful diagnostic
ing and practice. Don't be surprised or concerned if you information in this setting and so he desisted.
are unsuccessful sometimes: this also happens to expe- Ravi was diagnosed as having viral croup of mild to
rienced paediatricians. Try coming back to the exami- moderate severity. 29
nation at a different time or with a different approach.
 2.1 CLINICAL ASSESSMENT

Most paediatricians develop their own techniques or during the physical examination as a guide only – don't
‘tricks’ for obtaining a child's cooperation with aspects use it as a checklist for every child.
of the examination. Some techniques rely on distrac-
tion (e.g. producing a previously unseen toy just prior
General observation and behaviour
to auscultation of the precordium). Some may use an
incremental approach to obtaining the child's con- What are your first impressions of the child? Does she
fidence. For example, in an anxious child, one might look well or unwell, is she happy and relaxed, or does
commence auscultation of the lungs by placing the she seem tense and uncomfortable? Is she in pain? Is
stethoscope on a less threatening area than the chest, she of normal appearance or different from what you
such as the child's thigh, then moving it on to the chest expect? Is she normally grown or small/large/obese/
once the child has learned that it is not uncomfortable. malnourished? Does she respond normally and in
Alternatively one might auscultate the father's arm or an age-appropriate way to her parents and siblings?
back first so the child can see that nothing unpleasant How does she respond to you and to the surround-
is involved. With practice you need to learn methods ings? Is her understanding and language or other com-
that suit your own style of interacting with children of munication age-appropriate? Does she appear to hear
various ages. These skills cannot be learnt simply from and see normally? Is there anything obvious such as
a book but must be gained from experience of working noisy breathing, increased work of breathing, jaun-
with children of various ages. dice, cyanosis, bruising, an abnormality of limb move-
It is important to emphasize that successful physical ment, skin rash or abnormal pigmentation? Does she
examination of children is not only about ticking boxes move/crawl/walk/run/climb normally? Are her fine
in a checklist. Knowing exactly what to examine in any motor movements while playing, drawing or getting
given situation, how to perform the examination tech- undressed and dressed normal?
niques in children of differing ages and how to inter- These initial impressions can be of great importance
pret the results are much more important, and come and provide useful clues for your overall assessment
only from experience in caring for children. Box 2.1.1 of the nature of the child's health problems and their
includes a list of the items that are commonly included impact.

Box 2.1.1 Items commonly included in the physical examination

• Height* • Head circumference • Respiratory rate*

• Weight* • Pulse rate* • Blood pressure*
General appearance Head
• Looks well/unwell/sick/very sick* • Size/shape/posture
• Alertness* • Fontanelles: presence/shape/tension
• Distressed/cooperative • Bruit/percussion
• General body build
• Overall development including speech Eyes
• Facial appearance/dysmorphism* • Appearance/blinking/ptosis/nystagmus
• Posture, movement • Visual acuity/fields
• Interaction with parents* • Ocular movements/squint
• Lids/discharge
• Fundoscopic appearance
Skin • Light and corneal reflex
• Colour/pigmentation/jaundice/cyanosis/pallor*
• Bruising/petechiae/rashes/scars Ears
• Turgor • Position/shape
• Visible blood vessels • Discharge
• Subcutaneous fat • Hearing*
• Appearance of tympanic membranes
Nails/hair
Nose
• Cyanosis/pallor/clubbing
• Shape/flaring with respiration/discharge/bleeding
• Haemorrhages
• Patency of airway/mucosal appearance/polyps
• Distribution and colour of hair
Mouth/lips/teeth/gums/palate/pharynx
Lymph nodes • Colour of lips, tongue and buccal mucosa
• Size/mobility/tenderness of nodes in each group (cervical, • Presence of exudates/coating/ulcers
occipital, axillary, inguinal, etc.) • Lip swelling or scaling/fissuring
30
Continued
 The clinical consultation 2.1
• Number of teeth and presence of caries • Enlarged organs/palpable mass
• Breath odour/salivation • Anus/rectum (avoid examination in children unless
• Petechiae/bleeding specifically indicated)
• Colour of pharyngeal mucosa
• Size, colour and presence of exudate on tonsils Genitalia
• Development (Tanner stage)
Chest/lungs • Presence of testis in scrotum
• Shape/symmetry/deformities (including Harrison's sulcus, • Scrotal swellings/hernia
rickety rosary) • Urethral/vaginal discharge
• Expansion of chest and pattern of breathing • Evidence of injury
• Soft tissue indrawing with respiration
• Pattern and rate of breathing
Spine
• Cough/stridor/wheezing
• Posture/deformity/hair/dimples/tenderness
• Percussion note
• Breath sounds/added sounds
Limbs
Breasts • Deformity/contractures
• Development (Tanner stage) • Muscle development
• Hip dislocation (see Chapter 8.1)
Heart • Joints: tenderness/swelling/range of movement
• Appearance of precordium: deformity/activity • Temperature/colour
• Pulse: rate/rhythm/strength/nature
• Blood pressure Nervous system
• Apex beat/cardiac impulse/thrills • Alertness/responsiveness/general ability
• Percussion of cardiac dullness • Abnormal movements/gait/posture
• Heart sounds/added sounds • Tone/power/coordination/symmetry of movement
• Features of cardiac failure • Reflexes/primitive reflexes
• Special sensory examination
Abdomen • Sensation
• Shape/distension/visible mass/movement with respiration • Cranial nerves
• Visible veins/peristalsis
• Percussion/ascites Developmental assessment
• Tenderness on palpation • See Chapter 2.2

Items marked with an asterisk (*) are usually included, whereas others will be noted in selected situations only.

Measurements
Except in emergencies, measurement of weight and
height (or length) and plotting these variables on cen-
tile charts should be a routine part of the examination
for all children. Children are ideally weighed in only
light undergarments, and in babies the nappy should be
removed. In children under 2 years of age linear growth
is assessed by measuring a lying length (Fig. 2.1.2), and
the head circumference should also be measured and
plotted. Length is best measured using a horizontal sta-
diometer. Head circumference should be measured using
Fig. 2.1.2 Measuring the length of a young infant.
a tape measure that will not stretch. The aim is to mea-
sure the child's largest head circumference to the near-
est millimetre. As a guide, place the tape measure above a teenager, and the required information can often be
the ears, midway between the eyebrows and the hairline gathered from history and self-report rather than direct
at the front and on the occiput at the back, then adjust inspection (see Chapters 3.11 and 19.1).
to obtain the maximal measurement. Repeat this once
or twice and record the largest measurement. After 2
Specific examination
years of age, linear growth is assessed by vertical height,
and is best done using a stadiometer. In adolescents, it is It is assumed that the reader already has a good
important to assess the pubertal stage. This is obviously understanding of normal examination technique and 31
a delicate and potentially embarrassing ­examination for expected findings for adult patients. There are many
 2.1 CLINICAL ASSESSMENT

differences in the techniques and expected findings in harsher on auscultation than in older children and
children; these are emphasized below. adults. These normal differences in auscultation find-
ings are even more pronounced in the upper parts
of the right lung, sometimes leading inexperienced
Vital signs
examiners to suspect pathology in this area in young
Normal ranges for heart rate, respiratory rate and children when in fact the breath sounds are normal
blood pressure vary with age. Table 2.1.1 gives approx- for this age. Part 14 outlines the findings you would
imate values for children at rest. Note that upper nor- expect with various respiratory illnesses.
mal values for blood pressure can be different in boys
and girls. If hypertension is suspected, consult age-
Cardiovascular system
and sex-specific graphs for blood pressure. Selection
of an appropriately sized cuff for the age and size of Cardiac disease affects approximately 1 in 100 chil-
the child is important for accurate measurement of dren in developed countries, with the majority of these
blood pressure. The measuring of blood pressure can being congenital heart disease (CHD). Thus the focus
be quite upsetting so it is often best left until late in the of the cardiac examination in children is to detect signs
examination. of CHD, including potential secondary heart failure.
Again, if the child is quiet, take the opportunity to
start with auscultation before moving on to the other
Respiratory system
components of the cardiac examination. Listen to
Respiratory presentations are very common in chil- the heart rate: is it regular? Pay attention to the heart
dren, so it is important to have a good understanding sounds: What is the quality and intensity, particularly
of how to examine the respiratory system in chil- of the second heart sound? Is there abnormal splitting
dren. Initial inspection should look for any signs of or an added heart sound? Are there any murmurs? If
increased work of breathing, such as nasal flaring, so, are they systolic or diastolic? What is the quality
use of accessory muscles, head bobbing in infants, and location of the murmur? Does it radiate? Then, if
intercostal and subcostal recessions. The pattern of the child remains cooperative, you can go on to com-
respiration in young infants often has a large abdom- plete a full cardiovascular examination if indicated.
inal component. The chest wall is compliant, so A thorough description of examination of the child with
conditions that cause reduced lung compliance or suspected heart disease is provided in Chapter 15.1.
airway obstruction will more readily be manifest by
­indrawing of the soft tissues of the chest wall, and
Abdomen
in more serious disease the rib cage itself may be
drawn in during inspiration. You should also inspect Compared with older children, the abdomen of a
the shape of the chest wall and look for any asym- young infant appears protuberant, and the umbilicus
metry of chest wall movement. Listen for any added may be everted as a normal finding. The liver is nor-
respiratory sounds such as an expiratory grunt or mally palpable up to 2 cm below the right costal mar-
inspiratory stridor. As mentioned above, it is impor- gin, and it is sometimes possible to feel the tip of a
tant to be opportunistic, so if the child is settled you normal spleen and the lower pole of the right kidney.
may want to start with auscultation prior to moving When examining the abdomen it is important to
on to other aspects of the respiratory examination. consider the reason for the examination and thus what
The breath sounds in infants are more readily heard you are expecting to find or exclude. Is it simply part
because of the thin chest wall, and they often sound of a routine physical examination and you want to

Table 2.1.1 Some normal ranges for vital signs at different ages in childhood

Age Respiratory rate (breaths/min) Heart rate (beats/min) Systolic blood pressure (mmHg)

Newborn 40–60 100–160 50–75

1 week to 3 months 30–50 80–160 50–85

3 months to 2 years 20–40 80–140 60–100

2 years to 10 years 14–24 60–100 70–110

32 > 10 years 12–20 50–100 85–120

 The clinical consultation 2.1
exclude any asymptomatic masses or hernias, are you Musculoskeletal system
doing it for recurrent abdominal pain or a possible
As with the neurological system, a great deal of infor-
acute surgical abdomen? The indication will deter-
mation regarding the musculoskeletal system can be
mine how you approach it. If there is pain, remember
obtained by observation, and a full formal exami-
to start away from the pain; while palpating, always
nation is required only when it involves the primary
look at the child's face for indications of discomfort
problem. An important exception to this is that exami-
that would otherwise be missed.
nation for developmental dysplasia of the hips should
When palpating the abdomen, the ideal position of
be routine in young infants (see Chapter 8.1).
the patient is lying flat on an examination couch, with
relaxed abdominal muscles. This will often not be pos-
sible in young children as they will become d ­ istressed Special senses
and cry, thus tensing their abdominal muscles. For
From the history and general observation, you should
young children it is often possible to examine them
be able to assess that the child can see and hear ade-
lying on their parent's lap, or a combination of the
quately. Screening examination for hearing and vision
parent's and examiner's laps. If this is not successful,
must be age-appropriate (see Chapters 22.1 and 22.2),
you may need to resort to palpating the abdomen with
and formal assessment by an audiologist or optome-
the patient sitting or standing.
trist should be organized if there are concerns.
Rectal examination should not be performed rou-
tinely. If indicated by the presenting problem, it should
be undertaken only once and by the person who will be Development
making management decisions based on the findings
(e.g. a surgeon). A brief screen of developmental achievements and
progress should be undertaken; a significant amount
of information regarding development will again be
Genitalia gained from observing the child. Can she walk? How
In infant boys, assessment of the penis and scrotum well does she manipulate the toys? Is she using appro-
should be considered part of the normal routine exam- priate language for her age? Detailed assessment is
ination, as unsuspected inguinal herniae, undescended not routine unless indicated by the clinical problem,
testes and urethral abnormalities may be detected. It is or concerns are raised during the consultation (see
normal for the prepuce to be non-retractile and adher- Chapter 2.2).
ent to the glans up to around 4 years of age.
In girls, examination of the genitalia is usually
Head and neck
undertaken only when indicated because of a spe-
cific problem. In instances where a genital examina- In babies it is important to examine the head shape,
tion beyond simple external observation is required in to palpate the fontanelles and the sutures, and to plot
a girl, this should be done by an appropriate specialist. the head circumference as outlined above. The poste-
rior fontanelle is often closed by 2 months of age, and
the anterior fontanelle usually closes between 8 and 24
Central nervous system
months of age. However, there is a wide range of nor-
Formal examination of the nervous system is time- mal with some closing by 3 months. The more impor-
consuming and many aspects require cooperation from tant factor to consider, however, is head growth; it is
the patient. In young children, observation of move- reassuring if this is tracking along the centiles.
ment and behaviour can provide most of the necessary Examine the teeth, if present, for their number, pat-
information, with specific neurological e­xamination tern of eruption, and the presence of caries or abnor-
being reserved for children where the primary concern malities (see Chapter 22.3). Take this opportunity to
is the nervous system. Routine sensory examination is remind parents of the importance of good dental care
necessary only rarely. and of regular attendance at a dentist.
Examination of the mouth, throat and ears requires
good cooperation or appropriate positioning of the
Skin
child. It also has the potential to upset the child, so
Examination of the skin is important not only in der- is usually best left until last. For examination of the
matological problems: congenital skin lesions may give ears, the recommended positioning is to have the
diagnostic clues to other conditions. For example, the child sitting on their parent's lap facing sideways; the
characteristic pale patches of tuberous sclerosis may ­parent then cuddles the child's head into the chest
provide the diagnosis in a child who is being assessed for with one hand and places the other over the child's
33
developmental delay and seizures (see Chapter 21.1). arms (Fig. 2.1.3), and if necessary has the child's legs
 2.1 CLINICAL ASSESSMENT

Examinations at specific ages

There are several specific ages that differ sufficiently
from your general paediatric examination that they
deserve individual mention. They include the exami-
nation of the newborn, the 6-week review and the
approach to an adolescent.

Newborn
It is recommended that all newborn infants have a
full and detailed physical examination within the
first 48 hours of life. The findings of this examina-
tion should be recorded in the child health record
and conveyed to parents. The purpose of this exami-
nation is to check that the infant is healthy, check for
significant abnormalities, and establish a baseline
including weight, height and head circumference for
Fig. 2.1.3 Holding a child ready for ear examination. Note the future assessments. A detailed outline of the new-
position of the mother's hands. born examination is provided in Chapter 11.1.

6-week review
between theirs, while the ear is examined. The child is
then turned to face the opposite direction and the pro- This is generally the first medical review and exami-
cedure is repeated to examine the other ear. To exam- nation of a baby after leaving hospital. It provides
ine the mouth and throat, the child is then turned to an opportunity for health promotion advice, and
face forwards; the parent then cuddles the child's head for the parents to express any concerns. The main
into their chest again with one hand and the other purpose of the examination at this age is to detect
cuddles their arms (Fig. 2.1.4). The doctor can then congenital heart disease, developmental dysplasia
examine with or without the aid of a tongue depressor. of the hip, congenital cataracts and undescended
Observation of experienced practitioners will assist testis.
with learning these techniques.
Adolescence
Concluding the examination
This is often a time of increasing self-awareness and
As for taking the history, it can be helpful to ask the self-consciousness regarding body and appearance.
parent or child whether there is anything else they This can mean that the idea of a physical examination
would like you to check at this point. Your examina- is quite confronting. It is important that this is han-
tion may also have revealed findings that prompt you dled in a sensitive manner. This is covered in detail in
to return and take further details in the history. Chapter 3.11.

Note-taking
It is important that you produce an accurate and clear
record of the history and examination findings. This
will be needed to help you later and as a record for
future staff involved in the child's care. A few items
will need to be jotted down briefly as you go along,
but the rest of the record should be written after the
consultation is completed. You will not develop a good
rapport with the family if you are constantly gazing at
your papers and writing notes.
In younger children, you will have adapted the order
Fig. 2.1.4 Examining the throat. Note the mother's hands of the physical examination to fit the clinical prob-
34
restraining the child's head and arms. lem and their tolerance of the examination process.
 The clinical consultation 2.1
Whatever the sequence in which you obtain your infor- and one that may have frightening associations for
mation, it is still important to record your findings in them. They may not know who exactly you are nor
a logical and structured format. It is also vital that you whether you are the best person to help them with
record what your assessment is, including a differential their child's problem.
diagnosis and what your short- and long-term man- You will be in a position to help ease at least some
agement plan is. The use of the SOAP note format may of the family's anxieties long before you have even
facilitate this. arrived at a diagnosis. You can achieve this by being
friendly, by explaining who you are, and by convey-
ing that you are genuinely interested in their concerns
and that you value their time and opinions as much
The consultation as part of the as your own. Use language they understand, give
them time and opportunities to express their concerns
therapy fully, be gentle and caring during your examination,
Doctors often think of the management of a clini- and give a clear explanation of what you think the
cal problem as a chronological sequence commenc- problem might be and the nature and purpose of any
ing with history-taking and examination, followed by investigations or treatment that you recommend. In
formulation of a differential diagnosis, appropriate this way, you will help to obtain the family's confi-
investigations, final diagnosis, treatment, assessment dence and trust, which in turn will improve their will-
of response and outcome. Most families who have ingness to cooperate with the plan of investigation
an ill child will not arrive at the consultation with and treatment that is required.
you with that same perspective. They will have come You will not acquire all of these skills overnight but
because they perceive that their child has a problem learning them is rewarding and fun, and you will be a
and they will often be anxious that it might turn out much more effective doctor for children and their fam-
to be serious. They will be in a foreign environment ilies at the end of the process.

35
 2.2 Developmental surveillance
and assessment
David Starte, Carolyn Cottier

about their child's progress, such as ‘Tell me how she is

Introduction getting around’, as they are more likely to elicit revealing
Development as part of life answers than ‘Is she walking now?’. This process is time-
consuming and parents need to feel relaxed and unhur-
We continue to develop new skills throughout life, but ried if they are to give their best information. Some of
it is during childhood, particularly the first 5 years of the information may well be sensitive, especially when
life, that the majority of basic skills are acquired. there are problems, and a private setting without inter-
Doctors learning about child development often ruptions is important. Developmental interactions are
wish to memorize lists of milestones, but fail to appre- best scheduled for a well-child visit or review to avoid
ciate the diversity of normal variation. We do not confusing illness behaviour with developmental delay.
expect an even distribution of talents among adults,
yet we often assume children all develop similarly. It
is the variability in normal patterns of development Clinical example
that makes the area fascinating and creates complex
­challenges in screening and diagnosis. Sinclair, a 3-year-old child of English-speaking
parents, had a vocabulary of only 20 words.
His medical history was normal. The parents
Parents know their own children best were reassured by his normal hearing
assessment, as well as by the father's own history of
Child development starts with a good history. Parents
initial poor speech development as a child. However, the
are often remarkably accurate at recalling recent devel- preschool staff became concerned about the degree of
opmental achievements and changes, but more d ­ istant his language difficulty and whether it was part of a global
events may require prior notice so that sources such developmental delay. The words he knew were used singly,
as relatives and baby books can be reviewed. A s­ imple were clearly articulated and were used in their appropriate
questionnaire filled in before the interview can allow context, but, to indicate his needs, he resorted to leading
parents to consider these details in the w
­ aiting room or an adult by the hand. No phrases or small sentences were
heard. He understood two-step commands and used
at home. Parents should be asked open-ended q ­ uestions
facial expressions, hand gesturing and eye-to-eye contact
appropriately. At preschool, he was interested in the other
children, but they often excluded him in play when he
couldn't talk properly. He showed examples of imaginative,
Practical points constructive and cooperative motor play. There were no
behavioural concerns and he was an affectionate child.
• Always take any parental concerns or history of regression Assessment with the Griffiths Mental Developmental
in skills very seriously (worried parents are usually right!). Scales showed that his abilities tested within the average
• Surveillance and screening take place to ensure there are range for his age, other than a mild delay in speech and
no warning signs of potential problems – if in doubt refer language skills. During the assessment, he was cooperative
for therapy/intervention and then review. and persevered with the tasks at hand. Sinclair therefore
• False reassurance must be avoided. Do not reassure had an isolated expressive language disorder of presumed
unless you are certain of normality. familial origin, and was referred to a speech pathologist for
• All developmental diagnosis is dimensional across different assessment, therapy and liaison with the preschool teacher
areas of development and behaviour. It's not black and to modify his preschool curriculum.
white, but which shades of which colours blend to make up
the rainbow.
• Discussion of diagnosis/prognosis requires time, privacy,
empathy, honesty, cultural sensitivity and both parents
History is everything
whenever possible. Details of what is said may be A good developmental history starts with the ­pregnancy
forgotten, so written reports are essential.
and delivery, and progresses through the neonatal,
• Each assessment must produce a practical written action
plan that is given to the family and others involved. infancy, toddler and preschool years; it should be a
Otherwise, it is at risk of being ineffective. routine part of all paediatric interactions. The doctor
36
requires a working knowledge of normal development
 DEVELOPMENTAL SURVEILLANCE AND ASSESSMENT 2.2
age of achievement. By definition, half of the popu-
Table 2.2.1 Areas of development
lation will not meet median milestones, and their use
Area Description can worry parents unnecessarily (‘milestones are mill-
stones’). It is preferable to use the normal ranges in
Gross motor Large muscle movements – walking, Table 2.2.2. Many developmental patterns are familial,
running, jumping, climbing and riding
but so are many developmental disorders, so it is unwise
Fine motor Small muscle movements – grasp, to accept delay as a normal variation. Just because an
release, drawing, speech clarity uncle did not talk until he was 4 years old does not mean
he did not also have a developmental language disorder
Language Receptive – understanding others or deafness. Other ‘causes’ such as being a twin, bilin-
Expressive – own thoughts output gualism or tongue-tie can produce minor variations,
Pragmatic – social use, conversation
but not significant delays needing more formal diag-
Social and daily Adult and child interaction
nostic assessment. Assuming that the child's delay is
living skills Feeding, dressing, washing, toileting caused by these minor variations is a common source
of late diagnosis and delayed effective intervention. The
most important conclusion that needs to be drawn from
and needs to be aware of the significance of variations this surveillance is that there are no warning signs of a
that may indicate a developmental disorder. Child potential problem (Table 2.2.3). Should doubt exist, it is
development progresses in many areas simultaneously always better to seek a second opinion and to arrange
(Table 2.2.1). It is as necessary to know the various some therapy or intervention than to provide false reas-
developmental systems as it is to know the physical sys- surance. It may make you feel better to reassure, but
tems. Each will have its component parts, and the rate families who waste months ­finding help for their child
of progress in all of these components may be similar will often feel let down.
(when all are delayed, this is described as global delay)
or discrepant (described as a specific delay in one area). Any interaction is an opportunity to examine
As each area is reviewed through the different stages
Checking the normal (surveillance) of childhood, any apparent delays or unusual fea-
tures can be clarified with the family. This allows the
What are the normal ranges?
developmental examination to be targeted. Although
The key is to look for areas of development delayed many children are shy and perhaps fearful, a quiet and
beyond the normal range and not to compare the child patient approach will often bring out the show-off
with ‘normal milestones’, which are merely the average in children, especially for tasks about which they are

Table 2.2.2 Normal ranges for children's developmental progress (approximately 25th to 90th percentile)

Age Gross motor control Vision and fine motor Language and hearing Social and daily living skills

2–4 months Head steady in sitting Follows object through 180° Squeals with pleasure Smiles

5–8 months Sits without support Passes cube from hand to Turns to soft voice Feeds self biscuit
hand Baba/Gaga babble
(to 10 months)

9–14 months Stands with support Neat pincer grasp of raisin Mama or Dada Indicates needs by gesture
specifically

12–16 months Walks well alone Stacks two cubes (to 21 Three words Drinks from a cup
months) (to 21 months)

15–24 months Walks up steps Scribbles spontaneously Points to one body part Removes garment

21–36 months Jumps on the spot Draws vertical line in Uses plurals and Puts on clothing
imitation phrases Plays tag with other children

3–4½ years Balances on one foot Copies a ladder Understands cold, tired Separates from mother
for 5 seconds Draws a face and hungry
Asks ‘Wh’ questions 37
 2.2 CLINICAL ASSESSMENT

Table 2.2.3 Warning signs to worry about; be concerned if the child is not doing this (but items marked with an asterisk (*)
are a worry if they are present)

Age (months) Gross motor control Vision and fine motor Language and hearing Social and daily living skills

3 Complete head lag* Following with eyes Searching for sounds Smiling
with eyes

6 Persistent Moro reflex* Preference for one hand* Head turn to soft voice Interest in people
Squint*

9 Sitting with support Persistent hand regard* Ba-ba-ba babble Awareness of strangers

12 Pulling to stand Pincer grasp Trying one or two words Constant mouthing*
Standing with support

18 Walking alone Constructive play with blocks Six words Pointing at items
Casting toys* Constant dribbling* Finger-feeding

24 Running Turning book pages Fifty single words Interested in other children
Helps with dressing

36 Kicking a ball Drawing lines 2–3-word phrases Interactive play with peers
Preference for one hand Echolalia*

48 Pedalling and hopping Drawing a face Sentences and ‘Wh’ Imaginative role play
questions Toilet-trained by day

confident. For this reason it is best to start looking at Refusal to cooperate is a regular occurrence and it is
non-verbal areas (blocks, puzzles, drawing, etc.) and better to reschedule than to persist and teach the child
having appropriate furniture at the child's height will the sessions are going to be unpleasant.
enable you to get down to the child's eye level. Simple The aim of the medical examination (see Chapter 2.1)
equipment (Table 2.2.4) can be used to elicit a range is to detect any condition that might be causing the devel-
of skills and the session should remain a play activity. opmental delay, or indeed any general medical problem
Remember that too much direct eye contact, especially that may be exacerbating it. You should note the child's
from above, can be threatening, and a relaxed tangen- growth parameters, especially head circumference, and
tial approach across the child may be more successful. any signs of dysmorphism or neurocutaneous disorders.

Table 2.2.4 Developmental equipment

Area Equipment Activity

Gross motor Steps Crawling and walking up and down

Tennis ball Throwing, kicking and catching
Tricycle Riding and pedalling

Fine motor Raisins Pincer grasp and feeding

Small blocks Building, colour matching and counting
Inset puzzles Matching and sorting shapes
Crayon Scribbling, drawing lines and shapes
Paper (with child scissors) For above plus cutting and folding

Language Doll Identifying and naming body parts

Simple picture book Pointing to items and describing the action
Toy telephone or dictaphone Encouraging speech samples

Social and daily living skills Mirror Watching baby's response to self
38 Toy cup, plate and cutlery Feeding the doll and pretend tea party
 DEVELOPMENTAL SURVEILLANCE AND ASSESSMENT 2.2
Although a thorough physical examination is desirable, • physiotherapists, with skills in movement and
particular attention needs to be paid to the neurologi- coordination
cal system, looking for signs of cerebral palsy and other • speech pathologists, with language and oromotor
neuromotor disorders (see Chapter 17.2). Some ingenu- assessment skills
ity may be needed after a long developmental session to • occupational therapists (OTs), with daily living
­re-engage the child in play. skills, seating and manual dexterity expertise.
Vision and hearing are vital for children's learning.
For intervention to be as effective as possible, these Team benefits
senses need to be sharp. It may therefore be of more
service to the child to arrange an opinion from a vision In good teams, all members learn from one another
or hearing professional than to perform a rough screen- and considerable role release can occur. Some special-
ing test, which can miss minor problems that are easily ized teams will need specific expertise from orthop-
remediable. Again, avoid false reassurance at all costs. tists, audiologists or orthotists, as well as technical
support personnel to help with specific equipment.
Clinics specializing in developmental assessment may
be located in major hospitals with paediatric services
Looking for problems (screening) or in ­community-based health centres.
Screening is the process of detecting presymptomatic It is important to be clear about the family's expec-
disorders in order to intervene and change their natu- tations of the assessment, so that their agenda is cov-
ral history. Screening uses tests of known accuracy in ered fully. It may be helpful to arrange a home visit
healthy or at-risk populations to uncover those with by one of the team initially to break the ice with the
the target problem before symptoms arise. Further family and see the child in more natural surround-
diagnostic testing can then be performed, before ings. Most families are understandably anxious about
appropriate intervention is carried out. In the develop- a ­formal developmental assessment, as it may lead to
mental context, tests are sometimes used to formalize bad news. Anything done to reduce the family's appre-
the screening process. Examples are: hension will also be likely to reduce the child's fears
• Parent's Evaluation of Developmental Status and improve the reliability of the assessment as a sam-
(PEDS) – 10 simple questions about parental ple of the child's development. To this end, the venue
concerns (www.pedstest.com) for the assessment should not be overly clinical and the
• Denver II – American observation schedule of four staff should be understanding and welcoming.
areas of development (www.denverii.com)
• Australian Developmental Screening Test
(ADST) – Australian observation schedule (www. Clinical example
pearsonpsychcorp.com.au) Max was a 3-year-old boy with an
• Ages and Stages Questionnaires (ASQ) – structured unremarkable past medical or family history.
parent questions for different ages (www. However, from the age of 2 years there had
brookespublishing.com). been concerns about his development, in
As developmental delays produce detectable symptoms, particular his language and gross motor skills. A previous
regular review of the various developmental areas at all speech pathology assessment revealed a mild receptive
and expressive language delay. Despite progress with
doctor visits may well be a more effective method of
speech therapy, a review of his general development was
detection than formal screening procedures at specified requested because of concerns that he was also stumbling
intervals. This surveillance is enhanced when c­ ombined when running. Compared with his sister, he was slightly
with parent education about child development. later in sitting (8 months) and walking (15 months), and
he initially had difficulties in climbing frames, but he still
could jump or kick a ball well, and walked up and down
stairs one step at a time. Max was examined using the
Diagnosing disability (assessment) Griffiths Mental Developmental Scales, which showed age-
appropriate puzzle skills, low-average range for fine motor
Whilst this process is broadly a more detailed v­ ersion and language skills, and slightly more delayed gross motor
of simple surveillance, it is common for doctors with skills. On examination, he had a lordotic posture, a waddling
particular experience in the area to be involved in gait, only slightly overdeveloped calf muscles, and mild
teams with other professionals with specific expertise. difficulty getting up from a sitting position on the ground.
These professionals may be: A proximal myopathy was suspected in association with his
very mild developmental delay. The initial creatine kinase
• social workers or community nurses, who are skilled level was 33 000 units/litre and a dystrophin gene analysis
in family support/interactions was arranged. Max went on to have a muscle biopsy, which
• psychologists, skilled in intelligence testing and showed the typical changes of Duchenne muscular dystrophy. 39
behavioural interventions
 2.2 CLINICAL ASSESSMENT

Important aspects of the developmental assessment • large head, central nervous system or skin signs:
process are: computed tomography (CT)/magnetic resonance
• multidisciplinary team approach imaging (MRI); consider neurologist opinion
• colleagues working as equals • small head: TORCH titres; mild maternal
• good information gathering before the assessment phenylketonuria; MRI, consider neurologist
• standardized tests of development and intelligence opinion
• standardized behavioural questionnaires • loss of speech skills: sleeping electroencephalography
• specific therapist reviews as clinically indicated (EEG); neuro-metabolic tests
(physiotherapist, OT, speech therapist) • old houses, renovations, pica: blood lead
• ample time and privacy to discuss the findings with • syndromic or dysmorphic features: genetics opinion
the family before specific DNA studies.
• written reports to the family with a plan of action
• follow-up on any recommendations made.
Clinical example
Test batteries
Most teams attempt some form of formal test of When Jesse was 2 years 1 month old, he was
referred for assessment of his development
developmental status, often carried out by the psychol-
because of speech and language delays. On
ogist or doctor, to assess the degree and distribution the developmental assessment he displayed
of any developmental delay or disability. This is not a mild developmental delay overall, with an age equivalent
just to gain a score, but to provide a structured way level of 1 year 5 months. His weaknesses were in the areas
of reviewing all aspects of cognitive development in of personal–social, language and fine motor skills, which
an age-appropriate framework. In young children, this were moderately delayed (1 year age equivalent level). His
may be a developmental test such as the Griffiths or strength was in gross motor skills, which were normal (2
years 4 months age equivalent level). Speech therapy and
Bayley scales. In older children a standard intelligence
occupational therapy were arranged and when he started
test is often used such as the Weschler tests (WPPSI or preschool an individualized educational programme was
WISC), or the Stanford–Binet scales. established for him. Jesse was reviewed again at the age of
A developmental quotient (DQ or GQ) derived 3 years 11 months and still showed an overall mild delay (2
from the former tests includes aspects of self-care and years 7 months). Gross motor skills remained his personal
motor development, and is a broader concept than strength, being within normal limits, and his puzzle-solving
intelligence quotient (IQ), which relates more specif- skills had improved to a borderline level. However, his
weakest areas continued to be language and fine motor
ically to cognitive capacity. It is usual to talk about
skills, which were still moderately delayed.
a delay in development when the child is young (say Speech therapy and occupational therapy programmes
under 3 years of age) and the prognosis uncertain. continued, and a special needs teacher was arranged to
When it seems that the child has a permanent devel- provide further educational support at preschool. At the
opmental disorder, it is better to call it a disability, as age of 5 years 2 months a reassessment was arranged to
many parents assume that any delay will eventually plan for school placement based on his general learning
progress and support needs. He was assessed using the
resolve. In addition, specific behavioural question-
Differential Ability Scales (an IQ test), which demonstrated
naires may be used to assess the severity of symptoms a general conceptual ability around the first percentile (IQ
suggestive of autism, attention deficit/hyperactivity = 63), in the mild deficit range. When considered together
disorder (ADHD), or other behavioural disorders such with parental, teacher and therapist reports, and his two
as oppositional defiant disorder or anxiety disorders. previous developmental assessments, it was clear that
Jesse had a long-term intellectual disability of mild degree.
Medical investigations Mainstream kindergarten placement with integration support
was arranged, with possible progression to an appropriate
Investigations that may be useful and should be consid- smaller support class at primary school age. Gross motor
ered in situations of possible developmental delay are: skills are not a good guide to intellectual development.
• formal hearing and vision testing
• low average to borderline delay alone: consider
degree of variation from family norms to judge It should be remembered that investigations in these
need for investigation situations should be explained and offered rather than
• mild/moderate/severe/profound delay with language being just ordered: not all families are as focused on
delay: chromosomes or comparative genomic aetiology as medical staff. (See http://www.­genetics.
hybridization (CGH) array, DNA for fragile X, edu.au/factsheet for patient-friendly information
thyroid function, creatinine kinase about inheritance and genetic conditions.) Many par-
40 • severe intellectual deficit: as above, plus lactate/ ents' decisions about investigations will be influenced
pyruvate, amino and organic acids by whether they are planning to have further children.
 DEVELOPMENTAL SURVEILLANCE AND ASSESSMENT 2.2
Many children referred to developmental teams will to review any investigations or to help establish inter-
already have a diagnosis such as Down syndrome or vention services. Many parents feel a sense of grief if
cerebral palsy, but some conditions are less obvious and the child has a serious developmental problem, and it
need particular vigilance, for instance velocardiofacial may be necessary to provide written material and coun-
syndrome, fragile X syndrome (see Chapter 10.3), thy- selling to help them understand that this is a ­normal
roid deficiency or lead excess and, in boys, muscular reaction. Failure to resolve the grief reaction can lead to
dystrophy. Investigations or further opinions should ongoing anger, depression or marital conflict, and may
be recommended to families as needed, to help exclude delay important remedial action for the child.
any conditions that appear possible. Modern genetic
arrays looking for known deletions and rearrange-
ments have the highest positive yield in most develop-
mental presentations. Imaging and EEG testing are Clinical example
less rewarding unless specific signs or symptoms of
neurological disorder are present. At 4 years 3 months, Adrian had only three
recognizable words. He avoided eye-to-eye
contact, and paid little attention to what was
Practical outcomes asked of him, preferring to play alone. He
made sounds as he wandered around a room, laughing
A feedback session after team members have discussed and giggling for no apparent reason, looking at himself in
their opinions can be scheduled on the same day or the mirror and often flapping his fingers close to his face.
later. It is always helpful if both parents are present He was quiet, becoming upset only with the sound of a
and any close family supports they request, such as vacuum cleaner or a passing police car siren. He appeared
distant, not giving or accepting affection spontaneously. He
grandparents. Once the team's view has been clearly was toilet trained and could undress completely, but needed
stated, it is normal to ask for the family's reaction and assistance to get dressed. He could not pedal a tricycle, and
to ­discuss this. This will hopefully lead to discussions had poor ball-playing skills and an immature pencil grip with
covering investigation, aetiology, prognosis, genetic only circular scribbling. At preschool he needed constant
advice and a plan of action. Recommendations can direction and encouragement by the staff, and he had not
be formulated with the family as to what needs to be developed any friendships.
Assessment with the Griffiths Mental Developmental
done by whom, where and when. This all needs to be
Scales indicated a moderate developmental disability with
recorded ­carefully and copies given to the family on non-verbal skills at around 2–2.5 years, but his verbal
the day, as much of what is said may be forgotten, espe- skills were found to be further delayed at 12–18 months.
cially when the news is shocking. However, the manner His behaviour was consistent with a diagnosis of autistic
in which it is imparted is likely to be remembered for disorder, as he had a specific impairment in forming social
all time, and care taken with the time available, privacy relationships, in communicating and in playing imaginatively,
and, if ­necessary, the use of interpreter services will in addition to his developmental disability. Adrian had
high support needs and required intensive educational
help to optimize a potentially traumatic session.
programming and behaviour modification to develop to his
All parents need copies of all the reports generated; optimum potential. It was suggested that he be enrolled in a
further copies can be sent to professionals involved with special school for children with disabilities.
the child if the family agrees. Follow-up can be arranged

41
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 3
PART

SOCIAL AND
PREVENTATIVE
PAEDIATRICS

43
 3.1 The child and the family
Neil Wigg

• Opportunities for play, recreation and

Introduction companionship
The ecological model of the determinants of chil- • Opportunities to learn and explore
dren's health, development and wellbeing places the • Sensitive responses to emotional needs during
child at the centre of expanding spheres of influence. illness, particularly in chronic illness
Surrounding the child is the family, the family's com- • Recognition of each child's individuality
munity and the wider society. A child's family exerts • Recognition of the basic rights of every child, as
direct influences on the growing child and mediates the outlined by the United Nations Declaration of the
potential influences, both positive and negative, of the Rights of the Child.
community, society and culture of origin. To meet the physical, social and emotional needs of
The vast majority of the developmental health needs their children, parents and others in a caring role must
of children are met within the context of their family. fulfil their own needs. Caregiver needs include:
A healthy child is one who is physically well, whose • adequate housing and transport
emotional needs are met and who is socially adjusted. • freedom from unnecessary economic stress
Each of these needs has several parameters, which are • freedom from community and domestic violence
discussed below. • easy access to family support and early childhood
services, such as child care, health and education
services
The physical needs of the child
• knowledge of how to access community supports
• Care and protection from violence and services
• An adequate diet to provide for nutritional needs • social networks and extended family supports,
• Protection against heat and cold in early life, and community and cultural connections
protection against physical dangers, such as fire, • an understanding of child development and
electricity, water, poisons and motor vehicles behaviour.
• Prevention of illness through good living standards, The growth and development of a child in the fam-
education, health surveillance, immunization and ily and community context are determined by the
other public health measures. A home environment interplay of genetic, physical, social and emotional
that is free of tobacco smoke, lead and other toxins. factors, and experience. The balance of risk and
Children grow and thrive in the context of close and resilience factors influences a child's developmental
dependable relationships that provide love and nurture, pathway.
security, responsive interaction and encouragement of Risk factors preventing optimal progress might
exploration. Without at least one such relationship, include:
development is disrupted and the consequences can be • family conflict and disintegration
severe and longlasting. • economic disadvantage (low household income)
• parental mental health disorders
• individual child factors, such as low intellectual
The emotional and social needs of the child
ability or difficult temperament
• The opportunity to grow up in a family context • external factors, such as unsafe neighbourhoods,
with close and dependable relationships with one or environmental threats, war, etc.
more adults (parents) Balanced against these are resilience factors, which are
• Consistent, positive caregiving protective and promote wellbeing:
• Reasonable limits to be set on the child's behaviour • safe, nurturing home environment
• Feelings of being worthwhile and concern for the • consistent, supportive caregiving
wellbeing of others • individual factors, e.g. normal intellectual ability
• The development of self-help skills and a sense of • sense/experience of success, self-determination and
achievement achievement.
44
 The child and the family 3.1
The building blocks for should be carried out within the cultural and values
intellectual development framework relevant to the child.
There are many components of the family and soci-
etal environment that are important in the intellectual Clinical example
development of the child. Some of these are:
• a loving and nurturing caregiving/family environment Leanne was the 4-year-old daughter of
• child-rearing beliefs and practices that are designed professional parents who had migrated
to promote healthy adaptation from another country in Asia. Her behaviour
was demanding, overly active and often
• the opportunity to play, learn, explore and communicate aggressive. Her communication skills were delayed. Both
• the growth of self-regulation of physiological parents stated that in their families of origin children were
systems, emotions, behaviours and social interactions not disciplined until school age and were cared for by the
• positive and consistent human relationships extended family.
• access to developmentally appropriate educational
settings: children are active participants in their
own development and learning
• good physical health. Behavioural intervention needed to include these
As a child grows from a newborn infant to an inde-
views of parenting.
pendent young adult, his or her social environment
Traditionally, Australian families have been made up
expands and diversifies. A young infant has all its
of mother (usually at home), father, and two or more
needs met within the immediate family. Contact with
children. However, this picture of the ‘nuclear’ fam-
other young children is important for the social and
ily no longer represents the Australian family. Families
emotional development of the preschooler. A young
may be comprised of:
teenager may spend more time with peers than with
• couples with or without co-resident children of any
her or his family. The structure of the family, the style
age (85% of Australian families in 2006–2007)
of parenting and the capacity to support the grow-
• lone parents with co-resident children of any age
ing child's progressive independence are all important
(14% in 2006–2007)
determinants of the health and wellbeing of children.
• other families of related adults, where no couple or
parent–child relationship exists (1%).
The proportion of Australian couple families with
The family children has been decreasing over the last 10 years
(down to 45% of couple families in 2006–2007). The
‘Families are big, small, extended, nuclear, multigenera-
proportion of one-parent families with children of
tional, with one parent, two parents, and grandparents. We
live under one roof or many. A family can be as temporary
any age declined slightly in 2006–2007 compared with
as a few weeks, as permanent as forever. We become part of previous years (14% in 2006–2007, down from 15% in
a family by birth, adoption, marriage or from a desire for both 2003 and 1997).
mutual support. As family members, we nurture, protect, Many families in Australia do not contain depen-
and influence each other. Families are dynamic and are dent children. The Australian Bureau of Statistics
cultures unto themselves, with different values and unique (ABS) reports that, in 2006–2007, for families with
ways of realizing dreams. Together, our families become the dependent children aged 0–17 years:
source of our rich cultural heritage and spiritual diversity. • 80% of children lived in couple families (73% with
Each family has strengths and qualities that flow from both natural parents, 4% in step families and 3% in
individual members and from the family as a unit. Our
blended families)
families create neighbourhoods, communities, states and
nations.’
• 20% of children lived in one-parent families
• of children living in one-parent families, 85% lived
(Developed and adopted by the New Mexico Legislative with the mother and 15% with the father (17% and
Young Children's Continuum and New Mexico Coalition 3% of all families with children, respectively)
for Children, June 1990.) • in 2006–2007, there were also 7000 foster families
where there was one or more co-resident foster
child.
Three demographic trends have altered the structure
The Australian family of Australian families with children:
Australian society is multicultural, with pluralistic • the rate of parental separation and divorce
values and child-rearing practices. Child- and family- • the age of having the first child
centred health care of children and young people • the decision of women/couples not to have children. 45
 3.1 SOCIAL AND PREVENTATIVE PAEDIATRICS

During the past 20 years, marriage rates have fallen, Coincident with these changes in families and com-
and the age at first marriage and age of first birth have munities, the incidence of child abuse (physical, emo-
increased. The median age of first birth is now over 28 tional and sexual) is thought to have risen over the past
years. Consequently, family size is smaller. three decades; however, data about the rates of abuse
• In 2006–2007, 15% of all adults reported that are incomplete and much goes unrecorded.
while they were children (under 18 years of age)
their parents or guardians had either divorced or
separated. Clinical example
• There has been an increase in de facto relationships,
which have become more socially acceptable in the Lone parent Sharon, aged 24, and her three
last 20 years, including those in which children are preschool-aged children live in an outer
involved. Marriage rates are not a measure of family metropolitan suburb in a shared house. Jack,
formation. her second child, has delayed speech development and
• Family size and fertility rate are falling for all difficult behaviour. Jack was diagnosed by the local general
practitioner as having chronic middle ear disease, but
Australian women, both Indigenous and non-
the waiting list for ear surgery at the children's hospital in
Indigenous, although these remain higher for town is almost 2 years. Sharon cannot afford private health
Indigenous women. insurance (and faster access to surgical care) or the long-
term medication required for Jack.
Families at work
Workforce participation rates for family members have
increased in many developed countries in recent years.
However, unemployment is also common, particu- Children of families in distress
larly in single-parent families. These changes have the
Economic disadvantage/poverty
potential for significant effects for children.
• In 2003, in couple families where the youngest child Poor people are more likely to have poor health. There
was under the age of 15 years, at least one parent is a gradient of socioeconomic effects on health: the
was in employment in 94% of families. Both parents more affluent you are, the more likely you are to expe-
worked in 59% of these couple families. rience good health; the poorer you are, the worse your
• In lone-mother families where the youngest child health is likely to be. There is no particular cut-off
was under 15 years of age, nearly 55% of mothers point for economic advantage above which health is
were not employed. protected.
• In lone-mother families where the youngest child Low household income is associated with lower pur-
was aged 0–2 years, only 28% of mothers were chasing power, material deprivation and reduced abil-
employed. ity to participate in everyday community activities.
• Couple families with children under 15 years of Low-income households tend to occur in neigh-
age had an average income 2.8 times that of lone- bourhoods that have fewer communal resources and
parent families. where the social and physical environments are haz-
• The proportion of all children under 15 years ardous. Being poor is often also associated with much
living in families without a parent employed fell greater stress, feelings of lowered self-worth, power-
from 19% in June 1994 to 17% in June 2004. lessness and helplessness. Mental and physical health
In 2006–2007: problems follow.
• Both parents were employed in 63% of couple International standards define poverty as a house-
families with co-resident dependent children. hold income of less than 50% of the median income
• There were 508 000 dependent children (10%) living for that nation or state. In 2005, 12.8% (1 in 8) of
in a household where no-one was employed. Australian children lived in poverty.
• For lone mothers with dependent children, 34% Single-parent families are much more likely to live
of those whose youngest child was 0–4 years were in poverty. The resulting inadequate diet, lack of
employed, mostly on a part-time basis. opportunities and emotional stress may be coupled
For many Australian families with children it is with the emotional turmoil that children and par-
essential financially for both parents to have paid ents experience in separation and divorce. In general
employment. ‘Mum at home and Dad at work’ is not terms, children in one-parent families have poorer
the reality for most children. Accessible and afford- mental and physical health than their peers in two-
able childcare, family day care, after-school care or parent families. However, much of this difference
other informal childcaring/minding arrangements can be explained by lower household income and the
46
are needed. stress of financial hardship. Fortunately, the ­majority
 The child and the family 3.1
of children in one-parent families still experience Approximately half of all Aboriginal and Torres
good health. Strait Islander Australians now live in major
Low family income may affect the health of the chil- metropolitan areas. Family structures and supports
dren in many ways, such as: and communities are increasingly diverse and
• lower birth weight ­non-traditional. The health care of each individual
• lower rates of breastfeeding Aboriginal and Torres Strait Islander child and f­amily
• poor vaccination rates needs to take these changes into consideration, and
• poor growth ­provide care with respect given to family, community
• higher rates of infectious disease. and cultural expectations.
A recent study by the Benevolent Society (2010) of
unemployment and the well-being of children aged
Immigrant families
5–10 years demonstrated a marked increase in con-
duct problems, peer relationship problems, emotional Multicultural Australia includes many immigrant
problems and hyperactivity problems of children from groups whose children are at greater health risk. Many
‘unemployed families’ compared with those from fam- families come to Australia to escape persecution and
ilies where an adult was employed. civil disruption in their own countries, and they bring
with them the legacy of trauma and loss.
The major problems experienced by ethnic minor-
Indigenous families ity groups include lack of employment opportunities
Indigenous Australians (Aboriginal and Torres Strait (and associated low household income), social isola-
Islander peoples) have poorer health than other tion, unfamiliarity with health care and other social
Australians. Indigenous children have poorer nutrition services, and barriers due to communication problems
and growth, higher rates of infectious disease, higher and cultural differences.
injury rates, and high rates of infant and child mortal- Culturally sensitive health-care services that include
ity (see Chapter 3.2). bilingual workers and interpreter services are essential.
The reasons for the persistence of the relatively Doctors and other child health workers should recog-
poor health of Indigenous children are complex. nize tvhe vast range of child-rearing and health-care
Certainly living conditions, fewer educational oppor- practices of ethnic groups in Australia.
tunities, and poor access to goods and services all
contribute. So do cultural disruption, high levels of Families affected by mental health problems
poverty, lack of access to culturally acceptable health and drug abuse
care, and racism.
The meaning and structure of family varies with Children's early development and health depends on
culture. Aboriginal and Torres Strait Islander peoples the health and wellbeing of their parents. Postnatal
have diverse and enduring cultures that endow families depression is relatively common, affecting about 15%
with special responsibilities for the care of children, of mothers. Severe postnatal depression impacts
the social life of communities, and the continuance of on the establishment of infant–mother relation-
culture and customs. Family takes on more than bio- ships (known as attachment). Disorders of attach-
logical and parenting relationships to include commu- ment result in infant health problems, such as sleep
nal, customary and spiritual relationships. In many problems, failure to thrive, disturbed behaviour such
parts of Australia, Indigenous cultures are under as excessive crying, and subsequent emotional and
major threat. behavioural problems.
Children who grow up in families where one or
both parents have a mental health problem frequently
experience inconsistent parenting and disturbed rela-
tionships within the family. The scene is set for such
Clinical example children to develop behavioural, emotional and men-
tal health problems.
Taliah is the third child of a 21-year-old The Western Australian Child Health Survey in
Aboriginal mother. The family lives in a small 1995 identified that 20% of 12–16-year-olds had a
town in the Northern Territory. Taliah is 6 months significant mental health problem. Thus 1 in 5 teen-
old, growing and developing well, is breastfed and is free of age schoolchildren will have a mental health prob-
illness. Her older brother and sister have much poorer health.
lem and most will not seek or receive treatment (see
Before her birth, Taliah's mother had joined the local ‘strong
women, strong babies, strong communities’ programme. Chapter 4.2).
Alcohol is by far the most widely used and abused drug
47
in our society. Drinking alcohol is not only accepted
 3.1 SOCIAL AND PREVENTATIVE PAEDIATRICS

but is expected behaviour in Australia. Approximately • Information sharing. Health-care practitioners

two of three men and one in two women drink alcohol communicate and share complete unbiased
at least once a week. Of those who drink, about 10% of information with patients/families: patients/families
men and 6% of women are in the medium- to high-risk receive timely, complete and accurate information
groups. The abuse of alcohol by one or both parents in order to participate effectively in care and
has a profound effect on the family. decision-making.
• Participation. Patients and families are encouraged
and supported in care and decision-making at the
level they choose.
Clinical example • Collaboration. Patients/families are also included in
service policy and development, facility design and
Six-year-old twins Jonas and Jonno are now professional education.
in long-term foster care, after lengthy periods
of intermittent parental and temporary out-of-
home care arrangements. Jonas is overactive, aggressive
toward other children and his caretakers, and attention-
seeking. Jonno is failing at school and is encopretic. Formal Services for the child and family
developmental assessment of both boys indicates ‘normal
potential’. The boys’ mother has a history of substance
General or primary care practitioners (family doctors)
abuse, postnatal depression and ongoing mental health provide the mainstay of health services for children and
issues. Alcohol abuse and violence perpetrated by their families. These primary health-care services are com-
father led to parental separation 2 years ago. plemented by a range of government-funded commu-
nity health and social services, and non-governmental
services. The following are given as examples and con-
stitute a ‘system of services’ that promotes the develop-
Children of alcohol-dependent parents suffer anx- mental health of children and support families in the
iety and unhappiness, and may be exposed to vio- care of children.
lence and argument. In many cases this leads to the For families with young infants:
child becoming antisocial, engaging in alcohol/drug • well-child care in child health centres
use, and developing mental health problems such as • home visiting programmes for families with additional
depression. Alcohol and drug (e.g. heroin) addiction needs, e.g. Family Care Program, Good Beginnings
frequently leads to financial stress in a family, together • residential services
with deterioration in family relationships and parental • parent help lines, child health lines (24-hour, 7-day
separation. The consequences on children are severe. telephone advice lines)
• printed and online information services.
For families with preschoolers:
Family violence
• health surveillance, including immunization and
Some 16% of Australian couples experience violence health promotion
in the relationship. For 4% of couples the level of • injury prevention and safety promotion
physical violence is such that physical harm is a likely • health service component to childcare and
outcome. preschool services
Our society tolerates high levels of violence in • telephone and other information services
the media, in sport and in the community generally. • health screening prior to school entry – provided by
However, violence in the family context has a profound child health nurses, general practitioners (Healthy
effect on children. Violence between parents is fre- Kids Check)
quently associated with violence towards their children. • developmental assessment clinics and early
Children who witness violence as a ‘problem-solving’ intervention services.
technique at home may adopt similar patterns of behav- For families with school-aged children:
iour, particularly when they themselves become parents. • support services provided by education
departments, e.g. guidance officers, counsellors
• assessments of children by child health nurses
• health education
Family-centred care • community mental health services
The hallmarks of family centred care are: • school oral health (dental) services.
• Respect and dignity. Health-care practitioners listen The Federal government in Australia provides a num-
to and honour patient and family perspectives and ber of pensions or benefits administered by Centre
48
choices. Link and the Department of Family and Community
 The child and the family 3.1
Services. These include the family allowance, childcare The field of family support services is complex and
supplements, supporting parents and carer benefits. accessing ‘the right service at the right time’ is fre-
State governments and non-governmental agen- quently a major problem for families experiencing dis-
cies (often church-affiliated) provide many family and tress. Family doctors and other child health workers
community support services. need to know about the child and family services avail-
Similar government-funded services are provided able in their area, and about government benefits for
for families in many other countries. families.

49
 3.2 Indigenous culture
and health

The word Indigenous, meaning native, is used to There are Indigenous populations in countries
describe the ancient or native population of a coun- throughout the Asia–Pacific region, as well as elsewhere
try. Indigenous populations have almost always been in the world. For this chapter, the editors asked Paul
affected by colonization and migration of other popu- Bauert and Francis Abbott to write about Aboriginal
lations and are almost always in a position of social and Torres Strait Islander children in Australia, and
disadvantage relative to the rest of the country's popu- Leo Buchanan to write about the Maori and Pacific
lation. This social disadvantage is reflected in major island populations in New Zealand.
inequalities of health.

PART 1 ABORIGINAL AND TORRES STRAIT ISLANDERS

Paul Bauert, Francis Abbott
• North-east Arnhem Land, Northern Territory
A definition of Aboriginal and – Yolngu
Torres Strait Islander people • Tiwi Islands, Northern Territory – Tunuwi
• Jabiru region, Northern Territory – Binjing.
In Australia, the word Indigenous is used to refer to
the Aboriginal and Torres Strait Islander peoples
of Australia and is used by the Australian Bureau
of Statistics (Indigenous Statistics for Schools), Health care and cultural safety
which also outlines the most widely adopted defi-
Expressions such as ‘cultural awareness’, ‘cultural
nition of Aboriginal or Torres Strait Islander (the
safety’, ‘cultural security’ and ‘cultural competence’
'Commonwealth working definition'):
are often used and discussed in the literature in rela-
‘An Aboriginal or Torres Strait Islander is tion to organizations, health services and health care,
• a person of Aboriginal or Torres Strait Islander and to individual service providers’ abilities to inter-
descent, act appropriately and effectively with people of other
• who identifies as being of Aboriginal or Torres Strait cultures. Individual cultural competence has been
Islander origin and described by the Northern Territory Government as
• who is accepted as such by the community with which
having four components:
the person associates.’
• Awareness of one's own cultural world view
Australian Indigenous peoples are many diverse • Attitude towards cultural differences
groups, with varying cultural ways, languages, tradi- • Knowledge of different cultural practices and world
tions and names for themselves. The health-care pro- views
fessional should use a formal, accepted and respected • Cross-cultural skills.
name that people in the local community use to refer Many jurisdictions and organizations, both govern-
to themselves, some examples of which are: mental and non-governmental, have developed orga-
• New South Wales – Koori nizational policies, frameworks, resources and training
• Victoria – Koorie around this cultural competence continuum. The
• Queensland/North New South Wales – Murri National Health and Medical Research Council pro-
• South Australia – Nungah duced a guide to cultural competency, and a number
• Western Australia (south-west) – Noongar of regions have developed various frameworks and
• Tasmania – Palawa resources based on this guide.
50
 Indigenous culture and health 3.2
None of our diverse cultures, including Australian and social and cultural disruption and disintegration’
Indigenous culture, can be adequately described in (Year Book Australia, 1994 – Australian Bureau of
one short chapter. However, this information can be a Statistics). ‘The decline of the Indigenous population
starting point in the progression from cultural aware- continued well into the twentieth century’, according to
ness to cultural competence. Online generic courses Australia's Health 2010, the 12th biennial health report
concerning Indigenous culture are also available, of the Australian Institute of Health and Welfare.
including both free and accredited courses. Cultures, By 2009, the estimated Indigenous population
including Australian Indigenous culture, are never had increased to about 550 000, comprising 2.5% of
static but constantly changing with time, and there is Australia's population (Australian Bureau of Statistics).
much diversity within cultures. These figures include 6% who identified as being of
Generic information and courses need to be built Torres Strait Islander origin and 4% as being of both
on by accessing any available face-to-face courses, Aboriginal and Torres Strait Islander. These increases
resources and local Indigenous ‘cultural brokers’, in are ‘in excess of those which can be attributed to nat-
order to learn location-specific and role-specific cul- ural increase in the Indigenous population’. ‘Changing
tural information, historical information, cultural social attitudes, political developments, improved statis-
contexts and protocols concerning the community tical coverage, and a broader definition of Indigenous
being served. ‘Cultural brokers’ may be people such origin have all contributed to the increased likelihood
as: community elders, community workers, Aboriginal of people identifying as being of Aboriginal or Torres
Health Workers, people working in Aboriginal Liaison Strait Islander origin’ (Australia's Health 2010). Some
roles, community/local councils, local Boards, and 32% live in major cities, 43% in regional areas, and 25%
Aboriginal Controlled Services. in remote or very remote areas. Approximately 30% of
the Northern Territory population are Indigenous peo-
Implications for a health-care professional's ple, the highest proportion in Australia. In comparison,
practice Victoria has the lowest proportion, at 0.7%.
The Aboriginal and Torres Strait Islander popula-
• For an individual to be ‘culturally competent’ requires tion of Australia is very different from the rest of the
a willingness to change, to be empathic, adaptable and population in age range as a result of higher birth rates
‘other centred’, and to develop along a continuum and earlier age at death. In 2006, the median age was
that starts with a level of awareness, to being able to 21 years for Indigenous people and 37 years for the
practice in a culturally competent manner. non-Indigenous population.
• All health-care professionals working with Indigenous
people should endeavour to access cultural Implications for a health-care professional's
competency training and resources relevant to practice
Australian Indigenous culture in order to achieve this.
• Research any cultural competency guides, • Find out whether the population in the area your
frameworks and resources that may have been health service covers includes Indigenous people.
developed for the local region and health services. • Consider whether the service is accessible and
• Organizations' and individuals' cultural competence culturally appropriate for those people.
affects Indigenous people's ability and willingness • Consult with the community as to what measures,
to be able to access and use services. if any, the people would like to see introduced to
• Find out who are the appropriate local cultural assist with this.
brokers to learn from. • Are there local Indigenous people employed in the
service, or training and employment opportunities
to help increase the numbers of Indigenous people
Population in the organization?
• Are there health programmes that cater for
Accurate figures for the number of Indigenous people the needs of the Indigenous community's age
living in Australia at the time of white settlement are demographics?
not known. Anthropologists and others have suggested
various numbers ranging from 300 000 to 1 000  000.
Archaeological research has suggested that the land could
have supported 750 000 people before white settlement.
Mortality
Whatever the numbers were before 1788, they The Australian Institute of Health and Welfare
‘declined dramatically under the impact of new diseases, (AIHW) considers data from New South Wales,
repressive and often brutal treatment, d ­ ispossession, Queensland, Western Australia, South Australia and
51
 3.2 SOCIAL AND PREVENTATIVE PAEDIATRICS

the Northern Territory as the most complete. The passed away should use a relationship term instead,
combined data from 2003–2007 demonstrate that such as ‘your aunty’, ‘grandfather’, etc., or the local
mortality rates for all age groups of Indigenous males term specifically used for this situation.
and females were approximately twice as high as for
non-Indigenous people, except for those aged 75 years
and over, where the ratio was only 1.2.
Life expectancy at birth is approximately 67 years Health and illness beliefs
for Indigenous males and 73 for females (compared A definition of health as perceived by Aboriginal peo-
with 78 and 83 years respectively for non-Indigenous ples was developed by the National Aboriginal Health
males and females). Strategy in 1989:
The AIHW considers that the mortality rate for
children aged under 5 years is a key indicator of the "Aboriginal health" means not just the physical wellbeing
general health and wellbeing of a population. In the of an individual but refers to the social, emotional and
cultural wellbeing of the whole community in which each
period 2003–2007, the 692 deaths of Aboriginal and
individual is able to achieve their full potential as a human
Torres Strait Islander children aged 0–4 years was
being thereby bringing about the total wellbeing of their
around twice the rate for non-Indigenous children dur- community. It is a whole of life view and includes the
ing this period. ‘For injury and poisoning, and respi- cyclical concept of life – death – life.
ratory diseases, which were common causes of death
among children of this age group, Indigenous children For many Indigenous people, the spiritual or supernat-
died at 3 and 4 times the rate of non-Indigenous chil- ural side of life remains an unquestioned reality. Many
dren respectively’ (Australia's Health 2010). still retain a strong traditional belief in the causes
of illness different to that of the western biomedical
model, even if that is well explained, understood and
Implications for a health-care professional's accepted. The cause can be attributed to ‘sorcery’ or
practice as a consequence of having transgressed some tradi-
tional law. The person may have to put this right to
• Indigenous people accessing care away from home bring about a complete cure; they may want to con-
may need assistance with planning for early return tinue ‘western’ medical treatment but may also need to
home as they may be culturally obliged to return return home to carry out correct traditional practices
for funeral ceremonies and ‘sorry business’ and/or to restore health. Many people still access their own
may want the company of family while grieving. traditional healer, traditional medicines and healing
• Unresolved or ongoing grief is highly likely to be practices.
impacting on the mental health and social and Men's business/Women's business: This term refers
emotional wellbeing of people who have relatively to health and treatment matters of a personal nature
frequent losses of close relatives. concerning the bowels, bladder, genital areas, sexual
• There may be reluctance to attend a health service matters, childbirth, etc. It is usually very difficult and
where a relative has died. There may be a need to ‘shameful’ for a male or female Indigenous person to
have a ceremony to ‘cleanse’ such an area. Seek discuss these or be treated in this area by someone of
guidance from local Indigenous people as to their the opposite sex. However, Indigenous people, like
wishes regarding this. others, are of course practical and, with adequate and
• People will be likely to want (and have a right to) respectful explanation, appreciate that sometimes a
a thorough and meaningful explanation of the same-sex staff member is not available, although it is
cause of death of a family member. Keep in mind really preferable not to cross these boundaries.
and respect the fact that people may also have their
own cultural explanations for the cause of death.
• A dying person will usually want to return to
Implications for a health-care professional's
‘country’ (the land they are connected to) and
practice
family for particular processes and ceremonies
associated with dying and to pass away there. • When providing a service, keep in mind the holistic
The health-care professional may need to put definition of health as defined above and work
processes in place to help facilitate this as soon within this.
as possible. • Be guided by any available community cultural
• Many Indigenous people do not use the name of brokers as to people's concept of health and any
a deceased person for a long time, if at all, after traditional resources they access.
someone has died. A health-care professional • If the community wishes, collaborate in
52 talking with a family about someone who has incorporating these in the service.
 Indigenous culture and health 3.2
• If the person is far from their community accessing (‘7 out of 10 Indigenous children were living in
health care, it may be necessary to help facilitate families that had experienced three or more major
ongoing care and return to the community so life stress events such as death in the family, serious
that the person can also attend to cultural matters illness, family breakdown, financial problems or
surrounding their illness beliefs. arrest … and 22% had experienced seven or more
• Endeavour to have sufficient numbers of both of such events’); respiratory diseases; type
male and female staff, including Indigenous staff, 2 diabetes; chronic kidney disease; and injury.
employed in the service. • Co-morbidity of cardiovascular disease, diabetes
• If possible and appropriate, when no professional and chronic kidney disease often occurs in the
of the same sex as the client is available, have general population. However, this particular
a ‘chaperone’ of the same sex as the person to co-morbidity is even more common among
accompany and support the professional and Indigenous Australians.
client while treating or discussing ‘men's/women's • Cancer rates are lower for Indigenous people, but
business’ matters. cancer death rates are approximately 1.5 times
higher for Indigenous males and females than
for non-Indigenous people. The main causes
of Indigenous cancer deaths include cancers of
History, disadvantage and health the digestive organs and lung cancer. Among
Indigenous people, smoking-related cancers are
For a discussion on Australian Indigenous history
more common than among non-Indigenous people.
since 1788, and its devastating impact on past and cur-
rent health and welfare, the reader is encouraged to • Ear disease and hearing loss is higher than for the
general Australian population, predominantly
examine the Australian Indigenous HealthInfoNet.
among children and young adults.
Dispossession, introduction of new diseases, epidem-
Other determinants and risk factors impacting on the
ics causing depopulation and consequent disruption in
health and welfare of many Indigenous Australians
family systems and culture, loss of autonomy, destruc-
include: lower socioeconomic status; lower employ-
tion of traditional food and economic systems and
ment and educational levels; overcrowded housing
ceremonial life and culture, separation of families and
conditions; remoteness (which includes lack of access
family members (including policies and practices that
to health services and adequate food supplies); food;
led to the Stolen Generations), and loss of control over
poor nutrition; physical inactivity; overweight or obe-
much of daily life, are among the many contributing
sity; higher rates of smoking (Indigenous people are
factors discussed. The ‘clear relationship between the
more than twice as likely to be daily smokers than
social inequalities experienced by Indigenous people
other Australians); alcohol consumption (although
and their current health status’ is described. Loss of
Indigenous people are considerably less likely to drink
control over daily life is increasingly acknowledged as
alcohol than other Australians, many of those who do
a significant cause of chronic stress, a contributor to
drink, tend to drink at risky or high-risk levels). Low
chronic disease.
birth weight, ear infections (leading to hearing loss)
In their regular reporting of key indicators of
and gastrointestinal infections also impact negatively
Indigenous disadvantage, the Productivity Commission
on child health.
describes six ‘headline indicators’: post-secondary
education; disability and chronic disease; household
and individual income; substantiated child abuse and
Implications for a health-care professional's
neglect; imprisonment and juvenile detention; fam-
practice
ily and community violence. In all of these indica-
tors, Australian Indigenous people suffer substantial • Find out the historical and social history of
disadvantage compared with the rest of the popula- the community and build relationships and
tion, despite some minor gains in some indicators over collaborations with any Indigenous-controlled
recent years: organizations to help increase access to the health
• Australian Indigenous people endure an overall service by the local community.
burden of ill-health that is 2.5 times that of the • People may experience a feeling of powerlessness
total Australian population. in the face of large organizations such as hospitals
• The leading causes of morbidity and mortality and health services.
for Australian Indigenous people include: • People are likely to be reluctant/uncomfortable
cardiovascular disease (including rheumatic fever accessing health services where there are no
and rheumatic heart disease); mental health Indigenous people employed or that do not have
problems and social and emotional wellbeing issues culturally safe systems in place. 53
 3.2 SOCIAL AND PREVENTATIVE PAEDIATRICS

• They may take a while to develop rapport, Kinship relationship has a bearing on roles, respon-
preferring to take time to see whether the health- sibilities, obligations to each other in caring and shar-
care professional is caring, friendly and respectful. ing, giving physical and emotional support, marriage,
• They may have been separated from family and child-raising and teaching of culture. Old people
supportive kinship systems. (elders) are highly regarded and respected. The ‘rules’
• Many are likely to have a loss of control over and the way the kinship system works varies across dif-
many aspects of their life; this has implications for ferent areas.
following health-care advice and treatments. In many regions of Australia, the family related by
• What are the common physical health problems ‘blood’ and marriage follows the pattern outlined in
among the local community's Indigenous people, Figure 3.2.1. For a person in this system: your moth-
and are there treatment resources available? er's sisters are also your mothers and, therefore, their
• Are there culturally appropriate mental health and children are your brothers and sisters. The oppo-
social and emotional wellbeing services available? site applies on the father's side: your father's broth-
• It may be appropriate to advocate for, or support ers are also your fathers and their children are also
the people's efforts to advocate for, socioeconomic your brothers and sisters. Accordingly, for an adult,
and community development – particularly you also have obligations and responsibilities towards
Indigenous community-controlled services and the children of your sisters or brothers as they are
primary health care. also your children. Various fathers, mothers, aunts
• Issues such as a lack of financial resources, and uncles in this system have varying levels of sig-
transport, homelessness and food security may nificance and are afforded particular respect, espe-
impact on a person's ability to follow lifestyle cially in relation to providing cultural knowledge and
advice, attend for appointments and treatment, learning.
and purchase prescription and over-the-counter People not necessarily related by blood or marriage
medicines. may be ‘adopted’ into a kinship system, or given a kin-
ship title (e.g. aunty, uncle, etc.) as acceptance or as a
means of the family knowing how to relate to that per-
son. Aboriginal people, who may or may not be related
Family and kinship by blood or marriage, are often also related to one
Most Aboriginal people are members of an exten- another by a relationship system loosely termed ‘Skin
sive, close kinship system and are very relationship Groups’. This has nothing to do with skin colour, but
focused. Relationship underpins most interaction, with relationships, and is also often connected to moi-
activities and responsibilities of daily life and com- eties. ‘Skin’ groupings and names vary across areas in
munication. Some people may have lost connection to number and ‘rules’. Aboriginal people from near or
kinship systems but often still retain some relation- far, known or unknown, from various related or unre-
ship practices passed on, which originated in these lated language groups, can find a relationship from
kinship systems. within this ‘Skin Group’ relationship system.

Uncle Mum (aunty) Dad (uncle) Aunty

Mum Dad

Cousins Brothers/sisters Sister Ego Brother Sisters/brothers Cousins

(cousins) (cousins)

Nieces/ Sons/ Sons/ Nieces/

nephews daughters daughters nephews

2nd cousins Sons/daughters Sons/daughters Nieces/nephews 2nd cousins

(nieces/nephews)

54 Fig. 3.2.1 The basic kinship family. Terms in italics denote the Caucasian Australian equivalent.
 Indigenous culture and health 3.2
Within the kinship system avoidance relationships
exist (sometimes referred to as ‘poison cousins’), Language and communication
which is a reverence/respect relationship and involves styles
various levels of avoidance. This varies from area to
area, but some examples are: a man may not be able Although many Australian Indigenous people speak
to speak to his mother-in-law; he may not be able to English as their first language, others speak it as their
touch his brother or say his sister's name or be alone second, third or more language, speaking Indigenous
with her. languages on a daily basis. There are varying levels
Thus, an Aboriginal person is most likely to have of English proficiency among Indigenous language
many people to whom they are closely related, are speakers, from very proficient to those who rarely
probably in frequent contact with, and/or who live in speak it. Indigenous people may also regularly use
their area or community. When having to leave home Kriol or ‘Aboriginal English’.
to access health services many, many kilometres away, Communication styles often differ a lot from
separation from family members and familiar sur- Caucasian Australian styles. Indigenous people often
roundings is usually very stressful for Indigenous peo- take time to ‘size people up’. Most are good at observ-
ple and they often feel isolated, alone and scared. They ing body language and can see when there is a genuine,
are often also worrying about the welfare of their chil- caring approach and the speaker wants to communi-
dren and family back at home. cate properly. Communication usually requires a gen-
These kinship systems are usually collectivist based tle and respectful approach with lowered tones.
and have a consensus decision-making process which Obvious attention to them can make an Indigenous
therefore differs from the ‘mainstream’ individualist- person feel very uncomfortable, as most do not like
based culture of much of Australia and Australian to be made to ‘stand out in the crowd’ and describe
health-care systems. this as a feeling of ‘shame’. An abrupt, ‘bossy’ or loud
assertive manner is, of course, most inappropriate and
cuts off all hope of good communication.
Implications for a health-care professional's
Many Indigenous people do not always answer a
practice
question immediately as it is generally considered
• Be aware of the family relationship system of the rude to do so because, out of respect for the ques-
person/family you are working with. tioner, the question deserves to be considered before
• Find out whether they wish to involve other family it is answered. Where English is not the first language,
members and help facilitate this if necessary. there is also much mental exercise going on listening
• In some cases there may be a family spokesperson across languages and interpreting the question and
who will speak for the patient. answer before answering. A lot of direct questioning
• Often an Indigenous person culturally cannot can be intimidating and may cause the person to ‘clam
really give consent to treatment by themselves but up’ or to say what they think you want to hear, because
should involve various family members in care- they wish to please, or in the hope that further in to the
planning whenever possible. Some relations can conversation they will gain more understanding.
discuss relatively minor medical issues, but when Prolonged eye contact during conversation can
the issue is complex or serious often only certain make some Indigenous people feel uncomfortable. It
persons in the kinship system can be involved. is generally not a polite thing to do in their commu-
Check with the client and/or those involved before nication with each other. They may not be looking
these discussions. at the speaker, but may have eyes downcast or look-
• More than one person may be ‘next of kin’, ing in another direction. This can vary, as some are
depending on the particular situation. more used to using direct eye contact with people
• Usually, family relationships and obligations are than others.
more important than individual autonomy. Unnecessary, unfamiliar body contact – sitting too
• An adult presenting with a child for treatment close and close touching – may offend unless you have
may not necessarily be the child's birth parent but established a good rapport with the patient. Many
another relative who also has responsibility for will use handshakes, both among themselves and with
the child and who may also have more say in that non-Indigenous people. However, if this is not done it
child's welfare than the birth parent. should not be taken as an offence.
• A person accessing care may need extra A lot of medical and general health information
support from family members if available and/ given to patients may be new information. Many
or Indigenous staff such as Indigenous Health Indigenous people have a world view and explana-
Workers or Indigenous Liaison/Social tions for body and organ function that may not cor-
Support staff. relate with much of the biomedical world view. They 55
 3.2 SOCIAL AND PREVENTATIVE PAEDIATRICS

have a right to this information and a right to consider • Use pictures/diagrams where possible to assist
it at length, discuss it with family and revisit it with understanding.
staff. Research has shown that Indigenous people want • Do not assume understanding or a lack of
to have the full story about their condition and treat- understanding – find out what the person
ments and that in many instances, for many years, this knows and build from the known to the
has not been provided in their interactions with health unknown.
services. Many people who speak Indigenous lan- • It is necessary to be a good listener and not
guages do not use abstract thinking and concepts and, interrupt ‘pause intervals’. When an Indigenous
if used, the abstract is still grounded in the reality of person can see someone knows how to listen,
the issue being discussed. For a good discussion on this they will often volunteer more information than
and the resulting miss-communication that can occur expected.
when non-Indigenous people use abstract concepts in • Try to reduce some ‘routine’ questioning by getting
communication with Indigenous language speakers, information from a person's file, if available and
the reader is encouraged to read: White Men Are Liars appropriate.
– Another Look at Aboriginal–Western Interactions (by • Avoid asking two questions at once as this can
M Bain, published by AuSIL, Alice Springs, 2005). be confusing and difficult when listening across
Indigenous staff, interpreters and family members languages.
can help with good communication, especially when • Ask open-ended questions rather than questions
the person appears quiet and withdrawn. Some areas that need just a ‘yes’ or ‘no’ answer.
such as the Kimberley region of Western Australia and • If English is not the first language, try to learn
the Northern Territory have formal interpreter services. some of the language used, such as commonly
used words and phrases. As well as helping
communication, this helps build rapport and
Implications for a health-care professional's
mutual respect.
practice
• Check frequently that your message has been
• When working with or without an interpreter, when understood. Asking ‘Do you understand?’ is
English is not the person's first language, speak not a valid way to assess comprehension. Ask the
clearly, use plain standard English, slow it down person to tell you what they think you have said
(not too slow) and break it up. in their own words and summarize/check your
• Avoid using jargon and colloquialisms. understanding of what they have said.
• ‘Aboriginal English’ and Kriol are languages with • If direct eye contact is not being used, take cues
their own distinct structures. Do not attempt to from the person. You can be beside them so both
speak these by using your own version of ‘broken are looking to the front.
English’ as it will probably not make sense (and • Find out whether there are Interpreter services in
may sound insulting). the area and if so, how to access these.

PART 2 MAORI VIEW OF CHILD HEALTH AND ILLNESS

Leo Buchanan

Practical points • Some clinical problems are uncommon but important

conditions of genetic origin.
Key cultural concepts • Physical abuse of children is distressingly common amongst
Maori.
• A child can never be seen in isolation from the
family. Some potential key ways forward
• Full health involves the integration of spiritual, emotional and • For many Maori to regain familiarity with what it is to be truly
physical matters along with family health. Maori.
• The child is seen as a gift. • For the skilled sensitive promotion of significant
breastfeeding consistent with World Health Organization
Clinical problems in Maori children recommendations.
• Some clinical problems are a reflection of persisting • For more doctors of good will to become familiar with and
socioeconomic disadvantage for many Maori. responsive to Maori cultural values.

56
 Indigenous culture and health 3.2
is also the word for the child's more immediate ­family;
Maori children in New Zealand whenua is the word for the placenta, but is also the word
Maori children are an interesting, colourful and at for land. Again the meaning of words illustrates the
times challenging part of the New Zealand landscape. difficulty of seeing areas of health as being containable
They accounted for 22% of New Zealand's 64 120 in isolated compartments. The word for intense anger
births in 2009. They are, therefore, highly visible in is pukuriri – literally ‘fighting within the stomach’.
both urban and rural New Zealand. They also have Likewise, the word for depression is manawapouri –
a significant presence throughout Australia as part of ‘blackness within the heart’.
what is whimsically described as the 120 000-strong In essence, the concept of health and wellness is
Ngati Skippy Maori immigrants. The broad ethnic therefore seen as always involving an interplay between
breakdown of New Zealand's children under the age spiritual matters, thoughts and feelings, the physical
of 15 years in the 2006 census was as follows: functions of the body, the family and the environment.
European 56% In te ao Maori (the Maori World), all manner of possi-
Maori 22% ble explanatory links between events occurring around
Pacific Island 11% the same time or on a certain day would be considered
Asian 10% as potentially contributing to an illness. There is empa-
thy within Maoridom with the kind of Hippocratic
notion that medicine is primarily an art that uses sci-
ence for its own purposes on occasions. Maori would
Who is Maori? struggle with the idea that the only proper approach in
Until the 1980s, the official census definition was based medicine should hinge around randomized controlled
on a child having ‘half or more’ Maori origin. Now, trials or other manifestations of evidence-based med-
however, census data and common usage define Maori icine. A Maori doctor's practice would look to both
as a person of Maori ancestry who chooses to identify science and art for guidance. This approach would be
as Maori. It is important to be aware that the unify- seen as no different from that of a brilliant scientist
ing term Maori really dates from the time of European such as Pascal believing firmly in the basic Christian
occupation of New Zealand. Historically, tribal divi- concept that God could become human.
sions were quite marked. Informed observers as recently
as the 1930s referred to Aotearoa (New Zealand) as a
series of islands joined by narrow strips of land. The significance of the child
within Maori culture
The fourth concept of the four walls of health helps
What are the particular features place the child – Taha whanau. The health of the child
defining health for Maori? cannot be considered without regard to the family as a
whole. The child is seen as a taonga (a special gift) to
Sir Mason Durie brilliantly summarized the wholeness the whanau (family). The child brings a continuation of
or wellness of Maori as being thought of as the four the inheritance lines (whakapapa). The child is seen as
walls of a house – each needing to stand to support the the hope for the future. The care and upbringing of the
others. The four walls were listed as: child would be seen as not belonging just to the parents
• Taha wairua (recognizing the intrinsic spiritual but to the extended family, with grandparents playing a
nature of humans) special role. Maori has been described as a culture that
• Taha hinengaro (concerned with thoughts and feelings) puts others before self, so that a young child would be
• Taha tinana (the physical side of body functioning) expected to receive considerable arohatanga (warmth
• Taha whanau (the role of the extended family). and love) and awhinatanga (help and assistance).
Measuring all these aspects of health is not easy, with
the spiritual side perhaps being the most challenging.
Yet some would see Taha wairua as the most important
aspect – the need to acknowledge or have a faith in a Historical issues of significance
‘life force’ – a God outside of yourself. to Maori health
This turning outwards is consistent with the impor-
The Treaty of Waitangi
tance for Maori of being at one with the environment.
Indeed, the special relationship between the person The document serving as a partnership for the English
and the created environment is reflected in the shared Crown with Maori and thus forming the basis for the
meaning of some key words: whanau means birth, but modern New Zealand nation was the Treaty of Waitangi.
57
 3.2 SOCIAL AND PREVENTATIVE PAEDIATRICS

Maori far outnumbered Europeans in the New In all situations, the approach to the family has to be
Zealand of the 1840 Treaty signing. The Treaty was con- one of courtesy and respect. Welcoming or acknowledg-
structed in both Maori and English with debate continu- ing every member of the supporting family is a good
ing to this day over important nuances in the differing start. Some general enquiries about what is happening in
meanings of key words in the English and Maori ver- the family and where they are from are advisable in the
sions. In the discussions over what the Treaty might have non-emergency situation before plunging into defining
guaranteed for the health of Maori, importance is placed the particular concerns about the child. This comment
on the second article promising protection to Maori of illustrates the importance of hastening slowly in work-
their taonga (treasures). Health is seen as one of these. ing with Maori families. Polynesians as a whole prefer
Likewise attention has been frequently drawn to the not to be rushed in exchanges as important as those con-
third article promising to Maori the same rights (taken cerning health. Ward rounds need to be a bit longer if
to include health rights) as their new English brothers the real face-to-face and heart-to-heart encounters that
and sisters. Other commentators have drawn attention Maori seek in these matters are to be achieved.
to the importance of the so-called fourth clause of the A doctor, especially if young, should tend towards for-
Treaty in recognizing the spiritual component of health mality in dress code when working with Maori. In one
for Maori. This was read only at the important first sign- sense the doctor may be partly seen as having a similar-
ings at Waitangi itself. It read: ‘The Governor says the ity within Maoridom to a tohunga – a person with spe-
several faiths of England, of the Wesleyans, of Rome and cial training and responsibilities to guard things that are
also the Maori custom, shall alike be protected by him.’ special and sacred. In outpatient clinic settings, some
distance and space between the doctors and the whanau
The New Zealand wars should be organized, as this initial encounter can then
mimic the rituals of engagement when Maori first meet
Overlapping with the implications for Maori health aris- in the very special area within Maori reserves called
ing from breaches of the Treaty of Waitangi are the New marae. Consultants on teaching ward rounds or in multi-
Zealand land wars. These were strung out over about 40 disciplinary clinic sessions might like to introduce or refer
years from the late 1840s and led to huge confiscations of to others present with them as their supporting whanau.
Maori Land by the Crown as ‘Reparation’ for the armed
conflicts that arose especially in the Waikato and Taranaki
areas. The land confiscations suited the Government's
purposes admirably to give it an income and to meet the
The organization of health
land demands of rapidly escalating numbers of British services for Maori
immigrants. The land confiscations were quite dispropor- In the 2006 census, only 3% of New Zealand medical
tional to the numbers of soldiers killed or costs incurred. practitioners identified themselves as Maori, whereas
In Taranaki, for instance, nearly two million acres of the total Maori population was 15%. Even among doc-
land were taken. These conflicts led to the loss of life tors identifying as Maori, a wide variation exists in their
of key Maori leaders; the loss of land on which Maori knowledge of Taha Maori (Maori things). Currently,
could stand tall as well as land from which to generate an fewer than 10 of New Zealand's 292 vocationally reg-
income; and for some a sense of shame and identity con- istered paediatricians have any Maori affiliation, so in
fusion that persists to this day. In recent years the govern- the short to medium term it is difficult to deliver health
ment has attempted to readdress these land confiscations services by Maori for Maori – which is the preferred
and Treaty of Waitangi breaches, with combinations of option for many Maori. Rather, non-Maori medical
apologies and very modest monetary compensations. practitioners of good will – sensitive to Maori nuances –
need to support Maori children and their families.
Doctors working with children should become familiar
Cultural competency in working with specific local Maori health initiatives that relate to
children. Most public hospitals have a definitive Maori
with Maori families liaison service, and community-based Maori health
Cultural competency has come more to the fore in facilities are becoming more common.
New Zealand since a legislative change initiated by the
Medical Council of New Zealand that any medical prac-
titioner must be culturally competent as well as clinically Socioeconomic and cultural
competent. My own view has always been that it is not
possible to be clinically competent without being cultur-
contact issues
ally competent. A working diagnosis of cultural com- Maori continue to be significantly over-represented in
petency could be the capacity to recognize and interact less favourable socioeconomic clustering within New
58
respectfully with any individual's particular culture. Zealand. Socioeconomic disadvantage includes lower
 Indigenous culture and health 3.2
income levels, higher unemployment rates, greater use
of temporary or rental accommodation, and lower Genetics and environment
levels of education achievement. The higher hospital- in clinical situations
ization rates of Maori infants (in 2009, Maori infants
comprised 35% of all public hospitalizations com- There is a tendency to look towards adverse environ-
pared with 22% of births) and high rates of respiratory mental conditions as major contributors to those clini-
illness, rheumatic fever and skin sepsis are all seen as cal conditions seen more commonly in Maori children
examples of the price of socioeconomic disadvantage than in children of European ethnicity. These are cer-
as conventionally defined. One frustration for Maori, tainly significant factors in the markedly increased
though, is that the measurements of ‘Internal Forces’ incidence of rheumatic fever, skin sepsis, respiratory
that may shape health or wellbeing are more problem- tract infections and glue ear. However, other condi-
atic. How does one measure the presence or absence tions such as α-thalassaemia trait (10% incidence), a
of shame at having too much or too little Maori, at particular type of congenital nephrotic syndrome, and
losing contact with one's own tribal roots, being cut the rare but fatal non-ketotic hyperglycinaemia are
off from extended family, or just losing the notion of entirely genetic in origin. It is likely that the increased
what it is to be Maori? The 2006 census showed that incidence of biliary atresia in Maori is also genetic
84% of Maori now live in urban areas. Contact with in origin. Yet other conditions, such as the common
Taha Maori (Maori things) is likely to be more of a entity of attention-deficit disorder, would appear to
challenge in urban areas. It is true that some measur- reflect both genetic and environmental factors.
able socioeconomic markers have improved for Maori In infancy, gastro-oesophageal reflux, infantile colic
over the last 10 years. Maori unemployment rates, for and food allergies, although all occurring amongst
instance, may be dropping, but what if this is at the Maori, are much less often presented to paediatricians
price of family-unfriendly work hours or is associated as a perceived problem by Maori families. Whereas
with the increased frequency of Maori infants and obesity may be over-represented amongst Maori,
toddlers spending substantial amounts of time in day- anorexia nervosa appears to be very uncommon –
care arrangements away from their family? partly one suspects in both situations a result of cul-
tural perceptions of desirable body size.
In the development and behavioural areas, practi-
tioners need to be careful not to attribute the various
Clinical example behavioural manifestations associated with either
attention-deficit/hyperactivity disorder (ADHD) or
Rangi is a 6-year-old boy who presented to the autism to the Maori child living in a dysfunctional
emergency department (ED) with a history of family. The family dysfunction may well result from
intermittent fevers for some days and then, on the fact that the same conditions are present to vary-
the day of referral, a complaint of back pain on
walking and some abdominal pain. He was admitted under
ing degrees in one or both parents.
the general surgeons who noted a C-reactive protein (CRP) It is always important to consider what special sig-
level of 122 mg/L and haemoglobin level of 85 g/L, and felt that nificance a child's diagnosis may have to the whanau
appendicitis was possible. A normal appendix was removed (extended family). The word tuberculosis may trigger
and the child's symptoms seemed to settle before discharge
home. Rangi re-presented to the ED 2 weeks later with a
history of limping on the left leg and intermittent fevers over
a week. There was evidence of swelling over the left ankle Clinical example
and tenderness of the left big toe. His CRP level was 174 mg/L
and there was a persisting normochronic anaemia and mild Rawinia is an 18-month-old toddler referred to
neutrophilia. He was admitted under the orthopaedic service paediatric outpatients because of anaemia,
with a suspected diagnosis of osteomyelitis or septic arthritis. unresponsive to iron. A blood count aged
The left ankle was aspirated, with 56 000 white cells 15 months, performed by her GP because
found in a murky aspirate. Treatment for osteomyelitis of recurrent upper respiratory tract infections, showed a
was commenced, but 1 week later there was again haemoglobin level of 95 g/L and a mean corpuscular volume
evidence of arthritis of the left ankle and no growth from (MCV) of 60 fL. Microcytosis and hypochromia were noted on
the aspirate. A general paediatrician was consulted for the film smear. A repeat blood count after 6 weeks of oral iron
the first time and heard a pansystolic murmur at the apex. showed no improvement. The paediatrician was confident that
An urgent echocardiogram showed moderate mitral the iron had been given and, noting the Maori ethnicity of the
valve incompetence. Antistreptococcal antibody titres child, established that iron and ferritin levels were normal after
were markedly raised. Rangi was diagnosed as having finding no clinical abnormality on examination. He suspected
acute rheumatic fever. Rheumatic fever should be strongly the harmless entity of α-thalassaemia trait, which needs no
considered in the differential diagnosis of any Maori child treatment, and in due course confirmed this suspicion with
presenting with persistent fevers and joint pains or arthritis. appropriate DNA studies. 59
 3.2 SOCIAL AND PREVENTATIVE PAEDIATRICS

recall of the ravages this malady caused to family parenting programmes or offering intervention ser-
members in earlier generations. Likewise, a diagno- vices quickly to families dealing with a powder-keg cri-
sis of asthma or epilepsy will have added meaning if sis such as a persistently screaming baby. Regrettably,
any family members have died from these conditions. the truth is that none of these interventions seems to
Finally, in assessing various diagnostic possibilities, it have had a major impact on lowering the incidence of
is worth remembering that some conditions such as cys- physical abuse.
tic fibrosis or coeliac disease are much less likely amongst
children with a major Maori ethnic component.

A way forward
Could the key in reality to this challenge be the need to
The physical abuse problem work toward an attitudinal change within Maoridom
Notwithstanding the shadows over morbidity and towards children – to recapture the idea that children
even mortality data arising from the infections are a gift? One of the oldest words in Maori for defin-
amongst Maori children, the longest blackest shadow ing a woman is Ukaipo – literally the breastfeeder in
in my view is that of physical abuse. Compared with the night. Yet the breastfeeding rate amongst Maori
non-Maori children, Maori are two to three times now is lower at 17% at the 6-month mark than for any
more likely to be hospitalized for injuries sustained other ethnic group in New Zealand. It does not seem
as a result of deliberately inflicted physical harm than unreasonable to suggest that a vigorous but sensi-
any other ethnic group. The death rates and perma- tively promoted plan of supporting the World Health
nent serious neurological handicap rates in Maori Organization's recommendations that women should
from the shaken baby syndrome are amongst the high- significantly breastfeed to at least 12 months of age
est recorded internationally for any ethnic group. might, through its bonding powers, reduce physical
It may be a matter of opinion as to whether any link abuse in the young as well as reduce early respiratory
can be construed between these facts and the high rate tract infections and glue ear. Such a programme, how-
of induced abortions evident amongst Maori women ever, would have to be part of a wider undertaking to
in more recent years. What is undeniable is that Maori promote to all Maori a clearer appreciation of what it
birth rates have plummeted dramatically since the is to be truly Maori. In this way Te Rangi Hiroa's 1930
1970s to be now only a little higher than non-Maori claim that Maori is a culture that puts other before self
rates, except amongst adolescents. might have a more robust ring to it. One starting point
A number of one-off solutions to the Maori phys- for such an undertaking could be an emphasis on Sir
ical abuse scourge have been suggested. They have Mason Durie's notion that four walls of the house
included lowering the relatively high teenage preg- need to be in order if true full health is to become real-
nancy rate; targeting alcohol and drug abuse; recogniz- ized. It is a case of back to the future.
ing and reducing family violence; promoting positive Kia Kaha! Kia Manawanui! Tihei Mauriora!

60
 Nutrition
Zoe McCallum, Julie Bines
3.3
Adequate and appropriate nutrition is vital for a child's In 2003, the Australian National Health and
optimal growth and development. Many diseases in Medical Research Council (NHMRC) released a doc-
adult life have their antecedents in childhood nutri- ument that includes ‘Dietary Guidelines for Children
tion, including, hypertension, type 2 diabetes, obesity, and Adolescents in Australia’ (available at: http://
hyperlipidaemia and some cancers. In the hospital- www.nhmrc.gov.au/_files_nhmrc/file/publications/
ized child, nutritional requirements may be increased synopses/n31.pdf). These guidelines provide com-
as a result of inadequate intake, malabsorption or due plete nutritional advice for healthy children from
to disease-related increased requirement for specific birth to 18 years of age. They have been updated
nutrients. In some situations oral feeding may be inad- and will be available from 2011 on the website www.
equate to support weight gain and growth. Options for nhmrc.gov.au.
nutritional support and nutritional therapy including
specialized enteral formulas and supplements or par-
enteral (intravenous) nutrition may be required.
Dietary Guidelines for Children and Adolescents
in Australia (National Health and Medical
Research Council 2003)
Practical points Encourage and support breastfeeding
Children and adolescents need sufficient nutritious
• Nutrition in childhood, starting from in utero, is a key foods to grow and develop normally
determinant of a child's growth and development, and • Growth should be checked regularly for young
future adult health status. children
• Nutritional assessment requires a dietary history, physical • Physical activity is important for all children and
examination and sometimes blood tests. adolescents
• Breastfeeding has many benefits over infant formula for
Enjoy a wide range of nutritious foods
both mother and infant.
• A range of infant formulas are available with differing • Children and adolescents should be
protein sources and indications. encouraged to:
• Solids may be introduced after 6 months. • Eat plenty of legumes and fruits
• ‘Fussy’ toddler eating is a normal developmental • Eat plenty of cereals (including breads, rice,
phenomenon; threats, scolding, bribery and use of food as pasta and noodles), preferably wholegrain
a reward are likely to create rather than resolve problems. • Include lean meat, fish and poultry and/or
• Water is the best non-milk drink for children (not juice or
alternatives
other sugar-sweetened drinks).
• Low-fat milk is appropriate for children over the age of • Include milks, yoghurts, cheese and/or
2 years. alternatives
• Reduced fat milks are not suitable for young
children under 2 years, because of the high
energy needs of young children, but reduced fat
Nutritional requirements varieties should be encouraged for older
children and adolescents
Nutrients and dietary guidelines
• Alcohol is not recommended for children
Nutrients are food components that are required for • And care should be taken to:
optimal growth, development and body function. • Limit saturated fat intake and moderate total
Macronutrients (protein, fat and carbohydrate) are the fat intake. Low-fat diets are not suitable for
basic building blocks for energy, lipid and nitrogen compo- infants
nents of the body, and are essential for cellular homeosta- • Choose foods low in salt
sis. Micronutrients (vitamins, minerals and trace elements) • Consume only moderate amounts of sugars
are required in much smaller amounts. Individual nutrient and foods containing sugars
requirements vary with age, size, growth and health status. Care for your child's food: prepare and store it safely
61
 3.3 SOCIAL AND PREVENTATIVE PAEDIATRICS

Energy Physical examination and anthropometry

Food is metabolized and provides energy required by Physical examination gives a general impression of nutri-
the body for growth and synthesis of new tissue, for tional status, including signs of anaemia, jaundice, wast-
metabolic processes, and for physiological functions ing, oedema, lethargy, muscle weakness and fat stores.
and activity. Examination may reveal evidence of specific micro-
Fat, carbohydrate and protein provide energy, which nutrient deficiency, including pallor, bruising or
is measured in kilojoules (kJ) or kilocalories (1 kcal bleeding, skin, hair and gum abnormalities, and neu-
provides 4.182 kJ). Fat provides a concentrated source rological or ophthalmological disorders. In adoles-
of energy, contributing 37 kJ/g, approximately twice cents, the stage of puberty should be documented.
that provided by an equivalent amount of protein or Anthropometry refers to the measurement of physi-
carbohydrate. Fat contributes 50% of the total energy cal dimensions and body composition. Measurement
in breast milk or standard infant formula. The average of height/length and weight gives the most useful
diet of older children provides 30–40% of total energy assessment of overall nutritional status, although nor-
from fat, 45–55% from carbohydrate and about 15% mal growth can still occur in marginally malnourished
from protein. Most of the energy intake in children is children. Serial measurements of growth add valuable
used for growth and development. Recommendations information about the impact and chronicity of nutri-
for energy intake are difficult to determine, even tional compromise. The following routine measure-
for individuals of similar age, sex and size, because ments are used:
requirements vary. The NHMRC recommends that for • recumbent length before 2 years of age, or height
children aged 5–14 years approximately 30% of energy after 2 years of age
intake should be fat, with no more than 10% coming • weight for age
from saturated fat. • weight for length/height
• head circumference (used until 36 months of age)
• growth velocity
• skinfold thickness (triceps and other sites as
Nutritional assessment indicated)
• mid-arm circumference.
Nutritional assessment is the process by which Growth charts for height or length, weight and head
the individual is evaluated for normal growth and circumference are used to monitor growth at differ-
health, for risk factors contributing to disease, and ent chronological ages (see Chapter 19.1). Specific
for early detection of nutritional deficiencies and ethnocultural and syndrome-specific (Down, Turner)
excesses. growth charts exist. Intrauterine growth curves have
Comprehensive nutritional assessment includes: been developed for gestational ages 26–42 weeks using
• dietary assessment birth weight and length data for infants born at suc-
• physical examination, including anthropometry cessive weeks of gestation. Premature infants should
• laboratory studies. have the weight corrected until the child is 24 months
of age, length until the child is 36 months of age, and
head circumference until the child is 18 months of age.
Dietary assessment
Patients requiring long-term monitoring of nutri-
The primary care giver(s) should be asked what the tional status should have serial measurements of mid-
child usually eats in a typical day, in all settings that arm circumference and triceps skinfold thickness to
the child is in (i.e. home, child care, outings). Children assess fat and muscle stores.
derive up to 30% of their energy from snacks, so it is
important to include these in the assessment of all
Body mass index
food and fluids consumed.
Qualitative methods include a dietary history and Serial body mass index (BMI) is used as a repre-
food frequency questionnaire. These do not allow for sentative measure of body fatness in children (see
the precise calculation of energy or nutrient intakes Chapter 3.4). It cannot, however, distinguish between
but rather determine the pattern, style and types of excess weight produced by adiposity, muscularity or
foods eaten. oedema. In children with nutritional deficiency, and
Quantitative methods calculate precise energy and in the setting of overweight and obesity, it is a useful
nutrient intakes and include a 24-hour food record and measure of adiposity. It is calculated from the formula
a 3-day food record. BMI = weight [kg]/height [m]2. A BMI greater than
If the initial dietary assessment raises concerns, the 85th percentile is defined as overweight and a BMI
62 referral should be made to a dietitian. greater than the 95th percentile as obesity.
 Nutrition 3.3
Table 3.3.1 Laboratory parameters for assessing
nutritional status
Breastfeeding
Breastfeeding is the best form of nutrition for the
Status Parameters growing infant. Australian hospitals are encouraged to
Protein Albumin, total protein, pre-albumin, adopt the ‘10 steps to successful breastfeeding’ listed
urea, 24-hour urinary nitrogen, in Box 3.3.1.
carnitine The weight percentiles and body composition of
breastfed infants differ from those who are formula-
Fluid and electrolyte, Serum electrolytes, acid–base,
fed. In general, breastfed infants tend to grow rapidly
and acid–base urinalysis
in the first few months and then grow at a slower rate
Glucose tolerance Serum glucose, HbA1c, insulin than current percentiles. This may result in their weight
appearing inadequate when plotted on current growth
Iron Serum iron, serum ferritin, full blood charts, even when they are healthy. Current NHMRC
examination recommendations for weight gain in infancy are 150–
200 g/week at age 0–3 months, 100–150 g/week at age
Minerals Calcium, magnesium, phosphorus,
3–6 months, and 70–90 g/week at age 6–12 months.
alkaline phosphatase, bone age,
bone density Preterm breastfed infants require iron supplements
from 4–8 weeks of age. Those born at a gestation
Vitamins Vitamins A, D, E/lipid ratio, C, B12, of less than 32 weeks usually require fortification of
folate, PT/PTT breast milk with protein and calories in the preterm
period to prevent growth failure. All breastfed infants
Trace elements Zinc, selenium, copper, chromium, should receive vitamin K on the first day of life.
manganese
Breastfeeding has many benefits for both the infant
Lipids Serum cholesterol, HDL cholesterol, and the mother. Breast milk is tailored to the infant's
triglycerides, free fatty acids needs and contains many factors protective against infec-
tion (see Infant formulas, below) and growth ­factors.
HbA1c, haemoglobin A1c; HDL, high-density lipoprotein; PT,
prothrombin time; PTT, partial thromboplastin time.

Box 3.3.1 Ten steps to successful breastfeeding

Laboratory assessment
Every facility providing maternity services and care for
Laboratory assessment is used to detect subclinical newborn infants should:
deficiency states or to confirm a clinical diagnosis. 1. Have a written breastfeeding policy that is communicated
It provides an objective means of assessing nutri- routinely to all health-care staff
tional status. Laboratory assessment is summarized in 2. Train all health-care staff in skills necessary to implement
Table 3.3.1. this policy
3. Inform all pregnant women about the benefits and
management of breastfeeding
4. Help mothers initiate breastfeeding within half an hour of
Nutrition in utero birth
5. Show mothers how to breastfeed, and how to maintain
Research into the fetal origins of adult health has iden- lactation even if they are separated from their infant
tified fetal nutrition as being of critical importance. 6. Give newborn infants no food or drink other than breast
milk, unless indicated medically
Maternal nutrition is a powerful epigenetic determi-
7. Practise rooming-in (allow mothers and infants to remain
nant of not only birth size and subsequent growth, together), 24 hours a day
but also the future risk of metabolic syndrome (hyper- 8. Encourage breastfeeding on demand
lipidaemia, hypertension, coronary artery disease, 9. Give no artificial teats or pacifiers (also called dummies or
type 2 diabetes) in adult life. The ‘Barker’ hypothesis soothers) to breastfeeding infants
states that adaptations undergone by the starved fetus 10. Foster the establishment of breastfeeding support groups
and refer mothers to them on discharge from hospital or
in utero to become ‘thrifty’, that is to make maximum
clinic
use of scarce nutrients, may in the setting of adequate,
or even abundant, nutrition become counterproductive. Source: World Health Organization 1989 Protecting,
Most in utero malnutrition in Western societies, how- promoting and supporting breastfeeding: the special role
ever, results from placental insufficiency. Periconceptual of maternity services, a joint WHO/UNICEF statement. WHO,
Geneva. Available at: http://www.unicef.org/newsline/
and antenatal folate supplements markedly reduce the
tenstps.htm
risk of neural tube defects and are advised. 63
 3.3 SOCIAL AND PREVENTATIVE PAEDIATRICS

Breastfed infants, in comparison with formula-fed i­nsufficient milk supply is often perceived to be a
infants, have improved neurodevelopment and a lower major problem, which may lead to unnecessary ces-
incidence of infection, diabetes, necrotizing enterocolitis sation of breastfeeding. Most women are physiologi-
and gastro-oesophageal reflux. Although there is some cally able to produce sufficient milk. Appropriate
evidence that breastfeeding may protect against allergic education, encouragement and support may be all
disease in atopic families, the evidence for a population- that is needed.
wide protective effect is inconclusive. Breastfeeding may
partially protect women against premenopausal breast
cancer, ovarian cancer and osteoporosis. Lactational
amenorrhoea may act as a contraceptive adjunct, espe- Infant formulas and other milks
cially in the developing world.
When breast milk is not available, an infant formula
is required. All infant formulas used in Australia are
Breastfeeding initiation required to be manufactured in accordance with the
Australia New Zealand Food Standard Code, which
Information about the advantages and management
specifies the requirements for composition, quality
of breastfeeding, including where to obtain advice
and labelling for infant formulas.
and support, if needed, should be made available to
Although the nutritional composition of infant for-
all new mothers. Reasons given by mothers for stop-
mulas resembles that of human milk, it is not possible
ping breastfeeding include pain and discomfort (e.g.
to incorporate the many immunological factors that
sore nipples, mastitis, thrush), anxiety regarding the
have been identified in human milk. These include
adequacy of milk supply, and a return to work.
specific immune factors such as immunoglobulin A,
maternal lymphocytes and macrophages, and other
Common problems with breastfeeding non-specific protective factors such as lactoferrin and
lysozyme.
Problems may exist with both maternal breastfeeding
technique and anatomy, as well as with the infant's
suck and oropharyngeal anatomy. In ­ addition, Feeding requirements of infants
The infant's appetite determines the volume and num-
ber of feeds required. Demand feeding for bottle-fed
infants is appropriate. Term infants require approxi-
Clinical example mately 120–160 mL per kg per day to meet their fluid
Isabella was born at term following an and nutrient needs during the first 4–6 months of life
uneventful pregnancy and delivery. Her when milk feeds provide the sole source of nutrition.
mother was very keen to feed her first baby The number of feeds per day changes as the infant
but experienced considerable pain from sore, grows, and the number of feeds per day decreases with
cracked nipples soon after discharge from hospital. She increased feed volumes. Infants under 6 weeks of age
returned to the hospital to seek advice from a lactation usually feed every 3 hours and rarely sleep through the
consultant, who noted that Isabella was incorrectly
night before 8 weeks. Infants experience an appetite
positioned and attached.
Correct positioning and attachment, which is vital for spurt at 2 weeks, 6 weeks and 3 months.
successful breastfeeding, resolved the problem of sore Establishment of a feeding pattern is often easier for
nipples, enabling Isabella's mother to continue to breastfeed mothers of breastfed infants, as they respond to the
without discomfort. infant's demands and do not focus on the volume con-
Isabella breastfed on demand, approximately 3-hourly. sumed at each feed. The actual number and volume of
At 4 weeks of age she started sleeping longer between
feeds taken by bottle-fed infants causes considerable anx-
feeds and suckled less vigorously. Her mother became
very anxious and was concerned that her milk supply was
iety for some parents. Reassurance should be provided
inadequate, particularly as it became apparent that Isabella that the infant's appetite is the best guide, and as long as
had not gained weight when weighed at a clinic visit. It was the infant gains weight consistently, but not excessively,
evident that the feeding difficulty was the result of infrequent and is thriving and active, intake is satisfactory.
feeding and maternal anxiety. She was encouraged to feed
her baby more frequently, including during the night, and to
ensure that Isabella drained the first side before offering the Composition of standard infant formulas
second. Her husband was encouraged to bring Isabella to Standard infant formulas are recommended for
her for feeding during the night. As a result, the milk supply
increased and Isabella gained weight appropriately. Timely
healthy term infants who are not breastfed. The nutri-
advice, and encouragement and support prevented this ent compositions of these standard formulas are very
mother from ceasing breastfeeding unnecessarily. similar, with minor variations in the protein, fat and
64
carbohydrate content (Table 3.3.2).
Table 3.3.2 Breast milk and artificial formula compositions

Energy (kJ Carbohydrate

(kcal)/100 mL) Protein source Fat source source Indication Concerns

Breast milk 289 (69) Protein source is Short-, medium- Lactose The preferred infant feed HIV infection in mother
whole protein and long-chain fats

Breast milk fortified with 432 (103) Protein source is Short-, medium- Lactose Preterm infant
FM85 (5%) and Poly- whole protein and long-chain fats
Joule (4.2%)

Preterm formula (e.g. 340 (81) Whey : casein: Coconut, oleic, Lactose Preterm infant Does not contain immunoglobulins,
S26-LBW LCPs) 60 : 40 palm, soy. LCPs, and other non-specific protective and
MCT (12.5%) growth factors

Term formula – cow's 273 (65) Whey : casein: Oleo, coconut, soy, Lactose If breast milk not available Does not contain immunoglobulins,
milk based (e.g. S26, 60 : 40 oleic, palm, canola, and other non-specific protective and
Nan1) corn growth factors

Soy formula (e.g. 274 (65) Soy isolate Oleo, coconut, soy, Corn syrup Soy formulas should be used in The presence of phytates in soy
Infasoy) oleic solids, sucrose galactosaemic infants, and for formulas may inhibit absorption of
infants of vegetarian families minerals, particularly calcium. Up to
reluctant to use cow's milk 50% of children with cow's milk protein
intolerance will also be allergic to
soy protein; it is preferable for these
children to be given a formula with
hydrolysed protein

Continued

Nutrition
3.3
65
66

3.3
SOCIAL AND PREVENTATIVE PAEDIATRICS
Table 3.3.2 Breast milk and artificial formula compositions—cont'd

Energy (kJ Carbohydrate

(kcal)/100 mL) Protein source Fat source source Indication Concerns

Lactose modified 286 (69) Casein dominant Vegetable oil Maltodextrin, Low-lactose or lactose-free In older children with lactose
formulas (e.g. De-Lact) glucose, formulas are the feeds of choice intolerance, enzymatic drops
galactose for formula-fed infants with true containing lactase may be used with
lactose intolerance cow's milk

Hydrolysed formulas 280 (67) Whey hydrolysate, Vegetable oil, MCT Corn syrup Semi-elemental formulas are These formulas are expensive and
(peptide) (e.g. The protein in (50%) solids designed to meet the needs of should be used only with medical
Pepti-Junior, Alfare) these formulas infants who are intolerant of intact guidance
is partially protein, who maldigest protein and
hydrolysed to fat, or who have problems with
peptides and free severe diarrhoea, food intolerance
amino acids or allergy

Extensively hydrolysed 298 (71) Amino acids Safflower, soy, Dried glucose Infants with multiple food allergies These formulas are expensive and
(amino acid) formulas (elemental) coconut syrup or abnormal gut may require should only be used with medical
(e.g. Neocate, EleCare) elemental formula in which the guidance. Taste bitter
protein has been totally hydrolysed
to amino acids

HIV, human immunodeficiency virus; LCP, long-chain poly-unsaturated fatty acids; MCT, medium-chain triglycerides.
 Nutrition 3.3
• Protein. All standard infant formulas have cow's ­ reparation of formula. Both diluting and concentrat-
p
milk protein as a basis, which is modified in order ing formula can lead to serious electrolyte disturbance
to produce a protein composition more like that in the infant and should be avoided.
of human milk. The cow's milk protein is modified Breastfed babies do not require other fluids, even
through heat treatment processes, with the addition in hot weather, if they are fed frequently. Formula-
of whey in order to modify the casein : whey ratio fed infants may be offered small amounts of cooled,
so that it is similar to that of human milk. Despite boiled water between feeds during very hot weather.
this, the amino acid profiles of infant formulas
remain different from those of human milk. Other milks
• Fat. The fat sources in standard infant formulas
are a mixture of vegetable oils with or without Cow's milk is appropriate to be introduced to infants
butterfat. It is possible to achieve ratios of over 12 months. The fat in milk is an important source
saturated to unsaturated fatty acids that are of energy, fat-soluble vitamins and fatty acids for
similar but not identical to those of human milk. young children.
Although the degree of saturation may be similar, Cow's milk has lower iron content and higher levels
the structure of the fats is not the same, resulting in of protein, sodium, potassium, phosphorus and calcium
differences in digestion and absorption. The fatty than human milk or formula. It also has a higher renal
acid composition of human milk also varies with solute load and lacks vitamin C and essential fatty acids.
the maternal diet, and can be modified favourably Low-fat (2%) cow's milk can be given to children over
by substituting some of the saturated fats in the diet 2 years of age. Skim milk (no fat) is not recommended
with appropriate mono- and poly-unsaturated fatty unless there is a specific medical condition, such as
acids. Some manufacturers now add long-chain hypercholesterolaemia. Soy milk should not be used for
poly-unsaturated fatty acids to formulas, as there children under 2 years of age. Calcium-supplemented
is evidence that these play an important role in brands should be chosen if used for older children.
infant development, with advanced visual pathway Goat's milk is not recommended for infant feeding.
maturation and a postulated benefit for intelligence. It has a similar macronutrient composition to cow's
The fat composition in formulas may also promote milk but there are micronutrient deficiencies. If par-
the formation of soaps in stools, contributing to ents insist on using goat's milk, a goat's milk infant
constipation in some infants. formula fully supplemented with vitamins and min-
• Carbohydrate. The carbohydrate source in standard erals should be used, because goat's milk is markedly
infant formulas is lactose. deficient in folate and other vitamins. If fresh goat's
All formulas are supplemented with vitamins and miner- milk is used, it must be pasteurized or boiled and
als. These standard infant formulas are suitable for the ­supplemented with folic acid and vitamins B12, B6, A
first 12 months of life. The practice of changing from one and C. Infants with cow's milk protein intolerance are
formula to another because an infant is irritable or unset- usually also intolerant to goat's milk protein.
tled should be strongly discouraged. This usually does
not help settle the infant and has the potential to lead to
mistakes in reconstitution, as scoop size and methods of Clinical example
preparation can vary between formula brands.
Thao brought her 13-month-old child, Madison,
Soy formulas are sometimes recommended for use in to the doctor for review of her cold. She reported
infants with suspected cow's milk protein intolerance, that Madison constantly had a cold and was
colic, and in an attempt to prevent allergies. However, always tired, but she had attributed this to the fact
up to 50% of children with cow's milk protein intoler- that Madison was still little and had recently started child care.
ance will also be allergic to soy protein; a hydrolysed Madison's height and weight were both on the 50th centile.
formula may be more appropriate. The GP noticed that she was pale, however, and asked about
her diet. Thao replied that Madison was a ‘fussy eater’ but
loved her milk. On further questioning the GP discovered that
Preparation of formula she had commenced cow's milk at 9 months of age and was
currently consuming 800 mL per day. Iron studies and a blood
Having selected an appropriate formula, it is essential count revealed iron-deficiency anaemia. Thao was advised
that it is prepared correctly and hygienically, using safe to reduce Madison's milk intake to less than 500 mL daily and
water and sterilized utensils and equipment. Formulas to offer a diet rich in meat and leafy green vegetables. It was
explained that the cow's milk was ‘filling Madison up’ but was
should be prepared according to the manufacturer's
not providing her with iron and the other vitamins essential for
directions, using the scoop provided to measure the her growth. Madison was commenced on an iron supplement.
powder carefully. Studies have highlighted signifi- Thao was advised to delay the introduction of cow's milk until
cant inaccuracies in measuring the amount of pow- after 12 months of age in future children. 67
der for formula reconstitution, and other mistakes in
 3.3 SOCIAL AND PREVENTATIVE PAEDIATRICS

of foods. Often a child's natural satiety and refusal to

Nutrition in the well child in the finish all food provided is interpreted as ‘fussy eating’.
community Unrealistic expectations may create feeding problems.
Parental education regarding appropriate portion sizes
Timing of introduction of solids for children and the concept of offering a new food on
Breast milk or an appropriate formula is sufficient to many (on average eight!) separate occasions is required.
meet the needs of the healthy, growing infant until 4–6 Threats, scolding, bribery and use of food as a reward
months of age. At this time solid foods can be intro- are likely to create rather than resolve problems.
duced safely, supplementing the milk intake, which If a very limited diet is consumed, a dietitian should
remains the major source of nutrition until about be consulted in order to assess the adequacy of energy
12 months of age. and nutrient intake. Speech pathologists can assist
By 4–6 months of age infants have lost the tongue with oral stimulation and the introduction of different
thrust or extrusion reflex, have head control, and are tastes and textures.
able to sit without support, allowing them to manipu- Bottle-feeding should be avoided beyond 18 months
late solid foods. Most infants at this age are showing of age. Excessive milk intake may result in iron defi-
an interest in the world around them and are recep- ciency. Infants should not be settled in bed with a
tive to trying new foods. Healthy full-term infants are bottle, as this can cause nursing-bottle caries (see
born with iron stores that are sufficient for the first 4–6 Chapter 22.3).
months of life, after which these become depleted and Excessive intake of milk or fruit juice may reduce
milk feeds need to be supplemented with other dietary appetite and, as a result, may limit the variety of food
sources of iron, particularly haem-derived iron. intake. Excessive fruit juice consumption, particularly
Introduction of solids before 4 months of age can apple and pear juice, can result in toddler diarrhoea
displace breast milk or formula, but the solids do not due to saturation of the facilitated diffusion of fruc-
necessarily supply sufficient energy and nutrients for tose. Fruit juice is high in sugar and does not contain
the rapidly growing infant. Solids can also result in the vitamins and fibre that are found in fresh fruit. It
decreased breast milk supply, as a result of reduced should not replace the consumption of water as the
frequency and intensity of sucking. Delaying the best drink for children.
introduction of solids until later during the second
6 months of life may compromise growth and nutri- Daily food needs of preschoolers
tional status, as breast milk alone is insufficient after
Many parents are surprised at how little children of
6 months to supply energy and micronutrient needs.
this age need.
• Milk group: 2 servings
The first foods 1 serving = 250 mL milk, 200 mg yoghurt or 35 g
The introduction of a variety of foods is often referred cheese
to as the ‘educational diet’ as it begins the child's life- Full-cream products recommended up to
time experience of food. The first foods to be intro- 2 years; from 2 years, reduced fat products.
duced should be soft and smooth, although the infant • Bread and cereal group: 4–5 servings
quickly learns to manage foods of different textures, 1 serving = 1 slice of bread, ½ cup pasta or
with the ‘chewing reflex’ using the gums developing 2 cereal wheat biscuits.
around 7–9 months. Iron-fortified infant cereals are • Fruit and vegetable group: 4 or more servings
usually introduced first, as these can be mixed to the 1 serving = 1 piece of fruit or 2 tablespoons of
desired consistency with breast milk or formula. Fruit vegetables; focus on variety rather than quantity.
and vegetables are introduced gradually. Sources • Meat or protein group: 2 servings
of haem iron such as meat and poultry are recom- 1 serving = 30 g lean meat, fish or chicken,
mended at about 7 months of age. Custard, yoghurt ½ cup beans or 1 egg.
and cheese can also be introduced. Most infants
will be eating a variety of modified family meals by Specific nutritional concerns during childhood
12 months of age.
Vegetarian diets
The lower energy and higher fibre content of vegetar-
Feeding the toddler
ian diets can limit children's total energy intake, as they
Between 1 and 3 years of age, growth and appetite slow may not consume sufficient volume to meet their needs.
markedly. The child displays independent thought and Children on well planned semi-vegetarian, lacto or
action. Young children have limited control over their lacto ovo vegetarian diets are adequately nourished if
68
food choices and rely on caregivers to provide a variety appropriate attention is given to selection of suitable
 Nutrition 3.3
iron sources, and sufficient vitamin C is consumed to and calcium accretion may play a role in osteoporosis
maximize iron absorption. Vegan diets place children later in life. Limiting sources of iron, such as red meat,
at risk of iron deficiency anaemia. Children on vegan can lead to iron deficiency. Appropriate nutrition edu-
diets require calcium-fortified soy milk to ensure cation and role modelling needs to be provided both at
adequate calcium intake. The risks of vegetarian home and in the school setting.
diets for adolescents, particularly vegans, are signifi-
cant, because of the rapid growth that occurs during
puberty. Sufficient energy and an adequate intake of
iron, calcium, zinc and, if vegan, vitamin B12 must be Overnutrition
ensured. The dramatic rise in the prevalence of obesity amongst
Providing that the mother is consuming an adequate Australian children over the last three decades indi-
vegetarian diet, infants can be successfully breastfed. cates that the aetiology is not purely genetic. Clearly
Strictly vegan mothers who are not receiving vitamin there are complex genetic and environmental fac-
B12 place their child at considerable risk of profound tors at play. These are discussed fully in Chapter 3.4.
neurological impairment. Vegetarian mothers who Importantly, overweight children may still be at risk
formula-feed prefer not to use formulas based on cow's of micronutrient malnutrition, such as iron, vitamin D
milk. An appropriately fortified infant soy formula and calcium deficiency. A poor-quality diet rich in
may be used. Solid introduction should commence in excess calories may lack adequate micronutrients.
the usual way, between 4 and 6 months of age, but par-
ticular attention needs to be given to iron, if haem iron-
containing foods are being avoided. Infants placed on
vegan diets are most at risk of nutritional deficiencies. Undernutrition
Children who develop iron deficiency anaemia may
Malnutrition
be at risk of persistent minor neurocognitive impair-
ment, even with iron repletion. Breastfed infants Malnutrition is the leading cause of childhood mor-
whose mothers get little direct sunlight (including bidity and mortality worldwide. Currently ample food
cultures where women are veiled), require vitamin D is produced to feed the world's population but social
supplements to prevent rickets. and political forces, such as war, lack of transport
infrastructure and degradation of arable land, con-
spire to keep food from the most needy.
Hypoallergenic diets
A malnourished child has a weight-for-length (or
There is a role for elimination diets in children with height) of less than 70% or less than −3 standard devi-
documented multiple food allergy. However, food ations (sd) of the normalized reference figure (2009
restriction in children places them at risk of macronu- World Health Organization Child Growth Standards
trient and micronutrient deficiency. This highlights the and the Identification of Severe Acute Malnutrition in
importance of communication with the treating doc- Infants and Children; available at http://www.who.int/
tor and/or dietitian to ensure that the diet is nutrition- child_adolescent_health/documents/malnutrition/en/
ally sound. index.html/). Children below 60% of weight-for-age
may be stunted, and not severely wasted.
The reduction of all food intake or starvation leads
Nutrition issues in adolescence
to protein-energy malnutrition, resulting in marasmus
Common features of teenage eating include skipping (from the Greek ‘to waste away’). Children who have
meals, consumption of a limited variety of foods, a proportionately greater deprivation of protein than
frequent consumption of high-fat, high-sugar, low- energy may develop kwashiorkor (from the Ghanaian
nutrient foods, a lack of fibre and fad dieting. Fast- ‘deprived child’). These children are malnourished
food consumption may contribute to the increasing and oedematous. Children with kwashiorkor have a
prevalence of adult obesity in Western society, partic- typical appearance consisting of a protuberant belly,
ularly when combined with a sedentary lifestyle (see muscle wasting, dependent oedema, flaking skin with
Chapter 3.4). Poor and sometimes inappropriate body depigmentation (‘flaky paint’ dermatitis), glossitis
image may account for the fad diets that are quite com- and angular cheilitis. Children suffering from severe
mon among teenage girls and boys. Girls, in particular, protein-energy malnutrition may also have vitamin
often modify their diets to avoid foods that they see as deficiencies, especially deficiencies of B vitamins such
being high in fat and energy, such as meat or milk; this as thiamine, leading to beriberi, and niacin, leading
may result in an entire food group being omitted from to pellagra. Vitamin A deficiency can result in blind-
their diet. The avoidance of milk and milk products ness and may significantly worsen mortality from diar-
69
during the time of peak accumulation of bone mass rhoea and measles. Long-term consequences include
 3.3 SOCIAL AND PREVENTATIVE PAEDIATRICS

insulin-dependent diabetes mellitus secondary to trop- In Australia, marasmus rarely develops in a mal-
ical pancreatitis, and also a significant reduction in IQ nourished child, usually because of intervention
and school performance. from social agencies or because medical interven-
If malnutrition has occurred relatively acutely, tion occurs. Kwashiorkor is virtually never seen,
height and weight discrepancies may result. If malnu- even in the Indigenous population, where protein-
trition has been severe and protracted, stunting may energy malnutrition often occurs. Both food intake
occur and often future growth is compromised, even and increased metabolic demands secondary to infec-
after adequate energy provision. tious disease burden contribute to protein-energy
malnutrition.
Malnourished children may also have specific vita-
Malnutrition in the developing world
min and trace element deficiencies. These should be
Malnutrition and kwashiorkor frequently date from assessed and corrected. By far the most common defi-
the interruption of breastfeeding due to maternal ciencies in developed societies are in iron and folate
ill-health, work requirements or the arrival of a new and vitamin D. Low vitamin D levels have been
infant. In some parts of the developing world, high- increasingly recognized as a health problem in children
quality protein, particularly meat, poultry and fish, is over recent years.
in short supply. Breast milk has many immune factors
that provide passive protection as well as promoting
the infant's own immune system; therefore, it is not
surprising that cessation of breastfeeding predisposes
the child to respiratory and diarrhoeal disease. The
Nutrition in the hospitalized child
increased metabolic demands of infection may result Acute and chronic protein-energy malnutrition is not
in further nutritional ‘stress’. Infection with human uncommon in children in a tertiary hospital (Fig. 3.3.1).
immunodeficiency virus (HIV) is a major contributor Malnutrition in hospitalized patients is associated with
to malnutrition in the infected mother and her child, increased infectious and non-infectious complications,
particularly in Africa. These factors all combine to mortality, costs and length of stay.
contribute to the synergistic spiral of malnutrition and Nutritional assessment of patients at admission
disease. and during the period of hospitalization provides the
basis for the identification and treatment of nutrition
deficits. Indicators for early nutritional intervention
Malnutrition in the developed world
include:
Poverty plays a role in malnutrition in the developed • height-for-age and weight-for-age percentages or z
world. However, other factors such as ignorance, food scores more than 2sd below the mean for age
faddism and psychopathology also contribute. • height-for-age <95% expected

Needs
• Gestation and birth weight (SGA)
• Current health status
Intake (cardiorespiratory status, Absorption
• Gestation (?adequate suck?) sepsis, acute or chronic illness) • Gastrointestinal transit
• Developmental stage • Losses (diuretics, diarrhoea, (peristalsis and patency)
• Respiratory status vomiting, insensible, stomal losses) e.g. bowel atresia or pseudo-
• Neurological status obstruction
• Conscious state • Gastrointestinal anatomy
• Orofacial and GIT anatomy and mucosal (e.g. coeliac or
• Emotional state (depressed, inflammatory bowel disease
anxious) Child’s nutritional status or short gut)
• Previous diet/nutritional
• Growth parameters • Enzyme presence and function
practices
• Body composition e.g. pancreatic insufficiency or
• Current health status (cardio-
• Macronutrient status lactase deficiency
respiratory status, sepsis)
• Micronutrient status
• Drugs

70
Fig. 3.3.1 Factors affecting a hospitalized child's nutritional status. GIT, gastrointestinal tract; SGA, small for gestational age.
 Nutrition 3.3
• weight-for-height <90% expected or >120% feeds are fully established (i.e. 150–200 mL per kg
expected per day) unless the baby has a condition requiring
• height velocities <5 cm/year after 2 years of age. fluid restriction (e.g. congestive cardiac failure or
In contrast to prolonged fasting, which responds to chronic lung disease). In addition, VLBW babies
simple protein-energy repletion, the nutritional man- may require folate, iron, sodium and vitamins C, D
agement of a patient with metabolic stress due to and E. Iron should not be started until 12 weeks of
critical illness requires consideration of glucose metab- age and VLBW babies who receive multiple blood
olism, and specific micronutrient and energy require- transfusions may not need supplemental iron.
ments. Energy requirements during critical illness are • If breast milk is not available, an infant formula
usually reduced but will increase during the rehabilita- is required. Low birth weight (LBW) formulas are
tion phase. The total energy expenditure (TEE) is the designed for very premature (<32 weeks) babies.
sum of: These formulas contain more energy, protein,
calcium, phosphorus, trace elements and certain
TEE = BMR + Eactivity + E growth + Elosses
vitamins than standard formulas. They include
+ Thermic effect of feeding ( ∼ 10%). long-chain poly-unsaturated fatty acids as part
of their fat content, based on evidence that this
Basal metabolic rate (BMR) is the largest compo- improves neurodevelopmental outcomes. LBW
nent of TEE and can be estimated in children using formulas are used until a weight of 2.5 kg is achieved.
predictive equations (e.g. Schofield equation). BMR • Standard infant formulas provide approximately
is increased by clinical conditions including fever, 280 kJ/100 mL (20 kcal/30 mL) and 1.5 g
major surgery, cardiac failure, sepsis and burns. See protein/100 mL. Fortification (to 350 kJ/100 mL or
Table 3.3.3. 420 kJ/100 mL) should be implemented only under
the supervision of a paediatrician or dietitian.
Feeds for infants • Infants and young children who develop an
intercurrent gastroenteritis should have all
• Breast milk feeding should be the primary aim for fortification ceased until vomiting and diarrhoea
very sick babies. If too premature or ill to suckle at resolve, to avoid the potential complication of
the breast, expressed breast milk (EBM) can be fed hypernatraemic dehydration.
via a nasogastric or orogastric tube until the baby is
well enough to be placed on the breast.
• Breast milk fortifiers are available to add to EBM Feeds for children
to increase its content of protein, energy and other In some cases additional energy needs to be added to
nutrients in very low birth weight (VLBW – birth oral feeds, via:
weight lies below the 10th centile for gestational • energy supplements, such as glucose polymers or fat
age) babies. Fortifier should be added only once emulsions added to oral foods and fluids
• complete supplements (e.g. PediaSure, Fortisip or
Sustagen drinks), which can increase energy, protein
Table 3.3.3 Reference values for energy and protein and nutrient intake.
enteral requirements

Age Energy (kcal per Protein (g per kg Routes of feeding

kg per day) per day) Acute illnesses such as gastroenteritis and respiratory
0–6 months 115 2.2 infections can result in inadequate oral intake to meet
increased metabolic needs. This usually results in tran-
6–12 months 95 2.0 sient weight loss. Children may require supplemen-
tal hydration, receiving fluids by either nasogastric
1–3 years 95 1.8
tube or the intravenous route. Children with chronic
4–6 years 90 1.5
illness, however, may require long-term assistance
to meet nutritional requirements. This may be in the
7–10 years 75 1.2 form of supplemental feeding through either a naso-
gastric tube or a gastrostomy tube. The latter form of
11–14 years (male/ 65/55 1.0 feeding is especially useful in chronic illness or neuro-
female) logical compromise, such as cystic fibrosis or cerebral
palsy, and in children with chronic illness for whom
15–18 years (male/ 60/40 0.8
re-establishment of oral feeding has not been possible
female) 71
(Table 3.3.4).
 3.3 SOCIAL AND PREVENTATIVE PAEDIATRICS

the latter is tolerated at sufficient volumes for growth

Table 3.3.4 Diseases that increase micronutrient
requirements
and development.

Disease Increased requirement

Chronic illness
Burns Vitamins C, B complex,
Monitoring of nutritional status should be an integral
folate, zinc
component of the routine care of children with chronic
HIV/AIDS Zinc, selenium, iron illness. Malnutrition and growth failure is common
in children with cerebral palsy due to abnormalities
Renal failure/dialysis Vitamins C, B complex, folate in feeding skills, oromotor incoordination, gastro-
(reduce or omit copper, oesophageal reflux, constipation and behavioural prob-
chromium, molybdenum)
lems. Nutritional deficits place these patients at increased
Haemofiltration Vitamins C, B complex, trace
risk of pressure sores, skeletal abnormalities and infec-
elements tion. Enteral nutrition provided by a nasogastric or
gastrostomy tube has been associated with improve-
Protein-energy malnutrition Zinc, selenium, iron ment in energy levels, behaviour and mobility. Patients
with renal disease, liver disease and cystic fibrosis are at
Refeeding syndrome Phosphate, magnesium, risk of developing specific micronutrient abnormalities
potassium
in addition to protein-energy malnutrition.
Short bowel syndrome, Vitamins A, B12, D, E, K,
chronic malabsorption folate, zinc, magnesium, Short bowel syndrome
states selenium
Short bowel syndrome (SBS) is the clinical syndrome
Liver disease Vitamins A, B12, D, E, K, of severe malabsorption and maldigestion that occurs
zinc, iron (reduce or omit after a major surgical resection or a congenital short-
manganese, copper)
ening of the intestine. In a full-term neonate the small
High fistula output, chronic Zinc, magnesium, selenium, intestine is about 250 ± 40 cm at birth. SBS occurs
diarrhoea folate, B complex, B12 when the small bowel remnant is less than 30% of
normal length, equivalent to less than 75 cm. Some
Pancreatic insufficiency Vitamins A, D, E, K patients with SBS require long-term parenteral nutri-
tion to provide the nutrition, fluid and electrolytes nec-
Inflammatory bowel disease Folate, B12, zinc, iron essary to sustain life (Fig. 3.3.2). Failure to wean from
HIV/AIDS, human immunodeficiency virus/acquired immune parenteral nutrition in children with SBS is associated
deficiency syndrome. with less than 30 cm jejunoileum, lack of enterocolic
Source: Thomson K, Tey D, Marks M (eds) 2009 Paediatric continuity, residual disease of the intestine and lack of
handbook, 8th edn. Wiley, Chichester. early feeding tolerance.

Parenteral nutrition
Some children are unable to feed enterally and
require parenteral (intravenous) nutrition. These Infants and children who are unable to feed enterally
include extremely premature or ill neonates, children require intravenous nutrition using a combination of
recovering from intestinal surgery and children with nutrient and lipid solution (Fig. 3.3.3). These are deliv-
intestinal failure. ered either by a peripheral intravenous line (maximum
dextrose concentration of 10%) or via a central venous
line (maximum dextrose concentration of 30%). The
Prematurity
nutrient solution is comprised of amino acids (both
Premature infants have increased nutritional metabolic essential and non-essential), glucose, electrolytes, min-
demands due to a rapid growth phase, tissue develop- erals, vitamins, trace elements and water, and may con-
ment, stress of illness, poor temperature control and tain heparin. The main source of non-protein calories
the increased demands of small for gestational age is d-glucose (dextrose). The lipid emulsion is a concen-
(SGA) infants. These factors, combined with imma- trated source of calories with low osmolarity. Patients
ture organ function, poor nutrient stores and altered receiving parenteral nutrition require daily weighing
feeding patterns, mean that the majority of premature and fluid balance. Baseline and frequent subsequent
infants require a combination of parenteral and/or blood tests are required to monitor for electrolyte
specialized enteral nutrition. The former provides the imbalance, glucose metabolism and to tailor the par-
72
recommended fluid and electrolyte requirements until enteral nutrition accordingly.
 Nutrition 3.3
­ alnourished patient. In particular, the delivery of
m
intravenous or enteral carbohydrate loads may precip-
itate these potentially fatal electrolyte disturbances.
The potential metabolic disturbances that may occur
include hypokalaemia, hypophosphataemia, hypo-
magnesaemia and hyponatraemia. Potential side-
effects of these electrolyte and mineral disturbances
include: cardiac failure, respiratory compromise, sei-
zures, myocardial infarction and arrhythmias.
Under most circumstances of prolonged starva-
tion or significant weight loss, renourishment should
commence slowly with small increases in nutrition
delivered once electrolyte and mineral disturbances
­
have been corrected. For example, commence feed-
ing at basal energy requirements, increasing to full
requirements over 7–10 days. Patients most at risk dur-
ing refeeding include those with anorexia nervosa and
those with weight loss more than 10–20% body weight,
prolonged fasting or a minimal intake of longer than
7–10 days.

Practical points

• Malnutrition is the leading cause of childhood morbidity

and mortality worldwide.
• Malnutrition continues in Australia's own Indigenous
population, with up to 20% of hospitalized Aboriginal
Fig. 3.3.2 Twelve-month-old boy born with gastroschisis, children in Australia's Northern Territory estimated to be
complicated by bowel resection resulting in short bowel malnourished.
syndrome. Treatment involved a nasogastric tube for enteral • The most common micronutrient deficiencies in developed
feeds and a central venous catheter for parenteral nutrition. societies are of iron and folate and vitamin D.
• Hospitalized children are at particular risk of malnutrition
and require careful nutritional assessment of needs,
losses, intake and absorption.
Parenteral nutrition can be complicated by life- • Nutrition is safer when given enterally. Parenteral
threatening electrolyte imbalance, hypoglycaemia, nutrition should be used only when enteral nutrition is
hyperglycaemia, line sepsis, thrombosis and extrava- contraindicated or unsuccessful.
sation of the nutrient into the tissues, resulting in a • Refeeding syndrome describes the metabolic
complications that occur when aggressive nutritional
parenteral nutrition ‘burn’. Most infants and chil-
therapy is used to treat the severely malnourished
dren are on parenteral nutrition for short periods of patient in which the delivery of intravenous or enteral
time during acute illness or recovery from surgery. carbohydrate loads may precipitate potentially fatal
However, children with intestinal failure may require electrolyte disturbances.
lifelong total parenteral nutrition (TPN). In addition
to the acute complications, these children are at risk of
vitamin and micronutrient deficiency, growth failure,
parenteral nutrition liver disease and vascular access Monitoring of refeeding is essential and includes
complications. daily/regular monitoring of glucose, electrolytes, urea,
creatinine, phosphate, magnesium and fluid balance
until stable. Enteral or parenteral feeds may need
Refeeding syndrome
to be ceased until electrolytes have been corrected.
Refeeding syndrome is the term used for the meta- Supplementation of potassium, phosphate and mag-
bolic complications that may occur when aggres- nesium may be required during the initial feeding
sive nutritional therapy is used to treat the severely period, guided by blood levels.

73
 Nutritional assessment
History, examinations, investigations

Is the gastrointestinal tract functioning?

Partial
No Yes

Parenteral nutrition Enteral nutrition

Recovery of 1 Determine the route of

gastrointestinal function administration (oral,
NG, NJ, gastrostomy,
jejunostomy)
2 Formula choice
No Yes depends on
• Patient’s age
• Gastrointestinal
function

Gastrointestinal function

Abnormal Normal

Specialized diet Polymeric diet

<2 years of age <2 years of age
• Breast milk, or semi- • Breast milk, or cow’s milk-
elemental infant formula (e.g. based infant formula
Pepti-junior, Meocate, Alfare) (e.g. S26, Nan, Karicare
Infant)
>2 years of age
• Elemental formula (Neocate >2 years of age
Advance, Elcare Plus, • Polymeric formula (Nutrini,
MCTpeptide) Nutrison)

Are feeds tolerated and Are feeds tolerated and

nutritional goals achieved? nutritional goals achieved?

Yes No No Yes

Transition to polymeric Consider supplementary Transition to oral/

formula ± oral diet parenteral nutrition feeds diet

Fig. 3.3.3 Nutrition support algorithm. NG, nasogastric; NJ, nasojejunal. (Adapted from Bines J, Titchen T, Humphrey M, Jessen D
74 1997 A practical guide to paediatric nutrition support. Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital,
Melbourne.)
 Obesity
Louise A. Baur
3.4
Introduction How is paediatric overweight and
Paediatric obesity is a major public health problem obesity defined?
in both developed and developing countries. Obese Body mass index – a measure of total body
children and adolescents may suffer from a host of fatness
co-morbidities, some of which are immediately appar-
ent, whereas others act as warning signs of future Body mass index (BMI; weight/height2; kg/m2) is a sim-
disease. Obesity can be a serious, chronic, relapsing ple measure of body fatness. BMI varies dramatically
disease. It is a disorder of energy imbalance that arises with age and sex during childhood and adolescence:
as a consequence of a complex interaction between it increases in the first year, falls during preschool
genetic, social, behavioural and environmental factors. years, and then rises once more into adolescence. The
Although investment in primary prevention is vital in point at which BMI starts to increase again, between
curbing the epidemic, effective treatment of those chil- 4 and 7 years of age, is termed the point of ‘adiposity
dren and adolescents who are currently obese is also rebound’ (Figs 3.4.1–3.4.4).
needed to improve both their immediate and long- Several countries have their own BMI-for-age
term health outcomes. growth charts that can be used clinically to chart an
individual's BMI and monitor changes over time. The
World Health Organization has also developed BMI-
for-age charts for international use for children aged
0–5 and 5–19 years (see Figs 3.4.1–3.4.4). Until further
research helps establish the relation between BMI-for-
Practical points age cut-points and health outcomes in childhood and
adolescence, the decision as to which specific centile
lines denote overweight and obesity in clinical settings
• Obesity is a chronic disorder of energy imbalance – focus
upon both sides of the energy balance equation: energy in ultimately remains arbitrary.
and energy out.
• Measure body mass index (BMI) and plot on a BMI-for-
age chart. Measure and record waist circumference, and Waist circumference and waist : height
calculate waist : height ratio. ratio – measures of fat distribution
• In pre-pubertal children, weight maintenance or
reduction in the rate of weight gain, may be appropriate In children and young people, just as in adults, waist
goals of therapy. Weight loss is often necessary circumference is correlated with abdominal fat, as well
for moderately obese younger children, and for as with cardiovascular risk factors. Although waist cir-
adolescents. cumference charts are available for some individual
• For younger children, focus upon the parents as countries, there are no internationally accepted crite-
agents of change. Adolescents will require a different,
ria for high- or low-risk waist circumference in this age
developmentally sensitive, approach.
Long-term behavioural change is required, involving group. Nationally developed waist circumference-for-
•
an increase in incidental physical activity, a reduction in age charts can be used to monitor clinical progress of
sedentary behaviour and a sustainable change to a lower an individual patient.
energy intake. Waist-to-height ratio (waist/height) is an additional
• There is a role for drug therapy in adolescents who have measure of fat distribution that is easy to calculate and
moderately severe obesity, or those with clinical insulin reasonably independent of age and sex for individuals
resistance.
Prevention of obesity requires a whole-of-system
aged above 6 years. Waist-to-height ratios greater than
•
approach in which many aspects of the broader food and 0.5 are associated with increased cardiometabolic risk
physical activity environment are targeted. factors. The clinical message is: ‘Keep your waist to
less than half your height’.
75
 3.4 SOCIAL AND PREVENTATIVE PAEDIATRICS

97th
28 28

26 26
85th
24 24

22 22
BMI (kg/m2)

BMI (kg/m2)
50th

20 20

15th
18 18

3rd
16 16

14 14

12 12
5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Age (years)

Fig. 3.4.1 Body mass index-for-age chart for girls aged 5–19 years. Source: 2007 World Health Organization Reference. Available at:
http://www.who.int/growthref/cht_bmifa_girls_perc_5_19years.pdf

97th
28 28

26 26
85th

24 24

50th 22
22
BMI (kg/m2)

BMI (kg/m2)

20 20
15th

18 3rd
18

16 16

14 14

12 12
5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Age (years)

Fig. 3.4.2 Body mass index-for-age chart for boys aged 5–19 years. Source: 2007 World Health Organization Reference. Available at:
http://www.who.int/growthref/cht_bmifa_boys_perc_5_19years.pdf
76
 Obesity 3.4
21 21

20 20

19 19
97th

18 18

17 85th 17
BMI (kg/m2)

BMI (kg/m2)
16 16

50th
15 15

14 14
15th

13 13
3rd

12 12

11 11

10 10

1 2 3 4 5
Age (years)

Fig. 3.4.3 Body mass index-for-age chart for girls aged 0–5 years. Source: World Health Organization Child Growth Standards.
Available at: http://www.who.int/childgrowth/standards/cht_bfa_girls_p_0_5.pdf

Racial and ethnic variations in definition

What is the prevalence of
There are racial and ethnic variations in the bio-
logical response to excess adiposity. Among adults, paediatric overweight and
Asians generally have a higher percentage body fat obesity?
for a given BMI and an associated increased health
International prevalence rates and secular
risk at lower BMI values compared with Europeans,
trends
whereas Pacific populations generally have a lower
percentage body fat and a decreased health risk at Worldwide, approximately 10% of school-aged chil-
the same BMI levels. These differences are also likely dren and adolescents are overweight, with 2–3% being
within the child and adolescent age group, and ulti- obese. Prevalence rates vary across regions, with higher
mately require the development of ethnic- or race- rates in children from the Americas, Europe and the
specific definitions or criteria for obesity. Pacific than in those from sub-Saharan Africa or Asia. 77
 3.4 SOCIAL AND PREVENTATIVE PAEDIATRICS

21 21

20 20

19 19

97th
18 18

17 17
85th
BMI (kg/m2)

BMI (kg/m2)
16 16

50th
15 15

14 14
15th

13 3rd 13

12 12

11 11

10 10

1 2 3 4 5
Age (years)

Fig. 3.4.4 Body mass index-for-age chart for boys aged 0–5 years. Source: World Health Organization Child Growth Standards.
Available at: http://www.who.int/childgrowth/standards/cht_bfa_boys_p_0_5.pdf

In 2007 in Australia, approximately 1 in 4 children and

adolescents were overweight or obese. In 2006–2007 in What are the complications
New Zealand, 29% of children and adolescents were of paediatric obesity?
overweight or obese, with higher rates being found in
Pacific and Maori children. The complications of obesity among children and
Of most concern are the rapid changes in obe- ­adolescents may be immediate or may not manifest
sity prevalence in many countries in several conti- until the medium- to long-term. They affect many
nents. Several Asian countries that are experiencing body systems, as outlined in Table 3.4.1.
rapid changes in urbanization and nutrition have
seen increasing rates of obesity in paediatric popula- Complications during childhood
tions in recent years. For example, urban Chinese and and adolescence
Vietnamese younger children now have similar obe-
Psychosocial complications
sity rates to those of children in Australia. In addition,
overweight children are heavier than in the past. Such The most common consequences of obesity in child-
findings have very significant implications for future hood and adolescence are those related to psychoso-
78
population health strategies. cial dysfunction and social isolation. In pre-adolescent
 Obesity 3.4
children, physical appearance and athletic competence
self-esteem are lower than in their normal weight peers, Management
although global self-esteem appears to be preserved. The GP arranged to see Trudy and her mother,
separately and together, initially every 3 weeks, and
In adolescent girls, excess weight is significantly related
then less frequently. Two visits to a local dietitian were
to body dissatisfaction, drive for thinness and bulimia. also arranged; more frequent follow-up could not be
Cross-sectional studies of teenagers show an inverse organized. Trudy was encouraged to set her own goals
relationship between weight and both global s­ elf-esteem for food and activity changes; these goals were re-visited
and body-esteem. The pervasive, negative social mes- at the consultations. She was helped to look at ways in
sages associated with obesity in many communities which eating cues could be recognized and modified. The
may have a particular impact during adolescence. family was supported to make changes to their eating
patterns and the use of the television in the home.
There are differences in health-related quality of life
between obese and non-obese children. In randomly Progress
sampled populations, the physical and social domains In time, Trudy's mother lost some weight as a result of
of health-related quality of life for obese children are altered cooking practices and being more active. Water
was offered at the evening meal instead of soft drink, less
lower than for non-overweight children. Severely obese
healthy snacks were no longer stored in the cupboards,
patients have significantly reduced health-related qual- and the family started eating more vegetables and had
ity of life compared with healthy children, having sim- smaller meat and rice/potato portions at the evening
ilar quality of life scores to children diagnosed with meal. Trudy ate something for breakfast each morning
cancer. and started walking to and from school. She started
tennis lessons and found an interest in tap dancing.
Ten months later, Trudy's weight was 69.3 kg, height
163.0 cm, BMI 26.1 kg/m2, waist circumference 81 cm and
Clinical example waist : height ratio 0.50. She reported being fitter and said
she was greatly enjoying school and was no longer being
Trudy, a 13-year-old girl with obesity bullied. A repeat fasting blood test showed an improved
Trudy presented to her general practitioner lipid profile (total cholesterol 4.8 mmol/L, HDL cholesterol
(GP) with a respiratory tract infection. Her 1.0 mmol/L, triglycerides 1.4 mmol/L) and a decreased
mother commented incidentally that Trudy insulin concentration (85 pmol/L), consistent with a
was concerned about her weight and was being teased at reduction in central obesity.
school. Indeed, she had left her previous school because of
bullying and now it appeared to be starting afresh in the new
school. Orthopaedic complications
Trudy is an only child, with a good relationship with her
parents and some peers. She is in good general health, Slipped capital femoral epiphyses occur much more
apart from the weight gain. Several family members are commonly in obese young people and much earlier
obese (mother and three grandparents), her paternal than in non-obese patients. Blount disease (tibia vara)
grandfather has type 2 diabetes, and her maternal is a deformity of the medial portion of the proximal
grandfather has hypercholesterolaemia and ischaemic tibial metaphysis that arises as a result of increased
heart disease. Trudy leads a sedentary lifestyle: she enjoys
weight-bearing on cartilaginous bone with subse-
playing music, sewing, reading and talking on the phone.
Trudy is driven to and from school each day and watches quent compensatory overgrowth and bowing of the
3 hours of television per day. Her dietary intake includes tibia. Obese young people also have low bone area
skipping breakfast, full-cream milk, ‘something nice’ for and bone mass relative to their body weight, making
morning and afternoon tea, buying food at the milk-bar in them more prone to fractures than lean individuals.
the afternoon, a daily intake of 500 mL of soft drink and free Minor orthopaedic obesity-associated complica-
access to biscuits at home.
tions include knock knee (genu valgum), a decreased
On examination, Trudy's height was 161.5 cm (<75th
centile), weight 74.3 kg (>97th centile), BMI 28.4 kg/m2
recovery from soft tissue ankle injuries, and flat, wide
(>95th centile for age; adult overweight range), waist feet with increased static and dynamic plantar pres-
circumference 89 cm (adult female ‘at significant risk of sures. These conditions may seem relatively trivial in
metabolic complications’ range) and waist : height ratio health terms, but could have a significant impact on a
0.55 (>0.5, indicative of cardiometabolic risk). She was in child's ability to participate fully in activities.
mid-puberty, and had abdominal and upper thigh striae.
Blood pressure was 120/80 mmHg. A fasting blood test
showed a normal glucose (4.6 mmol/L; normal range Hepatobiliary complications
3.5–5.5), mild hyperinsulinaemia (115 pmol/L) and a lipid
profile characteristic of central obesity: total cholesterol Obese children and adolescents may experience a
5.3 mmol/L (normal range 2.6–5.5), high-density range of gastrointestinal and hepatobiliary disorders,
lipoprotein (HDL) cholesterol 0.8 mmol/L (normal >0.9), the most significant being non-alcoholic fatty liver
triglycerides 1.9 mmol/L (normal range 0.6–1.7). disease (NAFLD). NAFLD is an umbrella term that
79
includes steatosis as well as steatohepatitis. It typically
 3.4 SOCIAL AND PREVENTATIVE PAEDIATRICS

Table 3.4.1 Potential obesity-associated complications in children and adolescents

System Health problems

Psychosocial Social isolation and discrimination, decreased self-esteem, learning difficulties, body image disorder, bulimia
Medium and long term: poorer social and economic ‘success’, bulimia

Respiratory Obstructive sleep apnoea, asthma, poor exercise tolerance

Orthopaedic Back pain, slipped femoral capital epiphyses, tibia vara, ankle sprains, flat feet

Hepatobiliary Non-alcoholic fatty liver disease, gallstones

Reproductive Polycystic ovary syndrome, menstrual abnormalities

Cardiovascular Hypertension, adverse lipid profile (low HDL cholesterol, high triglycerides, high LDL cholesterol)
Medium and long term: increased risk of hypertension and adverse lipid profile in adulthood, increased risk of
coronary artery disease in adulthood, left ventricular hypertrophy

Endocrine Hyperinsulinaemia, insulin resistance, impaired glucose tolerance, impaired fasting glucose, type 2 diabetes mellitus
Medium and long term: increased risk of type 2 diabetes mellitus and metabolic syndrome in adulthood

Neurological Benign intracranial hypertension

Skin Acanthosis nigricans, striae, intertrigo

HDL, high-density lipoprotein; LDL, low-density lipoprotein.

presents as an asymptomatic increase in the level of medications, have more wheezing episodes and expe-
aminotransferases. The degree of steatosis is associ- rience more unscheduled visits to hospital. Obese
ated with the severity of obesity, a central fat distri- children also have a lower exercise tolerance than
bution, hypertriglyceridaemia, insulin resistance and their lean peers, presumably compounding their
the presence of raised aminotransferases, with an obesity.
increased level of alanine aminotransferase being most Potentially more serious is the complication of
specific for steatosis. Liver fibrosis and even evolving obstructive sleep apnoea. Between 1 in 10 and 1 in
cirrhosis have been identified in liver biopsy findings 4 obese children have obstructive sleep apnoea.
of paediatric patients with NAFLD. Obstructive sleep apnoea is associated with sever-
Several clinical audits from paediatric surgical units ity of obesity, insulin resistance and dyslipidaemia.
have demonstrated an association between cholesterol Profound hypoventilation and even sudden death have
cholelithiasis and obesity in children and adolescents. been reported in severe cases of obesity-associated
Gastro-oesophageal reflux is more prevalent in obese sleep apnoea.
individuals, possibly secondary to increased intra-
abdominal pressure.
Risk factors for cardiovascular disease
Risk factors for cardiovascular disease are one of
Neurological complications
the most common problems facing the obese young
Idiopathic raised intracranial pressure (pseudotumour person. In the famed Bogalusa Heart Study from the
cerebri) is a rare but potentially very serious compli- USA, 60% of overweight 5–10-year-olds had one car-
cation of obesity. The role played by obesity in the diovascular risk factor, such as hypertension, high
pathogenesis of the disorder is unknown. low-density lipoprotein (LDL) cholesterol or high tri-
glycerides, and over 20% had two or more risk factors.
Overall, when compared with their lean peers, over-
Asthma and sleep-disordered breathing
weight children were 2.4 times as likely to have raised
Respiratory outcomes can be poor in obese children. total cholesterol and diastolic blood pressure, and 4.5
Asthma is more prevalent in obese than non-obese times as likely to have increased systolic blood pres-
children. Compared with lean children with asthma, sure. A central fat distribution is particularly associ-
overweight and obese children use more antiasthma ated with clustering of cardiovascular risk factors.
80
 Obesity 3.4
Endocrine complications overheated areas as skin-folds or the groin. Striae can
also occur, particularly on the abdomen and thighs.
Overweight children are much more likely to have raised
Acanthosis nigricans can occur in insulin-resistant
fasting insulin concentrations (indicative of insulin
states, such as obesity. It is characterized by thickened
resistance), impaired fasting glucose or glucose intol-
areas of hyperpigmentation, with later development
erance than their lean peers. Although still rare among
of hypertrophy and sometimes papillomatosis (see
children and adolescents, the incidence of type 2 dia-
Fig. 3.4.5). The skin lesions typically occur in inter-
betes mellitus is increasing and is inextricably linked to
triginous regions such as the base of the neck, axillae,
the prevalence of obesity among young people. Type
groin, antecubital and popliteal fossae, and umbilicus.
2 diabetes is more common in adolescents and those
The condition occurs more frequently in dark-skinned
who are obese, have acanthosis nigricans (thickened
ethnic groups.
pigmented skin at the base of the neck and in flexures,
characteristic of insulin resistance; Fig. 3.4.5), have a
family history of type 2 diabetes or are female. Adult complications arising from child
The metabolic syndrome, a term describing a cluster and adolescent obesity
of highly prevalent disorders in Western countries that
Obesity in adulthood
are linked to insulin resistance and central obesity, was
initially identified among adults. Among adolescents The most significant health risk faced by obese young
in the USA, the overall prevalence of the metabolic people is that they are at risk of becoming obese
syndrome is approximately 10%, but the syndrome adults, who are at increased risk of cardiovascular dis-
affects almost one-third of overweight adolescents. ease, diabetes and some cancers. Tracking of obesity
from childhood and adolescence through to adult-
hood is more likely with a family history of parental
Reproductive system complications
obesity, the presence of obesity in late childhood or
Menstrual abnormalities occur more frequently in adolescence, or with increased severity of obesity.
obese girls, including the early onset of puberty and
menarche, as well as menstrual irregularities and poly- Long-term cardiovascular complications
cystic ovary disease. There is a strong association
between abdominal fat, increased levels of androgenic Obesity in childhood and adolescence is associated with
hormones, hirsutism, insulin resistance and polycystic an increased risk of cardiovascular disease risk fac-
ovaries, which grouped together is termed polycystic tors, and an increased carotid intima–media thickness
ovary syndrome. in young adults. Long-term (>50 years) follow-up of
cohorts in the USA and the UK show that both all-cause
and cardiovascular mortality is associated with higher
Skin complications adolescent BMI: study participants who, as young peo-
Obese children suffer from overheating as their fat ple, were heavier than the 75th centile for BMI were
tissue acts as insulation, resulting in profuse sweat- twice as likely to die from ischaemic heart disease than
ing with any physical activity. Thrush occurs more those who had a BMI between the 25th and 75th centile.
­commonly in obese subjects, especially in such moist,
Long-term endocrine and metabolic complications
Childhood BMI predicts the development of diabetes
in adulthood. Results from the Bogalusa Heart Study
show that childhood obesity is the strongest predictor
of the development, in adulthood, of the cluster of
risk factors that characterize the metabolic syndrome:
children in the top quartile of BMI were 11 times more
likely to develop the metabolic syndrome as adults
than their lean peers.

Long-term psychosocial complications

Overweight in adolescence may also be associated with
later social and economic problems. Obese adolescent
Fig. 3.4.5 Acanthosis nigricans, seen at the base of the neck of females and young women are more likely, as adults,
an adolescent male with obesity and hyperinsulinaemia. to have lower family incomes, higher rates of poverty
81
 3.4 SOCIAL AND PREVENTATIVE PAEDIATRICS

and lower rates of marriage than women with other Twin, family and adoption studies suggest an overall
forms of chronic physical disability but who are not heritability of BMI and body composition of 25–50%.
overweight, a finding suggesting that discrimination
plays a role in adverse outcomes. However, obesity
limited to childhood does not appear to be associated Genes associated with common obesity
with adverse socioeconomic, educational, social, and More than 200 different candidate genes have been
psychological outcomes in adulthood. associated with obesity-related phenotypes. The
range of actions, or presumed actions, of the many
gene products of candidate genes is extremely var-
What causes obesity? ied, reflecting the numerous physiological pathways
influencing total body energy balance and fat dis-
Obesity is a complex condition, with interactions
tribution. Thus, genes influencing appetite and sati-
between genetic, metabolic, behavioural and envi-
ety signals, fat-cell differentiation, fat-cell signalling,
ronmental factors all contributing to its development
adrenal action, resting metabolic rate, diet-induced
(Fig. 3.4.6).
thermogenesis, nutrient partitioning, peripheral insu-
lin action, deposition of visceral fat and obesity-
Physiological basis of obesity related co-morbidities are all the subject of intense
Obesity is a chronic disorder affecting the balance investigation.
between energy intake and energy expenditure. This
balance is influenced by a complex set of physiological
Monogenic forms of obesity
pathways, of which the hypothalamus acts as the cen-
tral regulator of energy homeostasis and energy intake. Mutations in several genes that encode proteins
The resultant energy regulation system is very protec- with probable roles in central appetite regulation
tive against weight loss, which has been the dominant have been described but are rare. Most of the muta-
physiological threat to the individual until the past cou- tions are associated with severe early-onset obesity
ple of decades in most westernized societies. However, and have a recessive form of inheritance, with the
the system is not protective against weight gain. exception of mutations in the melanocortin-4 recep-
tor gene, which has an autosomal dominant mode of
Genetic associations of obesity inheritance.

The heritability of obesity

There is a strong familial association with obesity,
Syndromic forms of obesity
with numerous studies indicating that a major part of Many rare syndromes that are caused by discrete
this association is via a shared genetic ­predisposition. genetic defects or chromosomal abnormalities have
obesity as one of a constellation of physical and devel-
opment abnormalities. The most frequent of these
Genetic predisposition
syndromes is Prader–Willi syndrome, characterized by
diminished fetal activity, obesity, muscular hypotonia,
mental retardation, short stature, hypogonadotropic
hypogonadism, and small hands and feet, as well as a
Numerous
Chronic energy number of other features.
environmental
influences imbalance

Environmental and behavioural associations

of obesity
The increased prevalence of obesity in recent decades
Energy in genetically stable populations highlights the central
expenditure role of recent important environmental trends in the
Energy development of the obesity epidemic.
intake

Television viewing

Fig. 3.4.6 Obesity is a disorder of chronic energy imbalance. The association between television viewing and obe-
Many environmental factors influence energy balance, through sity in childhood and adolescence has been dem-
82
the filter of genetic predisposition. onstrated in both cross-sectional and longitudinal
 Obesity 3.4
studies, although as yet there are no clear data linking dietary fibre, low glycaemic index foods, and school
obesity with the viewing of interactive video games, environments that support healthy food choices for
computers or other ‘small screen’ recreation. Several children. The relative contributions of dietary fat (ver-
possible mechanisms for the association between tele- sus energy) intake, portion sizes and specific eating
vision viewing and obesity include: patterns to the development of obesity remain unclear,
• increased exposure to food marketing although all may play an important role.
• increased snacking of energy-dense foods and
drinks while watching television
Socioeconomic conditions
• displacement of time spent in more physical
activities Overweight is high among the poorer children in devel-
• reinforcement of sedentary behaviour oped countries and the richer children in developing
• reduction in basal metabolic rate while watching countries. Potential contributors to obesity in urban-
television ized developing countries include increased availabil-
• television viewing is a proxy for a generally obesity- ity of cheap energy-dense foods and widespread access
conducive lifestyle, reflecting parenting style and to television which would favour a more sedentary,
limit-setting around food choices and recreational indoor lifestyle.
choices.
Medical conditions associated with obesity
Physical activity and sedentary behaviour Obesity may occur secondary to a range of medical
conditions, some of which are outlined in Table 3.4.2.
Lower physical activity levels and sedentary behav-
iours are associated, cross-sectionally, with a higher
prevalence of obesity in children. Prospective studies Other factors associated with obesity
suggest that physical activity has a protective effect
on the development of excess weight gain in child-
• Growth patterns associated with an increased risk
of subsequent obesity include an earlier adiposity
hood. Major changes in urban and transport plan-
rebound and rapid catch-up growth in the first
ning and the broader physical activity environment
2 years.
have contributed to a reduction in physical activity
and an associated increase in obesity through the
• Parental obesity more than doubles the risk of
adult obesity among both obese and non-obese
following:
children aged less than 10 years, and having two
• loss of public recreation space
obese parents increases the risk of mid-childhood
• increased high-rise housing
obesity by a factor of more than 10 when compared
• increased motorized transport
with children where neither parent is obese.
• decreased access to public transport
• Parental (especially maternal) dietary disinhibition
• increased use of passive forms of entertainment
is associated with development of excess weight
(e.g. television, computers)
gain in the child.
• perceptions of lack of safety in local
neighbourhoods.
Table 3.4.2 Medical conditions associated with obesity

Dietary intake and eating patterns System/effect Conditions

The increased prevalence of obesity in recent decades has Endocrine Hypothyroidism,
resulted, in part, from changes in dietary intake. Factors hypercortisolism, growth
that are likely to have contributed to this include: hormone deficiency or resistance
• an increased consumption of energy-dense,
nutrient-poor foods Central nervous system Hypothalamic–pituitary damage
damage due to surgery, trauma or cranial
• a high intake of sugar-sweetened drinks irradiation
• heavy marketing of energy-dense foods and
fast-food outlets Postmalignancy Acute lymphoblastic leukaemia
• increased dining at fast-food restaurants
• early feeding style – parental feeding restriction is Side-effects of drug Glucocorticoids, some
associated with increased child eating and weight therapy antiepileptics (e.g. sodium
valproate), some antipsychotics
status.
(e.g. risperidone, olanzapine),
Breastfeeding has a small but protective effect against insulin 83
obesity. Additional protective factors include high
 3.4 SOCIAL AND PREVENTATIVE PAEDIATRICS

Physical examination
How is child and adolescent
Features to be sought on physical examination
obesity managed? include:
Clinical assessment • hypertension (ensure that cuff width is
adequate)
Clinical history • skin findings (e.g. acanthosis nigricans, striae,
The clinical history should be conducted sensitively. intertrigo, skin chafing, hirsutism)
The features that should be covered in a clinical his- • adenotonsillar hypertrophy
tory are outlined in Table 3.4.3. • clinical signs of asthma
• hepatomegaly (fatty liver; note – may be difficult
to palpate), right upper-quadrant tenderness
Anthropometry
(gallstones)
BMI, waist circumference and waist : height ratio are • an abnormal gait due to joint or other
most useful when measured serially and used to moni- musculoskeletal problems; clinical signs of hip,
tor change over time: knee or ankle problems; bowing of the tibia.
• BMI is calculated as weight/height2 and then Findings on physical examination that may indicate
plotted on a BMI-for-age chart (see Fig. 3.4.1). other causes for obesity (e.g. hypothyroidism, hyper-
• Waist circumference is measured at the midpoint cortisolism or Prader–Willi syndrome) and which call
between the lower edge of the ribs and the iliac for further assessment include:
crest, approximately at the level of the umbilicus, • short stature
although in severely obese patients with a fatty • dysmorphic features
apron this measurement can be difficult to ascertain. • violaceous striae
• Waist : height ratio greater than 0.5 in people • intellectual disability
aged above 6 years is associated with increased • visual or neurological defects indicative of a central
cardiometabolic risk factors. nervous system lesion.

Table 3.4.3 History to be sought as part of the clinical assessment of the obese patient

History Details

General Pregnancy details, including maternal gestational diabetes

Early medical history
Ethnicity

Weight History of obesity including onset and duration of obesity

Pubertal history (including menstrual history if relevant)
Impact of obesity on the life of the patient and their family
Reasons for seeking clinical help

Complications Psychological effects of obesity, including teasing and bullying

Presence of sleep apnoea/disturbed sleep
Asthma
Specific symptoms such as knee/hip pain
Menstrual history (girls)
Exercise tolerance

Family history of obesity and disorders Relative weights or BMIs of family members
associated with insulin resistance Family history of obesity, type 2 diabetes, cardiovascular and cerebrovascular disease,
fatty liver disease and obstructive sleep apnoea

Lifestyle Physical activity, including transport to/from school, participation in organized sports or
other activities, access to recreation space or equipment for games, availability of
friends or family for games or play
Sedentary activities including television, video games, computer use, other passive
entertainment time, mobile phone use
Dietary history including meal patterns, fast-food intake and snacks, soft-drink intake

84 BMI, body mass index.

 Obesity 3.4
Laboratory investigations • a developmentally appropriate approach
For overweight and mildly obese children, laboratory
• long-term behaviour change
investigations are generally not necessary. However, if
• long-term dietary change
a child or adolescent is very obese (especially if cen-
• increased physical activity
trally obese), has a family history of disorders associ-
• decreased sedentary behaviour.
ated with insulin resistance, or history and examination
suggest the presence of complications of obesity or Conventional treatment approaches
other risk factors, the following biochemical screening
Family focus
for dyslipidaemia, insulin resistance, glucose intoler-
ance and liver abnormalities is recommended: Long-term maintenance of weight loss (i.e. from 2 to
• Fasting lipid profile (total cholesterol, LDL 10 years) is achieved when the intervention is fam-
cholesterol, HDL cholesterol, triglycerides) ily based. Families influence food and activity hab-
• Fasting glucose its, and thus it is not surprising that effective therapy
• Liver function tests (specifically alanine of obesity must take this into account. Altered food
aminotransferase) patterns within the whole family, as well as sup-
• Consider fasting insulin port of the child and parental reinforcement of a
• Consider oral glucose tolerance test. healthy lifestyle, are important factors in successful
Further assessment of liver function (e.g. liver ultra- outcomes.
sonography, exclusion of other causes of liver dysfunc-
tion) may be required. More detailed endocrinological
assessment may be needed if there is short stature, hir- A developmentally appropriate approach – pre-
sutism or menstrual irregularities. If obstructive sleep adolescent children
apnoea is suspected then referral for polysomnography Treatment of pre-adolescent obesity with the parents
is warranted. as the exclusive agents of lifestyle change is superior, in
terms of long-term weight and psychosocial outcomes,
Defining treatment outcomes to a child-centred approach. Thus, when dealing with
the obese pre-adolescent child, sessions involving the
The goals of therapy should be clarified initially with
parent or parents alone, without the child being pres-
the parents or young person, as appropriate. Markers
ent, are likely to be the most effective.
of a successful outcome of therapy may include:
• changes in weight status: weight loss, and, in pre-
pubertal children, slowing of weight gain or weight Adolescent-focused interventions
maintenance
With adolescents, consider separate sessions for the
• a decrease in waist circumference or waist : height
ratio (‘waist loss’) is a useful indicator of reduction young person and parents. Short-term weight man-
in abdominal obesity agement success is associated with a range of inter-
ventions, all involving intense support for behavioural
• resolution of medical complications
change, such as increased physical activity, ­phone- and
• improvement in self-esteem and psychosocial
functioning mail-based behavioural interventions initiated in
­primary care settings, pharmacological therapy and a
• an increase in level of fitness or aerobic capacity
low glycaemic load diet.
• improvement in family functioning.
Education of the family and, where appropriate, the
young person about the nature of obesity, including the Behaviour modification
realization that it is a chronic disorder of energy balance,
is also important, as the need for long-term changes in There is a range of potential behavioural modification
behaviour will then be more readily apparent. Helping strategies that can be used in the management of child-
the family or young person identify small, achievable hood obesity, including:
goals is important; examples may include aiming ini- • monitoring behaviour (e.g. weighing weekly,
tially for two extra walks per week, or reducing televi- keeping a television-time chart)
sion viewing by 1 hour per day every few weeks. • setting goals
• rewarding successful changes in behaviour through
praise
Broad principles of management
• controlling the food and physical activity environment.
The broad principles of management include: The nature of each of these strategies will vary
• clarification of treatment outcomes depending upon the age and developmental status of
85
• family involvement the patient.
 3.4 SOCIAL AND PREVENTATIVE PAEDIATRICS

Dietary management Dietary interventions should follow national nutri-

tion guidelines and have an emphasis on the items
Involvement of the entire family in making the change
listed in Box 3.4.1.
to a sustainable and healthy food intake is vital.
The focus should be on behaviour change, healthier
food choices, and a reduction in the consumption of Physical activity and sedentary behaviour
energy-dense, micronutrient-poor foods and high-
Participation of obese children in a lifestyle pro-
sugar drinks. Avoidance of severe dietary restriction
gramme (e.g. walking, running, cycling or swimming,
may be important both in helping the development of
based on the family's preference) leads to greater long-
the child's capacity to self-regulate dietary intake and
term reductions in overweight when compared with a
in avoiding the subsequent development of disordered
programme of isocaloric programmed aerobic exer-
eating.
cise. Targeting decreased sedentary behaviour may be
as effective as targeting increased physical activity in
terms of medium-term weight and fitness outcomes.

Clinical example
Peter, a 15-year-old boy with central obesity Box 3.4.1 Interventions for changes in dietary intake,
and metabolic syndrome physical activity, sedentary behaviour and weight
Peter, an Australian boy of Lebanese ethnic
origin, with a strong family history of central Dietary interventions
obesity, type 2 diabetes, premature heart disease and • Modified eating patterns (e.g. regular meals, eating
hypertension, had significant central obesity (weight breakfast, eating together as a family, avoiding eating
102.8 kg, BMI 39.3 kg/m2, waist circumference 115 cm and while watching the television)
waist : height ratio 0.71). He had a very sedentary lifestyle • Parents modelling healthy food choices
and a large intake of soft drink and ‘fast food’ meals. • Food choices that are lower in energy and fat, and that
Peter was aware that he was ‘not able to keep up with my have a lower glycaemic index
mates’, but was otherwise unconcerned about his large • Increased vegetable and fruit intake
size. He had a wide circle of friends. Findings on physical • Healthier snack-food options
examination included hypertension (blood pressure • Decreased portion sizes
130/85 mmHg with a wide cuff; >95th centile for age, sex • Reduction in soft-drink (‘soda’), cordial, other sweetened
and height) and marked acanthosis nigricans at the base drinks and fruit juice intake
of his neck and in his axillae and groin flexures, indicative • Water as the main beverage
of insulin resistance.
Fasting blood tests showed normoglycaemia Physical activity and sedentary behaviour
(4.8 mmol/L), hyperinsulinaemia (280 pmol/L), low • Focus on increasing incidental activity (e.g. playing with
HDL cholesterol (0.8 mmol/L), hypertriglyceridaemia friends or family, walking to the local shops, helping with
(2.2 mmol/L) and a mildly raised alanine housework)
aminotransferase level (60 U/L; normal range 10–50). An • Look at active transport options (e.g. walking, cycling,
oral glucose tolerance test excluded glucose intolerance using public transport)
and diabetes. Liver ultrasound findings were consistent • Choose organized activities that the child enjoys
with diffuse fatty infiltration (in keeping with NAFLD). • Improve access to recreation spaces and play equipment
Thus, Peter had several features of the metabolic (e.g. balls, frisbees, skipping ropes)
syndrome: hyperinsulinaemia, dyslipidaemia, central • Limit time spent watching television, or using the
obesity, hypertension, acanthosis nigricans and fatty liver computer, playstations or other such ‘small screens’, to
disease. less than 2 hours per day
Peter was encouraged to limit his television viewing and • Consider alternatives to motorized transport
he also took out gym membership, although he found it
difficult to attend regularly. A dietitian counselled about Other behaviour modification strategies to promote
dietary change and provided initial frequent review, but healthy behaviours and monitor outcomes
again Peter was unable to sustain the lifestyle change, • Monitor behaviours (e.g. television viewing, time on
largely because of lack of motivation for change. Weight Facebook and other recreational computer pursuits),
gain continued. Orlistat was prescribed, but Peter found having breakfast
the side-effects (bloating, steatorrhoea, abdominal pain) • Monitor weight during weight loss phase (e.g. weekly,
unacceptable and discontinued therapy. After review by a keep a record)
paediatric endocrinologist, Peter was commenced on the • Role-modelling of healthy lifestyle behaviours by family
insulin-sensitizing agent, metformin. There was some initial members
weight loss on this therapy (2 kg in the first month of therapy), • Stimulus control (e.g. avoid having biscuits, soft drinks and
but Peter was relatively non-adherent to therapy after the unhealthy snack choices in the household, or on display in
first couple of months. the home)
86
 Obesity 3.4
Recommendations regarding physical activity and
sedentary behaviour are also listed in Box 3.4.1. The GP sensitively raised the issue of Anna's excess
weight gain with Anna's mother and encouraged a whole-
family approach to lifestyle change. Support for change was
Settings for treatment given by the GP, and the mother also attended a children's
healthy nutrition group programme offered in the local
Time-efficient interventions such as group sessions,
community health centre. Changes that occurred over the
holiday camps or mail- and phone-based behavioural next 6 months included offering the children water instead
interventions may do at least as well as individual of soft drink, reducing portion sizes at the evening meal
sessions in the management of child and adolescent and providing healthy snack choices. The parents instituted
obesity. some rules about television viewing, limiting it to less than
90 minutes per day. The children, including Anna, were
encouraged to play outside more often. The sandpit was
Non-conventional approaches to therapy covered and Anna spent more time in active play.
Six months later, Anna's weight remained unchanged
In adolescents, orlistat (a gastrointestinal lipase
and her height was now 97 cm (97th centile for age). The
inhibitor) may play a role in management of moder- resultant BMI was 21.0 kg/m2, which was still above the 95th
ately severe obesity. Metformin should be considered centile, but there was a marked 2.4-unit decrease over the
in obese adolescents with evidence of clinical insulin time period.
resistance. Both forms of drug therapy should be used
only when the benefits of therapy have been weighed
over the risk of adverse events. There is as yet little
information to guide the use of Very Low Calorie
Diets in adolescents. Any such therapies should occur Primary prevention of child and
in the context of a behavioural weight management
programme and be restricted to specialist centres with adolescent obesity
expertise in managing severe obesity. Because child and adolescent obesity is so common in
There is one randomized controlled trial of bariatric many countries and has such pervasive consequences,
surgery (laparoscopic banding surgery) versus lifestyle it is important that not just the overweight and obese
intervention in adolescents with moderately severe are targeted with treatment interventions, but that
obesity. The study showed improved weight outcomes effective primary prevention strategies are also iden-
at 2 years in those who underwent surgery. There are tified and put into place. Interventions simply focus-
very few nationally relevant position statements on ing on educating individuals and communities about
bariatric surgery in adolescents. behaviour change have had limited or no success
in modifying obesity prevalence. This is because the
broader environment in many communities does not
Clinical example readily support healthy food choices for physically
active lifestyles.
Anna, a 2-year-old girl with excess Many upstream factors (physical, economic and
weight gain sociocultural) contribute to obesity in individuals
At a consultation for an intercurrent illness,
and can operate at both a microenvironmental level
Anna, aged 2 years 2 months, had her height
and weight assessed by her GP. Her height was 92 cm (97th (the settings where individuals live, eat, play or go to
centile for age) and she was noted to be obese, with weight school) as well as at a macroenvironmental level (the
of 19.8 kg (>97th centile for age) and BMI 23.4 kg/m2 (>95th broader sectors that ultimately influence dietary intake
centile for age). and physical activity and that are beyond the ability
Anna's birth weight was 3.7 kg. Review of her growth of an individual to influence). Microenvironments rel-
records showed that her weight had tracked along the 90th
evant to obesity include homes, schools, community
centile for the first 6 months, and that from 12 months of age
her weight had steadily veered above the 97th centile. In the
groups (e.g. clubs, churches), food retailers (e.g. super-
past 14 months, Anna had been eating the same foods as markets), food service outlets, recreation facilities and
her parents and two older siblings. This included two or three local neighbourhoods (e.g. cycle paths, street safety).
‘fast food’ meals per week, several ‘treat’ snacks per day Macroenvironments relevant to obesity include food
(e.g. biscuits or a packet of crisps) and a regular soft drink production and importing, food manufacturing and
intake. When outside, Anna tended to sit and play in the importing, food marketing (e.g. fast-food advertising),
sandpit rather than play actively. There were three televisions
the sports and leisure industry (e.g. instructor training
in the household and Anna was estimated to watch
3–4 hours of television per day. Both of Anna's parents were programmes), urban and rural development (e.g. town
mildly obese and her siblings were also overweight. planning, local government) and the transport system
(e.g. public transport systems).
87
 3.4 SOCIAL AND PREVENTATIVE PAEDIATRICS

Considering this, a range of opportunities exists for • Comprehensive community-based interventions

prevention strategies in a given community or country. • Employers that support healthy eating and
These might include: physical activity
• Reshaping the food supply and encouraging • Town planning and building design that
physical activity: encourage physical activity (e.g. public
• Review taxation systems to enable access to transport, cycle paths, footpaths, protect open
healthier foods and active recreation (e.g. tax spaces)
breaks for fitness products and providing healthy • Incentive schemes that encourage healthy
foods in schools and workplaces; tax energy- behaviours (e.g. gym memberships, active travel
dense foods and sugary drinks) included in expense policies).
• Regulate the amount of fats, trans-fats, sugar and • Primary healthcare and public health workforce to
salt in foods support people in making healthier choices.
• Subsidize transport of fresh foods to rural and • Encouraging and supporting breastfeeding.
remote areas. • Closing the gap for disadvantaged communities.
• Curbing inappropriate marketing of unhealthy • Monitoring the prevalence of obesity and
foods and beverages. obesity-conducive behaviours, and evaluating the
• Improving public education and information: effectiveness of interventions.
• Effective long-term marketing to improve eating • Implementing national food strategies that
and physical activity harmonize policies related to sustainability of the
• Develop national systems of simple, food supply, agriculture, food production, food
comprehensible food labelling to support healthier distribution and health.
food choices. Such interventions will require intersectoral and inter-
• Reshaping urban environments towards healthy governmental cooperation, supported by adequate
options: resourcing and significant community ownership.
• School communities that support healthy eating
and physical activity

88
 Immunization
Peter Richmond
3.5
Immunization provides protection against specific infec- pregnancy, and breastfeeding supplies IgA antibody at
tious diseases and is one of the greatest achievements of the mucosal surfaces of the gastrointestinal tract.
medical science and public health. It is the right of every Passive immunization as a means of disease preven-
child to be protected against vaccine-preventable dis- tion is used in the form of:
eases: parents, caregivers and health professionals need • normal human immunoglobulin for protection
to ensure that immunization is available to all children. against measles and hepatitis A, and in children
Protection against subsequent infection after surviv- with immunodeficiency
ing the initial challenge has been recognized for many • specific high-titre preparations against
centuries for some infections. The use of material from cytomegalovirus (CMV), varicella, tetanus,
smallpox lesions for vaccination was practised in early rabies, hepatitis B and diphtheria (for use as ­post-
dynasties in China. Edward Jenner recognized that exposure prophylaxis in high-risk situations or in
vaccination with cowpox virus could protect against immunocompromised children), and as
challenge with smallpox. Smallpox was declared eradi- • humanized monoclonal antibody against
cated worldwide in 1979. respiratory syncytial virus (RSV) infection (may
Diphtheria immunization began in the 1920s, and be used as primary prophylaxis in children with
immunization campaigns against pertussis (whooping chronic cardiac and lung disease).
cough) were initiated in the 1940s. In the 1950s, triple Passively acquired immunoglobulin has a relatively
antigen vaccine (DTP: diphtheria, tetanus and pertus- short half-life and does not lead to active immunity or
sis) was introduced and polio immunization campaigns long-term protection.
began, leading to its elimination in the developed world.
It is likely that poliomyelitis will be the second vaccine-
preventable disease to be eradicated worldwide. Measles Active immunization
immunization has been available for more than 40 years, Active immunization involves administering a vaccine
and the last decade has seen the introduction of many antigen so that a protective immune response ­develops
new vaccines with rapid impact on rates of serious infec- that is similar to that occurring after naturally acquired
tions such as meningococcal and pneumococcal disease. infection. This immune response should be one that
Immunization remains one of the most important entails the development of persistent immunological
public health priorities in developed and developing memory, and long-term protection from the infectious
countries. In the developing world, many millions disease.
of childhood deaths occur each year from vaccine- Active immunization to prevent infection or the effects
preventable diseases such as tetanus, pneumonia, of infection may be performed using:
diarrhoea and measles because of lack of access to • whole organisms (live attenuated or killed)
vaccines and vaccine provider services. Thus, immu- • purified components of organisms (subunit
nization and its promotion remains one of the major vaccines, polysaccharide vaccines)
activities of the World Health Organization, with the • modified products of the infecting organisms
aim of achieving universal immunization for children. (toxoid vaccines)
• manufactured components of organisms
(recombinant vaccines).
Principles of immunization
Requirements of vaccines
Immunization may be passive or active.
Ideally, a vaccine should:
• give complete protection from the disease caused by
Passive immunity
the infection
Passive immunity refers to the acquisition of pre- • give lifelong protection
formed antibody. The fetus receives maternal immu- • cause minimal transient adverse effects 89
noglobulin (Ig) G antibodies during the later weeks of • need to be given once only
 3.5 SOCIAL AND PREVENTATIVE PAEDIATRICS

• be able to be given in combination with other the most common strains that cause disease out of
vaccines more than 90 strains of pneumococci.
• be able to be administered easily and without • The nature of the immune response at different
discomfort ages. For example, Haemophilus influenzae type
• be stable under a wide range of storage conditions b (Hib) vaccines, meningococcal C vaccine and
• have a long storage life pneumococcal vaccines are much
• be easy and cheap to manufacture. more effective in infants when given as
polysaccharide–protein conjugate vaccines rather
than purified polysaccharide vaccines because of
Principles of vaccine selection
the poor immune response to polysaccharides at
Common infectious diseases and the vaccine types this age.
used for prevention of these diseases are listed in • The effects of maternal antibodies on vaccine
Table 3.5.1. The immunization strategies used for these responses in infants. Measles immunization is not
diseases have been developed to take account of the undertaken until the age of 9–12 months in most
following factors: countries because passively acquired maternal
• The nature of the disease process. For example, antibody remains in sufficiently high concentration
toxoid vaccines are used to prevent diseases in to neutralize the administered live attenuated
which exotoxins are responsible for the disease such vaccine virus strain in the infant prior to this age.
as diphtheria and tetanus. • The age at which children are most susceptible to
• The route of infection. For example, oral rotavirus infection. Meningococcal C conjugate vaccines
vaccines have been developed to provide protective are given as a single dose at 12 months of age in
mucosal immune responses to rotaviruses, which Australia as meningococcal C disease was rare
are a major cause of severe gastrointestinal tract before that age, whereas in the UK it is given to
infections in infants. infants at 2, 4 and 12 months of age as the peak
• Variability of the organisms causing disease. incidence was between 6 and 12 months of age.
For example, influenza vaccines need annual • The ability to reduce transmission in the community
modification to provide protection from prevalent and induce herd immunity. For example, rubella
circulating strains; polio vaccines (oral and immunization is given to all children to provide
inactivated) contain the three strains of the longlasting immunity for girls before their
poliovirus that cause disease, and pneumococcal childbearing years, and to decrease the circulation
vaccines contains polysaccharide from 7 to 23 of of rubella in the community, and therefore the

Table 3.5.1 Vaccine types for schedule vaccines and other commonly available vaccines

Disease Vaccine type

Schedule vaccines
Hepatitis B Recombinant subunit vaccine
Diphtheria Toxoid (formaldehyde-treated toxin)
Tetanus Toxoid (formaldehyde-treated toxin)
Pertussis Acellular vaccine containing 2–5 protein antigens from Bordetella pertussis
Haemophilus influenzae type b (Hib) Polysaccharide protein conjugates (PRP-OMP, PRP-T)
Poliomyelitis IPV: inactivated poliovirus vaccine (types 1, 2 and 3)
Measles, mumps and rubella Attenuated live viruses (freeze-dried)
Varicella Attenuated live virus (freeze-dried)
Pneumococcal infections Conjugate vaccine containing 7, 10 or 13 pneumococcal serotypes
Meningococcal C disease Meningococcal C conjugate vaccine

Other commonly used vaccines

Influenza Subunit vaccine derived from inactivated virus
Hepatitis A Inactivated hepatitis A strain
BCG Live attenuated bacteria
Pneumococcal infections Polysaccharide vaccine containing 23 pneumococcal serotypes (not conjugated)
Meningococcal infections Quadrivalent vaccine containing A, C, W135 and Y polysaccharides (both conjugated
and unconjugated available)

90 BCG, bacille Calmette–Guérin.

 Immunization 3.5
risk of exposure of pregnant women to rubella.
Table 3.5.2 National Health and Medical Research Council
These strategies have resulted in a dramatic National Immunization Programme for Australian children
decrease in fetal rubella infection and the associated
malformations that occur in early pregnancy Age Vaccine Route
(congenital rubella embryopathy).
Birth HBV IM
• The ability to optimize immunization coverage for
the high-risk population. A targeted strategy of 2, 4 and 6 months DTPa* IM
hepatitis B vaccination in newborns of mothers Hib* IM
who are hepatitis B carriers to prevent perinatal IPV* IM
transmission was ineffective in immunizing the HBV* IM
at-risk infants so universal newborn hepatitis B PCV IM
RV Oral
immunization has been implemented in Australia.
12 months MMR SC
Hib† IM
MenCC† IM
Immunization schedule for
18 months Varicella SC
routine childhood immunization
4 years DTPa-IPV IM
The national immunization schedule in countries is
OPV Oral
generally recommended by an expert committee and MMR SC
is then funded by the government at a later stage. The
current Australian schedule is presented in Table 3.5.2. 12–15 years dTpa IM
There are differences in the schedule in individual Varicella‡ SC
countries and sometimes within countries because of HBV§ IM
variations in the epidemiology of some diseases, the HPV¶ IM
registration and prices for supply of different types of *These antigens are currently given as a single injection as
vaccine, and national priorities and public demand. part of a hexavalent vaccine in infants in Australia and New
The immunization schedule has changed significantly Zealand, whereas HBV is not routinely used in the UK.
in recent years with the availability of new vaccines †
May be given as a combined Hib–MenC conjugate vaccine
and is likely to change frequently in the future, so it is (also used in the UK as a 2–4–12-month schedule).
important to keep up to date. ‡
Varicella vaccine is given only where children have not
Vaccines are provided to registered immunization previously received varicella vaccine and have no history of
providers and generally are free of charge for children. chickenpox.
§
This course of HBV (2 doses of adult formulation) is only for
Immunization providers are general practitioners,
children not previously vaccinated against hepatitis B in infancy.
local authority immunization services, some hospital ¶
Currently, HPV vaccine is only given to girls as a 3-dose
services (particularly in children's hospitals), and some schedule, but is also licensed for boys.
maternal and child health agencies. All immunization HBV, recombinant hepatitis B vaccine; DTPa, infant
providers must be familiar with: formulation of acellular diphtheria, tetanus and pertussis
• the immunization schedule vaccine; Hib, Haemophilus influenzae type b conjugate
• vaccine storage and handling requirements vaccine; IPV, inactivated poliovirus vaccine; OPV, oral
• requirements for informed consent for vaccine poliovirus vaccine; PCV, pneumococcal conjugate vaccine
(3 licensed formulations containing 7, 10 or 13 serotypes);
administration
RV, rotavirus vaccine (2 licensed formulations given as
• adverse effects of immunization either 2- or 3-dose schedule); MMR, measles, mumps and
• potential contraindications to immunization. rubella vaccine (a combined formulation with varicella
Information regarding schedules, vaccines and pro- vaccine (MMRV) is also licensed); MenCC, meningococcal
cedures needs to be updated regularly; in Australia C conjugate vaccine; dTpa, reduced antigen formulation
this is provided at regular intervals by the National of diphtheria–tetanus–acellular pertussis vaccine for
Health and Medical Research Council (NHMRC) adolescents and adults; HPV, human papillomavirus vaccine
(both bivalent and quadrivalent HPV vaccines are licensed);
Immunization Technical Advisory Group as The
IM, intramuscular; SC, subcutaneous.
Australian Immunisation Handbook, which is made
available to all immunization providers and to other
health-care providers who have a role in immuniza- exist in ­electronic and hard copy format in the UK
tion services, and is also available as an up-to-date (http://www.dh.gov.uk/en/Publicationsandstatistics/
electronic version on the internet (http://www.health Publications/PublicationsPolicyAndGuidance/
.gov.au/internet/immunise/publishing.nsf/content/ DH_079917) and New Zealand (http://www.moh.govt.
91
handbook-home). Similar immunization handbooks nz/moh.nsf/indexmh/immunisation-handbook-2011).
 3.5 SOCIAL AND PREVENTATIVE PAEDIATRICS

used routinely prior to each immunization episode.

Administration of vaccines The questionnaire should enquire whether the child:
Storage of vaccines • has had any previous severe reactions to any vaccine
• has any condition that may lower immunity (for
Most vaccines need to be stored in a temperature range example, treatment with systemic steroids or
between 2° and 8°C. Maintenance of the cold chain chemotherapy, pre-existing immune deficiency
is required from the time of manufacture until the disorder or disease affecting immunity, such as
time of administration. Vaccine storage t­emperature leukaemia) or lives with someone with lowered
conditions must be monitored c­ontinuously, using immunity
thermometers capable of recording maximum and • might be pregnant (for girls of childbearing age)
minimum temperatures, preferably in a purpose-built • has had a vaccine containing live viruses within the
vaccine refrigerator. Generally, freezing of v­ accines is last month
more deleterious to vaccine efficacy than short periods • has any severe allergies (although this is not a
of time above the recommended temperature range. contraindication to scheduled immunizations)
• has received a blood transfusion or
immunoglobulin preparation in the last 3 months
Clinical example • identifies as being Aboriginal or Torres Strait
Holly was brought in by her mother to her
Islander person (to ensure that they receive any
general practitioner (GP) at 18 months of age to additional immunizations required).
discuss her varicella immunization. Her parents Children should be assessed to ensure that they are
were confused as they had heard she was better well enough to have vaccine administered: immuniza-
off getting chickenpox as an infection because it gave longer- tion should be deferred only rarely, but may be delayed
lasting immunity and giving the vaccine at this age would temporarily if there is a temperature over 38.5°C, if the
put her at risk of more severe disease as an adult. Also they
child has diarrhoea or vomiting (for oral vaccines only),
were concerned that, if she had the vaccine, she would be at
risk of giving the disease to her brother Tom (4 years of age)
or if he or she is obviously unwell for other reasons.
who was undergoing chemotherapy for acute lymphoblastic
leukaemia and had not had chickenpox or been vaccinated.
Sites of vaccine administration
The GP advised Holly's parents that varicella vaccine provided
good long-term protection against varicella infections and any Intramuscular vaccine administration in infants under
breakthrough infections (1–2% per year) were mild. In contrast, the age of 1 year should be at the junction of the upper
although chickenpox infection is generally self-limiting, there are
and middle one thirds of the anterolateral thigh. If
risks of severe varicella infection or secondary bacterial infection,
which results in 1 in 200 children being hospitalized. The GP also three separate intramuscular vaccines are being given,
advised that vaccinating Holly was the best way of protecting two vaccines are given in one thigh at least 2.5 cm apart
her brother, as vaccinated healthy children do not pass on the and the other vaccine in the other thigh. In children
infection and this will decrease the risk of her brother being over the age of 1 year, intramuscular vaccines are given
exposed to a potentially dangerous infection. into the mid-deltoid region of the upper arm. Vaccines
should not be given in the buttocks because of possible
suboptimal immune response or sciatic nerve damage.
Consent for immunization
Parents or guardians must be given adequate informa- Adverse effects of immunization
tion that will allow them to make an informed decision
about immunization for their child. The information Immunization promotes a protective immune response.
given should include: As part of this, there is often some evidence of minor
• the benefits and risks of immunization inflammation in association with parenterally admin-
• the common side-effects of the various vaccines. istered vaccines which may result in local redness and
This information preferably should be available in swelling at the injection site or mild transient systemic
written form, and is provided in a form suitable for symptoms including crying, irritability and fever. These
parents and guardians in The Australian Immunisation were more common with whole-cell ­pertussis vaccines
Handbook. Valid consent is necessary prior to each and are now much less frequent with the a­ cellular per-
immunization episode. tussis combination vaccines and ­conjugate vaccines.
Large local reactions may occur, especially in older chil-
dren. Measles immunization may be f­ ollowed by a mild
Pre-immunization questionnaire
and transient measles-like illness, with fever and a brief
In some circumstances, the risk of adverse reactions rash, about 7–10 days after immunization. All of these
to immunization is increased in the presence of some side-effects are generally transient, require no specific
92
conditions. A standardized questionnaire should be treatment and do not preclude further vaccination.
 Immunization 3.5
Rarely, there may be major events in association risk of infectious diseases and generally achieve similar
with immunization procedures. Anaphylaxis is very protection following vaccination as term infants. For
rare (less than 1 in 100 000 immunizations), but every some vaccines such as hepatitis B and Hib, extremely
immunization provider must have the appropriate premature infants (< 29 weeks' gestation) may require
equipment and training for dealing with anaphylaxis. additional doses to ensure protection.
The most important components of management of
anaphylaxis are maintenance of the airway and the
administration of adrenaline (epinephrine).
Clinical example
Convulsions sometimes are seen in association with
immunization procedures. Simple febrile convulsions Jake was born at 26 weeks' gestation after
may occur in conjunction with febrile responses to any his mother unexpectedly went into premature
vaccine in children predisposed to febrile convulsions; labour. He had significant respiratory distress in
however, these are not contraindications to further the first 3 weeks after birth, requiring surfactant,
immunization. Immunization is not associated with and he was ventilated for 2 weeks. He then needed
supplementary oxygen for 4 weeks. He needed parenteral
sudden or unexpected infant death syndrome (SIDS).
nutrition for the first 4 weeks of life, then nasogastric tube
Several studies, including a recent well controlled study feeding for 4 weeks, before he was able to suck and be fed
in New Zealand, have shown that the relative risk for expressed milk from a bottle.
SIDS is decreased in immunized children. The day he was born, Jake received his first dose of
hepatitis B vaccine as part of the routine schedule of
Disorders that are not contraindications to vaccines. At 8 weeks after birth, when he was still equivalent
immunization to 34 weeks' gestation, he received pneumococcal conjugate
vaccine (PCV), DTPa vaccine, Hib and inactivated polio
Immunization is not contraindicated in children: vaccine, and his second dose of hepatitis B vaccine as part of
• with minor upper respiratory tract illness (colds, the routine immunization schedule. The DTPa , IPV, hepatitis
cough, sore throat) or low-grade fever at the time B and Hib vaccine were given as a single combination
vaccine, DTPa–HBV–IPV/Hib, into his lateral thigh, and the
immunization is due
PCV vaccine was given at the same time into the other thigh.
• using inhaled steroid medications for control of His equivalent gestation when he was discharged was
asthma, or topical steroids for dermatitis 38 weeks. At the time of discharge, arrangements were
• with allergies made for Jake to have his 4-month schedule immunizations,
• receiving antibiotics DTPa–HBV–IPV/Hib and PCV, 4 weeks after discharge, when
• with controlled epilepsy, a history of febrile he was 4 months old and again at 6 months of age. This
was followed by meningococcal C, MMR and Hib on his first
convulsions, a family history of epilepsy or stable
birthday.
neurological disorders
• who have been premature or who are growing poorly.
Children who have documented egg allergy can be
safely immunized, as egg proteins are not found Missed or delayed immunizations
in ­
vaccines in the routine childhood immunization If a child has not received immunization at the appro-
schedule, including measles–mumps–rubella (MMR) priate ages, ‘catch up’ immunization schedules are used.
vaccine. However, advice should be given about immu- The immunization schedule does not have to be recom-
nization with influenza and yellow fever vaccines, menced and additional doses of vaccine are not needed.
which are not recommended for children with anaphy- Schedules for catch-up immunization for DTPa com-
laxis to egg due to the trace amounts of egg protein in bination, hepatitis B virus (HBV), pneumococcal and
these vaccines. Hib vaccines are outlined in the immunization hand-
book. Many opportunities for catch-up immuniza-
tion are missed when children present to their general
Specific immunization ­practitioner or hospital for unrelated problems and an
considerations accurate immunization history is not taken or checked in
the parental hand-held record or immunization register.
Prematurity
Premature infants should receive their i­mmunizations
Live virus vaccines
at the appropriate age after birth, regardless of their
gestational age. For example, an infant born 8 weeks Live virus vaccines such as MMR and varicella can
prematurely should commence the immunization be given on the same day if necessary, for example for
schedule at the age of 2 months, even though the catch-up immunization; however, if different live virus
­gestational age would only be at ‘term’ if not born pre- vaccines cannot be given on the same day, they should
93
maturely. Premature infants are generally at greater be given at least 4 weeks apart.
 3.5 SOCIAL AND PREVENTATIVE PAEDIATRICS

• identification of the immunization service

Comparison of effects of provider
diseases and vaccines • the date at which the next immunization is due.
This information should be recorded in a parent-held
The benefits of immunization greatly outweigh the Child Health Record, and in the records of the immu-
risks of any adverse events associated with administra- nization service provider. It should also be entered in
tion of vaccines used in the childhood immunization nationwide immunization databases. The Australian
schedule. Table 3.5.3 lists some comparisons for vaccine-­ Childhood Immunization Register (ACIR) was com-
preventable diseases and adverse effects, which may be menced in 1996 for this purpose, and similar registers
associated with the corresponding vaccines. A more com- are used in New Zealand and the UK. The register is
plete listing of adverse events is available in immuniza- used for providing a reminder system to inform p ­ arents
tion handbooks and vaccine product information sheets. and caregivers when the next immunization is due for
their child, as well as for monitoring vaccine coverage.
Uptake of immunization may be encouraged by using
financial incentives for both parents and immuniza-
Recording of immunization tion providers.
administration
Accurate recording of vaccine administration is essen-
tial. This must include:
• the vaccine administered
Other vaccines
• the vaccine batch number and any other appropriate Other vaccines are available that are not part of the
identifying information routine childhood immunization schedule.

Table 3.5.3 Benefits and side-effects of childhood immunizations

Infection Effects of infection Side-effects of immunization

Hepatitis B Persistent carrier state common after infection Minor fever in 2–3%; local inflammation in
Long-term risk of chronic hepatitis and primary 5–15%
liver cancer

Diphtheria Toxin causes nerve and heart damage DTPa may cause minor local reactions such
Mortality rate 1 in 15 as swelling, redness and discomfort in
approximately 15% of recipients

Tetanus Toxin causes nerve and muscle changes resulting As for diphtheria
in paralysis, convulsions
Mortality rate 1 in 10

Pertussis Whooping cough. Mortality and morbidity rate As for diphtheria

highest in infants. Mortality 1 in 200 if infected in
first 6 months of life

Poliomyelitis Febrile illness, followed by paralysis in many Paralysis related to vaccine strain virus in 1 in
Mortality rate 1 in 20 hospitalized patients 2.5–5 million recipients or close contacts
Permanent paralysis in many

Haemophilus Systemic infections such as meningitis, epiglottitis, Discomfort or local inflammation in 5%; fever
influenzae b bone and joint infections in 2%
Meningitis mortality rate 1 in 20; longlasting
morbidity 1 in 4

Measles, mumps and Measles encephalitis in 1 in 1000–2000; mumps Minor fever, local inflammation in up to 10%
rubella encephalitis in 1 in 200 1 in 1 million may develop measles
Congenital rubella syndrome if infected in first vaccine strain encephalitis; 1 in 3 million
trimester of pregnancy may develop mumps vaccine strain
encephalitis

94 Source: Modified from The Australian Immunisation Handbook, 9th edn, National Health and Medical Research Council, 2008.
 Immunization 3.5
Influenza vaccine Meningococcal quadrivalent ACW135Y
polysaccharide vaccine
The H1N1 influenza pandemic in 2009 highlighted the
at-risk groups for hospitalization with influenza and This is used for the control of outbreaks of meningo-
its complications, as well as confirming the burden of coccal disease, in those with complement deficiency
influenza in young children. disorders, in those with asplenia or splenic dysfunc-
Annual immunization with influenza vaccine is tion, and is required for pilgrims attending the Hajj
­recommended for: as well as being recommended for travellers to sub-­
• children receiving immunosuppressive therapy, for Saharan Africa, and other countries where these
example chronic steroid use and with malignancy, strains are common. Protection following the poly-
and those with human immunodeficiency virus saccharide vaccine is short term so the quadrivalent
(HIV) infection ACW135Y conjugate vaccines are likely to become the
• children over 6 months with chronic heart preferred vaccine for these conditions.
conditions, including cyanotic congenital heart
disease
• children with chronic suppurative lung diseases, Clinical example
including cystic fibrosis
• children over 6 months of age with chronic illnesses Joshua, aged 6 months, was brought to the
requiring regular medical follow-up (diabetes community health centre by his 18-year-old
mellitus, chronic renal failure, chronic metabolic mother to see a doctor for advice about a
rash on his cheeks, behind his ears and over
disorders, haemoglobinopathies)
his upper trunk. The rash was due to infantile eczema. On
• contacts of high-risk patients, particularly questioning, it was found that he had not yet received any
household members. of his childhood immunizations. His mother said that this
was because he always seemed to have a runny nose when
Bacillus Calmette–Guérin (BCG) due for immunization, and she had been concerned that
immunization might make his rash worse.
Immunization with BCG is no longer provided for all She was reassured that immunization was not
children in most developed countries where the overall contraindicated in the presence of rhinitis or eczema and
prevalence of tuberculosis is low. However, it may be that immunization was important in infancy. Advice on
the management of eczema was given. Joshua received
recommended for:
his first DTPa, Hib, hepatitis B, IPV (poliovirus vaccine)
• neonates in Aboriginal and Torres Strait Islander and pneumococcal immunizations that day from the
communities in regions of high incidence health centre's immunization clinic. The immunizations
• neonates or young children in households containing were recorded in his health record and in the Childhood
immigrants from countries of high incidence Immunization Register, and appointments were made
• children who are going to live in countries with a for further DTPa, Hib, hepatitis B, IPV and pneumococcal
immunizations at ages 8 and 10 months. He achieved
high tuberculosis prevalence.
his second immunization ‘milestone’ by receiving MMR,
meningococcal C vaccine and HBV on his first birthday.
Hepatitis A vaccine
Hepatitis A vaccine normally is given as a two-
dose schedule for travellers to endemic areas, and is
­recommended for Aboriginal and Torres Strait Islander
Immunization in special
children at 18 months of age in northern parts of
­ circumstances
Australia, owing to the incidence of hepatitis A with Travel
significant morbidity in that population, and in c­ hildren
with chronic liver disease. Advice for specific vaccines to protect against infection
while travelling in other countries depends on the nature
of endemic infections in those countries. Information
Pneumococcal vaccines
can be obtained in Australia from the Commonwealth
In addition to infants, pneumococcal immunization Department of Health and Aging, the National Travel
also is important in older children at high risk of Health Network and Centre in the UK, the World
pneumococcal disease, such as those with nephrotic Health Organization, or from the US Centers for Disease
syndrome, asplenia, sickle cell disease, immune
­ Control and Prevention. It is important for all children
­deficiency, immunosuppressive therapy, renal failure, travelling to be up to date for all their routine childhood
cardiac d ­ isease, cancer or chronic lung disease. These immunizations as these infections are prevalent in many
children may require additional boosters of pneumo- countries, and for parents to be aware of simple hygiene
95
coccal c­ onjugate vaccine or polysaccharide vaccine. and protective measures for preventing infection.
 3.5 SOCIAL AND PREVENTATIVE PAEDIATRICS

HIV infection
Future vaccines and vaccine
Infected or potentially infected infants and children
should receive the standard immunization schedule development
including MMR vaccine, and it is recommended that Potential changes to immunization strategies for chil-
inactivated poliovirus vaccine (IPV) be given in place dren in the near future in Australia and many other
of OPV if still used. Pneumococcal conjugate vaccine countries include:
booster is recommended for HIV-infected infants, and • new combination vaccines such as MMR–varicella
pneumococcal polysaccharide vaccine for older children. • meningococcal B vaccines for infants (a strain-specific
Varicella vaccine can be given to HIV-infected children vaccine has already been used in New Zealand
who are asymptomatic or mildly affected with a normal with great success).
CD4 count. Annual influenza vaccination is also recom- Other developments in immunization during the next
mended. BCG should not be given to ­children with HIV 5–10 years are likely to lead to the a­ vailability of serotype-
infection because of the risk of disseminated disease. independent pneumococcal vaccines, ­ live-attenuated
nasal vaccines for RSV, parainfluenza virus and geneti-
Bone marrow transplantation cally modified chimeric d ­ engue virus vaccine. There is a
great need for vaccines against malaria and other par-
Following allogeneic and autologous stem cell asitic diseases causing widespread m ­ orbidity globally,
transplantation, pre-existing immunity to vaccine-­ and for vaccines with greater ­efficacy against tubercu-
preventable diseases is completely or partially lost and losis. Public health strategies will have as their primary
re-immunization is necessary. All routine childhood focus procedures and community campaigns to ensure
immunizations should be included, although the t­ iming the highest possible uptake, in both developing and
and number of doses required will vary between units developed countries, of the highly effective vaccines
and the degree of the patient's immune reconstitution, already available.
and expert advice should be sought.

Asplenia
Children with asplenia (congenital; after splenectomy, Practical points
for example for hereditary spherocytosis or trauma) or
splenic dysfunction (for example in sickle cell d
­ isease) • Immunization is one of the most effective medical
interventions for children to maintain their health.
should receive pneumococcal vaccine (­conjugate ­vaccine
• Immunization coverage needs to be maintained to prevent
if less than 5 years of age and polysaccharide vaccine recurrence of infectious disease epidemics.
for older children) and meningococcal C conjugate • There are few contraindications to immunization, and
vaccine followed by quadrivalent meningococcal poly- opportunistic immunization needs to be considered by all
saccharide vaccine. Hib vaccine should be given if it health providers.
has not been received in infancy. • Informed consent needs to be taken from parents with an
outline of potential benefits and adverse events prior to
immunization.
Primary immunodeficiency disorders • The effectiveness of immunization has led to the frequent
introduction of new vaccines into the routine schedule, so
Live viral vaccines and BCG should not be used in immunization providers need to keep up to date.
children with primary immunodeficiency disorders.

96
 Trauma
Danny Cass
3.6
This chapter will firstly cover the sequence of care
Introduction of the individual paediatric trauma patient, secondly
Children have never been safer. The rates of death describe specific injuries and their management, and
and serious injury in developed countries have never finally discuss prevention strategies.
been lower. In many OECD countries the decrease
over the last 25 years has been in the order of 300%.
Nevertheless, it is a testament to the size of the prob-
lem of paediatric trauma that, despite this signifi-
Paediatric trauma care
cant decrease, trauma is still the largest single cause Skill, knowledge and the ability to make decisions with
of death and severe disability in children. A lot has incomplete information are essential. There is nothing
been done but there is still significant room for further potentially more terrifying to a clinician to be stand-
improvement. ing next to an injured child with no clear idea as to
what body systems may be injured or how severely.
Will this be a simple fracture or could there be a
potentially fatal haemorrhage or a lurking extradural
Practical points ­haematoma? However, with a systematic approach,
the care of the injured child is straightforward and
• Injury is the leading cause of death in children over 1 year should not be daunting.
in developed countries.
• Injuries are not ‘accidents’ but predictable, preventable
events. Preparation
• Cognitive and physical factors contribute to the
developmental vulnerability of the child to injury. The care of such an injured child starts well before the
• Environmental modification is more effective at preventing arrival at your clinic or hospital. At medical school,
injury than education and supervision. ensure that you have done a first-aid course. After
• Falls are the leading cause of injury in children of all ages. graduation, enrol in a trauma course suitable to your
• In toddlers, drowning is the leading cause of death and level of experience and vocation. Each of these skills
poisoning the most common cause of admission to
courses teaches a systematic approach that deals logi-
hospital.
cally with the sequence of potentially life-threatening
• Bicycles are the most common consumer product
associated with injury in children. injuries, work in teams, and how to communicate with
• Suicide is the leading cause of death in children aged the broader trauma system.
10–14 years. When starting any new job, ensure that you know
the local trauma system. Is there a trauma team?
What is your role? Are you likely to be the only clini-
In developing counties the epidemic of trauma is cian at some time during the night or weekend? Where
increasing or at a peak. It is sad to see that rapid eco- is the equipment? How do you contact more senior
nomic development in these developing countries has clinicians?
not included measures to prevent the errors devel-
oped countries had made during their phases of rapid
Initial care
urbanization after World War II. With the lessons
learnt, many of the injuries could have been avoided. Remember that most (97%) paediatric trauma is simple
The priorities of children have again been overlooked and involves a single system of the body. These inju-
and the same struggles for childhood safety have to be ries are easily dealt with calmly with a careful, well
repeated. It behoves clinicians in developed counties to documented history, a detailed documented examina-
assist childhood advocates in developing countries to tion, appropriate investigations and, if necessary, refer-
accelerate improvements and where possible avoid the ral to the appropriate surgical registrar. There can be
unnecessary loss of life as a result of injury. tricky penetrating injuries such as a fall on to k
­ nitting
97
 3.6 SOCIAL AND PREVENTATIVE PAEDIATRICS

needles with an entry point on the flank resulting in a then the heart and brain are getting sufficient oxy-
spinal cord injury, but these are usually identified with gen, and fluids can be given judiciously. The respira-
the routine medical process described above. In the case tory rate is a good indicator of cellular hypoxia and
just noted, it was the lack of passing urine and a per- metabolic acidosis (see Chapter 5.2 for age-associated
cussible bladder that alerted the clinician to a poten- normal values). Brain function is an exquisite indica-
tial spinal cord injury. The most common error in these tor of cellular function. Even when the child is pale
injuries is lack of history-taking, a cursory examina- and has tachycardia, if he or she can have a coherent
tion, with poor and illegible documentation and poor conversation then hold off excessive fluids as this can
handover. restart bleeding. Where there is continuing severe blood
About 3% of paediatric trauma cases are potentially loss the patient is confused and breathing rapidly, often
more serious and involve multisystem injuries. These leading to confusion that the patient has a head or chest
patients need a different structure of care. The essen- injury. It is these patients who need rapid and aggressive
tial ingredients are to transport such a patient quickly fluid resuscitation.
to a facility that can provide definitive care of the inju- In this early phase, making decisions is more impor-
ries. If such a patient is brought by parents to your tant than defining the precise diagnosis. The child
surgery or small hospital, then management of the should go directly to theatre if there is uncontrolled
airway, pressure on points of obvious bleeding and bleeding. However, this is a rare event. With faster
arranging of transfer is all that is possible. computed tomography (CT), especially if located in
Ideally, such patients have an emergency call that the ED, a head and chest and/or abdominal scan can
brings emergency services to the scene, and with mod- be performed. In children we are reluctant to perform
ern communication there is often forewarning that the whole-body scans routinely because of the radiation
child is coming to your hospital. doses. Every test should be done looking for an injury
Upon arrival in the emergency department (ED) that may need early treatment. CT is especially indi-
there is a structured and pertinent handover from the cated for neurosurgical injuries where the precise loca-
prehospital team. The first examination (primary sur- tion and extent of the injuries assists surgery.
vey) identifies and corrects immediate life-threatening Handover in the acute trauma situation is para-
injuries. Then focused tests (such as a chest or spinal mount. There needs to be clear and concise communi-
X-ray) can be done and quick adjuncts to care instituted cation, both spoken and written. For this reason, the
(e.g. inserting a urinary catheter or nasogastric tube) trauma team leader should be the most senior person
followed by a comprehensive secondary survey, which is who can also offer continuity of care. A consultant may
a head to toe examination in association with a detailed be able to offer more expert care for a few minutes of
history. In children, the same process is followed as care but then have to hand over. Frequent handover in
in adults, but with refinements that take into account the acute, fast-moving situation will often fail to hand
paediatric anatomy, physiology and psychology. In the over small but potentially critical pieces of information.
moment of immediate care, if in doubt, do not hesitate A registrar who can be with the patient for some hours
because the patient is an injured child: do the same as is often a better team leader, because continuity of care
you would for an adult. If the conscious state is such up to the point of deciding on the need for definitive
that you would intubate in an adult, then do not try to surgical care outweighs the transient expertise of a con-
get by with a bag and mask in a child because of uncer- sultant. A key contribution to care is clear, legible notes.
tainty: intubate. If the child is screaming and agitated,
do not become so anxious that you are feeling you must
Ongoing care
intubate. Be guided by the objective signs and symp-
toms, as you would in an adult. The next day it is important to review the whole sit-
However, in your training take every opportunity uation (tertiary survey). This includes a complete his-
to understand the refinements of paediatric trauma tory as many aspects at the scene and in the first few
care. In this way you will provide optimal care for the hours can be confused or misinterpreted. Therefore,
injured child. The fluids must be calculated on a mil- it is important to start afresh and not merely to tran-
ligram per kilogram (mL/kg) basis. The endotracheal scribe the ambulance or ED notes. A tertiary history
tubes have to be the correct size. is a precise description of the injury events including
It is increasingly realized that trauma patients do not diagrams, documentation of safety issues such as seat
need aggressive fluid resuscitation in many instances. In belts or helmets, previous injuries and social circum-
fact, this can be counterproductive. The aim is to support stances that may verge on child neglect. A complete
cellular function, not to return all physiological param- physical examination looks for any injuries that may
eters to normal. It is best to insert an intravenous line have been overlooked initially, for example forearm
and be poised to give fluids. If there is a palpable radial fractures close to a drip site or a fractured jaw in an
98
pulse and the child is speaking or c­ rying ­appropriately, initially intubated patient.
 Trauma 3.6
A comprehensive discharge summary that ensures Head injuries
the local doctor is fully informed and an outpatient
The greatest concern is of an extradural or large sub-
follow-up for all multisystem-injured patients con-
dural injury, where early recognition and removal of
tributes to optimal care. Often, problems with sleep-
the compressive blood clot can transform a potentially
ing, fatigue, behaviour and school performance will be
fatal injury into a full recovery. History of a lucid
identified in outpatients. Sometimes a new aspect of
interval, and localizing signs are the classical features.
the history comes to light.
The more frequent use of CT has assisted.
In general, CT is recommended if consciousness
is lost for more than 5 minutes. The practical prob-
lem is clearly documenting the period of any loss of
Specific organ injuries consciousness.
Spleen From a practical point of view, the attending clini-
cian should take and document a complete history and
The spleen is one of the most commonly injured
examination. After this, if there are no clear indica-
organs. Over the last 25 years surgeons have gradually
tions for CT, it is reasonable to observe for a 4–6-hour
learned that most splenic injuries can be treated non-­
period and be prepared to perform CT if there is clini-
operatively. The key observation is to treat the patient
cal change.
clinically and not be overly influenced by radiologi-
cal appearances. Most splenic injuries result in a brisk
bleed, which quickly settles. Treatment is required only Cervical spine
when there is significant continuing bleeding. Only A frequently controversial area is when and how to
about 50% of the most serious splenic injuries (grade 5) clear for the potential of a cervical spine injury. In an
require surgical or radiological intervention. awake cooperative patient, lack of any midline tender-
ness and active movement is sufficient. The problem
Liver is the intubated unconscious patient who was ejected
from a car and needs to go to surgery the next day for a
A similar strategy has evolved for paediatric liver inju-
complex facial flap, as this will require repeated reposi-
ries. Most lacerations and haematomas resolve with-
tioning of the patient's neck and head. In this instance,
out surgical intervention. However, at the severe end
CT and magnetic resonance imaging are thought by
of the spectrum liver/caval injuries result in persistent
some clinicians still to be inadequate.
blood loss and require early aggressive surgery aimed
at damage control, which consists of compressive
packing of the liver. Limb fractures
Limb fractures are the most common injuries requir-
Kidney ing hospitalization and surgical treatment. Most are
straightforward single-system injuries. However, the
Renal injuries almost never need acute surgical inter-
clinician must be alert to a ‘limb at risk’, as indicated
vention. The bleed is usually contained by fascia and,
by an absent or weak pulse, or a white cold limb. Such
although it can be considerable on CT, there is usu-
rare cases can be a problem as many children's hos-
ally no clinical deterioration. Surgery is reserved for
pitals may not have the vascular surgery expertise on
significant urinary leaks with fever, and then usually
staff and arrangements may have to be made with
consists of insertion of a double J stent.
adult institutions or plastic surgery to provide this
service.
Small bowel perforation
This can be difficult to diagnose and can be fatal if
missed, especially in the very young where the resultant
peritonitis can be fulminant over a 24-hour period.
Prevention
There is usually a history of focused force to the abdo- Although there is evidence that a fully function-
men, such as a handlebar of a bicycle or a pole or rock. ing trauma service can reduce the mortality rate by
CT may not show free gas, but there are often subtle 20%, most reductions in childhood mortality have
features such as small bubbles of air, a thickened bowel been achieved by prevention. Analysis of injuries
wall or unexplained free fluid. Repeated examination, reveals interventions that can prevent the incidence
preferably by the same clinician, is the best way to or ­minimize the resultant harm. By a combination of
pick up the evolving clinical deterioration and operate education of the public, engineering of the environ-
99
before serious complications result. ment and enforcement of laws, many injuries can and
 3.6 SOCIAL AND PREVENTATIVE PAEDIATRICS

have been prevented. The concepts are often simple Falls

but strong advocacy, constant education and a public
As developed countries respond to increasing urban-
that accepts the benefits of changes in behaviour are
ized populations by encouraging high-density living,
required to achieve tangible results.
more children will live in high-rise accommodation.
Any window opening or balcony above 2 metres is a
Road trauma serious potential health risk to children. Falls from
windows have increased in most developed countries.
Road trauma is the single biggest cause of death and
It is a fundamental lack of the concern for infants
serious injury (40–50%) in almost all countries. In
and young children (often in their own bedrooms)
developed countries a concerted effort over 40 years
that has allowed building codes that do not make
has resulted in a significant improvement. Most of
window openings safe. The simple solution is to be
the reduction in paediatric trauma deaths has been
able to restrict lower openings to 10 cm. This should
the result of road trauma initiatives. The restraint of
be engineered at the time of building, but existing
passengers, including age-appropriate child restraints,
dwellings could be modified for as little as $10 and
random alcohol testing and an acceptance by the pub-
10 minutes’ work.
lic that drink driving is a serious crime, safer vehicles,
Childhood injury prevention requires effort by
bicycle helmets, and school and school-bus speed
the whole community, with all clinicians (medical
restrictions have all contributed to a reduction in road
students, doctors, nurses, ambulance, allied health
trauma.
professionals and administrators) in important lead-
Problems such as low-speed rollover injuries con-
ership roles. Clinicians have to look after paediat-
tinue to recur, and engineering of vehicle cameras
ric trauma patients and therefore know the details
and education to ‘spot the tot’ is required to achieve
of the injuries intimately, are motivated and have
further reductions. Newer hobbies such as off-road
community credibility. They are therefore ideally
vehicles need analysis to determine patterns of injury
placed to be at the forefront of ongoing prevention
and to balance these against the benefits to children's
efforts. Meticulous tertiary trauma histories dur-
development.
ing the admission (often taken by medical students
In developing countries road trauma is increasing
and interns) help to develop prevention data and
and there needs to be advocacy by clinicians to try to
guide likely solutions. Injury prevention information
stem the epidemic.
in doctors’ surgeries and EDs helps to educate the
community.
Drowning Most injury prevention campaigns are assumed to
be based on careful data collection with this infor-
Prevention is almost the only strategy for reducing
mation then resulting in engineering and legislative
this important cause of childhood death. Immediate
change. However, this is rarely the case, with vehicle
resuscitation can help, but the main messages are
manufacturers, building industries and bureaucra-
direct arm's length supervision backed up by fencing
cies often resisting change. It often requires strong
and pool gate barriers. There has been a reduction
persistent advocacy by clinicians, parents and con-
in deaths over the last 25 years, especially in relation
cerned citizens for change to occur. Some impor-
to the number of private swimming pools. However,
tant injury prevention changes have occurred as the
with a new generation of parents of toddlers every few
result of a single person being aware of a problem,
years, campaigns need to be continuous and relentless.
devising a solution and advocating until change has
Until recently it was not appreciated how large a
occurred.
problem childhood drowning was in developing coun-
tries. Most deaths never came to the attention of hos-
pitals or health authorities. More detailed community
analysis has shown drowning to be a significant prob-
lem and advocacy has started.
Summary
Paediatric trauma is an important health issue as it is
still the greatest cause of death and serious disability
Burns and scalds
in most countries.
The incidence of burns and scalds has decreased sig- Medical students can prepare by doing first-aid
nificantly in European countries but still remains a courses, and being involved in detailed history-taking
problem in many communities. Almost all burns and during their clinical rotations.
hot water scalds could be prevented by public cam- Interns and residents can improve their skills by
paigns that separate children from flames and boiling attending trauma training courses, and being meticu-
100
water. lous in their history-taking and physical examination.
 Trauma 3.6
Registrars and consultants can attend more advanced prepared, sticking to basics in history-taking and
skills courses in trauma team training, advanced surgi- examination, writing clear, legible notes regarding
cal techniques and trauma conferences, and participate their decision-making, and using the skills that they
in websites on trauma topics, multicentre studies (i.e. feel comfortable with. When the situation is progress-
spinal cord injuries) and consensus statements. ing beyond your skills level, discuss the issues with a
Trauma care is mostly simple, but occasionally very more senior clinician.
challenging. Clinicians can contribute most by being Trauma prevention is everyone's responsibility.

101
 3.7 Failure to thrive Daryl Efron

Satisfactory growth is a key marker of good health

in infancy and early childhood, and so the failure of Growth patterns
a child to grow as expected is naturally a cause for When a child is failing to thrive, weight gain is affected
­concern for parents and health professionals. Failure first, but if the problem persists, length also may be
to thrive (FTT) can result from a broad range of affected. If length is affected disproportionately, the
organic and environmental factors, with a ­combination possibility of a skeletal dysplasia syndrome or endo-
of influences usually operating. The family often feel crinopathy should be considered. Head ­circumference
confused, worried and guilty, so evaluation needs to be is affected only when failure to thrive is severe.
conducted sensitively. Irrespective of birth weight, full-term infants tend
to assume their genetically determined growth pattern
some time in mid to late infancy. This often results in
babies who were born large ‘crossing down’ to reach
Practical points
their predestined track on the growth chart. Measures
should be plotted against age corrected for prematu-
• Failure to thrive is commonly due to a combination of rity until 2 years of age.
factors, with psychosocial issues often prominent.
It is often possible to identify a critical point or period
• Chronic illness in any system can result in failure to
thrive. at which a child's growth began to falter. This may enable
• Investigations are unlikely to reveal a cause that was recognition of an important factor that has adversely influ-
not apparent from a thorough history and examination. enced growth, such as the introduction of a food to which
• A multidisciplinary approach is necessary, with input the child is intolerant, intercurrent infection or change in
from paediatricians, maternal and child health nurses, environmental circumstances causing family stress.
dietitians, speech pathologists and sometimes mental
health professionals.
• Admission to hospital is required in severe malnutrition,
unwell infants, or where there are concerns about the Causes
child's care at home.
• Infants who have had a period of failure to thrive In developed countries, failing to thrive usually relates
are at risk of long-term problems with growth and to inadequate caloric intake in the context of psy-
development. chosocial difficulties. Poverty, parental mental illness,
substance abuse, social isolation, family violence or
intellectual disability may result in limited parental
capacity or other priorities competing with adequate
care of the child. The relationship between mother
Definition and infant is often disturbed. Maternal depression is
FTT can be defined using various criteria. The term very common in these s­ituations, often present from
is generally applied to infants, although on occasion it the postnatal period or developing as a consequence
is used in children up to 2–3 years of age. Concern is of feeding difficulties and associated FTT.
often raised when an infant's weight is below the third Prematurity, intrauterine growth retardation and
centile, that is, more than approximately two stan- embryopathic intrauterine exposures increase the risk
dard deviations below the population mean. However, of FTT. Chronic or recurrent illness in any system can
this occurs normally in 3% of infants, most of whom result in impaired growth (Table 3.7.1).
are healthy but who are genetically destined to be Mechanisms of growth failure include reduced intake
small. Of more interest are the weight :length ratio, (most common), inadequate nutrient absorption and, in
and ­particularly the growth trajectory with time. The some cases, increased energy utilization. Malnourished
­criterion of weight crossing two major centile lines infants are vulnerable to infection, which may further
with time is more meaningful clinically, and a ­useful compromise their nutritional state.
standard by which to decide when to describe an infant In some cases, parents hold alternative belief
102
as having FTT, and to evaluate accordingly. ­systems that influence their care of their child. These
 FAILURE TO THRIVE 3.7
Table 3.7.1 Organic causes of failure to thrive

System Examples

Craniofacial Cleft palate

Pierre Robin syndrome

Neurological Cerebral palsy with pseudobulbar palsy

Raised intracranial pressure (vomiting)
Embryopathy (e.g. in utero infection, fetal alcohol syndrome)

Genetic Chromosomal abnormality (e.g. trisomy 18)

Dysmorphic syndrome (e.g. Smith–Lemli–Opitz syndrome)

Gastrointestinal Gastro-oesophageal reflux disease

Malabsorption (e.g. coeliac disease, lactose intolerance)
Chronic liver disease

Renal Recurrent/persistent urinary tract infection

Chronic renal failure
Renal tubular acidosis

Respiratory Chronic lung disease (e.g. bronchopulmonary dysplasia, cystic fibrosis)

Chronic upper airway obstruction

Metabolic Inborn errors of metabolism (e.g. amino acidopathies, mitochondrial disorders)

Cardiac Chronic congestive cardiac failure

Endocrine Thyroid disease

Adrenal insufficiency

Immunological Severe atopic disease

Food protein allergy
Severe combined immune deficiency

Infectious Human immunodeficiency virus

Tuberculosis

may include unconventional diets and feeding prac- should be plotted against gestation, and then serial
tices, opposition to immunization and mistrust of weight, length and head circumference should be
mainstream health-care providers. These cases can be plotted on percentile charts through to the present
extremely challenging and great skill is required to time. Where available, it is preferable to use a chart
maintain a therapeutic relationship with the family. ­constructed from a population of the child's particu-
There are often multiple contributing causes for fail- lar ethnic group or syndrome (e.g. Down syndrome).
ing to thrive. For example, an infant may have an under- Mid-parental height gives an indication of the child's
lying syndromic diagnosis that is associated with growth genetic growth potential. The point at which growth
restriction but also results in recurrent infections, began to falter may provide a clue as to the cause, for
gastro-oesophageal reflux and irritability with poor
­ instance after the introduction of wheat products in
feeding behaviour. Psychosocial problems may also be coeliac disease.
present in the family of a child with organic illness.

History
Assessment A careful evaluation of dietary intake is necessary in
the assessment of a child with FTT. A detailed history
Growth pattern
of feeding patterns is required, including frequency,
The initial step in the evaluation of a child who is fail- duration and quality of breastfeeds, or total daily vol-
ing to thrive is to chart the growth pattern to deter- ume of formula. If the infant is breastfed, the mother's 103
mine whether it is a cause for concern. Birth measures milk supply should be assessed. If formula-fed, check
 3.7 SOCIAL AND PREVENTATIVE PAEDIATRICS

that the feeds are being prepared correctly. It is impor-

tant to know both the range and quantity of solids Clinical example
being consumed, and how well the child can manage
foods of different textures. A 3-day feed diary can be James, aged 9 months, was referred by his
maternal and child health nurse with concerns
helpful in quantifying the nutritional intake. This his-
about his weight crossing the major centiles.
tory can be difficult to obtain reliably when there is He was born at 38 weeks’ gestation with a birth
psychosocial disadvantage or neglect. weight of 3.6 kg (90th centile) and his current weight was
A detailed systems review is necessary to identify 7.9 kg, which was just above the 10th centile. He had generally
any organic illness that might be contributing to the been a healthy infant, apart from some upper respiratory tract
growth failure, either as the primary cause or as an infections (URTIs) and had had a nocturnal cough for 3 weeks
exacerbating factor. Particular enquiry needs to be since his most recent URTI. He was still breastfed. Solids were
introduced at 6 months and he was taking small amounts of
made about vomiting, diarrhoea, respiratory symp-
rice cereal, vegetables and fruits, as well as some meat and
toms, lethargy and irritability. chicken. Examination was normal. He was an alert, interactive
Failing to thrive is commonly associated with devel- infant and responded well to his mother.
opmental delay. Infants with FTT often fall behind in His mother's height was 154 cm (3–10th centile) and his
their gross motor development. Poor muscle bulk and father's was 170 cm (10th centile).
tone results in immature truncal and neck posture, and James’ parents were reassured that he appeared to
generalized weakness. Commonly the infant's emo- be a healthy infant and seemed to have settled into his
genetically determined growth pattern. Arrangements
tional development is also delayed. Malnourished
were made to see James again in 2–3 weeks to ensure
and deprived infants may demonstrate apathy, anx- that the cough had settled, or, if not, for a chest X-ray to be
iety, irritability and poorly regulated behavioural performed. He would have ongoing review to ensure that he
states. Some underfed infants become depressed and continued to gain weight along the 10th centile as expected.
withdraw from social contact with primary caregiv-
ers. Important signs include gaze aversion, lack of a
responsive smile, and lack of interest in social overture
or reciprocal play activities. On the other hand, poor needs to be examined carefully for signs of malforma-
feeding may result from neurodevelopmental impair- tion or disease. Candidiasis raises the possibility of an
ment, with irritability, oromotor dysfunction and an immune deficiency, although this is more likely to be
abnormal swallowing mechanism. secondary to malnutrition than the primary cause.
A good social history is critical. The family's social A developmental assessment should be completed
circumstances may be a central factor in the cause of as part of the examination. Direct observation of the
the growth failure, and may also influence therapeutic child's feeding is important to enable better understand-
effectiveness. ing of the feeding behaviour, for instance the inten-
sity of demanding/interest in food, parent's feeding
­technique, coordination and vigour of suck and swal-
Examination low, acceptance or rejection of bottle/spoon, duration
A thorough physical examination is required in infants of the feed (e.g. rushed or prolonged), ­distractibility
with FTT. The child's general appearance is impor- and fatigue. Videotape recordings (taken by the parents
tant. Note whether the child appears small but well at home) can be valuable in outpatient settings. Observe
(i.e. good colour, alert, active) or malnourished and how the parents respond to the child's distress or signs
unwell (i.e. pale, miserable, lethargic). of hunger (such as the rooting reflex, or ­biting his or
A poor state of hygiene such as unclean skin and her own fist in hunger), and how they hold, comfort
clothes, as well as a marked flattening of the occiput and care for the child. Does the ­parent appear to enjoy
with hair loss, raise the possibility of neglect. The qual- caring for the child, or appear ­disengaged or coercive?
ity of the child's interaction with the mother should be
noted. Is there good eye contact and reciprocal warm
engagement? Temperamental characteristics should be
noted. Irritability, withdrawn behaviour or an anxious,
Investigation
hypervigilant appearance are important signs. If there are no specific signs or symptoms, a diagno-
Gross indicators of nutritional state include fat sis of organic disease is uncommon. Investigations
stores, particularly around the buttocks and thighs, ­undertaken to identify a hidden cause for FTT have a low
and muscle bulk. The severely malnourished infant yield. It is appropriate, however, to check e­ lectrolytes,
has prominent ribs, thin limbs, sparse hair and a bony serum creatinine, full blood examination, ferritin,
face. Signs of micronutrient deficiency include pal- and urine microscopy and culture. Other investigations
lor, rashes and sparse hair. Dysmorphic features raise may be indicated if there are specific findings on history
104
the possibility of a genetic syndrome. Each system or examination. These might include i­nflammatory
 FAILURE TO THRIVE 3.7
markers, thyroid function tests, sweat test, karyotype, a ­nasogastric tube. This must be done carefully to
immune function tests, stool microscopy, coeliac dis- avoid complications such as vomiting, diarrhoea,
ease serology, urine organic acid profile and brain and electrolyte disturbances such as hypophospha-
imaging. If severe malnutrition is present, additional taemia, hypomagnesaemia and hypokalaemia (see
laboratory investigations are indicated, including liver Chapter 3.3).
function tests, alkaline phosphatase, calcium, phos- The desired feeding pattern for care at home needs
phate, vitamin D, zinc, vitamin B12 and folate. to be established first in hospital. On discharge a
clear, written feeding plan is essential. Professional
supports in the community need to be engaged to
­continue ­monitoring and support. Frequent medical
Management review is necessary initially. Children who have suf-
The management of FTT depends on the severity, fered severe FTT in infancy or early childhood are at
whether the child appears healthy or unwell, and psy- risk of long-term growth, developmental and behav-
chosocial factors. Establishment and maintenance of ioural p­ roblems, and so should be followed up by a
rapport and trust with the family is an essential ele- ­paediatrician into the school years.
ment of successful treatment. Clearly, any identified
organic causes need specific therapy.
Mild FTT in an otherwise well child can be man- Clinical example
aged initially with dietary advice and close monitoring.
Catch-up growth requires increased caloric intake. If Taylah, aged 11 months, was brought for
the infant is breastfed, supplementation after breast- assessment by her mother, who was concerned
feeds, with either expressed breast milk or formula by that she ‘wouldn't eat’. Her mother also said that
Taylah would not sleep during the day, whinged
bottle, may be necessary. For formula-fed infants, an
too much and was often ‘so worked up she made herself
increased caloric intake can be achieved by increas- vomit’. Taylah's mother said that she was finding it extremely
ing the concentration of formula by 25%, or by add- difficult to look after Taylah on her own. She reported that
ing a spoonful of glucose polymer powder to bottles. Taylah had diarrhoea at times, as well as a constantly runny
Depending on the age of the infant, the introduction of nose. She was bottlefed but lately had not been enjoying her
solids or adding extra calories to solids (using formula milk. She had little interest in solids.
milk, butter, cream or margarine) may be indicated. Taylah's birth weight was 2.3 kg at 36 weeks (10th centile).
Her mother did not have the Child Health Record and
Admission to hospital may be necessary for children
reported that she did not like the local maternal and child
with severe FTT, those who are unwell, where the par- health nurse. Her mother did not interact with Taylah, who
ents are very anxious, or where there is concern about was sitting in the pram during the consultation. At one point,
the quality of care of the child. A thorough evaluation when Taylah cried, her mother said: ‘See! This is what she's
of the feeding behaviour and routines, mother–infant like all the time!’ Taylah's mother appeared pale, thin and
interaction, and the emotional status of both mother anxious. She appeared defensive and angry when asked
some questions about her support system.
and infant can be achieved over several days. A multi­
On examination, Taylah appeared thin, pale and
disciplinary team approach is optimal in the assess- miserable. Her clothes were soiled. She had an extensive
ment and management of these children. This includes nappy rash, as well as facial and scalp dermatitis. Her hair
a dietitian to assess nutritional intake, a speech pathol- was sparse, particularly over the occiput, which was flat.
ogist to assess feeding, and a social worker to assess Her weight was 6 kg (below the third centile, corrected for
psychosocial stressors and the family's support system. prematurity). Her length was 68 cm (10th centile) and her
In some cases a mental health assessment of mother head circumference was 43 cm (2–50th centile). Physical
examination was otherwise negative. She was unsteady
and/or infant is required. Contact should be made, with
when placed in a sitting position. It was not possible to elicit
parental permission, with professionals in the com- a smile from her. Her urine was negative on a dipstick test.
munity who have been involved with the family. This Taylah was referred to a paediatrician, who admitted her
may include a lactation consultant, maternal and child to the regional hospital. Taylah spent a week in hospital,
health nurse, general practitioner and/or psychiatrist. where she fed well and gained 300 g within a few days. The
Child protection services may need to be involved if hospital arranged a mental health assessment for Taylah's
there are concerns regarding the child's care. Strengths mother. Her mother was diagnosed with chronic depression
and anxiety, and a follow-up appointment was arranged for
in the family should be identified and promoted.
soon after Taylah's discharge. The enhanced home visiting
Satisfactory growth with feeding in hospital (or maternal and child health service was engaged for home-
out-of-home care) suggests that the FTT is psychoso- based support, along with close paediatric follow-up.
cial. In some cases, refeeding may be required using

105
 3.8 Developmental disability
Michael O'Callaghan

Definition General issues of management

Disability describes lack of skill in important areas Developmental disabilities are chronic disorders, and
of development that affect age-appropriate func- this perspective is also required for management, in
tions and participation of the child in the a­ ctivities addition to the interventions that are specific for indi-
of daily life. The World Health Organization vidual disorders. Four important general aspects of
International Classification of Function (ICF) for management are:
disability and health describes not only how a con- • Family-centred care. This includes an ongoing
dition affects body structures and function but also partnership with families, advocacy, the provision
its influence on how a person may perform their per- of information regarding the disorder, support
sonal, family and social roles, together with personal groups, access to treatment and respite services,
and environmental ­factors that affect this. Legislative and to sources of financial support. When
frameworks, recognition of rights, opportunities for initially discussing the diagnosis with families,
education and work, access and community attitudes the consultation should include the presence, if
all influence participation and ultimate quality of possible, of both parents, sufficient uninterrupted
life. The biopsychosocial approach, with emphasis time, a realistic and balanced acknowledgement
on the child as a person and on their overall func- of potential problems and strengths, and the
tion and wellbeing, together with a strong develop- opportunity for follow-up discussion. Long-term
mental and family perspective, provides a necessary care of the person with severe developmental
framework for care of children with developmental disability is likely to be stressful to parents, siblings
disability. and marriages, with major transitions such as
A developmental disability may arise from genetic commencing or finishing school and adolescence
causes, during pregnancy, perinatally, or during and transition to adult services often being
childhood. Approximately 3–5% of children have a challenging periods.
­moderate to severe disability and up to 20% have a • An individual child. The focus is not only on the
mild disability. Many of these disorders are more com- management of the medical disorder or disability
mon in males. The disability may affect movement, but also the child's longer-term growth, health,
­cognitive, speech and sensory functions or behaviour, development, emotional wellbeing, independence and
and it may vary in severity. A child may have multiple adult function. Associated behavioural difficulties
disabilities. may be of equal or greater concern to the family than
Commonly included low and higher prevalence dis- medical aspects of the disability, and also influence
orders are shown in Box 3.8.1; because they affect brain successful function in the school and community.
function, they are also called neurodevelopmental dis- • Prevention. Knowledge of the genetic implications,
orders. Although the lower prevalence disorders are natural history of a disorder, and common
usually more severe, all of these conditions may have management issues may allow prevention of some
a substantial effect on the quality of life for the child problems and early identification of others (see, for
and family. A number of low-prevalence severe disabil- example, Table 3.8.2).
ities affecting the brain, including hearing and visual • A team and a plan. As interventions are frequently
impairment, cerebral palsy, spina bifida and autism, multidisciplinary and may involve more than one
are covered in other sections of this book. The focus professional or service, they should be coordinated,
of this section includes general issues of m
­ anagement have an outcome focus and should involve families
for all children with a developmental disability; the in considering realistic short- and long-term goals.
child with intellectual impairment and selected syn- Interventions should begin early and be focused on
dromes associated with this; and children with high the needs of the child and family with programmes
prevalence but less severe disorders o
­ ccurring singly or that occur, where possible, in the child's own home
106 in combination. or community.
 DEVELOPMENTAL DISABILITY 3.8
Box 3.8.1 Developmental disabilities Intellectual impairment
Low prevalence Terminology
• Cerebral palsy
• Moderate–severe intellectual impairment Medical terms such as mental retardation (Diagnostic
• Autism and Statistical Manual of Mental Disorders, e­ dition
• Spina bifida IV; DSM-IV), intellectual impairment and ­ general
• Severe sensory impairment learning difficulty are often used synonymously.
Although these terms all focus on important deficits in
Higher prevalence
• Developmental delay
the child, they may be offensive to families, and do not
• Mild intellectual impairment describe competencies of individual children.
• Speech and language
• Developmental coordination disorder Definition
• Learning difficulty
• Attention-deficit/hyperactivity disorder Mental retardation, the term used in DSM-IV, is
• Mild autistic spectrum disorder defined as significantly sub-average intellectual func-
tioning accompanied by limited adaptive function,
with onset before 18 years. Adaptive function describes
The medical role in the management of a develop- activities of daily living and social competence. Tests
mental disability includes initial diagnosis, advocacy, of general intellectual function, such as the Stanford–
accessing services, and meeting normal and specialist Binet and Weschler Intelligence Scales, have a distri-
health and developmental needs of the child. Trials of bution that is approximately normal, with a mean
medication to modify genetic expression are occurring intellectual quotient (IQ score) of 100 and a standard
in a number of syndromes, including fragile X, and deviation of 15. The individual's score is, however,
specific therapeutic medical interventions may emerge an estimate, as performance is affected by a range of
in future. Management is facilitated by seeking to child, tester and environmental factors.
understand the ‘predicament’ of the child and family – Mild intellectual impairment is diagnosed in c­hildren
how they may feel, think and experience the situation. with an IQ score between 70 and 55–50 who also have
There is a need also for an evidence-based approach impaired adaptive function. Although the normal curve
in discussing traditional and alternative interventions. distribution suggests that 2–3% of c­ hildren will be in this
The role requires acceptance of cultural and ethnic category, studies generally report a lower prevalence and
differences, realistic hope, advocacy and helping fami- an association with social ­disadvantage or family history
lies to maintain their overall wellbeing. The needs of a of similar difficulties. The children may present with speech
child and family, however, can be met only by a range or behavioural difficulty, or may be identified with devel-
of professionals. opmental concerns in early childhood education centres or
with learning d ­ ifficulty in the early school years. Physical
and neurological examinations are usually normal.
Clinical example Moderate intellectual impairment is defined as an IQ of
35–50, with more severely or profoundly affected children
Angie was aged 6 years and had a mild having an IQ score below this. Only approximately 0.3%
intellectual impairment of unknown aetiology. of children have an IQ score lower than 50. These chil-
Her behaviour had always been difficult and dren often have a dysmorphic appearance, a recognized
had recently become more difficult. She also syndrome or other known aetiology for their intellectual
had a diagnosis of attention-deficit/hyperactivity disorder
disability. Presentation may be by recognition at birth or
in association with aggression that was only partially
responsive to stimulant medication. Reviewing the situation
with global developmental delay during early childhood.
using a biopsychosocial approach, her doctor realized that Inexperienced parents may present with concerns regard-
her behaviour had become worse when her father started ing specific speech and gross motor delays. More severely
working away from home, as a result of which Angie's affected c­ hildren may also have other physical and sen-
mother, who always assumed the majority of Angie's care, sory disorders, with many having multiple disabilities.
had to cease her studies. Her mother described feeling
socially isolated and depressed. Angie was in an integrated
classroom with a modified programme, although she was
Medical assessment
acutely sensitive to her lack of academic success compared A standard medical and family history and p ­ hysical
with her peers. Medication was still required and the dose
and neurological examination are ­ important, as is
adjusted, although this further understanding allowed
additional interventions that markedly improved Angie's understanding the family's concerns, their belief
aggressive outbursts and adjustment. regarding this, and the outcome they hope for from the
107
consultation. Development is assessed from ­maternal
 3.8   SOCIAL AND PREVENTATIVE PAEDIATRICS

concerns, milestones, current abilities on history and examples. Although an approximate stereotype of disor-
testing as required. Milestones are helpful if delay or ders is described, the expression of the disorder varies and
regression has occurred, whereas developmental test- each child requires individual assessment.
ing also allows the opportunity to interact with the
child and informally assess social engagement, atten- Investigations
tion and quality of performance. The aetiology is Investigations and their indications are shown in
not always identified, especially for children with less Table 3.8.1. Genetic testing is evolving rapidly and may
severe disorders, but is more likely if there are: require consultations with the geneticist or laboratory.
• minor physical anomalies present (e.g. simian crease
or low-set ears)
• disturbances of growth (e.g. microcephaly or Practical points
macrocephaly, extremes of stature or weight)
• abnormal skin lesions (e.g. multiple depigmented or Assessment goals for the child with developmental
pigmented naevi) disability
• malformations or abnormal findings in several • Developmental diagnosis
organ systems • Aetiological diagnosis
• behaviour characteristics of specific disorders (i.e. • Presence of associated disorders (co-morbidity)
behavioural phenotype) • The psychosocial context (predicament)
• family history of a similar disorder.
Fragile X syndrome
X-linked intellectual impairment may explain the
Practical points
male predominance among children with intellectual
impairment. It exists in overlapping syndromic and
Examination of the child with suspected developmental
disability
non-syndromic forms (see Chapter 10.3).
Informal observation Fragile X syndrome is the commonest form of
• Appearance X-linked intellectual impairment and is the most com-
• Behaviour (eye contact, social engagement, attention, mon inherited cause, with population estimates in
activity level and anxiety) males of approximately 1 in 3600. The condition arises
• Play (symbolic, imaginative or repetitive) because of an expanded CGG triplicate repeat sequence
• Movement (skills, symmetry and quality) at Xq27.3 that interferes with the production of fragile X
Formal observation mental retardation protein (FMRP). A repeat sequence
• Developmental assessment (strengths and weaknesses) of less than 55 is considered normal, and a sequence
• Minor physical anomalies of more than 200 copies results in loss of function of
• Vision and hearing the gene affecting biochemical pathways. Individuals
• Physical and central nervous system examinations
with 55–200 repeats, a premutation, are usually normal,
• Growth (plot percentiles)
although they may have learning, behavioural, mild cog-
nitive difficulties or, later, early ovarian failure or develop
an ataxic–tremor syndrome. Clinical testing should
Differential diagnosis
include DNA studies for the trinucleotide repeats.
The differential diagnosis of intellectual impairment The condition predominantly affects males as they
includes children: have a single X chromosome. Girls are less commonly
• who have been severely deprived or abused affected and the expression of the disorder is less
• with a progressive neurodegenerative disorder or marked. Genetic counselling is complex as expansion
unrecognized epilepsy of the repeat sequence occurs only in female carriers in
• with severe sensory or specific developmental disorders pregnancy, though the extent of this is not predictable.
• where the child's apparent lack of skills is due to Males with this disorder will have normal sons and all
cultural differences, mental health disorders, ill of their daughters will be carriers.
health or refusal to participate Affected individuals may look normal, especially
• infants with severe movement difficulties. when younger. Typical physical characteristics and
There are many prenatal, perinatal and postnatal aetiolo- ­co-morbidities are shown in Box 3.8.2. Recurrent oti-
gies for intellectual impairment and m ­ ultiple associated tis media, strabismus or refractive errors in vision, and
syndromes. A child with intellectual i­ mpairment may have seizures may also occur. The intellectual impairment
other associated specific developmental delays, behaviour is usually of a moderate degree. DNA testing for frag-
problems and health difficulties. This section describes a ile X syndrome should be considered in all children
108
limited number of causes of intellectual impairment as with intellectual impairment, and especially in males,
 DEVELOPMENTAL DISABILITY 3.8
Table 3.8.1 Investigations and indications for mental retardation

Test Indication

Chromosome microarray (CMA) Identifies submicrosopic deletions and duplications

Different types of arrays available. Because of normal copy number variation between
individuals, interpretation may be difficult and require geneticist

Chromosomes (G banded karyotype) Recognized chromosomal syndrome, a family history of chromosomal rearrangement
(balanced translocation)

Fragile X Consider in all children with intellectual impairment, especially male children, those with a
family history of X-linked intellectual impairment or children with other clinical features of
the syndrome

Fluorescent in situ hybridization (FISH) Quicker than CMA and may be useful for specific clinically identified syndromes
e.g. Williams

Thyroid function Short stature, constipation, dry skin or hair, goitre or no neonatal screen

(CPK) If muscle weakness or prominent calves are present. Duchenne dystrophy is associated
with developmental disorders

Metabolic screen Hypoglycaemia, acidosis, altered consciousness level, unusual odour or multiple body
systems affected. Low yield if neonatal screening program

Ca, PO4 Short fourth metacarpal, short stature in pseudohypoparathyroidism

Electroencephalography (EEG) If clinical seizures or history of sleep-related seizures

Magnetic resonance imaging (MRI) or If abnormal neurological signs, possible regression or moderate-severe intellectual
computed tomography impairment of unknown cause. MRI also for developmental disorders of brain

Lead Exposure history, at-risk environment

Ferritin Iron deficiency anaemia associated with delayed development

Other tests For specific rare clinical indications

where there is an X-linked family history of intellec-

tual impairment, or the child's appearance or behav- Clinical example
iour is characteristic of fragile X syndrome.
Raymond was 4 years old, and his mother
had become concerned that his development
Box 3.8.2 Clinical features of fragile X syndrome was mildly delayed for his age and that he
was active and impulsive. On questioning, her
Appearance particular concern was that Raymond might be intellectually
• Prominent jaw impaired, as were her own brother and maternal uncle.
• Long, narrow face Physical and neurological examinations were normal.
• Large ears Genetic testing indicated that Raymond had fragile X and
• Joint hypermobility that his mother was a carrier for this disorder. Genetic
• Testicular enlargement in adolescence counselling and formal assessment were provided.

Development
• Moderate mental retardation
• Reduced coordination Down syndrome
• Risk of epilepsy
Down syndrome or trisomy 21 (see Chapter 10.3) is
Behaviour the commonest genetic cause for moderate intellectual
• Attention-deficit/hyperactivity disorder impairment, with an overall incidence of approximately
• Social shyness
1 in 800 births. Risk varies, however, increasing especially
• Autistic spectrum disorder features 109
with maternal age. Screening programmes in pregnancy
 3.8   SOCIAL AND PREVENTATIVE PAEDIATRICS

vary though may involve combinations of first- and have congenital heart disease. A spectrum of cardiac
­second-trimester serum markers such as low α-fetoprotein lesions may be found, although abnormalities of the
levels and pregnancy associated plasma protein A, high ­atrioventricular canal or ventricular septal defect are
human chorionic gonadotrophin levels, low blood oestriol most common. Gastrointestinal malformations that
levels and ultrasound findings including nuchal thicken- may be found include duodenal atresia, imperforate
ing or characteristic malformations (see Chapter 10.1). anus and Hirschsprung disease.
Chromosomal studies indicate a full ­trisomy 21 second- Intellectual impairment is generally moderate, with
ary to non-disjunction in 95% of affected children, with a high risk of Alzheimer disease from 40 years of age
translocation or more rarely mosaicism in the remainder. onwards. The majority of children do not exhibit marked
At birth, the diagnosis is usually made from the over- behavioural difficulty, although there is an increased
all dysmorphic appearance of the infant and clinical prevalence of oppositional and autistic disorders. Health
findings (Table 3.8.2). Confirmation by genetic test- surveillance recommendations are shown in Table 3.8.2.
ing is always necessary. Children with Down syndrome
have an increased risk of malformations; 30–50%
Prader–Willi syndrome
This is a rare disorder (1 in 25 000 live births per annum)
Table 3.8.2 Down syndrome: clinical features and due to loss of paternal expressed genes at 15q11–13. In
surveillance 75% of cases, a paternal deletion is ­present, whereas in
20% of children two maternal copies of the gene are
Issue Comment present. A small number of children with Prader–Willi
Neonatal clinical Hypotonia syndrome have other rare genetic causes i­nvolving this
features Brachycephaly region. Prader–Willi syndrome illustrates the c­ omplex
Eyes slanted, epicanthic folds, nature of developmental disabilities, the b ­ urden on
Brushfield spots families especially when behaviour difficulty is marked,
Tongue appears large and the need for multidisciplinary services.
Ears poorly formed and small Children with Prader–Willi syndrome have a char-
Hands broad, simian crease
acteristic appearance and clinical expression involving
Gap between first and second toes
health, growth, development, learning and behaviour,
Health surveillance with the last often being the greatest burden for fami-
Growth Use Down syndrome growth charts lies. Initial severe neonatal hypotonia, often with a need
Initial feeding difficulties common for nasogastric feeds, is followed by the development of
Avoid obesity excessive appetite, lack of satiety and risk of obesity from
3 to 5 years. During this period, marked behavioural diffi-
Thyroid Yearly thyroid tests
culties emerge, including food-seeking, oppositional and
Coeliac disease Consider testing if symptoms, or obsessive compulsive behaviour, difficulties with concen-
screen at 3–4 years tration and often mild features of autistic spectrum dis-
order. Skin picking may be a particular problem. The risk
Neck X-ray atlantoaxial joint if symptoms of psychosis as an adult is increased. Gross motor skills
of neck pain or central nervous and speech are initially most markedly delayed in associa-
system signs in legs
tion with hypotonia. Affected children are usually mildly
Leukaemia No routine screen, although
intellectually impaired and experience learning difficul-
increased risk of leukaemia or ties. Endocrine problems secondary to hypothalamic dys-
neonatal leukaemoid reaction function affect growth, and the risk of type 2 diabetes
is increased. Sleep disorders with central and obstructive
Hearing Initial screen and repeat as indicated apnoea are common and need to be monitored if growth
for chronic otitis media hormone is given. The risk of scoliosis is increased.
Angelman syndrome is a similarly complex, although
Sleep Risk of obstructive sleep apnoea
different, neurodevelopmental disorder arising from
Vision Cataracts, refractive errors, strabismus loss of maternal expressed genes in the same chromo-
somal region. The children are generally happy, ataxic,
Development Early intervention/educational plan lack speech, and have severe intellectual impairment
Specific therapy if needed and a characteristic appearance.
Behaviour/adjustment/autism

Family Genetic counselling, knowledge of Microdeletion syndromes

110 condition, support, groups, respite,
financial benefits Velocardiofacial syndrome arises from a chromosomal
microdeletion at 22q11.2. There is a wide ­spectrum of
 DEVELOPMENTAL DISABILITY 3.8
clinical findings including cardiac anomalies, ­commonly need, however, to understand that ‘global develop-
involving the conotruncal region, thymus-associated mental delay’ does not imply either that their child will
immune deficiencies, developmental problems of necessarily ‘catch up’ or that the extent of the delay
speech, often in association with nasal escape from in months is fixed. The ratio between developmental
a cleft of the soft palate, intellectual and learning and chronological age, sometimes termed the develop­
­difficulties, behavioural difficulties and risk of later mental quotient, is more stable and a ­better guide
psychosis. to ­longer-term prognosis, whereas the actual gap in
Smith–Magenis syndrome arises from a chromo- months may increase with age.
somal deletion at 17p11.2. It has a wide spectrum of
findings, and is associated with severe behavioural
­difficulty, particularly involving sleep and aggression
to self or others. Clinical example

At age 2  years, John's parents were concerned

Environmental causes that he was not speaking. He was able to jump
and run, and responded to his name and ‘no’,
Teratogens in pregnancy include intrauterine infec- although he knew no body parts and had just
tion and significant alcohol intake. Fetal alcohol syn- begun to attempt to stack blocks and use a pencil. From
drome is an important cause of developmental delay the Denver Test, his skills, apart from age-appropriate gross
and, in more severely affected children, is associated motor skills, were approximately those of a 12-month-old
child. Referral for further assessments and investigation
with microcephaly, growth retardation, characteristic confirmed that John had a global developmental delay
facies and later intellectual, learning and behaviour and possible intellectual impairment. When John was
­problems. Brain damage from causes such as i­nfection seen at age 4  years, his skills developmentally were at
or trauma and severe emotional deprivation and approximately a 2-year level. He had continued to gain
neglect can all lead to intellectual impairment. Severe skills in accordance with his developmental quotient of
neonatal encephalopathy leads only rarely to isolated approximately 50, although his delay in development has
increased from 12 to 24  months.
intellectual impairment and is usually associated with
the presence of other disabilities, especially cerebral
palsy. The interaction of both nature and nurture are
important in influencing the development and health
Speech and language impairment
of children.
Disorders of communication may affect voice,
fluency, articulation of words, grammar, compre-
­
hension, the pragmatics of language and non-­verbal
High-prevalence disorders communication. The term ‘pragmatics’ describes the
social use and understanding of communication.
Developmental delay
Because of the number of areas of speech and lan-
Children show a broad range of skills at any age. guage that are potentially affected and the continu-
Separating normal variation from mild delays is ous nature of the distribution of these skills, defining
­difficult and depends on the degree of delay or d ­ isorder, what constitutes a meaningful delay to parents or
although it is also influenced by the extent of parental child health ­professionals may be imprecise unless
concern, the past medical and developmental history delays are ­moderate or development disordered. The
of the child, and family history, including the develop- doctor has a responsibility to consider the differential
ment of siblings and parents. A developmental disabil- diagnosis of speech and language delays (Box 3.8.3).
ity results in a clinically meaningful degree of functional For any child with speech or language impairment
impairment. The pace of development may vary in indi-
vidual children and predictors from early childhood
have limited accuracy unless development is substan-
tially delayed or disordered, or is associated with a Box 3.8.3 Differential diagnosis of speech and language
condition of known poor prognosis. Delays may affect disorders
all or most areas of development, or may be restricted • Hearing impairment
to specific domains such as speech or coordination. • Intellectual impairment
Because ill-health, motor or sensory impairment, and • Autism
family adversity may all affect performance in young • Environmental deprivation
children, the term ‘global developmental delay’ is • Anatomical (e.g. palate abnormality)
often used initially, even if intellectual impairment is • Bulbar or pseudobulbar palsy
• Seizures (Landau–Kleffner syndrome) 111
suspected. The term may also be applied where two
• Developmental speech and language disorder
or more aspects of development are affected. Parents
 3.8   SOCIAL AND PREVENTATIVE PAEDIATRICS

a formal hearing test is mandatory. Children with i­mportant to consider mild forms of cerebral palsy, cer-
global developmental delay or intellectual impair- ebellar ­disorders including progressive spinocerebellar
ment will present not only with problems of speech ­disorders or tumour, and neuromuscular conditions in
and comprehension but also with impaired non-­ the d
­ ifferential diagnosis. There is an association with
verbal abilities with block construction, puzzles or learning difficulty, especially problems with writing,
drawing, and deficits in self-care and social skills. and with behavioural disorders, including attention-
Children with associated autism will manifest the deficit/hyperactivity disorder and Asperger syndrome
behavioural features of that disorder. (see Chapter 4.3).

Learning difficulty
Clinical example
The largest group of children likely to experience
Mary presented at age 3  years with speech learning difficulty is the approximately 14% of chil-
delay. She recited jingles but did not use words dren who are slow learners, with intellectual abilities in
to communicate. The doctor assessing her the borderline range of 70–85 IQ points. Generally, all
was unable to gain her attention or make eye subject areas are affected.
contact with her. Her parents stated that they experienced
Specific learning disorders occur in particular sub-
similar difficulties with Mary and that she spent her time
in isolated repetitive play, lining up toys, rather than in
ject areas where there is an unexplained discrepancy
imaginative play. She was not interested in other children between intellectual ability and the level of academic
and became distressed if they attempted to join her play. attainment in that subject. The DSM-IV describes spe-
A diagnosis of autism was later confirmed. cific learning difficulties in reading, maths and writ-
ing. The medical term dyslexia describes a specific
language-based reading disorder, usually with prob-
Where other causes of speech and language delay lems in mastering phonetics. Dyscalculia is a medi-
are excluded and development is otherwise normal, the cal term describing difficulties with calculation and
term ‘developmental or specific speech and ­language mathematics. Dysgraphia is difficulty with w ­ riting.
disorder’ is used. Twin studies indicate a strong genetic Behavioural problems are common in children with
role in aetiology. Co-morbid disorders, especially diffi- learning difficulty particularly attention-deficit/hyper-
culties with attention and coordination, are common. activity disorder, anxiety and loss of self-esteem or
More moderate or severe delays may be followed by ‘learned helplessness’ where the child ‘gives up’. As in
learning, cognitive and social difficulties as adults. all ­developmental disorders, learning and behaviour
Interventions include not only assistance provided may also be affected by the educational environment,
by a speech pathologist but also recognition of the ­family stress and ill-health in the child.
importance of playgroups, educational programmes Although physical and neurological examination
and management of co-morbidities. are generally normal, it is important to ensure that
the child is in good health, with normal hearing and
vision, that there are no associated co-morbidities, and
Developmental coordination disorder
that other family and environmental factors are not
Other terms used to describe the lack of motor adversely affecting opportunities for learning. It is also
skills in these children include dyspraxia or clumsi- important to advocate for educational assessment and
ness. Developmental coordination disorder is a diag- support within the school including, if needed, mod-
nosis made when other neurological and muscle ification of the curriculum, and to maintain a focus
diseases have been excluded, usually on the basis of on the child's strengths and their social–emotional
history and examination. Although uncommon, it is development.

112
 Child abuse
Terence Donald
3.9
primary attachment relationship between infant and
Development of current concepts carer (usually the mother).
The sanctity and privacy of the Western family and The concept of the ‘continuum of child protection’
its unfettered authority over its children was not chal­ has been developed to incorporate the prevention,
lenged by society as a whole until the late 19th and early intervention, recognition and management of
the first half of the 20th century. For example, in children who might need child protection or who have
Australia, legislation against neglect of children was been harmed through abuse or neglect. The ‘contin­
enacted in the early 1920s. uum of child protection’ links together families who
Subsequently, state child welfare departments were are experiencing adversity (which implies there is a
created and their officers authorized to intervene potential for abuse to occur) with those in which abuse
on behalf of neglected children through the state or neglect has been established. Therefore, even though
Children's Courts. The action often led to children there is no predictable causal relationship between the
being removed from their family, being made state presence of adversity and the occurrence of abuse or
wards and placed in state institutions. neglect, the population of families suffering significant
The impetus for the introduction of specific child adversity will contain the majority of children who
protection legislation was led by US paediatrician will experience such harm. Consequently, child protec­
Henry Kempe, who coined the term ‘battered baby tion from the health professional's perspective begins
syndrome’ to describe the physically abused infant. with the identification of family adversity in preg­
Such legislative provisions, related initially to physi­ nancy or early childhood leading into the provision of
cal or psychological harm and subsequently to sex­ services to assist in the eradication of the adversity or
ual abuse, were introduced first in the USA and then, the minimizing of its effects. Such services are gener­
beginning in the 1970s, in other Western countries ally community-based and are equivalent to secondary
including Australia, New Zealand and the UK. prevention strategies. Their focus is to lessen a family's
Child protection legislation asserts the right of chil­ social isolation, strengthen the interpersonal relation­
dren to be free of harm from abuse or neglect caused ships of the parents, assist the parents’ understanding
by their parents or carers. Most child protection legis­ of the developmental demands of young children and
lation states that the safety of children in their fam­ provide practical home-based parenting advice. There
ily environment is of paramount importance and must is evidence to support the efficacy of such preventa­
always be considered above the rights or opinions of tive programmes in families where adversity is present
the parents or carers. but abuse has not occurred, but no clear evidence that
A web link to the various Australian states’ child indicates similar programmes reduce the recurrence of
protection legislation is: http://www.aifs.gov.au/nch/ incidents of abuse or neglect once they have occurred.
pubs/issues/issues22/issues22.html. Hence, to maximize successful intervention, it is criti­
• Child abuse is physical or psychological harm from cal to identify and address adversity before children
acts of commission by parents or carers. are harmed.
• Harm from omission occurs when nutrition, Once children have been harmed through abuse or
hygiene, health and housing needs are neglected. neglect, tertiary level services must become involved;
• Between 50% and 70% of parents who harm their these include statutory welfare agencies, the police and
children were harmed when they were children. often tertiary forensic health services.
Significant psychosocial adversity is present in all fam­ This primary, secondary and tertiary approach
ilies where abuse occurs. The adversity includes poor to child protection has been called the public health
education, poverty, young parental age, s­ ingle parent­ model of child protection intervention.
hood, mental ill-health, intellectual ­ disability, sub­ Similar patterns of psychosocial adversity are prev­
stance abuse and intrafamilial violence. Premature and alent in families whether or not abuse has occurred.
complicated birth is also over-represented in abused or There is no reliable way of predicting which children are
neglected children, as well as poor d­ evelopment of the likely to become victims of abuse or neglect; therefore, 113
 3.9 SOCIAL AND PREVENTATIVE PAEDIATRICS

‘Public Health’ approach

Statutory
needs
3º Statutory
system

en tory

No orga
Targeted services

rnm Terri
ts

n-g nis Com

and programmes for

ov atio mo
‘at risk’ families
go and

ern ns
2º and children Service
ve
te

me
Sta

needs

nt
nw
Early intervention services

ea
targeted to vulnerable families

lth
and children

1º
Universal preventative initiatives
to support all families and children

Fig. 3.9.1 Pyramid approach to public health.

the early identification of adversity, even in the ante­ There is no mandatory reporting requirement in
natal period, is an important strategy. Identification of the UK or in New Zealand, but an expectation that
family adversity can lead to the provision of services to the authorities will be informed of children suspected
address and ameliorate its presence and effects. This is of being abused. The mandatory reporting require­
a child abuse primary prevention strategy. ment varies throughout continental Europe; generally,
The Australian National Child Protection Frame­ reporting is not mandatory.
work represents the public health approach as a Mandatory reporting was introduced when child
pyramid (Fig. 3.9.1). abuse was considered to be manifest primarily as
physical abuse. It was reasoned that physically abused
­children would usually be brought to medical atten­
tion and the abuse would be suspected by the doctor. It
Child protection and the concept allowed a doctor to make a notification to the s­ tatutory
authority and not be in breach of patient confidential­
of mandatory reporting ity, and when a doctor suspected abuse then the legal
When child protection legislation was introduced requirement for notification did not require the doctor
in the USA, Canada and Australia it contained the specifically to challenge the responsibility of the par­
requirement for mandatory reporting, which refers to ents in relation to the suspicion.
the legal requirement placed on specified individuals Most child protection legislation requires that the
to notify the designated statutory authority (usually anonymity of notifiers be maintained and provides
the statutory welfare authority) when the individual protection of notifiers against legal action that might
has reasonable grounds to suspect that a child has be initiated by parents or carers.
been harmed by abuse or neglect. The value of mandatory reporting in the manage­
Each state in the USA and each of the Canadian ment of suspected child abuse is still debated. Those
provinces has the mandatory reporting requirement. regions in which it is not present argue against its
Each Australian state and territory has some level of introduction. No region that has mandatory reporting
legislation requiring mandatory reporting to the state has withdrawn it.
or territory statutory agency of a suspicion of harm A useful summary of the issues related to the man­
owing to child abuse or neglect. The breadth of pro­ datory reporting of child abuse was published by the
fessionals mandated to report varies widely across the Australian Institute of Family Studies in 2005 (web
states and territories in Australia; medical practitio­ reference: http://www.aifs.gov.au/nch/pubs/sheets/rs3/
114
ners are always specified as mandated notifiers. rs3.html).
 Child abuse 3.9
i­ ncidence of child abuse range between 10 and 20 cases
Physical, sexual and per 1000 live births.
psychological abuse: a general In Australia a large proportion of investigations of
suspected child abuse are not substantiated. The pro­
overview portion of finalized investigations that were substanti­
Physical abuse is injury inflicted on a child by a care­ ated varied from 29% in New South Wales to 62% in
giver, including injury from physical discipline. The Victoria. Overall, emotional abuse was the most com­
intent to injure is not relevant when considering physi­ mon type of substantiated abuse, and sexual abuse the
cal abuse. least common.
Psychological abuse is a repeated pattern of care­ Accurate national data on death due to child abuse
giver behaviour or extreme incidents that convey to are not available in Australia. The most vulnerable are
children that they are worthless, flawed, unloved, those less than 2 years of age, with most deaths occur­
unwanted, endangered or of value only in meeting ring in infants aged under 12 months.
another's needs. Such behaviour has significant effects
on the developing brains of children, its consequences
being manifest in behaviour and developmental prob­
lems in preschool children, learning problems in older Child protection systems – the
children, and antisocial and criminal behaviour in interagency child protection
adolescents.
Sexual abuse has occurred whenever dependent,
process
developmentally immature, children and adolescents This refers to the systems and the services contained
are involved in any sexual activities that they do not within them that are specifically responsible for child
fully comprehend, to which they are unable to give protection at either a state or country level.
informed consent or that violate social taboos or fam­ The provision of services to children anywhere on
ily roles. the child protection continuum (as described above)
Sexually abusive behaviour may have serious psy­ occurs through the cooperation and collaboration of
chological consequences for the child. It is particu­ different agencies, within both the government and
larly harmful when it occurs on multiple occasions non-government sectors. No single professional or
over a period of time, when it is associated with physi­ agency can adequately provide fully comprehensive
cal injury, threats of physical harm if others are told, services across the whole continuum.
bribery or coercion, or when family members become
aware of the allegations but don't believe the child.
Psychological harm is of primary concern as a
consequence of both physical and sexual abuse. For Principles of interagency practice
­example, it can cause problems in children's person­
ality development, their ability to self-regulate their
in relation to the management
behaviour and to interact socially. of suspected child abuse or
neglect
This refers to the tertiary level statutory system that is
Prevalence of child abuse responsible for the management of children who enter
the child protection system because of a suspicion that
in Australia they have been abused or neglected and in whom abuse
The Australian Institute of Health and Welfare (www. or neglect is established.
aihw.gov.au) is responsible for collecting and collat­ The agencies that comprise the tertiary level system
ing child protection data from throughout Australia. are the statutory welfare agency, the police and, often,
The total number of notifications made nationally, tertiary forensic health services. The important princi­
reflecting the number of children in whom child abuse ples that support and enable tertiary interagency prac­
or neglect is suspected, has increased annually from tice are:
107 134 in 1999–2000 to 339 454 in 2008–2009. New • the presence of policies, procedures and guidelines
South Wales contributed 63% of the total notifica­ to address roles, responsibilities, referral practices,
tions. The increase reflects changes in child protec­ timeframes for assessments
tion policies and practices, and an increased public • a process for the exchange of information in
awareness of child abuse. It is not clear whether the relation to children who are suspected of having
increased rate of notification is due to an increase been abused in the context of what is legally
115
in child abuse. In Australia, estimates of the current appropriate and professionally ethical
 3.9 SOCIAL AND PREVENTATIVE PAEDIATRICS

• a joint decision-making process between tertiary

agencies specifically related to the outcomes Clinical management of
and interpretations of assessments, the types of suspected child abuse and
intervention and the provision of treatment to
abused children.
neglect
The health services, community services and the police A. Recognition of the child who may have been
have specific roles and responsibilities in managing abused or neglected
suspected child abuse and neglect. B. Initiation of the interagency process to ensure
optimal assessment of the suspicion
Health C. The forensic medical assessment
D. Establishment of the ongoing management
• Recognition of adversity in families and ensuring needs of the child when abuse or neglect is
its active resolution
confirmed
• Recognition of children in whom abuse/neglect may E. The health professional's ongoing responsibility
have occurred
to the child in whom abuse or neglect is suspected
• Ensuring that the child's situation is properly and to their family.
assessed in relation to health and safety needs
• Complying with local legal notification
requirements for suspected abuse/neglect A. Recognition by health professionals of children
• Determining the ongoing role of the health agency who may have been abused or neglected
according to agreed interagency practice
• Working to maintain an ongoing professional Suspicion of abuse/neglect in a child should be
relationship with families after abuse has been reported to the local statutory child protection
suspected agency, whether or not there are local mandatory
• Provision of specialist forensic health services reporting requirements. Reports will bring to light
to children suspected of having been abused or any previous, similar concerns either in the family
neglected, complementing community services or involving current family members, ensure a coor­
and the police. These include forensic medical and dinated response and facilitate the optimal assess­
psychosocial assessment and therapeutic services. ment and investigation of the suspicions. An optimal
assessment will enable informed decisions to be made
Community services in relation to the child's need for ongoing protection
and therapy.
• Investigation of notifications/reports of suspected The suspicion that a child may have been abused or
child abuse/neglect neglected arises in one or more of three ways.
• Coordination with health units and police of each
agency's respective role
• Facilitation of the assessment of children in whom 1. An allegation is made on behalf of a child
abuse/neglect is suspected to a professional by another person
• Establishment of the level of danger/safety of
children who have been abused or neglected These allegations are most often made by one parent
• Seeking of court child protection orders, when against another (from whom they are estranged) or by
considered necessary, for abused/neglected children, a family member against a parent. They are often in
particularly for those who remain in unsafe the context of Family Court proceedings relating to
circumstances the residency and visitation arrangement of the child.
• Optimal placement of children removed from their The role of the doctor in such situations is to:
families because of abuse/neglect • facilitate a notification of suspected child abuse to
• Ensuring that adequate therapy is provided to children the appropriate statutory authority
in whom abuse/neglect has been substantiated. • establish what, if any, clinical findings are
present that support or refute the allegations; for
example, when a suspicion of sexual interference
Police
has arisen based solely on dysuria, the suspicion
• Investigation of the criminal aspects of child abuse/ may be resolved if a urinary tract infection is
neglect confirmed
• Coordination with community services and health • ensure that if the child has any other medical
units through agreed interagency practices problems they are understood in relation to the
• Prosecution, when appropriate, of those who have allegations of abuse (e.g. Henoch–Schönlein
116
abused, molested or neglected a child. purpura and the appearance of ‘bruising’).
 Child abuse 3.9
The doctor should never discount the allegations on specifically indicative of abuse having occurred, but it
the basis of a lack of supportive physical findings. All should be considered.
suspicions should be reported and assessed optimally Engagement of such children and adolescents in a
through the interagency process. counselling process may lead to an allegation of harm
When allegations relate to sexual abuse it is neces­ being made. The allegation must then be notified.
sary for the doctor to conduct only a superficial genital
examination to check for external genital inflamma­ Presentations that of themselves
tion, discharge or bleeding. The definitive examina­ should raise suspicions
tion must be undertaken by an experienced paediatric • Injury in infancy and early childhood that is either
forensic physician and will occur as part of the foren­ unexplained (e.g. a skull fracture with no history
sic medical assessment, which will be initiated by the of blunt trauma) or inadequately explained (e.g.
interagency process. a spiral fracture of the femur in a 6-month-old
When there are physical findings present that may noticed when she was having her nappy changed).
support the allegations, they must be documented The younger the injured child, the lower the threshold
carefully and thoroughly. For example, superficial for suspecting the injury may have been inflicted. It is
or genital injury must be recorded photographically. rare for infants who are not independently mobile to
Normally, this is the responsibility of a paediatric sustain any significant injury. Adequate independent
forensic physician and is part of the forensic medical mobility is rare before 14 months of age.
assessment. Infants who injure themselves manifest patterns of
injury that reflect their mobility, for instance bruising
and abrasions over bony prominences of the forehead,
2. An allegation is made directly to a professional chin, knees and shins. Facial bruising over soft areas
by a child or young person and bruising over muscle masses (thighs, calves, upper
This may occur as part of a clinical presentation arms), the anterior trunk or abdomen are all rare in
related to the allegation or may arise during an appar­ young children, especially if not mobile. When bruis­
ently unrelated consultation. For example, in the pro­ ing occurs in any of these sites in infancy, inflicted
cess of assessing a child for behaviour disturbance an injury should be suspected.
allegation of physical abuse or emotionally harmful Fractures in normal infants are rare and the forces
parenting may be made. When allegations arise in this necessary for their production are able to be self-gen­
way, they must always be notified. erated only when young children are able to run and
When the complainant is an older child or adoles­ climb or when another person, usually an adult, is
cent it is critical that they are informed of the doctor's involved (e.g. young infants may sustain skull frac­
obligation to notify. In addition, they must be assisted tures from being dropped from the carrying height of
to deal with the issues that subsequently arise, par­ a parent).
ticularly whether or not they are safe to return home Fractures of the femur, tibia, humerus (from grab­
when they have made an allegation against a parent. bing, twisting or bending) and ribs (from direct
The role of the doctor in these situations is to establish impact or extreme chest compression) in infants
whether there are any clinical findings that support or should always raise suspicions and be assessed thor­
refute the allegations. oughly. The torsional forces necessary to produce a
A forensic medical assessment may be organized spiral fracture in either the femur or tibia are able to
after the notification has been made and the inter- be self-imposed only by young children who are able
agency process begins. to run and climb.
Scalds are the commonest heat injury in infants and
young children. Most often the scalds involve children
3. The suspicion arises out of a clinical pulling down cups of hot drinks or containers of hot
assessment undertaken for other reasons liquids on to themselves. Sometimes these incidents of
self-injury are indicative of poor parental supervision
Concerns may arise in the context of a consultation
or neglect.
and be related to non-specific presentations, presenta­
Immersion scalds occur when a child is immersed in
tions that raise suspicions, and the injury history.
hot liquid or the liquid surrounding a child becomes
Non-specific presentations hot. The circumstances surrounding immersion scalds
These include sexualized behaviour in young chil­ require careful and thorough evaluation. Often there
dren; aggressive or antisocial behaviour in preschool is a suspicion that a scald may have been inflicted or
and primary school children; adolescents who are occurred through parental neglect. When such suspi­
self-harming or manifesting dangerous and repetitive cions arise they should be reported to the statutory
117
risk-taking behaviour. None of these behaviours is agency.
 3.9 SOCIAL AND PREVENTATIVE PAEDIATRICS

Clinical example

A 2-month-old baby girl, one of twins, was

brought into the emergency department in
the early evening by her mother, who said
she became concerned when she took off her
baby's nappy and found that the ‘skin was peeling off’. She
said there had been no signs of any abnormality earlier in
the day. The children had been in her care for the whole
day; her grandmother had been helping her with the babies
during the afternoon.
The doctor considered that the finding was a scald and,
because there was no explanation, he considered that it
may have been inflicted, so made a notification. A forensic
medical assessment was undertaken and confirmed that the
abnormality was an immersion scald.
The great grandmother of the baby was interviewed. She Fig. 3.9.3 Recent immersion scald.
said she had changed the baby's nappy in the mid-afternoon.
The baby had passed a large amount of faeces and the
grandmother had had to wash her buttocks. She described The sequence of events leading to any serious injury
filling a bowl with water straight from the hot tap, lowering in infancy should be easily ascertainable by speak­
the baby into the water without testing the temperature. She ing with the infant's carers. Serious injuries include
said the baby was crying at the time and difficult to settle head injury, abdominal injury, chest injury or wide­
afterwards. She put another nappy on the child.
spread multiple injuries. When no adequate history
When this explanation was discussed with the mother,
she confirmed that the hot water was at a high temperature is available, a report of the suspicious nature of the
and she had not warned her grandmother of that fact. injury/injuries should be made to the statutory welfare
The assessment was that the great grandmother's agency. Subsequently, a comprehensive forensic medi­
explanation adequately accounted for the scald and the cal assessment will ensure that the best informed opin­
suspicion was resolved. ion in relation to the injury mechanism is able to be
The features of the scald that indicate it was caused by
formulated.
immersion are:
• the ‘tide-mark line’ that demarcates the scald from normal
The threshold for suspicion of abuse in such infants,
skin particularly when head injury is the presenting prob­
• the sparing of the skin in the creases from the hot water. lem, must be low. Head injury in infancy may be mani­
See Figures 3.9.2 and 3.9.3. fest as blunt trauma to the cranium with or without
intracranial haemorrhage, or may present solely as
intracranial haemorrhage without any obvious exter­
nal signs of injury. Such head injury is most likely to
be a manifestation of intracranial acceleration/decel­
eration injury, which may occur from such harmful
behaviours as violent shaking, and is often associated
with severe blunt trauma as well.

Clinical example

A baby boy of 2.5 months was presented by his

parents after reportedly having vomited and
having a seizure in his father's arms. There was
no external sign of injury on examination.
Computed tomography scan of the baby's head
(Fig. 3.9.4) showed a recent right-sided subdural
haemorrhage that was suspicious of inflicted injury because
there was no history of trauma.
A skeletal survey showed healing fractures of the posterior
aspects of the 4th to 7th left ribs (Fig. 3.9.5).
After initially denying any incidents of trauma, the father
said he had forcibly grabbed the baby around the chest and
118 thrown him into his cot 8 days before presentation and, on
Fig. 3.9.2 Recent immersion scald.
 Child abuse 3.9
intake is normal and controlled (e.g. in hospital or
the early evening of his presentation, had got angry with out-of-home care).
the baby and thrown him on to the couch. The seizure and Each of these presentations should be reported to the
vomiting occurred soon after.
appropriate statutory agency. Interagency discussions
The father was charged and given a suspended sentence.
He received psychological treatment.
will then lead to a comprehensive forensic medical and
The child remained with his mother. psychosocial assessment being undertaken. A forensic
psychosocial assessment in this context involves the
interviewing of children who are sufficiently develop­
mentally advanced.

The injury history

It is not always clear to the doctor who first sees an
injury whether or not it is adequately explained.
Generally parents of children less than 3 years old will
either be aware of how their child was injured (because
they witnessed the incident) or will clearly state that
they lost visual contact with their child for a period of
time and heard but did not see the incident of trauma
that caused the injury.
In both of these situations there will be readily avail­
able useful detail to help the doctor decide whether the
injury has been adequately explained or not. When an
injury has not been adequately explained, it should,
generally, be considered suspicious.
The following is a useful protocol to follow when
Fig. 3.9.4 Recent subdural haematoma (arrows). assessing injury in a child.
• When did the injury occur? This refers to the date
and time.
• Where did the injury occur? This refers to the exact
location.
• What actually went wrong? This refers to the detail
of what caused the injury.
• Was the incident actually witnessed and, if so, by
whom?
Parents who claim that the incident ‘must have happened
when …’ are not providing useful witness information
but merely speculating as to the cause of the incident.
Such a speculation is not an explanation, and an injury
in that context should usually be considered suspicious.
An injury history must always address the develop­
Fig. 3.9.5 Healing rib fractures. mental capabilities of the child, particularly in relation

A systematic, structured approach to the taking of

an ‘injury history’ assists in evaluating the adequacy of Practical points
the provided history and therefore in deciding whether
the injury should be considered suspicious.
The injury history
• Injuries where the mechanism is apparent and indicates When did the injury occur? – This refers to the date and time.
that the injury has been inflicted (e.g. a patterned Where did the injury occur? – This refers to the exact location.
bruise to the face indicating a slap mark or punch). What actually went wrong? – This refers to the detail of what
• Infections that are normally considered to be caused the injury.
transmitted by sexual contact (e.g. gonorrhoea, Was the incident actually witnessed and, if so, by whom?
syphilis, human immunodeficiency virus) or that may On review of the history, has the child had any previous
injuries?
be transmitted by sexual contact (e.g. herpes simplex
What is the developmental level of the child, particularly in
virus, genital warts from human papilloma virus). relation to their gross motor abilities (sitting, crawling,
• Infants with unexplained poor growth who gain walking, running, climbing)? 119
weight quickly in an environment where their
 3.9 SOCIAL AND PREVENTATIVE PAEDIATRICS

to gross motor skills, as with independent movement • formal interview of a child (when developmentally
self-caused injury becomes a consideration. possible and appropriate) to establish the child's
account of events
B. Initiation of the interagency process to • evaluation of the child's psychological state in
ensure optimal assessment of the suspicion relation to the suspicions or allegations.
The forensic psychosocial assessment is most impor­
A suspicion of abuse or neglect begins with an inter- tant in children in whom there are suspicions of
agency response initiated by the child protection noti­ sexual abuse because rarely in such cases is there sup­
fication and involves the statutory welfare agency, the portive physical evidence or first-hand witnesses to
police and the tertiary health service. the abuse.
At this time, the primary concern of the doctor The opinion that is formulated at the completion
should generally be the immediate safety and protec­ of the forensic medical assessment is important to
tion of the child. The doctor must decide whether or the statutory welfare agency and the police, and may
not to inform the child's parents of the suspicion and influence their ongoing investigation. The outcome of
will be guided in this decision by factors such as his a forensic medical assessment may be that physical evi­
or her previous relationship with the parents and their dence supports the suspicion or allegation of abuse. It
behaviour at the time of the presentation of the child. may conclude that an injury was or was not likely to
With infants and young children in whom physical have been inflicted.
abuse or neglect is suspected, the issue of safety is not Doctors who are not trained and experienced in
always clear and is often best addressed by admission forensic paediatric medicine should not undertake
to hospital. This allows the optimal assessment and forensic medical assessments. A forensic medical
management of the suspicious injury, the child and assessment is not an extension of a standard paediatric
the family. medical assessment, primarily because it is undertaken
Early discussions must occur between the manag­ to enable the formulation of a diagnosis or opinion for
ing team in the hospital, the statutory welfare agency potential legal purposes.
and the police to clarify roles and responsibilities and Forensic physicians must also ensure that general
to ensure the ongoing safety of the child during the health and developmental concerns of the children
assessment and investigation process. they assess are identified and managed. Forensic med­
The statutory agency workers will explain to the ical assessments provide information that may be use­
parents the ‘child protection process’ and the immedi­ ful in the statutory agency and police investigation.
ate plans for the investigation. They will seek the par­ The most important forensic principle is the ‘chain
ents’ cooperation for the child to remain in hospital. of evidence’. The chain of evidence is a legal concept
If there is resistance from the parents to the manage­ which requires that the origin and history of any clini­
ment plan, the statutory workers may consider apply­ cally gathered material that may be presented as evi­
ing to court for a child protection order to enable the dence in a court must be clearly demonstrated to have
process to continue. followed an unbroken chain from its source to the
court, so that there is no chance of its contamination.
In the conduct of a forensic medical assessment the
C. The forensic assessment in children in whom
‘chain of evidence’ relates specifically to:
abuse or neglect is suspected
• documentation (by clinical description and
These assessments are undertaken after a notification photography) of the physical findings related to the
of suspicion has been made and the statutory agency suspicion of abuse or neglect
has either requested or supports the assessment. There • accurate recording of the explanation offered (when
are two components to an optimal ­forensic ­assessment: available) to account for the physical findings
the forensic medical and the forensic psychosocial • proper collection of forensic specimens (e.g. swabs
assessments. of saliva, genital swabs).
The forensic medical assessment establishes the There are five steps in a forensic medical assessment:
extent of injury in a child and whether or not the 1. Determining the extent of obvious injury
injury is considered to have been inflicted. When sex­ (ascertained by physical examination). A complete
ual abuse is suspected, a forensic medical assessment physical examination is required including
will establish whether or not there is any sign of geni­ neurological assessment and fundoscopy.
tal injury or other condition (e.g. a sexually acquired 2. Establishing the biomechanics or mechanism of each
infection) that could support the suspicion. injury. This means the types of ‘force’ involved
The forensic psychosocial assessment is best under­ (tensile or impact, torsional, bending, thermal
120 taken by a psychosocial clinician, a social worker or and combinations) or how the injury was caused
psychologist, and involves: (incision, blunt trauma).
 Child abuse 3.9
3. Ascertaining the history provided for the injury/ • adequate X-rays to attempt the ageing of fractures
injuries. The explanation(s) must account for the • laboratory studies, in particular ‘organ enzymes’
appearance and biomechanics of the suspicious (liver enzymes, pancreatic enzymes)
injury in the context of the child's developmental • bleeding/clotting studies, including the
capacity (e.g. if an injury is reported to have measurement of the coagulation factors, platelet
occurred by an infant rolling off a flat surface of numbers and function
table height then the infant must be observed to • toxicology studies to analyse for the presence of
establish that rolling is possible). drugs and poisons.
4. Assessing the relevance of additional information, The results of these assessments add to the formul­
for example site visit evaluation, witness ation of the forensic medical opinion (Fig. 3.9.6).
statements. Site visit evaluation is undertaken
by the police to document features of the site
where the injury is said to have occurred (e.g. the D. The ongoing management needs of the
height of a table, the temperature of hot water, child when abuse or neglect is confirmed
the composition of the reported impact surface).
The primary ongoing issues once abuse has been con­
Witness statements are only taken by the police.
firmed are:
Their content may assist in establishing an injury
timeframe (e.g. the time a neighbour heard an • The child's safety and any ongoing need for protection.
infant scream or whether a facial bruise was • If there is a need for protection then legal
intervention leading to placement away from the
present when the child visited the neighbour the
abuser may be necessary.
day before the suspicion was reported).
5. Formulating an objective opinion based on the • The physically injured child may have ongoing
medical needs.
identified injuries. The forensic opinion must be
based solely on the result of the medical evaluation. • Addressing the psychological effects of abuse as
part of a comprehensive therapeutic programme.
Factors such as the known level of violence in the
child's family and a previous history of physical
abuse are critical in the management decisions that
E. The health professional's ongoing
will be taken by statutory welfare agencies and the
responsibility to the child and family when
police, but such factors cannot influence the forensic
abuse or neglect is suspected
opinion. When they do, the forensic opinion is
subjective and of no value in the legal context. Families involved in the child protection system often
The forensic medical assessment may resolve the sus­ isolate themselves from health services because they
picion (e.g. the skull fracture was explained adequately); fear being ‘targeted’ as abusers. Previous health-care
if the possibility that the injury was inflicted remains, providers should try hard to provide ongoing care to
further assessments are required to find evidence of any such families from as early as possible in the child pro­
covert skeletal trauma or organ injury or toxic substance tection process.
administration. The additional assessments include: Health-care providers should ensure that abused/
• imaging studies (skeletal survey, radionucleotide neglected children are provided with therapy and those
bone scanning, intracranial imaging), which should placed in out-of-home care have their ongoing health
be undertaken in infants less than 18 months of age needs systematically identified and addressed, because
and considered in children aged up to 3 years of their high rate of morbidity.

PHYSICAL EXAMINATION – related to the ‘suspicious’ injury

HISTORY – explanation for the injury’s occurrence
SITE VISIT – in the company of police
Practical points INVESTIGATIONS – as indicated by the child’s presentation, for example the X-ray of a limb
with severe bruising, the CT/MRI scan of an infant with a head injury.
These investigations are distinct from the specific forensic investigations that are
undertaken in young children if, after assessment, an injury is considered inflicted.
The five steps of a forensic medical assessment
1. Determining the extent of obvious injury.
2. Establishing the biomechanics or mechanism of each injury.
3. Ascertaining the history provided for the injury or injuries. Suspicion Suspicion
4. Assessing the relevance of additional information – site sustained resolved
visit evaluation, witness statements.
5. Formulating an objective opinion based on the identified
Specific ‘forensic’ No further investigations
injuries. investigations necessary
The forensic opinion must be based solely on the result of the
medical evaluation. Fig. 3.9.6 Forensic medical assessment of a ‘suspicious’ injury. 121
CT, computed tomography; MRI, magnetic resonance imaging.
 3.9 SOCIAL AND PREVENTATIVE PAEDIATRICS

needs notification and investigation. It is not good

The wellbeing of health professional practice to offer to make deals with
professionals involved with child parents when abuse is suspected (e.g. ‘If you tell me
what happened then I can help sort out this problem
protection quickly’).
Any clinician who deals with children or families As a general principle, doctors should have in
may become suspicious that a child has been abused place a support system that enables them to debrief
or neglected. An open and honest approach with difficult interactions with patients and should be
parents/carers is the best policy, unless there is a pos­ used when child protection issues arise, and also col­
sibility of physical danger. It is helpful to assure par­ leagues with whom they can discuss child protection
ents that they are not being accused, but the s­ uspicion concerns.

122
 Sudden unexpected 3.10
death in infancy
Barry Taylor, Dawn Elder

Despite a remarkable increase in knowledge about increasingly used for well babies at home, especially
the aetiology of sudden unexpected death in infancy when it was realized that infants went to sleep faster in
(SUDI) over the past few decades, it remains a sig- this position and that it was also associated with less
nificant clinical problem in Australasia and interna- gastro-oesophageal reflux.
tionally. This chapter reviews what we currently know In the 1970s and 1980s high rates of sudden infant
about SUDI, how diagnosis and clinical management death were recognized throughout the world and were
has changed over time, and how we should assist fami- considered to be so high that a number of large epide-
lies who experience the sudden death of an infant. miological studies were set up to try to determine the
reason for these deaths. It was usual at this stage for
the term ‘sudden infant death syndrome’, or SIDS, to
be applied to these deaths. Both Australia and New
Practical points
Zealand were found to have some of the highest rates
of SIDS in the world at this time. The apparent emer-
• A sudden unexpected death in infancy (SUDI) is one not gence of a new condition was almost certainly mainly
anticipated 24 hours before death occurred.
related to diagnostic transfer as health professionals
• All SUDI deaths must be referred to the coroner for
investigation. and coroners increasingly used the term (recognized
• After autopsy, an explanation will be found for some SUDI with an International Classification of Diseases (ICD)
deaths. 9 code of 798 in 1977 and an ICD10 code of R95 in
• If no explanation is found after examining the 1992). This is strongly suggested because total post-
circumstances of death, the clinical history and the neonatal mortality (within which are almost all SIDS
autopsy findings, the diagnostic label sudden infant death
cases) did not increase as SIDS rates rose. Case–control
syndrome (SIDS) may be used.
studies identified a number of risk factors associated
• Parents of SUDI infants should be offered follow-up with a
clinician who can discuss the autopsy and other findings with SIDS, and the dramatic decrease in SIDS and
in regard to their child's death. post-neonatal mortality in countries that intervened
• Advising new parents to sleep their infant supine in a around these risk factors (primarily the prone sleep
safe sleep space and to avoid smoking in pregnancy are position) strongly suggest a causative relationship.
important ways to prevent SUDI. This early research was followed by a plethora of basic
• A safe sleep space is one designed to make sure that the science research to try to establish the mechanism by
face is always clear, that there are no risks of wedging or
strangulation and that enables a baby to maintain thermal which the risk factors contributed to any individual
balance. infant's risk of sudden death.
Despite these efforts there remain a significant num-
ber of infants who die suddenly and unexpectedly each
year. It has increasingly been recognized that these
Historical perspective infants represent a particular group and that many
have been found sleeping in an unsafe sleep position
Sudden death in infancy has been reported since the or situation. For this reason, terminology has changed
earliest times. In the Book of Kings in the Bible there over time and this group of deaths is now more com-
is a report of an infant being overlain and found dead. monly discussed under the label ‘sudden unexpected
From Medieval to Victorian times babies were taken death in infancy’ (SUDI).
into their parents' beds in the winter to protect them
from the cold and some were found dead in the morn-
ing. As socioeconomic conditions and the care of new-
born infants improved, these types of death became
less common. In the 1960s, many babies in newborn
Definitions
intensive care units were nursed prone because of SUDI (sudden unexpected death in infancy), some-
increased stability of the chest wall and better oxygen- times described as SUD or SUID, is a term used for all
ation in this position, and this sleep position became unexpected infant deaths, whether the explanation is 123
 3.10 SOCIAL AND PREVENTATIVE PAEDIATRICS

determined after a thorough investigation or remains Many studies have described the characteristics of
unknown. Traditionally all unexplained SUDI deaths babies who die from SIDS, and risk factors have been
have been labelled as sudden infant death syndrome elucidated by a series of case–control studies. There
(SIDS), but since the mid-1990s a number of foren- has been much speculation as to why very few babies
sic pathologists are becoming increasingly reluctant to die in this manner in the first month of life, with the
use this diagnosis as a cause of death when certain risk peak age of death at 24 months of age. Other factors
factors are present (co-sleeping, prone positioning, such as prematurity and growth restriction at birth are
issues surrounding appropriate parental care, minor more understandable, as are many risk factors that
pathological changes, etc.), preferring to use the terms are difficult to change such as socioeconomic depriva-
‘unascertained’, ‘borderline SIDS’, ‘undetermined’, tion. More recently there has been concern that these
‘unspecified’ or ‘unknown’ when they report their find- deaths appear to be occurring more frequently in the
ings to the coroner. The formal definition of SIDS has first month of life.
undergone several revisions since the term was initially The focus of much research has been on identify-
coined by Beckwith in 1969, with the broad definition ing ‘modifiable’ risk factors – by comparing the cir-
from 1989, ‘the sudden death of an infant less than one cumstances around the baby who has died with those
year of age which remains unexplained after a thorough of babies (matched for age) who have not. The key
case assessment, including performance of a complete modifiable risk factors are nicely summarized by the
autopsy, investigation of the death scene, and review of International Society for the Study and Prevention of
the clinical history’, still being the most widely used. Perinatal and Infant Death (ISPID) and are:
Subsequent suggestions have involved including the • prone and side sleep position
need for the death to have occurred during sleep, and • maternal smoking during pregnancy as well as
also several subclassifications have been suggested, postnatal second-hand smoke
none of which has entered into general usage. • unsafe sleeping environments – especially parents
falling asleep with their baby on the same sleeping
surface, or in unusual sleeping places such as sofas
• bedding arrangements that allow the face to
Incidence and risk factors become covered.
As can be deduced from the discussion above, the Two key protective factors have been described –
problems of definition make comparisons over time breastfeeding and immunization – with some ongoing
and between countries problematic! Figure 3.10.1 discussion over consistent data from many studies sug-
shows both SIDS mortality and total post-neonatal gesting that the use of a pacifier or dummy at the time
mortality in 1990 (before risk reduction campaigns in of going to sleep is also protective.
these countries) and in 2005, 15 years later.

5 Aetiology of sudden death

in infancy
SIDS deaths per 1,000 live births

4 Much research has been undertaken in the past few

decades to try to find a reason for the death of infants
where the clinical history, examination of the scene
3 of death and autopsy has not found a fatal diagnosis.
These infants have been labelled as dying from SIDS,
and research has indicated that they do have some
2 common characteristics. For 20–30% of infants who
appear to have died suddenly and unexpectedly, a clear
cause of death is found through either the clinical his-
1 tory, death scene examination or autopsy. These cases
can then be considered explained SUDI deaths.
0
nd
s nd Explained SUDI
alia da
gla
nd an rla ala A
str na Jap the Ze US
Au Ca En Ne ew
N Infection
SIDS 1990 SIDS 2005 PNNM 1990 PNNM 2005 Sudden and overwhelming infection is a possible cause
Fig. 3.10.1 SIDS and post-neonatal mortality in selected of sudden infant death. Pneumococcal or meningococ-
124
countries in the years 1990 and 2005. cal septicaemia or meningitis are often of particularly
 Sudden unexpected death in infancy 3.10
sudden onset, especially in the young infant. The diag- diagnostic tests to be done. These deaths should be
nosis should be clear at autopsy. As evidence of minor occurring less often as the diagnosis for many of these
infection may be found in infants who have a final conditions (including MCAD) can be made by use
diagnosis of SIDS, the pathologist must be convinced of tandem mass spectrometry on blood collected on
that the evidence of infection found is of a degree suf- Guthrie cards in the newborn period.
ficient to explain the death.
Other
Homicide Other disease states that have been discovered at
Homicide must always be kept in mind, especially autopsy after sudden death include haematological
in the situation where there have been other siblings disorders such as leukaemia, gastrointestinal disorders
who have apparently died from SIDS. In general, it is and intracranial haemorrhage.
thought that less than 5% of SIDS cases may in fact
be homicide. As intentional suffocation is virtually
Unexplained SUDI
impossible to distinguish from SIDS at autopsy, this
diagnosis may not be confirmed unless there are other If a specific cause of death is not found after a com-
significant injuries or a confession. plete history and thorough post-mortem examina-
tion, the death may be labelled as SIDS or the label
Accidental asphyxia SUDI–unexplained may be used. Sometimes it will be
For some infants it is clear at the death scene that death considered that insufficient information about the cir-
has been due to accidental asphyxia. Some infants have cumstances of death is available to rule out a diagnosis
been found dead caught in the bars of their cot or found of accidental asphyxia, and the death may be labelled
strangled on a stray piece of cord. It is likely that any as undetermined. Despite using a definition for SIDS
infant would die if they got themselves into such a situ- that excludes other causes of death and implies that
ation. For other infants, the scene may have been suspi- the infant was otherwise healthy prior to death, it has
cious for accidental asphyxia, for example if the infant become more apparent over time that the infant who
was found lying under a parent, but it cannot be proven dies suddenly and unexpectedly in seemingly inexpli-
that the infant's airway was completely obstructed cable circumstances is not completely normal.
at the time of death. The question then arises as to The triple risk model provides a useful way to con-
whether the particular infant may have been more vul- ceptualize the information currently known about the
nerable in a potentially unsafe sleep situation than an factors that may contribute to risk of sudden death in
otherwise normal infant would be expected to be. infancy (Fig. 3.10.2). The model proposes that death
Cardiac arrhythmias occurs when a vulnerable infant is exposed to an exter-
Genetic cardiac channelopathies such as prolonged QT nal stressor at a critical period of development. It has
syndrome are thought to account for 5–10% of SUDI become apparent over time that more than one final
deaths. A family history of sudden death or deafness mechanism of death is likely.
should be sought and would suggest that other family
members should be screened for these disorders by elec-
trocardiography or 24-hour Holter monitoring. A genetic The vulnerable infant
diagnosis for these disorders can be made after death from The major epidemiological risk factors for SIDS and
stored blood, but this is still not a routine procedure. SUDI that define the vulnerable infant are exposure
to maternal smoking in pregnancy, prematurity, intra-
Congenital anomaly
uterine growth retardation, lack of breastfeeding and
Occasionally an infant will die suddenly and unexpect-
environmental smoke exposure after birth. There are
edly, and be found at autopsy to have a significant con-
also a number of anatomical and physiological factors
genital anomaly that has not been recognized in life.
that mark the vulnerable infant. Pathological abnor-
Both cardiac and pulmonary anomalies occasionally
malities present in the central nervous system of SIDS
present for the first time in this way.
victims include gliosis, delayed central nervous sys-
Metabolic tem myelination and arcuate nucleus hypoplasia. The
A small percentage (<1% in the UK) of babies dying degree of brainstem gliosis varies with the amount of
from SIDS probably die as a result of medium-chain maternal smoking during pregnancy in SIDS infants.
acetyl coenzyme A deficiency (MCAD). MCAD or Other findings found at autopsy suggest that SIDS
another metabolic disorder should be suspected if the infants may have been exposed to chronic or intermit-
baby had decreased oral intake before death or if there tent hypoxia prior to death. These episodes of hypoxia
was any unusual smell about the baby. An experienced may be secondary to obstructive apnoea, which is more
pathologist will usually suspect a metabolic cause common in infants who go on to die from SIDS than
125
of death at autopsy and arrange for the appropriate control infants. A major area of research has been the
 3.10 SOCIAL AND PREVENTATIVE PAEDIATRICS

Pre-term and growth restricted

Maternal smoking
Inherited narrow upper airways
Lack of breastfeeding
Genetic polymorphisms
(in serotonin pathway)

Vulnerable baby

Prone sleep position 1–7 months

Head becoming covered Learning to roll over
Overheating Narrowing of upper airway
Unsafe sleep environments Environmental Developmental Arousal responsiveness
• Co-sleeping insult stage
• Sofas
Infection

Fig. 3.10.2 The triple risk hypothesis for sudden unexpected death in infancy.

investigation of whether vulnerable infants may have The risks associated with bed-sharing have pro-
poor arousal responses and are therefore not able to voked some controversy. Initially it was thought that
protect themselves in any situation that compromises bed-sharing with an adult was only a risk when the
their breathing in some way. Future SIDS infants infant had been exposed to maternal smoking in
also show less arousal during sleep than controls, and utero. It is now clear that small infants not exposed to
infants of smokers have impaired arousal responses. smoking are also vulnerable, especially in the first few
Decreased arousal in quiet sleep has also been shown months of life. In addition, small infants in bed with
in infants following infection and in sleep-deprived large adults or adults under the influence of alcohol or
infants. This may be important as histological and drugs are at greater risk. Babies are also very vulner-
microbiological evidence of recent viral infection has able if they are on a couch with a sleeping adult, so it is
been found in some SIDS infants. Overheating may critical that caregivers are alert when they are feeding
also contribute to decreased arousability. and holding their infant.
Alterations in autonomic function have been found
in infants at risk of SIDS, including decreased heart
The contribution of developmental age
rate variability and diminished heart rate responses
after tests of autonomic function. These differences The newborn infant has poorly developed muscle tone
may make it harder for the vulnerable infant to have and poor head control. This means they have very
an appropriate cardiovascular response when stressed limited physical ability to reposition themselves to
by overheating or by an asphyxial episode. improve their airway when it becomes compromised.
The airway of immature infants is particularly vul-
nerable when they are in a car seat, when their head
The contribution of exogenous stressors
flops forward or to the side, or in a bed-sharing situa-
It has been established for a number of years that the tion. The prone sleep position is particularly danger-
prone sleep position is a major risk factor for SIDS. ous when an immature infant sleeps in this position
Side positioning is also a risk because the infant often for the first time, especially if they have not had expe-
falls into the prone position from side sleeping. Other rience in prone while awake to improve neck muscle
sleep environment factors that have been found to control. The 3–5-month age range was previously
be important are having the head covered, becoming thought to be the most common time for SIDS deaths,
overheated and becoming too cold. Lying on bedding but sudden infant death is increasingly being recog-
that is too soft or using a pillow are also risk factors, as nized as occurring in younger infants and even in the
126
is having toys around the infant in the cot. first weeks of life.
 Sudden unexpected death in infancy 3.10
Disruption of serotonergic mechanisms assessed and is designed in particular to facilitate
and sudden infant death research and epidemiological data collection about
SUDI deaths internationally. The classification cate-
The areas of the brain that are abnormal histologi-
gories are as follows:
cally in SIDS infants are areas containing serotonergic
0 Incomplete investigation (classified SUDI)
neurons, and levels of serotonin have been shown to
/0 Extension used to denote a potentially
be decreased in these areas. The so-called medullary
important piece of information is missing
5-hydroxytriptamine (5-HT) system is abnormal in at
Ia No notable factors identified (classified SIDS)
least 50% of SIDS cases. This system is important for
Ib Notable factors identified but unlikely to have
central chemoreception and cardiovascular control,
contributed to death (SIDS)
and is conceptualized as a ‘defence network’ that pro-
IIa Factors(s) identified that possibly contributed to
tects against stresses to the vital functions of respiration,
the death (SIDS)
blood pressure control, airway patency, thermo-
IIb Factors(s) identified that probably contributed
regulation, sensory input and arousal. Studies are now
to the death (SIDS)
reporting that exposure to smoking in pregnancy has a
III Factors(s) identified that provide a cause of
direct effect on serotonin mechanisms.
death (classified explained SUDI)
Gasping is an important autoresuscitation mecha-
nism that appears to fail in some SIDS victims. This
may be because serotonin is required for pacemaker
generation of respiratory rhythm during hypoxia.
Serotonin is also involved in the chemoreceptor
Procedures when an infant dies
response to carbon dioxide. Failure of this response suddenly and unexpectedly
system may be critical for infants exposed to a poten-
When an infant has been found to have died without
tial rebreathing situation. Serotonin deficiency may
an apparent cause, a death certificate cannot be writ-
also lead to altered heart rate variability and impaired
ten and the local coroner must be notified. It would be
baroreceptor function. The presence of abnormali-
usual then for the coroner to direct that a post-mortem
ties of serotonergic mechanisms in the brain therefore
examination should be done. The infant autopsy
explains some of the physiological findings found in
should ideally be undertaken by a paediatric or peri-
infants at risk of SIDS.
natal pathologist. The police will also investigate the
As well as what appear to be acquired lesions in
death on behalf of the coroner. Investigation should
the serotonin network, genetic abnormalities of sero-
include careful examination of the scene of death and
tonin metabolism have been described and been asso-
a review of the events leading up to the death. This is
ciated with an increased risk of SIDS. These include
often completed very well by the police, but a medical
variation in serotonin transporter genes, FEV gene
history is also required to establish whether there are
mutations, genes associated with a primary cardiac
any contributory factors related to the general health
channelopathy, and other genes pertinent to auto-
and development of the infant, as well as to consider
nomic nervous system development. It is likely that
whether there is any risk (environmental or medical)
these genetic abnormalities explain some of the eth-
to other children in the household. Where the child
nic variation in prevalence of SIDS and also why some
that has died is one of twins, it is generally consid-
infants are at risk even when sleeping in the recom-
ered essential for the twin to be admitted to hospital
mended sleep position.
for careful review and monitoring for at least 24 hours.

Classifying SUDI Parent support after an

A proposal for the international classification of
SUDI was presented at the 17th Nordic Conference
unexpected infant death
on Forensic Medicine in 2009. The starting point is Sudden unexpected death of an infant is devastating to
that all initially unexpected deaths will be labelled parents, extended family and indeed staff. Empathetic
as SUDI. An unexpected death is one that was not care is needed for all concerned, and dealing with the
anticipated as a significant possibility 24 hours before family in this situation is usually the job of senior and
the death occurred or where there was an unexpected experienced staff. Parents will be reassured if a care-
major collapse followed by resuscitation and survival ful history and examination is done, as they are usu-
for more than 24 hours. The SUDI classification is ally keen to find out why their baby has died. Some
made when the available information, including his- parents, often from Indigenous cultures, object to the
127
tory, death scene examination and autopsy, has been need for a post-mortem examination, or may ask for a
 3.10 SOCIAL AND PREVENTATIVE PAEDIATRICS

limited autopsy. In this situation careful explanations

about why it may be useful for the family to know the Prevention
cause of death (e.g. to enable genetic counselling and Increased knowledge about the major risk factors
detect possible health threats to other family mem- for sudden infant death has lead to prevention pro-
bers), as well as reassurances about the respect and grammes being put in place around the world. Because
care that will be given to the baby by the patholo- of these programmes, many infant lives have been
gist and staff, will lead to acceptance of the need. saved. The main prevention measures are based on the
Ultimately, the coroners of both Australia and New known factors that place infants at risk, which have
Zealand can direct that a post-mortem examination be already been discussed. Efforts at prevention must
done without parental consent. start early in pregnancy if the risk of maternal smok-
Parents and family have a complex and difficult ing in pregnancy is to be decreased. Other times when
grieving task. After initial denial, feelings of guilt can prevention should be discussed with parents are at the
be especially difficult as most babies that die from time of birth, prior to discharge from initial maternity
SUDI have clear risk factors, some of them chosen by care and during well-child checks in the first months
the parents. Giving support and clear information is of life. The International Society for the Study and
important, and for families that identify as Indigenous, Prevention of Perinatal and Infant Death (ISPID)
early involvement of a social worker or support person website lists the messages that should be given to par-
from their own culture is important. ents (http://www.ispid.org/prevention.html):
Special attention should be paid to other chil- Always (day and night) place the baby on his/her back
dren in the family and to grandparents. Children when it's time to sleep
who have a sibling die often have ‘magical think- • The most significant proven risk factor is the sleep
ing’ – they believe that their thoughts and deeds may position. The risk of SIDS is over three times
have caused the death. Clearly telling them that this higher for a baby sleeping on the stomach.
is not so is an important task for adults in the family • The practice of always placing the baby on his/her
to do, often many times over the subsequent months. back when its time to sleep should begin at birth.
Grandparents in this situation feel a double loss – the The baby will become accustomed to sleeping on
loss of their grandchild, but also the pain of seeing the back and will have no problems falling asleep.
their children suffer. They often feel that they have to • Make sure every caregiver uses the "back to sleep"
support their own children and can have no support or position. A caregiver placing a baby to sleep on his/
outlet for their own grief. Recognizing this, and talking her stomach or side when the baby is accustomed to
with them, sometimes separately, can be helpful. sleeping on the back raises the risk of SIDS 18-fold.
• Place the baby on the stomach only when he/she is
awake and under adult supervision.
Clinical example Always keep the baby's environment smoke-free
• Do not smoke during pregnancy. The more you
A 17-day-old baby was found dead in bed by smoke, the greater the risk for SIDS.
her mother. She was born at 38 weeks with a • Second-hand smoke is also a risk factor: stay in a
birthweight of 2700g. Antenatal ultrasonography smoke-free environment when pregnant.
had detected intrauterine growth retardation. The
mother smoked 20 cigarettes per day, also used marijuana
• Always maintain a smoke-free environment for the
and was obese. The baby was in bed with the mother for a baby.
breastfeed. The mother was tired and couldn't remember the Make the sleeping environment as safe as possible and
baby finishing the feed. The mother was the only adult in the avoid overheating
bed, which was a Queen size bed. When the mother awoke • Place the baby to sleep in its own cot next to the
the baby was reported to be lying on her back on her mother's parents' bed for the first six months (room sharing).
arm. There was no sign of life.
• Never share a bed with baby if you or your partner
No abnormalities were found at post-mortem examination
to explain the death. Because the infant was thought to be
smoke. Babies whose parents smoke are at increased
in an unsafe sleeping environment (in bed with an obese risk of SIDS while co-sleeping.
mother who smoked) it was felt a diagnosis of SIDS could not • Never share a bed with baby when you have had
be applied. The cause of death was listed as ‘undetermined’. alcohol or drugs. (Don't use alcohol or drugs when
Accidental asphyxia was thought to be the cause, but caring for your baby, especially ANY TIME you
could not be proven because the only report of how the may fall asleep.) Babies whose parents have recently
baby was found came from the mother who was very tired
used alcohol or drugs are at increased risk of SIDS
and could not remember all the circumstances clearly. For
research purposes this would be classified as SIDS IIb (factors (and accidental suffocation) while co-sleeping.
identified that probably contributed to the death). • There is a slightly increased risk of SIDS with bed
128 sharing for infants less than 3 months even if they
 Sudden unexpected death in infancy 3.10
were not exposed to cigarettes, particularly if the • Use a safe, firm mattress that fits the cot properly.
baby was small (less than 2.5kg) at birth or born • Use a mattress that is in new or used and in good
prematurely. condition (no tears).
• In some countries there is a recommendation to A word about breast feeding and pacifiers
avoid all bed sharing, although some disagree • Breast feeding is always recommended for its
and advise avoiding bed sharing only if there are numerous benefits for babies and mothers (as a
other risk factors present such as smoking or source of multiple necessary nutrients, disease
alcohol use. protection and as a contributor to mother–baby
• Never sleep with baby on a couch or sofa. This bonding). Several studies show that breastfeeding
increases the risk of SIDS and fatal sleep accidents. also offers a risk reduction for SIDS.
• Keep the cot free of soft objects and anything loose • Research suggests that using a pacifier may reduce
or fluffy (bedding, toys, bumpers, pillows, duvets). the risk of SIDS. Start using a pacifier after one
• Do not allow the baby's head to be covered with month of age when breast feeding is usually well
bedding/blankets. established. Give a pacifier when you put the
• Keep the room temperature at 18°C to 22°C and baby to sleep, but do not force it. Some but not
avoid overdressing (i.e. too many layers of clothes; all studies have shown that pacifiers may have an
particularly avoid the use of a hat when indoors) adverse effect on breast feeding.
when placing the baby to sleep. Overheating has Immunization
been cited as a risk factor for SIDS in the past, • Infants that are immunized have half the risk of
however, it has been shown that thermal factors are SIDS and are protected against diphtheria, tetanus,
less important if the infant sleeps on the back. whooping cough, etc.

129
 3.11 Care of the adolescent
Susan Sawyer, Andrew Kennedy

world also ­recognize the subspecialty of adolescent

What is adolescence? health, all doctors must learn the knowledge, attitudes
Adolescence describes the developmental stage and skills to manage young people's health concerns,
between childhood and adulthood. The World Health regardless of their likely future roles.
Organization defines the ages of an adolescent as
10–19 years, and defines youth as 15–24 years. We
commonly combine these definitions (10–24 years)
and use the encompassing term ‘young people’.
Adolescent development
The onset of puberty has long been accepted as Just as all paediatricians need sound knowledge of child
the starting point of adolescence, whereas key social development, they must also have a ­ sophisticated
and role transitions such as completion of education, understanding of adolescent development. The
financial independence, marriage and children have division of adolescent development into the three
historically marked the end of adolescence. These end- domains of physical, cognitive and psychosocial can
points formerly occurred within the few years from be a helpful framework for monitoring develop-
the late teens to the early twenties. As young people ment. An additional approach (if simplistic) is to
now commonly participate longer in education and are divide adolescent development into early, middle
marrying and having children later, the end of adoles- and late stages. Using this approach, early adoles-
cence has become less distinct. cence ­corresponds to physical development, middle
The majority of adolescents rate their own health, relates primarily to cognitive maturation, and late to
including their mental health, as good. Many adoles- ­psychosocial aspects.
cents describe the period of adolescence as enjoyable Early adolescence (around 10–14 years old) is char-
and exciting, and as a time of satisfaction in achiev- acterized by the physical changes of puberty that mark
ing many milestones such as first relationships, com- the acquisition of reproductive capacity. It can be a
pleting school, getting a job and learning to drive. In time of increased physical activity and may also be a
contrast, adolescence was historically described by time where mood changes are noticed by the family.
adults as a period of turmoil. Certainly, it is a time of The developmental tasks associated with this period
increased health risk for healthy young people as well are about establishing a realistic body image and also
as for those with chronic illness, and there are a signifi- becoming aware of oneself as a sexual being with a
cant number of young people for whom adolescence sexual orientation. In response to these hormonal
is not ‘smooth sailing’. Furthermore, although many changes, the prepubertal unisex silhouette becomes
health indicators in younger children and older adults characterized by a larger, muscular male physique and
have improved (e.g. tobacco use), a wide range of pub- a more rounded female shape.
lic health indicators in young people has remained Mid-adolescence (around 15–19 years old) is char-
static or have declined (e.g. rates of obesity and sexu- acterized by increasing independence, commonly
ally transmitted infections). with more time spent with peers outside the home.
In many parts of the world, specialist children's Education is more demanding of young people's
hospitals still effectively ‘end’ at 14 years of age, but maturing cognitive skills. The developmental tasks
adolescence is increasingly recognized as an impor- of this stage include a stronger sense of oneself as
tant developmental period within the discipline of an individual and a greater focus on personal and
paediatrics (which is increasingly referred to as ‘child social values. Neurocognitive maturation is responsi-
and adolescent health’). Young people up to the age ble for an increased capacity for abstract thinking, the
of 18–19 years are now commonly managed in ter- capacity to think about thoughts. Given how much of
tiary children's hospitals and paediatric programmes health management relates to future health outcomes,
in Australia and New Zealand. The upper age of understanding young people's cognitive maturation
many community-based children's health and welfare is an important element of the monitoring of adoles-
130 services has also risen. Although many parts of the cent development and of working with young people
 CARE OF THE ADOLESCENT 3.11
clinically. Clinical strategies that might influence self- Dramatic social changes in the developed world
management behaviours in adults who are motivated have resulted in young people being generally health-
by future health goals will not be influential in adoles- ier, wealthier and better educated than previous gen-
cents, who are more motivated by events in the ‘here erations. More young people now complete 12 years
and now’. Neurocognitive maturation is now believed of school than previously, with more continuing on
to continue into the early twenties. with some form of post-secondary training or study.
Late adolescence (20–24 years old) is characterized Social roles have widened for females as well as males.
by a greater focus on vocational goals, the transition In Australia, the mean age of marriage is older than
between school and work, and a greater enjoyment in previous generations, as is the age that women have
of intimacy, including sexual intimacy. The develop- their first child, which recently exceeded 30 years.
mental tasks are to establish adult roles and respon- In the 1950s most people had left school, got a job,
sibilities, including longer-term relationships and less got married and had children by their early twenties.
reliance on a peer group. Psychosocial development Most contemporary young people achieve these mile-
is characterized by aspects of personal individua- stones much later. Access to new technologies provides
tion, such as the development of a coherent sense of a much larger peer group and virtual community for
self and an understanding of individual versus fam- young people, with uncertain consequences.
ily responsibilities, coming to terms with one's physical These same changes are also occurring for young
self, understanding one's sexuality and being able to people in low- and middle-income countries. In these
provide for oneself financially. countries, rapid urbanization, rapid social change and
These stages are listed in Table 3.11.1 with an a loss of many of the traditional pathways to adult
approximate age at which each stage occurs, the main life contribute to many young people in these commu-
feature of each stage and a key developmental ques- nities experiencing different pressures during adoles-
tion for young people at this stage. cence than previous generations, with consequences
While there is close association between the dif- for their health.
ferent domains of development, adolescent develop- However, there are still many aspects of adolescence
ment is characterized by being uneven and complex: that have not changed over the centuries. Socrates is
like earlier child development, it is influenced by the reported to have written in 450 bc that:
environment, is mediated by relationships and is trig- ‘Our youth love luxury. They have bad manners
gered by social participation. Chronic illness and dis- and contempt for authority. They show disrespect
ability can affect each of these domains but the effects for their elders and love idle chatter in place of
are inconsistent. For example, although chronic illness exercise. Children are now tyrants not the ser-
and disability may delay the physical changes of the vants of the household. They contradict their
adolescent growth spurt and of pubertal timing, expo- parents, chatter before company, gobble up their
sure to challenging life decisions or to friends dying food and tyrannize their teachers …’
can result in earlier engagement with more spiritual
elements of life.
The increasing cultural diversity of Australia and
New Zealand results in many young people having par-
ents who were born overseas, or who may hold differ-
Burden of illness in adolescence
ent views of what adolescence is or should be about. Adolescence has long been considered the h
­ ealthiest time
Adolescents in these families can sometimes struggle of life. However, dramatic improvements in infant
with the discrepancy between the different expectations and child mortality globally have brought greater vis-
of their Australian peers and their family about the ibility – and concern – about adolescent and young
general aspects of role and identity, as well as specific adult mortality, as this age group has experienced far
elements of what is acceptable behaviour at given ages. less improvement in mortality than younger children.

Table 3.11.1 The stages of adolescent development

Developmental stage Age (years) Main feature Key question at this stage

Early 10–14 Biological Am I normal?

Middle 15–19 Cognitive Who am I?

Late 20–24 Emotional/Social Where am I going?

131
 3.11 SOCIAL AND PREVENTATIVE PAEDIATRICS

Worldwide, there are at least 2.6 million deaths in Generally, the earlier the onset of these ‘risk behav-
10–24 year olds annually. There is also a marked iours’, the greater the likelihood of poor health out-
rise in mortality from early adolescence (10–14 comes. For example, although 80% of adult smokers
years) through to young adulthood (20–24 years), start smoking in adolescence, the onset of smoking
with the reasons varying by geographical region and at an early age marks a greater risk for continuing
sex. Mortality rates are almost 4-fold higher in low- smoking as an adult. In other words, the earlier health
and middle-income countries than in high-income behaviour is ‘learned’ the longer it is likely to persist.
countries. Importantly, the majority of deaths in ado- Young people with one identified health risk behaviour
lescence are preventable, with prominent causes being are more likely to have other ‘co-morbid’ behaviours.
road traffic accidents, violence, self-inflicted injury, A number of common risk factors predict earlier
human immunodeficiency virus/acquired immune engagement in many different health risk behaviours
deficiency syndrome (HIV/AIDS) and tuberculosis. and mental health and social outcomes. These include
Maternal conditions are a leading cause of female factors within the individual, family, peer and commu-
death, especially in low-income countries. In 2007, the nity. There are important additive or synergistic asso-
leading causes of death in 12–24-year-old Australians ciations between such risk factors. For example, being
were injuries (65%), cancer (10%) and diseases of in a peer group where most of an adolescent's friends
the nervous system, including cerebral palsy and smoke increases their later risk of smoking; this risk
epilepsy (5%). is even greater if the adolescent is depressed. Lack of
The burden of illness in adolescents differs greatly family connectedness or support, lack of engagement
from that of infants and young children, who are dis- with friends, bullying at school and poor academic
proportionately affected by congenital disorders and performance are risk factors for a wide range of poor
acute infectious disease respectively, and of adults for health and social outcomes, such as substance use,
whom ischaemic heart disease and cancer predominate. poor mental health, early school-leaving and antiso-
Some 60% of 12–24-year-old Australians have a long- cial behaviours. Chronic illness and disability in ado-
term health condition, and 11% of young Australians lescence is always considered a risk factor.
have a disability that causes some form of limitation or Identifying risk-taking behaviours and their conse-
restriction. Many other causes of ill-health are more quences is an important part of any adolescent health
commonly psychosocial than biological in adoles- assessment, but protective factors are also important to
cence, and tend to reflect unhealthy patterns of risk identify. These are factors that can ameliorate risk factors
behaviours and mental disorders. or increase the likelihood of positive health and social
Thus, the leading causes of mortality and morbid- outcomes. Important protective factors are an intact and
ity in the adolescent age group are from accidents well functioning family, connectedness with school, com-
and injuries (unintentional and self-inflicted), men- munity and peers, and participation in enjoyable extra-
tal health problems and behavioural problems such curricular events such as sport or creative activities.
as substance use and abuse. Other prominent health Put simply, the more protective factors in a young
issues are unplanned pregnancy and sexually transmit- person's life, the more likely they are to make health-
ted infections. ier choices in adolescence. Although many family fac-
Some of the major health issues affecting young tors cannot be changed or ‘treated’, efforts to alter the
people in Australia are summarized in Table 3.11.2. school environment can be especially powerful.
The data refer to 12–24-year-old Australians unless Many adolescent health problems are a consequence
stated otherwise. of health risk behaviours (see Table 3.11.2) and devel-
opmental challenges. As a consequence, knowledge
and assessment of adolescent development, includ-
ing exposure to risk and protective behaviours, is the
foundation of the clinical approach to working with
Risk and protective factors teenagers. Health problems in adolescents don't occur
Learning by doing is a normal part of adolescence, in isolation; one identified health problem raises the
but some behaviour can have harmful consequences. likelihood that there will be other health risk behav-
The onset of puberty marks a time of growing risk in iours and various family, peer and community ante-
relationship to certain behaviours and mental health cedents. Some behavioural concerns in teenagers have
states. Although learning about the harmful effects their onset in childhood, but others have their onset in
of alcohol by drinking some alcohol can be consid- adolescence. Once established, there is a greater risk of
ered normal in Australia, binge drinking is associated these behaviours continuing into adult life where they
with many harmful effects such as later regretted sex- contribute to the adult burden of illness. Early identi-
ual activity, alcohol dependence in early adult life and fication and intervention is a desired outcome of any
132
death from road traffic accidents. contact by adolescents with the health-care system.
 CARE OF THE ADOLESCENT 3.11
Table 3.11.2 Some of the key health issues and selected risk factors affecting young Australians

Health issue Burden of illness

Emotional distress 9% of 16–24-year-old Australians had high or very high levels of psychological distress in 2007,
and 1 in 4 experienced a mental disorder

Obesity and overweight 35% of young Australians were estimated to be overweight or obese (23% overweight but not obese;
12% obese in 2007–2008)

Risky substance use 11% of young Australians were daily smokers, 30% drank alcohol at risky or high-risk levels for short-
term and 12% for long-term harm, and 1 in 5 had used an illicit substance in 2007

Chlamydia notifications Over the past decade, there has been a large increase in notifications for sexually transmitted
infections, particularly chlamydia (5-fold increase)

Sexual intercourse in 27% of year 10 students and 56% of year 12 students had experienced sexual intercourse. Two-thirds
year 10 and 12 students of sexually active students (68%) used a condom at their most recent sexual encounter

Violence 7% of young adults were victims of physical or sexual assault and almost half were victims of alcohol-
or drug-related violence in 2007

Chronic health condition 60% of young Australians have a long-term health condition in 2007–2008. The prevalence of
long-term conditions has declined since 2001 among 15–24 years from 71% to 64%.

Disability 11% of 12–24-year-old Australians had a disability with specific limitations or restrictions; a quarter
of these had profound or severe core activity limitations (2008)

Abuse and neglect 4 in every 1000 young people aged 12–17 years were the subject of a substantiated report of abuse
or neglect in 2008–2009. Indigenous young people were over-represented at 5 times the rate of other
young people

Parent health 16% of parents living with young people rated their health as fair or poor, and around one-fifth had
poor mental health. An estimated 16% of young people lived with a parent with disability

Source: Australian Institute of Health and Wellbeing (AIHW) 2011 Young Australians: their health and wellbeing 2011. Cat. no. PHE
140. AIHW, Canberra.

Practical points Medicolegal context

and confidentiality
Teenagers, adolescents, youth and young people
• Most teenagers are healthy and happy. Historically, children were legally viewed as prop-
• Like younger children, adolescents continue to develop erty items of their parents. The law now recognizes
physically, emotionally and cognitively. All consultations the growing maturity of adolescents and their capac-
with young people should involve an assessment of ity to make independent choices and judgements on
adolescent development. matters affecting their future, including their rights to
• As children mature through adolescence, they are autonomy and privacy in health care, even when they
exposed to greater health risks from involvement in
behaviours with significant health consequences, such as are not legally mature (i.e. under the age of 18 years
drugs and alcohol and sexual intercourse. in Australia). This legal view is consistent with the
• The burden of illness in youth differs from younger children medical evidence. Studies demonstrate that concerns
and from adults, being disproportionately affected by about confidentiality are a major barrier to young peo-
mental health problems, the consequences of drug and ple accessing health services. Once young people have
alcohol use, accidents and self-harm, and complications accessed health-care services, they are more willing to
of sexual activity.
disclose honestly important information about health
• Healthy adolescent development results from complex
interactions between risk and protective factors within the risk behaviours, seek health care and return for
individual, family, peers, school and community. ­follow-up when they understand a service is confiden-
133
tial. Thus, attention to confidentiality should be as
 3.11 SOCIAL AND PREVENTATIVE PAEDIATRICS

much a cornerstone of clinical relationships between

doctors and adolescents as it is with adults. Nearly A pregnancy test revealed that Jennifer was indeed
1 in 10 adolescents report not visiting their health- pregnant. The doctor had a brief discussion about available
care provider in the previous year – despite wanting to options and offered to help Jennifer tell her mother, to
discuss briefly the various options with her mother and to
do so – because of the fear that their parents would arrange for them to come back for a more detailed visit.
find out. However, many adolescents appreciate the Jennifer agreed with this plan. Although her mother was
opportunity to share sensitive information with their very surprised and upset, these discussions were able to
parents (even when it has been obtained confidentially take place, as well as discussion about the importance of
by the doctor), as long as this is handled sensitively, future contraception. The doctor also asked about Jennifer's
and they are actively engaged in deciding what will (or partner, because of child protection concerns. Her partner
was her 16-year-old boyfriend.
will not) be shared.
Jennifer and her mother left the surgery relieved that
Judgement about whether to maintain confidential- it was ‘out in the open’ and having been made aware
ity in consultations with younger adolescents is linked of the various supports and available services. At a later
with assessment of maturity. In deciding whether a appointment Jennifer said she would never have been able
person is competent or mature enough to consent to to say anything at the time without seeing the doctor alone.
medical treatment, a doctor must decide whether the As they went out of the door, Jennifer turned to her mother,
young person is able to understand the nature of the saying, ‘What are we going to tell Dad?’
problem, the nature and side-effects of any proposed
treatment, and other treatment options.
The doctor can accept consent provided that the
treatment is in the young person's best interests and The clinical approach
the treatment is not likely to have serious conse-
quences. For more complex or contentious procedures, Meeting the patient
doctors must balance several factors in making a deci- Many younger adolescents, especially those with chronic
sion, including the age, maturity and characteristics of illness, will only have consulted doctors together with
the adolescent, the gravity of the presenting illness and their parents and may therefore not expect anything
treatment, and family issues. It is important to remem- else. Doctors can actively promote engagement with
ber that all doctors have a legal and ethical duty of medical consultations by reinforcing that the young
confidentiality to competent young people. This duty person, not the parent, is the patient. The doctor
should be breached only in serious situations such as should introduce themselves to the young person first,
risk of self-harm or suicide, or in cases of suspected then ask them to introduce the accompanying adult.
abuse, as well as some other exceptions discussed This immediately signals to the young person that they
below. Doctors should become familiar with the spe- have some control in the consultation. First impres-
cific laws on this issue in the state or region where they sions matter.
practise. In all Australian states and territories, anyone
over the age of 15 years can have their own Medicare
card, and a doctor may bulk-bill a consultation with- Confidentiality
out advising the parents. Following introductions, an important step is to
explain the confidential nature of health consultations
as it cannot be assumed that young people understand
Clinical example or expect this. We encourage a confidentiality state-
ment to be made when parents are also in the room – as
Jennifer, a 15-year-old girl, was taken to her
they also need to know. A brief discussion of the limits
general practitioner by her mother because
she had been moody and tearful for the last
of confidentiality is also encouraged (the main limita-
few weeks. She had also been missing school tions are risk of suicide or self-harm, risk of homicide
regularly and often complained of an ‘upset stomach’ in the or harm to others, and any disclosure of abuse). With
mornings. On direct questioning, Jennifer offered very little practice, this only takes a minute or so:
information about the nature of her symptoms or possible
causes. The doctor then asked Jennifer's mother to leave the ‘What we talk about is confidential, which means
room for a short time, after having explained confidentiality I won't discuss it with anyone else without your per-
and its limitations. After the assurance of confidentiality and mission. There are three exceptions to this, which
by taking a psychosocial history, Jennifer felt comfortable are if I am worried that you are at risk of harm-
enough to tell the doctor that she had had unprotected sex ing yourself, at risk of harming others, or are being
about 5 weeks ago, had not had a period since, and was abused and are not safe. If these things come up we
worried that she might be pregnant. She had been too will deal with them together. I will involve you in
134 fearful to tell her parents, stating ‘They would kill me!’ any decisions that need to be made around who we
need to talk to.’
 CARE OF THE ADOLESCENT 3.11
Negotiating for time alone range of behaviours and mental health states that have
­significant health implications. This approach to taking
Seeing doctors alone for at least part of the consulta-
a psychosocial history extends the consultation beyond
tion is a mechanism by which, over time, young peo-
treatment of the presenting complaint to a greater
ple can develop the confidence to speak for themselves.
focus on more preventative and health-promotional
The metaphor of ‘bicycle training wheels’ can be help-
aspects of common behaviours. Thus, in addition to
ful to highlight to parents and young people alike that
being a framework for psychosocial assessment, it is
adolescents need practice consulting with doctors by
equally useful as a method of engaging adolescents in
themselves. The adolescent years are an ideal time to
the medical consultation, a mechanism for identifying
practise, when there is still ‘back-up support’ avail-
both risk and protective factors, and a framework for
able from parents. When framed this way, most parents
delivering relevant anticipatory counselling.
appreciate the opportunity for young people to spend
This approach to psychosocial assessment should be
time alone with the doctor and value the opportunity
explained to the young person, as it may be confusing
for their son or daughter to discuss sensitive issues. It is
to be asked about personal behaviours such as drug use
important, however, not to undermine the role of par-
when seeing a doctor for asthma. One approach is to say:
ents and to make sure that they are actively included.
This is commonly done by inviting them back at the end ‘When doctors do check-ups with older people
of the consultation to discuss the diagnosis and man- they measure physical things like blood pressure.
agement, having previously negotiated with the young Younger people are more likely to be physically
person whether anything needs to be kept confidential. healthy, but their health can be affected by different
This is generally not difficult for new consultations. behaviours, which I'm now going to ask you about.
However, it can be harder where a family doctor or This is something we do with all young people.’
paediatrician has seen a child together with the parent
There is no need for the HEADSS topics to be dis-
for many years. There is no set age to start seeing young
cussed in any particular order, although generally
people alone within medical consultations. However, it
clinicians prefer to start with less sensitive questions
is generally appropriate to offer some time alone from
and proceed to more personal topics. For this reason,
about the age of 13–14 years. Initially, the young per-
many clinicians actually start with questions about
son may be seen alone for only a short time. Gradually,
education, as questions about home can be challeng-
however, more time will be spent with the young person
ing when young people have complex family arrange-
alone and less time with the parents and young person
ments. At times, it will not be possible to complete a
together, as young people develop the skills that enable
full HEADSS assessment at the first consultation. It
them to be more independent within consultations and
is, however, important to ensure that the issues are dis-
more capable of managing their health condition.
cussed at a later date, and recurrently over time.
Most doctors discuss the presenting complaint first
and then move on to the psychosocial assessment
Psychosocial screening (HEADSS)
using the HEADSS framework. It is often useful to
Health risk screening is an important component of remind young people about confidentiality again at
the clinical care of all adolescents. One approach to this stage and to also let them know that they don't
health risk screening has become known by its mne- have to answer questions if they feel uncomfortable.
monic, HEADSS. This approach, first described in the It is important to remember to ask about and
USA in the early 1980s, helps clinicians to remember discuss protective as well as risk factors. The use
the key aspects of the psychosocial history that are of open-ended questions is encouraged to engage
important to assess: young people more actively beyond simple ‘yes or no’
H – Home responses. One of the main reasons for the success of
E – Education/Employment, Exercise and Eating the HEADSS approach is that, when used sensitively,
A – Activities (peer-related) it empowers adolescents to discuss their health seri-
D – Drug Use ously with a professional. It also provides opportu-
S – Sexual Health and Sexuality nities for questions that would not usually be asked
S – Suicide, Self-harm and Safety of doctors. Discussions such as this are uncommonly
The HEADSS mnemonic has been consistently added initiated by young people, but the majority partici-
to, with an extra ‘E for eating and exercise’ in recogni- pate willingly when given the opportunity to do so
tion of increasing rates of overweight and disordered confidentially. This approach gives the doctor an
eating, for example. important opportunity to frame what is going well
The HEADSS framework for psychosocial assess- with young people, to identify areas of concern, to
ment facilitates a holistic approach in which the engage in anticipatory counselling and to develop a
135
­doctor can engage the young person in discussing a plan of action.
 3.11 SOCIAL AND PREVENTATIVE PAEDIATRICS

­ rofessional and skilled rather than being ‘cool’ or act-

p
Practical points ing like a friend.
It is important to ask questions in a way that makes
A summary of psychosocial screening (HEADSS) no assumptions. ‘Who lives at home with you?’ and
• Home ‘Are you in a relationship?’ are preferable to questions
• Where do you live? that may assume a nuclear family and heterosexuality.
• Who lives with you? It is also best to avoid questions that can be answered
• Who are you closest to at home? yes or no. Asking ‘What year are you in at school?’ is
• Is there anyone at home you can talk about personal better than ‘Do you go to school?’
issues with?
Questions about activities are a good opportunity
• Education and Employment
• Do you go to school? What year are you in? to focus on peer relationships. Questions about future
• What are your grades like? life and career goals are a useful approach to explor-
• Have you changed schools recently? ing cognitive maturation. In questioning about drug
• Do you have many friends at school? use it is important to normalize experimentation with
• Do you have any problems with bullying at school? drugs without condoning drug use. Reference to the
• Do you work? third person can be a helpful technique, such as: ‘Some
• How many hours a week?
• Eating/Exercise young people your age try drugs. What have been the
• Has your weight changed recently? experiences in your group of friends? And what about
• Have you dieted in the last 12 months? you?’ Most clinicians start by asking about cigarettes
• Does your eating ever seem out of control? and alcohol. Questions about what sexuality educa-
• How much exercise do you do per week? tion the young person has received at school can be a
• Activities helpful starting point for this sensitive topic, or about
• What do you and your friends do for fun?
whether a teenage girl has been vaccinated against
• Do you play sport?
• Are you in any clubs or groups? human papillomavirus (HPV). Other approaches
• What are your hobbies? include normalizing statements, such as: ‘Many young
• Drugs people your age are starting to develop more mean-
• Do you smoke cigarettes? ingful relationships. Are you in a relationship at the
• Do you drink alcohol? moment?’ A brief reminder of confidentiality and a
• Do you use any other drugs? reiteration that your interest is health-related some-
(If yes to any of the above then need to quantify)
times puts nervous teenagers at ease when moving to
• Sexuality
• Do you have a partner currently? OR Are you in a questions about drugs and sexuality.
relationship currently? Without being judgemental, it is reasonable to com-
• Have you been sexually active? ment supportively on healthy choices that the young
• Have you been pressured into sex? person may describe. Some young people report that
• What do you understand by the term ‘safe sex’? they would simply prefer to be asked directly about
• Suicide and depression issues like sexual activity and safe sex (contraceptive
• How would you describe your mood lately? (Can ask for
score out of 10) and condom use). A degree of judgement is always
• Are you ever sad or tearful for no reason? required as to an adolescent's maturity and stage of
• Do you have any trouble sleeping? development.
• Have you lost interest in things you used to enjoy? The final S in HEADSS refers to suicidality and
• Have you ever felt like hurting yourself? safety. It is perhaps better thought of as a depression
• Have you had any suicidal thoughts? screen but it is important to ask directly about sui-
• Have you ever made a suicide plan?
cidal ideation and plans, and to act promptly if there
• Have you previously attempted suicide?
• Safety are concerns. Contrary to claims that discussing such
• Have you ever been seriously injured? issues ‘puts ideas into their heads’, talking about sui-
• Do you ever drive with people who have been drinking or cide does not increase suicidal behaviour in young peo-
taking drugs? ple who are not suicidal but can be protective in those
• Is there any violence at home? who have been thinking of it but have not discussed
• Have you ever been physically or sexually abused? it with anyone. Questions about safety from abuse of
any sort, particularly sexual abuse or violence, should
also be asked. Even if no disclosure is made, it is sug-
In consultations with young people, doctors are gested that the young person be informed that shar-
urged to be respectful, unhurried and non-judgemental. ing this information with others is important and that
It is not a good idea to try to use current slang or to you would always be available to talk to them about
be ‘chummy’ with adolescents. Young people, like all this and any other issues they would like to raise in
136
patients, are more concerned that their doctors are the future.
 CARE OF THE ADOLESCENT 3.11
Physical examination There is a greater prevalence of young people with
chronic illness in our community because of improved
Adolescence is a time of increased sensitivity about one's
survival rates from various paediatric illnesses that, as
body and appearance in general. Thus, even a ‘routine’
recently as 20 years ago, were associated with extremely
physical examination may be a confronting prospect for
poor prognoses. Examples include childhood leukae-
a young person. It should therefore be conducted in a
mia and other cancers, congenital heart disease and
professional, respectful and sensitive manner.
cystic fibrosis. Improved medical technologies result in
This must obviously be balanced with the need for
the survival of more young people with complex and
a thorough clinical examination. In all cases, measure-
severe health-care needs who are reliant on advanced
ments of height, weight and pubertal assessment are rec-
technology and multifaceted health-care support. In
ommended. Ensure that the patient will not be exposed
addition to improved survival, most developed coun-
if someone else enters the room by using curtains or
tries have experienced a true increase in the incidence
screens. Avoid unnecessary exposure of the body. When
of certain conditions, such as asthma and allergy, dia-
a particular area must be examined, the judicious use of
betes, obesity, mental disorders and leukaemia.
clothing and sheets is recommended to keep other areas
It is important to remember that young people with
covered. A screening test of pubertal assessment can be
chronic illness are first and foremost adolescents.
made by adolescent self-report of the standard pictures
Thus, while it might be assumed that adolescents with
of Tanner staging on growth charts and confirmed clin-
chronic illness would not add further risks to their
ically if there are specific concerns.
health profile by engaging in risky behaviours, there is
Although not a legal requirement, the use of chap-
no evidence that this is the case. Instead, there is some
erones for a physical examination is increasingly
evidence that young people with chronic illness might
recommended, especially when male doctors are
be even more likely to participate in health risk behav-
examining female adolescents, in order to make the
iours than their otherwise healthy peers.
patient feel more comfortable and reduce allegations
Furthermore, many young people with chronic ill-
of misconduct.
ness have a greater attributable risk from these behav-
iours. For example, in addition to the universal risks of
smoking, smoking in young people with asthma, cystic
fibrosis or diabetes mellitus can be readily conceptual-
Practical points
ized as being ‘more risky’ in terms of their underly-
ing health condition. Another example is the greater
Engaging young people in clinical consultations
attributable risk from alcohol use in young people with
• Introduce yourself to the young person and then the
parent. diabetes mellitus or epilepsy.
• Explain confidentiality, including limitations, to all Adolescent development is not a simple linear jour-
adolescents and families. ney but is a dynamic process that is experienced dif-
• Be relaxed and non-judgemental. ferently by each individual. Thus, chronic illness and
• Avoid jargon or slang but use simple language that the disability can affect adolescents in diverse and com-
young person will understand.
plex ways. Physical growth and pubertal development
• See the young person alone for part of each consultation.
can be delayed, although pubertal development can
• Psychosocial screening should start with less sensitive
questions before proceeding to more personal also commence earlier (precocious puberty) in other
questions. conditions (e.g. spina bifida). In addition to these uni-
• Be sensitive and respectful during physical examinations. versal elements of adolescent growth and develop-
ment, adolescence is a time where various physical
changes commonly become more significant (e.g. scars
from previous surgery such as cleft lip repair or infant
bowel obstruction, longstanding clubbing or scoliosis,
Chronic illness or the more acute side-effects of steroids) as cognitive
Children and adolescents with special health care maturation brings greater capacity for both the imagi-
needs have been defined as those who ‘have or are at nation of an ideal body as well as critical comparison
increased risk for a chronic physical, developmental, with one's peers. This sense of physical inadequacy can
behavioural or emotional condition requiring health be associated with complex adjustment problems in
and related services of a type beyond those required terms of body image, self-esteem, bullying, peer rela-
by children generally’. According to this definition, tionships and mental disorder.
15–20% of children and adolescents have a signifi- Some adolescents with chronic illness and disability
cant, ongoing health-care need. The prevalence of spe- may be less well developed socially because of extended
cial health-care needs is higher in adolescents than in hospital admissions over many years, reduced parent
137
younger children. expectations or reduced opportunity for normal peer
 3.11 SOCIAL AND PREVENTATIVE PAEDIATRICS

relationships. More specifically, certain chronic illnesses Towards self-management

or disabilities can be associated with reduced cognitive
Adolescents with chronic illness and disability are nat-
or intellectual functioning. As a result, these young
urally interested in and able to play a greater role in
people may be relatively more reliant on their parents.
looking after themselves as they mature. However, the
Regardless of the explanation, poor peer relationships
skills for self-care do not develop magically but must
and fragile educational engagement can reduce educa-
be practised by young people and supported by their
tional achievement and limit career opportunities and
parents and health professionals.
future socioeconomic status.
Little is known about the age at which adolescents
Chronic illness in adolescents can also affect wider
begin to take on more responsibility for different ele-
family functioning, including sibling experiences and
ments of self-care (such as taking medications, making
parent marital relationships. Attention to the wider
appointments or seeking care when unwell). Further,
family and its functioning is an important part of
it is not known what effect disease severity or intellec-
looking after adolescents with chronic illness and
tual capacity has on these practices. In practical terms,
disability.
health professionals should encourage parents to sup-
port the emerging capacity for self-care in their children
as they mature through adolescence. Health profes-
sionals can do this by educating the family about ado-
Clinical example lescent development. For example, many parents can
Karen, a 19-year-old woman with cystic fibrosis,
become frustrated when their teenager no longer sim-
was soon to be transferred to a specialist adult ply ‘does what they are told’ in relation to adherence
cystic fibrosis centre for ongoing care. However, with requests by parents and doctors to ‘take their med-
during the last few admissions, concerns had icine’. Informing parents of the developmental appro-
been raised about her mental state as well as the fact that priateness of this behaviour and of ways of making it
she had twice discharged herself early against medical more likely that young people will adhere to treatment
advice. The adolescent team was informed that her usual
regimens is an important educational role for health
treating team felt her mood was ‘pretty flat’.
In taking a detailed psychosocial history, the adolescent professionals. Promoting greater self-management in
team identified that Karen had discharged herself against young people with chronic illness is a specific part of the
advice as she had a part-time job and an active social broader ‘package’ of working with young people that
life. These were more important to her than her health, as includes understanding adolescent development, health
another few days ‘never made any difference’. It emerged risk screening, appreciation of the value of confidential
that Karen had told no one outside of her immediate family health care, and understanding the transition to adult
of her illness, including her current boyfriend. Her workplace
health care. This can be summarized as the provision of
was also unaware she had cystic fibrosis or had been
admitted to hospital. Until recently, she had not required developmentally appropriate health care to adolescents.
hospitalization for some years. She had hidden the recent
admissions by keeping in touch with friends by mobile
phone. She finally revealed that the main reason for keeping
her illness secret was that a previous boyfriend had broken Practical points
up with her when she had told him about her cystic fibrosis.
Karen's depressed mood was confirmed and was thought Self-management in adolescents with chronic illness
in most part to be due to the stress of living a ‘double life’. • Ensure parents appreciate that, although their love
Although, at least superficially, she denied the severity of her shouldn't change, their role in managing their teenager's
respiratory status, it was considered that the implications health will change gradually with time.
of her lung disease (there had recently been discussions • As young people mature, they should be encouraged to
about the role of lung transplantation) were likely to have take on more responsibility for managing their health, with
contributed to her depressed mood. She was very poorly less reliance on their parents for day-to-day care.
adherent with physiotherapy and regular clinic review, but • Seeing young people alone for at least part of the
had better adherence with antibiotics. consultation will help build young people's confidence
As a result of these and other discussions, Karen was and skills in communication with doctors and health
supported in revealing her illness to some close friends professionals.
and work colleagues, who were relieved there was an • Normalize the challenges of adherence in adolescents.
explanation for her significant coughing and supportive of Have realistic expectations.
her taking time off for treatment. There was further frank • Rather than focusing on problems, work with the young
discussion about the severity of her illness, and Karen felt person to develop practical solutions.
gradually more able to discuss aspects of day-to-day care, • Short-term adolescent-focused goals are more likely to
including adherence with treatment and transfer to the adult motivate self-care than longer-term health-orientated goals.
clinic, as well as the possible need for transplantation. Her • Development of self-management skills is an important
lung function stabilized. part of young people's transition towards adult health care.
138
 CARE OF THE ADOLESCENT 3.11
Adherence with treatment with their medication, some young people report that
parent ‘nagging’ makes them less likely to want to
The terms ‘adherence’ and ‘compliance’ are often
take their medication responsibly! Negotiating a short
used interchangeably, but there are subtle distinctions
period of ‘no nagging’, especially when combined
between them. Compliance is defined as the extent to
with strategies to promote the development of treat-
which a patient is obedient and follows the instruc-
ment routines (consider a diary chart for a week, or
tions and prescriptions of health professionals. In
mobile phone reminders), can be helpful. Following
contrast, adherence is defined as a more active, vol-
such approaches, some young people are sobered into
untary and collaborative involvement of the patient
understanding how much they need their parents to
in a mutually acceptable course of behaviour aimed
assist them, and some parents realize that their teenag-
at producing a therapeutic or preventative outcome.
ers can actually manage quite well!
Most adolescents, like adults, wish to be included
Attention to adherence should be part of every con-
in the decision-making process regarding treatment
sultation with teenagers.
options. The main practical implication of using the
term ‘adherence’ denotes that adherence behaviours
are not exclusively the responsibility of patients but
are a reflection of the doctor–patient relationship Clinical example
and the support that young people receive from their
families. Paul is a 14-year-old boy with attention-deficit/
hyperactivity disorder (ADHD) who had been
Adolescents are commonly conceptualized (and
treated with stimulant medication for many
judged) as being ‘non-compliant’. Like adults, many years. His mother was concerned because he
adolescents struggle to achieve sufficient adherence had recently stopped taking his medication and his school
with treatment. However, there is little evidence that marks were deteriorating quite rapidly. She said that Paul
adherence in adolescents is substantially worse than was impossible to talk to about it, as he just shouted at
in adults. Indeed, it is worth remembering that many her when she tried to broach the subject. Paul somewhat
reluctantly admitted that the medication helped his
studies show that adherence to treatment in adults with
concentration but he didn't care about educational success
chronic illness is as low as 50%. Young adults can find so he didn't feel there was much point in taking it.
adherence behaviours especially challenging as parents Paul was referred to an adolescent specialist, who saw
by this stage are generally less actively involved. him alone. The specialist identified that Paul was being
Strategies to improve adherence in adolescents need teased and bullied at school, particularly about his ADHD,
to take into account the challenge of adolescent devel- which had contributed to him stopping taking the lunchtime
opment and the ways in which parents can both sup- dose at school. He also hated the way his mother nagged
him in the morning to take his tablets as though he were a
port and hinder adherence behaviours. Young people
‘stupid little kid’. Paul revealed that his mood was very low
are less influenced than adults by the concept of health and that during the last few months he had occasionally
as a general life goal, or by specific longer-term health wished he was dead. He had no active suicidal plan. After
risks. For example, adults with diabetes may be con- a discussion with Paul and his mother, he was changed to
cerned about long-term complications, but young peo- a long-acting form of the medication that had to be taken
ple are generally more influenced by things in the ‘here only in the morning. Discussions were held about how Paul
and now’. For adolescents, rather than threats to long- could take greater responsibility for remembering to take the
medication, which included a conversation about medication
term health, development of routines and a focus on
routines, reminder charts and ‘dosettes’.
short-term goals are more likely to be influential. After a few months of regular follow-up, Paul's mood and
Questioning adherence behaviours in a normaliz- school performance gradually improved. Initially he was still
ing and non-judgemental way is helpful. The phrasing a bit forgetful about taking the medication but, with the help
‘Many people I see your age have trouble fitting their of his mother, he developed a morning bathroom routine
… (medication/treatment/monitoring) into their day. that included his medication. His mother no longer ‘nagged’
him but instead ‘checked in’ now and then to monitor the
Firstly, are you taking any? … Great….Tell me, which
situation. Paul and his mother were communicating much
dose do you find hardest to remember, the morning better about this and other issues.
or the evening dose?’ can readily lead to greater dis-
cussion about the medication itself, and about routines
that they have or do not have around different medica-
tion. This approach can help young people find their
Transition to adult health care
own solutions. Questions need to be specific for each
different aspect of the treatment regimen. An important component of self-management for
Many young people feel that their parents constantly those young people who will continue to require spe-
‘nag’ them about their medication. Notwithstanding cialist health care as young adults is that their care is
that the young person might need parental support transferred from a paediatric to an adult health-care 139
 3.11 SOCIAL AND PREVENTATIVE PAEDIATRICS

setting. Managing young adults in an adult setting ­ etabolic disorders, intellectual disability) or the lack
m
promotes their ongoing development and indepen- of multidisciplinary services within the adult health-
dence, whereas retaining their care in a paediatric set- care setting. Funding may perversely reduce the desire
ting is likely to have the opposite effect. to transfer care, for example if elements of health
In relation to the provision of health care to ado- care such as total parenteral nutrition or dressings are
lescents with special health-care needs, transition is funded within the paediatric but not the adult setting.
defined as ‘the purposeful, planned movement of Lack of established communication channels between
young people with chronic physical and medical con- facilities and health-care providers may be another
ditions from child-centred to adult-oriented health- barrier to transferring care.
care systems’. Thus, the physical transfer of care There is no single model or ideal transition model
from one setting to another is part of a broader pro- to follow. Rather, a set of principles has been devel-
cess of transition to adult health care, which builds oped that promote timely transfer to adult settings.
on supporting the young person to gain the requisite Preparation is a key component of transition plan-
self-management skills. ning, which should start years before any planned
There are many barriers to transition to adult health physical move. Each individual should have a health
care, with a significant proportion being ­attitudinal. professional in the paediatric setting who has the pri-
The young person may fear the unknown and be reluc- mary responsibility for developing a transition plan.
tant to leave the security of a system and a group of The family doctor or primary health-care provider is
health professionals that they have come to know and an important link for continuity for the patient and
trust. Parents may be concerned that they will be ‘shut family, and should be actively involved.
out’ of the decision-making process in the adult setting. Although it has been argued that transfer to adult
This fear may be more acute if parents have continued settings should not occur until the young person has
to be very actively involved in m ­ edical ­consultations the skills to function in an adult service, it can be
without the young person starting to take on greater equally argued that young people may develop the
responsibility. required skills only once they experience a more chal-
Some paediatricians (and parents) fear that the lenging environment. If possible the transfer should
young person will receive less optimal care in the adult occur when the adolescent's health is in a relatively sta-
setting. Others have trouble ‘letting go’, especially if ble phase.
they have looked after the young person for many There is no correct age for transfer, and different
years. Some adult physicians may fear taking on ‘pae- approaches have developed in different countries. In
diatric’ patients, as they may be uncomfortable com- Australasia, most children's hospitals plan to transfer
municating with patients in this age group. young people to the adult setting once they have com-
Other barriers are more structural, such as the lack pleted their secondary education, commonly in their
of specific expertise (e.g. congenital heart disease, 18th or 19th year.

140
 Gynaecology
Sonia R. Grover
3.12
Gynaecological problems in childhood are usually
minor but not infrequent. Common gynaecological
Congenital anomalies affecting the genital tract can problems in pre-pubescent girls
be seen in association with endocrine and congenital
anomalies, although quite a number do not p ­ resent Labial fusion or adhesions
until the girl fails to go through puberty, menarche Labial fusion or labial adhesions are:
does not occur, or she develops significant atypical • not present at birth but may develop within a
period pain. Although surgical correction to repro- few months; the onset correlates with the decline
ductive tract anomalies may be undertaken as part of in maternal oestrogen effects on the skin of the
the correction of these anomalies, for example in girls newborn and infant
with congenital adrenal hyperplasia, bladder extrophy • thought to occur secondary to skin irritation
or cloacal anomalies, follow-up and possible interven- • relatively common in childhood
tion from the genital tract perspective may be required • often first noted by the maternal and child health nurse.
at the onset of puberty, when referral to a gynaeco- As persistent labial adhesions are not seen in a­ dolescent
logist with experience with these anomalies may be girls, it can be safely presumed that the natural history
appropriate. of labial adhesions is spontaneous ­resolution. In the
Gynaecological problems in adolescence have some past, the use of lateral traction, ­surgical ­division, or the
similarity to adult problems, although the approach to use of topical oestrogen cream was ­recommended, but
examination, investigation and management are often there is a high relapse rate with these approaches. As
very different. labial adhesions rarely cause any significant symptoms
apart from occasional dribbling p ­ost-micturition,
no intervention is necessary and parents should be
Practical points reassured.

• Vaginal examination is inappropriate in paediatric

patients. Ultrasonography or examination under
anaesthesia (depending on the clinical problem) will Clinical example
provide the required information.
A 3-year-old girl was noted by the maternal
• For adolescent patients, vaginal examination is
infrequently undertaken unless they are sexually active and child health nurse to have an ‘abnormal
and have given consent for this examination. perineum’. The possibility of an absent vagina
was raised, and the mother was advised to take
• Transabdominal ultrasonography will almost always
provide the necessary information in the adolescent her daughter to the doctor.
population. On examination of the perineum, the urethral and vaginal
openings could not be visualized, as the labia appeared to
be joined in the midline. A midline stripe was visible and the
general practitioner was able to reassure the parents that
the diagnosis was labial adhesions, which would resolve
spontaneously. Her parents requested further reassurance
Gynaecological problems that the vagina was actually present, as they had been
in neonates reading about vaginal agenesis on the internet. Further
reassurance was given that vaginal agenesis is a rare
• Vaginal bleeding – the decline in maternal problem – and that investigations by any imaging technology
oestrogens within the first week or 2 of birth – may to identify a vagina in this age group were unreliable. Instead
arrangements were made to review the girl when she was
result in a small vaginal bleed. No investigations are
older.
required. Review 3 years later revealed that the adhesions had
• An imperforate hymen, may present as a perineal almost completely resolved, and the urethral and vaginal
lump. The hydrocolpos can be drained and opening with hymenal edge were now visible. 141
corrected with surgical incision of the hymen.
 3.12 SOCIAL AND PREVENTATIVE PAEDIATRICS

Vulvovaginitis Occasionally, small foreign bodies can be flushed

from the lower vagina using a syringe and saline, but
• Occurs in the context of low oestrogens, with thin, usually a general anaesthetic to enable a careful exami-
atrophic vaginal and vulval skin.
nation is required.
• Is seen in girls from early childhood through to the If itch is a significant component of the symptoms:
establishment of puberty.
• pinworms need to be excluded
• The normal flora in the vagina of young girls is
• eczema superimposed on the vulvovaginitis may be
mixed bowel flora (candida is not found in the non-
present. Look for evidence of generalized eczema.
oestrogenized young girl).
The approach to management is the same as for
• Overgrowth of the bowel flora in the vagina is vulvovaginitis, with the addition of topical steroids
thought to irritate the atrophic skin, causing a
to settle the eczematous component.
discharge which then irritates the vulval skin.
• lichen sclerosis, with whitened skin changes and
• The affected skin is primarily the contact surfaces superficial splitting of skin, may be present,
between the labia.
secondary to the vulvovaginitis but can also
Symptoms are usually intermittent and consist of:
be due to a relatively uncommon autoimmune
• offensive vaginal discharge skin problem. In the presence of vulvovaginitis
• skin irritation symptoms and findings, the management of lichen
• burning with micturition. sclerosis is as for vulvovaginitis, with the addition
The possibility of sexual abuse needs to be considered
of topical steroid cream. A more potent steroid may
in a child with vulvovaginitis, but other symptoms or
be required for a short duration. Betamethasone
problems are usually present (see Chapter 3.9).
(Diprosone) and methylprednisolone (Advantan)
Investigations cream are often best tolerated, with others having
irritant components in the cream or ointment base.
• Swabs are rarely required as no specific organism is
found, only mixed bowel flora.
• Take swabs when there is a profuse discharge or Vaginal bleeding
skin erythema extends beyond the contact surfaces
of the labia majora. In these cases a single organism • Foreign body (see above)
may be responsible for the problems and specific • Precocious puberty as a result of the ovarian
activity (see Chapter 19.1)
antibiotics may be required.
• Rare childhood lower genital tract malignancy –
Management rhabdosarcomas (sarcoma botryoides); may
• Application of a simple barrier cream (such as also present as sultana-like polyps at the vaginal
zinc–castor oil or Vaseline). introitus.
• Bathing – the addition of vinegar (half a cup to a
shallow bath) is often advocated. Vaginal pain
• Parents need reassurance that the natural history is
intermittent recurrence until puberty. Distressing vaginal pain waking a pre-pubertal girl at
• In the presence of this skin irritation it is advisable night is likely to be worms. The worms get ‘lost’ in
to avoid other potential irritants such as bubble the vagina and when they crawl on the hymen, which
baths and soaps. is very sensitive in this age group, they cause signifi-
• Faecal soiling as a consequence of poor toileting cant pain.
habits may also be an issue. Treatment is as for worms – but additional courses,
• When the skin irritation extends beyond the contact usually once weekly for 3 weeks, are required.
surfaces of the labia, additional irritants such as
prolonged periods in wet bathers may have an
aetiological role.
Adolescent gynaecology
Overview of puberty, adolescence
Blood-stained vaginal discharge and the menstrual cycle
Vaginal foreign body needs to be considered in the • The average age of menarche is 12.5 years.
presence of a persistent vaginal discharge, particularly • Although breast bud development is usually the
if blood stained. Vaginal foreign bodies are most often first sign of puberty, followed by pubic and axillary
found to be a small amount of toilet tissue, although hair, variations to this can occur (see Chapter 19.1).
142 occasionally there may be beads and other small • Breast development may be asymmetrical initially
objects that can be seen on ultrasonography. and may be mistaken for a ‘breast lump’.
 Gynaecology 3.12
• In general, the time from commencement of breast with polycystic ovary syndrome being the ­commonest.
development to first menses is less than 4 years. Scant pubic and axillary hair in the presence of good
• Absence of menses at age 16 years is suggestive of breast development is seen in complete androgen
the need for further investigation. insensitivity syndrome. Palpable gonads (testes) may
• With the onset of puberty, multiple (15 to 20) be found in the groin or labia, but they may also be
follicles can be seen on ultrasonography; this is intra-abdominal.
normal. The presence of normal secondary sexual charac-
• An ovulation cyst or follicle can be 3–4 cm in teristics and intermittent abdominal pain suggests that
diameter. On ultrasonography this will appear as a menstruation may be occurring but an o ­ bstruction
simple ‘cyst’, which can be expected to resolve and is present. The commonest cause is an imperforate
disappear during the next 2–6 weeks. It is important hymen, which can be confirmed simply by viewing
to reassure young women that this cyst is normal the perineum while applying gentle pressure to the
and demonstrates that the reproductive system is abdominal mass. Pelvic ultrasonography can assist in
functioning normally. confirming the presence of cryptomenorrhoea and in
• Ovulation can be associated with some pain clarifying the level of the obstruction. The obstruction
(Mittelschmerz or mid-cycle pain). Occasionally, can involve a transverse vaginal septum or segmental
haemorrhage into an ovulation cyst can occur, vaginal atresia, which will require referral to a centre
giving rise to a more complex appearance of the with some expertise in these uncommon anomalies.
cyst on ultrasonography (haemorrhagic corpus Uterovaginal agenesis is absence of the vagina and
luteum). uterus. Ovarian function is normal, as are all second-
• Irregular menses in the first 2–3 years is common ary sexual characteristics. The creation of a vagina
and normal because of anovulation. is most often achieved with the use of dilators (and
Consultation with young teenage girls needs to be sexual activity). In the absence of a uterus, carrying
undertaken with careful consideration for their a pregnancy is clearly impossible, although surrogacy
developmental and cognitive stage, recognizing that can now be offered, as ovarian function is normal.
­consultation without a parent may be essential to
explore relevant issues (see Chapter 3.11).
Adolescent health risk behaviours need to be Clinical example
­identified, as they can impact on reproductive health.
Eating disorders may be responsible for menstrual At the age of 16 years, Tanya was brought to see
problems (amenorrhoea and infrequent menses); her general practitioner because of delay in the
onset of menses. Her breast development began
smoking may influence choice of medications; sexual
at the age of 12 years. She was a state champion
activity raises concerns regarding the need for contra- gymnast and trained intensively 7 days a week. She was of
ception and risk of sexually transmitted infections; slight build. Examination revealed normal breast development
and drug and alcohol intake significantly impacts on at Tanner stage 3, and pubic hair at Tanner stage 3.
the chances of risky, unsafe sexual activity. The provisional diagnosis was hypothalamic hypogonadism
secondary to the level of physical activity. Follicle stimulating
hormone (FSH), luteinizing hormone (LH) and oestrogen
Delayed onset of menses – primary concentrations were found to be low. Thyroid stimulating
amenorrhoea hormone (TSH) and prolactin concentrations were normal.
Pelvic ultrasonography demonstrated a small normal uterus.
The onset of periods usually correlates with ­exposure Tanya was reassured that there was no significant
to oestrogens over some months, during which time underlying problem and that her relatively low weight
breast development, pubic hair and axillary hair combined with her exercise level was the cause for the delay.
growth have occurred. Assessment of the time of onset
of breast development and onset of pubic and a­ xillary
hair growth is useful to assess whether progression
through puberty has been normal. It is important to Practical points
establish the general health of the young woman as
well as the activities in which she participates. • In the presence of a problem that has an impact on the
If the young woman has no secondary sexual long-term reproductive health of the young woman, care
­characteristics, the investigations are guided by the and sensitivity with respect to the impact of this diagnosis
potential causes of delayed puberty (see Chapter 19.1). on her self-esteem are critical.
Assessment of the presence and extent of hair growth • Careful use of appropriate language, open discussion and
disclosure, psychological support, and the opportunity to
can give valuable clues to the diagnosis (see hirsutism; become involved in a support group are all considered
see Chapter 21.2). Excess hair can be familial and may important components in care. 143
be related to ethnic origin or due to ­hormonal causes,
 3.12 SOCIAL AND PREVENTATIVE PAEDIATRICS

Irregular periods • Changing soaked super pads (or tampons) 2-hourly

is probably a reasonably heavy period.
The pattern of the periods can be quite irregular during
the first few years after the onset of menarche. This can
• Anaemia (in the absence of other dietary or
gastrointestinal problems) is supportive evidence.
be attributed to an immature hypothalamic–pituitary–
ovarian axis. Unless the irregularity is the cause of signif-
• Having flooding or ‘disasters’ regularly is suggestive
of heavy loss.
icant problems, simple reassurance is all that is required.
Multiple follicles (15 to 20) may be seen on ultrasonog-
• The presence of clots is usually not significant
unless the clots are large (>4–6 cm). Small clots are
raphy, but this is a normal finding in over 20% of young
normal and simply mean that there is adequate
women. Unless there is evidence of hyperandrogenism
time between blood leaving the endometrial surface
(i.e. significant acne or hirsutism), the term ‘polycystic
and reaching the perineum to allow coagulation to
ovary syndrome’ should not be used.
occur.

Polycystic ovary syndrome Management options

• Non-steroidal anti-inflammatory drugs (NSAIDs) –
The diagnostic criteria for this condition are for adults
reduce menstrual loss by 30%. Where there is
and have serious limitations when applied to teen-
concern about a potential bleeding disorder
agers because of the common findings of irregular
it would be wise to avoid NSAIDs in the first
­menstrual cycles and mild acne in this younger popu-
instance.
lation. Classically there is evidence of the metabolic
• Tranexamic acid (500 mg, two tablets q.i.d. p.r.n.)
syndrome (see Chapter 3.4) and hyperandrogenism
on days of heavy bleeding – reduces loss by 50%.
(excess hair and acne). The investigation findings may
• Oral contraceptive pill (OCP) – used cyclically or
demonstrate a raised FSH to LH ratio; ultrasonogra-
continuously.
phy may show 20 to 30 follicles with increased ovarian
• Depot medroxyprogesterone acetate.
stromal density; glucose tolerance test results may be
• Levonorgestrel intrauterine system has an
abnormal.
important place for significant, but difficult to
Management consists of improving the diet
control, heavy menses.
and increasing the amount of exercise. Additional
• Acute heavy bleeding – tranexamic acid (as above)
approaches such as hormonal treatment to regulate
combined with progestogens may be helpful in
irregular and heavy periods, and cyproterone ace-
stopping a heavy period. Provera 10 mg b.d. to
tate or spironolactone to reduce hair growth, may be
t.d.s., or norethisterone acetate (NEA) 5–10 mg
added in some cases.
b.d. to t.d.s. but up to 2-hourly, can be used and
then tapered during the next week. Complete
Heavy periods withdrawal of progestogens is usually associated
with a withdrawal bleed, so continuation for a
Heavy menses in teenagers is often the result of anovu-
total of 3 weeks is advised. Ongoing use of cyclic
latory bleeding. The possibility of a bleeding disorder
progestogens at a lower dose (Provera 10 mg daily,
also needs to be considered; 10–15% of girls with men-
or NEA 5 mg daily, for 21 days with a 7-day break to
orrhagia (in a population without known bleeding
allow a withdrawal bleed), or alternatively the OCP
disorders, and without predisposing factors such as
can be used as a follow-up for the next 3–6 months.
chemotherapy or warfarin usage) may have an under-
• Acute, very heavy, bleeding (metrostaxis) –
lying bleeding disorder such as von Willebrand disease
resuscitation including blood transfusion may be
or platelet dysfunction (see Chapter 16.2 on bleeding
required. High-dose oestrogen may be necessary
disorders and Box 3.12.1).
(estradiol valerate 2–4 mg 6-hourly), combined with
Assessment tranexamic acid. This can be followed by the OCP,
• Care needs to be taken when taking a history of commencing 48 hours later.
menses as what is ‘normal’ or ‘heavy’ may vary with
different individuals and in different families.
Secondary amenorrhoea
Periods can stop for a range of reasons other than
Box 3.12.1 Useful investigations in menorrhagia pregnancy – from central (hypothalamic) causes to
pituitary and ovarian abnormalities. A careful h
­ istory
• Full blood examination, iron studies will correctly identify several of these underlying
• Prothrombin time, activated partial thromboplastin time
causes of secondary amenorrhoea.
• Von Willebrand antigen/factor VIII studies
144 • Platelet aggregometry or platelet function assays Useful investigations for secondary amenorrhoea
are presented in Table 3.12.1.
 Gynaecology 3.12
Pelvic pain
Table 3.12.1 Investigation of secondary amenorrhoea
Dysmenorrhoea
Cause of amenorrhoea Investigation result
• Primary or prostaglandin-induced dysmenorrhoea
Central (hypothalamic) Low FSH, low LH, normal TSH, low
is usually not present during the first menses but
oestrogen, normal prolactin
may begin within a few periods.
Pituitary • It may occur in ovulatory or anovulatory cycles.
Thyroid disease Abnormal TSH
Prolactinoma Raised prolactin (needs to be Symptoms
increased on more than one • May precede the menses by a few days, or occur on
occasion) the first or second day of bleeding.
• Are usually absent by the final days of the bleeding.
Ovarian/gonadal FSH and LH very high, oestrogen
failure low
• May be exacerbated by stress.
• Consist of:
Pregnancy Raised bHCG • cramping lower abdominal pain and low back pain
• nausea (present in >30% of girls with
bHCG, β-human chorionic gonadotrophin; FSH, follicle dysmenorrhoea)
stimulating hormone; LH, luteinizing hormone; TSH, thyroid • vomiting
stimulating hormone.
• diarrhoea or constipation
• headaches, dizziness, fainting
• pallor, lethargy and generalized aches.
These symptoms are generally attributed to prosta-
Hypothalamic causes glandins, which play a role in coordinating the onset
of menstruation.
In a slim young woman, having established a good
rapport while using HEADSS as a screening tool Management
(see Chapter 3.11) to explore the young woman's • General approaches, such as exercise, reduce
physical activities and self-perception, the young stresses.
woman who is undertaking a great deal of exercise • NSAIDs, optimally commenced prior to onset of
or the teenager with the eating disorder should be symptoms.
identified. Weight loss associated with other med- • Oral contraceptive pill.
ical c­ onditions can also be responsible for central Retrograde menstruation occurs in almost all women.
causes of amenorrhoea. This is menstrual flow upwards through the fallopian
tubes and into the peritoneal cavity. The presence of
Pituitary causes free fluid in the peritoneal cavity causes a variable
amount of pain. It can cause pain with ­defaecation and
Pituitary problems related to prolactinoma or thyroid micturition as well as pain on movement. Reducing the
disease can cause secondary amenorrhoea. menstrual loss by the use of NSAIDs or tranexamic
acid usually reduces this amount of retrograde loss
and hence lessens the pain.
Polycystic ovary syndrome
Weight gain and associated insulin resistance and evi-
dence of acne or hirsutism make up the syndrome of Endometriosis
polycystic ovary syndrome, which can be responsible Endometriosis is the presence of ectopic endome-
for amenorrhoea or oligomenorrhoea (see above). trium in the peritoneal cavity. As endometrial cells
are present in the retrograde menses it is likely that
Ovarian causes most endometriosis can be attributed to this origin.
Endometriosis can vary in severity from a few small
Ovarian failure can be due to gonadal dysgenesis spots to extensive endometriosis with adhesions and
(most commonly Turner syndrome (see Chapter 10.3) cyst formation (endometriomas). It is now gener-
or premature ovarian insufficiency. ally agreed that mild endometriosis is a physiological
­finding. Endometriosis can be found in adolescents.
Care needs to be taken to exclude or adequately man-
Pregnancy
age other causes of period and pelvic pain, and to
The sexually active teenager is at risk of secondary ensure that menstrual loss is reduced, as heavy and/ 145
amenorrhoea related to pregnancy. or frequent periods are known to be risk factors for
 3.12 SOCIAL AND PREVENTATIVE PAEDIATRICS

e­ndometriosis. Consideration of other factors that Pelvic inflammatory disease

may be contributing to the symptoms also needs to be
Sexual activity (or a gynaecological surgical proce-
given (careful screening using HEADSS is valuable).
dure) enabling pathogens to access the upper genital
Pelvic ultrasonography should be done prior to con-
tract is the prerequisite for the development of pelvic
sidering a diagnostic laparoscopy if symptoms are not
inflammatory disease (PID).
controlled by other interventions.
The commonest pathogen causing PID is chla-
mydia. Tubal disease and damage as a consequence
Atypical dysmenorrhoea of PID is a significant cause of infertility, and early
diagnosis and adequate treatment are important. For
Dysmenorrhoea that progressively worsens through
the young woman who is sexually active and is febrile
menstruation and lasts beyond the end of bleeding is
with significant pelvic tenderness, intravenous antibi-
atypical and an obstructive müllerian (reproductive
otics should be used to cover the possibility of polymi-
tract) anomaly needs to be considered. Pelvic ultraso-
crobial infection. The antibiotics chosen should cover
nography can often be more helpful in diagnosis than
chlamydia, Neisseria gonorrhoeae and other anaerobic
laparoscopy. Assessment for an absent kidney can also
and aerobic organisms.
give useful supporting evidence for the likelihood of a
Screening for chlamydia in sexually active young
müllerian anomaly.
woman under the age of 25 years is recommended due
to reported rates of asymptomatic infection in up to
Ovarian cysts 15% of young women. Treatment with a single dose of
azithromycin is effective and ensures good compliance.
Ovarian cysts can be physiological (see above), occur-
Identification of young women with silent carriage
ring in the context of normal ovarian activity, or they
should lead to contact tracing of partners. Follow-up
can be pathological. Benign dermoid cysts are the
should be offered, and further discussion regarding
most common non-physiological cysts, although even
contraception and safe sex is essential.
these are relatively uncommon in the paediatric and
adolescent setting. Many ovarian cysts are asymptom-
atic even when they are very large, and may be found Contraception
incidentally at the time of other investigations. They Discussing and providing contraceptives to teenagers
may cause vague lower abdominal pain or may present requires careful consultation. The need for contracep-
more acutely if torsion of the ovary occurs. tion will often not be raised by teenagers, but if part of
the consultation has occurred without parents and has
Ovarian torsion utilized a careful assessment of social activities and
relationships, the young woman who is sexually active
(See also Chapter 20.1.) should be readily identifiable.
This can be a difficult diagnosis because of the rela- Ideally, involvement of an adult in the decision-
tively non-specific nature of the symptoms. Failure to making process regarding contraception is preferred,
consider this diagnosis can lead to loss of an ovary. but the younger teenager who demonstrates a clear
• Ovarian torsion is more common in childhood and understanding of the risks and benefits can be pro-
adolescence than in adulthood. vided with contraception. Careful documentation and
• There is abdominal pain, often colicky. assessment of the competency of the teenager in dem-
• There is associated vomiting and dizziness. onstrating their understanding is essential (a House of
• The ovarian cyst/ mass may not be palpable; it Lords ruling in 1984 on this issue has given rise to the
is essential to consider the diagnosis if there is expression ‘Gillick competence’ for this assessment).
significant and persistent localized tenderness. Ensure the teenager is aware of the need for ­condoms
• Pelvic ultrasonography demonstrating an enlarged for ‘safe sex’ to reduce her risk of acquiring a sexually
ovary corresponding to the side of maximal transmitted infection.
tenderness is supportive evidence.
• Exploration with laparoscopy may be the only way
Options for contraception
to clarify the diagnosis and is necessary if the ovary
is to be preserved. Emergency contraception
In the post-menarchal adolescent a history of regular This form of contraception is now usually provided as
menses with onset of pain occurring approximately a single-dose progestogen, and is used as soon as pos-
mid-cycle may be adequate to diagnose mid-cycle sible after unprotected intercourse. The success of this
pain, or Mittelschmerz. However, consideration of contraception method correlates with the time interval
the diagnosis of torsion needs to be made if there is since unprotected intercourse. It is important to do a
146
­significant tenderness. pregnancy test prior to use.
 Gynaecology 3.12
Oral contraceptive pill (OCP) Teen pregnancy
• A wide variety of OCPs are available.
Teenagers often present late with their unplanned
• For simplicity, be familiar with two or three
pregnancy. If the presentation is early in pregnancy,
variations.
the opportunity to explore choices with respect to the
• A standard monophasic pill (which allows the
pregnancy needs to be offered. Young women who
possibility of altering the time of the withdrawal
are part of a positive educational environment with
bleeds and allows the option of skipping
career plans are more likely to decide to terminate a
menses for several months at a time) using
pregnancy.
ethinylestradiol and levonorgestrel is a good first-
For teenagers who are pregnant, antenatal care
line contraceptive pill.
in a young women's clinic offers the opportunity to
• If acne is a major concern, an OCP-containing
address their specific needs, using a multidisciplinary
cyproterone acetate can be valuable.
team. Careful assessment is required to identify their
• For young women on anticonvulsants, use an
housing and financial support requirements. Dietitian
OCP with a higher oestrogen content (using
involvement is valuable to ensure that eating disorders
ethinylestradiol 50 mg) as liver enzymes are induced
or poor nutrition secondary to lifestyle and poverty do
and metabolism of the OCP is accelerated.
not impact on the health of the young woman and the
Progestogen-only pills fetus.
These pills contain low-dose progestogen only and Alcohol, smoking and illicit drug-taking need to
require greater reliability in use, with the pills need- be explored, with links made to appropriate services.
ing to be taken at the same time every day (± 1 hour) Screening for sexually transmitted infections needs to
This is usually difficult for teenagers to manage in be offered to all pregnant young women as the preva-
their daily routine and hence is usually not considered lence, particularly of chlamydia, in the under 25-year-
a good or reliable choice for contraception for this age old age group is significant. Exploration of possible
group. past physical or sexual abuse should be undertaken as
their sexual activity may be a result of this trauma.
Injectable – depot medroxyprogesterone It should not be presumed that any of the preced-
acetate (Depo-Provera) ing issues will be volunteered spontaneously. A posi-
This is a very reliable contraceptive and is usu- tive rapport is essential to gain the confidence of the
ally administered every 3 months as an intramuscu- young woman. Linking the pregnant young woman
lar injection. Measurement of β-human chorionic to educational resources and opportunities may be
gonadotrophin (bHCG) must be carried out if an required, as limited education is a significant factor in
injection is overdue, as ongoing amenorrhoea may be lifelong poverty.
due to a pregnancy rather than to effective menstrual Pregnancy in teenagers is generally low risk although
suppression. gastroschisis occurs more frequently in the babies of
teenage mothers.
Etonogestrel Parenting as a teenager poses real challenges because
This is a subcutaneous hormone released from a fil- of the conflicts between adolescent and p ­arenting
ament inserted into the upper arm, which provides tasks. The developmental tasks of adolescence include
contraception for 3 years. It is a very reliable form seeking independence, risk-taking, being part of a peer
of contraception but causes irregular bleeding in up group and participating in peer activities. As a parent,
to 30% of young women, resulting in requests for provision of a stable environment with responsible
removal. An alternative approach, where there are and committed time to the care of a baby is clearly in
concerns regarding the reliability in taking the OCP, ­contrast to adolescent tasks.
is to leave the etonogestrel in place (as a reliable con-
traceptive) but to add a low-dose OCP to correct the Intellectual disability – menstrual
irregular bleeding. In this context, if the pill-taking is and contraceptive management
erratic the consequences are breakthrough bleeding
rather than pregnancy. With the onset of puberty, parents and carers of
young women with an intellectual disability often
Progestogen-releasing intrauterine device (IUD) become acutely concerned by the further challenges
The levonorgestrel intrauterine system is a very reli- that this sexual development may pose. Although
able contraceptive. It is effective for 5 years and causes ­concerns regarding the capacity of the young woman
a 98% reduction in menstrual loss. It has an important to cope with menstruation itself are often the reason
place in some specific adolescent populations, includ- for p
­ resentation, underlying worries about the need
ing those with heavy periods and those unable to use for contraception, and risks of pregnancy and sexual
147
oestrogens. abuse, are usually also present.
 3.12 SOCIAL AND PREVENTATIVE PAEDIATRICS

It is impossible to predict exactly when menstrua- impact on bone density. The young woman with
tion will begin. Likewise it is impossible to know what reduced mobility has additional risks for osteoporo-
problems, if any, the young woman will experience. As sis. In young women already at risk of negative bone
for other young women without disabilities, a range of influences, any technique that lowers oestrogen levels,
options is available to assist in the management of men- such as the use of depot medroxyprogesterone acetate,
strual difficulties, and these need to be used in response should be avoided or used only if replacement oes-
to the specific problems and issues for the individual. trogen is also provided. For the young woman with
Assistance with menstrual management results in posi- unstable epilepsy, seizures may occur cyclically, and
tive benefits to the quality of life of these young women. achieving a stable hormonal state may be helpful in
Identification of associated medical problems will reducing frequency of seizures.
assist in management decisions. All young women Menstrual and contraceptive management in the
with chronic illness have an increased risk of vitamin young woman with intellectual disability is summa-
D deficiency and the subsequent potential n ­ egative rized in Table 3.12.2.

Table 3.12.2 Menstrual and contraceptive management in the young woman with intellectual disability

Management Clinical effects Additional comments

Non-steroidal anti-inflammatory Reduce dysmenorrhoea No contraceptive effect

drugs Reduce menstrual loss

Tranexamic acid Reduces menstrual loss No contraceptive effect

Cyclic progestogens May reduce dysmenorrhoea No contraceptive effect

Regulate bleeding pattern
May reduce menstrual loss

Oral contraceptive pill Reduces dysmenorrhoea Contraceptive

Reduces menstrual loss

Continuous oral contraceptive pill May eliminate menses Contraceptive

May reduce cyclic seizures

Depot medroxyprogesterone May eliminate menses Contraceptive

acetate (Depo-Provera) May reduce cyclic seizures
May have a negative effect on bone density
and require replacement oestrogen

Etonogestrel May reduce menstrual bleeding but Contraceptive

significant risk of irregular bleeding

Levonorgestrel IUD Significantly reduces menstrual loss (often Contraceptive

achieves amenorrhoea)

Tubal ligation No impact on menstrual symptoms Contraceptive

In Australia requires Family Court of Australia
approval for those less than 18 years of age

Hysterectomy Eliminates menses and dysmenorrhoea Contraceptive

In Australia, requires Family Court of
Australia approval for those less than
18 years of age

Endometrial ablation Reduces menstrual loss (may achieve Not contraceptive

amenorrhoea) In Australia, requires Family Court of
Australia approval for those less than
18 years of age

148 IUD, intrauterine device.

 Sleep problems
Sadasivam Suresh, Helen Heussler
3.13
amount of information available to attribute the
Introduction ­following functions to sleep:
Sleep is a universal phenomenon in the animal • Sleep is noted to restore and recuperate the human
­kingdom. The role of sleep in human beings has been body to optimal daytime functioning (restoration
studied with increasing interest over the last 60 years. theory). NREM sleep is thought to function
This has resulted in increased awareness of sleep in reparation of body tissue and REM sleep in
­medicine as a separate entity. This chapter focuses on restoration of brain tissue.
some of the aspects of paediatric sleep medicine: the • Sleep is considered important in the process of
­physiology and function of sleep, development and learning and memory (learning theory). The
maturity of sleep, parasomnias, behavioural aspects unlearning theory complements this process by
of children's sleep, the spectrum of paediatric sleep handling the clutter of information and removing
disorders and its role in future morbidity of the non-essential information in an orderly fashion,
individuals. thereby facilitating enhanced learning.
• Sleep is considered a facet of evolutionary
‘If sleep does not serve an absolutely vital f­ unction, development, and complexity of sleep is attributed to
then it is the biggest mistake the ­evolutionary the complex nature of the human physiological system.
process ever made.’
Dr Alan Rechtshaffen, Sleep Research Pioneer
Development and maturity of sleep
Similar to many aspects of development, sleep also
The physiology and function undergoes changes with age. The physiological aspects
of sleep that evolve during the early years are maturation of
the EEG, development of cardiorespiratory reflexes,
Sleep is defined as ‘a natural and periodic state of rest establishment of the circadian rhythm and consoli-
during which consciousness of the world is s­ uspended’. dation of sleep architecture. Some 95% of infants
This is brought about by complex interactions between cry with a night awakening that requires a parental
the reticular activating system and the diffuse set of neu- response. By the age of 1 year, 60–70% of these infants
ronal centres that facilitate different aspects of sleep. are able to go back to sleep on their own. The ability to
The most important factor appears to be the desyn- self-soothe and return to sleep is the most important
chronization with the cortical centres that are related aspect for consolidated sleep as awakenings are a nor-
to consciousness. Sleep has been further differentiated mal part of a night sleep, even in adulthood. Self-sleep
with the help of electroencephalography (EEG) and the initiation is a learned phenomenon and is essential for
current convention for staging of sleep is EEG based. establishment of sleep continuity (‘sleeping through’).
In infancy it is differentiated as active and quiet sleep, Minor arousals will continue to be seen, but will not
and as the development progresses characteristic fea- require external intervention. Sleep maturation is
tures are noted and the sleep is broadly divided as rapid linked to intellectual development in children.
eye movement (REM) and non-rapid eye movement
(NREM) sleep. The usual pattern is to cycle through
these stages throughout the night and to arouse (often
at stage changes) a number of times during the night. Behavioural aspects
This structure is often referred to as sleep architecture.
The total amount of sleep from birth to adolescence is
of children's sleep
shown in Figures 3.13.1 and 3.13.2. Unlike adults, infants and young children do not
Although sleep has been studied extensively over often present with problems in their sleep. The parents
the past few decades, the exact function of sleep has present their problem. It is important to evaluate the
149
not been fully discerned. However, there is a reasonable symptoms properly and assess whether there is a sleep
 3.13 SOCIAL AND PREVENTATIVE PAEDIATRICS

Total sleep time through the ages are common in children with attention-deficit/hyper-
18 activity disorder (ADHD) or autistic spectrum disor-
ders, as well as in some typically developing c­ hildren.
16
They can also relate to poor routines, limit-setting
14 problems and anxiety issues inherent in the child. It is
important, as with adult insomnia, to address what is
12
Sleep time (hours)

going on at this time and predisposing factors that may

10 contribute to the difficulty settling. A sleep initiation
problem will often lead to a circadian shift and thus
8 to difficulties in getting up in the morning. Practical
6 issues need to be addressed and can be done so with:
• a stable routine that helps with entrainment
4 (external factors that help keep circadian scheduling
in a regular pattern)
2
• settling procedures/relief of anxiety
0 • entrainment of circadian schedule with regular and
1 wk 1 Mo 3 Mo 6 Mo 12 Mo 2 Yr 5 Yr 10 Yr 16Yr stable wake-up and bedtimes
Age • comfortable non-stimulatory environment
• removal of technology from the bedroom (e.g.
Fig. 3.13.1 Total sleep time through the ages. televisions, mobile phones, game equipment).
Children will generally need to learn how to self-settle.
Methods such as controlled crying work but are often
difficult for tired parents to implement. Often, focus-
Ontology of REM and NREM sleep ing on the sleep initiation and utilizing a camping-out
25 technique are more acceptable to parents.

20
REM Practical point
NREM
Total sleep time

15 • Camping out involves a parent sleeping on a mattress or

chair in the child's room until the child is going to sleep in
his/her own bed and then gradual removal of the parent
from the room.
10

5
Sleep phenomena or
parasomnias in children
0
28 Wk 35 Wk Term 1 Mo 5 Mo 12 Mo 2 Yr 5 Yr 10 Yr 16 Yr
Parasomnias are undesirable motor, autonomic or
experiential phenomena that occur exclusively or pre-
Age
dominantly during the sleep state. Parasomnias have
Fig. 3.13.2 Total sleep time with a rapid eye movement (REM)/ sleep state-related features and most of them are
non-rapid eye movement (NREM) split. benign. The majority of these decrease in frequency
as the child gets older. Some of them exhibit f­amilial
links and may change with time. The predominant
disorder present or just a variation of the normal. The management issue is safety. Parents should be alerted
treatment, if any, should be for the child primarily and if a child is sleepwalking; this can usually be man-
not necessarily to fulfil parental desire. Age-specific aged by bells or alarms placed on a child's doors or
common non-respiratory sleep problems are shown in windows. Night terrors can be particularly alarming
Table 3.13.1. for some, but the child usually remains unaware of
Common problems encountered are those of the problem – unlike nightmares, where a child will
­difficulties with sleep initiation, sleep maintenance and awaken after a bad dream and have good recall of the
circadian scheduling problems. Sleep initiation prob- dream. Night terrors usually occur earlier in the night
150 lems often are related to not being able to self-settle and and, like most parasomnias, can become worse if the
 Sleep problems 3.13
Table 3.13.1 Commonest non-respiratory sleep disorders

Infant/toddler (1–2 years) Preschool child (3–5 years) Primary school child (6–12 years) Adolescent (13–18 years)

Behavioural insomnia of Behavioural insomnia of Insufficient sleep Insufficient sleep

childhood childhood

Rhythmic movement Sleep terrors Bedtime resistance Narcolepsy

Rhythmic movement Sleepwalking

Source: Moore M, Allison D, Rosen CL 2006 A review of pediatric non-respiratory sleep disorders. Chest 130:1252–1262.

child is woken. They are often also worse if a child is

tired; hence many children present with night terrors Polysomnography in children
as they begin to give up their daytime sleep. The main investigative tool in children with sus-
Table 3.13.2 gives a simplified summary of paraso­ pected sleep disorder is polysomnography (PSG).
mnias with prevalence rates from a large population Like other investigations in medicine, PSG should
study. be performed only after obtaining a proper clini-
cal history and examination. PSG comprises mul-
tiple channels and would traditionally include EEG,
electro-oculogram (EOG), electromyogram (EMG),
Clinical example thorax and abdominal respiratory bands, orona-
sal flow sensor, oxyhaemoglobin saturations, trans-
James is a 5-year-old boy who presents with a cutaneous/end-tidal carbon dioxide sensor ± video
story of frequent night waking with screaming. monitoring (Fig. 3.13.3). This helps in ascertaining
He has trouble getting off to sleep and has
sleep stages accurately and the nature and severity
been very tired, often falling asleep on the drive
home from school, but when it comes to time for bed he of sleep related breathing disorder, if any. Children
won't sleep unless his mother lies down with him. He will then are significantly different from adults, and criteria
wake frequently during the night with two types of episode – for scoring vary with modified definition for abnor-
one usually before his parents go to bed and others later in mal thresholds. Various forms of limited-channel
the night. The first ones are the worst, where he is so upset PSG have been used and, when carefully planned, the
he cannot be comforted. In the later ones during the night, information obtained is beneficial in managing paedi-
James wakes crying and comes to get a parent but then
won't go back to bed unless they are with him.
atric sleep problems. If seizures in sleep are s­ uspected,
full EEG leads will be required. Most sleep studies
What other information might you like? have limited EEG channels, which are used primarily
Family history is important, as these problems tend to have for sleep staging and not for assessment of seizures.
a familial pattern. Children usually have no daytime nap by
the age of 5 years and continuation of daytime napping will
have impact on night sleep patterns. The dietary intake of
children could have an impact on sleep routine. Habituation Spectrum of paediatric
of sleep patterns are important and exactly what his mother
does at each wake time will have an impact on either
sleep disorders
exacerbating or reducing the problem. The general physiological patterns seen as part of vari-
What three processes are going on here? ous sleep disorders in children for the most part are sim-
1. Night terrors. ilar to those in adults. Some differences exist, mainly
2. Nightmares. reflecting aspects of behaviour, psychology and develop-
3. Sleep association and maintenance issues. ment. The International Classification of Diseases (ICD)
How would you manage this child? includes paediatric sleep d
­ isorders in its most recent ver-
• Reassure that the waking and parasomnias are normal sion. Children experience a broad range of sleep dis-
phenomena that are often worse when tired. turbances including obstructive sleep apnoea (OSA),
• Normalize James' sleep onset associations (he needs to insomnia, parasomnia, delayed sleep phase, narcolepsy
be able to get off to sleep on his own). The camping out and restless legs, but their clinical presentation, evalua-
technique may be useful but requires an individual approach. tion and management may differ from those in adults.
• Consider organizing with the school an early afternoon or
late morning nap, as James has just given this up in his
Although snoring and sleep apnoea may be the most
first year of full-time school. common indication for an overnight sleep study in a
child, one-quarter of children presenting to a sleep clinic
151
 3.13 SOCIAL AND PREVENTATIVE PAEDIATRICS

Table 3.13.2 Parasomnias with population prevalence

NREM related REM related Sleep state independent

Normal Hypnogogic imagery Dreams Bruxism 28%

Sleep starts Nightmare 10–50% Rhythmic movement disorder 17%
Confusional arousals 17% Sleep-talking 55%

Abnormal Night terrors 17% Sleep paralysis Periodic leg movement

Sleepwalking 14% REM behaviour disorder

NREM, non-rapid eye movement; REM, rapid eye movement.

Source: Moore M, Allison D, Rosen CL 2006 A review of pediatric non-respiratory sleep disorders. Chest 130:1252–1262.

management of paediatric OSA. The main ­clinical pre-

sentation is that of snoring, witnessed pauses, sleep dis-
turbance and poor performance at school. A detailed
sleep history supplemented by clinical examination
and assessment of breathing during sleep will help in
diagnosing OSA. Full PSG remains the ‘gold stan-
dard’ for diagnosis; however, overnight oximetry, when
performed and analysed by experienced staff, hastens
the clinical diagnosis in view of its very high positive
predictive value (97%).
The mainstay of treatment in the paediatric age
group is adenotonsillectomy, with a resolution rate
close to 90%. In a small proportion of children OSA
persists and requires further investigation and treat-
ment. Treatment of any underlying medical condition
Fig. 3.13.3 Child in the sleep laboratory undergoing and control of weight gain contribute significantly
polysomnography. in reducing the severity of OSA. Supportive therapy
during sleep in the form of continuous positive air-
for evaluation will have a second sleep diagnosis, which way pressure (CPAP) therapy has been proven to be
is often ­non-respiratory in nature. Especially in children, beneficial similar to that in adult patients with OSA.
­ruling out OSA is rarely the endpoint of the sleep evalu-
ation. Clinicians involved in sleep ­medicine must be pre-
pared to recognize, evaluate and manage plans for sleep Complications of untreated OSA
disorders across the lifespan of the patient. Severe forms of untreated OSA have been associ-
ated with cor pulmonale, developmental delay, fail-
Snoring and obstructive sleep apnoea syndrome ure to thrive or death. Over the last decade there has
been increased understanding of the morbidity from
Snoring and OSA is one of the outstanding examples untreated OSA, even when the OSA is in the mild
of the seamless transition from normal phenomenon to moderate category. There is also evidence emerg-
to an abnormal pathology. Snoring is noted in at least ing that primary snoring might not be as benign as
20% of the paediatric population at any one stage and thought previously, and might also be associated with
is considered benign when it is not associated with any some sequelae. Neurocognitive and learning deficits
other sleep symptomatology. This is called primary have been associated with OSA, and early diagnosis
snoring or habitual snoring. William Osler in 1892
stated: ‘At night the child's sleep is greatly disturbed,
the respirations are loud and snorting, and there are
sometimes prolonged pauses, followed by deep, noisy Practical points
inspirations’ in a textbook of paediatrics describing
clinical features of tonsillar enlargement. In spite of • Snoring is a very common symptom in childhood with a
prevalence of 10–15% .
such a lucid description, the importance of OSA in
• Obstructive sleep apnoea occurs in 2–5% of children.
children has been recognized only in the last 30 years.
• Early recognition and treatment can have an impact on
The American Academy of Pediatrics has ­published sleep quality, growth and neurocognitive development.
152
a consensus guideline regarding the diagnosis and
 Sleep problems 3.13
and appropriate treatment appears to reverse some of Central hypoventilation
these. However, in some children the changes appear and respiratory failure
irreversible and it is postulated that the older the
Congenital central hypoventilation (Ondine's curse) is
child at treatment institution the lesser the chance of
a rare disorder wherein the respiratory drive in sleep
reversing the deficits. Untreated OSA in adulthood
is absent or significantly blunted. This results in sig-
is associated with increased cardiovascular and cere-
nificant hypoventilation and respiratory failure. A
brovascular morbidity, and it is likely that some of
defect in the homeobox gene PHOX2B is found in this
the changes have their origins in childhood.
condition. Early diagnosis in the neonatal period and
institution of ventilatory support via tracheostomy is
needed to manage the condition.
Clinical example Sleep-related hypoventilation is more commonly
noted in neuromuscular conditions, and usually
Ricky is a 4-year-old boy with a history of presents in the second decade of life with worsen-
snoring and sleep disturbance, as well as ing weakness. Poor sleep quality followed by increas-
recurrent upper respiratory tract infections.
ing hypoxia and hypercapnia are noted on PSG.
What further details in clinical history are needed? Vital capacity below 40% predicted is usually asso-
The daily sleep routine needs to be ascertained. The nature ciated with onset of sleep-related hypoventilation.
of snoring, timing of snoring, variability with posture, time
Diagnosis is by demonstrating hypercapnic respira-
or intercurrent illnesses need to be established. Associated
features of snoring such as witnessed pauses or gasps need tory failure on PSG, and treatment is usually by non-
to be enquired about. The nature and frequency of upper invasive mask ventilatory (NIV) support. Treatment
respiratory infections will need further exploration. A history of has demonstrated improved life expectancy and qual-
tonsillitis with difficulty in handling solids/chunky food points ity of life in patients, especially those with Duchenne
to tonsillar hypertrophy. A history of mouth breathing with bad muscular dystrophy (DMD).
breath may be found in some preschoolers. Symptoms of nasal The increasing epidemic of obesity in childhood
obstruction and seasonal variation need to be enquired about.
has also resulted in another subgroup of patients who
What are the important features of clinical examination? present with significant sleep-disordered breathing
Anthropometric measures of height and weight are
and need either CPAP or NIV to correct this.
important to assess the impact and chronicity of the problem.
Examination should include a complete ear, nose and throat
Children with the following specific syndromes
(ENT) assessment, including checking for nasal passages, are at risk of sleep-disordered breathing, both OSA
oropharyngeal space and tonsillar size. Auscultation and hypoventilation: trisomy 21, craniosynostosis
should be performed for a loud second heart sound, which ­syndromes, achondroplasia, spina bifida and P ­ rader–
might be present in severe cases of OSA. Blood pressure Willi syndrome (amongst others).
measurement should be performed.
What further investigations are appropriate?
X-ray of the lateral neck to assess adenoidal pad could be a Complications of insufficient sleep
useful investigation in the outpatient setting. PSG is the ‘gold
Research in this area in children has been limited;
standard’ for diagnosing OSA. Screening oximetry could be
performed to ‘rule in’ OSA, to expedite further management. however, there is now emerging evidence that as little
as 1 hour less a day can have significant impact on a
PSG findings and the next management step
PSG demonstrated obstructed breathing with a respiratory
child's performance at school, particularly in areas of
disturbance index (RDI) of 10/hour, more marked in REM vigilance and sustained attention, as well as working
sleep with an RDI of 22/hour (normal rate <5/hour in memory.
young children and <1/hour in older children). What would
be the next management step?
The first line of treatment for OSA would be assessment by
an ENT surgeon with a view to considering adenotonsillectomy. Rare conditions
Ricky went on to have this operation. His snoring symptoms
resolved, with improvement in quality of sleep without sleep Some disorders that present in sleep include nocturnal
fragmentation. His appetite improved and he was able to epilepsies. These occur rarely and are often associated
manage a wide variety of foods, including chunky food. with repetitive and stereotypical movements, often
After the management step what follow-up arrangements associated with an intermittent decrease in d ­ aytime
are needed? performance.
Provided the symptoms resolve completely, no further medical Other disorders to be aware of include:
follow-up is warranted. However, with a proven diagnosis of
OSA there is a chance that the symptoms might return either
• Narcolepsy – a triad of hypersomnolence with
with significant weight gain or during pubertal years; Ricky and an uncontrollable urge to sleep, cataplexy and
his family should be advised to seek medical help if this occurs. short REM latency. This commonly presents in
153
early adulthood, adolescence or late childhood,
 3.13 SOCIAL AND PREVENTATIVE PAEDIATRICS

but most people with the diagnosis may have had hypersomnolence, hyperphagia and hypersexuality.
symptoms for up to 10 years. The condition is episodic, often for periods of
• Klein–Levin syndrome – a disorder that presents 10–14 days, where the patients describe it as ‘like
mostly in adolescent males and involves being in a dream’. Most adolescents will ‘grow out
of this’, although mild cognitive/memory deficits
have been noted in some.

Clinical example

Keith is a 13-year-old boy with DMD who Conclusion

complains of sleep difficulty. He has been
wheelchair-bound since the age of 11 years and Sleep is a widespread biological phenomenon and its
has developed a mild scoliosis. His parents are scientific study is proceeding at multiple levels. Marked
concerned, as he appears very tired during the day and does progress is being made in answering three ­fundamental
not appear to have energy to go beyond 2 p.m. questions: what is sleep? what are its mechanisms?
What clinical features would you elicit to assess Keith's and what are its functions? Sleep is critical for health
sleep-disordered breathing? and is undervalued both in our 24-hour society and
The sleep routine for Keith, including his daytime resting in ­paediatric clinical practice. Sleep p ­roblems are
pattern, needs to be ascertained. A history of daytime extremely common during childhood, from infancy
somnolence is reflective of poor overnight sleep quality.
A history of snoring, multiple wakenings, early morning
to adolescence. Childhood sleep disorders are often
headaches and increased sweating during sleep all point under-recognized and undiagnosed, despite being
towards sleep-disordered breathing and hypoventilation in either preventable or treatable. Sleep impacts on
an adolescent with DMD. A history of weight gain (secondary almost all aspects of a child's functioning, and thus
to reduced activity) or loss (secondary to incipient respiratory the increased recognition and treatment of sleep disor-
failure) is also relevant. ders will have a positive effect on a child's well-being.
What investigations would you plan?
Spirometry performed in the outpatient setting will help
in assessing the respiratory reserves. Vital capacity
below 40% predicted is usually associated with nocturnal Practical points
hypoventilation and respiratory failure. PSG performed in a
sleep laboratory will give information on overall sleep quality, • Sleep is a short- and long-term health investment.
sleep architecture, adequacy of gas exchange and severity • Do not forget to obtain sleep history as part of a routine
of respiratory failure, if any. paediatric clinical history.
What will be your management strategy?
Given the history, it is highly likely that Keith will have chronic
hypercapnic respiratory failure and, after confirmation with
a sleep study, treatment options including initiation of non-
invasive mask ventilation (NIV) during sleep-time need to
be discussed with Keith and his family. NIV is well tolerated
and shown to improve respiratory failure with symptomatic
improvement and improved quality of life.
What other specialists might need to assess Keith?
In addition to the neurologist and respiratory and sleep
pediatrician, Keith would benefit from an assessment by
paediatric cardiologist to assess his right ventricular function
and the extent of cardiomyopathy, if any, and appropriate
treatment commenced. With the increased risk of scoliosis
in this group of patients, Keith would benefit from a spinal
assessment and correction of scoliosis if that was considered
as a reasonable treatment option.

154
 Refugee health
Georgia Paxton, David Burgner
3.14
Refugee children, young people and families:
Introduction • are usually resourceful and resilient
This chapter highlights some of the key health issues • will have experienced major transitions with
commonly encountered in refugee children and their migration and settlement, affecting their family,
families. The focus is on refugee health in Australia, education and community structure
but the concepts are relevant to refugee children and • may have had inadequate food, water, shelter
their families settling in other countries. and safety
The protection of people who have been forced to leave • may have spent a prolonged period in refugee camps
their homes due to armed conflict and human rights • are likely to have come from situations where health
abuses is a major global challenge. In 2009, there were care is inadequate
approximately 15 million refugees worldwide, 1 million • will have health conditions reflecting their area
people seeking asylum and 27 million people displaced of origin and country of refuge, with exposure to
within their own countries because of c­onflict. The communicable and vaccine-preventable diseases
majority of refugees remain in their area of origin. Only • will need catch-up immunization
about 1% of all refugees are resettled in a third country, • may have an incorrect birth date on their paperwork
and only about 1% of these are r­ esettled in Australia. • are likely to have disrupted education
Annually, Australia currently accepts 13 750 ­ people • may have been separated from their family, or lost
under its humanitarian programme, and New Zealand family members
accepts 750 refugees. In total, more than 140 000 ­people • may have experienced physical or sexual violence,
of a refugee background have arrived in Australia since including torture and severe human rights violations
the mid-1990s, representing a significant population • may have mental health problems
group, with unique health needs. The current Australian • may not be familiar with preventative health care
humanitarian intake is mainly from Burma (Myanmar), • may also have more familiar paediatric health issues.
Iraq, Afghanistan, sub-Saharan Africa and Bhutan.
Refugee arrivals include a high proportion of ­ children
and young people; over half the intake is less than 25 years
of age. Families are often large, with women heading the
Refugee health assessments
household, and there may be many children within a f­ amily
group. Some children and young people arrive as unaccom- Practical points
panied humanitarian minors, defined as those aged less
than 18 years with no parent to care for them.
• Refugee children have usually not had pre-departure
health screening in their country of origin.
• Health assessment for refugee children/young people is
Definition of refugee and asylum recommended after they settle in a new country; including
seeker an assessment of general health, nutrition, immunization
status, infectious diseases (malaria, parasites, hepatitis,
A refugee is a person who: tuberculosis risk) and mental health.
‘Owing to a well-founded fear of being persecuted for • There are additional diagnoses to consider for common
reasons of race, religion, nationality, membership of a presentations in refugee children/young people.
particular social group, or political opinion, is outside
the country of his nationality, and is unable to or,
owing to such fear, is unwilling to avail himself of the Refugees settling in developed countries should
protection of that country.’ be offered voluntary health screening. Screening
Article 1, The 1951 Convention Relating to the ­protocols vary depending on countries of origin and
Status of Refugees
settlement, and may also vary with refugee/asylum
An asylum seeker is a person who has left their country
of origin, has applied for recognition as a refugee in another seeker status. Health screening may be ­ completed
country, and is awaiting a decision on their application. ‘offshore’ (before leaving the source country) or
155
after arrival in the new country, and may include
 3.14 SOCIAL AND PREVENTATIVE PAEDIATRICS

­ resumptive treatment for infectious diseases. Many

p It is important to take a routine background h ­ istory,
countries use a combination of offshore and post- as for any patient, although there are different fac-
arrival screening. tors to consider in children from a refugee back-
ground. Access to antenatal and perinatal care may
have been limited, and child health screening (neona-
Pre-departure screening
tal, vision, hearing screening) may have been limited
In Australia, health screening and treatment prior or non-existent. Access to health care, dental care and
to departure is limited for children and younger ­education varies widely. We have found it helpful to
adolescents. The visa health assessment, completed
­ ask s­pecifically about chronic d ­ iarrhoea and malnu-
for any permanent arrival to Australia, not just refu- trition in infancy, hospital admissions overseas, epi-
gee entrants, is directed at excluding active tuberculosis sodes of malaria and/or coma, and trauma, as it is
(TB), and includes a physical examination, urine ward surprising how frequently these issues are not revealed
test (age ≥ 5 years), chest X-ray (age ≥ 11 years) and initially.
human immunodeficiency virus (HIV) serology (age Understanding the migration pathway, together with
≥ 15 years). There are no other routine screening tests. the language and education transitions, is ­important in
Humanitarian entrants may have additional offshore appreciating the child's and family's experiences and
pre-departure medical screening (PDMS). This varies the effects on health and development. This must be
with port of departure, but may include malaria screen- handled sensitively, as there may have been ­significant
ing (and treatment if needed), empiric antihelminth trauma. It is not usually appropriate to ask about this
treatment and a single mumps, measles, rubella (MMR) directly on the initial visit (unless the family ­volunteers
vaccination (age from 9 months to 30 years). PDMS is a this history). Useful questions include, ‘Who is in
voluntary process and uptake is not complete. your family in Australia?’ and ‘Do you still have family
overseas?’, rather than asking specifically about fam-
ily members. It is also helpful to ask what people did
Post-arrival health assessment
overseas, recognizing the breadth of occupations/edu-
It is important to explain the concepts of health cational levels within refugee cohorts, and acknowl-
assessment, screening and disease prevention; f­ amilies edging that people are not simply defined by their
(and adolescents individually) need to understand refugee experience.
the importance and implications of health screen- Key points in history and examination related to
ing and give informed consent. A professional health screening investigations are shown in Table 3.14.1.
interpreter will be needed in the majority of consulta- Some groups may need additional screening
tions. It is never appropriate to use a family member investigations based on prevalence data from their
or friend as an interpreter. It is important to explain ­country of origin, or conditions prior to departure.
the bounds of confidentiality for both the medical In a­ddition, children with clinical symptoms may
consultation and working with an interpreter, and require a­dditional investigations. Other differential
this may help families feel more comfortable. One of diagnoses to consider in refugee children are shown
the simplest clinical points – often forgotten – is that in Table 3.14.2.
working with an interpreter takes twice as long: every-
thing is said twice and this needs to be factored into
­appointment times.
Assessment of newly arrived refugee children and Specific health issues
adolescents should focus on:
• parent (or self-identified) concerns
• excluding acute illness Practical points
• confirming the reported birth date
• immunization status and catch-up
• Low vitamin D levels are common in refugee children/
• screening for TB young people, who may have multiple and ongoing risk
• symptoms of parasite infection, including malaria factors for vitamin D deficiency and may need long-term
• nutritional status and growth treatment.
• significant developmental issues, including vision • Refugee children and young people have high rates
and hearing of parasites, positive tuberculosis screening test results,
• dental health and hepatitis, reflecting the prevalence of these health
issues in their country of origin.
• mental health issues, particularly features of post-
• Refugee children/young people need an assessment
traumatic stress disorder (PTSD) of their immunization status and will all require catch-up
156 • issues arising during resettlement (housing, vaccinations.
financial stress, education).
 Refugee health 3.14
Table 3.14.1 Key points in history and examination related to screening investigations

Suggested initial post-arrival screening

History Examination investigations

• Fever (malaria, TB, other infections) A thorough physical examination of all • FBE and film
• Night sweats/malaise/weight systems is required: • Ferritin
loss/poor growth/chronic cough/ • Growth parameters • Vitamin D, calcium, phosphate, ALP
contact and family history, health • Nutritional status • Vitamin A
undertakings (TB) • BCG scar • Malaria screen (thick and thin
• Low-grade bony and muscular pain, • Pallor (anaemia, haemoglobinopathies) films, and rapid diagnostic test)
pain with exercise, dairy intake, • Oral health (dentition, periodontal • Hepatitis B screen (HBsAg, HBsAb
symptoms of low calcium (muscle disease) and HBcAb)
cramps), access to outside spaces/ • ENT (chronic middle ear disease) • Hepatitis C serology
time spent outside, skin colour, • Goitre (unscreened thyroid disease) • Schistosoma serology
covering (vitamin D) • Features of rickets (swelling of wrists/ • Strongyloides serology
• Tiredness, diet (excessive milk, ankles, deformity (which reflects the • Faecal specimen (ideally fixed)
weaning, solids, meat), food access, age/growth of child when low • Mantoux test
family history, blood loss (anaemia, vitamin D status occurred), delayed • STI screen (Neisseria gonorrhoeae
iron deficiency) dentition, late closure of anterior and Chlamydia trachomatis urine
• Jaundice, RUQ pain, family history, fontanelle, bossing nucleic acid detection; syphilis
transfusion, shared needles • Skin, hair, nails (dermatophytes) serology (TPHA) - consider in all
(hepatitis) • Hepatosplenomegaly (e.g. malaria, children, to exclude congenital
• Abdominal pain, diarrhoea, blood Schistosoma, HIV) infection) in sexually active
PR, macroscopic worms, rashes, • Conditions that would usually adolescents or if there is a history
skin nodules (parasites) be assessed during childhood of sexual violence
• BCG status, history of chickenpox, and may have been missed (e.g. • HIV screening - Consider in all
immunization documentation and cardiac murmurs, inguinal hernia, children, should be completed
PDMS (immunization status) undescended testes) in sexually active adolescents,
• Epigastric pain, early satiety, poor • Culturally specific findings (e.g. if there is a history of sexual
appetite, family history of ulcer uvulectomy, teeth removal, scarification) violence, or where parents are
disease (Helicobacter pylori) deceased/missing/known to
• Pregnancy, genital pain, discharge, be HIV positive, or if clinical
ulcers, lumps and contact history symptoms/signs
(STI screening) • Helicobacter pylori faecal antigen
testing if suggestive symptoms

ALP, alkaline phosphatase; BCG, bacille Calmette–Guérin; ENT, ear, nose and throat; FBE, full blood examination; HIV, human
immunodeficiency virus; HBcAb; hepatitis B core antibody; HBsAb, hepatitis B surface antibody; HBsAg, hepatitis B surface antigen;
PDMS, pre-departure medical screening; PR, per rectum; RUQ, right upper quadrant; STI, sexually transmitted infection; TB,
tuberculosis; TPHA, Treponema pallidum haemagglutination assay.

Nutrition and growth

It is important to take a good dietary and gen-
Nutritional issues are common in children from a ref- eral history, and to ascertain access to and quantity/
ugee background. Fussy eating and concerns about quality of food overseas and after settlement. Clarify
weight gain (too little or too much) are often a fam- the correct age/birth date, and chart growth param-
ily priority. Specific issues include low weight and/ eters. Linear growth is similar in children aged under
or height for age, low vitamin D status, other vita- 5 years worldwide, although growth must be consid-
min deficiencies, iron deficiency and anaemia. Several ered in the context of parent height (which should be
studies suggest the rate of overweight/obesity is low measured accurately), ethnicity (Australian growth
in recently arrived cohorts of refugee children/ado- charts are derived from American and European
lescents; however, immigrant cohorts are observed data) and pubertal status. Children may have differ-
to have an increased prevalence of overweight/obe- ent parameters to their Australian born peers and
sity after settlement and in subsequent generations. still have normal growth; it is important to remember
There are limited data on the prevalence of vitamin the Australian prevalence of childhood overweight/­
deficiencies: low vitamin A levels have been found in obesity is above 20%.
up to 40% of African refugee children in Australia; an An early severe nutritional insult or chronic d
­ isease
early history (overseas) suggesting thiamine deficiency during infancy will affect final height (­stunting); this
is sometimes seen in Burmese children; and B12 and history is usually easily elicited. Consider organic
157
folate deficiency have been noted in Afghani refugees. disease early in a refugee child with poor growth or
 3.14 SOCIAL AND PREVENTATIVE PAEDIATRICS

Table 3.14.2 Common presentations and differential diagnoses to consider in refugee children

Presentation Common causes Additional considerations

Fever Common viral and bacterial infections • Malaria*

(check for localizing features, etc.) • Dengue and other arboviral infections*
• Typhoid*
• Dysentery*
• TB in any site, especially if prolonged
• Dental disease (often missed)

Respiratory symptoms Consider the usual causes of respiratory • Whooping cough – pertussis vaccination may not have
symptoms relevant to the age group, been available in country of origin
such as viral respiratory tract infection, • TB should be considered in children with cough
pneumonia, asthma, bronchiolitis > 2 weeks
and croup • Sickle cell disease may present with acute chest
syndrome
• Parasite infections may (very rarely) cause wheeze/
respiratory symptoms

Abdominal pain Consider the usual causes, such as • Parasite infection – diarrhoea, rectal bleeding,
acute infection, constipation, surgical or constipation, hepatic symptoms, haematuria
gynaecological problems • Helicobacter pylori gastritis – early satiety, anorexia,
family history of similar symptoms, nausea/vomiting
• Hepatitis

Diarrhoea Consider the usual causes of viral and • Bacillary* and amoebic dysentery are common in the
bacterial gastroenteritis developing world
• Parasitic infections are common
• Lactose intolerance may be more common in some
racial groups

Rashes Eczema; dermatophyte (Tinea) infections • Strongyloides infection may cause an intermittent
urticarial rash lasting a few days (larva currens); this
may be located anywhere but is most typically on the
buttocks/perianal region
• Skin nodules or a depigmented rash on the lower shins
suggest parasite infections; specialist consultation is
required

Continence issues Typical nocturnal or diurnal enuresis, • Chronic urinary tract infection may not have been
bladder irritability detected/treated
• Consider mental health issues as a cause of secondary
enuresis
• Consider female genital mutilation (FGM) as an
additional possibility/contributor in girls (seek advice on
how to broach this)

Musculoskeletal pain Low vitamin D status is an extremely

common cause in refugee children/
young people with risk factors

Fussy eating Behavioural issues; excess milk intake • Food insecurity (not being able to afford/access
adequate food) is well documented in refugee families
after resettlement
• Helicobacter pylori gastritis is a common cause of poor
appetite and fussy eating
• Other gastrointestinal infections
• Dental disease – pain with chewing may restrict
food intake

*More likely shortly after arrival.

TB, tuberculosis.
158
 Refugee health 3.14
reduced ­appetite, including gastrointestinal infections Vitamin D deficiency and insufficiency
(Helicobacter pylori gastritis, Giardia intestinalis,
Vitamin D is essential for bone and muscle health
other parasites), other infections (including TB), low
(see Chapter 19.5). Groups at risk of low vitamin D
vitamin D levels/rickets and dental disease. Mental
include:
health issues may also be a cause of poor intake/
growth.
• people with naturally dark skin colour
Iron deficiency may affect appetite and compound
• people with limited sun exposure/excessive time
indoors (this should be considered in complex
poor intake. Excessive cow's milk intake is a common
disability/chronic illness), covering clothing
cause of iron deficiency. Tea drinking may contribute
to iron deficiency in older children as tea chelates iron
• people with conditions affecting the metabolism
of vitamin D (end-stage liver disease, renal
and reduces absorption.
failure, some medications, e.g. isoniazid,
Fussy eating is often due to high calorie intake
anticonvulsants)
in the form of drinks/juice at the expense of solids/
mealtimes. It may also be due to a mismatch between
• babies born to women with low vitamin D
food the child is used to and food offered at childcare/
• breastfed babies with other risk factors.
Up to 90% of African Australians living at low
school.
­latitude have low vitamin D levels, and rickets has
Once an initial screen has been completed and
­re-emerged as a paediatric health issue (Fig. 3.14.1).
treatment initiated as necessary, a period of moni-
Low vitamin D levels are also seen commonly
toring growth is often appropriate. The p ­ rinciples of
in ­refugee cohorts that wear covering clothing
healthy eating are universal and should be ­discussed
(Afghani, Iraqi), and are increasingly recognized in
with families; essentially this is an opportunity
other ­population groups.
for health promotion in the post-arrival screen.
Referral to a local dietitian may be appropriate.
Screening
Breastfeeding should be promoted. Encourage
introduction of solids at 4–6 months, introduction • Measure vitamin D levels, calcium, phosphate and
of meat before 12 months, and an appropriate diet alkaline phosphatase (ALP) in all children with
containing vegetables, legumes, fruit, cereals, meat risk factors. If the initial vitamin D level is normal,
and dairy products. Milk should be limited to less repeat at the end of the first winter in Australia.
than 600 mL daily after 12 months; in children with • Also measure PTH in children with low calcium
lactose intolerance, regular yoghurt and cheese are intake, symptoms/signs or multiple risk factors.
appropriate sources of calcium. Adequate calcium • Children with hypocalcaemia or rickets need urgent
intake is essential for all children, but has additional specialist assessment and will require further
implications in groups at risk of low vitamin D sta- investigations.
tus. Home-cooked food and maintaining families' • Levels at the start and end of winter can be
cultural food preferences is usually healthier and useful to judge the frequency of dosing. Clinical
more economical. photography is useful to monitor bony deformity.

A B

Fig. 3.14.1 (A) Rickets at age 2 years, caused by a combination of low vitamin D and low calcium intake in the setting of cow milk
allergy. (B) Radiographic improvement (in a different child) of severe vitamin D deficiency with vitamin D therapy.
159
 3.14 SOCIAL AND PREVENTATIVE PAEDIATRICS

Management Anaemia is usually multifactorial in refugee

c­ hildren and young people. Contributors include iron
Prevention is key, so attention to pregnancy and
­deficiency, malaria and parasite infection/infestation.
maternal vitamin D status and screening children/
Iron deficiency is usually nutritional, but may be due
adolescents at risk is important. Promote breastfeed-
to gastrointestinal loss or possibly associated with
ing and recommend daily multivitamin supplements
H. pylori infection.
­containing vitamin D until 12 months of age for all
breastfed infants at risk of low vitamin D levels.
• Symptomatic rickets/hypocalcaemia (including Immunization catch-up
tetany, stridor, seizures – more likely in infants)
requires hospital assessment, with or without Vaccine-preventable diseases are endemic and/or epi-
admission. These children may require an demic in humanitarian countries of origin, and dis-
intravenous calcium infusion. High doses of ruptions to health care may affect vaccine quality and
vitamin D can worsen hypocalcaemia (by access to immunization. Most refugees do not have
promoting deposition into bones) if there are written documentation of immunization, and immu-
inadequate calcium stores. nization records are not a pre-departure requirement.
• Low vitamin D status can be treated with either If present, written records are considered reliable
daily dosing (1000–2000 IU orally daily) or a single ­evidence of vaccination status. Serological testing for
high dose (up to 150 000 IU stat orally in children vaccine-preventable disease is not recommended; there
aged over 12 months, sometimes called ‘Stoss is no significant cost benefit, it requires additional
therapy’). Children with levels below 25 nmol/L blood sampling, and combination vaccines mean that
may require a repeat high dose in 6 weeks. In the the same vaccine will be required if there is inadequate
longer term, children on high-dose therapy will immunity to any of the vaccine components.
require repeat dosing every 3–12 months depending Specific information on catch-up vaccination infor-
on levels/clinical situation. mation is available from national resources, such as the
• Ensure an adequate dietary calcium intake Australian Immunisation Handbook. Key principles
after administration of vitamin D. Calcium include:
supplements may be needed in patients with • No-one arriving as a refugee will be vaccinated
a low dairy intake. and up to date according to the Australian or
• Repeat bloods 3 months after starting treatment. New Zealand immunization schedule, owing to
Children with ongoing risk factors require o ­ ngoing differences in country of origin immunization
surveillance/management. Although it is worthwhile schedules.
recommending time outside, this may not ensure • People of a refugee background should be
adequate levels during winter at low latitude. There vaccinated so that they are up to date according to
is no single public health message for sun exposure the national immunization schedule equivalent to a
in ­children that can account for skin colour/­latitude; local born person of the same age.
in practice, encourage full sun protection during • Post-vaccination serology is recommended for
September to April and encourage play outside before, household contacts of hepatitis B.
during and after school. Children with naturally very • Consider bacille Calmette–Guérin (BCG)
dark skin have a much lower risk of skin cancer, and vaccination in children aged 16 years or less, if
can tolerate intermittent sun exposure without sun- not given previously, and TB screening tests are
screen throughout the year, but should still wear a hat negative, including for Australian-born siblings.
and sunglasses. • Enter immunization data into national registries
where available.
Haematology issues • Provide a written record and a clear plan for
ongoing immunizations.
The prevalence of anaemia in resettled paediatric • Remind families to plan early for travel
refugee cohorts is 10–30%; higher rates are reported immunizations (many families travel, and may be at
in studies of children in refugee camps. Iron defi- increased risk when visiting friends and relatives in
ciency affects a similar proportion. Vitamin B12 and their country of origin).
folate deficiency have been reported in refugees from • Translated health information sheets are available.
Afghanistan and Sri Lanka. Haemoglobinopathies
are more common in African, Asian and Middle
Tuberculosis screening
Eastern populations. This means many children
will be carriers with mild anaemia (actual disease TB is due to infection with Mycobacterium tuberculo-
is uncommon). Lead toxicity has been reported in sis (MTB) complex. Transmission occurs by exposure
160
­refugee children. to aerosolized droplets from people with respiratory
 Refugee health 3.14
infection. Approximately one-third of the world's If they have symptoms or signs suggesting active
population is infected, but only 5–10% of people ­ isease, further investigations may be needed. Children
d
with infection develop TB disease. Latent TB infec- with LTBI have a lifetime risk of 5–15% of develop-
tion (LTBI) refers to the presence of TB infection (i.e. ing TB, although the risk is higher in recently infected
positive screening test for exposure to MTB) without infants and younger children. Isoniazid preventative
evidence of active disease on history, examination treatment for 6 months reduces the risk of TB disease
and chest X-ray. People with LTBI are, by definition, by 50–90%. Children with TB disease require special-
asymptomatic and non-infectious. ist management.
TB disease may be either primary or reactiva-
tion of LTBI. Primary disease develops as a con- Parasites
sequence of initial infection, reactivation disease
Malaria
occurs after a latent period, which may be many
years. The risk of progression from TB infection to Malaria is caused by infection with protozoan
TB disease is highest in young children, relatively parasites transmitted by mosquitoes. Most severe
­
high in adolescents, and increased in the first years malaria and cerebral malaria is caused by Plasmodium
after migration. Up to 50% of infants and 15% of falciparum and the highest burden of disease is in
older children with LTBI will develop TB disease young children. Patients with P. falciparum disease
within 2 years of being infected, hence the impor- can deteriorate rapidly. People l­iving in endemic areas
tance of TB screening and treatment of both TB typically develop immunity during childhood and may
disease and LTBI. be infected but asymptomatic. They are at increased
BCG vaccine has been used to vaccinate against risk of symptomatic infection after migration as their
tuberculosis since 1921, and worldwide coverage is immunity wanes. The prevalence of malaria was 5–10%
80%. Protection varies: meta-analysis shows that BCG in Australian paediatric refugee cohorts from Africa;
is about 50% protective against respiratory TB, but this has reduced since the introduction of PDMS.
more protective against meningitis (64–85%) or death Malaria screening is a priority in any recently arrived,
(70–85%). BCG vaccination leaves a scar in 75–99% of febrile refugee. Children with malaria always require
recipients. In Australia, BCG is given in the left del- hospital assessment, and ­usually hospital admission.
toid; however, it is given in different sites overseas, and
scars may be located on the deltoid, forearm, scapula
Schistosomiasis
or thigh (either side).
Positive TB screening tests are found in 35–55% of Schistosomiasis affects 200 million people worldwide
resettled paediatric refugee cohorts. This reflects the and is endemic in Africa, but is also found in Asia and the
prevalence of TB in their countries of origin/transit; Middle East. It is often called ‘­bilharzia’, and ­families
however, children may also be infected after settlement may know this name. The prevalence of Schistosoma
through contact with adults with TB disease, including infection is 12–38% in African refugee cohorts.
visiting friends and relatives. Active disease is uncom- Schistosomiasis is caused by infection with one
mon in refugee children; respiratory disease is the most of five species of trematodes (flukes) through con-
common form, although non-pulmonary or dissemi- tact with infected fresh water. The manifestations
nated/severe disease is more frequent in children than of chronic infection depend on the species c­ausing
in adults. Younger children with pulmonary TB dis- ­infection; ­end-stage pathology occurs as a result of
ease are rarely infectious owing to their pattern of dis- ­granulomatous inflammation in response to the flukes.
ease (lack of cavitating lesions, low bacterial load) and S. ­haematobium is associated with ­haematuria and long-
lack of tussive force. term bladder pathology, whereas S. ­mansoni causes
The Mantoux test remains an appropriate first- gastrointestinal symptoms (pain, ­diarrhoea/blood per
line screening test and can be used at any age. The rectum) and portal hypertension. Schistosomiasis is
Mantoux test is administered as an intradermal injec- treated with praziquantel.
tion, and induration (not erythema) is measured
48–72 hours later. BCG status affects interpretation
Strongyloides infection
of the Mantoux test, but does not preclude its use.
Essentially a Mantoux test induration ≥ 10 mm is con- Strongyloidiasis is a nematode (worm) infection trans-
sidered positive in children from endemic areas, and mitted through contact with infected soil. Humans
≥ 5 mm is considered positive for household contacts are the host for Strongyloides and the infection can
of TB cases. Interferon-γ release assays are an alterna- last for decades through a cycle of autoinfection.
tive screening test in adolescents and adults. Children The ­prevalence of Strongyloides in recent Australian
and adolescents with a positive TB screening test and ­refugee cohorts is 1–9%, although a higher preval­
161
normal history and examination require a chest X-ray. ence is reported internationally in African refugees
 3.14 SOCIAL AND PREVENTATIVE PAEDIATRICS

(23–49%). Most people with Strongyloides infection Clinical manifestations depend on age of acquisition,
are asymptomatic; however, in the setting of immuno- viral load and host immune response. Infected children
suppression (including steroids) it can cause a hyper- are less likely to have acute symptoms and more likely
infection syndrome that has a high case fatality rate. to develop chronic infection, which is a­ ssociated with
Children from Strongyloides endemic areas should cirrhosis, liver failure and liver cancer. Adolescents
have screening prior to starting immunosuppression. and adults usually develop acute symptoms, but clear
Treatment is with ivermectin. the infection. Chronic HBV is found in approximately
5–8% of refugee children/young people and requires
specialist follow-up and lifelong monitoring. HBV is
Faecal parasites
a vaccine-preventable disease, and ­immunization of
Pathogenic faecal parasites are common in refu- household contacts is a priority.
gee children, and are found in 15–40% of children
on post-arrival health screening. Some refugee ser-
Other viral hepatitis
vices give empiric antihelminth therapy, which treats
many, but not all, parasites. Specific therapy is needed There are limited data on the prevalence of hepatitis
for Giardia; Schistosoma, Strongyloides, amoebiasis, C virus (HCV) infection in refugee children, although
Taenia spp and Hymenolepis nana (dwarf tapeworm). HCV is common in adults from Egypt, and other parts
Giardia intestinalis is the most common pathogen of Africa and Asia. Hepatitis delta screening is impor-
identified, with a prevalence of 10–20%. Pathogenic tant in children with chronic hepatitis B from Africa
faecal parasites are found in refugee cohorts from all and the Middle East. Many refugee children have evi-
areas, including Europe and the Middle East, as well dence of past infection with hepatitis A, although
as Africa and South Asia. Macroscopically visible few have a history of an acute illness with jaundice/
worms are likely to be tapeworms or ascarids. Parasite cholestasis.
infections may last for years and can affect for nutri-
tion, growth and function. In general, treatment is
Helicobacter pylori
usually a short course (often single dose) and well tol-
erated. Table 3.14.3 shows pathogenic parasites requir- H. pylori infection is common in refugee children with
ing treatment and parasites generally considered to be a prevalence of over 80% in recently arrived African
non-pathogenic. groups. The infection is usually asymptomatic, and its
significance is unclear, although H. pylori is classed as
a carcinogen and treatment is recommended in adults.
Other infections In practice, it is practical to treat children with symp-
toms, and the effect is usually dramatic.
Hepatitis B
Hepatitis B is a viral infection affecting the liver that is
Dental issues
transmitted through exposure to infected body ­fluids
(usually bloodborne or sexual). Horizontal transmis- Refugee children have high rates of dental disease,
sion is important in young children and household con- with over half having dental caries or other problems.
tacts of people with hepatitis B virus (HBV) ­infection. Access to dental services may be problematic.

Table 3.14.3 Pathogenic and non-pathogenic parasites

Pathogenic parasites requiring treatment Non-pathogenic parasites (no treatment required)

Entamoeba histolytica Entamoeba coli

Ascaris lumbricoides Entamoeba hartmanii
Giardia intestinalis Entamoeba gingivalis
Ancylostoma or Necator (hookworm) Endolimax nana
Strongyloides stercoralis Iodamoeba butschlii
Schistosoma spp. Dientamoeba fragilis*
Taenia solium or T. saginata (tapeworm) Blastocystis hominis*
Trichuris trichiuria (whipworm) Chilomastix mesnili
Hymenolepis nana (dwarf tapeworm) Trichomonas hominis

162 *Rarely implicated as a pathogen.

 Refugee health 3.14
of refugee children grow up to be well-adjusted adults
Mental health and make significant contributions to their countries
of resettlement.
Practical points

• Refugee children and young people may have witnessed or Assessment of development
experienced significant trauma, although this history may not
be given offered until a therapeutic relationship is established. and learning
• Refugee children and young people are at high risk for
mental health problems, although the reported prevalence
of conditions such as PTSD, depression and anxiety varies.
• Most refugee children grow up to be well-adjusted adults. Practical points

• Refugee children often have additional risk factors

for developmental problems, including disrupted or
Children and adolescents of a refugee background
inadequate education, language transitions, mental health
will, by definition, have experienced conflict, signifi- and trauma issues and severe medical problems.
cant upheaval and transitions with migration and • Refugee children and young people may not have had
resettlement that may affect their mental health. screening for vision or hearing impairment.
They may have witnessed or experienced physical or • Consider migration, language and environment transitions
sexual ­ violence and been exposed to life-threaten- when establishing a child's developmental milestones.
ing situations. They may have witnessed significant • Refugee children and young people may have an
incorrect birth date on their paperwork; this history may
trauma, including seeing family members killed. Other not be given, but has significant effects on development
­experiences may include bereavement, being separated assessment, school placement and using age-
from family and community, disruption to school- standardized testing.
ing or routines, and prolonged periods of dislocation
with uncertainty around the future. A history of these
­profoundly ­traumatic events is unlikely to be given Development may be affected by any combination of
during the ­initial assessment; it may emerge once a biological, environmental, social and emotional fac-
therapeutic relationship has developed. tors. Considerations in children of a refugee back-
Responses to trauma include depression, anxiety, ground include:
post-traumatic stress, low self-esteem and guilt. These • Biological: malnutrition, chronic disease, severe
may manifest in a variety of ways including ­behavioural infection (including meningitis and cerebral
problems, problems with sleeping and eating, poor malaria), hearing impairment, visual impairment,
school performance, difficulty ­making friends, enuresis family history, prematurity
and psychosomatic symptoms. Mental health should • Environmental: living conditions, access
be considered in the broader family context; parents to schooling, access to food, exposure to
with mental health issues often have reduced coping communicable diseases, migration and language
and parenting skills. transitions (and the age at which they occurred)
There are difficulties with diagnosis and measurement • Social: loss of parents, parenting roles, family
of mental health issues across cultures. Studies of refu- disruption, roles and responsibilities
gee children and young people report widely v­ arying • Emotional: stress, trauma experiences,
prevalence figures for mental health problems in differ- displacement, uncertainty around future, mental
ent groups, partly because of different r­ ating scales are health problems.
used. Figures range from 3% to 94% for PTSD, 4% to Parental concern about a child's development is highly
47% for depression and 3% to 93% for anxiety problems. predictive of developmental delay/disability; how-
The largest pooled analysis of mental health problems ever, absence of concern is not necessarily reassuring.
in people of a refugee background found that the prev- Families with multiple children will usually readily
alence of PTSD was 11% in children. Unaccompanied identify if one child's development is different to that
minors and people with uncertain visa status are at of their siblings.
higher risk of mental health problems. Completing a thorough developmental and edu-
Although refugees may have experienced signifi- cational assessment in refugee children/adolescents
cant trauma, there is good evidence that they often presents challenges. Like any other child, a develop-
have great resilience and positive social adjustment. mental and family history is essential; however, migra-
Experience of trauma does not always predict worse tion, education and language transitions in relation to
mental health outcomes, and mental health symptoms development should be considered. There are d ­ ifferent
163
may not result in functional impairment. The majority aetiologies to consider in ­ developmental/learning
 3.14 SOCIAL AND PREVENTATIVE PAEDIATRICS

problems in refugee children, and basic screening friends and community connections. There may be a
for contributors such as vision, hearing and men- tension in prioritizing settlement needs, and families
tal health problems is frequently missed. There are may have multiple conflicting appointments, which
many issues regarding the timing and validity of for- should be considered when organizing referrals and
mal language or intelligence testing in a child's second follow-up. Settlement is an ongoing process, which
language. Incorrect birth dates create additional com- takes time, sometimes many years; however, people
plexity. A detailed assessment takes time and requires stop being a refugee as soon as they get off the plane –
close liaison with the family, and the help of a skilled they are Australians, or New Zealanders, of a refugee
interpreter. background.

Incorrect birth date Clinical example

Refugee children may have an incorrect birth date on
Sar Po Lay, an 18-month-old child from Karen
their visa paperwork, which becomes the basis for all State in Burma arrived in Australia 4 months ago
the official documentation in the country of settlement. from a refugee camp on the Thai–Burma border.
This issue is not uncommon and may have significant He has been referred because his height and
effects on school placement, developmental assessment weight are below the third percentile. His background history
(including formal assessments such as IQ testing) and includes an uncomplicated pregnancy, delivery at home, and
access to welfare. The reasons for an incorrect birth date he was noted to be a small baby (birth weight unknown).
He breastfed well, but had chronic diarrhoea from the age
are often complex; it may be unknown, due to error, or
of 2 months until arrival in Australia. He had one set of
changed owing to family circumstances/conditions in immunizations at 6 weeks of age. He is still breastfed, and
the country of origin. Any child with a birth date of eats two small bowls of rice porridge daily.
01/01/(year) is almost certainly younger. Families may Sar Po Lay's mother is 18 years old; she is 148 cm tall and
be reluctant to raise this as an issue, and fearful of los- weighs 38 kg. She has no print literacy and is very shy. They
ing their visa, and it often emerges as an issue some are living with friends and have limited settlement support;
they are spending most of their time inside.
years after settlement. Correcting a birth date requires
Physical examination shows a symmetrically small boy,
an assessment of the family narrative, documenting with reduced subcutaneous fat stores, pale conjunctivae,
any existing paperwork or known milestones, and an delayed dentition and a scar on the right shoulder. Sar Po Lay
assessment of the child's age and ­development. A bone has not had a refugee health check and needs blood tests,
age X-ray may be helpful. a Mantoux test and a faecal specimen, with initial additional
investigations including folate, vitamin B12 and thyroid
function testing because of his poor growth.
Second language acquisition These tests reveal Giardia intestinalis and a collection
of (non-pathogenic) protozoa (likely reflecting water
Immigrants usually achieve conversational profi- contamination), low vitamin D and raised ALP levels,
ciency 2–3 years after starting a new language; how- microcytic anaemia, undetectable ferritin, hepatitis B
ever, it takes much longer to achieve academic success infection, and a Mantoux test of 20 mm. A subsequent chest
in a new language, especially when schooling occurs X-ray is normal.
in the new language. Large international studies in Sar Po Lay is treated with metronidazole and high-dose
advantaged children with age-appropriate schooling vitamin D, and starts iron supplements. He is given his
first set of catch-up immunizations and a plan is devised
show that children aged 8–12 years when they migrate
for introducing an increased range of solid food, including
achieve academic language more quickly than other meat, dairy, vegetables and grain, after discussing how his
age groups; however, they take 5–7 years to reach the mother could access and afford these foods in Australia. He
standard of native-born speakers. Students from a has another visit organized in 2 weeks to discuss starting
refugee background are likely to have additional risk isoniazid prevention treatment for latent TB infection
factors for educational disadvantage, including inter- (6 months' duration, with vitamin B6 because of his poor
rupted or inadequate schooling, financial hardship, growth and monitoring liver function tests because of
hepatitis B). The family is referred for case management
mental health issues, cultural transitions and family support, with a plan to access housing support, local
stressors. maternal and child health, community support groups, a
community dietitian, English classes, and a health/mental
health assessment for his mother. Sar Po Lay's poor growth
is likely a combination of familial factors, low birth weight,
Settlement considerations chronic diarrhoea, malnutrition, prolonged breastfeeding
and delayed introduction of solids. He has severe iron
Health assessment is only one part of settlement for
deficiency and is at risk of other micronutrient deficiencies.
refugee children and families, who also need to estab- He will need long-term follow-up for his hepatitis B, and
lish housing, education, employment and the usual monitoring of his growth.
164
routines of daily life in a new country, as well as make
 4
PART

BEHAVIOUR AND
MENTAL HEALTH
NEEDS

165
 4.1 Life events of
normal children
Gehan Roberts, Harriett Hiscock

Although every child follows his or her own individ- development in the context of secure early relation-
ual developmental trajectory, most children achieve ships lays the foundations for future developmental
developmental milestones at predictable ages (see competence.
Chapter 2.2). These anticipated milestones provide an The child's behaviour and development are always
important yardstick against which to assess the indi- the result of a complex series of transactions between
vidual child's development. A departure from these the child and the environment. Assessment of the
expected developmental milestones, usually present- child's environmental context therefore, is a critical
ing as a developmental delay or behavioural prob- part of behavioural and developmental assessment.
lem, should prompt concerns that development is not
­proceeding normally.

Risk and resilience

Practical points
There are well-documented risk factors that make
the child vulnerable to a less than optimal outcome.
• Organic causes of infant crying are uncommon but should
be suspected if there is associated atopic disease (such Similarly, there are protective factors that increase the
as eczema), poor weight gain, frequent (more than three resilience of the child and increase the likelihood of a
times per day) vomiting or blood/mucus in the infant's good outcome. Some of the risk and protective fac-
bowel actions. tors are:
• In toddlers, low-priority misbehaviours (e.g. tantrums, • Child factors (e.g. prematurity or chronic illness
whining) are best managed by ignoring or distraction.
versus good language or social skills)
• High-priority misbehaviours (e.g. hitting, kicking) are best
managed by asking the child to stop and, if they do not, • Family factors (e.g. parental mental illness versus
by putting them in ‘time out’. stable income or family cohesion)
• A child with unexplained school-based behaviour or • Community factors (e.g. inadequate housing versus
learning problems usually needs a multidisciplinary participation in community activities)
assessment, including vision and hearing testing and, • Broader environmental influences (e.g. drought
where possible, cognitive testing by an educational versus universally available health care).
psychologist.
Parent and family relationships are some of the most
• Up to one in five adolescents will experience significant
physical or emotional problems. Screening questionnaires important protective factors in promoting optimal
that encompass home, school, recreational drug use, development. Recent research suggests the initial ‘map’
sexuality and suicide/depression issues can help to detect for brain development provided by genes is shaped and
these problems. sculpted by the caretaking environment. The develop-
ment of neural connections in early childhood is deter-
mined largely by environmental inputs.
The development of infants and young children is
Risk and protective factors tend to be cumulative,
determined by their genetic potential as expressed by
so that combinations of risk or protective factors are
their interaction with the environment. In the early
more powerful than individual factors.
years it is the parents, most often the mother, who
shape the infant's environment. Research in recent
years has served to re-emphasize the importance of
the caretaking environment on the developing brain,
which in turn impacts on functioning later in life.
Developmental stages
A key requirement for optimal child development is In the course of the child's development there are cer-
secure attachment to a nurturing and responsive care- tain important transition stages. Each stage is asso-
giver, with consistent affection and caring. A child's ciated with predictable developmental events and
and subsequently an adult's emotional health are sig- behaviours, stresses and challenges. The negotiation
166 nificantly influenced by these early relationships. Early of each of these transitions is an important ­milestone
 L ife events of normal children 4.1
that allows the child and the family to proceed to the Risk factors include maternal factors such as an
next level of development. Stresses and challenges unwanted child, prenatal complications, problems
that are commonly encountered during these tran- with bonding and attachment, maternal depression,
sitions but not managed appropriately may result social isolation, few or no identified supports, and a
in negative influences on the child's developmental stressful family situation. Infant risk factors include
trajectory. difficult temperament, excessive crying and irritability,
Important developmental stages are considered sleep problems and difficulty feeding.
below. Risk factors and professional interventions that Professional intervention. Providing support to
may be of assistance are outlined. parents is essential. Assisting parents with realis-
tic expectations and understanding of their baby's
developmental needs and linking them up with a
Pregnancy and birth
network of family and professional supports are
The goal is to produce a healthy, full-term infant, crucial interventions. Medication and frequent for-
together with a healthy mother who can cope with the mula changes are usually inappropriate for sleeping
inevitable stresses and change in lifestyle that comes and crying problems. Rather, parents need reassur-
with a newborn baby. ance that their infant is healthy and does not have
Risk factors include maternal factors such as phys- any underlying medical condition. They should aim
ical and mental illness, substance abuse, smoking, to settle their infant with a consistent approach that
inadequate folate intake, low maternal age, single enables the infant to fall asleep on his or her own
parenthood and poverty. Infant risk factors include rather than being held, rocked or fed to sleep. Some
genetic defects, birth trauma and prematurity. families find a routine of feeding the baby followed
Professional intervention. Regular antenatal care by a short play and then sleep helps. Mothers experi-
enables early detection and intervention for mater- encing problems with breastfeeding should be man-
nal and fetal complications. During labour the pres- aged by an experienced community nurse or lactation
ence of a supportive partner or friend has been shown consultant. Sometimes there are early clues as to
to decrease time in labour and reduce complications. serious dysfunction, such as maternal depression or
Early mother–baby contact facilitates breastfeed- major ­difficulties in the mother–child r­elationship,
ing and sets the stage for a positive mother–infant so that more intensive intervention may be required.
­relationship. While in hospital it is important to estab- All parents need to learn how to manage the follow-
lish links with postnatal services such as maternal and ing inevitable issues:
child nurses, general practitioners and home visiting • Crying. All infants cry. This is now understood to
services. be a normal part of development. However, some
infants are difficult to console and their crying
causes major stress for parents. About 10% of
Early infancy (0–6 months)
infants cry for more than 3 hours per day, 3 or
This is often a challenging time for the family. more days per week for 3 or more weeks. These
Parents and family aim to establish a routine incor- infants are often labelled ‘colicky’. Underlying
porating the needs and demands of the new infant. medical causes for crying are uncommon (< 5%)
Parents bring to this transaction their own beliefs and include cow's milk protein allergy, lactose
and experiences, with varying levels of confidence intolerance and possibly gastro-oesophageal
and competence, and skills at handling stress, uncer- reflux disease. Most crying abates by age 3–4
tainty and fatigue. Parents begin to understand their months, and crying persisting after this raises the
baby's visual, motor and verbal cues, and respond possibility of organic illness or concerns in the
appropriately. This is the beginning of a reciprocal mother–baby relationship.
relationship or ‘dance’ that shapes the baby's brain • Feeding. Most mothers want to breastfeed their
development. If things do not go smoothly, and the infant but not all mothers find breastfeeding easy.
mother perceives the infant as difficult and demand- Problems with incorrect attachment to the breast
ing, the long-term mother–child relationship can be are common and may lead to difficult and painful
compromised, setting the stage for possible future breastfeeding and early weaning.
parenting and behaviour difficulties. • Sleeping issues. Most infants establish a sleep
Establishing appropriate feeding patterns, preferably pattern after 3 months of age, although they
breastfeeding as this has many advantages, is another may not begin to sleep through the night until
crucial task. Another important task is the introduc- 6 months. Common parental complaints include
tion of solids, with many mothers beginning to think difficulties settling their infant and frequent night
about weaning between 4 and 6 months of age. waking. 167
 4.1 BEHAVIOUR AND MENTAL HEALTH NEEDS

for increasing periods of time to enable them to fall

Clinical example asleep on their own, or ‘camping out’ whereby a par-
ent ­gradually withdraws their presence from a baby's
A mother presented with her 7-week-old baby bedroom over a number of nights (see http://www.­
boy. She said he was crying for 2–3 hours a day raisingchildren.net.au). Good eating habits can be
and appeared hungry. She was breastfeeding
her baby every 11/2 hours and said she had no
established with regular mealtimes of a short dura-
milk so she wanted to wean to formula. Her baby vomited a tion (typically 20 minutes or less) and encouraging the
small amount after most feeds and her general practitioner older infant to finger-feed. Parents should offer a vari-
had prescribed a medication for reflux. After a careful ety of foods, understanding that their infant may try a
examination to exclude a physical cause of the crying, it was food many times before finally accepting it.
explained to her that all babies cry, and that crying reaches
a peak around 6–7 weeks of age and then decreases
Toddler period (1–3 years)
by age 3–4 months. She was shown the PURPLE crying
website (http://www.purplecrying.info/), which emphasizes This is a major transition time, as the child moves from
that crying is part of normal development and that not all being an infant to being an active, curious toddler with
infant crying can be soothed. She was encouraged to keep
an increasingly complex set of developmental compe-
breastfeeding and to space the feeds to every 2–3 hours so
that her baby had a good feed and was not snack-feeding. tencies, including language. One of the normal develop-
Tiredness signs in babies were discussed, and strategies for mental tasks in this age group is to develop autonomy
settling her baby when he was tired were explained. She and independence. Parents often perceive these ‘terrible
was asked to keep a feed/cry diary and to stop the reflux twos’ as a challenging time when their child becomes
medication. Two weeks later, her baby was crying less and oppositional and stubborn, seems always to be testing
was settling to sleep better. He was feeding every 3 hours
boundaries and likes to get his or her own way.
and seemed content.
Risk factors, such as the child having a difficult tem-
perament or the use of inconsistent or harsh parenting
strategies, make these issues more likely.
Late infancy (6–12 months)
Common problems in the toddler period
This is a time of rapidly emerging cognitive, develop-
mental and social competencies in the infant. The baby Temper tantrums are common, especially when the
is interested in the environment and will very often ini- child is frustrated at being unable to master a task, or
tiate interaction with caregivers, wanting to play and restrictions are placed on his or her autonomy. Sleep
to be stimulated in appropriate ways. Paradoxically, problems and problems around mealtimes also are
during this time the first signs of stranger anxiety and very common. Most children will begin, and some
separation protest appear. The infant becomes anx- will complete, toilet training during this time period,
ious around strangers and is no longer willing to be and this sometimes becomes a symbol of the struggle
picked up by an unfamiliar person. The infant also between the parents and the child regarding the child's
may become distressed when the parent is out of sight, autonomy. Signs of developmental delay, including
for instance at bedtime or if left in the care of a baby- language problems, may also become evident during
sitter or in childcare. this time period.
During this time, food issues become increasingly Professional intervention. The primary goal of inter-
important, with most mothers completing weaning vention is to teach parents to understand their child
and moving towards a varied diet with regular meals. better and to change maladaptive parenting strategies
Risk factors include maternal and family stress, into consistent, warm and logical strategies. Parents
inappropriate responses to increasing infant needs for also need to understand what is developmentally nor-
stimulation and social interaction, difficulty changing mal at this age. For example, temper tantrums can be
from breast/bottle-feeding to a solid diet, and sleep managed by:
difficulties. • staying calm
Professional intervention. Continued support for • walking away
parents, provision of accurate information about • ignoring the behaviour until the tantrum stops
developmental and other needs of their rapidly devel- • praising the child when appropriate behaviour
oping infant, and ensuring that there is a ‘goodness begins again.
of fit’ between the infant and his or her parents are Most tantrum behaviour will escalate initially and then
essential. Parents should realize that much of their will decline with this approach. For more aggressive
infant's behaviour is exploratory and that the infant behaviour, ‘time out’ may be used. This involves pla­
is not being deliberately naughty. Sleep problems can cing a child in a quiet room or corner for a m­ aximum
be managed with behavioural interventions such as of 1 minute per year of age whenever the undesired
168
‘controlled crying’, where parents leave their infant ­behaviour occurs. The child is allowed out from the
 L ife events of normal children 4.1
‘time out’ place when he or she is quiet. This is effective stressed, or feels powerless. The key to management
in children over 18 months of age and its use should is identifying the cause of the frustration or stress
be limited to only the two or three most problematic (e.g. not wanting to share a toy) then removing, redi-
behaviours. recting or distracting the child away from the cause.
Parents should respond promptly and calmly, telling
Preschool period (3–5 years) their child not to hit or bite when they remove the child
from the situation. As for toddlers, ‘time out’ is also an
During this period, there continues to be a rapid expan-
effective strategy.
sion in language, cognitive ability and social skills.
Tantrums are very common (see Toddler section
Enriching early learning settings such as kindergarten
above).
allow the child's natural curiosity to be stimulated by
Language delay affects around 10% of preschool
systematic input from trained preschool teachers and
children (see Chapter 2.2). Causes include simple
by exposure to same-age peers. Language continues to
language delay (expressive and/or receptive), deaf-
develop rapidly, as do the child's cognitive ability and
ness, autism spectrum disorder, global developmental
social–emotional skills.
delay and social–emotional deprivation. Referral for a
Risk factors in children include language or other
speech therapy assessment is recommended if a child
developmental delay, poor social skills, difficulty
uses fewer than 50 words at 2 years of age or has no
focusing attention, separation difficulties from par-
two-word combinations at 21⁄2 years of age, or does
ents and behaviour problems (especially aggression).
not understand simple instructions without gesture.
Family risk factors include low maternal educational
Any child with a language delay needs to be referred
levels, poverty and being a single parent.
for audiology testing to exclude hearing problems.
At the end of this period the child makes the very
A delay in toilet training may be due to a global
important and symbolic transition to school, so issues
developmental delay or may reflect a toddler's ‘battle’
of school readiness become apparent. There is an
with parents as the toddler tries to establish auton-
emerging understanding that ‘school readiness’ is not
omy. A programme of regular toileting together with
a threshold of skills that a child needs to achieve in
frequent praise and rewards (e.g. stickers) will often
order to start school, but rather an assessment frame-
achieve continence. Most children are toilet trained by
work for better understanding the child's unique pro-
4 years of age.
files of strengths and vulnerabilities, and risk and
Professional intervention: Parents of preschool chil-
resilience factors. School readiness has the following
dren often seek professional help for concerns about
three key dimensions:
language or developmental delay, behaviour problems,
• Children who are ready to learn delayed toilet training, or questions about school read-
• Schools that are ready for children iness. Feedback to families about the results of assess-
• Parents and communities who are able to support ments at this age needs to be cautious because of the
the child's development.
great variability in maturation rates. Providing par-
Readiness to learn is further divided into five skill
ents with information about realistic expectations in
areas
this age group and teaching basic skills in behaviour
• Health and physical development modification is often very helpful. Many problems are
• Emotional wellbeing and social competence minor and are often transient, and simple, short-term
• Approaches to learning interventions are often effective. However, in some
• Communication skills children there are emerging signs of more serious
• Cognitive skills and general knowledge. problems, including developmental delay, communi-
A number of tests assess school readiness but none is
cation problems, attention difficulties or more serious
sufficient in isolation. The decision to send a child to
behaviour problems. These children may require vision
school should be made by the parents, with input from
and hearing testing, a speech assessment and, where
those involved with the child, especially the preschool
an autism spectrum disorder is suspected, a multidisci-
and primary teachers. The rate of maturation during
plinary assessment.
the preschool period may be uneven and is certainly
not linear. The child who appears ‘immature’ at the age
of 4 years, for example, may mature rapidly during the School years (over 5 years)
following 6 months.
School is an important formative experience for all
children. Children who have difficulty functioning at
Common problems presenting in preschool
school, because of learning difficulties, attention or
Hitting and biting are common in the preschool setting. behaviour problems, or social difficulties, will almost
Occasional biting is usually experimental. Repeated always experience adverse outcomes beyond school.
169
hitting or biting may occur when a child is frustrated, Children who struggle academically or socially have
 4.1 BEHAVIOUR AND MENTAL HEALTH NEEDS

been shown to be at major risk in adolescence and later their own partners and children. Managing ­bullying
life for delinquency, unemployment and depression. involves the whole school, with increased awareness,
The early years of school are particularly impor- teaching students about conflict resolution and asser-
tant. Children who have difficulty reading from the tiveness training, peer counselling and improved adult
outset and who are not established readers by the end supervision.
of grade 2 are likely to continue to have problems Professional intervention. It is important to identify
throughout their school career. school learning and behavioural difficulties as soon as
Risk factors include chronic health problems, vision possible so that appropriate interventions can be put in
and hearing deficits, problems with concentration and place. The longer this is delayed, the greater the chance
subtle developmental weaknesses in the areas of motor of a poor outcome. Assessment should involve close
function, visual–motor integration, temporal sequen- evaluation of biological, developmental, behavioural
tial organization (problems remembering the order of and environmental factors that may be contributing
information) and language. Risk factors in the fam- to problems. Hearing and vision should be assessed.
ily include low parental education, low expectations of Often in this age group a multidisciplinary evaluation
school achievement, parenting difficulties and other that includes a special educational assessment is the
family dysfunction. Other risk factors include a poor most appropriate. Where possible, a child should be
match between the child's temperament and preferred referred to an educational psychologist for formal cog-
style of learning, and classroom placement or teacher nitive testing, including tests of intelligence. A detailed
expectations and teaching style. and comprehensive assessment will often point to the
need for specific developmental and educational inter-
ventions that address the individual needs of the child.
Common problems presenting at school
These may include remedial classes at school and/or
Attention difficulties may manifest in many ways, tutoring outside school.
including poor concentration, ‘day-dreaming’, quiet
withdrawal or disruptive behaviour. Causes include
attention-deficit/hyperactivity disorder (ADHD), learn-
Clinical example
ing difficulties, intellectual disability, language delay,
absence seizures, hearing and vision problems, and A mother presented with her 8-year-old son,
depression/anxiety. Each of these can affect a child's Ed. His teachers had complained that he was
learning. Treatment depends on the underlying cause ‘mucking around’ in class and was disruptive.
and health professionals need to liaise with the child's He had problems with spelling and writing. His
teacher to ensure that the teacher understands the father had had similar problems at school and left in year 10.
His mother said that Ed was fine at home and tended to play
child's difficulties and how they may affect learning
computer games or ride his bike. He was noted to be quiet
(see Chapter 4.3). during the consultation and he said he had few friends at
Learning difficulties occur when a child's academic school. His vision and hearing were assessed and they were
achievement in areas such as reading, spelling, writ- normal. A neurodevelopmental assessment was performed,
ing or mathematics is substantially below the level which revealed weaknesses in auditory sequencing and
predicted by their intellectual abilities. Learning dif- language processing. The school psychologist performed a
ficulties affect 10–15% of schoolchildren. Early rec- cognitive assessment, which revealed that Ed had normal
intelligence but a specific learning difficulty involving reading,
ognition, diagnosis and remedial teaching are vital writing and spelling. This was discussed with his teachers,
to ensure that the child does not lose confidence and who arranged remedial teaching and more computer time
become angry, depressed or frustrated. Children with for Ed's class work.
learning difficulties should also have their vision (see
Chapter 22.2) and hearing assessed and any problems
treated so that their ability to learn in the classroom
Adolescence
is optimized. Children with learning difficulties are
unlikely to ‘grow out of’ their difficulties, so reassur- Adolescence is a time of immense change (see
ances that the child will improve with maturity are Chapter 3.11). The young person needs to adjust to
usually inappropriate. physical and emotional change, acquire an appropri-
Bullying is the deliberate desire to hurt someone ate gender role, join peer groups, become emotionally
with words or actions. Children who are bullied may independent of parents and other adults, and prepare
refuse to go to school, be very tense and unhappy after for career and relationships in life. Although most
school, or show other signs of unhappiness such as dif- adolescents negotiate this period successfully, up to
ficulty sleeping. Children who bully may be physically one in five will experience significant physical or emo-
punished at home and are more likely to grow up to hit tional problems. Adolescents often experiment with
170
 L ife events of normal children 4.1
drugs, alcohol and cigarettes, and nicotine addiction to know what is normal during adolescence and be
usually begins in adolescence. given effective strategies for both communicating with
Risk factors include chronic health problems, learn- their adolescent and managing common problems.
ing disability, social isolation, parental physical or
mental illness, and family dysfunction.
Professional intervention. Health professionals need
to address the concerns of the young person as well as
Conclusion
the parents. Clarifying the professional obligation of Development, the progression from a newborn to a
confidentiality at the start of a consultation will reas- socially, physically and intellectually competent adult,
sure and facilitate rapport. In addition to addressing involves a complex interplay of genes and environ-
specific problems, screening questionnaires that encom- mental influences. Helping parents to understand the
pass home, school, recreation, drug use, sexual activity normal life events, developmental stages and transi-
and suicide/depression issues enable a full picture of the tion points in a child's life can help promote optimal
adolescent to emerge (see Chapter 3.11). Parents need developmental outcomes for their child.

171
 4.2 Common mental
health problems
Michael Sawyer, Brian Graetz

Child and adolescent mental health problems are possible to compare the number of ­problems reported
­common in the community. They have a significant for an individual child with the number typically
impact on the lives of children and parents, and also reported for others of the same age and sex in the
impose a substantial financial burden on families community. It is also possible to assess treatment
and communities. In Australia, the National Survey effectiveness by evaluating whether there is a reduc-
of Mental Health and Wellbeing estimated that 14% tion in problems.
of children and adolescents experience significant The second approach divides childhood m ­ ental health
mental health problems (Table 4.2.1). Adolescents
­ problems into a range of different mental ­disorders.
with ­mental health problems frequently exhibit other Each mental disorder consists of a different group
health risk behaviours, including smoking, drinking of symptoms. There are two main diagnostic classi-
and drug abuse (see Chapter 3.11). They also report fication systems that identify these symptom groups.
much higher rates of suicidal ideation and behaviour One is the International Classification of Diseases
than other adolescents in the community. A minor- ­developed by the World Health Organization (ICD-
ity of children and adolescents with mental health 10), and the other is the Diagnostic and Statistical
­problems receive professional help. Manual developed by the American Psychiatric
This chapter describes common mental health Association (DSM-IV; Table 4.2.2). This c­ategorical
problems experienced by children (for brevity, the approach is used widely in mental health services to
term ‘children’ will be used to refer to children and describe children's problems. A common feature of
­adolescents). It also describes practical steps that can both of these approaches is their focus on observ-
be taken to help children, parents and families. The able features of children's problems rather than on
chapter is divided into three components. The first their presumed aetiology. This has facilitated a broad
describes the features of common mental health prob- investigation of the aetiology of children's problems
lems, the second describes general approaches to the ­during the last three decades. Both the DSM and ICD
assessment and management of these problems, and ­classification systems are currently being revised, with
the third provides information about some specific DSM-V scheduled for release in 2013.
problems experienced by children.
Features of internalizing problems
Many children experience anxiety or sadness. However,
Features of mental health when these problems are severe, persist over time,
and are associated with significant problems with
problems daily functioning, they may indicate the presence of
Two approaches are used to describe childhood mental a mental disorder and the need for professional help.
health problems. One approach views childhood prob- Children with high levels of internalizing problems
lems as lying on a continuum from those with very few should be assessed for the presence of depressive
problems to those with a large number of problems. ­disorders or anxiety disorders, and for the presence of
Children identified as having a very large number of suicidal ideation.
problems are considered to fall in the ‘clinical range’ Children with depressive disorders feel sad, lack
of the continuum and to be in need of help. Typically, interest in activities they previously enjoyed, c­ riticize
problems are divided into two broad groups called themselves, and are pessimistic or hopeless about
externalizing problems and internalizing problems. the future. DSM-IV identifies two types of depres-
Externalizing problems include over-activity, aggres- sive disorder. Major depressive disorder consists of
sive and antisocial behaviour. Internalizing problems acute ­ episodes of depressed mood, loss of inter-
include anxiety, depression and shyness. Questionnaires est and ­pleasure in activities, reduced appetite, sleep
completed by children, parents and teachers can be ­disturbance, low energy, low self-esteem, poor con-
172 used to assess the level of problems experienced by centration and feelings of hopelessness. Children with
children. When a continuum approach is used, it is dysthymic disorder will experience similar problems,
 Common mental health problems 4.2
with the distinction being that their symptoms are
Table 4.2.1 Prevalence of mental health problems among
children and adolescents aged 4–17 years in Australia
less severe but more chronic. Children experiencing
depression may think that life is not worth living and
Child Behaviour Checklist Scale Prevalence (%)* they may contemplate suicide. It is essential that all
children exhibiting depressive symptoms be carefully
General areas
evaluated for suicidal risk (see Chapter 4.4).
Total problems 14.1
All externalizing problems 12.9 Fear and anxiety are common to the human condi-
All internalizing problems 12.8 tion, but some children experience anxiety that is well
beyond that which occurs during normal development.
Specific areas These children suffer personal distress and their anxi-
Somatic complaints 7.3 ety interferes with their daily functioning. Children
Delinquent behaviour 7.1 with anxiety disorders exhibit physiological symptoms
Attention problems 6.1
(e.g. tremors, sweating and palpitations), maladaptive
Aggressive behaviour 5.2
Social problems 4.6 behaviours (e.g. avoidance of feared situations) and
Withdrawn 4.3 maladaptive thinking (e.g. ‘I cannot talk in front of
Anxious/depression 3.5 the class because people will think I'm stupid’).
Thought problems 3.1 DSM-IV identifies a number of different types of
anxiety disorder. One of the most common among
Problem areas are not mutually exclusive, and thus ‘Total
problems’ does not equal the sum of externalizing and ­children is separation anxiety disorder, which is defined
internalizing problems. as excessive and developmentally ­inappropriate ­anxiety
*Percentage of children scoring in the clinical range on the regarding separation from home or from major attach-
Child Behaviour Checklist Scales in Sawyer MG, Arney FM, ment figures. Separation anxiety disorder is a common
Baghurst PA et al 2000 Child and Adolescent Component cause of persistent school refusal.
of the Australian National Survey of Mental Health and Obsessive–compulsive disorder is characterized by
Wellbeing. Commonwealth Department of Health and Aged
obsessions (persistent thoughts, impulses or images
Care, Canberra.
that are intrusive and distressing) and compulsions
(repetitive behaviours or mental acts employed to
reduce anxiety or distress). This disorder causes
considerable distress for children and parents. It is
important for medical practitioners to be familiar
with the typical symptoms of this disorder, because
effective interventions are available to provide help.
These include both psychotropic medications and
Table 4.2.2 Important DSM-IV disorders among children ­behavioural treatments.
and adolescents Social phobia, which typically begins during the
teenage years, comprises fear of social or perfor-
DSM-IV category Specific disorders
mance situations in which embarrassment can occur.
Disruptive behaviour Attention-deficit/hyperactivity This condition can adversely affect the development
disorders disorder of social skills and can also hinder academic progress
Conduct disorder
at school. Adolescents with this disorder may be reluc-
Mood disorders Major depressive disorder
tant to attend professional services because of their
Dysthymic disorder insecurity and fear of social embarrassment.
Bipolar disorder

Anxiety disorders Separation anxiety disorder

Features of externalizing problems
Social phobia Externalizing problems refer to problems such as
Obsessive–compulsive disorder
temper tantrums, aggressive behaviour, stealing
Post-traumatic stress disorder
and ­truancy. Boys are more frequently identified as
Learning disorders Reading disorders ­having externalizing problems than girls. Problems
Written expression disorders in this area, particularly those involving aggressive
behaviour, can persist over long periods of time.
­
Pervasive developmental Autistic spectrum disorders For example, infants with a difficult temperament
disorders may exhibit oppositional and defiant behaviour as
preschoolers, and may ­subsequently develop behav-
Elimination disorders Enuresis
ioural disorders during later primary school or high
Encopresis 173
school.
 4.2 BEHAVIOUR AND MENTAL HEALTH NEEDS

Two common mental disorders in this area are these problems. One way of organizing these factors
conduct disorder and attention-deficit/hyperactivity is shown below:
disorder (ADHD). The typical behaviour of those • Predisposing factors
with conduct disorder includes bullying, frequent • Precipitating factors
physical fights, deliberate destruction of other
­ • Perpetuating factors
­people's property, breaking into houses or cars, stay- • Protecting factors.
ing out late at night despite parental prohibitions, Information about children's problems should be
­running away from home and frequent ­truancy from obtained from children, parents and teachers. Children
school. are the key source of information about their internal
ADHD is defined as a persistent pattern of inat- state, including their experience of subjective feelings
tentive behaviour and/or hyperactivity/impulsivity such as anxiety and depression. Parents can provide
that is more frequent and severe than is typically information about more readily observed behaviour
observed in individuals of the same age. Children such as sibling conflict or school refusal, and are an
with inattentive behaviour problems make careless important source of information about the child's
mistakes with schoolwork, find it hard to ­persist early development and the chronicity and s­everity
with tasks and are distracted easily. Those with of the problems. Teachers can report on academic
problems in the area of hyperactivity/impulsivity ­progress and peer relationships. The assessment and
often fidget and talk ­excessively, interrupt others, treatment of ADHD relies heavily on reports from
and are described as constantly being ‘on the go’ (see teachers.
Chapter 4.3).
Young people attending clinical services often
have co-morbid conditions. For example, children with
behavioural problems may also have problems with Clinical example
anxiety or depression.
Peter, a 12-year-old boy, lived with his single
mother. Peter's mother had a history of
depression and his father had been treated for
Practical points alcohol abuse. Peter's mother sought advice
about how to manage his defiant and aggressive behaviour.
She said that, from the time he was born, she had struggled
Assessment of mental health problems
to cope with Peter's difficult temperament and behaviour.
• Careful assessment is essential before initiating any This problem had greatly worsened since she divorced
treatment programme for mental health problems.
Peter's father last year. Since the divorce Peter had had
• Assessment requires knowledge and understanding of little recent contact with his father and he was suspended
children's presenting problems, developmental history,
from school on one occasion after damaging property in
family and social environment.
the school science centre. Peter's teacher described him as
• Information must be obtained from multiple informants being easily distracted and impulsive during the past year.
(children, parents and teachers).
Despite these problems, Peter had continued to maintain
• Aetiological factors can be divided into predisposing, satisfactory academic progress and his teacher believed that
precipitating, perpetuating or protective factors.
Peter's intelligence was above average.
The following factors were important in this problem:
• Predisposing factor: family history of psychiatric disorder
• Precipitating factor: divorce of parents
Assessment and management • Perpetuating factor: rejection by father
• Protecting factor: child's intelligence.
of mental health problems
Assessment
Management
The onset of childhood disorders is usually due to
the combined influence of several biological, psy- To manage childhood mental disorders effectively it
chological and social factors. A careful assessment is necessary to address as many relevant biological,
of children's problems and the factors giving rise to psychological and social factors as possible that are
their onset is an essential prerequisite to effective giving rise to their onset and persistence. Many dis-
treatment. This should include information about orders persist over long periods of time (e.g. ADHD)
the child's current problems, a developmental his- or tend to recur (e.g. major depressive disorder). In
tory, and relevant information about the child's family the light of this, the development of long-term man-
and social e­ nvironment. It is important to develop a agement plans for these disorders is important. The
clear ­understanding of the nature of a child's present- development of such plans requires consideration of
174
ing problems and the factors that have given rise to several key issues.
 Common mental health problems 4.2
Firstly, it is important to recognize that specific
interventions are now available for many disorders. Practical points
Medical practitioners need to be familiar with these
interventions and to avoid ‘one size fits all’ meth- Treatment of mental health problems
ods of counselling. Secondly, the management of • Treatment plans need to be individualized.
children's problems often involves the use of a com- • It is important to obtain cooperation from children, parents
bination of biological (e.g. psychotropic medica- and teachers.
tions), p ­sychological (e.g. cognitive–behavioural • Psychological interventions should generally be employed
before the use of medication.
therapy) and social interventions (e.g. peer relation-
• In general, only medical practitioners with specialist
ship programmes). Finally, the management of chil- knowledge should initiate treatment of child and
dren's problems requires the cooperation of children, adolescent mental health disorders with psychotropic
parents and teachers. It is important to involve all medications.
of these groups when treating children with mental
health problems.
Psychological interventions available to help those psychotropic medications be used concurrently to
with mental disorders include: treat a child with a mental disorder.
• Individual psychotherapy, which focuses on helping
children
• Family therapy, which focuses on relationships Problems of infancy
between all family members
• Behaviour modification, which focuses on the Infant mental health is a rapidly developing field.
antecedents and consequences of children's Debates about nature versus nurture have been
behaviour superseded by interactional models that link the
• Cognitive therapy to address maladaptive thinking styles of parenting to an infant's psychologi-
styles. cal and physical health, developmental maturity
Recent reviews have drawn attention to the impor- and evolving personality. This is set in a cultural
tance of implementing these interventions cor- and extended family context. Attachment the-
rectly. It appears that failure to do this may explain ory describes the relationships that occur between
why their effectiveness, when delivered in clinic set- infants and ­parents. There is increasing evidence
tings, is often less than that achieved in the uni- that these interactional styles, already measurable
versity or research environments where they were by 12 months of age, predict ­children's ­interactional
developed. patterns later in life.
A wide range of medications is used to treat chil- Recent work has also shown that early experi-
dren with mental disorders. However, although many ences have a measurable effect on infant's brains.
of these medications have the potential to provide It is believed that tract and synapse development is
help, evidence of their effectiveness is often based significantly conditioned by the style of parenting.
on studies of adults. There has been particular con- An infant's brain has the potential to develop and
cern with antidepressant medications, which appear mature, and this potential can best be achieved by
less effective for treating children and adolescents parenting that is attuned to the needs of the infant.
than for adults. Several national authorities have Thus, appropriate parenting in which love and l­ imits
advised medical practitioners to be cautious when are evident, along with a focus on helping with
using antidepressant medications with children and developmental stages, is likely to promote neural
­
adolescents, because they increase the risk of suicidal tract development.
thinking. It is known that a wide range of parent and infant
When psychotropic medications are used to help issues can interfere with optimal parenting. These
children, very clear treatment goals should be iden- include postnatal depression and anxiety, troubled
tified, along with careful monitoring of effective- marital relationships, and compromised role models
ness and adverse effects. Pharmacological treatment of parenting and prematurity. Physical or emotional
should always be used as part of a broader manage- abuse has particular and longlasting consequences.
ment plan developed in conjunction with children A growing number of interventions are being devel-
and parents. Only one psychotropic medication oped to address these problems in the early years.
should be prescribed at a time. If a medication is There is also a growing body of knowledge about the
ineffective after an appropriate trial, an alterna- benefits of early (e.g. antenatal) identification of par-
tive may be selected. Only after consultation with ent risk factors, and the potential for health promotion
a child psychiatrist or paediatrician experienced in and early intervention at this early stage of an infant's
175
paediatric psychopharmacology should multiple development.
 4.2 BEHAVIOUR AND MENTAL HEALTH NEEDS

• Presence of a mental disorder (e.g. major depressive

Special issues disorder)
• Evidence of premeditation and planning
Suicidal ideation and behaviour
• An expectation by the young person that the
All suicide attempts should be treated seriously. Although attempt would result in death
suicidal ideation and behaviour are relatively rare before • A suicide attempt made while alone or isolated
the age of 12 years, they become more frequent dur- • Precautions taken to make discovery unlikely
ing adolescence (see Chapter 3.11). In the Child and during or after the suicide attempt.
Adolescent Component of the Australian National During the period of time that a young person remains
Survey of Mental Health and Wellbeing, 4% of ado- at high risk for suicide, it is important that they be in a
lescents reported a suicide attempt in the previous safe environment where their behaviour can be moni-
12 months. Furthermore, adolescents with more emo- tored. During this time their mental status should be
tional and behavioural problems reported substan- assessed and help provided to address personal or
tially more suicidal ideation and behaviour (Fig. 4.2.1). family problems. In some circumstances, such as when
Completed suicide is less common. Adolescent males a young person has a serious mental disorder or where
have higher rates than females (9–10 per 100 000 annu- they have no secure place of residence, it is necessary
ally for males, compared with 3–5 per 100 000 for to arrange hospital admission.
females). It is important to provide appropriate treatment for
Suicidal ideation and behaviour is often associated depressive disorders experienced by young people who
with symptoms of a depressive disorder along with make suicide attempts. This should include the use
a history of abuse of alcohol or other drugs. Many of specific counselling techniques such as cognitive–
young people who attempt suicide live in families behavioural therapy and, where appropriate, the use
where there is a high level of interpersonal conflict of antidepressant medication. Every effort should be
and where parents have a history of mental disorder or made to reduce the impact of ongoing stressors, such
drug and alcohol abuse. As well as a history of chronic as family conflict, that may precipitate further suicide
adversity, many young people report an immediate attempts. When appropriate treatment methods are
precipitant to their suicide attempt. This may involve employed, a high rate of recovery can be achieved.
an argument over parental or school discipline, or a However, major depressive disorder often recurs, and
difficulty in a relationship with a friend. it is important that young people and their ­parents
All children who report thoughts of suicide or who are advised of the continuing risk of further episodes
attempt suicide should be assessed carefully. This and the symptoms that may signal the onset of a
should include assessment of the mental state of the recurrence.
child and the seriousness of the suicidal attempt.
Characteristics that suggest that a suicide attempt was
Attention-deficit/hyperactivity disorder
serious include:
• Family history of suicide attempts This is covered in Chapter 4.3.
• Previous history of suicide attempts
School refusal due to anxiety problems
A small number of children exhibit high levels of
­distress when they first commence school, and this
Level of emotional and
may be associated with temper tantrums, excessive
Low High
behavioural problems Moderate Very high fearfulness and complaints of somatic symptoms (e.g.
60
stomach aches or headaches) for which no biological
50 cause can be identified. In some children, this pattern
40 persists and it may give rise to a situation where chil-
Percentage

dren do not attend school for long periods of time.

30
School refusal adversely affects these children in two
20 ways. Firstly, they are at increased risk of receiving
10
an inadequate education. Secondly, they miss out on
important socializing experiences. As a result, they
0 may enter later life lacking important social skills. For
Suicide Suicide Suicide
ideation plan attempt these reasons, school refusal is a very serious problem
that requires urgent and effective management. Often,
Risk behaviour
it will be necessary to provide help to children and
176
Fig. 4.2.1 Suicide ideation and suicidal behaviour. ­parents over long periods of time.
 Common mental health problems 4.2
Among younger children who refuse to attend practitioner, who can quickly assess a child and advise
school there may be a history of separation anxiety parents whether the presence of a physical illness pre-
disorder. Children with this disorder have a history of cludes school attendance. This support can reduce the
anxiety when separated from their primary caregiver, pressure on parents, who must decide whether or not
may insist on sleeping in their parents’ bedroom at to allow their child to miss further schooling. Where
night, and may refuse to stay overnight with friends. In there is no evidence of a physical illness, every effort
primary school, the children will describe their fear of should be made to ensure that children return to school
separation from parents, describe worrying at school at the earliest possible opportunity. Teachers can play
about their parents, and may be excessively anxious if a vital role supporting the child's return to school after
their parents are late to collect them from school. They an absence and helping to reduce anxiety at school due
may also express fear of punishment from teachers or to bullying or performance pressure.
concern about bullying by peers.
Adolescents who refuse to attend school may be suf- Enuresis and encopresis
fering from social phobia. Adolescents with this condi-
Nocturnal enuresis
tion experience marked fear of social or performance
situations. As a result, they are reluctant to attend Although most children have achieved bladder control
school where they have to mix socially with peers and by the age of 5 years, a significant number continue to
demonstrate adequate academic progress. have problems with nocturnal enuresis. This is embar-
Assessment should be initially broad-based and rassing for children and is a burden for their parents.
aimed at understanding the cause of children's prob- In the absence of physical causes, such as a urinary
lems. A ­developmental history should be obtained with tract infection, nocturnal enuresis is generally not a
a ­particular focus on symptoms of anxiety. Information serious problem. Indeed, it may simply reflect normal
should be obtained about the child's environment both variation in the development of bladder control, where
at home and at school. This should include information there is a familial tendency to later maturation of blad-
about family functioning, the classroom and school der control. Discussing this familial pattern with par-
environment, and peer relationships. It is important to ents may help them better understand the nature of
determine whether bullying by peers at school is a sig- their child's problem. Exposure to stressful events may
nificant precipitant or perpetuating factor for school also induce children with previously good bladder
refusal, and to be aware that it can take multiple forms control to recommence bed-wetting.
(e.g. verbal, physical, social, psychological or cyber For younger children, management consists of reas-
bullying). It is essential that contact be made with chil- surance and the establishment of a convenient pat-
dren's teachers to obtain information about these last tern of hygienic care of bed and clothing. Simple
issues, with parents being encouraged to raise any con- procedures such as fluid restriction at night or getting
cerns about bullying with school staff. Information children to empty their bladder when the parents are
should also be obtained about the severity, duration ready to retire may help. Incentive systems can be put
and pervasiveness of school non-attendance, noting in place to assist children's motivation to remain dry.
possible antecedents of the problem and consequences One method is to reward children for achieving a given
that may be responsible for maintaining the behaviour. number of consecutive dry nights, with the number of
A number of specific approaches can be used to help nights gradually extended over time.
children with school refusal due to anxiety problems. For more persistent cases of bed-wetting, an enure-
Implementing these requires the combined efforts of sis alarm has been shown to be an effective treat-
children, parents and teachers. Children need help to ment in the majority of cases. The alarm consists of
manage their anxiety better. This should include the a detector mat placed on a child's mattress. The mat
use of techniques such as: is connected to an alarm and when the child begins
• Relaxation training to urinate during sleep, a circuit is completed and the
• Systematic desensitization alarm sounds. The procedure (often called a ‘bell and
• Cognitive restructuring pad’) uses simple conditioning rules to train children
• Shaping and contingency management to achieve better bladder control. Many children's
• Life skills training. hospitals or chemists have such devices available for
Parents need to be taught how they can manage chil- hire. However, it is important to ensure that the mat
dren's temper tantrums and how to help children who and alarm both function properly, or they will not
report somatic complaints. In two-parent families, it is condition children to achieve better bladder control.
important that both parents participate in treatment Children who are not easily awoken by the alarm will
programmes. In situations of chronic school refusal, initially require parental assistance to finish voiding
assessing the significance of children's somatic com- in the toilet. This is important in ensuring that the 177
plaints can be helped by close liaison with a general ­conditioning ­treatment achieves success.
 4.2 BEHAVIOUR AND MENTAL HEALTH NEEDS

In recent years, desmopressin has been used as a the use of laxatives or microenemas. Less commonly,
short-term treatment for children with nocturnal it will be necessary to employ a bowel washout. Secondly,
enuresis. It is administered orally or as a nasal spray it is important to ensure that the diet ­contains ­adequate
and acts to decrease urine production at night. Studies fibre to reduce the likelihood of future constipation.
report varying success rates but relapse is high and Finally, it is important to establish a routine of regular
side-effects such as headache and abdominal pain toilet use, which can be difficult with children. There
have been noted. A Food and Drug Administration may be a history of conflict between parents and chil-
warning about the risk of hyponatraemic seizures dren about toilet use. Children may also be unclear
should be noted (http://www.fda.gov/Drugs/DrugSafety/ about the linkage between irregular toilet use and
PostmarketDrugSafetyInformationforPatientsand encopresis, particularly if previous interventions have
Providers/ucm125561.htm). Tricyclic antidepressants focused largely on punishing children who soil their
such as imipramine should no longer be used to treat clothes. Children may also be upset or embarrassed by
enuresis because of high relapse rates, possible cardiac their problem and may refuse to participate in treat-
adverse effects, and the risk of severe morbidity or ment programmes.
even death from overdose. It is important to ensure that children understand
why they are experiencing constipation and soiling.
A simple schematic diagram showing the key f­eatures
Encopresis
of the gastrointestinal system can be used to help
Encopresis affects between 2% and 8% of primary children understand the nature of their problem.
­
school children. It is more common among boys and a Children need to understand that constipation occurs
high proportion of children with encopresis have con- when there is a build up of faeces because of a failure
comitant constipation. The problem is distressing for to empty the bowel regularly. Once they understand
children and may be associated with conflict between this, it is easier to work with them to plan a programme
parents and children. Several types of encopresis have of regular toilet use.
been described: Small rewards given after each use of the toilet can
• Constipation with overflow be helpful with young children. In children with toi-
• Failed toilet training let phobia, rewards may be given initially for simply
• Toilet phobia sitting on the toilet for a few minutes, progressing to
• Stress-induced loss of control rewards provided when the child empties their bowel in
• Provocative soiling. the toilet. To achieve maximum effect, rewards need to
Considerable overlap occurs between these different be given immediately after children use the toilet, they
types of encopresis. However, the descriptions provide need to be inexpensive (because of the need to reward
a general indication of the types of issue that must each use of the toilet) and must be given consistently
be considered when assessing children with encopre- when the child uses the toilet. Jointly identifying
sis. Before treatment is commenced, it is important appropriate rewards can be used to build a t­ herapeutic
to identify the causes of the child's encopresis. This alliance with children and encourage their coopera-
should include a physical examination to identify tion with the treatment programme. Seeking children's
whether the child has constipation. active involvement in treatment planning can also be
There are three elements to the treatment of encop- used to reduce the conflict between children and their
resis. Firstly, it is important to treat constipation when parents, with the latter taking on a more supportive
this is present. This can generally be achieved through and advisory role.

178
 Hyperactivity and 4.3
inattention
Jill Sewell

Hyperactive and inattentive behaviours are common in learning, motivation, goals and movement, and nor-
children, ranging in a continuum from normal behav- adrenaline (norepinephrine), involved in maintaining
iours, especially in young children, to developmentally alertness and attention, particularly with novel stim-
inappropriate behaviours that impair daily activities at uli. Two candidate genes, the dopamine transporter
home and at school. and dopamine receptor genes, are reported to be asso-
Developmentally inappropriate levels of hyperactiv- ciated with ADHD.
ity and inattention may be the result of many factors,
both intrinsic and environmental. These risk factors
(Box 4.3.1) must all be considered in the assessment of Clinical example
children with difficult behaviour, especially when con-
sidering the diagnosis of attention-deficit/hyperactiv- Sammy, aged 6 years, was in his second year
ity disorder (ADHD). of school. His teacher complained that he never
sat still, did not complete tasks, talked too much,
interrupted, and was well behind with reading.
His mother recalled that he had been ‘on the go’ since
about 2 years of age, always preferred playing outdoors
Definition of attention-deficit/ rather than settling to games inside, never seemed to
remember instructions or the house rules, and acted
hyperactivity disorder without thinking about the consequences. He hated
ADHD is considered to be a developmental disorder homework and ‘often forgot’ to bring home his school
reader.
of self-regulation, characterized by inattention and
Sammy's problems are consistent with a diagnosis of
hyperactivity/impulsivity. The underlying neurobio- ADHD and learning difficulties. Stimulant medication and
logical pathway involves the frontal–striatal–cerebellar consistent structure at home and at school helped his
networks, with deficits occurring in executive func- behavioural symptoms, but he also required educational
tioning, particularly response inhibition, vigilance, assessment and specific reading support in the classroom.
working memory and planning.
The diagnosis of ADHD is made using DSM-IV
criteria. It is a descriptive diagnosis without imply- Many children with ADHD have associated neurode-
ing cause, as it is not a discrete entity and has multiple velopmental or mental health problems (co-morbidities)
causes. There must be developmentally inappropriate (Box 4.3.4). Because of overlapping features, separation
symptoms of inattention (Box 4.3.2) and/or hyper- into these diagnostic categories is complex; however, it
activity/impulsivity (Box 4.3.3) with onset before is helpful when completing a descriptive assessment and
7 years of age, impairing social, academic or occupa- recommending specific management programmes.
tional functioning across multiple settings, and these
symptoms are not a result of pervasive developmen-
tal disorder, psychosis or severe emotional disorders.
Subtypes include mainly inattentive, mainly hyperac-
Assessment
tive or combined. The assessment of children for ADHD with its mul-
ADHD is common. The prevalence in the school- tiple risk factors and co-morbidities requires skilled
aged population generally is considered to be 3–5%. interpretation of information from the child, family
Boys are affected more commonly, particularly with and teachers. Relevant factors include:
hyperactivity. There is a higher incidence in disrupted • medical
families and in those with low incomes, again particu- • developmental
larly with hyperactivity. There is a strong genetic fac- • family history
tor, with about 30% of siblings, 25% of parents and • family, social and cultural environment
80% of identical twins affected. Molecular genetic • the school setting
studies have focused on chromosomes that regulate • academic progress 179
dopamine, the neurotransmitter most associated with • socialization skills.
 4.3 BEHAVIOUR AND MENTAL HEALTH NEEDS

General family functioning, behavioural patterns over

Box 4.3.1 Risk factors for hyperactivity and inattention
time, antecedents and consequences of ­behaviours,
• Difficult temperament and family and school management of behaviours
• Poor parenting skills must be understood. Standardized behavioural rating
• Family dysfunction scales completed by parents, teachers and adolescents
• Child abuse, particularly deprivation help to put the behaviours into a normal commu-
• Developmental delay nity context. Thorough physical examination helps
• Language disorders
to exclude the rare associated medical conditions.
• Learning difficulties
• Anxiety/mood disorders
Neurodevelopmental assessment provides informa-
• Sleep disorders tion on motor skills and auditory and visual pro-
• Medical conditions, e.g. cessing. Many children require formal assessment of
• very low birth weight or small for gestational age auditory, cognitive, language and educational func-
• fetal alcohol syndrome tion. Neuroimaging, quantitative electroencepha-
• prenatal exposure to smoking and stress lography and neurophysiological tests, for example
• lead poisoning
of continuous performance, are research tools only
• acquired brain syndrome (head injury)
• chromosomal abnormalities (e.g. fragile X, at this stage and are not yet ready for use in clinical
velocardiofacial syndrome) diagnosis.
• food intolerance (rare) The diagnosis of ADHD can be made only against
a thorough understanding of normal patterns of
development and behaviour. This is particularly
important when considering the diagnosis in a pre-
Box 4.3.2 DSM-IV: Symptoms of inattention school-aged child, with wide variations expected
in normal behaviour, development and tempera-
• Poor attention to detail, careless mistakes ment, and vulnerability to adverse family and social
• Difficulty sustaining attention circumstances.
• Seems not to listen
• Seems not to follow through
• Difficulty with organization
• Avoids tasks requiring sustained attention
• Loses things Clinical example
• Easily distracted
• Forgetful Byron, aged 31/2 years, was extremely active,
aggressive and oppositional, and had a mild
language delay. Recently, his mother had
separated from Byron's father and begun a
new relationship. The family had moved several times and
Box 4.3.3 DSM-IV: Symptoms of hyperactivity/impulsivity
had been involved with a number of family support agencies.
His mother wanted Byron to go on stimulant medication, like
• Fidgets
his older half-brother.
• Often leaves seat
Byron was diagnosed with oppositional defiant disorder
• Runs, climbs excessively
and language delay, in the context of a dysfunctional but
• Difficulty playing quietly
committed family. He could also have been diagnosed with
• ‘On the go’
ADHD on DSM-IV criteria, but such a diagnosis at this age
• Talks excessively
might be misleading and could shift focus away from the
• Blurts out answers
critical issue of effective family support.
• Difficulty awaiting turn
• Interrupts others

Box 4.3.4 Co-morbidities with attention-deficit/ Management

hyperactivity disorder
ADHD is a chronic condition requiring long-term
• Learning difficulties (10–30%) management based on partnership with the child,
• Language disorder (30–50%) the family and the child's teachers from year to year.
• Oppositional defiant disorder (30–50%) Counselling on the nature, causes, risk factors and
• Conduct disorder (16–20%) course of ADHD, setting realistic expectations in the
• Anxiety, mood disorders
light of such understanding, and making accommoda-
• Developmental coordination disorder
tions at home and at school will help the child main-
180 • Tics, Tourette syndrome
tain confidence and self-esteem.
 Hyperactivity and inattention   4.3
Multimodal management includes:
• Stimulant medication Clinical example
• Parental behaviour management
• Classroom behaviour management Julie, aged 13 years, was in year 8 at school.
Although she had coped academically in
• Management of co-morbidities, e.g.
primary school, she was having difficulty
• special education support for learning with organizing herself, working through
difficulties assignments and getting homework completed on time.
• treatment of anxiety, depression Her written work was messy, she was distracted easily
• Structured parenting programmes, parent support and she daydreamed in the classroom. She was worried
groups. that she would not do well enough at school to go to
university.
Julie's assessment indicated long-term problems with
Stimulant medication attention, distractibility and impulsivity. She commenced
stimulant medication for her ADHD (inattentive type)
Stimulant medications, which increase dopamine and developed better organization, task completion and
levels in the brain (methylphenidate and dexamfet- interest in work, and neater handwriting. She began to
amine), are the most effective treatments for ADHD feel that she was much closer to reaching her academic
and improve target symptoms in about 75% of chil- potential.
dren with the condition. Improved concentration and
decreased hyperactivity, impulsivity and distractibility
lead to enhanced task completion, academic progress
Behaviour management
and social interaction, sustained over time.
These medications are safe and have a low profile Behaviour management programmes use a structured
of adverse effects, which either subside spontaneously setting to promote behavioural control, reinforcing
within the first 2–3 weeks of treatment or can be man- appropriate behaviours and reducing negative behav-
aged by altering the dose or timing of medication. iours with specific strategies. Emphasis should be on
Insomnia, appetite suppression and headache can be antecedent support and control, rather than on conse-
troublesome in some children. There is some evidence quences (i.e. anticipation of the difficulties and plan/
that height growth may be suppressed initially, par- teach to avoid) (Box 4.3.5).
ticularly with younger children and with higher doses, In the classroom, additional techniques include
and growth must therefore be monitored carefully. seating the child close to the teacher, breaking tasks
Extended-release preparations of methylphenidate down into small units, frequent exercise breaks (pref-
enable morning-only dosage. Atomoxetine, a norad- erably productive and responsible, such as taking a
renergic reuptake inhibitor, is used in those intolerant message to the office), structured teaching materials
of stimulant medication. adapted to the child's needs, and unrelenting positive
There is considerable community concern that too encouragement.
many children are taking stimulants and other psycho- Behavioural therapies are particularly important
tropic drugs, with over-diagnosis and medicalization when conditions such as persistent oppositional behav-
of social problems. There is community concern also iour and parent–child discord coexist with ADHD.
about a perceived risk of psychological dependence
on drugs instead of developing self-responsibility. The Alternative/complementary therapies
reality is that ADHD is a developmental disorder with
significant long-term risk factors in educational, social A small number of children react to synthetic food
and vocational outcomes, and only 2% of school-aged colours with severe irritability and restlessness. These
children in Australia have been prescribed stimulant children, who are very few in number, are helped by
medication, despite the prevalence of ADHD of at
least 3–5%. There is very good scientific evidence for
the long-term safety of these drugs. There is also clear
Box 4.3.5 Behavioural strategies
evidence that effective treatment with stimulants of
adolescents with ADHD protects against substance To reinforce: ‘catch ‘em being good’; use verbal praise and
abuse. concrete rewards
Medication treatment is only one of the treatment • Teach listening skills
modalities for ADHD. It is also critically important • Teach problem-solving skills (e.g. ‘game plan’)
for health professionals to advocate community ser- To reduce: ignore unwanted behaviours
vices and family support for children who are at risk • ‘Act, don't speak’ (i.e. clear discipline with minimal
reprimands and discussion)
for adverse developmental, behavioural and social • Logical consequences 181
outcomes, whether or not they have ADHD.
 4.3 BEHAVIOUR AND MENTAL HEALTH NEEDS

dietary restriction. There is no evidence that a sugar-

free diet, megavitamins, sensory integration training Prevention
or neuro-feedback are of therapeutic benefit. Externalizing behaviour problems such as hyperac-
tivity, oppositional defiance and aggression are very
common in young children, some of whom will go on
to a diagnosis of ADHD in the future. Group par-
Outcome enting programmes can help established externaliz-
Hyperactivity tends to diminish in adolescence, although ing behaviour problems by improving nurturing and
physical restlessness may continue. Inattention, impul- responsiveness, and diminishing harsh discipline.
sivity and distractibility can continue into adulthood, Evidence is now building regarding the prevention
although self-awareness and self-regulation improve of externalizing behaviour problems by using effec-
with developmental, cognitive and emotional matura- tive parenting programmes that start in infancy, rais-
tion. Co-morbidities, such as learning difficulties, subtle ing the possibility of universal prevention in primary
language disorders and conduct disorders, and associ- care settings.
ated risk factors, such as family dysfunction and poor From the above, it is clear that there are many rea-
educational opportunity, can contribute to adverse sons why children have hyperactive and inattentive
outcomes, including poor school retention, a limited behaviours. These behaviours must be interpreted
vocational outlook, and risk-taking behaviours in ado- with an understanding of normal development and
lescence and early adulthood. behaviour, and how these interact with family and
community function. When such behaviours are
excessive and pervasive, a diagnosis of ADHD may
be made, paying attention to causes, risk factors and
Practical points
co-morbidities.
Treatment of ADHD is multimodal, with stimu-
• Not all children with hyperactivity and inattention have lant medications being safe and most effective, but
ADHD.
adjunctive behavioural management and family sup-
• Genetic and environmental influences contribute to the
diagnosis. port are essential. Understanding and adjustment
• Assessment is complex – consider risk factors and in the school setting, with appropriate educational
co-morbidities. support, are paramount for the child's long-term
• Stimulant medication is safe and effective. wellbeing.
• Long-term behavioural, family and educational support is Universal prevention and targeted early inter-
required.
vention of externalizing behaviour problems may
• Adverse outcomes in adolescence and early adulthood
are common, particularly in association with reading help more children to start school with better self-­
difficulty and aggressive behaviour. regulation and capacity to learn, both academically
and socially.

182
 Major psychiatric 4.4
disorders
Brett McDermott

The major psychiatric disorders are characterized by • deterioration in school performance

relatively specific symptomatology and functional • failure to make friends, solitary interests.
impairment in the family, social and educational • Adolescence:
domains. The primary care physician's role in the • unexplained loss of weight, uncontrolled dieting
management of these disorders is early recognition, • secretive bingeing and vomiting
baseline risk assessment, diagnostic clarification if • deterioration in school performance
warranted, collaboration in shared care, and ensuring • social withdrawal and cessation of sporting/
maintenance of the patient's general health. A con­ recreational activities
temporary conceptualization is that individuals are on • disorganized thought processes, hallucinations,
developmental trajectories and, although variability delusions
in functioning and achievement over time is typical, • persistent or recurrent depressive mood
nevertheless the individual shows steady improvement • suicidal ideation or attempted suicide
in ability and mastery of their environment across • panic attacks
childhood and adolescence. Disorders can be devel­ • excessive risk-taking, running away from home,
opmental continuities: a child, although progressing, sexual promiscuity
is doing so on an impaired trajectory compared with • recent gravitation toward ‘bad companions’
their peers – the child more rapidly develops symp­ • unexplained school absences/truancy
toms and impairment. Examples of developmental dis- • frequent fighting/explosive rage
continuities include the onset of major depression • persistent, unexplained physical symptoms.
­disorder or obsessive compulsive disorder. In this chapter we describe some of the major psychi­
The following symptoms should alert the primary atric disorders that may occur at various ages in child­
physician to the possibility of a serious psychiatric hood and adolescence.
disorder:
• Infancy and early childhood:
• failure to thrive without physical cause
Practical points
• delay in spoken language
• failure to respond normally to parental physical
contact or voice The role of the primary care physician
• Recognize as early as possible the signs of a major
• stereotyped, repetitive movements (e.g. psychiatric disorder.
hand-flapping) • Exclude as quickly as possible non-psychiatric causes of
• concern by experienced parents that behaviour is the symptoms.
unusual or bizarre. • Refer as soon as possible to mental health consultant.
• Middle childhood: • Explain the nature of the problem and the reason for
• severe, persistent oppositional and/or aggressive referral to the patient and family.
behaviour • Collaborate with the psychiatrist in the shared extended
care of the patient.
• persistent stealing • Support the patient and family in adhering to the
• developmentally inappropriate sexual behaviour treatment plan.
• persistent fire-setting • Maintain the patient's general health.
• cruelty to animals
• truancy and/or unexplained absences from school
• persistent unexplained physical symptoms (e.g.
abdominal or limb pain) Infancy and early childhood
• severe, persistent separation anxiety (e.g. on
Reactive attachment disorders
leaving home to go to school)
• failure to speak outside the home Both infant and parent contribute to attachment.
• obsessions and compulsions However, attachment is best conceptualized as the qual­
183
• persistent low or irritable mood ity of the relationship between the two. Attachment
 4.4 BEHAVIOUR AND MENTAL HEALTH NEEDS

disorders do not include disorders with a biological

Box 4.4.1 Clinical features of autistic disorder
(proven or presumed) substrate. Hence impaired emo­
tional reciprocity seen in autism is not a feature of a • Marked impairment of eye-to-eye gaze and
reactive attachment disorder. Occasionally, the dis­ communicative gestures
tinction between pervasive development disorders and • Failure to develop peer relationships
attachment disorders can be difficult. Typically, the • Lack of socio-emotional reciprocity
infant fails to initiate or to respond appropriately to • Impaired capacity for joint attention
• Incapacity for make-believe play
social interaction, exhibiting social withdrawal, inhi­
• Failure to imitate others
bition, avoidance or, conversely, a superficial, undis­ • Delay of language development
criminating sociability. • Unusual use of language (e.g. for self-enchantment rather
Attachment disorders develop as a result of par­ than communication)
ent depression, psychosis, personality disorder or • Stereotyped, restricted interests and rituals
severe psychosocial stress; the parent has failed to • Motor mannerisms (e.g. finger-flicking or hand-flapping)
attend to the infant's basic needs for affection, contact
comfort and stimulation, or there have been so many
changes of caregiver that the infant has not been able
to develop a stable attachment. Attachment disorder The ­ incidence of all autistic spectrum disorders
should be distinguished from pervasive developmental may be as high as 3–6 per 1000 children. A major
disorder, intellectual retardation and developmental cause of varying prevalence is inconsistency in diag­
language disorder. nostic approaches. In approximately 50% of autis­
Non-organic failure to thrive is arrested physical tic children, a physical cause can be diagnosed (e.g.
and psychosocial development secondary to severe congenital rubella, fragile X syndrome, neurofibro­
attachment disorder, and should be differentiated matosis, phenylketonuria, tuberous sclerosis). There
from physical causes of failure to thrive. It is usually are numerous causal theories for pervasive devel­
encountered in children from 18 months to 7 years opmental disorders of unknown aetiology, such as
of age. Typically, during hospital admission the child deficits of interneuron communication, possibly
develops greater language and/or social ability as well dendritic spine morphological change, more so in
as gaining weight, only to stall after returning home. males. However, definitive statements about causa­
The prognosis for intellectual and social development tion are not currently possible.
is poor unless adequate surrogate care is provided The child suspected of autistic disorder should be
or the primary caregiver's parental capacity can be assessed as follows:
addressed. • Physical examination
• Dental examination
• Assessment of hearing and vision
Practical points • Psychological testing for cognitive level and pattern
of intellectual abilities
• Speech and language assessment
Reactive attachment disorder
• Genetic and metabolic testing to exclude known
• Caused by defect in infant's capacity to elicit parental care
and/or by failure of the parent to provide adequate or genetic and biological causes
consistent care • Electroencephalography.
• Reflected in the infant's failure to initiate or respond to Autistic disorder should be differentiated from:
social contact • Developmental language disorder
• Can lead to stunting of physical or intellectual growth • Intellectual retardation
• Must be differentiated from organic failure to thrive • Sensory impairment (e.g. deafness)
• Treatment involves the provision of adequate surrogate
parental care while the mother–child unit is treated • Selective mutism (see below)
• Severe psychosocial deprivation
• Mild forms of pervasive developmental disorder
(see below).
Pervasive developmental disorders
Although many parents become concerned that their
This group of conditions is characterized by a develop­ child is abnormal by the age of 6–12 months, autis­
mental continuity in delayed intellectual, communica­ tic disorder is often not diagnosed until much later in
tive and social development, together with stereotyped childhood. This is regrettable because the earlier the
behaviour and circumscribed interests. diagnosis, the sooner effective treatment can be pro­
Autistic disorder occurs in about 1 in 1000 chil­ vided. In a minority of cases, the child is described as
dren, with a male to female ratio of 3 : 1. The fea­ developing normally at first, only to regress into an
184
tures of autistic disorder are shown in Box 4.4.1. autistic state when 2 or 3 years old.
 Major psychiatric disorders 4.4
with this condition become frustrated by their lack of
Clinical example friends and the teasing or social rejection to which they
are prone. Treatment involves social–­ cognitive lan­
John, aged 4 years, was referred because his guage programming in the educational mainstream.
preschool teacher was concerned about his
As adults, people with Asperger's disorder are more
poor language and lack of interest in other
children. His mother said John had always
effective in jobs that make few social demands.
been ‘different’. He did not seek or give affection. He did not
play with toys like other children but preferred to line them
up or watch them falling, one by one, off a table. If anyone
interrupted this game, he would scream. He was fascinated Middle childhood
by light switches and electric fans, and liked to parrot
television commercials. John avoided looking at people by Disruptive behaviour disorder
averting his gaze to one side. He did not respond to the
Oppositional defiant disorder and attention-deficit/
doctor's questions. At one point, he suddenly became upset
and began to run around the office on tiptoes, flicking his
hyperactivity disorder (ADHD) are described in
fingertips. He was referred to a developmental paediatrician Chapters 4.2 and 4.3 respectively. Conduct disorder
for a full diagnostic work-up for suspected autistic disorder. refers to a group of children characterized by some or
all of the features listed in Box 4.4.2.
Conduct disorder can emerge first in adolescence
The best predictors of outcome are IQ and the pres­ but the more serious variant is continuity from opposi­
ence of functional speech at 5 years of age. Epilepsy tional defiant disorder of middle childhood. The preva­
occurs in approximately 20%, usually in adolescence. lence is 3% in Australian children and adolescents, with
Treatment may be specific if a known disorder is diag­ a male to female ratio of about 3 : 1. Conduct disorder
nosed (e.g. fragile X syndrome). In all cases, diagno­ is commonly associated with other problems, particu­
sis is multidisciplinary and involves a comprehensive larly ADHD (see Chapter 4.3), alcohol and substance
behavioural analysis that establishes targets for behav­ use, mood disorder, post-traumatic stress disorder
ioural interventions. Often behaviour is slowly shaped (PTSD) and learning disorder. In the clinical setting,
towards the desired outcome. Specific augmentation much of the most severe aggressive behaviour is dis­
and communication strategies are effective, especially played by children under child protection orders, often
if commenced early in life. Pharmacotherapy has a lim­ with multiple past abuse histories, dysregulated mood
ited role, and is of use mainly in children who exhibit and impulses, as well as significant self-harm. These
severe hyperactivity, aggressiveness or self-harm. adolescents may meet criteria for conduct disorder, but
Parents are not usually concerned about children the presentations are best conceptualized as either a
with Asperger's disorder until the child is 2–4 years old. complex PTSD or a reactive attachment disorder.
By middle childhood, the child exhibits the following The genetic background of conduct disorder is
characteristics: unclear, but twin and adoption studies suggest there
• impairment of non-verbal communication (e.g. is an inherited component. Current aetiological
impaired eye contact, lack of facial expression and models of conduct disorder highlight necessary (but
gesture, and monotonous vocal intonation but not sufficient) vulnerability factors, including genetic
intact language development otherwise) factors such as a functional polymorphism of the
• average or above average intelligence monoamine oxidase gene, early life exposure to coer­
• lack of interest in peer relationships cive parenting and/or early abusive and neglected
• lack of social reciprocity, shared enjoyment and parenting. Later contact with deviant peers is often
humour important. Significant associations include (early)
• circumscribed interests (e.g. fixated on earthquakes)
and inflexible routines
• mannerisms (e.g. hand-flapping) and motor
clumsiness. Box 4.4.2 Features of conduct disorder
It is unclear whether Asperger's disorder is a variant
• Persistently aggressive behaviour (bullying, intimidation,
of, or different from, autistic disorder, and whether it frequent fighting, cruelty, coercive sexual behaviour, use of
is distinct from non-verbal language disability, seman­ a weapon)
tic pragmatic processing disorder or related to later • Destructiveness (fire-setting, vandalism)
schizoid personality disorder. Because of uncertainty • Deceitfulness (breaking and entering, stealing, lying,
about the boundaries of this condition, its prevalence trickery)
is unclear. A useful approximation is an Asperger's • Rule violation (truancy, staying out late at night, running
away from home, refusal to accept rules at home or
to autism ratio of 5 : 1. Like autism, this condition is
school) 185
more common in males. By adolescence, many ­children
 4.4 BEHAVIOUR AND MENTAL HEALTH NEEDS

lack of ­empathy, relative school failure and early ini­ childhood. Selective mutism often coexists with panic
tiation into smoking, sexual activity, and alcohol or disorder or social phobia. The child, more often a girl,
drug taking. fails to speak in social situations outside the home or
If conduct problems do not first appear until ado­ to strangers. The average age of onset is 2–5 years. In
lescence, and few risk factors are operative, the indi­ about 30% of cases there has been a premorbid speech
vidual will probably not go on to become antisocial as or language problem. Selective mutism should be dif­
an adult. When behaviour problems begin at an early ferentiated from deafness, intellectual disability, devel­
age and many of the cumulative risk factors apply, it opmental language disorder, aphonia and the inability
is more likely that the individual will become an adult of a migrant child to understand English.
criminal. Children with conduct problems are usually Anxiety disorders frequently coincide with attention-­
referred for evaluation during late childhood or ado­ deficit disorder and depressive disorder. Given that
lescence. It would be preferable if this serious disorder parental anxiety (especially separation or social
could be detected and treated earlier. The combination ­anxiety) is highly contagious, treatment must therefore
of early educational intervention with parenting pro­ involve the parents.
grammes (e.g. triple P) designed to alter coercive child- Obsessive compulsive disorder (OCD) has the fea­
rearing have an increasing evidence base. Recently tures listed in Box 4.4.3. OCD has a 6-month preva­
multisystemic therapy involving goal-directed strategic/ lence of 0.5–1%. The onset is usually between 6 and 11
behavioural family therapy aimed at promoting effec­ years, with bimodal peaks, the latter being in the early
tive parenting, along with individual counselling and twenties. The male to female ratio is probably equal,
environmental interventions, has produced good although males predominate in the younger age group.
results. The placement of offenders in therapeutic Neuroimaging, neuropsychological and genetic stud­
foster homes has also shown promise. In foster home ies support the concept that the disorder is neuropsy­
programmes, the house parents are trained to be firm chiatric in nature. A subgroup of patients may have
and consistent in their discipline and to ensure that sustained an autoimmune reaction and are positive for
the adolescent does not associate with antisocial peers. antibodies to β-haemolytic streptococci. OCD should
Foster care without input from an evidence-based be distinguished from:
programme is not effective for this group. It is also • transient benign habits and rituals such as ‘not
ineffective to treat children with conduct disorder in stepping on the crack’ (no impairment)
community or institutional groups composed of like- • worries associated with generalized anxiety disorder
minded peers. ‘Boot camps’ and ‘scaring then straight’ (e.g. worries about daily events)
programmes have no evidence of effect. • Tourette disorder (associated with tics)
• pervasive developmental disorder (rituals are not
distressing and there is marked social impairment).
Anxiety disorders
OCD is commonly co-morbid with other anxi­
Separation anxiety disorder is described in Chapter 4.2. ety disorders, mood disorder, tic disorder and dis­
Generalized anxiety disorder is characterized by persis­ ruptive behaviour disorders. It often persists into
tent, excessive worrying about life events (e.g. school adulthood.
performance, dating) accompanied by physical symp­ Anxiolytic drugs (e.g. benzodiazepines) should be
toms (e.g. abdominal pains, headaches, fatigue, diar­ avoided in the treatment of anxiety disorders because
rhoea, urinary frequency). Children with this disorder they have addictive and sedative potential. Further,
are likely to have been behaviourally inhibited as pre­
schoolers and to have a parent with an anxiety disor­
Box 4.4.3 Features of obsessive compulsive disorder
der or high trait anxiety. Generalized anxiety disorder
overlaps with social phobia, in which the child is partic­ • Recurrent, distressing thoughts about such matters as
ularly fearful of performance situations that incur the germs, contamination or harming the self or others, or
scrutiny of others (e.g. reading in front of the class, ath­ preoccupation with excessive moralization or religiosity
letic competition). School phobia (or “school refusal”) (obsessions)
can be a severe anxiety disorder that requires multidis­ • Recurrent distressing rituals involving excessive washing,
repeating, checking, touching, counting or ordering
ciplinary intervention; indeed, 20% of school refusing
(compulsions)
children never return to the general classroom. • These thoughts or actions are regarded by the patient as
Panic disorder involves repeated attacks of sudden, abnormal and are resisted, but the patient is forced to
disabling anxiety, often without any apparent precip­ continue to think thus, or to continue the actions
itant, associated with the physiological concomitants • Symptom exacerbation in times of stress (e.g. starting at a
of anxiety (e.g. hyperventilation, racing heart, cold new school)
• Impairment of functioning (e.g. completing chores, getting
sweaty hands, choking sensations, dizziness, faint­
186 ready for bed, finishing schoolwork, relating to other family
ing) and a fear of dying. The onset of panic disorder members)
is most often in mid-adolescence; it is rare in middle
 Major psychiatric disorders 4.4
depression to be 3% in childhood and adolescence.
Clinical example Typically, there is an increased prevalence of depres­
sion in the families of depressed children. However,
Barbara's mother reported that she was the genetic background of the disorder is still unclear,
worried because Barbara, aged 10 years,
as is the nature of the interaction between genetic pro­
had begun to behave in an odd manner. She
would touch doorknobs again and again, and
pensity and the adverse life events that often precede
spent ages getting to bed because she had to arrange her depressive episodes.
teddy bears just so around her pillows and at the foot of the Depression often presents as a discontinuity from
bed. She had reluctantly admitted to her mother that she the previous developmental trajectory and so the cli­
arranged the teddy bears in that way in order to control a nician should be alerted to the possibility whenever
fear of being abducted at night. She would wriggle her toes school performance inexplicably drops or there is a
and clench her jaw in a special way, but did not know why
change in mood, control of temper, social involve­
she did so. When she tried to resist wriggling her toes, she
became very anxious and had to give in and do it. ment or sleep patterns. Information is needed from
both parent and child with regard to the clinical fea­
tures and contemporary psychosocial stressors. The
child should be assessed for risk of suicide; clinicians
they prevent habituation to anxiety and may therefore are reminded that talking about suicide will not intro­
perpetuate the condition. The most effective treatment duce the adolescent to this possibility. A differential
is cognitive–behavioural therapy (CBT). As parental diagnosis is an emerging personality disorder, often
anxiety is commonly associated with childhood anxi­ typified by chronic mood dyscontrol as well as impul­
ety disorder, parent involvement is always indicated. sivity, relationship instability, self-harm and an unsta­
In OCD, CBT involving exposure to anxiety-provok­ ble sense of self (see Chapter 4.2). The 2011 Australian
ing situations, systematic desensitization and the pre­ Clinical Practice Guidelines for Adolescent and Youth
vention of compulsive responses to anxiety-provoking Depression advise CBT or interpersonal psycho­
stimuli has been found to be effective. For OCD spe­ therapy as the treatment of first choice. There is evi­
cifically and other anxiety presentations with an inad­ dence for the effectiveness of the SSRI fluoxetine, but
equate response to CBT, selective serotonin-reuptake SSRIs are associated with a small rise in emergent sui­
inhibitors (SSRIs) are often effective and well toler­ cide thinking and behaviour from approximately 2%
ated. Family therapy is aimed at educating the family ­(placebo rate) to 4%. There is no evidence that tricyclic
and disentangling the parent's from the child's rituals. or heterocyclic antidepressant drugs are effective in
child/adolescent major depression. Furthermore, they
can have serious side-effects. There is evidence that
CBT combined with an SSRI modifies the danger of
Adolescence emergent suicidal thinking. Although most depressed
adolescents recover from depression within a year,
Major depressive disorder
many relapse and the risk of subsequent episodes con­
The prevalence of major depressive disorder rapidly tinues into adulthood.
increases during adolescence. The characteristic symp­
toms are listed in Box 4.4.4.
Depressive symptoms are commonly associated
Clinical example
with anxiety, conduct problems, post-traumatic symp­
tomatology, eating disorders, learning disability, sub­ Bill, aged 14 years, was referred because
stance abuse and school refusal. A recent Australian the school had become concerned about
population survey found the 6-month prevalence of his surliness, rebelliousness and tendency
to submit class assignments with macabre
content. His mother said that Bill would do nothing to help
Box 4.4.4 Symptoms of major depressive disorder her at home and spent most of his time in his bedroom
listening to ‘heavy metal’ rock music. Bill's father had left the
• Persistent depressed or irritable mood family several years before to live in a distant city and start
• Feelings of worthlessness and hopelessness a new family. Bill presented as a slim adolescent, dressed in
• Suicidal ideation black, with close-cropped hair and a nose ring. After initially
• Loss of pleasure in activities that were formerly enjoyed sparring verbally, he admitted that he hated his life. He
• Social withdrawal and cessation of sporting and said that he slept poorly and was too tired to concentrate in
recreational activities school. He had recently begun to smoke marijuana. He had
• Insomnia or hypersomnia no friends he could rely on except, maybe, other ‘stoners’.
• Loss or gain of weight He reported that he thought often about committing suicide,
• Loss of concentration and deterioration in school performance probably by jumping from a bridge. A mood disorder was 187
• Lack of energy, ready fatigue diagnosed and Bill was referred for psychiatric evaluation.
 4.4 BEHAVIOUR AND MENTAL HEALTH NEEDS

The treatment of bipolar disorder is primarily phar­

Practical points macological. Acute mania can be a medical emergency
requiring a rapid-acting antipsychotic and/or a ben­
Depressive disorder zodiazepine. Rapidly dissolving wafer forms of anti­
• Presents in adolescence with physical symptoms, psychotic medication (e.g. olanzapine) are preferable.
irritability, social withdrawal, deterioration in school Treatment of less acute presentations and ongoing
performance. maintenance are with mood stabilizers (lithium, val­
• Have a high index of suspicion for this disorder because of proate, carbamazepine) and atypical antipsychotics.
the potential for suicide.
In adolescent women, valproate is not advised given
• Usually associated with environmental stress (e.g.
parental divorce, abuse, bullying) or loss. its risk of major birth defects. Adjunctive psychoso­
• Refer early if condition is severe or patient is suicidal. cial interventions improve functioning and medication
• Psychotherapy is the first treatment choice. compliance.
• Selective serotonin receptor inhibitor (SSRI) medication
should be used only in moderate/severe cases.
• SSRIs are associated with emergent suicide thinking and Schizophrenia
behaviour.
Psychoses in general are heterogeneous in origin and
in paediatrics may be seen in individuals with velocar­
diofacial syndrome, Prader–Willi syndrome or other
rare developmental presentations. Schizophrenia is
Bipolar disorder
predominantly a disorder of late adolescence and
There is controversy over the validity of the diagnosis early adulthood. Schizophrenia may be acute or sub­
of bipolar disorder in childhood, and its prevalence. acute in onset, especially if triggered by illicit drug
It is clear, on the other hand, that bipolar disorder is use. For many individuals there is a prodrome phase
underdiagnosed in adolescence and many young peo­ that is more insidious and ­typified by:
ple with early-onset psychosis are later reclassified • social isolation or withdrawal
as having bipolar disorder. In bipolar I disorder, the • deterioration in functioning at home, at school, and
patient has experienced at least one manic or mixed in grooming and personal hygiene
manic–depressive episode. In bipolar II disorder, the • vague conversation with poverty of content
patient has experienced at least one episode of both • odd, overvalued beliefs (e.g. of telepathy), rituals or
major depression and hypomania, but no manic or magical thinking.
mixed episodes. Mania is characterized by the follow­ Symptoms typical of acute schizophrenia include:
ing symptoms: • hallucinations (most commonly auditory)
• abnormally elevated mood persisting for at least • delusions (e.g. of persecution, thought insertion,
1 week thought loss)
• grandiose thinking • thought disorder with disorganized or incoherent
• pressured speech, racing thoughts and distractibility conversation
• increased activity and recklessness • disorganized behaviour (e.g. posturing, catatonic
• marked deterioration in functioning at school, with stiffness, agitation)
peers and at home. • flattening of affect, poverty of speech, anergia.
Hypomania is characterized by similar but less Schizophrenia is a familial disorder with a complex
intense symptoms, and less functional deteriora­ mode of genetic transmission and variable expression.
tion. In a mixed episode, manic and major depres­ Schizophrenia should be differentiated from:
sive symptoms coincide. Adolescents with mania • mood disorder (especially bipolar I disorder)
often have hallucinations, paranoid ideas and marked • psychosis due to medical disease (e.g. epilepsy,
lability of mood, causing the aforementioned diag­ brain tumour, porphyria, acquired immune
nostic confusion with schizophrenia. The risk of sui­ deficiency syndrome [AIDS]) or substance
cide is increased in bipolar disorder, especially during abuse (e.g. stimulants, cocaine, hallucinogens,
depressive phases. phencyclidine)
Bipolar disorder is familial, although the mode of • psychosis associated with developmental disorders
genetic transmission has not been elucidated. Bipolar • other psychoses (complex PTSD with dissociative
disorder should be differentiated from schizophrenia, hallucinations, schizophreniform disorder).
major depression with agitation, PTSD, disruptive Patients with below-average IQ, premorbid signs of
behaviour disorder, and disorder of mood or delir­ Asperger's disorder or pervasive developmental dis­
ium secondary to a medical condition (e.g. hyper­ order, speech disorders or cardiac disorders should
thyroidism, porphyria) or intoxication with illicit or undergo genetic testing for known behavioural
188
prescribed drugs (e.g. amphetamines, phencyclidine). phenotypes.
 Major psychiatric disorders 4.4
Acute schizophrenia conveys a risk of suicide or, threat involves repeated exposure to coercive intra­
more rarely, danger to others. Acute presentations familial physical or sexual abuse when the child is
usually require hospitalization for diagnosis and sta­ unable to disclose or escape the abuse and when,
bilization. Patients are usually treated initially with an after disclosure, the non-abusive caregiver fails to
atypical antipsychotic medication, such as risperidone, provide adequate support. The clinical features
olanzapine and quetiapine, which are associated with of PTSD in childhood are very similar to those in
relatively few side-effects other than weight gain, seda­ adulthood:
tion and, in some cases, sexual dysfunction. Adjunctive • persistent intrusive imagery concerning the
benzodiazepines may be useful in highly aroused dis­ traumatic event (e.g. flashbacks, nightmares)
tressed individuals, especially as antipsychotic med­ • repetitious play representing the event
ication may take 2–6 weeks for significant symptom • generalized nightmares and trauma nightmares
reduction. Psychoeducation for parents is essential • the conviction that one is destined for an early
in order to foster compliance and independent living death and that there were omens before the
skills, and to counteract the high levels of emotional trauma
expression between family members that increase the • avoidance of things, people or situations that
likelihood of relapse. Liaison with the school is nec­ remind one of the event
essary. A poor prognosis is associated with early or • persistent autonomic arousal with an exaggerated
insidious onset, low socioeconomic status, family his­ startle response.
tory of schizophrenia, absence of precipitating stress When PTSD is caused by repeated physical or sex­
and severe negative symptoms. ual abuse, dissociative symptoms may be seen, for
example:
• amnesia for all or part of the event or events
• vagueness, daydreaming and the sense of being
Clinical example estranged from others
Annabelle, aged 15 years, had always been
• trance-like states
an emotionally fragile child who tended to • audiovisual hallucinations that represent
have intense, dependent relationships with fragmentary memories of the abuse
her peers. However, recently she had become • bodily symptoms (such as pseudoseizures or pelvic
withdrawn and self-absorbed, telling her mother that she pain) that represent somatic memories of the abuse.
wanted to drop out of school and pursue religious studies. PTSD is likely to be co-morbid with, or to be suc­
At interview, she was fearful and apparently distracted.
ceeded by:
She asked whether the interview was being videotaped.
After some time she revealed that she had been ‘chosen’ • mood disorder
to do something very important in the world. She had • anxiety disorder
become aware of this as a result of a revelation, recently, • hyperactivity, especially in boys
when the Earth shone and she ‘knew’ her destiny. Her • alcohol/drug use
conversation meandered and was often difficult to follow. • dissociative and somatoform disorders.
Several times during the interview she stopped talking Recent clinical research suggests that children under
and smiled to herself. Physical examination was normal.
the age at which sequential, narrative, autobiographi­
Annabelle was referred to a psychiatrist, who confirmed the
diagnosis of schizophrenia, admitted Annabelle to hospital, cal memory can be encoded and recounted (i.e. below
excluded organic pathology and commenced antipsychotic 3 years of age) can also manifest a form of PTSD. The
medication. After Annabelle's discharge, her medication outcome of acute stress is affected adversely if the
was monitored by her family doctor, and appointments were child is separated from parents, if the parents die, if
made for her to see the psychiatrist every 6 weeks. the parents develop psychiatric symptoms or if there is
a contagion of symptoms between children.
Interventions firstly emphasize hierarchy of needs,
hence immediate attention to physical and psychologi­
Post-traumatic stress disorder
cal safety. This is the case for all causes of emotional
PTSD occurs in response to the personal experience trauma. In this early stage, critical incident debriefing
of overwhelming, terrifying, potentially fatal stress is no longer recommended. Psychoeducation is appro­
directed toward the child or someone with whom priate. Children who continue to manifest symptoms
the child has a close attachment. In childhood and after 1 month should be referred for individual treat­
adolescence, the commonest kinds of threat causing ment. In PTSD associated with child maltreatment,
PTSD are motor vehicle accidents, burn injury, nat­ CBT and family therapy have proved helpful. CBT
ural or man-made disasters, animal attack, criminal must be trauma-focused. If medication is required, an
assault, observation of parental homicide or sui­ SSRI such as fluoxetine may be useful in alleviating
189
cide, and war. A particularly pathogenic stress or some anxiety symptoms.
 4.4 BEHAVIOUR AND MENTAL HEALTH NEEDS

Somatoform disorders • self-induced vomiting

This group of disorders is characterized by physical
• the use of dieting, laxatives, diuretics, enemas and
exercise to control or reverse weight gain.
symptoms that suggest an underlying physical dis­
Both eating disorders are much more common in girls
ease but for which either no such basis can be found,
than in boys; ballet dancers, gymnasts and athletes
or the symptoms are disproportionate in intensity or
are particularly at risk. It is likely the prevalence of
duration to a known physical disorder. Somatization
anorexia peaked during the 1980s; however, recent
disorder and hypochondriasis involve the conviction
trends include presentation of patients at a younger
that ­physical symptoms have a physical cause and the
age and more boys are presenting with anorexia. In
tendency to present repeatedly for medical care even
the 15–25-year-old group, bulimia is more common
though no physical cause can be found. The common­
than anorexia nervosa. The onset of anorexia occurs
est presentations are abdominal pain, headaches, or
during mid-adolescence. Bulimia usually begins in late
fatigue and muscle weakness. This kind of problem is
adolescence and may be a sequel of earlier anorexia
generally associated with other family psychopathol­
nervosa. The adolescent who develops anorexia ner­
ogy such as parental anxiety, depression or somatiza­
vosa is likely to have been a compliant, conscien­
tion, and may be based on the parent's conviction that
tious child who had enmeshed family relationships.
the child has a physical disease such as chronic fatigue
Secretive dieting and exercise often begin after a minor
syndrome. It is frequently encountered in sexually
precipitant, such as being told that one is overweight.
abused children. In conversion disorder, the dramatic
The child hides the amount of weight loss from her
symptoms suggest a physical disease but no such dis­
parents. Menses cease. The child becomes moody, irri­
ease can be found, and the symptoms are d ­ istributed
table and withdrawn. Eventually, the physical signs of
or displayed in accordance with a naive view of bodily
starvation appear:
functioning (e.g. glove-and-stocking anaesthesia). The
commonest conversion symptoms are paralysis, pare­
• emaciated facies and body
sis, seizures, anaesthesia, paraesthesia, vomiting, apho­
• fine body hair growth
nia, headaches, blindness and deafness. Conversion
• dry hair
disorder typically follows or accompanies a severe psy­
• cold hands
chosocial stress such as sexual abuse, bereavement or
• slow pulse
family conflict.
• low blood pressure.
The individual often resists medical help and is unable
The prevalence of somatoform disorders is proba­
to appreciate how emaciated she has become. The ado­
bly high. They are closely related to the emotional cli­
lescent with bulimia nervosa has dramatic weight fluc­
mate of the family and to parental psychopathology.
tuations and develops swollen salivary glands, abraded
The primary physician should investigate thoroughly
knuckles and dental caries. Eventually, as a result of
to rule out organic pathology, avoiding interminable
chronic metabolic alkalosis, kidney function may be
testing lest the symptoms become chronic and irre­
compromised.
versible. Psychiatric consultation should be sought as
Eating disorders are psychological conditions, often
early as possible. In conversion disorder, once the hid­
with marked physical complications. A useful concep­
den stressor is disclosed, symptoms usually dissipate
tualization is that initial dieting is a reinforced solution
with suggestive therapy such as graduated exercises. In
to the individual feeling distressed and out of control.
somatization syndromes, the family can be helped to
It is likely that a more enduring problem occurs in
interpret the symptoms as signs of stress and to man­
individuals with perfectionist personality traits with
age stress, for example with relaxation exercises.
over-regulated effect. Excessive dieting may represent
the pursuit of an idealized body image and self-control
by a child who perceives herself as helpless to direct
Eating disorders
her own life. Eating disorders must be differentiated
Anorexia nervosa is characterized by: from other disorders that can cause weight loss, such
• an intense fear of becoming fat or losing control of as malabsorption disorders, chronic infection, occult
eating malignancy, substance abuse, chronic depression, par­
• a relentless pursuit of thinness anoid schizophrenia and psychogenic vomiting.
• secretive food refusal, dieting and exercise causing Hospitalization and paediatric/psychiatric collabo­
marked loss of weight (below 85% of weight expected) ration are required if the patient is metabolically unsta­
• the perception of being overweight despite extreme ble, as evidenced by dehydration, inanition, electrolyte
thinness imbalance, bradycardia and low blood pressure, if she
• amenorrhoea. resists treatment, or if outpatient treatment has failed.
Bulimia nervosa is characterized by: Nasogastric feeding is required in extreme cases.
190
• binge-eating with a sense of loss of control The patient is not discharged from hospital until a
 Major psychiatric disorders 4.4
r­ easonable target weight has been attained. Treatment
plans should be individualized and goal-directed. For Practical points
patients aged 18 years and younger, family therapy has
the most rigorous evidence base. Bulimic patients, who Eating disorder
are usually older, generally respond best to CBT. Long- • Adolescents with eating disorders are skilled in their ability
term follow-up studies have revealed that patients with to conceal loss of weight and failure to eat.
anorexia have a variable course; 80% respond initially • Exclude other causes of weight loss as soon as possible.
to family therapy, although relapse and symptom chro­ • Hospitalize if the child is metabolically unstable
(electrolytes, heart rate, blood pressure, dehydration).
nicity also occur. The mortality rate associated with
• Otherwise, the child should be treated as an outpatient
anorexia is 3–5%, 50% of which is by suicide. Chronic with family and individual psychotherapy.
anorexia and significant co-morbid depression can be • The older the patient at presentation, the worse the prognosis.
a psychiatric emergency.

191
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 5
PART

PAEDIATRIC
EMERGENCIES

193
 5.1 Emergencies: causes
and assessment
Jeremy Raftos

There are many causes of collapse leading to the and more floppy epiglottis and soft palate. The nar-
need for emergency medical intervention in the child. rowest ­portion of their airway is below the cords at the
Table 5.1.1 lists some of the causes of common level of the cricoid ring, in contrast to adults, where
­paediatric emergencies. the narrowest portion is at the level of the vocal cords.
The following information outlines the r­ equirements The trachea is short and soft, and hyperextension or
for early assessment and reassessment in ­paediatric flexion of the neck may cause obstruction.
emergencies. Details of the emergency care of the Ensuring that the patient has a patent airway is of
­collapsed child are provided in the next chapter. the highest priority. In evaluating the airway a look,
In approaching the critically ill child, the diagnosis listen and feel approach is used.
is of secondary importance to: Look carefully for movement of the chest wall and
• primary assessment, which is a structured activity, the abdomen. Note the degree to which intercostal and
and other accessory muscles are being used to overcome
• timely resuscitation procedures. obstruction. Paradoxical movement of the abdomen
The primary assessment, sometimes also known as the may occur if there is upper airway obstruction.
primary survey, follows progression through the fol- Listen over the mouth and nose for air movement.
lowing A, B, C, D, E steps: Particular note should be made of inspiratory stridor,
• Airway which is a sign of tracheal, laryngeal or other upper
• Breathing airway obstruction. In severe obstruction, expiratory
• Circulation sounds may also be heard but inspiratory noises will still
• Disability (deficiency of cerebral function), with predominate. A stethoscope should be used to listen over
attention to the trachea and in the axillae for air movement.
• Exposure. Finally the examiner, by placing his or her face
This structured approach is based on the knowledge close to the child's mouth, may feel evidence of air
that the brain requires a continual supply of its two movement.
main metabolites: oxygen and glucose. An airway
problem, by depriving the brain of its oxygen sup-
Breathing
ply, will lead rapidly to death and therefore must be
corrected first. A breathing problem preventing oxy- In childhood, conditions that result in respiratory
gen moving into the lung and carbon dioxide out of compromise are the most common reason for emer-
the lung is the next priority. A circulatory problem gency intervention, and are the major cause of a poor
­preventing the oxygen being carried to the brain is outcome.
next, and so on. As with the airway, there are important differences
The resuscitation measures required and manage- between the child and the adult. Children have a higher
ment of the collapsed child are described in detail in metabolic requirement. They have more immature
Chapter 5.2. musculature, with easy fatigability of the diaphragm,
which is the major muscle of respiration. The chest
wall is more compliant and the ribs are more horizon-
tal, decreasing the efficiency of the bellows effect.
The primary assessment The airways in the child are proportionally smaller
and therefore produce an increased resistance to
Airway
air flow, especially when traumatized or inflamed.
Child and infant airways, compared with those of Resistance (R) across an airway is inversely propor-
the adult, present particular anatomical and physi- tional to the fourth power of the radius (r):
ological differences that increase their susceptibility
to compromise. Infants are obligate nose-breathers. R = 1 / r4
Infants and small children have smaller airways and Thus, halving the radius increases the resistance very
194
a smaller mandible, a proportionately larger tongue, significantly.
 Emergencies: causes and assessment 5.1
Table 5.1.1 Causes of paediatric emergencies

Airway Breathing Circulation Disability Exposure

Croup Asthma Congenital heart disease Seizure Hypothermia

Epiglottitis Bronchiolitis Duct dependent lesions: Meningitis Hyperthermia
Laryngeal foreign body Pneumonia  Critical aortic stenosis Encephalitis Inflicted injury
Bacterial tracheitis Foreign body Hypoplastic left heart Head injury
Trauma Congestive heart failure  Coarctation Raised intracranial pressure
Angioneurotic oedema Neuromuscular diseases Dysrhythmias: Hypoglycaemia
Retropharyngeal abscess Trauma: Bradycardia Metabolic disorder
Pneumothorax  Tachycardia Poisoning
Haemothorax   Supraventricular Envenomation
Lung contusion   Ventricular
Flail chest   Torsade de pointes
Near drowning   Fibrillation
Smoke inhalation Pulseless electrical activity
Metabolic acidosis: Shock:
 Diabetic ketoacidosis  Cardiogenic
Poisoning   Cardiomyopathy
Salicylates   Heart failure
Methanol   Myocardial contusion
Hypovolaemic
  Haemorrhage
  Vomiting/diarrhoea
  Burns
 Distributive
  Septicaemia
  Anaphylaxis
  Spinal cord injury
Obstructive
  Cardiac tamponade
  Hypertension
 Dissociative

Having established patency of the airway, evaluation s­ ternomastoid muscles must be recruited to raise the
for the presence and adequacy of breathing should fol- upper ribs further to increase ventilation.
low. It is helpful to divide this into three aspects: In infants and small children, flaring of the alae nasi
• effort of breathing may be seen. It must be remembered that, in this age
• efficacy of breathing group, 50% of airway resistance occurs in the upper
• effects of respiratory inadequacy on other organs. airway and flaring is an attempt to reduce this resis-
tance. This is a late sign and is indicative of severe
respiratory distress.
Effort of breathing
The effort of breathing is diminished in three c­ linical
Respiratory rate is age-dependent (Table 5.1.2). Tachy­ circumstances. These must be recognized, because
pnoea is an early response to respiratory failure. urgent intervention may be required. Firstly, exhaus-
Increased depth of respiration may occur later as respira- tion may develop as a result of the increased r­ espiratory
tory failure progresses. However, it should be noted that demands. The younger child is even more prone to
tachypnoea does not always have a respiratory cause and this due to immature musculature. Secondly, respira-
may occur in response, for example, to metabolic acido- tion requires an intact central respiratory drive centre.
sis. As the intercostal muscles and diaphragm increase Conditions such as trauma, meningitis and poisoning
their contraction, intercostal and subcostal recession may depress the respiratory centre. Thirdly, neuromus-
develop. In the infant, sternal retraction may also occur. cular conditions that cause paralysis, such as muscular
The ribs are horizontal in young children, in con- dystrophy and Guillain–Barré syndrome, may result in
trast to the downward slanting in older children and respiratory failure without increased effort.
adults. This reduces the ‘bellows’ effect that the inter- Symmetrical movement of the chest should be
195
costal muscles give to the latter. In the child, the ­confirmed. In the younger child the diaphragm is the
 5.1 PAEDIATRIC EMERGENCIES

Table 5.1.2 Vital signs by age

Age (years) Respiratory rate (breaths/min) Heart rate (beats/min) Systolic blood pressure (mmHg)

<1 30–40 110–160 70–90

1–2 25–35 100–150 80–95

2–5 25–30 95–140 80–100

5–12 20–25 80–120 90–110

> 12 15–20 60–100 100–120

main muscle of respiration; therefore, one should also

look for movement of the upper abdomen. increased effort of breathing? Are there inspiratory or expiratory
Inspiratory and expiratory noises should be noted. noises? Is grunting or flaring of the alae nasi present? Efficacy
Wheezing is heard with lower airway narrowing, as of breathing needs to be assessed by assessing the degree
in asthma, often with a prolonged expiratory phase. of chest expansion, breath sounds and oximetry. The effect of
respiratory inadequacy can be seen in an increased heart rate,
Crepitations may be heard with pneumonia and heart
change in skin colour and mental status.
failure. The infant was found to have a marked increase in effort
of breathing, flaring of the alae nasi, bilateral crepitations
and tachycardia. In addition to the cyanosis, he was drowsy.
Efficacy of breathing Assessment of the cardiovascular system showed normal
Auscultation of both sides of the chest will confirm air pulse volume, capillary return and blood pressure. A search
movement. Beware the silent chest! Oximetry is u ­ seful for evidence of heart failure revealed no gallop or heart
murmur, no liver enlargement and the presence of femoral
for providing a measure of arterial oxygen s­ aturation pulses.
(Sao2), which reflects the efficacy of breathing, but With high flow oxygen his colour improved, as did his
oximetry readings may be difficult to obtain in the mental status. A diagnosis of severe bronchiolitis was made.
cold or shocked child because of poor perfusion, and To complete the assessment the infant was found to
are less accurate when the Sao2 is less than 70%. have no rash, his initial temperature was 35°C, and with
appropriate warming his temperature rapidly reached 36°C.

Effects of respiratory inadequacy on other organs

The impact of hypoxia on the cardiovascular system is Circulation
to cause tachycardia, but pre-terminally it may cause
bradycardia. Cardiac output is the product of stroke volume and
Cyanosis is also a pre-terminal sign. Hypoxia may heart rate. The normal heart rate decreases with age
also cause peripheral shutdown and pallor secondary (see Table 5.1.2). Infants have a small, relatively fixed,
to sympathetic stimulation. cardiac stroke volume; thus they must increase their
The effect of hypoxia on the brain is to cause ­initial heart rate to respond to increased demand.
agitation and irritability in infants, followed by increas- Infants have a relatively larger intravascular ­volume
ing loss of consciousness. (85 mL/kg) that decreases with age to 60 mL/kg in
the teenager. The normal ranges for blood pressure
increase with age (see Table 5.1.2 and Chapter 18.2),
because systemic vascular resistance increases as the
Clinical example child gets older.

A 1-week-old infant presented after a 3-day

illness, cyanosed and with marked tachypnoea. Assessment of circulation
He was severely ill.
In this situation, rapid systematic assessment An increase in heart rate is the earliest response to any
and resuscitation measures must go hand in hand. The reduction in intravascular volume. As shock p ­ rogresses,
airway and breathing must be assessed first. This infant bradycardia may develop as a ­pre-terminal sign. It
was breathing fast and was cyanosed. Points that have to is important to assess pulse volume both peripher-
be considered urgently are: Is there intercostal, sternal or ally and centrally. Weak central pulses i­ndicate severe
subcostal recession, or use of accessory muscles indicating
shock. Capillary refill can be a sensitive indicator of
196
vascular status. To assess this, light pressure should be
 Emergencies: causes and assessment 5.1
applied to the skin over the sternum for 5 seconds. In be difficult to determine in the younger child because
the normal individual, capillary return of blood, seen of the relatively short, often chubby, neck. Listen for a
as a slight flush of the pallid area where pressure was gallop rhythm and for lung crepitations. Palpation of
applied, will occur in less than 3 seconds. Caution the abdomen may reveal an enlarged liver.
should be used in interpreting this sign in the child
who has been exposed to a cold environment.
Disability
In the shocked child, hypotension is a late
­pre-terminal sign. The assessment of neurological function as part of the
primary assessment has three main aims:
• to determine rapidly the level of consciousness
Effects of circulatory inadequacy on other organs
• to find localizing intracranial lesions
Circulatory inadequacy leads to poor tissue perfusion, • to determine whether there is raised intracranial
which in turn leads to metabolic acidosis. Tachypnoea pressure.
occurs to compensate for the acidosis. It must be remembered that respiratory and cardiovas-
Initial sympathetic stimulation may cause agitation, cular failure can cause decreased consciousness and
but later poor cerebral perfusion causes increasing must be dealt with first.
drowsiness and coma in the pre-terminal phase.
Pre-renal failure develops with hypovolaemia
Conscious level
and hypotension, with reduction of urine output.
Normal urine output is greater than 1 mL per kg per Conscious level can be rapidly assessed using the
h in the child and more than 2 mL per kg per h in AVPU method:
the infant. • A Alert
• V responds to Voice
• P responds to Pain
Signs of cardiac failure
• U Unresponsive.
The signs of cardiac failure should be sought. This is The child who is unresponsive or who responds only to
critical to assessment, because the finding of cardiac pain has a Glasgow Coma Scale (GCS) score of 8 or
failure will influence the approach to resuscitation less. The GCS has no place in the primary survey, but
­discussed in the next chapter. Raised jugular venous is a useful tool for monitoring changes in neurological
pulse height is important in the older child but may status after initial stabilization (Table 5.1.3).

Table 5.1.3 Glasgow Coma Scale and Children's Coma Scale

Glasgow Coma Scale (4–15 years) Child's Glasgow Coma Scale (< 4 years)

Response Score Response Score

Eye opening Eye opening

Spontaneously 4 Spontaneously 4
To verbal stimuli 3 To verbal stimuli 3
To pain 2 To pain 2
No response to pain 1 No response to pain 1

Best motor response Best motor response

Obeys verbal command 6 Spontaneous or obeys verbal command 6
Localizes to pain 5 Localizes to pain or withdraws to touch 5
Withdraws from pain 4 Withdraws from pain 4
Abnormal flexion to pain (decorticate) 3 Abnormal flexion to pain (decorticate) 3
Abnormal extension to pain (decerebrate) 2 Abnormal extension to pain (decerebrate) 2
No response to pain 1 No response to pain 1

Best verbal response Best verbal response

Orientated and converses 5 Alert; babbles, coos, words to usual ability 5
Disorientated and converses 4 Less than usual words, spontaneous irritable cry 4
Inappropriate words 3 Cries only to pain 3
Incomprehensible sounds 2 Moans to pain 2
No response to pain 1 No response to pain 1 197
 5.1 PAEDIATRIC EMERGENCIES

Posture and tone Circulatory changes in neurological failure

Hypotonia may be seen in the seriously ill child no Hypertension, bradycardia and hypoventilation form
matter what the underlying diagnosis. Hypertonia the Cushing triad. These are late signs of raised intra-
and posturing should be observed, if present, and any cranial pressure and must be acted on immediately.
asymmetry noted. Decorticate posturing is evidenced Hypotension is a pre-terminal event.
by flexed upper limbs and extended lower limbs,
whereas in decerebrate posturing both the upper and
lower limbs are extended. These are both pre-terminal Exposure
signs and must be acted on immediately. Infants and small children have a proportionately greater
surface area and therefore lose heat more r­apidly than
older children and adults. Infants are also less able to
Pupil size and reactivity respond to hypothermia. Early measurement of core
Examination of the pupils can give valuable infor- temperature is therefore important, and appropriate
mation. It is important to determine whether there is warming during resuscitation should be maintained.
dilatation, non-reactivity or inequality. Most impor­
­ Fever may indicate infection.
tantly, unequal pupils may indicate tentorial ­herniation It is important to expose the child fully for the
or a ­ rapidly expanding lesion on one side of the ­primary assessment, as valuable clues such as rashes
brain. Small, ­reactive pupils may indicate a metabolic in meningococcal disease or bruises in inflicted injury
­disorder or medullary lesion. may be missed.
The child may respond with fear or embarrass-
ment to exposure and therefore it must be undertaken
Practical points sensitively.

• In the collapsed child, a careful and orderly primary

assessment and timely resuscitation measures are of
more importance than the diagnosis. Reassessment
• Children differ from adults physiologically and anatomically.
• Conditions affecting respiration are a common pathway to Frequent reassessment should be undertaken,
collapse in the child. ­especially if there is any deterioration during the resus-
• Cyanosis and hypotension are pre-terminal signs. citation. A search for a definitive diagnosis should now
• Decerebrate and decorticate posturing are pre-terminal signs. be completed.

Respiratory patterns in neurological failure

Raised intracranial pressure can lead to a number of
Putting it all together
abnormal breathing patterns, ranging from hyperven- Table 5.1.4 summarizes the components of the ­primary
tilation to apnoea. assessment in table format.

198
 Emergencies: causes and assessment 5.1
Table 5.1.4 Putting it all together: the primary assessment

Airway – Assess patency

Look for Listen for Feel for

Movement of the chest wall Air movement Air movement

Intercostal and accessory muscle use Abnormal sounds – stridor

Breathing – Assess adequacy of breathing

Effort of breathing Effectiveness of breathing Effects of inadequate respiration

Recession Breath sounds Heart rate

Respiratory rate Chest expansion Skin colour
Inspiration or expiration noises Abdominal excursion Mental status
Grunting
Accessory muscle use
Flare of the alae nasi

Circulation – Assess adequacy of circulation

Effects of circulatory inadequacy on

Cardiovascular status other organs Signs of cardiac failure

Heart rate Raised jugular venous pulse height Gallop rhythm

Pulse volume (not in infancy) Crepitations in lungs
Capillary refill Respiratory rate and character Enlarged liver
Blood pressure Skin appearance and temperature
Mental status
Urinary output

Disability – Assess neurological function

A rapid measure of level of consciousness should be recorded – AVPU method
Note the child's posture and tone – especially any lateralizing features
Check pupils for size, equality and reactivity
Note the presence of convulsive movements

Exposure
Take the child's core temperature
Look for a rash or injury

Reassessment
Should be performed regularly, especially if there is deterioration

AVPU: Alert, Voice, Pain, Unresponsive.

199
 5.2 Resuscitation
Ed Oakley, Mike South

The term ‘collapse’ is used here to describe a state in With sufficient personnel available, diagnostic and
which a child's neurological and/or cardiorespiratory resuscitative procedures may progress in parallel.
function is acutely and severely impaired. One important investigation to consider early when
the cause of collapse is unknown is a blood glucose
estimation.

Diagnosis
Collapse may occur because of: a primary neurologi-
cal process; loss or reduction of oxygen supply to the Resuscitation
brain; or a metabolic disturbance or toxins affecting
If you find yourself responsible for the immediate
brain function. Collapse may be the result of many dif-
care of a collapsed child, you should be familiar with
ferent disease processes, some examples of which are
at least the procedures used in basic life support. The
shown in Table 5.2.1. A more thorough differential
general principles may be the same as those used in
diagnosis and approach to assessment of the collapsed
the resuscitation of adults, but specific techniques are
child is presented in Chapter 5.1.
required in children.
The primary aim is to restore an adequate sup-
ply of oxygenated blood to the brain – to prevent
Clinical example secondary brain damage. The resuscitation proce-
dures required will vary, depending on the degree of
David, a 21/2-year-old boy, was found collapsed physiological impairment, from simple ones, such as
in the bedroom while visiting his grandmother's
application of an oxygen facemask or administra-
house. He was taken immediately to a local
hospital where he was noted to be floppy and
tion of a bolus of intravenous fluid, through basic
poorly responsive to voice or physical stimulation. He had an cardiopulmonary resuscitation (CPR) to advanced
adequate airway, his breathing was a little shallow and slow, life support measures including endotracheal intu-
and he was slightly dusky in colour. His limbs were pink and bation, mechanical ventilation and the use of vaso-
felt warm, and he had strong pulses. active drugs.
David was placed on his side and oxygen was Resuscitation techniques for newborn infants are
administered by facemask; his colour improved immediately.
discussed in detail in Chapter 11.1.
He was afebrile, with normal blood glucose on bedside
testing, and no other physical abnormalities were found.
A careful history showed that he had been very well all
day. He had been playing unobserved in his grandmother's Life support
house for about an hour before he was found. His The environment is important: make sure you are in a
grandmother kept some sedative drugs (nitrazepam) in
safe situation – you will be of no value to the collapsed
the bedside cabinet, and a telephone call back to the
house revealed that the tablet bottle was lying open on the child if you, the rescuer, become a second victim (e.g.
bedroom floor. at a road accident scene). Get someone to summon
David continued to receive oxygen and close observation, sufficient extra help.
and his clinical condition improved steadily over the next Quickly evaluate the degree of collapse:
12 hours. He was discharged home well the following day. • Assess the child's response to verbal or physical
arousal (e.g. gentle shaking)
• Colour – pale or blue
Sometimes the cause of collapse is immediately • Temperature – cool peripheries.
obvious, as in head injury or drowning, but some- Then move quickly to the ABC. The term ABC
times it may be a diagnostic problem initially (e.g. is a useful reminder of not only the manoeuvres
sepsis or drug ingestion). In this latter setting, resus- required (Airway, Breathing, Circulation) but also
citation usually has to take priority over obtaining of the correct sequence in which to apply them.
200
a complete history, examination and investigation. Assessment of the airway and breathing should be
 Resuscitation 5.2
Table 5.2.1 Some causes of collapse in children

Category Diagnosis

Primary neurological Meningitis

process Head injury
Encephalitis
Seizures

Failure of oxygen Acute asphyxia (e.g. drowning, birth

supply to brain asphyxia)
Respiratory causes (e.g. severe
asthma, croup)
Cardiac causes (e.g. arrhythmias,
myocarditis)
Hypovolaemia (e.g. dehydration,
Fig. 5.2.1 Optimal head and neck position for airway
haemorrhage)
protection in an infant. Do not overextend the neck. This head
Sepsis
and neck position may be used with the child on its side or lying
Anaphylaxis
on its back.
Metabolic Hypoglycaemia
disturbance or toxins Hyponatraemia Airway
Drug or other toxic ingestion
Envenomation If conscious, the child will usually adopt the best pos-
Bacterial toxins ture to maintain his or her own airway: don't force the
child to lie down.
In an unconscious child, assess the adequacy of the
performed quickly, with emphasis on rapid progres- airway by observing the degree of chest movement and
sion to the circulation. by listening and feeling for breath at the mouth (place
In obviously more advanced states of collapse, do your ear close to the child's mouth).
not waste time on assessment but commence CPR An unconscious child with a patent airway should
immediately. be placed on the side: this improves the size of the air-
way (gravity pulls the jaw and tongue forward), allows
saliva and other secretions to drain from the mouth,
and reduces the risk of aspiration of gastric contents
Clinical example should they be regurgitated. Moving the child in this
Jodie, a 6-year-old girl, was a rear seat way may be harmful if there is a possibility of cervical
passenger when her family's car was involved spine injury (e.g. following road trauma); in this case,
in an accident while travelling at around work to obtain an optimal airway in the existing posi-
60 km/h. She was not wearing a seat belt. tion without excessive rotation, flexion or extension of
On arrival at hospital, she was awake but agitated with the neck.
multiple superficial abrasions to her face, trunk and limbs. If the airway is completely or partially obstructed, it
Within 20 minutes her state of consciousness deteriorated,
she developed increasing tachycardia and her blood
may be further improved by extending the neck to the
pressure had fallen. neutral, or slightly extended, position, and supporting
Jodie was intubated to protect her airway; during the the jaw in a forward position; this is easiest done with
procedure careful attention was paid to prevent excessive the child on their back (Fig. 5.2.1). This may be done
movement of her cervical spine. The doctor had already by placing your fingers behind the angle of the man-
inserted a large-bore cannula into a vein in her antecubital dible and applying gentle forward pressure. If secre-
fossa, and through this she was given 40 mL/kg saline. She
tions, gastric contents or food may be obstructing the
was re-examined for possible sites of hidden bleeding,
including the abdomen and limbs (especially fractured
­airway, suck them out, preferably with a wide-bore
femur). Her abdomen was noted to be distended and she rigid sucker.
underwent computed tomography (CT), which showed small If the airway is still not optimal, an oropharyngeal
lacerations of the liver and spleen. CT of her brain, performed airway device may be tried. It must be of the correct
at the same time, was normal. Jodie was managed with size and inserted appropriately. If too large, it may
supportive care, including mechanical ventilation and increase airway obstruction and induce laryngospasm;
blood transfusion. Surgical exploration of the abdomen to
it may also stimulate vomiting if the patient is partially
control bleeding was considered but not performed, as she
stabilized with medical treatment. She was discharged from conscious. The best size may be approximated by lay-
the intensive care unit 4 days later. ing the airway beside the face: select a size that reaches
201
from the front teeth to the angle of the mandible.
 5.2 PAEDIATRIC EMERGENCIES

If it is not possible to secure an adequate airway by to synchronize artificial breaths with any taken by the
these means, endotracheal intubation will be required patient. Additional breaths may also be required.
(see below). Respiratory support may take various forms:
expired-air breathing; bag and facemask breathing;
or endotracheal intubation and mechanical ventila-
Breathing
tion by machine or bag. The choice will depend on the
Once you are sure that the airway is patent, assess the state of the child, the availability of equipment and
adequacy of breathing: look at the rise and fall of the your experience. If inexperienced with endotracheal
chest and the rate of breathing. If strong breathing intubation, do not attempt this unless it is not possible
movements are present but they appear obstructed (with to provide adequate respiration by other means (this
poor chest expansion and indrawing of the soft tissues), is unusual in children). Appropriate sizes of endotra-
recheck and reposition the airway. If breathing remains cheal tube are given in Table 5.2.2.
inadequate or you are uncertain, commence artificial In children less than 1 year of age, expired-air resus-
respiration. Do not delay, as ongoing hypoxaemia and citation should be administered with the rescuer's
hypercarbia are dangerous to a child whose brain is likely mouth covering the entire mouth and nose of the
to be already compromised by the primary problem. infant; in older children, mouth to mouth respiration
Artificial respiration may be given to assist exist- is used (pinching the nose shut), as for adults.
ing breathing efforts, or as the sole source of gas Facemask and bag resuscitation may be performed
exchange. If you are assisting the patient's existing with a variety of systems. Those with self-inflating
but inadequate breathing efforts, you should attempt bags are easiest to use.

Table 5.2.2 Resuscitation card

Fluid
Min. Adrenaline ETT int. bolus
Weight sys. BP HR RR 1 : 10 000 Adrenaline diameter ETT lip/ DC shock 20 mL/kg
Age (kg) (mmHg) (bpm) (bpm) (mL) 1 : 1000 (mL) (mm) nose (cm) 4 J/kg (J) (mL)

Term 3.5 50 100–170 40–60 0.4 – 3.0/3.5 8.5/10.5 14 70

3 months 6 50 100–170 30–50 0.6 – 3.5 9.5/11 24 120

6 months 8 60 100–170 30–50 0.8 – 4.0 13/10 32 160

1 year 10 65 100–170 30–40 1.0 0.1 4.0 14/11 40 200

2 years 13 65 100–160 20–30 1.5 0.15 4.5 15/12 52 260

4 years 15 70 80–130 20 1.5 0.15 5.0 14/17 60 300

6 years 20 75 70–115 16 2.0 0.2 5.5 15/19 80 400

8 years 25 80 70–110 16 2.5 0.25 6.0 16/20 100 500

10 years 30 85 60–105 16 3.0 0.3 6.5 17/21 120 600

12 years 40 90 60–100 16 4.0 0.4 7.0 18/22 160 800

14 years 50 90 60–100 16 5.0 0.5 7.5 19/23 200 1000

17+ years 70 90 60–100 16 10 0.5 7.5/8.0 19/23 300 1000

Adrenaline 1 : 1000, volume of 1 : 1000 adrenaline (epinephrine) to give a dose of 10 μg/kg; adrenaline 1 : 10 000, volume of 1 : 10 000
adrenaline (epinephrine) to give a dose of 10 μg/kg.
bpm, Beats or breaths per minute; ETT int. diameter, endotracheal tube size (internal diameter); ETT lip/nose, depth of endotracheal
tube for fixation at lip (oral tubes) or nose (nasal tubes) – always verify that tube is in mid-trachea by clinical examination and X-ray;
DC 4, direct current shock energy in joules for 4 J/kg – use same values for both monophasic and biphasic defibrillators (exact
settings may have to be modified according to those available on the specific defibrillator); fluid bolus (saline), volume of saline for
20 mL/kg; HR, heart rate normal range; min. sys. BP, minimum acceptable systolic blood pressure; RR, respiratory rate normal range;
202 term, term newborn infant.
 Resuscitation 5.2
Ideally, any collapsed child should receive high con-
centrations of inspired oxygen. This may be by simple
facemask or through the circuit of the resuscitat-
ing bag. It is important to recognize that with most
­self-inflating bag systems a flow of oxygen is sup-
plied to the patient only when the bag is squeezed.
The appropriate delivery system for administering
oxygen to a spontaneously breathing child is a simple
facemask. Choose a facemask that covers the child's
mouth and nose.
Assess the effectiveness of delivered breaths by
watching the chest move. Ensure the administered
breaths are of sufficient volume, but try not to blow
excessively hard as this can lead to gastric disten-
sion. If there is no adequate chest movement, try re-­
establishing the airway as described above. Move on to
manage the circulation, but quickly return to artificial
breathing unless adequate spontaneous respiration has
commenced.
If there is difficulty with airway or breathing, or
concern about performing mouth to mouth ventilation,
move quickly to the circulation and return to the air-
way and breathing after 1 minute of external cardiac
compressions.

Fig. 5.2.2 In an infant, the chest may be compressed effectively

by encircling the chest with your hands, with the thumbs over
Circulation the lower sternum. This technique is not very suitable for solo
rescuers as it is time-consuming to re-establish the position after
The circulation is inadequate if: administering a breath; in this situation, compress the chest with
• no central pulses (e.g. carotid or femoral) are two fingers of one hand over the lower sternum.
palpable
• the heart rate is less than 60 in a collapsed child, or
• the pulses are weak, with other signs of poor tissue Clinical example
perfusion (pallor, coldness, poor capillary refill).
Cardiac compression is indicated for a child with no Marco, a 2-year-old boy, was found at the
pulses, weak pulses, bradycardia, or if there is any bottom of his uncle's unfenced swimming
uncertainty. pool during a family barbecue. No one knew
The pulse can be difficult to assess in an emergency how long he had been missing. When the
ambulance arrived, his father was giving CPR and Marco
situation. If in doubt, commence compressions – you will
was floppy and unresponsive, with no spontaneous
be unlikely to do any harm. respiration or palpable pulses. The ECG monitor showed
The optimal technique for chest compression varies asystole. Marco was intubated by a paramedic and an
with age: intraosseous needle was inserted. He received continuing
• Infant. Encircle the chest with the hands, with the CPR and multiple doses of intraosseous adrenaline
thumbs over the lower sternum (Fig. 5.2.2). This (epinephrine) during transfer to hospital. Despite 30 minutes
technique is not very suitable for solo rescuers as it of further resuscitation efforts in hospital, he remained in
asystole. It was clear that the prognosis for survival was
is time consuming to re-establish the position after
hopeless and resuscitation was discontinued.
administering a breath; in this situation, compress
the chest with two fingers of one hand over the
lower sternum. For children of all sizes, the chest should be com-
• Small child. Use the heel of one hand, centred one pressed around 100 times/minute, depressing the ante-
fingerbreadth above the xiphisternum. rior chest wall about one-third of the anteroposterior
• Larger child. Use the heels of both hands (one atop diameter. Push hard and fast.
the other), centred two fingerbreadths above the Any child who requires chest compressions will also
xiphisternum. require artificial respiratory support; the converse is
The aim for all ages is to compress the lower half of usually true also. For a single rescuer, chest compres-
203
the sternum. sion and artificial respiration should be given at a ratio
 5.2 PAEDIATRIC EMERGENCIES

of approximately 30 : 2, whereas with two or more

rescuers the ratio should be 15 : 2. Chest compres-
­
sions should be resumed towards the end of the child's
expiration. Once the child has an endotracheal tube
in place, chest compressions should not be interrupted
during the delivery of each breath.
Once CPR has commenced, a cardiac monitor
should be connected to the child as soon as it is avail-
able. The rhythm should be assessed as VF/VT or non-
VF/VT and management continued as in Figure 5.2.5A
and B below. Fig. 5.2.3 Insertion of a needle into the bone marrow at the
distal end of the tibia. The black handle facilitates the twisting
Fluid administration motion and application of steady pressure as the needle is
inserted. The handle, along with the attached stylet, is removed
Hypovolaemia is commonly an important factor in a once the needle is in place.
collapsed child. Rapid infusion of a fluid bolus should
be tried in any patient with signs of an inadequate cir-
the bone, remove the stylet and aspirate the needle with
culation. Again, if in doubt go ahead and give some
a small syringe. Aspiration of dark, blood-like fluid con-
fluid: you are unlikely to do any harm and you can
firms you are in the correct spot. Commercially avail-
assess the effects on the patient's circulation. Initial
boluses of 10–20 mL/kg are appropriate; these may be able needles usually come with a plastic fixation device.
repeated as necessary. Normal saline is usually used, If using a lumbar puncture needle, you can fashion a
but colloid solutions such as 5% albumin may also be suitable fixation from plaster of Paris. The aim is for
used. Avoid hypotonic fluids, such as dextrose solu- the needle to be well supported, to prevent it being dis-
tions with low concentrations of sodium. lodged and to prevent sideways movement and enlarge-
ment of the entry hole in the bone. Administration of
Vascular access fluid may require pressure on the infusion bag or the use
A collapsed child will need vascular access for the of a syringe and three-way tap.
administration of fluids and drugs. Appropriate sites for intraosseous needle insertion
Cannulation of a peripheral vein will provide ade- include:
quate initial access. Try to place a large cannula if pos- • the distal tibia (the medial aspect where the shaft of
sible, or more than one cannula, particularly if you the tibia meets the malleolus; Fig. 5.2.3)
suspect that the collapse is related to haemorrhage. • the proximal tibia, about one-third of the way
Cannulation of a peripheral vein can be very diffi- down from the knee to the ankle (on the flat part of
cult in a collapsed child; do not waste time trying for the anteromedial aspect of the tibial shaft)
more than a few minutes. Central venous catheteriza- • the anterior iliac crest.
tion is an option but can be very difficult in this set- The tibia is most suitable for children under 5 years
ting, even for experienced operators; it also takes a of age.
significant amount of time. A better alternative is the
insertion of an intraosseous needle, whereby a needle
Putting it all together
is inserted into the bone marrow (which is a vascular
space that cannot collapse because of the surrounding The basic life support approach to a collapsed child
bone cortex). This technique is simple, quick and pro- and the advanced management of established paedi-
vides access for the administration of fluids and drugs atric arrest are summarized in Figures 5.2.4 and 5.2.5.
that will reach the central circulation as quickly as if It is important that life support measures (espe-
administered into a peripheral vein. cially external cardiac compressions) are applied con-
Commercially available intraosseous needles that tinuously. They should be interrupted only very briefly
include a stylet and handle are most commonly used, to assess response, heart rhythm, etc. They should not
but a wide-bore lumbar puncture needle is a satisfac- be terminated until stability has been clearly achieved
tory alternative. With the stylet in place, insert the nee- or the decision to abandon further attempts has been
dle through the skin, perpendicular to the surface of the made definitively.
bone in all directions. Local anaesthesia is not required
unless the patient is conscious. Twist the needle back and
Ongoing resuscitation
forth along its long axis while firmly pushing it into the
bone. Do not rock it from side to side. A ‘give’ is usually If the child has persistently poor circulation despite
felt as the needle tip enters the marrow cavity. Once you the presence of sinus rhythm, and after 40–60 mL/kg
204
feel this, or once the needle has been inserted 1–2 cm into intravenous fluid has been given, look for causes of
 Resuscitation 5.2
­ articularly in an out-of-hospital setting, the progno-
p
Check if patient responds sis for recovery or survival is very poor.
to command/pain
Temperature control following resuscitation is an
area of controversy. Traditional teaching was to main-
tain normal body temperature using blankets and
Call for help overhead heaters. There is now animal research, and
some human studies, that suggest improved neuro-
logical outcome after cardiac arrest, or head trauma,
if body temperature is quickly lowered to around
Position patient 32–33 °C for a period of 48–72 hours following the
Check airway:
Ensure airway patent
insult. More research is needed before firm conclu-
sions can be drawn regarding the use of therapeutic
hypothermia in resuscitation of children.

Check breathing:
if inadequate, or if any doubt:
Practical points
Give assisted respiration
Use Bag & Mask with oxygen if available • Learn the basics of paediatric life support before you need
Check chest moves with each breath them – you won't have time to consult a textbook in an
Move quickly to assessment of circulation emergency.
(Do not delay providing good support
• Do not waste time assessing the adequacy of breathing
for breathing) and circulation in a collapsed child. Assessment can be
misleading and time-consuming.
• If the circulation or breathing are inadequate or you are
Check pulse: uncertain, administer cardiac compressions and artificial
if absent, too slow, or weak, respiration.
or if any doubt: • Never hesitate to give a trial of an intravenous fluid bolus
Give cardiac compressions to a collapsed child.
~100 compressions/minute • Learn the technique of intraosseous needle placement –
15 compressions then 2 breaths this simple technique can be life-saving.
(for 2 rescuers)
• Call for extra assistance early.
Pause compressions for each breath
if patient not intubated

Appendix
Move to advanced life support Resuscitation guide A
when possible
Table 5.2.2 provides a summary of acceptable physio-
logical parameters for children according to age, along
Fig. 5.2.4 Basic life support. with endotracheal tube sizes, DC shocks and doses of
adrenaline (epinephrine) used in resuscitation. This
hidden bleeding (especially abdomen, chest and frac- table can be photocopied (or downloaded and printed
tured femur); also consider the use of an inotropic from the internet at http://www.rch.org.au/clinical-
infusion such as dobutamine (10 μg per kg per min – guide/forms/resusCard.cfm). If folded horizontally at
put 15 mg/kg of the drug into 50 mL saline and run at the centre, it can be laminated and punched to attach
2 mL/h). conveniently to a hospital ID badge, so making it
If the child is successfully resuscitated, careful ongo- readily available for reference in the clinical setting. It
ing monitoring and treatment will be required. It is a is also available for download to display on an iPhone,
mistake to terminate intubation and mechanical venti- iPad, PDA and other smart phones.
lation too soon. Ensuing brain swelling may lead to a
secondary deterioration.
Resuscitation guide B
It is important to know when to stop if resuscita-
tion efforts are producing no effect. Except in cases Another useful aid to resuscitation can be downloaded
of extreme hypothermia, as occur in drowning in from the internet at http://www.rch.org.au/clinicalguide/
near freezing water, persisting cardiac arrest after cpg.cfm?doc_id=5137. It will run as a utility with any
20–30 minutes of good resuscitation is an indication recent internet browser. It produces a table of appropri-
of a hopeless prognosis. When hypoxia or hypovo- ate drug doses, DC shocks and endotracheal tube sizes
205
laemia has resulted in cardiac arrest with asystole, according to the age and weight of the patient.
 5.2 PAEDIATRIC EMERGENCIES

Start CPR
15 compressions: 2 breaths
Minimise interruptions
Pause compressions
only if not intubated

Attach
DefibriIIator/Monitor

Shockable? Assess rhythm Non-Shockable

(VF/pulseless VT) for maximum of (Asystole or PEA)
10 seconds

Adrenaline
Adrenaline 10 mcg/kg
10 mcg/kg after Shock
(immediately then
second shock then (4 J/kg or adult 200J) No
every second cycle)
every second cycle

Amiodarone
5mg/kg after CPR Return of CPR
3rd shock and 2 minutes spontaneous 2 minutes
only give once circulation?

Yes

Post Resuscitation care

A

Fig. 5.2.5A Advanced life support. CPR, cardiopulmonary resuscitation; DC, direct current; IO, intraosseous; IV, intravenous; VF,
ventribular fibrillation; VT, ventricular tachycardia.

206
 Resuscitation 5.2
Double check: Other drugs to consider
• ETT position Atropine
• Oxygen supply For persistent / bradycardia (20 µg/kg)
• Function of self-inflating bag (min 100 µg, max 600 µg)
• ECG leads in contact
• Defibrillator paddles in contact Amiodarone
• IV or IO access is secure If VF or pulseless VT persists after 3–4 DC shocks.
(5 mg/kg, max 300 mg) by bolus injection if patient
Cardiac compression is tiring unstable, or over 40 min if stable.
• Monitor technique Flush IV line well afterwards.
• Change operators every few minutes if possible
Lidocaine
Do not waste time when cardiac compressions Same indications as amiodarone (1 mg/kg)
might be given (0.1 mL/kg of 1%)
• Commence CPR immediately. Amiodarone is the preferred agent; use lidocaine
• If in doubt about circulation – give CPR. only if unavailable. Never give lidocaine after
• No prolonged attempts at intubation without CPR. amiodarone.
• During resuscitation cycles, do not check for pulse
unless ECG shows an organized rhythm. Magnesium sulphate
• Do not check rhythm immediately after DC shock – For hypomagnesaemia
give CPR for 2 min then check. or for polymorphic VT (torsade de pointes)
50% solution: 0.05–0.1 mL/kg
Correct treatable causes (0.1–0.2 mmol/kg) (max 2 g) by intravascular infusion
over 5 mins.
• Hypoxaemia
• Hypovolaemia
Sodium bicarbonate, calcium, and doses of adrenaline
• Hypo/hyperthermia
> 10 µg/kg have no place in routine resuscitation.
• Hypo/hyperkalaemia
• Tamponade
Other issues
• Tension pneumothorax
Blood gas analysis
• Toxins/poisons/drugs
Arterial (and to some extent venous) blood gas
• Thrombosis
analysis can help determine degree of hypoxaemia,
adequacy of ventilation, degree of acidosis, and
presence of electrolyte abnormalities such as
hyopmagnesaemia. It is not a priority in initial
resuscitation attempts, and obtaining a sample
should not distract from other resuscitation
manoeuvres.

B
Fig. 5.2.5B Advanced life support – notes. CPR, cardiopulmonary resuscitation; DC, direct current; ECG, electrocardiography; ETT,
endotracheal tube; IO, intraosseous; IV, intravenous; VF, ventribular fibrillation; VT, ventricular tachycardia.

207
 5.3 Poisoning
and envenomation
James Tibballs, Ed Oakley, Ken Winkel

Poisoning and envenomation are two important areas cardiorespiratory failure. Repeated doses or infusions
of emergency care that should be familiar to any of opiates should be confined to newborns who are
health practitioner involved with acute care of chil- mechanically ventilated, and, wherever possible, local
dren and young people. or regional anaesthesia should be employed for sur-
gical procedures. Local anaesthetic agents or opiates
administered to the mother during labour may poison
the newborn.
Poisoning Care should be exercised with the use of topical
antiseptics. Mercurochrome, commonly applied to the
Poisoning is a common health problem among chil- umbilical stump, may cause mercury poisoning if used
dren. It is responsible for numerous attendances to in excess. Hexachlorophene should not be used as a
emergency departments of children's hospitals. Over regular bathing solution because it is readily absorbed
3500 children aged 0–4 years are admitted annually to percutaneously, causing neurotoxicity. If used in
Australian hospitals as a result of poisoning incidents. excess, iodinated compounds may cause hypothyroid-
Worldwide, poisoning is the third most common cause ism. Occasionally, mistakes in the preparation of arti-
of death among young children. A great deal of effort ficial foods may cause serum electrolyte disorders and
is expended upon a problem that is largely preventable. dehydration.
A Poisons Information Centre serving a population of
5 million receives approximately 40 000–50 000 tele-
phone enquiries per annum; two-thirds concern actual Age 1–5 years
poisoning and, of those, 60–70% concern children Poisoning occurs most frequently in this age group.
aged 4 years and younger. Most instances are said to be accidental, in which the
young child discovers a drug or a household cleaning
or chemical agent. The majority of serious poisonings
Epidemiology
occur with prescribed drugs or with over-the-counter
The nature of poisoning varies for different age groups drugs. Parents are often unaware that drugs must be
in children. Although poisoning in childhood is usu- stored safely and they underestimate the capabilities
ally unintentional, the possibility of deliberate poison- of young children who, at this age, become increas-
ing in the younger child as part of child abuse should ingly mobile and curious. They eat substances that are
not be forgotten. Pharmaceutical substances are not palatable to adults, and tablets and capsules that
involved in 70% of poisonings. In hospitals, errors in resemble lollies (sweets).
drug administration are frequent causes of poisoning. The incidence and severity of accidental poisoning
from drugs has been reduced markedly by the use of
blister packs and containers with child-resistant lids.
Newborns Poisoning in the home often occurs between 10 am and
Poisoning is almost always iatrogenic in this age group. noon or between 6 pm and 8 pm when the child is active
For example, newborns are at risk at delivery, when or hungry and when supervision has lapsed because the
they may be given ergometrine instead of vitamin K, parent is involved in other household activities.
causing severe hypertension, convulsions and coagu-
lopathy. In intensive care units, the frequent use of
Age 6–12 years
potent cardiovascular drugs, gentamicin, barbiturates,
phenytoin, theophylline, digoxin, furosemide and opi- Poisoning is relatively uncommon in this age group
ates predispose the infant to poisoning. but it may be truly accidental, such as drinking a
It is not acceptable to perform noxious procedures poison from a bottle that has been labelled wrongly,
without analgesia and sedation, and it is commendable or when toxic agents have been stored inappropri-
that opiates are used in the newborn, but great care ately. A common example is storage of potentially
208
should be taken to ensure that overdose does not cause toxic liquids in soft-drink containers in garden sheds.
 Poisoning and envenomation 5.3
Although uncommon, deliberate self-poisoning in Often the diagnosis of poisoning is self-evident, but at
this age group may occur as drug abuse or manipu- times the diagnosis is not obvious. When a poison has
lative behaviour, or, less commonly still, genuine sui- been identified, it should never be assumed that other
cidal intent. poisons could not be involved. The symptoms and
signs of poisoning are diverse but dangerous drugs
threaten vital functions. Seriously poisoned patients
Age 13–17 years
present commonly with:
Emotionally disturbed adolescents and young adults • unconsciousness
may poison themselves deliberately, usually by inges- • cardiorespiratory failure
tion, to manipulate their environment, or they may • convulsions.
harbour a genuine suicidal intent. They may seek the If any of these are present and the cause is otherwise not
thrill of drug abuse by inhalation or injection, some- known, poisoning should be high on the list of differential
times as group behaviour. The peak incidence of diagnoses. A meticulous physical examination and his-
teenage poisoning is at 14–16 years of age. Repeated tory provides invaluable help in diagnosis and treatment.
episodes occur more frequently among girls but boys’ Laboratory investigations may be necessary to establish a
suicide attempts tend to be more successful. diagnosis, determine the amount of poison in the body,
and help determine specific treatment for certain poisons.
Management
Prevent absorption
The immediate aim in the management of poisoning,
whether serious or not, is to attend to the effects of Some poisons contaminate the skin, conjunctivae and
the poison on the patient. Later, attention should be mucous membranes, and other poisons are inhaled as
given to the circumstances with the aim of preventing gases. Surface contamination requires copious irrigation
a recurrence. There are innumerable poisons. All medi- with water, whereas inhalational poisoning may require
cines and many household substances are poisonous oxygen therapy and mechanical ventilation. The great
if taken in sufficient quantity. Upon presentation, the majority of poisons are ingested, for which the options
action to be taken, if any, will be determined by the for therapy include induced emesis (rarely), oral or gastric
substance involved, its amount, the interval between administration of activated charcoal, gastric lavage and
ingestion and presentation, and the effect of the poi- whole bowel irrigation. If the poison has been absorbed
son. The following principles of management may be already and has reached the vascular compartment, inva-
applied universally. sive techniques such as the following may be required:
In adolescents with intentional ingestions all medi- • plasmafiltration
cations should be removed from their person on arrival • haemofiltration
at hospital to prevent further ingestion. • charcoal haemoperfusion
• haemodialysis
Support vital functions • peritoneal dialysis
• exchange transfusion.
It is imperative to maintain and support vital functions The poison, its amount and the seriousness of its
if these are depressed. Many poisons are excreted ade- effects determine the treatment of the poisoned
quately or metabolized by the body if the vital functions patient. These must be weighed against the hazards of
are maintained. If the patient is unconscious, the air- removal. Unconscious or drowsy patients, or patients
way, the depth and frequency of breathing, and the cir- who cannot protect their own airway, should not
culation should be examined for adequacy. Chapter 5.2 undergo induced emesis or gastric lavage or be given
provides a full discussion on the management of defi- activated charcoal or colonic washout solutions. The
ciencies of the airway, breathing and circulation. consequences of aspirating gastric contents during
Loss of consciousness due to poisoning may be vomiting or regurgitation in a less than fully conscious
associated with cardiorespiratory failure and require state far outweigh the dangers of many untreated poi-
endotracheal intubation and mechanical ventilation, sons, as the mortality rate from severe pneumonitis
preferably given by experienced personnel. is approximately 50%. However, it is appropriate to
remove a wide variety of ingested poisons with either:
• activated charcoal
Establish the diagnosis
• whole bowel irrigation
It is important to establish: • gastric lavage, or
• what poisons are involved • a combination of these techniques.
• in what quantity Circumstances of presentation and ingestion dictate
209
• when exposure occurred. the choice of technique.
 5.3 PAEDIATRIC EMERGENCIES

Induced emesis, using ipecacuanha, was a commonly To be effective, activated charcoal should be admin-
applied form of therapy but has now been largely istered within 1 hour of ingestion by mouth or by a
abandoned because of limited effectiveness, the devel- nasogastric tube in a fully conscious patient, or by gas-
opment of more effective techniques (e.g. activated tric tube in a less than fully conscious patient after the
charcoal) and risk of aspiration of gastric contents. airway has been secured with an endotracheal tube.
Activated charcoal is probably the most appropriate Children may be more likely to drink it if it is cooled
therapy in the emergency department, although whole and offered in an opaque paper cup with a lid and a
bowel irrigation may be preferable for some agents. black straw. The dose of activated charcoal is 10 times
Gastric lavage should be reserved for a recent (within the ingested poison by weight or 1–2 g/kg of the child's
1 hour) serious life-threatening ingestion in a con- body weight. Continued or repeated doses of activated
scious patient or for serious poisoning in a less than charcoal, at doses of 0.25 g/kg 4–6-hourly, are useful if
fully conscious patient who has airway protection. It the poison is in a sustained-release preparation or if the
is preferable that all patients undergoing gastric lavage charcoal is known to increase the total body clearance
have the airway protected with endotracheal intuba- of the poison by interruption of its enterohepatic circu-
tion. The circumstances for the employment of each lation or by leaching it from the circulation of the gas-
technique are summarized in Figure 5.3.1. trointestinal mucosa. An alternative dosage regimen is
0.25 g/kg hourly for 12–24 hours. Activated charcoal
Activated charcoal
should not be administered if gastrointestinal ileus is
Activated charcoal is itself not absorbable but it
present, as this may cause regurgitation. Aspiration of
adsorbs many different poisons in the gastrointesti-
activated charcoal may have a fatal outcome.
nal tract and thus prevents absorption of poison into
Activated charcoal is often administered, probably
the circulation. However, activated charcoal does not
unnecessarily, with a laxative, notably magnesium sul-
adsorb some poisons, including some elemental met-
phate, to prevent constipation. If magnesium sulphate
als, some pesticides, ferrous sulphate, ethanol, cor-
is used, care should be taken to avoid hypermagnesae-
rosives and petrochemicals. There are many different
mia, a potential risk with repeated doses. Activated
preparations of activated charcoal, some with sorbitol
charcoal does not adsorb ipecacuanha and thus there
as a laxative, but with these excessive diarrhoea and
is nothing to be gained by administering it to the
hypernatraemic dehydration may result.
patient whose induced emesis is excessive.

Gastric lavage
Poisoned child Gastric lavage was a commonly applied form of ther-
apy but has now been largely abandoned. It is an inva-
sive procedure and is justified only for significant recent
Conscious Less than fully conscious poisoning when other techniques are contraindicated
or are unreliable. It may also be indicated when the poi-
son delays gastric emptying or forms concretions in the
stomach. To be effective, however, it must be performed
Serious Not Not Unconscious well and care must be taken to prevent complications.
or serious serious or It is preferable to protect the airway with endotracheal
potentially otherwise
serious serious
intubation in all patients. Endotracheal intubation
or should be performed only by a person experienced in
potentially rapid sequence intubation and resuscitation.
serious Gastric lavage should not be performed after the
ingestion of a corrosive substance because additional
damage to the oesophagus (perforation, mediastinitis)
Nasogastric Induced Intensive Tracheal and stomach (perforation) may occur. It is also unwise to
charcoal emesis nursing intubation perform gastric lavage after ingestion of p­ etrochemicals
or or and +/-
oral observation anaesthesia
or hydrocarbons as these substances have a very low
gastric
lavage charcoal + surface tension and cause severe pneumonitis, even after
+ charcoal or gastric minor contamination of the oropharynx, which may
after observation lavage occur after the passage of the lavage tube renders the
anaesthesia +/-
and bowel gastro-oesophageal sphincter incompetent. The risk of
tracheal irrigation causing or exacerbating chemical pneumonitis exceeds
intubation + charcoal the benefit of poison removal, despite the depression of
210 central nervous system function that may follow. Such
Fig. 5.3.1 Management of poisoning. patients recover if vital functions are preserved.
 Poisoning and envenomation 5.3
Gastric lavage is a potentially traumatic proce- ileus is present. Concomitant administration of acti-
dure, particularly to the oropharynx, even when indi- vated charcoal is counterproductive.
cated. Occasionally the oesophagus and stomach have
Removal from the circulation
been perforated. It is psychologically as well as physi-
If the poison reaches the circulation, an invasive extra-
cally traumatic. For physical safety, the child must be
corporeal technique may be necessary to achieve
restrained: this is best achieved by wrapping the child
removal. Usual techniques include forced diuresis,
in a sheet with the arms pinned by the side. The child
haemodialysis, plasmapheresis and charcoal haemo-
must be held in a lateral head-down position. For gas-
perfusion. These techniques are usually reserved for
tric lavage to be performed well, safely and atraumat-
recognized circumstances when there is deterioration
ically, it should be preceded by induction of general
of vital functions despite maximal therapy (mechanical
anaesthesia with endotracheal intubation.
ventilation, inotropic/vasopressor therapy and artificial
renal therapy) or the lack or failure of an adequate excre-
Whole bowel irrigation
tory or metabolic pathway (renal, hepatic) to eliminate
This is an effective technique to limit absorption of a
the poison. For these techniques to be effective, how-
poison. It is the preferred technique when the poison
ever, the poison must have a relatively small volume of
has passed beyond the pylorus and therefore cannot be
distribution. Peritoneal dialysis is not an efficient tech-
removed by gastric lavage and when the substance is a
nique to remove poisons from the blood. Occasionally,
drug or substance not adsorbed by activated charcoal.
the small size of a patient and the properties of a poison
Slow-release drug preparations may also be removed
permit its removal by exchange blood transfusion.
with this technique.
The agent used is a mixture of polyethylene glycol and
Administer an antidote
electrolytes that flushes out the contents of the bowel
without disturbing the serum volume, osmolality or Only relatively few poisons have antidotes, but knowl-
electrolytes. It is administered via nasogastric tube at a edge and use of these can be life-saving. The appro-
rate of 30 mL per kg per h for 4–8 hours until the rectal priate dose of each is determined by the amount of
effluent is clear. It should not be ­administered to a less poison and its effects. A list of common important
than fully conscious patient or when ­gastrointestinal antidotes is given in Table 5.3.1.

Table 5.3.1 Antidotes to some serious poisons

Poison Antidotes Comments

Amphetamines Esmolol i.v. 500 μg/kg over 1 min, then Treatment for tachyarrhythmia
25–200 μg/kg/min
Labetalol i.v. 0.15–0.3 mg/kg or phentolamine i.v. Treatment for hypertension
0.05–0.1 mg/kg every 10 min
Diazepam 0.2 mg/kg i.v. Controls agitation, aggression

Benzodiazepines Flumazenil i.v. 3–10 μg/kg, repeat 1 min, then Specific receptor antagonist
3–10 μg/kg/h

Beta-blockers Glucagon i.v. 140 μg/kg, then 0.2–1 μg/kg/min Stimulates non-catecholamine cAMP,
preferred antidote
Isoprenaline i.v. 0.05–3 mg/kg/min
Noradrenaline (norepinephrine) i.v. 0.05–1 μg/kg/min Beware hypotension

Calcium channel blocker Calcium chloride i.v. 10%, 0.2 mL/kg

Carbon monoxide Oxygen 100% Decreases carboxyhaemoglobin.

May need hyperbaric oxygen

Cyanide Dicobalt edetate i.v. 7.5 μg/kg (max 300 mg) over Give 50 mL 50% glucose after each dose
1 min, then 300 mg at 5 min
Sodium nitrite 3% i.v. 0.33 mL/kg over 4 min, then Nitrites form methaemoglobin–cyanide
sodium thiosulphate 25% i.v. 1.65 mL/kg (max 50 mL) complex. Beware excess methaemoglobin
at 3–5 min > 20%
Thiosulphate forms non-toxic thiocyanate
from methaemoglobin–cyanide
211
Continued
 5.3 PAEDIATRIC EMERGENCIES

Table 5.3.1 Antidotes to some serious poisons—cont'd

Poison Antidotes Comments

Digoxin Magnesium sulphate i.v. 25–50 mg/kg

(0.1–0.2 mmol/kg)
Digoxin Fab i.v: acute − 10 vials per 25 tablets
(0.25 mg each), 10 vials per 5 mg elixir; steady
state − vials = serum digoxin (ng/mL) × BW
(kg)/100

Ergotamine Sodium nitroprusside infusion 0.5–5.0 μg/kg/min Treats vasoconstriction. Monitor BP

continuously
Heparin i.v. 100 units/kg then 10 30 units/kg/h Monitor partial thromboplastin time

Heparin Protamine 1 mg/100 units heparin

Iron Desferrioxamine 15 mg/kg/h over 12–24 h if serum Give slowly; beware anaphylaxis
iron > 90 or > 63 μmol/L and symptomatic

Lead Dimercaprol (BAL) i.m. 75 mg/m 2 4-hourly for

6 doses then i.v. CaNa 2 edetate (EDTA)
1500 mg/m 2 over 5 days if blood level
> 3.38 μmol/L. If asymptomatic and blood
level 2.65–3.3 μmol/L, infuse CaNa 2 EDTA
1000 mg/m 2/day over 5 days or oral succimer
350 mg/m 2 8-hourly over 5 days, then 12-hourly
over 14 days

Methaemoglobinaemia Methylene blue i.v. 1–2 mg/kg over several

minutes

Methanol, ethylene Ethanol i.v. loading dose 10 mL/kg 10% diluted in

glycol, glycol ethers glucose 5%, then 0.15 mL/kg/h to maintain blood
level 0.1% (100 mg/dL)

Opiates Naloxone i.v. 0.01–0.1 mg/kg, then 0.01 mg/kg/h as

needed

Organophosphates and Atropine i.v. 20–50 μg/kg every 15 min until Blocks muscarinic effects
carbamates secretions dry
Pralidoxime i.v. 25 mg/kg over 15–30 min then Reactivates cholinesterase
10–20 mg/kg/h for 18 h or more. Not for carbamates

Paracetamol N-acetylcysteine i.v. 150 mg/kg over 60 min then Restores glutathione, inhibits metabolites.
10 mg/kg/h for 20–72 h or oral 140 mg/kg, then Give within 18 h according to serum
17 doses of 70 mg/kg 4-hourly (total 1330 mg/kg paracetamol level
over 68 h)

Phenothiazine dystonia Benztropine i.v or i.m. 0.01–0.03 mg/kg Blocks dopamine reuptake

Potassium Glucose i.v. 0.5 g/kg plus insulin i.v. 0.05 units/kg Decreases serum potassium rapidly.
Monitor serum glucose levels
Salbutamol aerosol 0.25 mg/kg Decreases serum potassium rapidly
Sodium bicarbonate i.v. 1 mmol/kg Decreases serum potassium slightly; beware
hypocalcaemia
Calcium chloride 10% i.v. 0.2 mL/kg Antagonizes cardiac effects
Resonium oral or rectal 0.5–1 g/kg Adsorbs potassium slowly

Tricyclic antidepressants Sodium bicarbonate i.v. 1 mmol/kg to maintain blood Reduces cardiotoxicity
pH > 7.45

212 BW, body weight; cAMP, cyclic adenosine monophosphate; EDTA, ethylenediamine tetra-acetic acid.
 Poisoning and envenomation 5.3
Recognition of poisons
Box 5.3.1 Common lethal/serious poisons and substances
There are literally thousands of poisons and no one
person can be expected to be familiar with them all. • Antihistamines
• Aspirin
However, it is vital to recognize that any substance that
• Barbiturates
has effects, or side-effects, on the central nervous sys- • Carbamazepine
tem, cardiovascular system and respiratory system is • Carbon monoxide
a potential serious poison. It is prudent to be famil- • Caustic soda
iar with serious poisons that are ingested commonly • Chloral hydrate
(Box 5.3.1) and those that have delayed actions, such • Clonidine
as colchicine, paracetamol and paraquat. The con- • Digoxin
• Disc batteries
tent of unfamiliar proprietary preparations should be
• Dishwashing powder
sought, as effects may not be obvious from common • Hydrochloric acid (spirit of salts)
usage. For example, the antidiarrhoeal drug Lomotil • Iron
contains atropine and the opiate diphenoxylate, which • Major tranquillizers
may cause respiratory depression. Swallowed disc or • Opiates
‘button batteries’ that impact in the oesophagus may • Paracetamol
cause ulceration into surrounding structures (trachea, • Theophylline
• Tricyclic antidepressants
aorta), whether by release of corrosive chemicals or by
• Verapamil
electrochemical activity, and must be removed urgently • Volatile substances
by endoscopy. In rural areas/developing countries: paraquat, chloroquine,
It is important to have access to a Poisons organophosphate insecticides
Information Centre by telephone, fax or e-mail. These
centres maintain a vast store of up-to-date informa-
tion and are usually accessible on a 24-hour basis. Out-of-date drugs should be discarded safely. House­
While Poison Information Centres provide an invalu- hold cleaning substances, fuels, and garden and work-
able service, the management of the poisoned patient shop chemicals should be stored in truly inaccessible
is the responsibility of the treating physician. places. This applies particularly to automatic dish-
washer powders and detergents, and to sink and oven
cleaners, all of which are highly caustic and corro-
sive to the gastrointestinal tract. Corrosive poisoning
Clinical example occurs most often when small children have access to
dishwashing powder or its residue in the receptacle of
Simon, a 15-month-old toddler, was noted by an open automatic dishwasher door.
his mother to be irritable, drooling saliva and to
Older children should be taught at home and at
have inflamed lips after tasting the residue of
the powder in their automatic dishwasher door. school of the dangers of drug abuse, including those
On examination, oropharyngeal ulceration was observed. of ‘street’ and pharmaceutical drugs, and that sniff-
An intravenous cannula was inserted for fluid and nutrition ing glue or hydrocarbons may cause a fatal dysrhyth-
therapy, and endoscopy of the upper gastrointestinal tract mia. In the case of self-poisoning by adolescents, the
was performed. Significant burns to the mid-oesophagus ­provocation is often the result of complex social and
were discovered; these healed with stricture formation,
necessitating repeated dilatation with bougies.

Clinical example

Amanda, a 3-year-old girl, was brought to

Prevention the emergency department by her parents.
Two hours previously she had been perfectly
Too many poisonings are so called ‘accidents’, par-
well when they were visiting friends, but
ticularly among young children. Every opportunity since that time had become progressively drowsy and
should be taken to educate parents about the dangers was unconscious on presentation. On examination, her
of drugs and toxic substances in the home. A warning respiration was shallow and her blood pressure was low.
should be issued whenever a drug is prescribed and No signs of external trauma or infection were obvious.
counselling given whenever poisoning occurs. It is Mechanical ventilation, intravascular volume support and
erroneous to believe that young children cannot open vasopressor therapy were necessary. In spite of the parents’
denial of drug ingestion, a high level of amylobarbital was
drawers, cupboards and handbags or gain access to
discovered in her urine, and the next day it was revealed that
benchtops. an opened bottle of tablets had been found in their friends’
All drugs, however common and easily available, house. Amanda recovered completely. 213
should be stored in a locked, childproof c­abinet.
 5.3 PAEDIATRIC EMERGENCIES

Clinical example Practical points

Mario, a 13-year-old boy in previous good
health but known to have experimented with • Childhood poison exposure is very common.
drugs, collapsed while in the garage of a • Most exposures carry minimal morbidity but some are
serious and can be fatal.
friend's house. The parents of the friend found
him unconscious and summoned an ambulance, whose • You should know the general principles of management
for poisoning.
officers diagnosed ventricular fibrillation. They attempted
to resuscitate him with mechanical ventilation and DC • Poison Information Centres can provide detailed
management advice.
shock but were unsuccessful. External cardiac compression
was continued, and on arrival at the hospital's emergency
department he was still in refractory ventricular fibrillation.
Numerous additional attempts at defibrillation using 4 J/kg
DC shock administered with amiodarone and adrenaline clearly written and, if abbreviations are employed,
(epinephrine) over 45 minutes failed to achieve sinus rhythm. such as ‘μg’ or ‘mcg’ for microgram, they must be
Eventually asystole occurred. Post-mortem blood samples recognized by all staff. If in doubt, longhand print-
revealed high levels of N-butane and isobutane, constituents
ing should be used. Care should be taken with a deci-
of cigarette lighter fluid, which presumably had been inhaled.
mal point. Equally, interpretation of a prescription
must be with care, and the ­preparation checked before
administration. All too often in h
­ ospitals, wrong drugs
psychological disharmony, making remedial action or wrong doses are given to the wrong patients.
lengthy and difficult (see Chapter 3.11).
All age groups are subject to iatrogenic poisoning
at home and in hospital. Most iatrogenic errors result
from mistakes in prescription (i.e. the dose of a drug
and its interval). It is particularly important for doctors
Envenomation
to refer always to a recognized prescription manual for Australia harbours a wide variety of terrestrial and
children rather than relying upon memory or extrapo- marine creatures. Of these, those that cause the most
lation from adult dosages, especially when dealing with frequent or serious envenomation are species of
infrequently used potent drugs. Prescriptions must be snakes, spiders and jellyfish (Table 5.3.2).

Table 5.3.2 Effects of Australian venomous animals and their treatments

Animal Main effects Main treatments

Snakes (many terrestrial and Paralysis (rapid) Pressure–immobilization bandage

marine species) Haemorrhage Antivenom with premedication
Endotracheal intubation and mechanical ventilation
Clotting factors if haemorrhaging

Funnel-web spiders Paralysis (rapid) Pressure–immobilization bandage

Antivenom
Endotracheal intubation and mechanical ventilation

Redback spider Pain Antivenom

Paralysis (slow)

Australian paralysis tick Paralysis (slow) Remove tick

Endotracheal intubation and mechanical ventilation

Bees, wasps, ants Anaphylaxis Adrenaline (epinephrine)

Australian Box jellyfish Paralysis Douse with vinegar

Hypotension Antivenom
Pain Endotracheal intubation and mechanical ventilation

Blue-ringed octopuses Paralysis (rapid) Pressure–immobilization bandage

214 Endotracheal intubation and mechanical ventilation

Stone fish Pain Antivenom

 Poisoning and envenomation 5.3
Snake bite onset of paralysis of large muscles, including respiratory
muscles, is preceded by paralysis of the bulbar muscles, so
Australia has over 100 species of snake, of which a
that it is imperative to enquire and seek evidence of dys-
dozen are among the world's most deadly. The aver-
function of the external ocular muscles (double vision,
age mortality rate from snake bite in Australia is two
ophthalmoplegia), facial muscles (ptosis), and the mus-
to three deaths per annum, approximately equal to the
cles of speech and swallowing (dysphonia, dysphagia).
mortality rate from bee-sting anaphylaxis. The species
The clinical diagnosis of envenomation may be con-
that have caused mortality and significant morbidity
firmed with the snake venom detection kit test (CSL
belong to the genera of:
Diagnostics, Australia). This is a rapid enzyme immu-
• Tiger snakes (Notechis) noassay designed for clinical use. It gives a result in
• Brown snakes (Pseudonaja) approximately 25 minutes and is capable of detect-
• Death adders (Acanthophis) ing venom in a concentration of as little as 10 ng/mL.
• Taipans (Oxyuranus) The test can be applied to a swab of the bite site or to
• Black snakes (Pseudechis) the victim's blood or urine. A positive result does not
• Copperhead snakes (Austrelaps) ­necessarily identify the snake but it stipulates which
• Rough-scaled snake (Tropidechis). antivenom to administer, if clinically indicated.
Tiger snakes and Brown snakes account for most
The principles of treatment for snake bite are:
envenomations. All Australian snakes are elapids,
• to prevent rapid absorption of the venom from
whose venoms do not cause severe local effects.
the subcutaneous tissue into the circulation by
The main components of venoms are:
application of a pressure–immobilization bandage
• presynaptic and postsynaptic neurotoxins, which
• to neutralize the venom by the administration of
cause paralysis
antivenom
• prothrombin activators, which cause disseminated
• to treat the effects of the venom, principally
intravascular coagulation and haemorrhage
respiratory failure and bleeding.
• anticoagulants, which cause haemorrhage The management of suspected and definite envenom-
• rhabdomyolysins, which may cause weakness and ation is summarized in Figure 5.3.2.
renal failure.
Different species have different effects, but the two
Pressure–immobilization first aid
most common acute threats to life are neuromuscular
Limbs sustain 95% of all bites. Snake venoms gain
paralysis causing respiratory failure and coagulopathy
access from the subcutaneous tissue to the circulation
causing bleeding. The combined effect is cardiorespi-
via the lymphatics. These channels can be effectively
ratory failure.
occluded by the application of a firm crepe (or crepe-
like) or elasticized bandage applied over the bite site
Management
and whole of the limb (Fig. 5.3.3). The application of a
Snakes may bite but fail to inject venom on approxi- splint that includes joints on either side of the bite pre-
mately 40–50% of occasions. In young children, par- vents the use of surrounding muscle groups and hence
ticularly, snake bite is suspected even though a snake decreases lymph flow. Although the technique is a first-
was not observed. In only 17–20% of such presenta- aid measure that should be applied at the scene of the
tions has both a bite and envenomation occurred. snake bite to prevent initial absorption of venom, it is
Thus, one of the difficulties in the management of also used in established envenomation in hospital to
snake bite is to determine whether envenomation has prevent additional absorption of venom while prepara-
actually occurred, irrespective of whether or not a bite tions are being made to administer antivenom.
by a snake was observed. The bandage can be left in place indefinitely as it
The syndrome of envenomation is characterized by should be no tighter than a bandage for a sprained
a rapid onset of paralysis accompanied by coagulopa- ankle. However, the bandage does not allow substan-
thy over many minutes to several hours. However, an tial inactivation of venom in the tissues and should
early diagnosis may be dependent upon subtle clini- be removed once the asymptomatic patient reaches a
cal signs and symptoms, abnormal laboratory tests hospital that has a stock of antivenom, or after the
of coagulation and a positive test for venom in the envenomated patient has been given antivenom. It
patient's urine or blood. The early reliable symptoms is dangerous to remove a bandage from an enveno-
of envenomation are: mated patient before administration of antivenom
• headache because its release allows a substantial additional
• abdominal pain quantity of venom to gain rapid access to the circula-
• vomiting. tion. The splint and bandage should not be removed
Abnormal laboratory tests of coagulation are also solely to allow inspection of the bite site of an enveno-
215
very sensitive and reliable after bite by a species with mated patient; instead, the splint should be removed
coagulopathic effects. Most species can cause serious temporarily and a window should be cut in the ban-
­coagulopathy with the exception of Death adders. The dage to allow a swab of the bite site to be taken for
 5.3 PAEDIATRIC EMERGENCIES

Real or suspected snake bite

Fang marks: apply pressure –

immobilization (P-I) bandage

Clinical symptoms or signs

of envenomation

Present Absent

Coagulation test

Child critically ill Child not critically ill Abnormal Normal

Venom Observe
Venom test,
Resuscitate test (12 hr)
coagulation test
Do not remove
bandage; apply if
absent
Antivenom Specific antivenom Specific
• Victoria: Brown ± coagulation factors antivenom
snake plus Tiger
snake
• Tasmania: Tiger Coagulation
snake test
• Other states and
territories:
polyvalent
Coagulation factors
if haemorrhaging
Venom test: bite
site, urine and
blood

Dangers and mistakes in management:

• Fang marks may not be visible
Coagulation test
• Premature removal of pressure-immobilization bandage
allows sudden systemic envenomation
• Erroneous snake identification may cause wrong antivenom
to be given. If in doubt give polyvalent antivenom
Titrate specific • Delayed onset of paralysis may be missed
antivenom dose and • Insufficient antivenom
coagulation factors • Antivenom without premedication (adrenaline [epinephrine]
against clinical and 0.005-0.01 mg/kg s.c.)
coagulation status • Antivenom without clinical or laboratory evidence of envenomation

Fig. 5.3.2 Management of snake bite.

216
 Poisoning and envenomation 5.3

Fang marks

A B

C D

Fig. 5.3.3 Technique for applying pressure–immobilization first-aid bandage. A–D, Lower limb; E, upper limb.

venom testing, then the bandage should be reinforced Antivenom

and the splint reapplied. Bites are usually visible as Specific monovalent antivenoms (Commonwealth
scratches or puncture wounds, but their presence and Serum Laboratories, Melbourne) are manufactured
appearance, or absence, does not prove or disprove against Tiger, Brown, Taipan, Black, Death adder and
­envenomation and does not allow identification of the Beaked sea snake (Enhydrina schistosa) venoms. These
217
snake involved. are effective against all known snakes in Australia and
 5.3 PAEDIATRIC EMERGENCIES

Papua New Guinea. A mixture of the five terrestrial in their absence a substantial coagulopathy is present.
antivenoms is available as a polyvalent preparation. Occasionally, venom can be detected in the urine but
The antivenoms are highly purified equine immuno- there is no clinical evidence of envenomation or only
globulins. Cross-reactivity between species is limited, a very mild coagulopathy. In this case antivenom may
so it is essential to administer the correct antivenom be withheld, but the patient's clinical and coagulation
according to the identity of the snake. status should be checked regularly.
If the identity of the snake is not known or uncer-
tain, the type of antivenom to be administered is Life support
based on the known geographical snake distribu- Bulbar and respiratory muscle paralysis in the severely
tion or according to the result of a venom detection envenomated patient requires endotracheal intubation
kit test (Commonwealth Serum Laboratories). In and mechanical ventilation. If antivenom therapy is
Tasmania, Australia, where dangerous snakes are a delayed, mechanical ventilation may be required for
Tiger snake and a Copperhead species, the appropri- many days.
ate antivenom is Tiger snake antivenom. In Victoria, Coagulopathy may cause massive haemorrhage
Australia, where the dangerous species are Tiger, from mucosal surfaces and subsequent peripheral cir-
Brown, Black and Copperhead snakes, the appro- culatory failure. Haemorrhage may occur into a vital
priate antivenom therapy is Tiger snake plus Brown organ, particularly the brain. It is essential to restore
snake antivenom. Everywhere else in Australia addi- the circulatory volume with blood transfusion and to
tional species exist and the polyvalent preparation normalize coagulation with antivenom and coagula-
should be chosen. tion factors (fresh frozen plasma). Antivenom neutral-
Although essential and life-saving, antivenoms izes venom but it does not, per se, restore coagulation.
are foreign (equine) proteins that may cause a life- Hepatic regeneration of clotting factors requires at
threatening anaphylactoid reaction. However, this least 6 hours after neutralization of venom with anti-
may be prevented by premedication with subcutane- venom. Repeated laboratory tests of coagulation (pro-
ous (not intravenous or intramuscular) adrenaline thrombin time, activated partial thromboplastin time,
(epinephrine) 0.005–0.01 mg/kg. Additional protec- serum fibrinogen and fibrin degradation products) or
tive agents such as a steroid (hydrocortisone) and a bedside test of whole-blood clotting time should be
an antihistamine may be indicated if the patient performed repeatedly to determine the need for more
has a known allergic history. Only one premedica- antivenom and coagulation factors. The coagulation
tion dose of adrenaline is required. The antivenom status is the most sensitive guide to the need for addi-
should be administered intravenously, diluted with tional antivenom after bite by coagulopathic species.
a crystalloid solution, over approximately 30 min-
utes. However, for severe envenomation it may be
delivered rapidly. If polyvalent antivenom or mul- Clinical example
tiple doses of monovalent antivenom are required,
a course of steroid therapy (prednisolone 1–2 mg/kg Martina, a 21/2-year-old child, collapsed with
daily for 5 days) should be given to prevent serum weakness, shallow respiration and weak
sickness. pulses soon after playing in long grass where
Tiger snakes had been observed. Mechanical
The dose of antivenom is never certain at the begin-
ventilation was necessary. A test of coagulation revealed
ning of treatment because the amount of venom prolonged prothrombin and activated partial thromboplastin
injected is unknown. Each vial of antivenom contains times, a depleted serum fibrinogen level, a low platelet count
enough to neutralize the average yield from ‘milk- and a high level of fibrin degradation products. Haematuria
ing’ – a process whereby venom is collected by induc- and melaena were observed. Venom was detected in the
ing a snake to bite a membrane stretched tautly over child's urine and blood, and from scratch and puncture
a receptacle. However, the venom injected on biting marks on the child's foot. Eight vials of Tiger snake antivenom
and transfusions of platelets, packed cells and fresh frozen
is highly variable and bites may be multiple. Children plasma were required before her coagulation status returned
are more susceptible than adults because of the larger to normal. Adequate spontaneous respiration was resumed
venom : body mass ratio. The majority of envenom- after 48 hours.
ations are treated adequately with one to three vials,
but this dose should never be relied upon; many
more vials are usually required in life-threatening
Spider bite
envenomations.
Antivenom should not be withheld if indicated, as Several thousand species of spiders exist in Australia.
there is no other satisfactory treatment. Antivenom However, only Funnel-web spiders and the Redback
should be administered either if there are clinical signs spider are known to be potentially lethal or to cause
218
or symptoms of envenomation after snake bite or if significant illness. However, all spiders have venom
 Poisoning and envenomation 5.3
and a few species may cause severe local injury. The pinprick-like bite. The site becomes inflamed and may
White-tailed spider is often suspected of causing local be surrounded by local swelling. During the following
tissue damage, but the number of cases where it has minutes to several hours, severe pain, exacerbated by
been clearly identified as the responsible spider is very movement, commences locally and may extend up the
small. limb or radiate elsewhere. The pain may be accompa-
nied by:
Funnel-web spider bite
• profuse sweating
• headache
Several species of the genera Atrax and Hadronyche • nausea
cause significant illness and are potentially lethal. • vomiting
The most well-known species, Atrax robustus (Sydney • abdominal pain
funnel-web spider), is a large, aggressive ­spider that has • fever
caused the deaths of more than a dozen people inhab- • hypertension
iting an area within an approximate 160 km radius of • paraesthesias
Sydney, Australia. The male is more dangerous than • rashes.
the female, in contrast to other species, and is inclined In a small percentage of cases, when treatment is
to roam after rainfall. In doing so it may enter houses delayed, progressive muscle paralysis may occur over
and seek shelter among clothes or bedding and give a many hours and will require mechanical ventilation.
painful bite when disturbed. Muscle weakness and spasm may persist for months
Bites do not always result in envenomation, but after the bite. Death has not occurred since the intro-
envenomation may be rapidly fatal. The early fea- duction of an antivenom in the 1950s. If the effects of a
tures of the envenomation syndrome include nausea, bite are minor and confined to the bite site, antivenom
vomiting, profuse sweating, salivation and abdominal may be withheld, but otherwise antivenom should be
pain. Life-threatening features are usually heralded given intramuscularly or intravenously. In contrast to
by the appearance of muscle fasciculation at the bite a bite from a snake or Funnel-web spider, a bite from
site, which quickly involves distant muscle groups. a Redback spider is not immediately life-threatening,
Hypertension, tachyarrhythmias and vasoconstric- but inadequate initial treatment may result in long-
tion occur. The victim may lapse into coma, develop term disability. There is no effective first aid, but appli-
hypoventilation and have difficulty maintaining an cation of a cold pack or ice may relieve the pain.
airway free of saliva. Finally, respiratory failure and
severe hypotension culminate in hypoxaemia of the
Jellyfish stings
brain and heart. The syndrome may develop within
several hours, but it can be more rapid. Several chil- The most venomous animal in the world is the
dren have died within 90 minutes of envenomation, Australian Box jellyfish (Chironex fleckeri) and related
and one died within 15 minutes. The active compo- species. It has caused at least 70 deaths in the waters
nent in the venom is a polypeptide that stimulates the off the north Australian coast. Other jellyfish species,
release of acetylcholine at neuromuscular junctions notably numerous carybdeid species, may cause a sig-
and catecholamines within the autonomic nervous nificant illness known as the ‘Irukandji syndrome’.
system.
Treatment consists of the application of a pressure–
Box jellyfish
immobilization bandage, intravenous administration
of antivenom and support of vital functions, which This large jellyfish has a cuboid body up to 30 cm
may include artificial airway support and mechanical in diameter, and multiple tentacles that trail several
ventilation. No deaths or serious morbidity have been metres. It is semitransparent and difficult to see by
reported since introduction of the antivenom in the anyone wading or swimming in shallow water, where
early 1980s. stings usually occur. The tentacles are lined with mil-
lions of nematocysts that, on contact, discharge
tubules (barbs) coated with venom. The tubules pierce
Redback spider bite
subcutaneous tissue, including small blood vessels
This spider is distributed all over Australia and is to be allowing intravascular envenomation. Contact with
found outdoors in household gardens in suburban and the tentacles causes severe pain and, if envenomation
rural areas. Redback spider bite is the most common is severe by contact with metre lengths of tentacles, it
cause for antivenom administration in Australia. The may cause death within several minutes. Death is prob-
adult female is easily identified. Its body is about 1 cm ably due to both neurotoxic effects causing apnoea and
in size and it has a distinct red or orange dorsal stripe direct cardiotoxicity. The protein venoms probably act
219
over its abdomen. When disturbed, it gives a painful by forming pores in cellular membranes. Although
 5.3 PAEDIATRIC EMERGENCIES

many stings are minor, the skin that sustains the injury Irukandji syndrome
may heal with disfiguring scars.
This is caused by the stings of some jellyfish belonging
First aid, which must be administered on the beach,
to the order Carybdeidae, including Carukia barnesi
consists of dousing the skin with acetic acid (vinegar),
(Barnes’ jellyfish). These are jellyfish with only four
to inactivate undischarged nematocysts. Adherent ten-
tentacles; they are small, transparent and very difficult
tacles can then be removed safely. Cardiopulmonary
to see in the water. A sting is usually very minor, but
resuscitation may be required on the beach. An ovine
after some 30 minutes the victim experiences severe
antivenom is available but prevention is of paramount
muscle pains, especially of the lower back, muscle
importance. Water must not be entered when this jel-
cramps, vomiting, sweating, agitation, vasoconstric-
lyfish is known to be close inshore. Wetsuits, clothing
tion, prostration and hypertension. The syndrome is
and ‘stinger suits’ offer protection.
in part due to release of catecholamines. Heart failure
and hypertensive stroke may occur. Treatment is par-
enteral analgesia, control of hypertension and cardio-
Clinical example respiratory support in severe cases.
A 12-year-old boy sustained a massive jellyfish
sting to his legs while wading in water close
to the shore. Immediately he experienced
excruciating pain but managed to reach
the shore, where he became apnoeic. His father gave
Practical points
mouth-to-mouth breathing. Vinegar was poured over the
wounds, typical Box jellyfish tentacles were removed and • Envenomation is a serious and potentially fatal problem.
an ambulance was summoned. Shortly before arrival at • Do not remove the pressure–immobilization bandage
hospital the boy became pulseless. Bag–mask ventilation from a child bitten by a snake until the child is in a facility
with oxygen, external cardiac compression and intravenous with resuscitation equipment, skilled staff and a supply of
adrenaline (epinephrine) were given. Spontaneous antivenom.
circulation was restored and he recommenced spontaneous • Many cases of suspected or confirmed snake-bite will not
respiration. In hospital, Box jellyfish antivenom was infused. require antivenom.
Thereafter the boy made a slow recovery, but pulmonary • Only give antivenom to symptomatic patients or those with
oedema necessitated oxygen therapy and diuretic and significant coagulopathy.
inotropic infusion for several days. The boy recovered fully, • Very large doses of antivenom may be needed for
but the stings healed with disfiguring scars. massively envenomated children.

220
 6
PART

FLUID REPLACEMENT

221
 6.1 Fluid replacement therapy
Trevor Duke, Sarah McNab

Safe management of the fluid and electrolyte needs of absolute fluid stores, making them more vulnerable to
unwell children requires knowledge of body water and dehydration.
electrolyte composition, fluid requirements ­during health ECF has relatively high sodium and chloride con-
and illness, an ability to recognize signs of ­dehydration tent. ICF has high potassium, phosphate, magnesium
and overhydration, an understanding of composition of and protein concentrations (Fig. 6.1.1). Small intes-
fluid replacement, and monitoring. tinal secretions are high in sodium, diarrhoea fluid
is high in potassium, gastric fluid is high in chloride
and pancreatic secretions are high in bicarbonate
(Table 6.1.2).
Body fluid composition Cell membranes are relatively permeable to water,
Body fluids are separated into two main compart- potassium and chloride, and relatively impermeable
ments, intracellular (ICF) and extracellular (ECF) to sodium, phosphate and protein. Sodium is actively
fluid. ECF is further separated into intravascular transported out of cells by energy-dependent sodium
and interstitial fluid. The proportion of body weight pumps. There is equilibrium in tonicity, hydrostatic
that is water falls from about 78% in a term new- and colloid osmotic pressure between plasma and
born to 60% in adults (Table 6.1.1). Intracellular interstitial fluid. Water leaves the arterial end of the
water accounts for about 40% of body weight. capillary under hydrostatic pressure and is drawn into
Intravascular fluid (plasma) accounts for only about the venous end of capillary beds by plasma oncotic
5% of body weight. Interstitial fluid is proportion- pressure.
ately higher than ­intravascular fluid in infants, with
an interstitial to plasma volume ratio of 5 : 1, com-
Regulation of extracellular fluids
pared with 3 : 1 in adults. Large changes in body
weight over 24 hours or less usually reflect changes The plasma osmolality, being the concentration of sol-
in total body water (TBW), because it takes a much ute particles, remains almost constant between 285 and
longer period for substantial weight change due to 300 mOsmol per kg H2O. The osmolality of plasma is
growth or ­subcutaneous tissue wasting. In the first controlled through a finely regulated feedback system
few days of life, there is a shift of water from ECF in the hypothalamus, the posterior pituitary and the
to ICF, accompanied by a 7% loss of TBW, so this is collecting duct of the nephron, which contain osmore-
a very vulnerable period for ­dehydration with illness. ceptors and volume receptors.
Body fat contains only 20% water, so obesity implies In health, the intake of water is regulated by thirst.
a relative reduction in p ­ ercentage of body weight as This is controlled by a centre in the mid-hypothala-
water. Conversely, malnourished children may have mus, which responds to changes in circulating blood
up to 80% of body weight as water. The clinical volume, via stretch and baroreceptors in the cardio-
­consequences are that: vascular system, or small changes (as little as 1–2%) in
• the severity of dehydration may be underestimated plasma osmolality.
in obese children In the kidney, nephrons regulate water and electro-
• nutritional wasting is easily confused with lyte excretion. The nephron comprises the proximal
dehydration as the clinical signs are similar tubule, the hypertonic medulla and ascending loop of
• fluid loads are poorly tolerated in severe Henle, the distal tubule and the collecting duct. The
malnutrition. precise regulation of fluids and electrolytes in the ECF
Water balance depends on intake, output and usage occurs by reabsorption of the glomerular filtrate into
for metabolism. Water is normally lost from skin, capillaries, secretion into the tubule lumen and even-
lung, intestine and kidney. Fluid and energy require- tual excretion in the urine.
ments as a proportion of body weight decrease from Each day normal adult kidneys filter 180 litres water,
infancy to adult life, so infants and children have 25 000 mmol sodium, 5000 mmol bicarbonate and
222 higher metabolic requirements than adults and smaller 700 mmol potassium. Under normal circumstances
 Fluid replacement therapy 6.1
Table 6.1.1 Body water distribution

Total body water ICF (% of body ECF (% of body

Age group (% of body weight) weight) weight) ECF : ICF ratio Blood (mL/kg)

Newborn 79 35 44 1.25 100

Infant 60 33 27 0.82 80

Child 62 41 21 0.51 70

Adult 58 39 19 0.49 60

ECF, extracellular fluid; ICF, intracellular fluid.

200 Anion Table 6.1.2 Typical composition of body fluids

SO42– gap
Mg2+ in children (mmol/L)
K+ HPO42–
150 Ca+ SO4– Protein Source Na+ K+ Cl− HCO 3
Mg2+ Anion
gap Blood 140 4 100 25
mmol/L

100
K+ Normal sweat 22 9 18 0
Na+ Cl– HPO42–
50 Bile 150 10 100 20

Gastric 50 15 125 0
HCO3– HCO3–
0 Na+
Pancreatic 140 10 100 45
Cations Anions Cations Anions
Interstitial fluid Intracellular fluid
Small bowel 140 8 60 70
Fig. 6.1.1 Electrolytes in body fluids.
Diarrhoeal stool 40 50 25 65

These are illustrative mid-range values but there is

most of this is reabsorbed. Approximately two-thirds considerable variation in individual values.
of the filtered sodium is reabsorbed in the proximal
convoluted tubule. Another 25% is reabsorbed in the
loop of Henle, which is used to create a concentra- water to reduce plasma osmolality. Conversely, a fall
tion gradient for the countercurrent multiplier sys- in plasma osmolality inhibits ADH secretion, result-
tem, allowing the production of concentrated urine. In ing in excretion of an increased volume of dilute urine.
adults, urine osmolality can vary from a maximal dilu- Circulating blood volume is contained in arter-
tion of 100 mOsmol/kg to a maximal concentration of ies (10%), the venous system (55%), and heart, lungs
1400 mOsmol/kg; newborns and young children have and capillary bed (35%). The volume and distribution
a more limited ability to concentrate and dilute urine. within the circulation is controlled by rapid feedback
The distal tubule reabsorbs only 5% of the filtered loops. Baroreceptors and stretch receptors in the heart
sodium, but the electrical gradient generated is used and large vessels detect changes in venous tone and
for potassium and hydrogen ion excretion into the dis- stimulate ADH secretion or inhibition and changes in
tal tubule. Renal sodium retention also occurs via the venous tone, cardiac output and arteriolar resistance
renin–angiotensin–aldosterone system. via the autonomic nervous system. Volume depletion
Water retention is regulated via antidiuretic hor- is the dominant stimuli to thirst and ADH release, and
mone (ADH) released from the posterior pituitary. so may stimulate water retention and oral intake at the
The primary action of ADH is to increase the per- expense of hypotonicity.
meability of the renal collecting ducts to water. A rise There are also non-osmotic drivers of ADH secre-
in plasma osmolality is corrected by increased ADH tion, which allows ADH to be released despite n­ ormal or
secretion, resulting in a reduced volume of urine, which low plasma osmolality. Many of these stimuli are pres-
is concentrated. This allows the body to conserve free ent in sick children and include intracranial p
­ athology 223
 6.1 FLUID REPLACEMENT

(e.g. meningitis, head injury), respiratory disease • Eating and drinking: frequency, thirst,
(pneumonia), surgery and pain. The potential for non- type of fluid intake (e.g. breast milk, oral
osmotic ADH stimuli must be considered when pre- rehydration solution, cordials, hypercaloric feed
scribing fluid replacement. ADH reduces the body's supplements)
ability to excrete free water and may lead to hypona- • Urine output: frequency, number of wet nappies
traemia if an inappropriately hypotonic fluid is given. • Associated symptoms: fever, cough, shortness of
breath, abdominal pain, seizures, rashes, etc.
• Nutritional status: view the child's growth chart
Practical points including trend in values. Check skin folds on
triceps and buttocks for presence of wasting. Also
• Antidiuretic hormone (ADH) helps maintain intravascular check weight for height, and height for age (low
volume and osmolality. height for age in a malnourished child is stunting,
• In unwell children, ADH secretion may occur despite which suggests chronic undernutrition).
normal or low osmolality. This decreases water excretion,
further decreasing plasma osmolality.
• This must be taken into consideration when considering Examination
the volume and composition of fluid replacement.
• General condition: drowsy, restless or irritable
• Vital signs: temperature, pulse volume and heart
Oedema rate, respiratory rate, blood pressure
• Eyes: sunken, no tears on crying
Oedema is increased interstitial fluid and occurs by
• Mouth and tongue: dry mucous membranes
several mechanisms:
• Skin: skin turgor reduced or central capillary refill
• increased hydrostatic pressure in the capillaries: time increased
venous obstruction, congestive heart failure
• Muscle tone: weak, floppy or unable to hold
• decreased plasma oncotic pressure: head up
hypoproteinaemic states such as nephrotic syndrome,
• Chest: deep acidotic breathing
protein-losing enteropathy, severe liver disease, and
• Abdomen: distended or tender, palpable masses.
severe protein-energy malnutrition or kwashiorkor
The signs of dehydration are listed in Table 6.1.3.
• increased capillary permeability: this can occur Precise estimation of percentage of dehydration
locally from insect bites, or in one organ, such as
is not possible using clinical signs, but an indica-
cerebral oedema from traumatic brain injury, brain
tion of the degree of dehydration, sufficient for
infection or other brain injury, or generally as in
­formulating a plan for fluid management, is possible.
capillary leak syndrome from severe septicaemia.
Combinations of these signs are more specific than
Oedema may also occur if interstitial lymphatic
any individual sign. Clinical signs may be combined
vessels are poorly developed (Turner syndrome) or
­
to classify a child as having mild (3–5%) dehydration
obstructed (e.g. filariasis, lymph node obstruction
(usually accompanied by few, if any, clinical signs),
from tuberculosis).
moderate (6–9%) dehydration, or severe (> 10%)
dehydration.

Assessment of dehydration Weight change

Clinical history and examination
When available, weight change from the immediate
A detailed history and examination is essential for premorbid state is the most accurate way of estimat-
the assessment of any child with suspected dehydra- ing the degree of dehydration. If the child has been
tion, overhydration or electrolyte imbalances. The weighed accurately in the last few days, the percent-
symptoms listed below are relevant to different cases, age weight loss will be approximately equal to the
although they may not always be available or reliably percentage dehydration. Another way of thinking of
elicited on history-taking. this is that the weight loss in grams is approximately
equal to the fluid deficit in millilitres. However, the
weights (premorbid and when sick) should be done
History
using a comparable method: similar scale accuracy,
• Diarrhoea: duration, frequency, basic estimate of unclothed, etc. If the premorbid weight was recorded
volume (small, large, profuse), presence of blood, more than a couple of weeks previously in young
mucus infants, the interpretation is less reliable and must
224 • Vomiting: duration, frequency, volume, presence of take account of the weight gain expected because of
bile or blood, whether projectile growth.
 Fluid replacement therapy 6.1
Table 6.1.3 Signs of dehydration

Degree of dehydration Mild, 3–5% Moderate, 6–9% Severe, ≥ 10%

(approximate deficit)* (30–50 mL/kg) (60–90 mL/kg) (100–150 mL/kg)

Validated signs
General appearance Well, alert Thirsty, restless, irritable Drowsy, floppy, limp ± comatose
Eyes Normal Slightly sunken Very sunken
Mucous membranes Moist tongue Sticky tongue Dry tongue
Tears on crying Present Decreased Absent
Capillary return Normal Sluggish (2–3 s) Slow (> 3 s)
Respiratory rate Normal Increased Fast
Skin pinch Goes back quickly Goes back slowly Goes back very slowly

Other signs
Thirst Drinks normally, but may Thirsty, drinks eagerly Drinks poorly or not able to drink
refuse ORS
Pulse Normal Fast Fast, weak
Hands and feet Normal Normal Cool, blue nail-beds

*In young children.

ORS, oral rehydration solution.

3. What type of fluid should I use?

Practical points 4. How much fluid should I give?
5. How will I monitor the child receiving fluid
Clinical evidence on assessing dehydration replacement?
• A change in weight, where available, is the most accurate The fluid requirements of acutely unwell children are
way to assess the degree of dehydration. dynamic, and frequent monitoring of clinical signs,
• Clinical signs will allow an estimation of dehydration, with weight, urine output and some laboratory tests are
combinations of signs performing better than individual
signs. essential so that appropriate modifications to fluid
• This classification is most reliable: administration can be made.
• no signs of dehydration (usually less than 5% dehydrated)
• some signs of dehydration (typically 6–9% dehydrated)
• many signs of dehydration/signs of severe dehydration Resuscitation for shock
(10% dehydrated or more).
Fluid resuscitation involves the rapid restoration of
• Additional history and laboratory tests (e.g. bicarbonate)
may be helpful in selected cases.
intravascular volume and is needed where shock is
present. The clinical signs of shock are poor peripheral
perfusion, cool pale extremities, tachycardia with low-
volume pulses, low blood pressure, high blood ­lactate
levels or large base deficit. Although hypotension is a
Fluid requirements sign of shock, this is usually a late sign in children; the
Before administering fluid replacement, five questions absence of hypotension should not delay appropriate
need to be addressed: treatment. Children with more than one of these car-
1. Why am I giving fluid? diovascular signs require intravenous fluid resuscita-
Reasons for giving fluid can be broadly grouped tion. If an intravenous cannula cannot be inserted in a
into: child needing fluid resuscitation, use the intraosseous
• resuscitation route to the circulation. A volume of 20 mL/kg of an
• deficit isotonic fluid should be administered as a bolus (i.e.
• maintenance run through as rapidly as possible). As this fluid will
• ongoing losses. replace intravascular volume, its osmolality should
2. How will I give the fluid? be similar to that of plasma. Examples of appropri-
Options include: ate fluids are: 0.9% sodium chloride (also known as
• oral normal saline) or Hartmann's solution (also known as
• nasogastric/percutaneous endoscopic Ringer's lactate solution) (Table 6.1.4). In severe s­ eptic
gastrostomy (PEG) tube shock in adults and in severe malaria in ­ children,
225
• intravenous. there is some evidence that outcomes are ­better when
 6.1 FLUID REPLACEMENT

Table 6.1.4 Types of intravenous fluid available

Na+ Cl− K+ Mg2+ Calcium Lactate Acetate Gluconate Glucose

(mmol/L) (mmol/L) (mmol/L) (mmol/L) (mmol/L) (mmol/L) (mmol/L) (mmol/L) (g/L)

0.18% sodium chloride 30 30 – – – – – – 40

(N/5) with 4% dextrose
(hypotonic)

0.45% (N/2) sodium 77 77 – – – – – – 50

chloride with 5%
dextrose (hypotonic)

Plasmalyte148 solution 140 98 5 1.5 – – 27 23 –

(isotonic)

0.9% sodium chloride 154 154 – – – – – – –

(isotonic)

Hartmann's solution 131 111 5 – 2 29 – – –

(similar in ionic
composition to Ringer's
lactate) (isotonic)

Many pre-manufactured fluids are available in Australia, some examples of which are listed above. When listing a fluid as
hypotonic, isotonic or hypertonic, we are referring to the in vivo tonicity. Given that dextrose metabolizes rapidly to free water,
the in vivo tonicity of fluids containing dextrose differs from the in vitro tonicity or osmolarity. The in vitro osmolarity refers to the
number of osmoles of solute per litre of solution, whereas the in vivo tonicity is the total concentration of solutes available to exert
an osmotic force across the cell membrane. For example, the in vitro osmolarity of 0.18% sodium chloride with 4% dextrose is
286 mOsm/L H20, which is the same osmolarity as plasma. However, 5% dextrose is rapidly metabolized to free water. This results
in an in vivo tonicity of 60 mOsm/L H20, which is markedly hypotonic.

a­ lbumin is used compared with crystalloids. If there (e.g. 7% dehydration in a 12 kg child =

is no improvement, a further 20 mL/kg should be 7 × 12 × 10 = 840 mL deficit).
administered. Any child receiving fluid resuscitation Deficits can be replaced either orally, via a nasogastric
should be monitored closely and reassessed immedi- (or PEG, where there is one present) tube or intrave-
ately after giving the fluid. If signs of hypovolaemia nously, depending on the severity of illness and other
persist despite two 20 mL/kg boluses of fluid, the child factors.
should be monitored in an intensive care unit. Check Oral rehydration salts are the mainstay of treatment
for signs that are suggestive of an underlying cause of dehydration from gastroenteritis for the majority
of shock (e.g. sepsis, cardiogenic, metabolic, diabetic of children. Specific oral rehydration solutions (ORS)
ketoacidosis, intussusception, poisoning). can be suggested (for further information on ORS, see
Fluid and electrolyte problems in specific illnesses –
gastroenteritis, below). Where vomiting is present, oral
Replacing the fluid deficit rehydration is best achieved by offering small volumes
A patient's fluid deficit refers to the degree of ­dehydration of fluid frequently. This may be achieved by offer-
at the time of presentation (see assessment of dehydra- ing fluid via a syringe every 10 min or by using ORS
tion above and Table 6.1.3). If shock is p ­ resent, this ­icy-poles, which are available commercially. In general,
should be corrected first as described above. aim for 10 mL/kg every hour.
If a recent premorbid weight is available, the volume ORS can be given via a nasogastric tube where
of fluid deficit in millilitres is equal to the weight lost adequate oral fluid is not tolerated and the child has
in grams. When a recent weight is unavailable, the per- moderate to severe dehydration, even if the child is
centage of dehydration must be approximated using vomiting. Nasogastric tubes can be unpleasant and
the guidelines for assessment outlined above. The vol- carry a risk of pulmonary aspiration. After insertion,
ume of fluid deficit may then be calculated using the the position of a nasogastric tube needs to be checked.
following formula: This is indicated by the presence of acidic gastric fluid
aspirated from the nasogastric tube. Deficit can be rap-
Calculated fluid deficit ( mL ) = idly replaced with ORS via a nasogastric fluid running
226 %dehydration × weight ( kg ) × 10 at 25 mL per kg per h for up to 4 h or until the ­deficit
 Fluid replacement therapy 6.1
is replaced. Where there is significant vomiting, the • 11–20 kg: (100 mL/kg for the first 10 kg = 1000 mL) +
rate of nasogastric replacement may be reduced and, 50 mL/kg for every kilogram above 10 kg
if the vomiting is due to gastroenteritis, ondansetron, • above 20 kg: (100 mL/kg for the first 10 kg =
an antiemetic, may be considered. A deficit should 1000 mL) + (50 mL/kg for the second 10 kg =
be replaced more slowly (over approximately 6–8 h) 500 mL) + 20 mL/kg for every kilogram above 20 kg.
in young infants or those with significant abdomi- The hourly maintenance requirement can be calcu-
nal pain. lated from the following formula:
Where oral or nasogastric fluid replacement is not • first 10 kg body weight: 4 mL/kg per h
tolerated or is contraindicated (e.g. suspected appen- • 11–20 kg: (4 mL/kg for the first 10 kg = 40 mL) +
dicitis), intravenous fluids are used. A fluid deficit 2 mL/kg for every kilogram above 10 kg
primarily involves loss of extracellular fluid and, as • above 20 kg: (4 mL/kg for the first 10 kg = 40 mL) +
such, should be replaced with an intravenous fluid (2 mL/kg for the second 10 kg = 20 mL) + 1 mL/kg
with a similar osmolality to the extracellular space for every kilogram above 20 kg.
(e.g. Hartmann's solution or 0.9% sodium chloride). This is summarized in Table 6.1.5.
Hypotonic fluids (containing significantly less sodium These volumes represent the water that is required,
than plasma) such as 4% dextrose with 0.18% sodium under normal physiological conditions, to excrete
chloride should never be used. These fluids can lead to the daily production of nitrogenous wastes the body
hyponatraemia, seizures and cerebral oedema. ­produces as urine that is isosmotic with plasma (i.e.
When replacing a deficit intravenously, the rate of that is neither overconcentrated nor overdiluted).
administration depends on the underlying condition. These maintenance volumes are only a guide, and they
In general, where the deficit has occurred rapidly (e.g. cannot be applied directly to all seriously ill children,
acute gastroenteritis, appendicitis), it may be replaced where water balance may be very different from nor-
rapidly (over approximately 4–8 h). Where the deficit mal physiology (Table 6.1.6).
has occurred over a longer period of time or there is Reduced free-water excretion is common in sev-
significant electrolyte imbalance, the volume should be eral conditions, including meningitis, encephali-
replaced more cautiously (over 24–48 h). In these cir- tis, bronchiolitis, pneumonia, perioperative states,
cumstances, the ongoing requirement for maintenance burns, nausea and vomiting, where ADH release
hydration must also be taken into consideration (i.e. is stimulated by a variety of non-osmotic stimuli.
the maintenance requirement should be given in addi- In the past, hypotonic saline solutions (such as
tion to the deficit replacement), plus additional fluid if 0.18% saline plus 4% dextrose) (see Table 6.1.4)
there are ongoing abnormal losses such as persisting were often used as maintenance fluid for hospi-
diarrhoea or vomiting. talized children. However, administration of such
Any child receiving fluid rehydration for a pre-exist- hypotonic solutions, which have a markedly lower
ing deficit should be monitored closely. They should sodium concentration than the intravascular space,
be weighed and clinically assessed prior to commenc- can lead to hyponatraemia, especially where free-
ing therapy and after 6 h of rehydration. Those who water excretion is reduced or when large fluid
are severely dehydrated should be assessed prior to volumes are administered. This can shift water
this. Where the deficit is being replaced intravenously, intracellularly, causing seizures, cerebral oedema
serum electrolytes should be repeated after 6 h of ther- and death in some patients. To avoid these compli-
apy (sooner if there is an electrolyte imbalance). See cations, solutions with a higher content of sodium
“Assessment of dehydration” for important features (such as Hartmann's solution, normal 0.9% saline
to note on clinical assessment. Examining a child for or half-normal 0.45% saline) should be the intrave-
signs of fluid overload is also important once fluid nous maintenance fluids of choice, and the volumes
therapy has been instituted. All children should be
reassessed after the deficit therapy is replaced to deter-
mine their ongoing fluid requirements. Table 6.1.5 Daily and hourly maintenance fluid
requirements

Maintenance fluids Maintenance fluid Maintenance fluid

Weight requirement for 24 h requirement per hour
Maintenance requirements involve replacement of
normal losses from urine, sweat, lungs and faeces, and First 10 kg 100 mL/kg 4 mL/kg
assume that any fluid deficit (dehydration) has been
replaced. Second 10 kg 50 mL/kg 2 mL/kg
The usual daily maintenance requirement can be
Subsequent 20 mL/kg 1 mL/kg
calculated from the following formula: kilograms 227
• first 10 kg body weight: 100 mL/kg per day
 6.1 FLUID REPLACEMENT

Table 6.1.6 Conditions affecting normal fluid requirements

Condition Response in terms of fluid requirements

Non-osmotic ADH (a) Decrease fluid requirements for bacterial meningitis, acute pneumonia, head injury
production (b) Decrease fluid requirements in stress (pain, surgery, emesis)
(c) Decrease fluid requirements with certain drugs (opiates, NSAIDs, vincristine)

Physical activity Increase if active, decrease if inactive

Body temperature Increase for fever, decrease for hypothermia

Metabolic rate Increase if high, decrease if low

Respiratory rate Increase for fast breathing

Humidity Decrease for high humidity

Environmental temperature Increase for sweating

ADH, antidiuretic hormone; NSAID, non-steroidal anti-inflammatory drug.

a­ dministered should take account of the reduced • children aged from 2 up to 10 years: 100–200 mL
free-water ­excretion that is common in many seri- (1⁄2 to 1 cup).
ous childhood conditions. Run the fluid rate as calculated for rehydration over
Although there is insufficient evidence from clinical 4 h, then review: weight, clinical examination includ-
trials to be certain how to avoid iatrogenic hypona- ing vital signs, ongoing losses, urine output and fluid
traemia and its serious consequences, after correction intake (including breast milk). Be prepared to change
of signs of dehydration with isotonic saline it is essen- the rate of administration depending on the above
tial to avoid rapid or excessive infusion of hypotonic findings.
fluids, to avoid overhydration and to monitor serum
sodium regularly in children on intravenous fluids,
particularly in conditions associated with increased
ADH release. Clinical example
Potassium is usually added to maintenance f­luids
unless the patient is in the immediate postoperative Lucy is a 15-month-old girl who presented to
period, has renal impairment or is hyperkalaemic. the emergency department with a 24-hour
history of decreased oral intake, profuse watery
Potassium requirements are around 2 mmol/kg daily,
diarrhoea and one or two vomits (clear liquid).
which equates to approximately 20 mmol/L running at She was diagnosed with gastroenteritis. Her weight was
standard maintenance rates. 10.5 kg. No recent premorbid weight was available. Based
Dextrose should be added to intravenous main- on clinical signs, she was assessed as being moderately
tenance hydration. Current practice differs between dehydrated. Her fluid deficit was calculated assuming a 7%
institutions, but ranges between 2.5% and 5%, and deficit, which equated to approximately 735 mL (7 × 10 × 10.5  kg =
sometimes up to 10% in neonates. 735 mL).
Her family had attempted oral fluid replacement at home
using a bottle. However, every time she was offered the
bottle, Lucy drank a large volume rapidly, which exacerbated
Ongoing losses her vomiting.
In the emergency department, it was explained that the
Ongoing loss most frequently refers to diarrhoea and
most successful way to facilitate oral rehydration is by giving
vomiting, although it also includes losses from stomas, small volumes of oral rehydration solution (ORS) frequently.
drains, etc. Losses are often difficult to quantify, so it Her parents were given a cup of ORS and a 10-mL syringe,
is better to review fluid balance, weight changes and and instructed to give Lucy 10–20 mL ORS every 10 min. This
clinical signs frequently, and adjust fluid rates accord- was well tolerated and her parents slowly increased the
ingly. Ongoing losses should be replaced in addition volume offered. Lucy was also given an ORS icy-pole, which
she enjoyed.
to deficit replacement and maintenance hydration. A
Lucy's parents felt well able to continue her fluid
rough estimate for the additional volume lost in any management at home. She was discharged following a
diarrhoeal stool is: period of observation.
228
• children under 2 years of age: 50–100 mL (1⁄4 to 1⁄2 cup)
 Fluid replacement therapy 6.1

Clinical example

How would you manage the first 24 h of fluid replacement for a 2-year-old child weighing 12 kg who is assessed to be
7% dehydrated, has normal electrolytes and is unable to tolerate oral or nasogastric fluid?

Fluids: deficit calculation

Intravenous rehydration Maintenance (24-h requirement) Total fluid (24-h requirement) Total fluid (hourly requirement)

7 × 10 × 12 kg = 840 mL (10 kg × 100) + (2 kg × 50) 840 + 1100 mL = 1950 mL + 1950/24 = 81 mL/h

= 1100 mL ongoing losses

• This child requires 1950 mL fluid replacement over the first 24 h, which equates to approximately 81 mL/h.
• The deficit may be replaced over 24 h in conjunction with maintenance replacement. Given the large deficit, it would be
appropriate to use an isotonic fluid for fluid replacement (see Table 6.1.4).
• The patient should be monitored clinically and have electrolytes determined after 6 h therapy. Ongoing losses should be
measured and replaced.

Management
Electrolyte disturbances
Intravenous
Severe electrolyte disturbances occur in a significant Unless the serum potassium is very low, commence an
proportion of hospitalized children in whom electro- IV infusion of appropriate fluid including 20 mmol/L
lytes are measured. Infants less than 6 months of age potassium. Monitor the serum level and increase to
and children with severe dehydration are affected dis- 40 mmol/L if the potassium level remains low. You
proportionately. Derangements of acid–base, sodium must always calculate both the K+ infusion rate (mmol
and potassium are the most common abnormalities. In per kg per h) and the K+ concentration (mmol/L).
Aboriginal children with acute gastroenteritis in north- Never exceed an infusion rate of 0.4 mmol per kg K+
ern Australia, two-thirds have metabolic acidosis and/ per h (as cardiac arrhythmias may occur) or an infu-
or hypokalaemia at the time of presentation. Children sion concentration of 40 mmol/L K+ (unless it is given
with diabetes, infants with pyloric stenosis, burns and via central vein), as it is irritating to peripheral veins.
adrenal insufficiency pose particular challenges.
Oral
Give 8–10 mmol per kg K+ per day in divided doses
Hypokalaemia 4–6-hourly. Large doses of oral potassium may induce
Potassium can be lost from the extracellular space in vomiting, so each individual dose should not exceed
diarrhoeal stools, especially with osmotic d ­ iarrhoea. 1.5 mmol/kg.
In severe dehydration, rehydration and correction
of metabolic acidosis may worsen hypokalaemia Hyponatraemia
as ECF potassium moves intracellularly. With high
The most common causes of hyponatraemia in young
aldosterone levels in dehydration, sodium and water
­
children are hypotonic dehydration and iatrogenic water
retention by the kidney may also lead to potassium
overload. This often occurs where there is ADH secretion
loss. Hypokalaemia may be manifest as hypotonia,
(the so-called syndrome of inappropriate ADH secre-
irritability, intestinal ileus with abdominal disten-
tion: SIADH) (see Table 6.1.6 and Chapter 12.3). Other
sion, and cardiac arrhythmias with T-wave changes
causes include salt-losing nephropathy and salt wasting
­(flattened or inverted T waves or U waves). The serum
in some intracranial pathologies. Hyponatraemia with
potassium concentration may not reflect the degree
dehydration often accompanies acute gastroenteritis
of total body potassium depletion, as most is stored
and is corrected by the standard rehydration protocols,
intracellularly (particularly in muscle and brain).
including treatment of the fluid deficit. It is unwise to
Before g­ iving potassium you must ensure that a child
infuse large volumes of hypotonic solutions in children.
does not have renal failure. In view of the cardiac
effects of extremes of plasma potassium concentra-
Management
tion, e­ lectrocardiographic monitoring is important in
severe hypokalaemia (< 2.5 mmol/L) and with intrave- • Reassess for signs of dehydration. Is hyponatraemia
nous infusions of potassium in concentrations greater associated with dehydration? If the child is more 229
than 40 mmol/L. than 5% dehydrated and the hyponatraemia is
 6.1 FLUID REPLACEMENT

due to gastroenteritis, rehydrate with an isotonic marked irritability and a ‘doughy feeling’ to the skin
solution (e.g. 0.9% sodium chloride or Hartmann's over their abdomen, due to loss of intracellular water
solution) as above. in the brain and soft tissues respectively. As the intra-
• Assess for signs of fluid overload. Is hyponatraemia vascular space is relatively well preserved, shock usu-
associated with oedema or fluid overload? Look ally occurs late and may be sudden. Cerebrovascular
for excessive weight gain, oedema, signs of cardiac thrombosis may occur because of hyperosmolarity.
failure. If signs of fluid overload are present,
decreasing the rate of administering fluid or ceasing
Management
IV fluid altogether is often all that is necessary.
• The use of hypertonic saline infusions (such as • Avoid rapid correction of hypernatraemia, as
3% sodium chloride) to correct hyponatraemia is rapidly falling serum sodium may shift fluid
indicated only in severely symptomatic children from the extracellular into the intracellular
(e.g. seizures when the serum sodium is less than space (following an osmotic gradient), causing
120 mmol/L) and should be given only to correct cerebral oedema or seizures. Adjust fluid volume
the sodium to a safe level (such as 5 mmol/L more and composition to return the serum sodium to
than the starting level) and until severe symptoms normal slowly (no more than 1 mmol/L every 2 h,
resolve. This should be done only after appropriate or 10–12 mmol/L per 24 h). Do not use hypotonic
consultation. maintenance intravenous fluids such as 4% + 0.18%
• After initial correction of any severe symptoms of saline, as this is likely to drop the serum sodium
hyponatraemia (e.g. convulsions), the rate of rise level too rapidly. Use Hartmann's solution, 0.9%
of serum sodium should not exceed 1 mmol/L every NaCl (normal saline) or 0.45% NaCl (half-normal
2 h. This is important to avoid causing osmotic saline) if intravenous fluids are necessary.
demyelination. The longer the child has had • Rehydration with oral fluids is a good alternative,
hyponatraemia, the slower the correction should be. correcting the fluid deficit over 24 h.
Large increases in plasma lipids due to hyperlipi- • Regardless of the method of rehydration, the child's
daemia or nephrotic syndrome may reduce the mea- electrolytes and clinical signs need to be monitored
sured plasma sodium concentration, but the overall frequently.
ECF sodium content may remain within the normal
range (artefactual hyponatraemia). In diabetes melli-
tus, hyperglycaemia increases ECF osmotic pressure Practical points
and draws water out of cells, causing a decrease in the
plasma sodium concentration (see Diabetic ketoacido- Electrolyte calculations
sis, below). • NaCl contains 17 mmol sodium and chloride per gram
• KCl contains 13 mmol potassium and chloride per gram,
0.75 g/10 mL = 1 mmol/mL K+
Hypernatraemia • Sodium bicarbonate contains 12 mmol sodium and
Hypernatraemia (Na+ > 150 mmol/L) may occur with bicarbonate per gram, and 8.4% NaHCO 3 contains
1 mmol/mL sodium and bicarbonate per millilitre
moderate or severe dehydration, especially if oral flu-
• Osmolality of serum = 2Na+ + glucose + urea (in mmol/L),
ids too high in solutes have been used for rehydra- which is normally 270–295 mOsmol/kg
tion. This occurred frequently when boiled skim milk • Anion gap = Na+ + K+ − ( HCO3 + Cl−), which is normally
and homemade salt–sugar solutions were used to less than 12 mmol/L.
treat diarrhoea, and unmodified cow's milk was used
for infant feeding. Fortunately this is now relatively
uncommon. More recently hypernatraemic dehy-
dration has occurred when hyperosmolar feeds (e.g. Acid–base balance
Poly-Joule) are continued in children with diarrhoea;
this can lead to persistence of osmotic diarrhoea and
Metabolic acidosis
hypernatraemia. Metabolic acidosis commonly complicates severe
In children with hypernatraemia, the degree of ­illness but will usually correct with treatment of the
dehydration is often underestimated because fluid primary disorder, provided there is normal renal func-
shifts from the intracellular to the extracellular space, tion and bicarbonate production. Acidosis warrants
maintaining plasma and interstitial fluid volumes; specific treatment only if the low pH is interfering with
therefore, the common clinical signs of intravascu- normal cellular function, often considered as pH < 7.15
lar dehydration (tachycardia, weak thready pulse) (normal range 7.35–7.45). In severe sepsis, asphyxia,
occur only when a child has very severe dehydration. multi-trauma and cardiovascular collapse, tissue oxy-
230
Children with hypernatraemic dehydration may have gen delivery or cellular oxygen utilization are impaired.
 Fluid replacement therapy 6.1
To produce sufficient energy for cell metabolism, ade- Causes of metabolic acidosis with normal anion gap
nosine triphosphate (ATP) is produced through anaer- (8–12 mmol/L)
obic glycolysis. Excess hydrogen ions (H+) in the form • Gastrointestinal loss of bicarbonate (diarrhoea)
of lactate are produced in this process. These are ini- • Renal loss of bicarbonate (renal tubular acidosis).
tially buffered by red cells, plasma proteins or bicar- Note that the urine anion gap will be negative with
bonate, or compensated for by increased removal of gastrointestinal causes of acidosis and positive
carbon dioxide by the respiratory system. The latter is with renal causes of acidosis (decreased ammonia
manifest by tachypnoea, and sometimes by Kussmaul excretion)
(deep sighing) respiration. Bicarbonate reacts with Causes of metabolic acidosis with increased anion gap
hydrogen ions to produce water and ­carbon dioxide: (> 12 mmol/L)
H+ + HCO3 H2O + CO2 . • Increased organic acid production (e.g. lactic
When buffers become limited, blood pH falls, caus- acidosis, diabetic ketoacidosis, organic acidaemias)
ing metabolic acidosis. pH and H+ have a logarith- • Ingestion of toxic substances (e.g. salicylates,
mic relationship, such that a fall in the pH to 7.1 methyl alcohol, ethylene glycol)
means the H+ level has doubled from 40 to 80 nmol/L • Decreased excretion of acid (e.g. acute and chronic
(Table 6.1.7). renal failure).
Metabolic acidosis often accompanies diarrhoea
with dehydration. There are a number of causes of aci-
dosis in diarrhoea, including: Alkalosis
• bicarbonate loss in stool – the most common Although much less common than acidosis, there are
mechanism a few conditions where alkalosis occurs in children.
• starvation ketosis Metabolic alkalosis occurs with recurrent vomiting in
• lactic acidosis – this is rare in diarrhoea and occurs pyloric stenosis and diuretic use, and respiratory alka-
only in severe dehydration with decreased tissue losis occurs in hyperventilation.
oxygen delivery
• diminished renal function.
Acidosis is corrected by fluid replacement, correction
of hypoxaemia, provision of calories and treatment of
any infection. Intravenous sodium bicarbonate is rarely Fluid replacement in specific
indicated in acidosis associated with diarrhoea and has illnesses
the disadvantage of transiently worsening the hypoka-
laemia. Persisting metabolic acidosis with diarrhoeal Gastroenteritis
disease may indicate the need for further rehydration Gastroenteritis is a common cause of dehydration
(i.e. the degree of dehydration has been underestimated). worldwide. In mild to moderate dehydration due to
gastroenteritis, rehydration with ORS is usually suc-
Anion gap
cessful. Oral rehydration salt is a powder containing
Measurement of serum chloride and the anion gap a specific balance of electrolytes and glucose, for-
(see Practical points: Electrolyte calculations) may mulated for use in children with diarrhoea. ORS is
be useful in determining the cause of metabolic based on the principle of glucose-facilitated intesti-
acidosis: nal sodium absorption. Soft drinks, sports beverages

Table 6.1.7 Acidosis and alkalosis

Acid–base status Clinical example pH Primary Compensatory Clinical feature

Metabolic acidosis Diabetic ketoacidosis ↓ ↓ HCO 3 ↓ Pco2 Deep breathing

Metabolic alkalosis Pyloric stenosis ↑ ↑ HCO 3 ↑ Pco2 Decreased respiration

Respiratory acidosis Severe asthma ↓ ↑ Pco2 ↑ HCO 3 Respiratory distress,

chest in-drawing

Respiratory alkalosis Hysterical hyperventilation ↑ ↓ Pco2 ↓ HCO 3 * Tetany

*May take several hours to develop, so is often not present initially.

Pco2, partial pressure of carbon dioxide. 231
 6.1 FLUID REPLACEMENT

and fruit juices are not appropriately constituted to In young children, rotavirus is the most common
be an ­effective ORS to treat dehydration, and may cause of acute gastroenteritis. Since mid-2007, the
cause osmotic diarrhoea and hypernatraemic dehy- rotavirus vaccine has been on the immunization sched-
dration. Cereal-based solutions (e.g. rice ORS) have ule for all Australian children at 2, 4 and 6 months of
no ­advantage over glucose solutions in non-cholera age. This vaccine has been proven markedly to reduce
diarrhoea. episodes of severe gastroenteritis.
The World Health Organization (WHO) ORS solu-
tion composition has been improved in recent years
Pyloric stenosis
(now 75 mmol/L Na+, compared with 90 mmol/L
Na+ in the solution that was used formerly). Reduced Severe or protracted vomiting causes a hypochlorae-
osmolarity ORS results in a decreased need for intra- mic hypokalaemic metabolic alkalosis. Hydrochloric
venous therapy and no increased risk of hyponatrae- acid is expelled in gastric juice. The kidneys aim to
mia compared with the ORS containing 90 mmol/L. correct the systemic alkalosis that results by retain-
Commercial solutions that have even lower sodium ing hydrogen ions at the expense of potassium ions.
content (60 mmol/L) are more widely used in devel- Infants with severe vomiting may have a serum chlo-
oped countries (Table 6.1.8). Continuation of feed- ride concentration below 80 mmol/L and bicarbonate
ing, particularly in breastfed infants, is important in above 40 mmol/L. In view of the alkalosis, Hartmann's
the management of gastroenteritis. Continued breast- solution is not an ideal rehydration fluid in pyloric ste-
feeding, or early semisolid feeding, within 4 h reduces nosis as it contains lactate as a bicarbonate precursor.
weight loss during illness and does not worsen diar- Normal saline with additional potassium can be used
rhoea or vomiting. to replace the deficit, followed by normal maintenance
The failure rate of oral rehydration when used for fluids. It is important to correct dehydration and alka-
gastroenteritis is low, at less than 5%. The main rea- losis before surgery, as severe alkalosis can result in
sons for failure of oral rehydration are persistent vom- postanaesthetic apnoea.
iting, high purging rates (stool output), electrolyte
disturbance (e.g. hypokalaemia), excessive drowsiness
Burns
and shock.
In gastroenteritis, the use of antiemetics (e.g. For children with a burn requiring fluid resusci-
ondansetron – available in wafers) has been shown tation (usually more than 10% body surface area
in randomized controlled trials to reduce episodes of burned), an appropriate starting formula is intrave-
vomiting, and may facilitate oral or nasogastric fluid nous Hartmann's solution 4 mL per kg per 1% burned
replacement. surface area. Half of this fluid is given in the first 8 h
Probiotics may be a useful adjunct to ORS in treat- and the remainder over the next 16 h, adjusting the
ing acute viral gastroenteritis, but may not bene- rate according to the patient's response, best measured
fit subgroups such as partially breastfed children or by the urine output. For adequate fluid resuscitation,
those with bacterial or parasitic causes of diarrhoea. children with burns may need to gain more than their
Antidiarrhoeal drugs (such as opioids and bind- preburn weight because of intracellular and intersti-
ing agents) and antimicrobials have no place in the tial oedema. During the second day after the burn,
­management of acute watery diarrhoea. oedema fluid starts to be reabsorbed and urine output

Table 6.1.8 Oral rehydration solutions (mmol/L of made-up solution)

Solution Na+ K+ Cl− Citrate (base) Glucose Osmolality

WHO (standard) 90 20 80 10 111 310

WHO (hypo-osmolar) 75 20 65 10 75 245

Gastrolyte-R 60 20 50 10 (111 as rice*) 226

Repalyte 60 20 60 10 90 240

Pedialyte 45 20 35 10 126 250

*80% amylopectin, 20% amylose.

232 WHO, World Health Organization.
 Fluid replacement therapy 6.1
should increase. A rough guide to fluid requirements adverse outcome. Many children have increased ADH
on day 2 is half of the first day's requirement, but as secretion, and some have dehydration due to vomit-
Hartmann's solution with 5% glucose. There is still ing, poor fluid intake or septic shock. Hyponatraemia
controversy about whether colloid should be provided occurs in about one-third of children with meningitis
in the early period of burns resuscitation. Children and is variously as a result of increased ADH secre-
with extensive burns or those involving the face or air- tion, increased urine sodium losses and excessive
way should be managed in specialized units. electrolyte-free water administration. Children with
meningitis require careful and regular monitoring of
clinical signs of hydration state, including signs of
Bacterial meningitis
overhydration, serum sodium and laboratory markers
Careful management of fluid and electrolyte balance of hypovolaemia, and the total fluid intake adjusted
is important in the treatment of meningitis since over- accordingly. The fluid rates suggested in Table 6.1.9
hydration or underhydration is associated with an are starting rates only. Enteral feeds should be started

Table 6.1.9 Recommended total fluid intake (mL/h for the first 24–48 h) for children with suspected or confirmed meningitis,
divided into four groups

A. Normal serum Na+ B. Serum Na+ < 135 mmol/L

and no dehydration, and no dehydration, C. Signs of dehydration D. Signs of raised ICP or
Weight (kg) oedema or raised ICP oedema or raised ICP or hypovolaemia generalized oedema

3 9 6 9 5

4 12 8 12 6

5 15 10 15 7

6 18 12 18 9

7 21 14 21 11

8 24 16 24 12

9 27 18 27 14

10 30 20 30 15

11 32 21 32 17

12 33 22 33 18

15 38 25 38 20

20 45 30 45 22

30 53 35 53 27

Group A. Normal serum Na+ and no signs of hypovolaemia, dehydration or raised intracranial pressure (ICP). Fluid guideline based
on giving 3 mL per kg per h up to a weight of 10 kg (about 70% of ‘maintenance fluid requirements’) as normal saline + 5% dextrose.
Group B. Hyponatraemia (Na+ < 135 mmol/L) but no signs of hypovolaemia, dehydration or raised intracranial pressure. Fluid
guideline based on giving 2 mL per kg per h up to a weight of 10 kg (about 50% of ‘maintenance fluid requirements’) as normal
saline + 5% dextrose. If the serum [Na+] is very low (< 130 mmol/L) refer to the intensive care unit (ICU).
Group C. Signs of dehydration or hypovolaemia at presentation. Give repeated boluses of 10–20 mL/kg normal saline until
hypovolaemia is corrected. Refer to ICU if signs of hypovolaemia persist. Ongoing fluid guideline based on giving 3 mL per kg per h
up to a weight of 10 kg as normal saline + 5% dextrose.
Group D. Signs of raised intracranial pressure or generalized oedema. Fluid guideline based on giving 1–2 mL per kg per h up to
10 kg (about 25–50% of ‘maintenance fluid requirements’) as normal saline + 5% dextrose. A child with any clinical signs of raised
intracranial pressure (e.g. very bulging fontanelle, unresponsiveness to painful stimuli or papilloedema) or of overhydration (e.g.
facial or generalized oedema) should have fluids restricted and be monitored in an ICU. Development of generalized oedema is a
major risk factor for serious adverse outcomes in meningitis, due, at least in part, to excessive fluid administration. 233
 6.1 FLUID REPLACEMENT

when the child is stable, but should be withheld in chil- approximately 48 h). Potassium should be added to
dren who are poorly conscious, vomiting or having the fluid as insulin will drive potassium intracellularly,
frequent convulsions. Children who are drinking well resulting in hypokalaemia.
should have intravenous fluids running very slowly or Patients should be monitored frequently (1–2 hourly)
the cannula capped. with a clinical assessment (including neurologi-
cal), fluid balance and venous blood gas (including
sodium, potassium and glucose). In treating children
Diabetic ketoacidosis
with DKA, the serum glucose should fall slowly and
Children with diabetic ketoacidosis (DKA) are at risk the serum sodium and osmolarity should rise; this pro-
of cerebral oedema. After initiation of insulin ther- tects against cerebral oedema.
apy, glucose moves into cells and serum osmolarity Cerebral oedema should be suspected if there is
falls, causing fluid to shift from the extracellular to the severe headache or any decrease in conscious state.
intracellular space. This can be exacerbated if hypo- Measures to reduce intracranial pressure (such as
tonic fluids are used for rehydration. Therefore, an iso- mannitol) should be started, computed tomography
tonic fluid (e.g. 0.9% sodium chloride) should be used performed, and the child managed in the intensive
and any fluid deficit should be replaced slowly (over care unit.

Clinical example Electrolytes

Sodium (mmol/L): 138 (132–144)
A 15-month-old Aboriginal boy presented with Potassium (mmol/L): 2.0 (3.2–4.8)
diarrhoea, floppiness and fast breathing. His Chloride (mmol/L): 111 (98–106)
mother said that he had had many watery Bicarbonate (mmol/L): 6 (18–27)
bowel movements over a short period of time. Anion gap (mmol/L): 23 (8–12)
On examination, he appeared unwell and was lethargic Urea (mmol/L): 5.3 (1.4–5.4)
with sunken eyes. His vital signs were: temperature 37.5°C, Creatinine (mmol/L): 44 (0–55)
heart rate 120/min, respiratory rate 60/min and blood
Blood gases
pressure 86/53 mmHg. Although alert and responsive, he
pH: 7.12 (7.35–7.4)
was noted to be floppy, with a dry mouth, absent tears on
Pco2 (mmHg): 20.3 (35–45)
crying, weak radial pulses, a capillary refill time of over
Base excess: −18 (−4 to +3)
2 seconds and slow skin pinch recoil. On auscultation, his
Blood lactate (mmol/L): 1.6 (0.8–1.8)
heart sounds were normal and his lung fields were clear.
The boy was rehydrated with 600 mL Hartmann's solution
His abdomen was soft and slightly distended with no
with 1 g/L KCl added (17.4 mmol/L) over 4 h, followed by
tenderness, masses or visceromegaly. Bowel sounds were
maintenance fluids at 24 mL/h with breastfeeding. By 24 h after
present. Neurological examination was normal except for
admission he had been given 1200 mL fluids and his condition
mild hypotonia.
had much improved. His weight was now 6.7 kg, which implied
His weight on admission was 6.1 kg and his height
that he had been about 9% dehydrated on admission (6.7 − 6.1 =
68 cm. These are all below the third centile. His head
0.6 kg; 0.6 ÷ 6.7 × 100 = 8.96%). His diarrhoea was settling
circumference was 43.6 cm, well below the second centile
and he was passing dilute urine.
for age (Z-score −3.0).
Over the next 24 h, however, he had six foul, watery stools
He was given a bolus intravenous infusion of 120 mL (20 mL/
containing large amounts of reducing substances. There
kg) 0.9% sodium chloride solution, and blood was taken for full
was also a decrease in his pH, bicarbonate and magnesium
blood count and urea and electrolyte estimation.
levels compared with 24 h previously. This relapse of osmotic
The laboratory findings were as follows (reference ranges in
diarrhoea was due to breast milk lactose overcoming the
parentheses):
lactase threshold in the small intestinal mucosal brush border.
Blood tests He improved on oral lactase drops (β-d-galactosidase) with
Full blood count breastfeeds. The stool microscopy result reported ova of
Haemoglobin (g/L): 82 (105–135) Strongyloides stercoralis.
Mean corpuscular volume (MCV) (fL): 53.9 (75–85) This is a fairly typical case of acute gastroenteritis in an
Red cell distribution width (RDW) (%): 24.1 (11.5–14.5) Aboriginal child from northern Australia, whose illness is
Platelets (×109/L): 724 (150–450) frequently complicated by osmotic diarrhoea, hypokalaemia,
White cells (×109/L): 15.6 (6.0–11.0) acidosis and iron deficiency. The underlying small bowel
Blood film report: Marked microcytosis and hypochromia, damage could be prevented by improving hygiene, reducing
moderate anisocytosis and poikilocytosis, neutrophil overcrowding, and prompt treatment of micronutrient
leukocytosis with no toxic changes and moderate deficiencies, which would then make community oral
eosinophilia. rehydration therapy more effective.

234
 7
PART

PRINCIPLES OF
IMAGING

235
 7.1 Imaging Rita L. Teele, Helen L.M. Bird

The equipment in the department of radiology should

Introduction be calibrated to provide images requiring low-dose irra-
The tools of the radiologist include plain radiogra- diation but still provide good diagnostic detail. Factors
phy, fluoroscopy (screening), intravenous, intracav- for image production from CT should be modified to
ity and gastrointestinal contrast media, angiography, suit the size and age of the patient. Dose measurements
nuclear medicine, ultrasonography, computed tomog- are expressed in units termed gray (Gy) (absorbed dose;
raphy (CT) and magnetic resonance imaging (MRI). 1 Gy equals 100 rad) or sievert (Sv) (equivalent dose;
Interventional radiology uses imaging for procedures 1 Sv equals 100 rem in the old terminology).
such as abscess drainage, sclerosis of vascular malfor- Every person is exposed to background radiation from
mations, biopsy and intravenous access. the world around them and from cosmic rays. Radon gas
There are many differences between imaging the child provides the major source of background dose. Total
and imaging the adult. Radiologists rely heavily on the annual background dose, per person, therefore depends
expertise of medical radiation technologists and sonog- heavily on the geographical location, and is estimated to
raphers in acquiring diagnostic images in sick or injured be 2–3 mSv (Table 7.1.1). This does not include medical
children. The child's physical and psychological welfare exposure, predominantly from CT, which in the USA
during diagnostic imaging must be considered. Imagine has recently doubled the average per person background
how the typical 2-year-old child, scheduled to have a dose to 4–6 mSv. For comparison, two radiographs of the
micturating cysto-urethrogram, would react when intro- chest give 0.02–0.08 mSv – less radiation than received on
duced to a stranger wielding a catheter. Cooperation a round trip by air across the Pacific Ocean.
from young children is not possible when procedures Conversely, advances in imaging have made diag-
are long and/or invasive; sedation is needed for many. nosis far more accurate and safe than in the past.
Paediatric ailments often differ from those of the Radiologists can often demonstrate the likely cause(s)
adult. Congenital disease as well as acquired disease for a child's symptoms and signs, enabling timely med-
must be considered in the differential list of diagno- ical or surgical treatment.
ses. History-taking and clinical examination of infants Paediatric radiologists play an important intermediary
and children is not easy; thus, information from imag- role between paediatrics and radiology, in both the con-
ing is crucial in certain situations. Radiation protec- duct and the interpretation of an examination. They are
tion is important both for the child and for society as a the clinician's friend and the patient's advocate. Imaging
whole; a child is 2 to 10 times more radiosensitive than has to be problem-oriented. The most important informa-
an adult. Some specific disease states and syndromes tion on a requisition form, apart from the child's name and
are associated with increased susceptibility to injury age, is the question to be answered. The next most impor-
from radiation (e.g. ataxia telangiectasia). tant items are the legible name and contact number of the
Radiation protection is provided by the following person asking the question. In this age of computeriza-
measures: tion, conversation on the telephone or, better still, face to
1. Limiting examinations to those that are likely to face is invaluable when a complicated situation arises. The
provide diagnostic help and influence treatment paediatric radiologist should do the least investigation to
decisions achieve the most information about a child's condition.
2. Using optimal technical factors in order to provide In concluding this introductory section, we note that
the lowest dose of X-rays for a diagnostic study reliable evidence-based information, to support many of
3. Limiting fluoroscopic time and using ‘last image the recommendations that are in print regarding appro-
hold’ techniques when possible priate algorithms for paediatric imaging, is difficult to
4. Using shielding whenever possible. access. There are few clinical situations and ethical guide-
Measures 2–4 are the responsibility of the radiologist lines that allow performance of several studies on a child
and radiographer, but the clinician is responsible for simply to compare their utility. Clinical information is
choosing imaging studies carefully. The radiologist frequently incomplete; ‘comparable’ studies are rarely
236 should be available for discussion of appropriate imag- comparable. Furthermore, local traditions, practitioners
ing for a given diagnostic consideration. in the area, available facilities and economic conditions
 Imaging 7.1
Table 7.1.1 Estimated equivalent background radiation for
various imaging procedures
Neurology
Acute head trauma, all ages
Study Estimated equivalent
background assuming See Chapter 3.6.
background of 2.5 mSv/year • CT of the brain following the CHALICE (Children's
Head injury ALgorithm for the prediction of
Chest X-ray, 2 views 3 days
Important Clinical Events) rule (Fig. 7.1.1).
Abdominal X-ray, 2 views 1 week

Extremity X-ray, 2–3 views 5 hours

Skull series X-ray, 3 views* 3 weeks

Upper gastrointestinal series* 6–12 months

Barium enema* 8–16 months

MCU (VCUG) 1–7 weeks

Chest CT 12–18 months

Abdominal CT 2 years

Cranial CT 8–12 months

CT, computed tomography; MCU, micturating

cystourethrography; VCUG, voiding cystourethrography.
*From adult data.

usually prevail in decision-making. If you have any ques- A

tion about the appropriate imaging for your patient, ask
for help from a radiologist who is experienced in paedi-
atric diagnosis. With these caveats, and encouragement
to you, the reader, to challenge algorithms when they
seem less than sensible, the following sections outline
appropriate imaging considerations for particular situa-
tions, and are arranged anatomically, for easy reference.

Practical points

• Find out whether there are clinical guidelines for your

department/institution. They may include guidelines for
imaging.
• Generally, in a complicated case, it is best to begin with
uncomplicated imaging, such as plain radiographs. They
may provide the diagnosis; if not, they can help point the
way to other studies.
• Provide relevant clinical information to the radiologist
when requesting examinations.
• Consult a paediatric radiologist, or one experienced in B
paediatric diagnosis, when you have questions about the
imaging of a specific clinical problem. Fig. 7.1.1 Axial computed tomograms of the brain in an 8-year-old
• Be prepared to answer questions from parents regarding involved in a high-speed motor vehicle accident: (A) bone window;
ionizing radiation and know whom to ask for more (B) brain window. The Glasgow Coma Scale score on arrival in
information. the emergency department was 7/15. The scan reveals a large
• Be familiar with the preparation, immediate complications comminuted and depressed skull fracture involving right frontal and
and sequelae of invasive imaging procedures. temporal bones with a small underlying extra-axial haematoma 237
and midline shift to the left.
 7.1 PRINCIPLES OF IMAGING

• Use NEXUS clinical prediction rule (altered Seizures

neurological function, intoxication, midline
See Chapter 17.1.
posterior spinal tenderness, and/or distracting
For acute non-febrile seizure:
injury) to identify which children and adolescents
• MRI or, if not available, CT (clinically significant
should have imaging of the cervical spine.
yield of 3–8%).
• MRI when CT findings are negative in an infant or
child with persisting abnormal neurological signs.
Notes
Notes Because of the variable availability of MRI, local pro-
tocols should be consulted for neurological diagnostic
Radiographs of the skull are poorly predictive of
work-up. Imaging following a single generalized non-
intracranial pathology. They are of use in the situation
febrile seizure in children is an area of controversy. Focal
of suspected inflicted injury (non-accidental injury)
non-febrile seizures will usually be investigated by electro-
where multiple fractures or fractures of different ages
encephalography (EEG) and cerebral imaging. Temporal
are helpful in establishing the diagnosis.
lobe lesions are more likely to be shown on MRI than CT.
For suspected injury to the neck, a lateral radio-
Simple febrile seizure (single or recurrent) does not
graph, in collar, can be followed by anteroposterior
usually warrant imaging.
(AP) view of the cervical spine and odontoid view.
Plain radiography can detect 94% of fractures. In
infants and young children, the immature anatomy Altered conscious state, suspected tumour
of the cervical spine along with the head being rela- and stroke
tively large in proportion to the neck, results in the
• MRI
upper cervical spine (C1–C3 vertebral bodies) being
• CT (if MRI not available).
more commonly injured than the lower spine, as seen
MRI is the preferred diagnostic test for a child present-
in older children and adults. For this reason, careful
ing with acute neurological signs (Fig. 7.1.2). If MRI
scrutiny of the upper cervical spine on plain radio-
is not available, CT can diagnose established infarction,
graphs is needed. In some centres, the upper cervical
haemorrhage and most tumours. MRI is the preferred
spine is scanned at the time of brain imaging in the set-
test as it detects infarction earlier, can provide perfu-
ting of significantly altered conscious state and major
sion imaging in the setting of stroke and angiographic
trauma. CT of the entire cervical spine, often routinely
sequences in the setting of vascular disease. It also pro-
acquired in adults, includes the thyroid gland and is
vides more detailed imaging (in multiple planes) for
used in children only when there is credible utility.
surgical planning in the setting of tumour.

Newborn Developmental delay

• Portable ultrasonography when screening for germinal • MRI.
matrix/intraventricular and intraparenchymal MRI is the preferred examination as it can assess
haemorrhage in the premature infant. white-matter volume and distribution along with grey-
• CT for suspected acute extra-axial collections matter abnormalities (sulcation, heterotopias and
(bleeding, infection). other migration anomalies) better than CT. Timing
• MRI for suspected non-haemorrhagic parenchymal for the examination needs to be considered, with chil-
disease (e.g. hypoxic–ischaemic insult, neuronal dren under 2 years undergoing progressive myelination
migrational disorders). (sometimes making white-matter signal assessment
more difficult) and most children below 6–7 years (and
Notes often later when developmentally delayed) requiring
general anaesthesia for the examination.
Follow local protocols for timing/frequency of ultraso-
nographic screening for premature infants. Generally,
a scan is performed at 3–4 days of age in infants who Spinal cord and cauda equina symptomatology
weigh less than 1500 g unless there is clinical concern
• MRI is the diagnostic test of choice in all age groups.
that prompts an earlier study.
Timing of MRI for hypoxic–ischaemic insult
Spinal dysraphism
depends on the availability of resources. One scan at
24–48 hours of life followed by a scan at 7–10 days of • Ultrasonography in neonates (first month of life;
life is ideal for both assessment of timing of injury and can be later if prematurely born)
238
severity of injury; a compromise is one scan at 3–4 days. • MRI in older children.
 Imaging 7.1

A B

E F

Fig. 7.1.2 Magnetic resonance images of brain and spine in this 15-year-old shows a large tumour in the posterior fossa. Sagittal T2
(A), axial T2 (B), axial T2 level with the lateral ventricles (C), axial T1 post-contrast (D) and sagittal T1 post-contrast through the spine
(E, F) are representative images from the study. On the T2 (water) weighted images, the tumour is predominantly bright in keeping
with ‘fluid’ contents; soft tissue is present along the posterior surface. This soft tissue enhances on the contrast sequences, in keeping
with mural nodules. The axial image at the level of the lateral ventricles reveals early ventricular dilatation and transependymal flow of
cerebrospinal fluid, in keeping with early obstruction (due to pressure from the tumour on the cerebral aqueduct and fourth ventricle). 239
No spinal metastases are identified. The tumour was a pilocytic astrocytoma.
 7.1 PRINCIPLES OF IMAGING

Notes
Spinal ultrasonography is unnecessary in cases of clas-
sical myelomeningocele; however, the accompanying
Chiari II malformation of the brain can be assessed
with ultrasonography or MRI, and the degree of
­ventricular dilatation after shunt placement or third
ventriculostomy can be monitored.
For neonates with midline dermal abnormality,
mass, abnormal sacral cleft/dimple, sacral agene-
sis, anorectal malformation or vertebral anomaly on
plain radiographs, ultrasonography can assess the spi-
nal canal, spinal cord and cauda equina. Ossification
of posterior elements as the child grows obscures the
sonographic window and, when this occurs, MRI is
used to assess the anatomy.

Cardiology
See Chapter 15.1.
Fig. 7.1.3 The anteroposterior radiograph of this newborn,
who presented in severe respiratory distress, has features that
Suspected congenital heart disease identify cardiac abnormality as the likely aetiology, although
the heart is normal in size. Note that the nasogastric tube is
(E.g. abnormal prenatal ultrasonography, cya­ nosis,
entering a right-sided stomach, whereas the apex of the heart is
murmur, unexplained oxygen requirement.) left-sided. The tracheostomy tube is deviated leftward by a right-
• Posteroanterior (PA) and lateral chest radiographs sided aortic arch and the umbilical artery catheter is in a right-
to include upper abdomen (Fig. 7.1.3) sided descending aorta. This infant had heterotaxy syndrome
• CT or MRI for anatomical detail of vascular rings with multiple cardiac anomalies. The venous congestion that is
as necessary. apparent in the lungs is from obstructed anomalous pulmonary
(Cardiac angiography/interventional procedures venous return, the major cause of the respiratory distress.
are arranged by paediatric cardiologists in most
centres.)
Pulmonary/airway
Central/cardiac pain See Chapter 14.5.
• Posteroanterior (PA) and lateral chest radiographs
to include upper abdomen. Cough and fever
• PA and lateral chest radiography.

Notes Pleuritic pain

Plain radiography is not an accurate screening test • PA and lateral chest radiography.
for presence or absence of structural cardiac dis-
ease, but has a role in the identification of coexis- Suspected sepsis in a neonate
tent airway and/or pulmonary abnormality, skeletal
• PA and lateral chest radiography.
anomaly that may direct investigation of other sys-
tems, and as a b ­ aseline study, particularly in regard
First episode of wheezing
to the state of the pulmonary vasculature in neonates.
Echocardiography, in most centres related to the See Chapter 14.3.
department of cardiology, is the ‘gold standard’ for • PA and lateral chest radiography
all patients in whom structural cardiac abnormality is • Fluoroscopy/screening if foreign body is suspected.
suspected. Most echocardiographic examinations are Imaging is usually indicated only when the history is
time-consuming; sedation may be needed for trans- suggestive of inhaled or ingested foreign body, the child
thoracic scanning and is always required for trans­ has no coryzal illness, or the child does not respond as
240
oesophageal scans. expected to treatment for bronchiolitis/asthma.
 Imaging 7.1
Unexplained stridor • Computed tomographic angiography (CTA) with
intravenous contrast if mediastinal, vascular and/or
See Chapter 14.2.
major airway injury suspected.
• PA and lateral chest radiography
• Lateral radiograph of the neck
• Fluoroscopy/screening/barium swallow depending Thoracic mass
on plain radiographic findings. • PA and lateral radiography (Fig. 7.1.4)
Trauma to the chest • CT or MRI or, occasionally, both, depending on
the organ(s) of origin and involvement
• AP supine chest radiography • Echocardiography for mass related to the heart.

A B

Fig. 7.1.4 (A) Posteroanterior (PA) and (B) lateral radiograph of the chest in an adolescent boy shows mediastinal widening and bulky
hilar regions on the PA view with a retrosternal mass on the lateral view. Axial (C) and coronal (D) computed tomography (CT) after
intravenous contrast confirms a large soft tissue mass involving the anterior and middle mediastinum, with areas of calcification. B-cell 241
lymphoma was the diagnosis after a CT-guided biopsy of the mass.
 7.1 PRINCIPLES OF IMAGING

Notes
Abdomen/gastroenterology
There is great debate as to whether a previously well
child who has clinical symptoms and signs of pneu- Abdominal pain
monia requires radiography at all. Likewise, there See Chapter 20.1.
is argument as to whether the workup of sepsis in • Supine and upright or decubitus radiographs for
an infant, and the first episode of wheezing (with- acute abdominal pain
out history of aspiration of foreign body), requires • No imaging, or ultrasonography only, for non-
imaging. Normal radiographs and fluoroscopy do specific periumbilical abdominal pain.
not rule out the presence of an endobronchial for-
eign body: there has to be enough obstruction of an Constipation
airway to provide radiographic evidence of its pres-
ence. Bronchoscopy should follow if there is a good • No imaging or single plain radiograph of the abdomen
history of aspiration. • Plain radiography then contrast enema for the
Some centres perform a single PA radiograph for neonate who fails to pass meconium.
indications such as suspected pneumonia as it halves
Notes
the radiation dose and often provides the diagnosis in
clinical settings such as sepsis/pneumonia. There Constipation/encopresis is a clinical diagnosis but
is no good prospective study that compares the utility some clinicians order a plain radiograph for the ini-
of the PA-only radiography with PA and lateral views tial evaluation of a child who has constipation. The
of the chest. There is anecdotal evidence that sup- radiograph is used for assessment of the degree of
ports the acquisition of both views. In many cases, distension of bowel, but this has poor repeatability
lower lobe pneumonia is difficult to diagnose from and does not alter treatment or predict response to
the PA view alone. The cardiac size is easier to judge therapy. It can be useful for examining the lumbosa-
when the shape of the chest is defined by two views. cral spine for occult dysraphism, but this has a very
When both radiographs are normal, the radiologist low yield in children with isolated constipation and
can state with ­certainty that the chest is normal to no neurological signs. Rarely do plain radiographs
radiographic examination. In some situations, it is reveal a specific cause for chronic constipation, and
just as important to document normality as to find many question their value in this setting. There is no
an abnormality. correlation between plain abdominal radiographs
There is general consensus that follow-up radi- and intestinal transit time. Evaluation of transit
ography for uncomplicated pneumonia is unnec- time through the gastrointestinal tract can be per-
essary. Follow-up radiographs are reserved for formed with sequential radiographs following inges-
children who have persisting symptoms of chest tion of radio-opaque markers or by nuclear medicine
disease or who have had unusual radiographs on ­studies following ingestion of an isotopic marker.
presentation. For the child who has chronic periumbilical abdomi-
Stridulous breathing implies narrowing of the tra- nal pain, ultrasonography is often used as a means
chea. A vascular ring, endotracheal haemangioma, of reassuring parents, child and clinician that there is
tracheitis or epiglottitis are all possible causes. If a vas- no anatomical abnormality of the liver, spleen, pan-
cular ring is obvious on plain radiography, MRI or CT creas and kidneys, but again this has a very low yield.
should follow. Imaging is not needed in children with Limiting radiographic imaging to patients who have
classical croup and can be dangerous in children who had previous abdominal surgery, suspected ingestion
are suspected of having epiglottitis. No child or infant of foreign body, abnormal bowel sounds, abdominal
with respiratory compromise should be sent for imag- distension or peritoneal signs identifies virtually all
ing without adequate safeguards for provision of an patients with significant disease.
airway. The evaluation of a child suspected of having appen-
A chest mass may be diagnosed on radiography dicitis (Fig. 7.1.5) is heavily reliant on the clinical prac-
after a child presents with pain, cough, respiratory tice guidelines established at the point of care. Many
compromise, etc. It may also be an incidental find- institutions rely on an approach that limits CT to those
ing; a posterior mediastinal mass may be clinically with negative findings on ultrasonography or those sus-
silent. The diagnostic approach is tailored to the pected of rupture/abscess. Ultrasonography requires
clinical situation. As examples, an anterior medias- competent practitioners and good equipment, and
tinal mass in the setting of T-cell leukaemia needs is far easier to perform and interpret in children who
no further imaging. A posterior mass with verte- are not obese. CT requires injection of contrast media,
bral involvement will require further cross-sectional irradiation and good interpretation of the resultant
242 imaging. images.
 Imaging 7.1
gastrointestinal in origin (e.g. intussusception) requires a
different approach from a mass that is hepatobiliary, such
as a choledochal cyst. When intussusception is diagnosed,
air enema for reduction is the first therapeutic method of
choice. Remember to consider pregnancy in an adolescent
female who has a pelvic mass! If a malignant tumour is
diagnosed, the affected child may be enrolled in treatment
protocols that have very specific requirements in terms of
imaging at staging and follow-up.

Abdominal trauma
• Supine radiography, with decubitus if possible
• Cross-table lateral view of lumbar spine if there
has been hyperflexion of the spine, such as with a
lapbelt injury
• CT with intravenous contrast (Fig. 7.1.7).

Notes
Many trauma protocols for evaluating the severely
injured child have been based on the approach to adults,
who have different mechanisms and types of abdomi-
nal injury. For example, a screening pelvic radiograph
is part of the ‘adult’ trauma series. Its use in children
has not been proved to be helpful. If any screening
view is considered, it should be an abdominal radio-
Fig. 7.1.5 Appendicitis is diagnosed with ultrasonography (A) when graph, which will include the pelvis. Peritoneal lavage
a non compressible, blind ending tubular structure is contiguous is not a helpful diagnostic test in paediatric trauma.
with the caecum and measures 6 mm or greater in diameter. There Major organ injury can occur without there being free
is often surrounding inflammatory change within the fat, as shown ­intra-abdominal fluid. Ultrasonography is not as sensi-
in this scan. The presence of a shadowing appendicolith, although
tive a method of diagnosis as CT, but in some remote
helpful in the diagnosis, is not a necessary feature. In another case
(B), retrocaecal appendicitis is evident on this slice from a computed
areas may be the only tool available to search for free
tomogram after intravenous contrast. The appendix (arrow) is thick- fluid, intraparenchymal laceration/haematoma and
walled, measures 8 mm in diameter and has adjacent inflammation, renal perfusion (with Doppler).
including thickening of the posterior peritoneum. A child should be stabilized before being moved to
a CT scanner. Craniospinal imaging can occur at the
Abdominal mass same time if needed. Oral contrast medium is not usu-
• Plain radiography of abdomen when aetiology of ally used for the following reasons: risk of aspiration;
the mass is in doubt, except for a female with a time needed to allow contrast to pass through intesti-
pelvic mass nal tract; and relative ileus in the situation of severe
• Ultrasonography injury. However, some centres use positive contrast
• CT if necessary (Fig. 7.1.6) and some instill water through a nasogastric tube to
• MRI for neurogenic tumour, soft tissue tumour, outline the duodenum.
bony involvement by tumour, choledochal cyst or
an unusual mass. Non-bilious vomiting

Notes See Chapter 20.1.

• Ultrasonography when pyloric stenosis is suspected
Besides usually demonstrating the mass and its locale, but a pyloric mass is not palpated (Fig. 7.1.8)
plain radiography also provides information regarding • Upper gastrointestinal series with barium.
the bases of the lungs, presence of calcification, effects
of the mass on contiguous organs, bones and/or gastro-
Bilious vomiting
intestinal tract. Most abdominal masses in childhood are
related to the retroperitoneum and, in particular, the kid- • Plain radiographs
ney. Examples are obstructive hydronephrosis, multicys- • Upper gastrointestinal series with barium if the
tic dysplastic kidney and Wilms tumour. A mass that is obstruction seems proximal. 243
 7.1 PRINCIPLES OF IMAGING

Fig. 7.1.6 Four-day-old neonate with a liver mass that had been diagnosed antenatally. The plain radiograph (A) suggests hepatic
enlargement. The longitudinal sonographic view (B) reveals a large heterogeneous mass within the right lobe of liver. Axial (C) and coronal
(D) computed tomograms though the abdomen, after intravenous contrast, reveal the large hypo-attenuating mass in the liver. Non-uniform
splenic enhancement on the axial image reflects the arterial timing of the scan. Biopsy of the hepatic mass revealed hepatoblastoma.

Chronic diarrhoea Gastrointestinal bleeding

• Upper gastrointestinal series with follow-through • Technetium-99m pertechnetate scintiscan when a
examination of small bowel when the cause is not Meckel diverticulum is suspected
obvious from clinical and laboratory data, cultures and • Upper gastrointestinal series with follow-through
small bowel biopsy. When Crohn's disease is suspected examination of small bowel and antegrade
clinically, but not proven, consider MR enterography. evaluation of colon and/or air-contrast barium
enema when all other investigations are unhelpful
(e.g. upper gastrointestinal endoscopy, colonoscopy
Subacute small bowel obstruction
and/or video capsule endoscopy).
• CT after ingestion of water-soluble oral contrast
Notes
is usually more revealing of the site and source of
obstruction than follow-through AP radiographs The availability of consultants trained in paediatric
244
after the ingestion of barium. ­gastroenterology and their skill in endoscopy is directly
 Imaging 7.1

B
A

C D
Fig. 7.1.7 This 9-year-old child had suffered severe blunt trauma to the abdomen. Axial arterial (A), axial portal venous (B) and
coronal (C) computed tomograms through the abdomen reveal a largely non-enhancing spleen and only partially enhancing left
kidney, indicating lack of vascular perfusion. There is a small volume of enhancing splenic tissue anterosuperiorly (supplied by collateral
vessels). The majority of the organ has lost arterial blood supply, owing to traumatic dissection of the splenic artery. Note the abrupt cut
off of this vessel (arrow) posterior to the tail of pancreas in (A). The splenic vein remains patent. A dissection has also occurred in the
left renal artery (D). Note the free fluid adjacent to the liver edge.

related to the need for radiological investigation of gastro­

intestinal diseases. The use of video capsule endoscopy
in paediatrics has also decreased reliance on imaging.
Normal infants regurgitate feeds. If the infant is
gaining weight normally, imaging is unnecessary.
Projectile vomiting warrants consideration of pyloric
stenosis, which can be imaged with ultrasonography
(see Fig. 7.1.8). Pulmonary symptomatology, failure
to thrive, feeding difficulty and gastrointestinal blood
loss are reasons to consider upper gastrointestinal
series.
Problems in the neonatal period, such as failure to
pass meconium, bilious vomiting and distension, tend
to be congenital in origin and the appropriate sequence
of imaging requires close cooperation between pae-
diatric surgery and radiology. Bilious vomiting may
Fig. 7.1.8 Ultrasonography was performed after this 4-week-
old infant presented with persistent vomiting. A scan along the
occur with distal obstruction. One cannot rely on
long axis of the antropyloric region shows the typical features of ultrasonography to confirm or exclude malrotation: a
pyloric stenosis with thickening of the muscle and elongation of contrast study of the upper gastrointestinal tract is the
245
the channel. current ‘gold standard’.
 7.1 PRINCIPLES OF IMAGING

Hepatobiliary
Neonatal jaundice
See Chapter 11.2.
• Ultrasonography to establish anatomy
• Magnetic resonance cholangiopancreatography
(MRCP) and/or radionuclide study with
technetium-99 m iminodiacetic acid derivative when
choledochal cyst, biliary hypoplasia or atresia is a
consideration (Fig. 7.1.9).

Right upper abdominal pain

• Plain radiography and, often, the addition of
ultrasonography. A

Notes
Right lower lobe pneumonia may present as severe
right upper abdominal pain; therefore, always look
at the bases of the lungs on abdominal radiographs.
Gallstones in childhood are more likely to be pig-
ment stones than cholesterol stones and may contain
enough calcium to be visible on radiography.

Juvenile/adolescent jaundice
• Ultrasonography of liver, biliary tract, pancreas
and spleen
• CT or MRI, depending on the results of
ultrasonography. B

Abnormal hepatic function

• Ultrasonography when the clinical situation is
atypical for hepatitis
• Ultrasound-guided biopsy if the diagnosis is uncertain.

Nephrology/urology
Urinary infection
See Chapter 18.1.
• Ultrasonography of the urinary tract in neonates,
at the time of infection, to rule out an obvious
surgical problem, such as obstruction C
• Ultrasonography and micturating Fig. 7.1.9 Ultrasonographic (A) and magnetic resonance
cystourethrography (MCU) in some infants and cholangiopancreatography (MRCP) (B, C) images show a type
children who have had a documented urinary tract 1 choledochal cyst. The cyst is separate from the collapsed
infection (Fig. 7.1.10) gallbladder and there is no dilatation of intrahepatic
• Technetium-99m diethylenetriamine penta-acetic bile ducts.
acid (DTPA) or Mag3 scans, with furosemide, for
evaluation of the child with possible obstruction at
the pelviureteric junction or ureterovesical junction
246
 Imaging 7.1
• MRI or CT with intravenous contrast if an endocrine
tumour such as phaeochromocytoma is suspected
from laboratory data. Most phaeochromocytomas
are intra-abdominal and adrenal in location.

Note
Examination of the kidneys with Doppler is difficult,
time-consuming and often insensitive to subtle vascu-
lar narrowing. Accessory renal vessels may be over-
looked. Mid-aortic syndrome and neurofibromatosis
are rare and, when present, typically have other signs
and symptoms. A ‘negative’ examination does not rule
out renal vascular disease.
CTA can define renal vascularity with greater clarity
than ultrasonography.

Haematuria unrelated to trauma

• Ultrasonography of urinary tract
• CT if there is a strong likelihood of renal/ureteral stone
that has not been identified with ultrasonography
• CT or MRI if a renal tumour is suspected
• MCU or retrograde urethrography if a distal site of
bleeding is suspected and cystoscopy is not available.

Fig. 7.1.10 Micturating cystourethrography reveals severe reflux

into the left kidney in this infant who presented acutely ill with
infection. This reflux is classified as Grade 5, due to the degree Musculoskeletal
of distension of the collecting system. Trauma
See Chapters 3.6 and 8.1.
• Technetium-99m dimercaptosuccinic acid (DMSA) • Two orthogonal radiographic views of the bone or
or Mag3 scans during the acute illness can support joint that has been injured (Fig. 7.1.11). Oblique/
the diagnosis of pyelonephritis, and/or after special views as needed of areas such as scaphoid,
infection has cleared can document renal scars. radial head, shoulder
• CT for special cases such as intra-articular fractures
Renal failure of ankle, pelvic fracture.
• Ultrasonography of urinary tract
• Ultrasound-guided biopsy of kidney, if necessary Fever/pain/swelling related
for diagnosis. to the musculoskeletal system

Note See Figure 7.1.12.

• Two orthogonal radiographic views of the
Ultrasonography, which does not rely on renal func- symptomatic bone or joint
tion for images, can usually aid in triage of the patient • Nuclear medicine technetium-99 m diphosphonate
by determining a surgical or medical cause for renal bone scan
failure. • MRI for difficult diagnoses, tumour, occult infection
• Ultrasonography for specific questions: localization
Hypertension of collection of fluid, joint effusion.
See Chapter 18.2.
Notes
• Ultrasonography of urinary tract and adrenal
glands MRI is fast replacing radionuclide studies in cases
• Nuclear medicine for quantitative, divided renal where there is localized pain or swelling and clini-
vascular flow and function cal concern regarding a single septic joint or focus of
• CTA/angiography in the rare situation of suspected osteomyelitis. Follow-up studies of children with diag-
renal vascular disease nosed bone tumour should be performed with MRI
247
 7.1 PRINCIPLES OF IMAGING

Fig. 7.1.11 Anteroposterior (A), mortise (B) and lateral (C) views of the ankle were obtained in this girl who had tripped while running.
Note that the fracture of the posterior malleolus (arrow) can be identified only on the lateral view. Views in two or more planes are
necessary for adequate diagnosis of bony injury.

rather than CT; MRI gives far more information asymmetrical limbs, the other arm and/or leg
regarding adjacent soft tissues and bone marrow. should also be imaged.

Metabolic disease
Developmental dysplasia of the hip
• AP plain radiograph of wrist and/or knee. See Chapter 8.1.
Notes
• Ultrasonography at 4–6 weeks of age if
developmental dysplasia of the hip (DDH)
Because metabolic disease such as rickets is more obvi- suspected but not obvious on physical examination,
ous in areas of rapid bone growth, the wrists and knees or if risk factors (female, breech, positive family
are more revealing of abnormality than other sites. history) present, or
Other views (hands, clavicles) may show changes of sec- • Plain radiography at 4–6 months of age if DDH
ondary hyperparathyroidism in those with renal failure. suspected but not obvious on physical examination.

Syndrome with potential skeletal involvement Notes

• Plain radiography of chest, spine, pelvis, This is another area of contention. Ultrasonography
skull, one leg and left arm to include hand of the infant's hips requires training and practice.
248 for determination of bone age. If patient has Early radiography of neonates is unhelpful because
 Imaging 7.1

A B D

C E

Fig. 7.1.12 This 8-month-old infant presented with a 10-day history of swelling around the distal forearm. Plain radiographs
(A, B) show marked soft tissue swelling about the distal radius with focal osteopenia involving the lateral aspect of the distal radial
metaphysis. A sonogram (C) shows the extent of the soft tissue swelling with several focal small fluid collections. Post-contrast T1
weighted coronal (D) and axial (E) magnetic resonance images show the full extent of the infection. The distal radial metaphysis
demonstrates contrast enhancement and there is significant enhancement with several small fluid pockets in the surrounding soft
tissue. The child had established osteomyelitis with several small abscesses.

Inflicted injury (non-accidental injury)

so much of the anatomy is cartilaginous. Radiographs
at 4–6 months are more informative and still allow See Chapter 3.9.
intervention if necessary. In some areas of Europe, • CT (in acute situation of cranial injury) or MRI of
­ultrasonography is used to screen all newborns. Such brain to assess extra-axial spaces, parenchymal injury
studies have a high false-positive rate of diagnosis of • Complete skeletal survey (infants) with high-detail
DDH. Repeated physical examination is the corner- images to search for evidence of fracture
stone of diagnosis. Infants may not have an obvious • Follow-up skeletal survey (infants) 2 weeks after
problem until after the neonatal period; hence the acute admission depending on original findings
change in name from CDH (congenital dysplasia of • Nuclear medicine technetium-99 m diphosphonate
the hip) to DDH. The availability of experienced pae- bone scan
diatric orthopaedic surgeons has an effect on the local • CT of abdomen, with intravenous contrast, if
imaging protocols. evidence of abdominal trauma. 249
 7.1 PRINCIPLES OF IMAGING

Notes
Abbreviations
Some centres use nuclear medicine in imaging proto-
cols for infants and young children if there is availabil- The following abbreviations are in common use in
ity and local expertise in interpretation. imaging:
Often a follow-up skeletal survey or limited survey AP, anteroposterior
may be very revealing. Periosteal reaction takes about PA, posteroanterior
7–10 days to appear. The acute fracture may be occult. These terms relate to the course of the X-ray beam
The radiology department needs a close relationship through the body. Anteroposterior, supine chest radio-
with child protection services within the hospital to graphs are much easier to accomplish in infants who
make sure that the appropriate studies, appropriately cannot sit without support. Magnification of the heart
timed, are performed. is not as significant an issue as it is in adults.
CT, computed tomography
CTA, computed tomographic angiography (rapid
injection of contrast with imaging in the arterial
Acknowledgements phase)
The support of the Paediatric Radiologists at Starship MCU, micturating cystourethrography
Children's Hospital, Auckland, New Zealand, dur- MRCP, magnetic resonance
ing the preparation of this manuscript is gratefully cholangiopancreatography
acknowledged. Radiation dose estimates were kindly MRI, magnetic resonance imaging
provided by Keith J. Strauss. US, ultrasound or ultrasonography

250
 8
PART

COMMON
ORTHOPAEDIC
PROBLEMS AND
FRACTURES

251
 8.1 Orthopaedic problems
Peter Cundy

See Chapter 12.2 for Bone and joint infections. the opposite foot. This is postural talipes equinovarus
and may be distinguished from true talipes equinovarus,
known as clubfoot deformity (which is rigid and not pas-
sively correctable). Postural talipes equinovarus resolves
Skeletal variations during growth spontaneously with assistance of simple stretches and
Parents can be anxious about whether their child is rarely a cast, if not improved at 6 weeks.
normal. They refer to adult posture, which is different
to that of infants and children. These ‘developmental’ Bow legs
postures can be due to: Bow legs (Fig. 8.1.2) are common up to 2 years of
• intrauterine posture, sometimes described as ‘packaging’ age; the parents will often be concerned that the legs
• developmental variants – not present at birth, but are bowed and the feet turn in. The condition is not
may appear during growth and then disappear caused by bulky nappies, because the bowing is in the
spontaneously. These include the common tibiae. It is a normal developmental process and does
conditions of bow legs, knock knees, flat feet not require treatment apart from parental reassurance.
and in-toeing. These conditions seldom require If the bowing is in one leg only, you should investigate
active treatment but parents do need informed with plain X-rays to exclude pathological causes such
reassurance, which must be based on accurate as a bone dysplasia or growth abnormality.
knowledge of the natural history of these variations
of posture in infants and children.
Knock knees
Intrauterine posture A large proportion of the population between the ages
of 2 and 7 years have knock knees (Fig. 8.1.3). This
The position of the child before birth is normally one condition has a strong tendency to correct itself by the
of flexion. The spine is flexed so that it forms a long age of 7 years and as a rule the only management nec-
curve with a concavity forward, the arms and legs are essary is parental reassurance that improvement will
flexed, and the feet may assume a variety of postures. occur. There is a rare form of knock knees (adolescent
In the newborn the intrauterine posture can be read- tibia vara) that presents in overweight children around
ily reconstructed by ‘folding’ the baby into his or her the age of 12 years and which may require treatment
most comfortable position, and this may indicate any by staple epiphysiodesis.
postural abnormality present.
Two common foot postures are seen in newborns.
Rolling in of ankles
Parents will frequently mention this, especially after it
Talipes calcaneovalgus
has been noticed by a concerned grandparent or shoe-
Many babies are born with the foot turned upwards at fitter. The rolling of the hind foot into valgus is due
the ankle so that the toes lie close to the front of the shin: to physiological joint laxity and requires no treatment.
this is known as talipes calcaneovalgus (Fig. 8.1.1). This The clinician can show the parents how the hind foot
posture can be corrected passively so that the foot can straightens when the child stands up on high tiptoes.
be brought down to a plantigrade position or even into This is the tiptoe test, which also demonstrates devel-
equinus. The condition has a strong tendency to correct opment of the medial longitudinal arch (Fig. 8.1.4).
itself spontaneously over a period of 2–3 months. Orthotics for ‘rolling in’ are not required (see below).

Postural talipes equinovarus Flat feet

Some babies are born with one or both feet in a position Flat feet in children are a frequent cause for parental
of plantar flexion at the ankles, and inversion of the concern. Usually this concern is unwarranted and the
252
remainder of the foot, so that the sole of the foot faces child's foot is normal for age (Fig. 8.1.5). Often parents
 Orthopaedic problems 8.1

Fig. 8.1.1 Calcaneovalgus foot in a newborn – this will correct

spontaneously.

Fig. 8.1.3 A 5-year-old child with pronounced knock knees.

Fig. 8.1.4 If the arch appears when standing on tiptoe, the feet
Fig. 8.1.2 Bow legs in a toddler: a normal phenomenon. are flexible. The flat arch is of no significance and requires no
treatment apart from explanation.

notice that their child's foot appears flat. Sometimes When a child first learns to walk, the stance is usu-
the attendant fitter at the shoe shop may comment ally wide to assist balance, and the feet roll. As the
on the shape of the child's foot. Children usually have child grows and ankle muscles strengthen, the foot
low arches because they are loose-jointed and flexible. gradually develops its mature shape with some medial
The arch flattens when they are standing. However, arch. Flat feet are common in preschoolers and are
the arch can be better seen when the feet are hanging present in over 10% of teenagers. The final shape of
free or the child stands on tiptoes (the tiptoe test; see the foot may also be influenced genetically, in that one
253
Fig. 8.1.4). or both parents may have low arches.
 8.1 COMMON ORTHOPAEDIC PROBLEMS AND FRACTURES

1 year 5 years s­andals, thongs or sneakers have any harmful influ-

ence on the feet. If the child has excessive wear on
the inner side of the sole of the shoes, advise parents
to look for shoes that have a stiffer heel area. Some
children with flexible flat feet are rather hard on their
shoes and this can be dealt with by selecting shoes of
stronger construction. This is usually much less expen-
10 years 40 years sive than elaborate and unnecessary orthotics.

Accessory navicular bone

The child with a prominent accessory navicular may
Fig. 8.1.5 Flexible flat feet are normal in infants and children. have some temporary discomfort, which may be
The arch develops whether the child wears shoes or goes relieved by wearing arch supports for a year or two.
barefoot. Frequently the ossicle either unites with the main navic-
ular bone or just becomes asymptomatic. Excision of
the accessory navicular bone is required only rarely.
Between the ages of 2 and 8 years, parents are often
concerned because a ‘second ankle bone’ appears on
the medial aspect of the foot. They are referring to Curly middle toe
prominence of the navicular bone, which is present
Sometimes the third toe curls inwards under the sec-
in most children who have flat feet. Unless the prom-
ond toe so that the second toe tends to lie above the
inence of this bone is causing symptoms, it can be
level of the first and third toes. Parents generally
ignored.
notice the abnormal posture of the second toe, but it
Children with flat feet generally have some valgus
is the third toe that is the cause of the problem. This
deformity of the heel; when viewed from behind the
can be safely ignored until the child is at least 2 years
heels do not point straight up and down, but tend to
old. Occasionally a flexor tenotomy is required and
slope outwards and downwards. The heels will correct
­provides excellent correction (Fig. 8.1.6).
and even swing into varus during the tiptoe test. This
seldom persists into adult life.
During the first 7 or 8 years of life the majority In-toe gait (pigeon toeing)
of children develop a medial longitudinal arch, but
In-toeing in childhood is common. It may appear
approximately 15% do not. Clearly, the results of
worse when the child is running or tired. It does not
any form of treatment for flat feet are excellent, as
cause arthritis or back problems later in life. It can be
some 85% improve whether or not they are treated.
due to one or more of the following:
Sometimes treatment with shoe inserts (orthotics) or
• inset hips
other forms of arch support/shoe modification are rec-
• internal torsion of the tibia
ommended by therapists. These may satisfy concerned
• metatarsus adductus.
parents but do little, if anything, to correct the ‘flat
foot’ and certainly do not make an arch where one is
not present. Orthotics for flexible flat feet are not nec-
essary for children.
Other treatments, such as splints, massage or special
shoes may be offered but there is little evidence that
these interventions alter the foot for the better.
Shoes
The only essential is that children's shoes should be
roomy enough. Shoes themselves are not necessary to
promote normal foot growth and development; they are
worn only for protection and need not be worn until
activities demand this protection. Boots are no better
than shoes, although parents may prefer boots for tod-
dlers in that they are less likely to fall off or be taken off.
It is not harmful to use ‘handed down’ shoes in good
condition from older children in the family, provided Fig. 8.1.6 Curly middle toes – flexor tenotomy is sometimes
254
they are roomy enough. There is no evidence that needed for severe cases.
 Orthopaedic problems 8.1
Inset hips (persistent femoral neck anteversion) have
internal rotation in excess of the range of external
rotation. The condition is more common in girls and
the feet seem to fly out sideways when running. The
pathology lies in the top of the femur where there is a
normal twist of 30° at birth, which unwinds gradually
by the age of 7 years. In severe cases, when there is a
major cosmetic problem unresolved by about 10 years,
derotation femoral osteotomy can be performed, but
this is rarely required.
Children with inset hips commonly sit between their
feet with their hips in full internal rotation, the knees
flexed and the legs splayed outwards (the ‘W’ position)
(Fig. 8.1.7). This is the only way they can sit comfort-
ably as they cannot externally rotate their hips suf-
ficiently to sit in a cross-legged fashion. It is almost
unknown for an adult to present with a complaint
of in-toeing, which tells us that the natural history is
spontaneous resolution.
Internal tibial torsion (a twist in the shin bone) is
usually due to intrauterine pressure and can ­persist
up to the age of 3 years and then spontaneously Fig. 8.1.8 A 3-year-old child with metatarsus adductus. Note
corrects. the metatarsals and toes curving inwards.

Practical points
Congenital abnormalities
• Bow legs and knock knees are common normal variants. Developmental dysplasia of the hip
• Flexible flat feet are normal and need no treatment.
This condition was previously called congenital
• Examine the child with in-toe gait to decide cause
(metatarsus adductus, tibial torsion or inset hips). ­dislocation of the hip (CDH); however, developmen-
• Provide brochure information to reassure. tal dysplasia of the hip (DDH) is now the preferred
term as it tells us that some of these hip problems
develop after birth. DDH is the most common mus-
culoskeletal abnormality in neonates. The incidence of
Metatarsus adductus (Fig. 8.1.8) is a condition in this ­condition in Australia and North America is 7 per
which the feet are banana-shaped, with the convex- 1000 live births. In some regions of Europe it is more
ity of the banana outwards and the toes directed common.
towards each other. This may be due to intrauterine
pressure; however, if it persists it is called metatar-
sus adductus. It is passively correctable and slowly
Clinical classification
rights itself, especially after walking commences. DDH can be classified clinically as follows:
Very rarely, manipulation and plaster immobilization • stable
is necessary. • subluxatable
• dislocatable
• dislocated, reducible
• dislocated, irreducible
• teratological.

Main risk factors

Some of the important risk factors for DDH (with the
degree of increased risk) are:
• breech presentation (10×)
• female baby (4×) 255
Fig. 8.1.7 ‘W’ sitting is easy for the child with inset hips. • oligohydramnios (4×)
 8.1 COMMON ORTHOPAEDIC PROBLEMS AND FRACTURES

• big baby > 4 kg (2×) any clunk. This is especially felt in premature babies
• first-born baby (2×) and requires repeated examination; frequently the
• family history. hip becomes normal without treatment but it must be
When diagnosed and treated from birth, it is possible ­followed carefully.
to produce a normal hip joint after a few months of Radiography has no place in the diagnosis of
treatment in an abduction splint. However, if the diag- ­developmental dysplasia of the hip in the neonatal
nosis is not made until after the child begins to walk, period (see Chapter 7.1). Ultrasound examination of
the treatment is long and tedious, and often ends with the hips gives the clinician useful information as to the
an imperfect joint. relationship of the femoral head to the acetabulum
and the existence of any acetabular dysplasia during
the first 6 months of life. Be aware that ultrasonog-
Diagnosis in the newborn
raphy has a high false-positive rate in babies under
The Barlow and Ortolani tests are used for diagno- 6 weeks of age and scans should only be performed
sis (Fig. 8.1.9). Every baby should be examined for under 6 weeks either to check whether a hip is ‘in joint’
hip dislocation during the first day of life and again while in a splint or to check a ‘doubtful’ hip when the
at discharge from the maternity ward, and at ages 6 Barlow or Ortolani tests are equivocal. Over the age
weeks, 3 months, 6 months and 1 year. The baby must of 4 months, the degree of ossification of the upper
be relaxed for the examination to be meaningful. If femur and acetabulum enables X-rays to be of value.
the baby is crying, a bottle or pacifier is offered or the If the dislocatable or dislocated hip is held in a flexed
baby is examined later when relaxed. With the legs and abducted position for 8–12 weeks, it will usually
extended, any asymmetry of the legs or thigh creases develop normally. The Pavlik harness or Denis Browne
is noted. The examiner then holds the leg to be exam- splint is used to maintain this position. Subluxatable
ined. With the knee flexed, the thumb is placed over hips can be observed with a later ultrasound examina-
the lesser trochanter and the middle finger over the tion after 6 weeks or radiography at 4 months. The use
greater trochanter. The pelvis is steadied by the other of double nappies is not recommended.
hand and the flexed thigh is abducted and adducted, All abnormal or treated hips require follow-up until
and any clunk or jerk is noted. normal hip morphology is ascertained.
It is very important to note that frequently a fine
Teratological hip
click can be felt in the hip joint without any laxity or
If there is considerable restriction of abduction in flex-
abnormal movement. Sometimes the click comes from
ion and the ‘clunk’ sign cannot be elicited, this u
­ sually
the knee joint. This is very common and is of no sig-
means that the hips are dislocated and irreducible.
nificance. Also, it is common in the first 2 or 3 days of
These hips require paediatric orthopaedic ­ surgical
life for the hip to be felt to subluxate smoothly without
assessment and probably operative reduction at a later
date.
Swaddling/wrapping
This has been popularized recently to help a baby
settle. However, swaddling infants with the hips and
knees in an extended position increases the risk of hip
dysplasia and dislocation. Hips should be positioned
in flexion and abduction, knees should be maintained
in slight flexion, and free movement in the direction
A
of hip flexion and abduction may have some benefit.

Diagnosis in the older infant

The Barlow and Ortolani tests become more difficult
to elicit after 3 months of age. In the abnormal hip, a
new sign of limited abduction appears due to tight-
ness of the adductor tendons. This sign is not diagnos-
tic but an X-ray is indicated when there is asymmetry
in the range of the abduction of the hips or when the
B range of abduction of both hips is inappropriate for
Fig. 8.1.9 (A) The Barlow test is positive if the hip can be the age of the child. In the first year of life the range
manually dislocated. (B) The Ortolani test is positive if the hip is of abduction in flexion is usually 60–90°; this arc
256
lying in a dislocated position and is manually reducible. ­normally lessens with age.
 Orthopaedic problems 8.1
The physical signs of late presenting dislocation include:
• higher greater trochanter
• wide perineum
• asymmetrical gluteal buttock crease
• short leg
• abnormal gait.
If a dislocation presents after walking age, an open
reduction operation is usually required and these hips
are rarely normal, with an increased risk of early hip
osteoarthritis. Hence early diagnosis and treatment of
DDH is the best way to prevent hip arthritis.

Practical points

• All babies should be assumed to have dislocated hips until Fig. 8.1.10 Club foot deformity is rigid and cannot be corrected
proven otherwise. passively.
• Re-examine babies’ hips at every well-baby check.
• If in doubt, do an ultrasound examination when 6 weeks opposite side. The face on that side is smaller and the
of age.
• Ensure that the sonographer is experienced in babies’
eye is lower on the side of the tight sternomastoid. Most
hips. patients will have presented in the first few months of
• Swaddling/wrapping increases the risk of hip dysplasia. life with a sternomastoid tumour – a palpable lump in
the middle of the sternomastoid muscle.
The cause of this condition is unknown. Treatment in
Congenital talipes equinovarus (club foot)
the first 6 months of life with a stretching programme
Congenital talipes equinovarus is the commonest supervised by a physiotherapist is usually effective, with
­congenital abnormality of the foot, occurring in about full resolution. If the condition does not resolve, surgi-
1 per 1000 live births. The male : female ratio is 2 : 1. cal correction at 2–4 years of age is required. At opera-
The condition is bilateral in 40% of cases and there is a tion, the muscle is divided transversely and the corrected
2% chance of a subsequent child being affected if there position maintained by the use of a collar.
is a positive family history. Alexander the Great (354 bc) is reported to have had
The deformity is a combination of: this condition, with statues showing a persistent head tilt.
• equinus of the hind foot
• varus of the hind foot
Trigger thumb
• adductus of the midfoot
• cavus of the medial arch. This presents with the parents suddenly noticing that
The degree of each deformity is variable, but all are their 1–3-year-old child has a bent thumb. At this age
rigid and are incapable of being fully corrected man- children start to handle objects and the thumb defor-
ually (Fig. 8.1.10). This is distinct from the ‘postural mity becomes obvious. The thumb is bent about 30° at
club foot’, which is due to intrauterine pressure and is the interphalangeal joint and cannot be straightened
fully passively correctable and resolves without treat- passively (Fig. 8.1.11).
ment, as described above. It is due to a constriction in the flexor tendon sheath
Club feet should start treatment in the first week and a nodule on the tendon itself. The cause is unknown
of life. Treatment involves serial plaster casting by and the treatment is surgical release of the tendon
Ponseti method for 6 weeks, and then Achilles tenot- sheath under general anaesthesia. Surgery should be
omy followed by a cast for a further 3 weeks followed performed around the age of 2 years to p ­ revent perma-
by ‘boots and bars’ until the age of 4 years. Sometimes nent joint changes.
later tendon surgery is required.
Scoliosis
Congenital muscular torticollis
Scoliosis (lateral curvature of the spine) is most
Torticollis usually presents in the first few months of life commonly seen in its adolescent idiopathic form
when some tilt of the head and limited l­ateral ­flexion (Fig. 8.1.12). However, there are other forms of scolio-
is noted. Sometimes it can remain undetected for 1–2 sis. The common ones are:
years. The head is held with a lateral flexion toward • Congenital – vertebral anomalies are responsible for 257
the shoulder and with rotation of the face towards the the curvature. Usually the deformity is minor and
 8.1 COMMON ORTHOPAEDIC PROBLEMS AND FRACTURES

• early-onset idiopathic scoliosis – a curve diagnosed

under the age of 10 years.

Adolescent idiopathic scoliosis

Some 90% of cases are in girls and the scoliosis pro-
gresses during the rapid growth spurt years.
For diagnosis, the child must remove all clothing
above the waist and stand with the back facing the
examiner (Fig. 8.1.13). In all but very minor curves, the
deformity will be readily apparent. Signs to look for are:
• uneven shoulders
• waist (flank) asymmetry
• a unilateral rib prominence when the child bends
forward (Fig. 8.1.14).
If the curve disappears completely when the child bends
forward, it can be labelled ‘postural’ and treatment is
not required. Should a rib hump become ­visible (due
to rotation of the vertebrae and consequent rib defor-
mity; see Fig. 8.1.14) the curve is labelled ‘structural’.
There are three main treatment options:
• observation for curves of less than 20°
• bracing for curves of 20–40°
• surgery for curves greater than 50° (due to high risk
Fig. 8.1.11 Trigger thumb (left hand) showing 30° flexion of continued progression in adult life).
deformity at the interphalangeal joint. Palpate a nodule at the
These are broad guidelines only. Larger curves may
level of the metacarpophalangeal joint.
not be treated if proven to be non-progressive in a skel-
etally mature patient. There is no scientific evidence
that exercises or physiotherapy/chiropractic t­ reatments
alter the natural history of the curve.
T4

L1

Fig. 8.1.12 Adolescent idiopathic scoliosis; the curve is usually

convex to the right side.

may be present at birth or develop during growth.

In only 5% is the deformity progressive.
• Neuromuscular – such as Duchenne muscular
dystrophy, cerebral palsy or spina bifida.
• Idiopathic – mostly adolescent idiopathic scoliosis.
Sometimes in younger children as:
• infantile idiopathic scoliosis – most commonly
seen in males and may be seen in association
with DDH and other congenital anomalies. The
258 natural history is for the curve to resolve in a high
proportion of cases. Fig. 8.1.13 Adolescent scoliosis in a male; 90% occur in females.
 Orthopaedic problems 8.1

Fig. 8.1.14 On flexion, a rib hump becomes readily visible.

Osteochondroses (osteochondritis)
Fig. 8.1.15 Osgood–Schlatter's condition presents with painful
These conditions involve the epiphysis. The pathology enlarged tibial tubercles.
consists of localized areas of ischaemic bone necrosis
and sometimes oedema of adjacent soft tissues. The
tendency is for healing to occur but this is dependent and can be concerned about a sinister cause such
on a number of factors, including age, the site of the as malignancy. The common age of presentation is
lesion, its blood supply and perhaps the method of 10–14 years and the natural history is resolution over
treatment. The aetiology is uncertain. a 12–18-month period. Warn the parents that a lump
The common osteochondroses are: will remain permanently but that it will be smaller
• Sever's condition of the heel: 10–12 years than when first seen. Normal activities within the
• Osgood–Schlatter's condition of the tibial tubercle: limits of the child's c­omfort are allowed. The tibial
10–14 years tubercle does not detach or pull off. Radiography is
• Chondromalacia patellae: 10–20 years not ­necessary for diagnosis. Simple measures such
• Slipped capital femoral epiphysis of the hip: 10–15 as quadriceps stretches and massage with a liniment
years can provide some symptomatic relief. Rarely, a small
• Scheuermann's condition of the thoracic spine: loose ossicle remains and can be excised after the child
12–16 years. reaches 15 years.

Sever's condition
Chondromalacia patellae
This is an apophysitis of the os calcis (heel) bone where
the Achilles tendon attaches. It is seen in children aged This condition has a number of other names, including:
between 10 and 12 years. It resolves over 12 months • anterior knee pain
and is best treated by reassurance, calf stretches and • lateral pressure syndrome
sometimes a simple rubber heel raise. Sport is allowed • maltracking of the patella.
within the child's level of comfort. It is particularly common over the age of 10 years. It
is characterized by pain in the knee after activities that
involve flexing the knee and quadriceps contraction.
Osgood–Schlatter's condition
The child complains of aching around the patella dur-
This is an apophysitis of the tibial tubercle and pres- ing or especially after exercise. Stairs precipitate dis-
ents with pain and swelling (Fig. 8.1.15). Children comfort, particularly walking downstairs. It is more 259
notice the pain and then an adult sees the swelling common in adolescent females, both in those who
 8.1 COMMON ORTHOPAEDIC PROBLEMS AND FRACTURES

enjoy sport and in those who wish to avoid physical

education lessons at school.
Clinically there is little to find, although occasion-
ally there is some patellofemoral crepitus and rarely an
effusion in the knee. Ensure that the hips are normal
and the symptoms do not relate to a slipped hip. The
diagnosis is based upon obtaining the relevant history.
Treatment involves education of the child and con-
cerned parents (explain that the ‘back of the knee cap
is soft’ and will toughen up with time), some limitation
of flexed knee/jumping activities, quadriceps stretches,
elastic knee support and tincture of time. Frequently,
children tolerate their symptoms and continue with their
sport. The natural history suggests spontaneous resolu-
tion of symptoms over 1–2 years in 90% of patients.
Some children are point tender at the inferior pole Fig. 8.1.16 Slipped capital femoral epiphysis often presents
of patella (apophysis) and have a condition called with thigh or knee pain – always exclude hip pathology when a
child presents with knee/thigh pain.
Jumper's knee. Treatment is massage with anti-­
inflammatory gels, quadriceps stretches and the expec-
tation that symptoms will resolve over 18 months. Scheuermann's condition
The adolescent is noted to have an increased kypho-
Slipped capital femoral epiphysis sis (round back) and complains of mid to low tho-
This is primarily a disorder of adolescents between racic back pain. The physis of the vertebral bodies is
the ages of 10 and 15 years. Approximately 40% of involved. Usually the condition is seen in the thoracic
cases are bilateral. Its aetiology is unknown but recent vertebrae but occasionally in the lumbar spine. Most
reports suggest that hormonal factors may be of merely require observation, encouragement to exercise
importance. Most cases present with pain and limp; and stand straight, and to be instructed in exercises by
pain is often referred to the knee and it is important to a physiotherapist. Some progress rapidly and require
consider hip radiography when children present with management in a brace. Rarely is surgery required.
distal thigh or knee pain. The condition is frequently ‘overdiagnosed’ in r­ adiology
Types of slip: reports and causes anxiety in families, e­specially when
• Acute – the child feels the hip ‘collapse’ and is the radiological changes are described as Scheuermann's
unable to walk. This is uncommon and needs ‘disease’. The term ‘condition’ is preferred.
urgent treatment.
• Acute on chronic – the child has months of
discomfort and then a worsening over a few weeks
with a pronounced limp.
Injuries in infancy and childhood
• Chronic – many months of thigh ache and a mild limp. Children are susceptible to injury because of their
Examination reveals limited internal rotation of the carefree play habits, and skeletal injuries are common.
hip compared with the other side and some joint irri- For practical purposes, sprains do not occur in chil-
tability. The diagnosis is confirmed radiologically, dren: ‘children break bones and adults tear ligaments’.
­especially with a frog lateral view (Fig. 8.1.16). Post-trauma pain, swelling and loss of function are
All cases of slipped capital femoral epiphysis require nearly always the result of a fracture or growth plate
surgery with screw fixation across the physis to prevent separation; therefore X-rays are obligatory.
further slip. Dislocations are rare in childhood, although shoul-
der and patella dislocations are seen in adolescents.
The type of injury that may produce dislocation of an
adult joint usually gives rise to a fracture or growth
Practical points
plate separation in a child.
Fractures are the commonest type of skeletal injury
• Knee/distal thigh pain often comes from the hip. in childhood; they generally unite in less than half the
• Always think of a slipped hip in adolescents with a limp or time the equivalent injury would take to heal in an
knee/thigh pain.
• Know the various apophysitis pains in children. adult, and non-union is almost unknown. Childhood
260 • Anterior knee pain is common in teenagers. fractures may unite in a position of deformity, with
the deformity correcting itself spontaneously over
 Orthopaedic problems 8.1
the ensuing 6–12 months, especially if the fracture is
near the ends of the bone where there is most growth.
Some shortening of bones also can be expected to cor-
rect spontaneously due to growth stimulation of the
­physis from prolonged increased vascularity to heal
the fracture.
Child abuse is an important cause of childhood
injury; it is important because, if unrecognized, fur-
ther abuse is likely to occur and might even be fatal.
When assessing a child after trauma, ensure that you
check the whole child, using the principles of emer-
gency management of severe trauma (EMST), and
look for hidden injuries.

Clavicle fractures
These are the most common fractures seen in children.
The fracture is usually midshaft and of greenstick
type. Complete fractures with overlap of the ends are
seen in older children and unite well. It is important
to warn the parents at the beginning that they must
expect to see a large lump develop: this is healing cal-
lus, which will remodel over 6–12 months without any
cosmetic or functional deficit.
Treatment is with a triangular sling inside the clothes
to support the elbow, regular analgesia and rest. The
clavicle will start to join within a week and the sling Fig. 8.1.17 Forearm fractures usually have dorsal tilt.
can usually be discarded by 4 weeks.
• Plum-coloured (venous congestion)
Forearm fractures
• Pulseless.
Approximately 30% of children's fractures involve the
Children's bones can break in several ways, namely: growth plate (physis). If the physis suffers permanent
• bend damage, the bone can end up:
• buckle • short (all growth of physis stops), or
• greenstick • angulated (one side of the physis stops growing).
• complete, with/without displacement and overlap. The Salter–Harris classification is used for growth
Most forearm fractures are of the buckle or green- plate fractures (Fig. 8.1.18). Type I is often seen in the
stick variety, and if there is minimal tilt or deformity distal fibula as the childhood equivalent of the adult
they can be treated in an above-elbow cast for 5 weeks. ankle sprain. Type II is the commonest variety and
It is important to perform check radiography after frequent in the distal radius. Types III and IV have a
7–10 days to ensure that the fracture has not tilted much higher risk of growth disturbance and usually
more. If it has tilted to an unacceptable position, the require accurate reduction and internal fixation to
fracture can still undergo a closed reduction before minimize the risk of growth arrest.
firm union occurs.
Fractures with visible deformity or significant tilt/
Supracondylar fracture of the humerus
displacement (Fig. 8.1.17) require closed reduction
and a similar time of cast immobilization. This fracture is often seen in children aged 4–10 years
Ensure that you complete and document a neuro- after a fall from a height, such as from monkey bars,
vascular examination of the limb initially. Provide or when running. Usually caused by hyperextension of
the parents with written instructions for neurovascu- the elbow joint with the olecranon acting as a fulcrum
lar observations at home and with emergency c­ ontact lever to cause the fracture.
details if excessive swelling or symptoms develop. Neuropraxia of the radial, median or ulna nerve is
Look for the five Ps: common. Occasionally displaced fractures cause dam-
• Pain in excess of that expected age to the brachial artery. Neurovascular assessment is
• Paraesthesia (compression of the sensory nerves) mandatory. Minimally tilted fractures can be treated in 261
• Paleness of the fingers a collar and cuff under the clothes for the first 2 weeks,
 8.1 COMMON ORTHOPAEDIC PROBLEMS AND FRACTURES

E E Practical points
I II
M M Rules of 2 for fractures
• 2 views (anteroposterior and lateral X-ray)
• 2 joints (X-ray the joint above and joint below to exclude
dislocation)
• 2 joints (immobilize the joint above and below the fracture
in a cast)
• 2 times (ensure the fracture has not shifted after 1 week)
• 2 sides (you can X-ray the contralateral side for
E E
comparison if needed)
III
M M

IV

Toddler fracture of the tibia

Fig. 8.1.18 Salter–Harris fracture: type I, the fracture passes This distal shaft fracture may not be visible on initial
directly through the physis; type II, a corner of the metaphysis (M) radiographs and often perplexes clinicians faced with
is broken off; type III, the fracture passes through the physis and a toddler who refuses to walk for days after a seem-
the epiphysis (E); type IV, the fracture passes through the epiphysis ingly minor trauma. The fracture can be diagnosed
and the metaphysis, causing a high risk of growth arrest.
clinically by twisting the good leg first and then noting
the cry or facial expression when twisting the affected
then outside the clothes for a further 2 weeks. Warn side. Warn the parents what you are going to do first!
the parents to expect elbow stiffness, especially loss of Treat the fracture in an above-knee cast and allow
elbow extension for several months. weight-bearing as the child dictates. Most will walk
Displaced fractures require accurate reduction to after 1 week in the cast, and the cast can be removed
avoid later deformity. Often the fracture will be held with at 3 weeks. Warn the parents to expect a limp for 1–2
K wires, which are removed at 4 weeks (Fig. 8.1.19). months; the limp will resolve spontaneously.

A B
262
Fig. 8.1.19 (A) Supracondylar fracture of the humerus may have a nerve injury. (B) Displaced fractures require reduction and K-wire fixation.
 Orthopaedic problems 8.1
Pulled elbow
The history is typical in all cases. The pathology is
The patient is usually a child aged 1–4 years who has believed to be a minor stretch of the annular ligament
been pulled along or up by the hand or treated to a around the radial head. It is treated by forced full flex-
‘whizzy’. The child presents with ‘pseudo-paralysis’ of ion and simultaneous full supination of the elbow.
the upper limb, with the limb held by the side with the Sometimes a satisfying click can be felt. A collar and
elbow extended and pronated. (Note that most elbow cuff sling in flexion is worn overnight with the expecta-
fractures present differently, with the elbow flexed and tion of ready return to full function. Warn parents that it
held across the body.) can recur and that it is best to avoid pulling on the hand.

263
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 9
PART

COMMON
PAEDIATRIC
SURGICAL
PROBLEMS

265
 9.1 Surgical conditions
in older children
Sebastian K. King, Spencer W. Beasley

meatus is not visible. Phimosis must be distinguished

The penis and foreskin from the normal adherence of the foreskin to the
The glans of the uncircumcised penis is protected by a glans. In most boys, phimosis can be treated by topical
layer of loose skin called the foreskin or prepuce. The application of steroid ointment (e.g. betamethasone
amount of foreskin present varies widely among boys. valerate ointment) to the tight, shiny part of the par-
At birth, and for many years afterwards, it is normal tially retracted foreskin. This usually obviates the need
for part or all of the undersurface of the foreskin to for circumcision. However, marked previous inflam-
be adherent to the glans. This adherence slowly sep- mation, infection, skin splitting and balanitis xerot-
arates during childhood. Forcible retraction of the ica obliterans (BXO) can lead to marked scarring of
foreskin before it is ready can damage the glans and the foreskin and phimosis, and in many of these chil-
may cause secondary phimosis. Therefore, the fore- dren the only reasonable treatment is circumcision.
skin should not be retracted forcibly. Spontaneous Sometimes the severity of phimosis is such that there
separation of these adhesions is normally complete is ballooning of the foreskin on micturition, and on
by puberty. rare occasions it may even cause urinary retention with
a distended bladder. A degree of phimosis is common
in infancy but tends to resolve spontaneously in the
Smegma first few years of life, and is not considered abnormal
in this age group.
Smegma is formed from desquamated cells and
­accumulates beneath the adherent foreskin. It appears
as asymmetrical accumulations of yellow-tinged mat­ Paraphimosis
erial, predominantly in the coronal groove beneath the
Paraphimosis occurs when a mildly phimotic fore-
foreskin (Fig. 9.1.1). There may be sufficient smegma
skin has been retracted over the glans and has become
to produce a noticeable swelling, which may be
stuck behind the coronal groove, causing oedema of
­misdiagnosed as a dermoid cyst or tumour. It is often
itself and the glans (Fig. 9.1.3). It is a painful and pro-
misinterpreted as being mid-shaft because a small
gressive process. Treatment involves gentle manipu-
child's coronal groove may be a long way from the tip
lation of the foreskin forwards; this may require a
of the foreskin. Smegma is normal, and is released
general anaesthetic. Circumcision is not performed at
spontaneously as the foreskin separates from the glans.
this time, but a few children may need it subsequently
When it is released, it may be associated with some
if the phimosis does not respond to topical application
redness and irritation of the foreskin for a day or so;
of steroid ointment.
this, too, is a normal process.

Hypospadias
Balanitis
It is important to recognize hypospadias when it
Infection can develop beneath the foreskin and, if is present (Fig. 9.1.4). The dorsal foreskin looks
severe, pus may appear from the end of the foreskin. square and hangs off the penis, whereas the ventral
Balanitis is often associated with phimosis. Infection foreskin is deficient, and the shaft of the penis is
may cause considerable redness and swelling of the bent ventrally. The two main problems in hypospa-
penile shaft, necessitating treatment with either ­topical dias are:
or oral antibiotics. • the location of the urethra (which can be found on
the ventral side of the shaft of the penis, proximal
to its correct position)
Phimosis
• chordee (ventral angulation of the shaft and
In phimosis the opening at the tip of the foreskin has glans) – correction of chordee to straighten the
narrowed down to such a degree that the foreskin penis is required to allow later successful sexual
266
­cannot be retracted (Fig. 9.1.2). The external urethral function. The operation is usually performed as
 Surgical conditions in older children 9.1

Fig. 9.1.2 In phimosis, the foreskin is narrowed and cannot be

A retracted.

Fig. 9.1.1 (A) Accumulation of smegma beneath the normal Fig. 9.1.3 In paraphimosis, the foreskin is stuck behind the
foreskin. The swellings caused by the smegma are in the region coronal groove.
of the coronal groove. (B) On retraction, smegma appears as
accumulations of material beneath a foreskin that has not yet
separated from the glans.
Circumcision
The indications for circumcision remain controver-
a single-stage procedure at 9–12 months of age, sial. Phimosis resulting from balanitis xerotica oblit-
often as day surgery. erans (see above) is the only undisputed indication.
Circumcision is absolutely contraindicated in hypo- In many countries, circumcision has been abandoned
spadias because the skin of the foreskin is used dur- in the neonatal period because of its relatively high
ing the hypospadias repair. Severe hypospadias may complication rate. Apart from the risk of septicae-
be indicative of an intersex abnormality. For exam- mia and meningitis when performed in the relatively
ple, when there is penoscrotal hypospadias and a bifid immunologically immature neonate, there are a num-
scrotum, the scrotum should be examined carefully for ber of problems that may occur during circumcision
testes, as some of these children may be females with at any age. These include removal of too much or too
congenital adrenal hyperplasia; the labioscrotal folds little foreskin, postoperative bleeding and infection.
are labia rather than scrota, and the presumed urethral Haemorrhage postoperatively occasionally requires
opening may in fact be the entrance to the vagina (see surgical reintervention. The most troublesome and
267
Chapter 19.3). common complication of circumcision is abrasion and
 9.1 COMMON PAEDIATRIC SURGICAL PROBLEMS

a­bdominal wall defects in which ectopia vesicae

­(bladder ­exstrophy) and cloacal exstrophy are the most
severe forms. Boys with epispadias are often inconti-
nent of urine because the sphincter of the bladder
neck is also deficient.

Clinical example

James was a 7-year-old boy who presented

following two episodes of balanitis. He also
complained of discomfort on micturition.
Examination revealed a tight foreskin that could
not be retracted; the urethral meatus could not be seen. After
1 month of topical application of betamethasone ointment
four times a day to the tight part of the foreskin, he was able
to retract it fully. Circumcision was not necessary.

The inguinoscrotal region

Inguinal hernia
After the testis has descended into the scrotum dur-
ing the seventh month of pregnancy, the canal down
which it migrates, the processus vaginalis, should oblit-
erate. Failure of obliteration of the processus vagina-
A lis may produce an inguinal hernia, a hydrocele or an
encysted hydrocele of the cord.
A widely patent proximal processus vaginalis allows
bowel (and, in girls, the ovary as well) to enter the
inguinal canal, producing a reducible lump in the groin
called an indirect inguinal hernia (Fig. 9.1.5). This
occurs in about 2% of infant boys but is less frequent
in girls. The greatest incidence is in the first year of life.
The usual presentation is that of an intermittent
swelling, overlying the external inguinal ring, that has
been noticed by a parent. At times it may appear to
cause discomfort. It is most likely to be obvious during
an episode of crying or straining, and in infants may
be seen during nappy changes. Inguinal herniae should
B be repaired as soon as practicable.
Strangulation of inguinal herniae is common, par-
Fig. 9.1.4 In hypospadias, the ventral shaft of the penis is ticularly during the first 6 months of life. Strangulation
angulated and shortened (chordee), the urethral meatus is can be recognized when the groin swelling becomes
ventrally placed and the foreskin is deficient on the underside.
irreducible. If left untreated, a strangulated hernia may
(A) Ventral aspect; (B) lateral aspect.
damage the trapped bowel and, occasionally, by com-
ulceration of the sensitive glans, particularly near the pressing the testicular vessels, may lead to testicular
urethral meatus. As the meatal ulceration heals it may atrophy. For this reason, an immediate attempt should
produce meatal stenosis and require a meatotomy to be made to reduce the hernia manually. This is done
re-establish an adequate urinary stream. by first manoeuvring the hernial contents through the
external inguinal ring, and then reducing them along
the line of the inguinal canal. Fortunately, most her-
Epispadias
niae that become stuck can be reduced manually; the
Epispadias is a very rare condition in which the hernia can then be repaired as an elective procedure
­urethra opens on to the dorsal aspect of the base of within a few days. This is best done in a s­pecialist
268
the penis. Epispadias is part of a spectrum of lower ­paediatric surgical centre.
 Surgical conditions in older children 9.1
felt within it. The upper limit of the hydrocele can be
­ emonstrated distal to the external inguinal ring, dis-
d
tinguishing it from an inguinal hernia where the swell-
ing extends through the external inguinal ring. There
is no impulse on crying or straining.
Hydroceles are common in the first few months of
life, do not cause discomfort and usually d ­ isappear
spontaneously within a year. Surgery involves an
inguinal herniotomy and is indicated only if the hydro-
cele persists beyond 2 years of age.

Undescended testis
Undescended testis (or cryptorchidism) is a term used
to describe the testis that does not reside spontane-
ously in the scrotum. Cryptorchidism occurs in about
2% of boys, being more common in premature infants.
Spontaneous descent of the testis is unlikely beyond
3 months post-term. Cryptorchidism is important to
Fig. 9.1.5 Large bilateral inguinal herniae. detect because it can result in reduced fertility if left
untreated. It is suspected that the higher tempera-
ture to which an undescended testis is subject impairs
Hydrocele
spermatogenesis.
A hydrocele presents as a painless cystic swelling The diagnosis is made by examining the inguino-
around the testis in the scrotum (Fig. 9.1.6). It con- scrotal region. Normally, the testis should be found
tains peritoneal fluid that has tracked down a nar- within the scrotal sac. In cryptorchidism the scrotum
row but patent processus vaginalis. It transilluminates looks empty (Fig. 9.1.7). The testis is ‘milked’ down
brilliantly. When the hydrocele is lax, the testis can be the line of the inguinal canal towards the scrotum with

269
Fig. 9.1.6 Right hydrocele. Fig. 9.1.7 Right undescended testis.
 9.1 COMMON PAEDIATRIC SURGICAL PROBLEMS

the left hand and pulled gently towards the scrotum

with the right hand. If the testis cannot be brought
into the scrotum, or will not remain there spontane-
ously, it is considered undescended.
Clinically, it may be difficult to distinguish a retrac-
tile testis from an undescended testis. In most normal
boys the testis resides in the bottom of the scrotum,
but the cremasteric reflex, which is prominent during
mid-childhood, may cause it to move upwards, some-
times completely out of the scrotum. A retractile tes-
tis found outside the scrotum initially can be brought
down into the normal position and should stay there
spontaneously, at least until the cremasteric reflex is
stimulated (Table 9.1.1). An undescended testis will not
stay in the scrotum spontaneously and usually cannot
even be coerced beyond the neck of the scrotum. It is
often smaller than the normal testis on the other side.
Undescended testes should be brought down into Fig. 9.1.8 An acutely painful scrotum in a child is most likely to
the scrotum surgically between 9 and 12 months of age. be caused by torsion of an appendix testis or torsion of the testis.
Unfortunately, in many boys the diagnosis is not made
until the child is older. The later the testis is brought
necrosis has already occurred) and the testis may be
down, the more likely it is that there will be damage
lying high within the scrotum. In older boys the pain
to spermatogenesis. Orchidopexy is performed as a
radiates to the ipsilateral iliac fossa and may be associ-
day case procedure. In general, the results are excel-
ated with nausea and vomiting, producing symptoms
lent when the procedure is performed by a specialist
similar to those of appendicitis. This association high-
paediatric surgeon.
lights the importance of always examining the scrotum
in boys presenting with lower abdominal pain.
The acutely painful scrotum
There are a number of conditions that cause an acutely Treatment
painful or enlarged scrotum (Fig. 9.1.8). Whilst torsion Urgent surgical exploration of the scrotum is required
of a testicular appendage is the most common, torsion to untwist the testis and epididymis and to suture
of the testis itself is the most important (Table 9.1.2). both testes to prevent subsequent torsion. A com-
In both conditions the boy complains of severe pain in pletely necrotic testis should be removed. A torted
the scrotum. In the early stages of torsion of a testicu- and infarcted testicular appendix should be removed.
lar appendage, a blue–black ‘pea-sized’ ­swelling which In this situation the testis should be checked to make
is extremely tender to touch may be seen through the sure that it has not twisted but otherwise it requires no
skin of the scrotum near the upper pole of the testis. treatment.
Palpation of the testis itself causes no or little discom-
fort. Later, a reactive hydrocele develops, the tenderness
Other causes of scrotal pathology
becomes more generalized and the ­clinical features may
make it difficult to distinguish from ­torsion of the testis. Epididymo-orchitis is unusual in children; it is most
If torsion of the testis has occurred, both the t­ estis often seen during the first year of life, where it may
and the epididymis are exquisitely tender (unless ­signify an underlying structural abnormality of the

Table 9.1.1 Comparison of undescended and retractile testes

Feature Undescended testis Retractile testis

Can be brought fully to bottom of scrotum No Yes

Remains in scrotum spontaneously for a period before retracting No Yes

Resides spontaneously in scrotum at times No Yes

270 Testicular size Normal or small Normal

 Surgical conditions in older children 9.1
Table 9.1.2 Causes of an acutely painful scrotum

Condition Comment Frequency

Torsion of testicular appendix Peak age 11 years > 75%

Unilateral tenderness

Torsion of testis Peaks in neonatal and adolescent age groups 20%

Surgical emergency

Epididymo-orchitis Usually in infancy Rare

Association with urinary tract abnormalities

Idiopathic scrotal oedema Usually in young child Rare

Bilateral oedema
Testes not tender

genitourinary tract. For this reason investigation

Table 9.1.3 Abnormalities of the umbilicus
involves renal ultrasonography and micturating cys-
tourethrography. Examination of the urine may show Abnormality Comment
leukocytes and bacteria. Mumps orchitis is extremely
Exomphalos See Chapter 11.5
rare prior to puberty. In idiopathic scrotal oedema
there is painless boggy oedema of the whole scrotum Gastroschisis See Chapter 11.5
and the testes are completely non-tender. Testicular
malignancy is occasionally seen in leukaemia and Umbilical hernia Common (most resolve)
­lymphoma, or with a primary testicular neoplasm. Asymptomatic
Skin covered

Umbilical sepsis Neonatal

(‘omphalitis’) Serious condition
Abnormalities of the umbilicus
Umbilical granuloma Common
The umbilical cord desiccates and separates ­several
Often pedunculated
days after birth, allowing the umbilical ring to close. Treat with silver nitrate
Sometimes the stump of the cord may become
infected, the umbilical ring may not close, or there Ectopic bowel mucosa Treat with silver nitrate
may be r­ emnants of the embryonic channels that pass
through the umbilicus before birth (Table 9.1.3). Patent vitellointestinal duct Sinus opening at umbilicus
Communication with ileum
Discharges faecal fluid
Umbilical hernia and gas

Failure of the umbilical ring to close after birth p

­ roduces Patent urachus Communication with bladder
an umbilical hernia (Fig. 9.1.9). Umbilical herniae are Discharges urine
common in neonates but most close spontaneously in
the first year of life. The skin overlying the umbilical
hernia never ruptures and strangulation of the con- of ­granulation tissue in the umbilicus, accompanied
tents is virtually unknown. Parents may be concerned by a seropurulent discharge. If it has a definite stalk
about the swelling, which will become tense when the it can be ligated without anaesthesia, but most often
infant cries or strains. Umbilical herniae normally do it is treated by topical application of silver nitrate.
not cause pain. If the hernia is still present after the age Ectopic bowel mucosa has a similar appearance but
of 3 years, it can be repaired as a day surgical procedure. has a smooth, red, glistening surface and discharges
mucus. Topical application of silver nitrate in patients
with ectopic bowel mucosa is typically less effective
Discharge from the umbilicus
than in those with an umbilical granuloma.
Discharge from the umbilicus may be pus, mucus, Persistence of part or all of the vitellointestinal
­faeces or urine. An umbilical granuloma is a common (omphalomesenteric) duct produces one of a number
lesion that first becomes evident after separation of of abnormalities, which usually present in early infancy 271
the umbilical cord. There is a small accumulation but may not be evident for some years. Complete
 9.1 COMMON PAEDIATRIC SURGICAL PROBLEMS

days. Examination of the anal margin shows a split in

the epithelium anteriorly or posteriorly in the midline.
Occasionally an anal fissure may occur in an older
child, and is usually related to constipation. The child
experiences severe pain on defaecation and becomes
reluctant to defaecate, further worsening the constipa-
tion. Treatment is directed at overcoming the underly-
ing ­constipation. A stool softener and lubricant (e.g.
paraffin oil) may be helpful. A chronic indolent, often
non-painful, fissure away from the midline may indicate
inflammatory bowel disease, such as Crohn's disease.

Perianal abscess
This is most likely to occur in the first year of life from
infection of an anal gland. The abscess points super-
ficially, a centimetre or two from the anal canal. The
abscess should be drained and the fistula between the
abscess and the anal canal laid open during the same
operation to reduce the likelihood of recurrence.

Rectal prolapse
Rectal prolapse tends to occur in the second and third
years of life in otherwise normal children. The rectum
prolapses during defaecation and returns spontaneously
afterwards. In some, manual reduction is required. The
prolapsed mucosa may become congested and bleed,
Fig. 9.1.9 Umbilical hernia. but causes little discomfort. Clinically, it needs to be
distinguished from prolapse of a benign rectal polyp
patency of the duct allows ileal fluid and air to discharge (a benign hamartomatous lesion seen in children) and
from the umbilicus. Persistence of one part produces a the apex of an intussusception (the child would have
sinus or cyst, which may become infected to form an other symptoms of intussusception). The passage of
abscess and may discharge pus. A vitellointestinal band time, and treatment of any underlying constipation, is
attaching the ileum to the deep surface of the umbilicus all that is required in the majority of toddlers. Rarely,
may cause intestinal obstruction. A Meckel's diverticu- for persistent cases, a sclerosant is injected into the sub-
lum represents persistence of the ileal part of the duct. mucosal plane of the rectum.
Vitellointestinal duct remnants are excised. In a few patients there is an underlying organic cause
Urinary discharge from the umbilicus suggests a for the rectal prolapse. Usually the reason is obvious,
persistent communication with the bladder in the form as in paralysis of anal sphincters in spina bifida and
of a patent urachus. Sometimes it may produce a cystic sacral agenesis, undernourished hypotonic infants,
mass or abscess in the midline just below the umbili- bladder exstrophy, cloacal exstrophy, following surgery
cus. Urachal remnants should be excised. for imperforate anus, or malabsorption.

The neck
The anus and perineum
Lesions of the neck fall into two broad groups: devel-
A variety of unrelated conditions affect the anus and opmental anomalies and acquired lesions. The exact
perineum in children. location of the lesion will usually provide a clue as to
its nature.
Anal fissure
Midline neck swellings
This is usually seen in infants and toddlers when passage
of a hard stool splits the anal mucosa, causing sharp pain The most common midline neck swelling in children
and often a few drops of bright blood. The condition is is a thyroglossal cyst (Table 9.1.4). Typically, there is
272
of little consequence and the fissure u
­ sually heals within a swelling overlying and attached to the hyoid bone
 Surgical conditions in older children 9.1
nodes can enlarge rapidly and become tender during
Table 9.1.4 Midline neck swellings
active infection, but usually settle with rest, analgesia
Cause of swelling Comment and antibiotics as required. In children aged 6 months
to 3 years, lateral cervical lymphadenitis can prog-
Thyroglossal cyst Most common (80% of midline ress to abscess formation: the lymph nodes enlarge
neck swellings)
Moves with tongue protrusion and
over 4–5 days and become fluctuant, although deeper
swallowing nodes may not exhibit fluctuation. The overlying skin
Attached to hyoid bone becomes red. Treatment involves incision and drainage
of the abscess under general anaesthesia.
Ectopic thyroid May be only thyroid tissue present Cystic hygromas are congenital hamartomas of the
Do thyroid isotope scan lymphatic system (Fig. 9.1.10). They vary greatly in
size and can involve the front of the neck or one or
Submental lymph Check inside mouth for primary
node/abscess infection
other sides asymmetrically. Complex cystic hygromas
Other cervical lymph nodes may be can contain cavernous haemangiomatous elements and
enlarged can extend into the floor of the mouth or the thoracic
cavity. They can enlarge rapidly from viral or bacterial
Dermoid cyst Small, mobile, non tender infection, or from haemorrhage. Depending on their
Yellow tinge through skin extent and location, the airway can be compromised,
In subcutaneous layer
leading to life-threatening respiratory obstruction.
Goitre Lower neck
Surgery involves excision or debulking of the lesion.
In some situations they are injected with sclerosants.
Cystic hygroma Hamartoma
Usually evident from birth
May be extensive
MAIS lymphadenitis
Cervical lymphadenitis due to atypical mycobacte-
rial infection is seen in preschool children. Infection
that moves on swallowing and tongue protrusion. It with MAIS (Mycobacterium avium, intracellulare,
can become infected to form an abscess with o ­ verlying scrofulaceum) may also be referred to as MAC
erythema of the skin. The thyroglossal cyst and the (Mycobacterium avium complex). It produces chronic
entire thyroglossal tract are best excised before the cyst cervical lymphadenitis and usually affects the jugulo­
becomes infected. Excision must include the middle digastric, submandibular or preauricular lymph nodes.
third of the hyoid bone (Sistrunk operation), o­ therwise The involved lymph node increases in size over several
recurrence is common. Ectopic thyroid ­tissue is a less weeks before erupting into the subcutaneous tissue as
common cause of a midline neck swelling. Clinically, it a collar-stud ‘cold’ abscess. Eventually, if untreated, it
can be difficult to distinguish from a thyroglossal cyst. may cause purple discoloration of the overlying skin
If suspected preoperatively, a thyroid isotope scan and will ulcerate through the skin to produce a chronic
will clarify the distribution of all functioning thyroid discharging sinus. MAIS infections respond poorly
tissue. to antibiotics. Treatment involves surgical removal of
Congenital dermoid cysts can occur along any line the collar-stud abscess and excision of the underlying
of fusion, including the neck where they are situ- infected lymph nodes.
ated in the midline. A midline cervical dermoid cyst
is ­occasionally mistaken for a thyroglossal cyst. It
­contains sebaceous material surrounded by ­squamous
epithelium. Dermoid cysts enlarge slowly. The most
common congenital dermoid cyst is the external
­angular dermoid, which is found at the orbital margin.
They are usually removed.

Lateral neck swellings

Most lateral neck swellings are acquired, being due to
infection of one or more of the cervical lymph nodes.
Persistently enlarged cervical lymph nodes are normal
in children with frequent upper respiratory infections:
they represent a normal response to infection (i.e.
273
­reactive hyperplasia) and require no treatment. Lymph Fig. 9.1.10 Cystic hygroma in a neonate.
 9.1 COMMON PAEDIATRIC SURGICAL PROBLEMS

Lymph node tumours

Table 9.1.5 Causes of torticollis
Primary tumours involving the lymph nodes tend to
occur in older children. Both Hodgkin and non-Hodg- Cause Comment
kin lymphomas may involve cervical lymph nodes. Sternomastoid tumour Not evident at birth
Rarely, other tumours may metastasize to the cervical Present at 3 weeks of age
lymph nodes (e.g. neuroblastomas and n
­ asopharyngeal Tight, shortened sternomastoid
tumours). muscle
Most resolve without treatment

Branchial remnants Postural torticollis Present at birth

Disappears in months
Branchial remnants arise from the branchial arch From intrauterine position
system. A variety of abnormalities occur, including
branchial cysts, branchial sinuses, branchial fistulae Cervical hemivertebrae
and persistent cartilaginous remnants. Branchial fis- Imbalance of ocular muscles (strabismus)
Lateral cervical lymphadenitis
tulae are present from birth but, because the opening
Tumours
is so tiny, they may not be noticed for some years. Atlanto-occipital subluxation
A drop of mucus or saliva may be observed leaking Benign paroxysmal torticollis of infancy
from the external orifice near the anterior border of
the sternomastoid muscle at the junction of its mid-
dle and lower thirds. Branchial cysts present later in
childhood with a mass beneath the anterior border
of the sternomastoid near its upper third. They may
become infected and should be removed. Sinuses or
fistulae usually arise from the second branchial cleft,
although ­ sometimes the first and third clefts are
responsible.

Torticollis
Torticollis, or wry neck, has many causes in child-
hood (Table 9.1.5). The most common cause is a ster-
nomastoid tumour that presents in the third week of
life with a hard lump in the neck and an inability to
turn the head to one side. The head is flexed slightly
to the side of the shortened sternomastoid muscle, but Fig. 9.1.11 Sternomastoid tumour in torticollis.
turned to the contralateral side. There may be a history
of breech delivery or forceps delivery. There is a hard,
painless swelling, usually 2–3 cm long, in the shortened
sternomastoid muscle (Fig. 9.1.11). Sometimes the
whole muscle may be involved. Rotation of the head Practical points
to the side of the tumour is limited. Plagiocephaly and
hemihypoplasia of the face may develop in subsequent • A degree of narrowing of the foreskin (‘physiological
phimosis’) is common in many boys during the first years of
months. The ‘tumour’ disappears within 9–12 months
life and usually resolves spontaneously without intervention.
in the vast majority of affected infants without treat-
• Inguinal herniae are common in boys (2%), and if they
ment. If fibrosis persists and causes permanent become strangulated should be reduced urgently.
­shortening of the muscle with persistent torticollis, the • The most important cause of an acutely painful scrotum
sternomastoid muscle should be divided. Occasionally, is testicular torsion, which requires urgent surgical
older children present with torticollis due to a short, exploration to untwist and salvage the testis.
tight and fibrous sternomastoid muscle; the ­ipsilateral • Umbilical herniae are common, but most resolve
spontaneously in the first years of life, and require surgical
shoulder is elevated, there may be compensatory
repair only if they persist.
­scoliosis, and the child has difficulty rotating the head • A thyroglossal cyst is the most common cause of a midline
towards the affected side. These children also require neck lump.
surgical division of the muscle.

274
 10
PART

INHERITED AND
METABOLIC
PROBLEMS

275
 10.1 Birth defects, prenatal
diagnosis and teratogens
Jan Liebelt, Neil Hotham

• Deformations result from moulding of a part by

Birth defects mechanical forces, usually acting over a prolonged
A birth defect is any abnormality, structural or func- period. Examples include talipes, congenital hip
tional, identified at any age, that began before birth, dislocations and plagiocephaly associated with
or the cause of which was present before birth. oligohydramnios.
Examples of structural birth defects include spina
bifida and cleft lip. Duchenne muscular dystrophy Causes
and Huntington disease are examples of functional
birth defects. Birth defects can be caused by a wide variety of mech-
With continued advances in obstetric and paediatric anisms including:
medicine, birth defects have become the most impor- • genetic abnormalities, both monogenic and
tant cause of perinatal and post-neonatal mortality in polygenic
developed countries. • chance events within the developing embryo (e.g.
Birth defects: vascular accidents)
• are the leading cause of perinatal death (20–25% of • environmental factors:
deaths) • teratogens generated by the mother (e.g. maternal
• are now the leading cause of post-neonatal deaths phenylketonuria and maternal diabetes)
(25–30%), as deaths due to sudden infant death • teratogens originating outside the fetomaternal
syndrome continue to decline unit (e.g. medications and infectious agents).
• are responsible for a major proportion of the Table 10.1.1 provides a framework for thinking about
morbidity and disability experienced by children causes of birth defects. Most have a multifactorial
and young adults basis, reflecting interaction between genes, environ-
• are the cause for 20–30% of the admissions to a ment and chance events within the developing embryo
tertiary paediatric hospital and fetus.
• have an immense impact on the emotional and
physical wellbeing of the children and their
Genes
families
• have a significant financial cost for the Early human development from fertilized ovum to
community. fetus involves numerous processes controlled by genes,
expressed sequentially in a defined cascade. The pro-
cesses and developmental phases include:
Types of structural birth defect
• definition of polarity
Classified on the basis of the mechanism by which • cell division
they arise: • formation of the germ layers
• Malformations arise during the initial formation • segmentation of the embryo
of the embryo and fetus as a result of genetic and/ • cell migration
or environmental factors during organogenesis • organ formation
(2–8 weeks post-conception). Malformations may • cell differentiation
include failure of formation, incomplete formation • interactions between cells, tissues and organs
or abnormal configuration. Examples include spina • programmed cell death.
bifida, cleft palate and hypospadias. There has been a recent, rapid increase in knowl-
• Disruptions result from a destructive process that edge of the genes that determine or predis-
alters structures after formation. Examples include pose to birth defects. This has resulted from
early amnion rupture causing amputation defects technological advances in molecular genet-
of digits, and vasoconstriction defects caused by ics, in phenotype delineation, gene mapping and
276 cocaine. gene discovery in humans and other species, and
 Birth defects, prenatal diagnosis and teratogens 10.1
Table 10.1.1 Causes of birth defects

Mechanism Example Cause

Whole chromosome missing or duplicated Down syndrome Trisomy 21

Turner syndrome Monosomy X (XO)

Part of chromosome deleted or duplicated Cri du chat syndrome Deletion 5p

Cat eye syndrome Duplication 22q

Sub-microscopic deletion or duplication of Williams syndrome Deletion 7q

chromosome material Velocardiofacial syndrome Deletion 22q
Charcot–Marie–Tooth disease 1A Duplication 17p

Mutation in single gene Smith–Lemli–Opitz syndrome 7-Dehydrocholesterol reductase

Holt–Oram syndrome TBX5
Apert–Crouzon–Pfeiffer syndrome Fibroblast growth factor receptor 2

Consequence of normal imprinting Prader–Willi syndrome Maternal uniparental disomy or paternal

deletion for 15q12

Imprinting errors Beckwith–Wiedemann syndrome Multiple mechanisms resulting in

overexpression of IGF-2
Angelman syndrome Mutations in UBE3A gene

Multifactorial/polygenic: one or more Isolated heart malformations, neural Complex interactions between genes and
genes and environmental factors tube defects and facial clefts environment

Non-genetic vascular and other ‘accidents Poland anomaly Subclavian artery ischaemia
during development’ Oculoauriculovertebral dysplasia Stapedial artery ischaemia

Uterine environment Talipes, hip dysplasia, Oligohydramnios, twins

Plagiocephaly Bicornuate uterus

Maternal environment Mental retardation Maternal phenylketonuria

Caudal regression Maternal diabetes mellitus

Wider environment Fetal rubella syndrome Rubella infection in pregnancy

Fetal alcohol syndrome Maternal alcohol ingestion
Microcephaly High-dose X-irradiation
Limb deficiency Thalidomide

IGF-2, insulin-like growth factor 2; TBX5, T-box transcription factor 5.

an understanding of the cascade of sequential The birth prevalences of the more common birth
gene expression during embryonic development in defects are shown in Table 10.1.2. They represent
other species. the frequency with which the defect occurred dur-
An example of these genes is the homeotic (HOX) ing development (its incidence), less the spontaneous
gene family. HOX genes are involved in the formation loss of affected fetuses during pregnancy. An almost
of structures developing from specific segments of the equal number of additional major abnormalities, par-
embryo. ticularly of the heart and urinary tract, will be recog-
nized by 5 years of age during clinical examinations or
because of symptoms.
Frequency
Minor birth defects:
Major birth defects: • are relatively frequent, but pose no significant
• are those with medical and social consequences health or social burden
• are present with the highest prevalence among • are recognized in approximately 15% of newborns
miscarriages, intermediate in stillbirths and lowest • are important to recognize, because their presence
among live-born infants prompts a search for coexistent, more important,
• are recognized at birth in 2–3% of live-born infants. abnormalities. 277
 10.1 INHERITED AND METABOLIC PROBLEMS

Multiple birth defects

Table 10.1.2 Prevalence of some common birth defects
Various terms have been used to classify multiple
Defect Rate per 1000 births* birth defects in the hope that the terminology will
Malformations of heart and great 12.0 convey information about aetiology, pathogene-
vessels sis and the relationship between the birth defects.
However, no system of naming meets all these crite-
Developmental hip dysplasia 6.9 ria or is able to meet all the situations encountered in
clinical practice. Some commonly used terms are syn-
Hypospadias 3.7
drome, association, sequence and developmental field
Talipes equinovarus 2.2 defect; these are defined in Chapter 10.3. Phenotype
is a useful general term that makes no assumptions
Hypertrophic pyloric stenosis 1.9 about aetiology or pathogenesis but registers the fact
that multiple birth defects are present and are related
Down syndrome 1.8 in some way. Complex and spectrum are alternative
terms that have been used in this context.
Cleft lip with or without cleft palate 1.1

Spina bifida 0.9 Diagnosis

Hundreds of patterns of multiple birth defects have
Anencephaly 0.7
been defined and the diagnosis for a child with mul-
Renal agenesis and dysgenesis 0.6 tiple birth defects is often not obvious.
The primary reasons for pursuing a diagnosis are
Tracheo-oesophageal fistula, 0.4 that a specific diagnosis allows:
oesophageal atresia and stenosis • discussion with the parents about the prognosis for
their child
Abdominal wall defects: 0.6
• parents to develop an understanding of how the
exomphalos and gastroschisis
birth defect arose
* Rate per 1000 births including terminations of pregnancy, • counselling of the parents regarding recurrence risk
stillbirths and live-births. and possibilities for reduction of this risk.
Source: South Australian Birth Defects Register 1986–2003. Thorough investigation, including autopsy if the child
dies, may lead to a diagnosis, and referral to a clinical
geneticist should be considered. Diagnosis is aided by
computerized syndrome identification systems such
Infants free of minor defects have a low incidence of as POSSUM (Physiological and Operative Severity
major malformations, approximately 1%. Those with Score for the enUmeration of Mortality and morbid-
one, two or three minor defects have risks of major ity) and the London Dysmorphology Database. In
malformations of 3%, 10% and 20%, respectively. spite of the large number of known syndromes, clini-
cians continue to encounter many children with birth
defects the cause of which cannot be diagnosed or
ascertained.

Practical points Birth defect/congenital malformation

registers
Birth defects
Birth defects registers were established in many coun-
• Birth defects are the leading cause of perinatal and post-
neonatal deaths, and result in substantial morbidity and
tries following the ‘thalidomide tragedy’ in which hun-
disability in developed countries. dreds of children were born with a range of anomalies
• There is a wide variety of mechanisms including genetic, following maternal use of thalidomide in pregnancy as
environmental and multifactorial. an antiemetic.
• Major birth defects affect 2–3% of live-borns, and minor Registers serve a number of purposes, including:
birth defects affect 15%. • early warning of new environmental teratogens
• Preventative strategies remain limited, but include • identifying precise prevalence figures for individual
maternal folic acid supplementation, reduction in
teratogen exposure, alternative reproductive options, birth defects and syndromes
prenatal detection and neonatal screening. • identifying geographical and temporal trends in
birth defects
278
 Birth defects, prenatal diagnosis and teratogens 10.1
Prevention
Clinical example
Despite considerable research efforts there are very
Susan and Craig's first child, Anna, was few preventative strategies that effectively reduce the
diagnosed soon after birth with a significant incidence of birth defects. Some effective population-
congenital heart defect (tetralogy of Fallot) that based examples include:
required surgery. No concerns had been raised at • oral folic acid supplementation at least 1 month prior
the mid-trimester ultrasound. Anna was also noted to have a to and in the early months of pregnancy can reduce
number of minor birth defects, including unusually shaped ears,
the incidence of neural tube defects by up to 70%
and a hemivertebra in the thoracic spine, seen on chest X-ray.
The family was referred to a clinical geneticist for an • education and legislation to reduce potential
opinion regarding the possibility of an underlying genetic exposure to teratogens:
condition to account for Anna's health issues. The geneticist • public health policy on rubella immunization
also noted that Anna had relatively long, slender fingers • restrictions on prescribing of known teratogens
and that her mother reported frequent nasal regurgitation such as thalidomide and retinoids
of milk during feeds, suggesting palatal dysfunction. This • education about avoidance of foods in pregnancy
combination of issues raised the possibility of a condition
that may predispose to maternal infection with
called velocardiofacial syndrome, caused by a microdeletion
on chromosome 22q. A chromosome array was arranged, known teratogenic agents (e.g. toxoplasmosis and
which confirmed the diagnosis. uncooked meat)
Some 90% of children with this condition are the first • genetic counselling and the development of
person in their family to be affected. However, 10% have alternative reproductive options, including donor
inherited the condition from an undiagnosed, mildly affected gametes and embryos, to allow avoidance of the
parent. The recurrence risk for further pregnancies differs risk of conception of a child with a birth defect
significantly between these two situations. Craig was found
also to have the microdeletion on chromosome 22q and,
related to a specific genetic condition
when his medical history was taken, he reported having • neonatal screening to detect children with those
required serial plastering for talipes as an infant, had types of birth defect that do not cause permanent
struggled academically at school and was now being treated damage before birth, with a view to early treatment
for depression, all of which can be features of this condition. and improved prognosis. Neonatal screening
Given the wide variability of potential medical issues for phenylketonuria, hypothyroidism and cystic
associated with velocardiofacial syndrome, a number of
fibrosis, and clinical examination for hip dislocation
screening tests were arranged for Anna and Craig to detect
any previously unrecognized birth defects. This included
are examples of highly successful screening
renal ultrasonography, immune function tests, serum calcium programmes.
levels, thyroid function tests, eye and hearing reviews, and At present, the primary approach to the prevention of
spine X-rays and cardiology review for Craig. The potential the birth of children affected by birth defects is prena-
long-term consequences of the condition were discussed tal diagnosis.
with the family and they were put in touch with the local
support group. Anna was referred to a general paediatrician
for ongoing medical and developmental follow-up. It was
discussed with the family that there would be a 50% chance
that any further children they conceived would also inherit the
Prenatal diagnosis
condition, but that they might experience more or less severe Prenatal diagnosis refers to testing performed in preg-
medical issues. nancy aimed at the detection of birth defects in the
A range of reproductive options was discussed with the
fetus. Depending on the type of birth defect identified,
couple, including sperm donation, prenatal diagnosis and
pre-implantation genetic diagnosis. Anna required multiple
the gestation of the pregnancy and the perceptions of
hospitalizations in the first few years of life related to her the parents, prenatal detection of a birth defect may
condition, which placed a great deal of stress on the family. allow:
Subsequently, in the couple's second pregnancy, they chose • the option of termination of an affected fetus
to have chorionic villus sampling (CVS) with testing for the • potential treatment in utero or postnatally to
microdeletion to assess whether the fetus had inherited improve prognosis related to the defect
velocardiofacial syndrome. The results showed that the
fetus had not inherited the condition and a healthy boy was
• preparation for the birth of a child with a specific
subsequently born.
medical condition.
The number of prenatal tests available and the range
of birth defects that may be detected are expand-
• assessment of the impact of population-based ing rapidly. Many chromosome abnormalities, struc-
prevention strategies and prenatal diagnosis tural anomalies, enzymatic and single-gene defects are
• collecting data for research into the epidemiology already potentially detectable prenatally. Advances in
of birth defects. knowledge regarding the aetiology of birth defects
279
 10.1 INHERITED AND METABOLIC PROBLEMS

and technical aspects of testing will expand this range • A computer-based algorithm, which takes into
further. Despite these advances, the majority of birth account the mother's age-related risk, the gestation
defects remain undetected until after birth. of the pregnancy and the analyte levels, is used to
In our society, it is an individual decision whether or calculate a risk figure for Down syndrome in that
not to utilize prenatal testing in a pregnancy. The pro- pregnancy.
vision of antenatal care must therefore ensure that par- • If the risk value is greater than a predetermined
ents are able to make informed decisions about testing ‘cut-off’ value, the risk is considered to be increased
and are supported throughout the testing process. and a diagnostic test is offered to clarify the
situation.
Types of prenatal test • Most programmes are designed so that 5% of
women having the test will receive an increased risk
Prenatal tests fall into two main categories: result. The majority of these women will go on to
• screening tests have healthy babies.
• diagnostic tests. • If all of these women chose to have a diagnostic
These are discussed further below. test, the screening programme would be expected to
detect up to 80% of cases of Down syndrome.
Screening tests • If AFP is one of the analytes used in second-
Prenatal screening tests: trimester MSS, the test can also be used to screen
• are aimed at all pregnant women for open neural tube defects, as AFP levels are
• assess whether an individual pregnancy is at increased when neural tissue is exposed to the
increased or low risk of a particular birth defect amniotic fluid. If the level is raised, the diagnostic
• generally pose no risk to maternal or fetal wellbeing test is tertiary-level ultrasonography to examine the
• are followed by an offer of a diagnostic test if an fetal spine.
increased risk is identified
• are aimed primarily at the detection of structural
anomalies and chromosomal abnormalities, in Ultrasonography
particular Down syndrome. Ultrasonography uses sonar waves to allow real-time,
Screening tests in pregnancy are evolving rapidly, with two-dimensional visualization of the fetus in utero.
the aim being earlier, more accurate and more acces- The fetus can be examined in different views and
sible tests. fetal movements studied. Improved technology and
training allow excellent views to be obtained to allow
Screening tests available detection of many specific structural anomalies. Most
antenatal care programmes now offer ultrasonogra-
Currently, screening tests are performed on a serum phy between 18 and 20 weeks of gestation to screen for
sample from the mother, or utilize ultrasonography. fetal anomalies.
Ultrasonography is usually considered a screening
Maternal serum screening rather than a diagnostic test, because:
• Maternal serum screening (MSS) is aimed primarily • some structural anomalies may not be readily
detected (e.g. transposition of the great vessels)
at the detection of Down syndrome and, in some
programmes, trisomy 18. • interpretation of a possible anomaly and its impact
on fetal development may be limited
• MSS involves measuring the levels of a number of
different analytes produced by the fetus in a blood • the detection rate of anomalies is dependent on
the skill of the operator, equipment and fetal views
sample from the mother.
obtained.
• The analytes have been selected on the basis
More recent advances that may enhance the value of
that large population studies have shown the
fetal imaging as a screening test in pregnancy include
levels of the analytes in maternal serum to differ
three-dimensional ultrasonography and alternative
significantly between pregnancies in which the fetus
imaging techniques such as fetal magnetic resonance
does or does not have Down syndrome.
imaging (MRI).
• MSS can be offered in the second trimester (around
15–18 weeks) using various combinations of
three or four analytes. These may include oestriol,
Nuchal translucency screening
α-fetoprotein (AFP), inhibin and the α and β subunits
of human chorionic gonadotrophin (hCG), or in During the past two decades, a new form of ultra-
the first trimester using analytes such as inhibin and sound-based screening for Down syndrome in the
280
pregnancy-associated plasma protein A (PAPP-A). first trimester has been developed, based on the MSS
 Birth defects, prenatal diagnosis and teratogens 10.1
model. This depends on the assessment of the nuchal • allow accurate clarification of whether an
(posterior neck) region of the fetus: individual fetus is affected or not
• All fetuses have a collection of fluid in the nuchal • usually pose a small risk of fetal loss; this risk
region that can be visualized as a translucent area relates to the need to sample fetal tissue for testing
and can be measured by ultrasonography at the end • are aimed primarily at the detection of
of the first trimester (11–13 weeks’ gestation). chromosomal abnormalities, enzymatic and single-
• Large population studies have shown that on gene defects.
average this nuchal translucency measurement is
increased in pregnancies in which the fetus has
Down syndrome.
• As with MSS, a computer algorithm that takes into Practical points
account the mother's age-related risk, the gestation
and the thickness of the nuchal translucency Prenatal diagnosis
measurement is used to calculate a risk for that • Prenatal diagnosis is aimed at detection of birth defects
individual pregnancy. prior to birth to allow options for parents.
• If the risk is above a predetermined ‘cut-off risk’, a • There are two main categories: diagnostic and
screening.
diagnostic test is offered.
• There is a move towards earlier, less invasive, testing
• The detection rate of a nuchal translucency options such as pre-implantation genetic diagnosis and
screening programme is dependent on the skill combined screening tests.
of the operator; however, detection rates of up to • The majority of birth defects remain undetected by current
70–80% of cases of Down syndrome have been prenatal diagnostic methods.
reported. • Prenatal diagnosis for specific genetic conditions usually
requires significant pre-pregnancy workup.
• Other chromosome abnormalities, in particular
Turner syndrome (45,XO) and triploidy, are
also often associated with an increased nuchal
translucency measurement. New diagnostic tests continue to be developed,
• An increased nuchal translucency measurement with the principal aim of increasing both the safety
in the presence of normal chromosomes may of the tests and the range of conditions that may be
be an indicator of other types of fetal anomaly, tested for.
such as cardiac malformations or skeletal
dysplasias. Detailed ultrasound follow-up is then
Indications for diagnostic prenatal tests
recommended.
Although all women are at risk of conceiving a baby
with a birth defect, for an individual woman there are
Combined screening
a number of risk factors that increase the risk above
In order to increase the detection rates of screening the background population risk. In general, diagnostic
tests, combinations of the different tests are being prenatal tests are offered to women whose risk of con-
explored. The most commonly utilized is the combi- ceiving a baby with a specific birth defect is considered
nation of a nuchal translucency measurement with the to be above an arbitrary level. This ‘cut-off’ level takes
measurement of two first-trimester maternal serum into account the risk of fetal loss related to the test and
analytes to give a combined first-trimester risk. This economic issues relating to the number of women who
allows increased detection rates for Down syndrome of would be offered testing.
up to 90%, with a 5% false-positive rate, and is increas- Some of the reasons why a woman may be offered a
ingly replacing second-trimester maternal serum prenatal diagnostic test include:
screening as the screening test of first choice, with the • advanced maternal age (see below)
added advantage of allowing an earlier diagnostic test • increased risk identified by a screening test (e.g.
to be offered. The best combination of screening tests maternal serum screening)
is continually being assessed by large multicentre trials • a previous child with a birth defect for which a
that are in progress to address this issue. prenatal test is available and an increased risk
of recurrence is recognized (e.g. chromosome
abnormality, neural tube defect, single-gene
Diagnostic tests
disorder such as cystic fibrosis)
Prenatal diagnostic tests: • a parent or couple known to carry a genetic
• are aimed at pregnant women who have been mutation for which testing is available and that
identified to be at increased risk of having a baby poses a risk of abnormality in offspring (e.g.
281
with a particular birth defect (see below) chromosome translocation or single-gene defects)
 10.1 INHERITED AND METABOLIC PROBLEMS

• other factors known to increase the risk of Diagnostic tests available

birth defects (e.g. exposure to teratogens such as
Most diagnostic tests involve sampling of fetally
maternal infection).
derived tissue, which can then be directly analysed
for abnormalities. The most common test performed
Advanced maternal age is chromosomal analysis. However, tissue may also be
As maternal age increases, there is an increased risk of used as a source of DNA for molecular genetic tests,
conception of a fetus with some specific chromosomal for metabolic tests or, more rarely, to look for evi-
anomalies, primarily trisomies (an additional copy of dence of fetal infection or histological confirmation
a single chromosome). Most fetuses conceived with a of abnormality of a specific tissue (e.g. the skin for the
trisomy miscarry. However, trisomy 21, 13 and 18 are diagnosis of epidermolysis bullosa).
potentially viable chromosomal anomalies leading to Amniocentesis and chorionic villus sampling (CVS)
the potential birth of a baby with specific constellations are the two principal diagnostic tests used. However,
of birth defects (see Chapter 10.3). Maternal age is not fetal blood samples, skin, liver or kidney biopsies
associated with an increased risk of other birth defects. may be required in very specific, rare circumstances.
Trisomy 21 (Down syndrome) is the most common Amniocentesis, CVS and fetal blood sampling are per-
chromosome abnormality seen at live birth in our popu- formed as outpatient procedures under ultrasound
lation. Many screening and diagnostic prenatal tests are guidance (Fig. 10.1.1). Each of these tests has advan-
therefore aimed at detection of this condition. Population tages and disadvantages in certain situations (Table
data exist that can be used to counsel women regard- 10.1.4).
ing their ‘age-related’ risk in order that they may make
informed decisions about prenatal testing (Table 10.1.3). Imaging techniques
In some circumstances, ultrasonography or other forms
of fetal imaging such as MRI, or even plain X-rays, are
Table 10.1.3 Age-specific risks for a live-born child with
Down syndrome
considered diagnostic and may be the only tool avail-
able for diagnosis of genetic conditions that do not
Maternal age (years) Risk (1 in) at expected time have a chromosomal, enzymatic or known molecular
of delivery basis. Examples include neural tube defects, skeletal
20 1441
dysplasias and congenital heart defects. Imaging tech-
niques, however, are dependent on gaining adequate
25 1383 views and appropriate interpretation of the views, and
are limited by the gestation at which some defects may
30 959 be identifiable; for example, hydrocephalus may not
become apparent in a fetus until the third trimester.
34 430

35 338

36 259 Transabdominal Ultrasound

scanner
37 201

38 162

39 113

40 84
Fetus
42 52

44 38

46 31

The risk of any chromosome abnormality is approximately

double these risks. Placenta Uterus Transcervical
After Gardner RJM, Sutherland GR 2004 Chromosome
abnormalities and genetic counseling (3rd edn). Oxford Fig. 10.1.1 Schematic representation of chorionic villus sampling
282 University Press, New York. showing transabdominal and transcervical routes. (Courtesy of
Ultrasound Department, Royal Women's Hospital, Melbourne.)
 Birth defects, prenatal diagnosis and teratogens 10.1
Table 10.1.4 Prenatal diagnostic tests

CVS Amniocentesis Fetal blood sampling or fetal biopsies

Tissue sampled Chorionic villi derived from the Amniotic fluid containing Fetal blood, liver or skin
same initial fertilized ovum as fetal cells
the fetus

Indications for test Increased risk of fetal As for CVS Increased risk of fetal chromosome
when chromosomal anomaly anomaly when rapid results are
required
Increased risk of specific Increased risk of fetal Diagnosis of fetal haemoglobinopathy
genetic conditions for which infection
a molecular or enzymatic Other less common Diagnosis of fetal conditions by
test exists indications, AFP tissue histology (e.g. some skin
measurements to assist in disorders)
diagnosis of neural
tube defects

Gestation at which Can be performed safely Can be performed safely Can be performed after 18 weeks’
test is performed after 10 weeks’ gestation; after 15 weeks’ gestation; gestation
most often done between most often done at
11 and 13 weeks’ gestation 16–18 weeks’ gestation

Risks 0.5–1% rate of miscarriage 0.5% rate of miscarriage 1–5% rate of miscarriage related to the
related to the test related to the test test, depending on the indication for
the test

Other issues 1% risk of a discrepant result 1% risk of failure of Potentially difficult access
between fetal and placental amniocytes to culture,
tissue (confined placental requiring a repeat test
mosaicism), requiring
amniocentesis to clarify

Timing of results Rapid chromosome analysis As for CVS Dependent on test performed
by FISH 24–48 hours*
Final chromosome, DNA
or enzyme test results
7–21 days

*FISH (fluorescence in situ hybridization) involves the use of labelled DNA probes designed to bind to specific regions of
individual chromosomes. This allows the number of a specific chromosome in an interphase cell to be ascertained within 24–48
hours.
AFP, α-fetoprotein; CVS, chorionic villus sampling.

Future options Prenatal diagnosis for specific genetic

conditions
Hope for ‘non-invasive’ diagnostic testing previously
rested on the concept of isolation of fetal cells found Rapid progress in knowledge of the underlying molec-
within the maternal circulation during pregnancy. More ular genetic aetiology of specific conditions allows an
recently, recognition of ‘free fetal DNA’ within the increasing number of genetic conditions to be diag-
maternal circulation during pregnancy, and the fact that nosed prenatally by utilizing specific DNA-based tech-
fetal cells can be isolated from cervical swabs during nology. In order that this can occur for any individual
pregnancy, has raised the potential for future options couple known to have an increased risk of conceiving
that would allow collection of fetal tissue for the pur- a child with such a disorder, a number of conditions
pose of testing without risk to fetal wellbeing. Current must be satisfied:
techniques do not yet allow this option to be used • accurate diagnosis of the condition in the affected 283
widely in a clinical setting; however, research continues. family member
 10.1 INHERITED AND METABOLIC PROBLEMS

• confirmation of the aetiology of the condition to prevent misdiagnosis. Thousands of babies have
by identification of a mutation in the causative now been born worldwide following PGD in a number
gene or an enzymatic defect that can be tested for of highly specialized centres. Continual improvements
accurately in fetal tissue (a process that may take in genetic techniques and pregnancy rates following
many months and may not be possible in some IVF will mean that PGD will continue to become a
cases) more common alternative to the well established meth-
• appropriate pre-test (preferably pre-pregnancy) ods of CVS and amniocentesis.
counselling regarding the process of testing and
implications and options relating to the potential
results of testing
• appropriate support throughout the process. Teratogens
Prenatal diagnosis in these circumstances is best pro- A teratogen is an environmental agent that can cause
vided by an experienced multidisciplinary team con- abnormalities of form or function in an exposed
sisting of an obstetrician, clinical geneticist, genetic embryo or fetus. It is estimated that between 1% and 3%
counsellor and experienced laboratory staff. CVS of birth defects may be related to teratogenic exposure.
is usually the preferred method for DNA-based and A teratogen may cause its effect by a number of dif-
enzymatic prenatal tests, as it often allows direct test- ferent pathophysiological mechanisms, including:
ing rather than a need for culturing of tissue prior to • cell death
testing. Examples of conditions that DNA-based pre- • alteration of cell division and tissue growth,
natal diagnosis may be available for include: Duchenne including cell migration
and Becker muscular dystrophy, fragile X syndrome, • interference with cellular differentiation.
cystic fibrosis and haemoglobinopathies. Examples include, alcohol and sodium valproate,
In some families, although the specific mutation which are believed to cause underdevelopment of the
causing the condition in the family has not been iden- mid-face and philtrum due to cell death in these areas,
tified, linkage studies using polymorphic DNA mark- whereas syndactyly can result from failure of pro-
ers close to or within the gene may be possible. This grammed death of cells between the digits.
requires further testing of family members and has a
margin of error related to the possibility of genetic
Requirements of a teratogen
recombination. For X-linked conditions in which the
gene has not yet been identified or a mutation cannot In theory, to produce a malformation a teratogen
be identified, identification of the sex of the fetus by must be present in a sufficient amount, at the appro-
chromosome analysis and termination of males (50% priate time, in a genetically susceptible individual,
of whom would be unaffected) may be the only avail- where other conditions do not prevent the effects from
able option. occurring.
Factors that can modify the effects of a teratogen
include:
Pre-implantation genetic diagnosis
• timing of exposure
Prenatal diagnosis with termination of affected preg- • dose to the fetus
nancies may not be an option for some couples, for • genetic susceptibility
ethical and moral reasons. Following advances dur- • access of the drug to the fetus
ing the last two decades in both reproductive and • interaction between teratogens
molecular genetic technology, the technique of pre- • maternal folic acid supplementation.
implantation genetic diagnosis (PGD) has become an
alternative option.
Timing of exposure
The principle of this technique is the genetic analysis
of an embryo produced by in vitro fertilization (IVF) The effect of an environmental agent may differ
technology, in order to select those embryos free from depending on the gestational age at which exposure
a specific genetic condition for transfer to the woman's occurs:
uterus to establish a pregnancy. • Exposure very early in embryogenesis, prior to
A single cell can be removed for genetic analysis on organogenesis (less than 2 weeks after conception)
day 3 to day 5 post-conception from an embryo cul- is likely to cause embryonic death rather than
tured in vitro. Genetic analysis may consist of specific malformations. This is seen as an ‘all or nothing’
mutation detection or a limited analysis of chromo- effect.
somes. The limited amount of material and the lim- • During organogenesis (2–8 weeks after conception),
ited timeframe available for analysis have provided the malformations may occur if the exposure is not
284
impetus for the development of specialized techniques fatal.
 Birth defects, prenatal diagnosis and teratogens 10.1
• Each organ develops during a specific time period
and will be susceptible to the malforming effects of Practical points
teratogens only during that critical period.
• During fetal development (after organogenesis), Teratogens
although malformations can still occur in slowly • Timing of exposure to teratogens is important: there may
forming organs such as the brain and kidney, this is be an ‘all or nothing effect’.
the time when functional effects, such as cognitive • The ‘dose’ received by the fetus may be critical.
impairment, or behavioural effects are more likely. All teratogens have a threshold dose, after which
abnormalities increase.
Teratogens such as vasoactive drugs (e.g. cocaine)
• Risk–benefit ratios need to be considered (e.g. maternal
may also damage structures that have already wellbeing versus teratogenic risk).
formed. • Genetic susceptibility may be important in exposure to
Classical examples include thalidomide, which affects some teratogens.
limb development only at the time when limb buds are • Access of the drug to the fetus should be considered. Is it
developing (between 27 and 41 days), and doxycycline, absorbed by the mother? Does it cross the placenta?
which causes staining of teeth if there is fetal exposure • Interaction between teratogens may increase risk (e.g.
polypharmacy of antiepileptic drugs).
after 18 weeks’ gestation.

Dose
Some important teratogens
The harmful effects of teratogens are dose-depen-
dent. A dose threshold is where the rate of abnormali- Selected teratogens that cause common clinical issues
ties rises. For example, there is no observed effect of are discussed below; a more extensive list is provided
X-rays at doses routinely used in diagnostic radiol- in Box 10.1.1.
ogy, whereas doses associated with nuclear explosions
cause microcephaly, mental retardation and growth
Rubella virus
failure.
Infection of the fetus by the rubella virus in the first
trimester can cause devastating birth defects, including
Genetic susceptibility
mental retardation, short stature, deafness, blindness
There are marked differences in genetic susceptibil- and congenital heart defects.
ity to environmental agents, both between species and • The risk is greatly reduced if the mother has been
between individuals of one species. It is likely that the immunized prior to pregnancy.
susceptibility to the harmful effects of many terato- • As immunity may wane, the immune status of
gens depends on the genetically determined efficiency women planning pregnancy should be reviewed.
of detoxifying metabolic pathways in both the mother
and the fetus. Thalidomide, again, forms an example
Alcohol
of this, in that it is not teratogenic in a large number
of species but is teratogenic in some rabbits and some The harmful effects of ethanol on the developing
primates, including humans. Phenytoin metabolism by human are well documented:
a fetus with low epoxide hydrolase activity may put the • Teratogenic effects of alcohol are dose-related,
fetus at risk of fetal phenytoin syndrome. ranging from clinically inapparent effects to
the fetal alcohol syndrome (FAS): prenatal and
postnatal growth failure, microcephaly, intellectual
Access
disability, a characteristic facial appearance, cleft
A teratogen must gain access to the fetus. Some poten- palate, microphthalmia and heart defects.
tially harmful agents are not teratogens because their • Heavy drinking throughout pregnancy is associated
molecular size, means of transport or binding prop- with a 10% risk of FAS and a 30% risk of
erties prevent or restrict them from crossing the pla- observable fetal alcohol effects (FAEs).
centa. Examples include heparin and pancuronium. • No threshold dose has been defined; therefore women
should be advised to avoid alcohol during pregnancy.
Interaction between teratogens
Antiepileptic medication
Ingestion of multiple medications can have additive
effects. An example is that the risk of fetal effects is Women with epilepsy receiving treatment with anti-
greater if a mother with epilepsy is taking multiple anti- convulsant medication have a 2–3-fold increased risk
285
convulsants (polypharmacy) rather than a single one. of giving birth to a child with a birth defect.
 10.1 INHERITED AND METABOLIC PROBLEMS

Box 10.1.1 Environmental agents that can adversely affect

• It is likely that individual susceptibility exists, based
human development on pharmacogenomics.
• Epileptic women must accept some additional risk
Infectious agents of birth defects in their infants, but the risk can be
minimized if epileptic control can be achieved with
Viruses: rubella, cytomegalovirus, varicella-zoster, Venezuelan a single drug at the lowest possible dose.
equine encephalitis, herpes simplex, [parvovirus B19]
Bacteria: syphilis, [Listeria]
Parasites: toxoplasmosis Vitamin A analogues: isotretinoin and acetretin
Physical agents These highly potent analogues of vitamin A are
Ionizing radiation, carbon monoxide, (heat) extremely teratogenic – even more so than thalidomide.
Drugs and chemicals • Their systemic use in early pregnancy is associated
Environmental chemicals: organic mercury compounds, with a high (greater than 35%) risk of birth
(polychlorinated biphenyls; PCBs) defects, including serious abnormalities of brain
Non-prescription drugs: ethanol, cocaine, (amphetamines), development, with microcephaly, hydrocephalus,
[tobacco smoking, marijuana smoking]
cortical blindness and intellectual disability, cranial
Prescription drugs: nerve palsies, dysmorphic facial features, microtia,
Anticancer drugs: aminopterin, busulfan, chlorambucil, cleft palate, heart defects, thymic hypoplasia and
cyclophosphamide, plicamycin, methotrexate, cytarabine, genitourinary abnormalities.
(dacarbazine, fluorouracil, procarbazine)
Anticonvulsants: phenytoin, sodium valproate, carbamazepine,
• No ‘safe’ period or threshold dose has been
trimethadione, (primidone, phenobarbital, lamotrigine) determined for these drugs.
Hormones: diethylstilbestrol, male sex hormones, strongly
androgenic progestogens
Antibacterials: tetracyclines, streptomycin, (gentamicin,
quinolones, fluconazole (high doses 400–800 mg daily),
trimethoprim) Clinical example
Antivirals: ribavirin, (ganciclovir, zalcitabine)
Anthelmintics: (albendazole) Kylie, a 25-year-old woman, has just found
Antimalarials: (chloroquine when used to treat malaria but out that she is 4 weeks’ pregnant. She has an
not when used for prophylaxis) artificial heart valve and has taken warfarin for
Retinoids: systemic isotretinoin, acetretin, (vitamin A, topical the past 6 months. She had been advised not
tretinoin and isotretinoin) to become pregnant and had used medroxyprogesterone
Immunomodifiers: (methotrexate), [interferon-β1b] depot for contraception. However, she had not recently
Miscellaneous: thalidomide, misoprostol, penicillamine, renewed it because of side-effects experienced after her first
warfarin, phenindione, lithium, intra-amniotic dose 4 months ago. Now condoms had failed. Kylie also has
methylthioninium chloride {methylene blue}, (diazepam, a urinary tract infection and treatment with trimethoprim was
antithyroid drugs, statins, mycophenolate, ACE inhibitors, being considered. Her partner, Adam, had taken large doses
angiotensin II receptor antagonists) of vitamins, including vitamin A, prior to conception and
had read that vitamin A can be harmful in pregnancy. They
Maternal disorders sought advice about risks to their unborn baby.
Insulin-dependent diabetes mellitus, maternal phenylketonuria Firstly, reassurance was given about the paternal exposure
to vitamin A. Drugs and chemicals taken by men have not
The above list should be considered illustrative only and may been proven to increase the incidence of abnormalities in
change in the light of new knowledge. their offspring (http://www.otispregnancy.org). Vitamin A
No brackets, teratogen; ( ), possible teratogen; [ ], not known analogues are potent teratogens when used by the mother.
to be teratogenic but may cause other effects, including It was important to treat the urinary tract infection; however,
embryonic/fetal death and/or growth retardation. trimethoprim, an antifolate antimicrobial, is not suitable in the
ACE, angiotensin-converting enzyme. first trimester. Another agent was recommended.
Warfarin treatment for Kylie was of concern. Four weeks of
pregnancy (4/40) is earlier than the time of warfarin's greatest
teratogenic susceptibility, at 6–9 weeks of gestation (6–9/40).
• Most anticonvulsants have not been shown to be safe However, Kylie's medical condition required anticoagulation
in pregnancy, and specific teratogenic effects have been with warfarin, which crosses the placenta, and she was
defined for phenytoin, sodium valproate, carbamazepine counselled that there was approximately a 5% chance of fetal
and trimethadione, particularly for neural tube defects. warfarin syndrome. Heparin does not cross the placenta and
is not teratogenic, but unfortunately is inadequate prophylaxis
• Periconceptional folic acid supplementation at a dose
for pregnant patients with artificial heart valves.
of 5 mg daily should be recommended for women on
In spite of negative product information, the
anticonvulsant medication because of this. medroxyprogesterone depot was not a cause for concern,
286 • The risk to the fetus increases if multiple even if Kylie had received the dose while in early pregnancy.
anticonvulsants are needed to prevent seizures.
 Birth defects, prenatal diagnosis and teratogens 10.1
• Many countries have restricted the prescribing • The period of greatest embryonic susceptibility is
of these drugs to particular groups of doctors: between 4 and 7 weeks after conception, although
women should use effective contraception for it is recommended that the drug should be avoided
1 month before and throughout treatment, and for throughout the first trimester.
a time after treatment stops. They should have a • Warfarin exposure limited to the second and third
pregnancy test before commencing treatment. trimesters has a low risk of causing brain and eye
• Isotretinoin is used orally and topically to damage, presumably as a result of haemorrhage.
treat severe cystic acne. Although it has a short • Heparin is not a teratogen as it does not cross the
elimination half-life, it is recommended that placenta.
pregnancy should be avoided for at least 1 month • Use of heparin instead of warfarin may be
after the last dose. appropriate when the indication is venous
• Acetretin is used to treat psoriasis and other thrombosis, but not when it is used for artificial
disorders of keratinization. It has a relatively heart valves. Low-dose heparin carries a significant
short half-life, but is converted to etretinate during risk of valve thrombosis, and high-dose heparin
therapy. Etretinate is readily taken up into adipose in the outpatient setting carries a risk of serious
tissue, and has a long elimination half-life of maternal and retroplacental haemorrhage.
120 days. It is recommended that pregnancy be
avoided for 2 years after the last dose.
Ionizing radiation
• Risks to the fetus are very low when performing
Clinical example diagnostic radiology in pregnancy.
• Women inadvertently exposed to diagnostic X-rays
Michelle is a nurse in a paediatric and women's in early pregnancy can usually be reassured,
hospital, and is unexpectedly pregnant. As an although they may find it hard to understand that,
occupational health and safety issue, she had
although public health policy strongly recommends
received a rubella vaccine about 6 weeks prior
to conception. A week before her positive pregnancy test she avoidance in pregnancy, the absolute risk to the
had an oral treatment with a single dose of fluconazole for baby is negligible.
vaginal thrush. • Doses delivered to the appropriately shielded uterus
Concern about the rubella vaccine, which is live- by modern X-ray equipment are well below the level
attenuated, and the fluconazole, can be addressed using that is teratogenic.
two facts. Both involve the key words of timing and dose.
• Very high doses of X-rays can affect the fetus,
No cases of congenital rubella have been proven
to be caused by this vaccination given just before or in
resulting in growth failure, microcephaly, ocular
early pregnancy. The waiting time recommended prior to defects and intellectual disability.
conception has been reduced from 3 months to 1 month. • If an undiagnosed pregnancy was irradiated during
Fluconazole single-dose therapy does not appear to cause radiotherapy, the dose and the risk should be
any increase in abnormalities above the background rate. assessed.
However, repeated doses of 400–800 mg daily have been • The sensitive period for these effects appears to be
associated with a consistent pattern of birth defects, similar
between 2 and 4–5 weeks after conception.
to those seen in animal studies.
• Ionizing radiation is not only potentially
teratogenic but also potentially mutagenic and
carcinogenic. It is likely that even low-dose
Warfarin
irradiation of the fetus, as with the child and
Warfarin is used in the treatment of thromboembolic adult, does have mutagenic and carcinogenic
disease and for individuals with artificial heart valves. potential, but the absolute size of the risk increase
• Warfarin crosses the placenta, is teratogenic and is very small.
may cause haemorrhage in the fetus.
• The teratogenic effects appear to result from
Diethylstilbestrol (DES)
inhibition of vitamin K and/or arylsulphatase E
activity during skeletal development. This drug, widely used in the 1950s and 1960s in the
• The fetal warfarin syndrome comprises nasal belief that it prevented miscarriage, is both a teratogen
hypoplasia, short fingers with hypoplastic nails, low and a prenatal carcinogen.
birth weight, stippling of epiphyses on X-ray and • Exposure, especially before 10 weeks’ gestation, can
intellectual disability. cause cervical abnormalities, uterine malformations
• The risk of fetal warfarin syndrome in the babies of and vaginal adenosis in girls. These areas of
women who require warfarin throughout pregnancy epithelium have an increased risk of progressing to
287
is low, around 5%. vaginal adenocarcinoma years later.
 10.1 INHERITED AND METABOLIC PROBLEMS

• This highlights that there can be a delay of although it is admitted that it would be very hard to
many years before the effects of fetal exposure see an effect against the significant background prev-
to environmental agents become apparent, and alence of birth defects in humans. It is theoretically
absence of birth defects in the earliest years of life possible that environmentally induced mutations
is not sufficient evidence to declare a drug safe in could contribute to the known paternal age-related
pregnancy. risk of new dominant mutations, for example for
• Exposed boys appear to have an increased risk of achondroplasia (http://www.otispregnancy.org/files/
testicular abnormalities, infertility and possibly paternal.pdf).
testicular malignancy.
Teratogen information services
Paternal exposures
Understandably, as a result of the thalidomide disas-
To date, there is no convincing evidence that pre- ter, there is public concern about possible effects of
conception paternal exposure to environmental exposure to environmental agents in pregnancy, and
chemicals is teratogenic, although paternal drugs a general uneasiness about environmental agents and
may affect fertility. For paternal exposure to be ter- health. This has resulted in the establishment of ser-
atogenic, it would have to involve mutagenesis of vices to provide information to health profession-
paternal DNA. A mutagenic agent could affect any als and the public. Teratogen information services
part of the genome, resulting in the spread of risk have access to online databases such as TERIS and
of mutation across a very large number of individual Reprotox, containing the most recent distillation of
genes. Although new dominant and X-linked muta- information about individual agents. They have expe-
tions could potentially occur, one would not expect a rience in assessing the significance of an exposure and
consistent pattern of birth defects in the children of counselling skills, and can usually be contacted by
exposed men. At present, any teratogenic risk from phone when the need arises. They are usually located
paternal exposures should be considered negligible, in large public obstetric hospitals.

288
 Modern
Sample geneticsTitle
for Chapter
Sample
Nicola for
Poplawski
Chapter Author
10.2
10.2
A clinical geneticist is a medical specialist who has • The entire ladder is twisted along its length into
expert knowledge of human clinical and labora- a conformation that is often called a ‘double
tory genetics. However, because genetic information helix’.
underlies the development and responses of every • The entire DNA sequence is called the human
individual, an understanding of human genetics is genome and is encoded by approximately three
essential for every medical practitioner. This chapter billion (3 × 109) nucleotides.
provides a brief overview of the principles of genet-
ics as they pertain to paediatrics, but readers are cau-
DNA is located in two different parts of a cell
tioned that there is much that is both important and
fascinating that cannot be covered in the space avail- The human genome is separated into two parts. The
able. It is strongly recommended that readers uti- smaller mitochondrial genome (mtDNA) is located in
lize other resources that are relevant to this section. the matrix of mitochondria and encodes just 37 genes.
Readers should also bear in mind that genetics is a The larger nuclear genome (nuclear DNA) is located in
rapidly developing field, and detailed information the nucleus of the cell and encodes more than 25 000
derived from any source may become outdated within genes.
a matter of months.
Many technical terms are used throughout this Nuclear DNA forms tightly coiled lengths
chapter and readers need to be familiar with these of DNA called chromosomes
terms. Many will be familiar from courses in genetics
or biochemistry. Nuclear DNA is packaged into 23 fragments of
varying length. During mitosis each fragment is vis-
ible down a light microscope as a short bundle or
chromosome. A gene is located at the same point
Genetic information on the same chromosome in all human individu-
als. A locus is the unique chromosome position that
Genetic information is encoded in DNA
defines the location of each individual gene or DNA
Deoxyribonucleic acid (DNA) is a complex mol- sequence.
ecule located within the nucleus of every cell of a • Human somatic (‘body’) cells have two copies of
body (Fig. 10.2.1.) It is the biological ‘library’ of the nuclear genome, one copy inherited from each
the genetic information needed for a fertilized egg parent; this DNA is packaged into 46 chromosomes
to develop into a complex and functional organism (23 pairs).
(a person) comprised of a wide variety of cell and • Sperm and ova (gametes) have a single copy of
tissue types. the nuclear genome packaged as 23 unpaired
• DNA is a linear molecule comprised of subunits chromosomes.
called nucleotides. • Fertilization of an ovum by a sperm restores the
• There are four different nucleotides; adenosine (A), usual amount of nuclear DNA in a somatic cell; 46
thymidine (T), cytosine (C) and guanidine (G). chromosomes; 23 pairs.
• Each nucleotide is linked to its immediate • In a karyotype, chromosome pairs are arranged
neighbour by a sugar molecule, deoxyribose, in a standard format based on their size, banding
forming a long chain. pattern and centromere position; the first 22 pairs
• Two chains of nucleotides are linked together by are called autosomes; the 23rd pair are the two sex
hydrogen bonds. chromosomes.
• Adenosine in one chain pairs with thymidine in the • In females there are two equivalent long sex
other chain, and cytosine pairs with guanidine. chromosomes called X chromosomes.
• The hydrogen bonds between the A–T and C–G • In males there is one long X chromosome and a
pairs are like the rungs on a ladder. small Y chromosome.
289
 10.2 INHERITED AND METABOLIC PROBLEMS

Chromosome
Nucleus
Chromatid Chromatid
Telomere

Centromere

Telomere
Cell

Histones
Nucleotide pairs

A
T G
C A DNA
C (double helix)
T T
G G
A
C

Fig. 10.2.1 Organization of our nuclear genome.

One X chromosome is inactivated in females • At the time of conception both X chromosomes in

a female conceptus are active.
The difference in the number of X chromosomes • After a few cell divisions, one X chromosome in
between males and females represents a profound dif- each cell is inactivated by methylation; the same X
ference in the amount of genetic information in the chromosome remains inactive in all daughter cells
cell. Females compensate for the presence of two derived from that ancestral cell.
X chromosomes by inactivating one X chromosome, a • The result is that both males and females have only
process called lyonization. one active X chromosome in each cell.
290
 Modern genetics 10.2
• On average, each of the two X chromosomes will be • Mitochondria and mtDNA are copied
active in half of the cells of a female's body. independently of the process of copying
• Because X inactivation is initiated when the nuclear DNA.
conceptus consists of a small number of cells, by • Mitochondria are maternally inherited – all the
chance approximately 10% of females have the mitochondria in an individual's cells are derived
same X chromosomes active in 90% or more of from the original ovum.
cells (skewed X inactivation). • The exclusive maternal inheritance of the
mitochondrial DNA is in marked contrast to the
bi-parental inheritance of nuclear DNA.
Mitochondrial DNA is a small, circular,
double-stranded DNA
Mitochondria are small organelles within the cell that
have an essential role in many metabolic processes The function of our genome:
including oxidative phosphorylation, the process that DNA, genes and proteins
generates adenosine triphosphate (ATP) via aerobic
Protein-coding genes
metabolism. Mitochondria contain more than 1000
different proteins, including over 60 proteins directly A unit of DNA sequence that encodes a protein is
involved in oxidative phosphorylation. Most, but not called a gene. The genetic information contained in the
all, of these mitochondrial proteins are encoded by gene flows from DNA to RNA to protein.
nuclear genes. • A gene consists of a sequence of nucleotides.
• mtDNA is a double-stranded loop, 16 569 nucleotides • Some genes are encoded by several hundreds of
long, that is joined end-to-end in a circle. nucleotides and others by many thousands.
• mtDNA encodes 13 proteins involved in oxidative • The DNA sequence of most nuclear genes is
phosphorylation, as well as 24 non-coding broken up into coding modules (exons), which are
ribonucleic acids (RNAs) important for normal separated from each other by regions of non-coding
mitochondrial function. DNA (introns) (Fig. 10.2.2).
• Each mitochondrion has 5 to 10 copies of • Mitochondrial genes do not have introns.
mtDNA and, depending on the type of tissue, a • Specific DNA sequences define the beginning and
single somatic cell may contain as many as 1000 the end of a gene.
mitochondria. • Exons are usually a few hundred nucleotides long.
• Tissues that are highly dependent on oxidative • Introns may be many thousands of nucleotides in
phosphorylation (e.g. neurons) have more length.
mitochondria per cell than tissues that are less • Introns have regulatory and evolutionary roles that
dependent (e.g. some epithelial cells). are poorly understood.

A A T C A C G T A
Exon Intron
DNA

Transcription
Exon Intron
RNA

Spliced exons U U A G U G C A U
mRNA
Codon Translation

Leucine Valine Histidine Protein Leucine Valine Histidine

Amino acid

Fig. 10.2.2 Transcription and translation.

291
 10.2 INHERITED AND METABOLIC PROBLEMS

Non-protein-coding genes encodes the amino acid sequence of protein polypep-

tides. By this view, a gene encodes a single protein
A unit of DNA sequence that encodes a functional,
polypeptide and is separated from its neighbour-
non-coding RNA transcript is also called a gene.
ing genes by long stretches of intergenic non-coding
• Non-coding RNA transcripts are not translated to ‘junk’ DNA. It is now clear that this is a simplified
make a protein polypeptide.
interpretation of the function of DNA, and of what
• Non-coding RNA transcripts help regulate the constitutes a gene. Below is a summary of our cur-
transcription and splicing of one or more genes (i.e.
rent understanding of the function of the genome,
they have a role in the regulation of gene expression).
but readers are again cautioned that this informa-
tion will rapidly become outdated and that other
The DNA sequence of a gene is transcribed resources should be consulted.
into RNA • About 5% of the human genome sequence has been
highly conserved by evolution, and most of this
To access the genetic information encoded in a gene, DNA is functionally important.
the enzyme RNA polymerase uses the gene's nucleo- • Around one-fifth of this conserved sequence
tide sequence as a template to synthesize a molecule of encodes proteins (protein-coding DNA).
RNA, a process called transcription (see Fig. 10.2.2). • Some protein-coding genes encode multiple
• RNA has a structure that is similar to DNA, proteins.
except it is usually single-stranded and uracil (U) • Some genes overlap other genes, or are embedded
substitutes for thymidine. within larger genes.
• DNA is transcribed to a primary RNA transcript; • Occasionally, parts of the sequence of two or
a series of processing reactions follow, including more different genes are spliced together at
removal of introns, producing a shorter, mature the RNA level to produce a functional
RNA transcript. transcript.
• There are many different types of mature RNA • The other four-fifths of this conserved sequence
that have a range of different functions, some is non-protein-coding DNA which encodes
unknown. functionally important RNA molecules that are
• Protein-coding genes encode a special form of not translated into proteins (i.e. non-coding RNA
mature RNA, messenger RNA (mRNA), which transcripts).
serves as a template for synthesis of a protein • Although the remaining 95% of the human genome
polypeptide. sequence is less conserved, it is estimated that
around 85% is transcribed to non-coding RNA
mRNA is translated into protein via a triplet transcripts.
nucleotide code • Transcription is pervasive and the distinction
between a gene and intergenic DNA is becoming
Protein polypeptides are made of many amino acids blurred.
joined end to end in a long chain with a specific • Cells are ‘full’ of these non-coding RNA
sequence. This chain of amino acids folds to form a transcripts but we have little understanding of
three-dimensional shape that is unique to each specific their function.
protein polypeptide.
• mRNA is translated (decoded) to make a protein
polypeptide at ribosomes.
• The information encoded in the mRNA sequence is Gene regulation
interpreted via a triplet nucleotide code (a codon),
which determines the exact amino acid sequence of The regulation of human gene expression
the protein (see Fig. 10.2.2). is incompletely understood
• There are also specific stop codons that indicate the Our understanding of the ways the human genome
end of a gene. is regulated and integrated within a cell (or an indi-
vidual) is rudimentary. It is beyond the scope of this
chapter to discuss all that is known or hypothesized
Our understanding of the function of DNA
about gene regulation, but the reader should be famil-
is changing
iar with two important concepts: inactivation of genes
Until recently the accepted understanding was that by methylation, and imprinting.
genes occur infrequently along the human genome Genes are controlled by regulatory DNA sequences.
and that these genes encode RNA, which in turn These regulatory sequences can be chemically altered
292
 Modern genetics 10.2
by the addition of methyl groups (−CH3) to the nucle- • Examples of imprinting disorders include Prader–
otides of the sequence, this is called methylation. Willi syndrome, Angelman syndrome, Russell–Silver
• Methyl groups interfere with the binding of syndrome and Beckwith–Wiedermann syndrome.
molecules to the regulatory sequence of a gene.
• The net effect of this methylation is inactivation of
Uniparental disomy
the gene.
• Methyl groups may also be removed, activating Uniparental disomy is the situation where a child
a gene. inherits two copies of a particular chromosome from
• Methylation provides a means for varying gene one parent and none from the other, rather than having
activity in normal cells. one copy from each parent. The total number of chro-
• Some genes are inactivated in cells of a specific mosomes is normal, but if any gene(s) on the chro-
tissue type(s), resulting in tissue-specific expression mosome is normally imprinted a functional genetic
of the gene. imbalance results.
• Some genes are inactivated at certain times during When the paternal copy of the gene is normally
development leading to developmental stage- imprinted:
dependent expression. • if both copies of the gene are inherited from the
• X chromosome inactivation in females is an father there are zero active copies of the gene
example of gene inactivation due to instead of the normal single active copy and a
methylation. ‘functional deletion’
The activation or silencing of a gene is usually inde- • if both copies of the gene are inherited from the
pendent of whether the gene was inherited pater- mother there are two active copies of the gene and
nally or maternally. An exception is genes that are a ‘functional duplication’.
imprinted. When the maternal copy of the gene is normally
• Imprinting is the selective inactivation of a gene imprinted:
according to the sex of the parent who passed on • if both copies of the gene are inherited from the
that gene. father there are two active copies of the gene and a
• Imprinting is a normal process and results in only ‘functional duplication’
one active copy of the gene in a cell. • if both copies of the gene are inherited from the
• Inactivation occurs because of methylation of a mother there are zero active copies of the gene
regulatory region of the gene. instead of the normal single active copy and a
• Some imprinted genes are selectively inactivated ‘functional deletion’.
when transmitted by sperm and selectively activated
when transmitted by an ovum (they are paternally
imprinted).
• Other genes demonstrate the reciprocal pattern and
Genes and networks
are selectively inactivated when transmitted by an A single gene does not produce its effect indepen-
ovum and selectively activated when transmitted by dent of the action of other genes. All processes
a sperm (they are maternally imprinted). within a single cell are regulated by an interacting
• Normally the methylation ‘imprint’ is removed in network of many genes. For example, a network of
sperm and ova so that inactivation of the imprinted several hundred different genes is involved in intra-
gene is always determined by the sex of the parent cellular galactose metabolism. This leads to a degree
of origin. of biological robustness because a mutation (genetic
• Imprinting is an example of an epigenetic error) in a single gene will not necessarily result in
mechanism; a heritable change in gene expression cellular dysfunction if the remainder of the genetic
that does not occur because of a change in DNA network is able to compensate for the mutated gene.
sequence. This network of genes is embedded within a network
Failure of normal imprinting results in overexpression of interacting cells within a single tissue or organ,
or underexpression of a gene, which may lead to a clin- which is embedded in a network of interacting tissues
ical disorder. and organs within a single individual. Individuals, in
• Failure to imprint a gene results in there being two turn, are embedded in social and environmental net-
active copies of the gene, producing a ‘functional works. The interplay and variation within and between
duplication’ of that gene. these genetic, cellular, biological, social and environ-
• Inappropriate imprinting of a gene results in there mental networks helps explain why the clinical features
being two inactive copies of the gene, producing a of a specific disorder can vary from one individual to
‘functional deletion’ of that gene. another.
293
 10.2 INHERITED AND METABOLIC PROBLEMS

The process of copying DNA and dividing it into two

Clinical example equivalent cells is called mitosis.
• The enzyme DNA polymerase copies DNA very
Cystic fibrosis (CF) is a common autosomal accurately, having an error rate of only one wrong
recessive disorder:
nucleotide pair per million processed; however,
• It affects approximately 1 in 2500 Caucasian
children.
given the size of the genome, this would amount to
• 1 in 25 healthy Caucasian adults are carriers of a mutation thousands of new errors every cell division.
that can cause CF. • There is a ‘proofreading’ mechanism that compares
• More than 2000 different mutations have been identified the original with the copied DNA strand and
in the CF gene (genetic heterogeneity). corrects any mismatched nucleotides on the new
• One mutation (deltaF508) accounts for about 80% of all strand; this mechanism reduces the overall new
mutations; other mutations are much less common.
error rate to approximately one wrong nucleotide
• Without treatment, children with classical CF usually die
during infancy. per billion processed (six new errors per cell
• With treatment, at least 50% of these children are alive in division).
their mid-40s. The accumulation of new errors is relentless. Each
The classical clinical expression (phenotype) of CF has person consists of billions of cells, each of which is
three major features: derived from the original fertilized egg. Every error
• Chronic respiratory infections leading to bronchiectasis. that was generated during any cell division will be
• Malabsorption of fat due to exocrine pancreatic
present in the descendants of that cell.
dysfunction.
• Raised sweat sodium and chloride concentrations. • By adulthood, every cell in the body has
Phenotypic variation (heterogeneity) occurs between accumulated hundreds of new errors that were not
affected individuals: present at the moment of conception.
• The survival of affected individuals (including siblings) can • Most of these errors occur in non-coding DNA and
vary by years or even decades. have no obvious adverse effect on the function of
• CF gene mutations are well documented in individuals
a gene; clinical geneticists often call such a change
with non-classical (milder) phenotypes of CF.
• Non-classical CF phenotypes include:
in the DNA sequence a non-pathogenic variant or
• typical CF respiratory disease without pancreatic polymorphism.
dysfunction • A small number of these errors occur in coding
• milder respiratory disease with no other clinical features DNA and have an adverse effect on the function of
of  CF a gene; clinical geneticists usually call a pathogenic
• male infertility due to congenital bilateral absence of the change in the DNA sequence a mutation.
vas deferens without other clinical features of CF.
Networks help explain the phenotypic heterogeneity:
• Different mutations have different effects; in general, Most genetic variations are common and do
mutations that severely disturb the function of the CF not cause disease
protein are associated with more severe disease.
• Variations in other genes influence disease severity The genome of different individuals is not exactly the
and survival; for example, genes encoding proteins in same. There are several different types of variation and
the immune system may modulate the severity of the most of these variations are non-disease causing.
respiratory infections.
Single nucleotide polymorphisms (SNPs) are com-
• Social factors are important; for example, good access
to health care and support from family and friends are mon changes to the nucleotide sequence of an individ-
associated with longer survival. ual's genome, compared to a reference sequence.
• Environmental factors such as aerobic fitness, nutritional • There are about three million SNPs in an
status, smoking and the colonization of the respiratory individual's genome.
tree by certain bacteria can affect disease severity and • SNPs are the most numerous variants in the human
survival. genome.
• Most SNPs are common and non-pathogenic
(benign); they reflect the normal variation in DNA
that exists between different individuals.
Genetic variation • SNPs play a central role in identifying and
analysing genes because they act as landmarks
What causes genetic variation?
along the DNA sequence.
DNA replication consists of accurately replicat- • A SNP that is located near a disease-causing gene
ing both copies of the three billion nucleotide-long may be associated (linked) with that disease, but is
genome that are within the nucleus of a cell. The not disease-causing.
294
resulting DNA must then be carefully separated into • A rare single nucleotide change within a gene that
two equivalent portions, one for each daughter cell. affects the function of that gene is a mutation.
 Modern genetics 10.2
A copy number variation, or CNV, is a region of DNA entire genome, a normal microarray result does not
with a variable number of copies of that particular exclude all abnormalities involving DNA.
DNA sequence compared to a reference genome; either • Microarray does not detect most single-gene
more copies (duplication) or fewer copies (deletion). disorders.
• There are about 100 large CNVs (longer than 1 • Microarray does not detect very small CNVs
kilobase or 1000 nucleotides) in an individual's beyond the resolution of the microarray.
genome; there are many more smaller ones. • Microarray does not reliably detect mosaicism (the
• Most CNVs are non-pathogenic; they reflect the situation where some but not all cells of the body
normal variation in DNA that exists between carry a genetic abnormality).
different individuals. • Microarray does not detect chromosome alterations
• Some CNVs cause or predispose to disease, usually that do not involve missing or extra segments of
by affecting the function of several or many genes. DNA (e.g. balanced translocations).

Pathogenic CNVs
Chromosome analysis using conventional cytogenetics Mutations
(a karyotype) can detect large pathogenic CNVs such
What types of mutation cause disease?
as gain or loss of a whole chromosome, or gain or loss
of a microscopically visible section of a chromosome. It is convenient to divide mutations into groups
However, chromosome analysis has relatively low reso- according to the scale of the mutation:
lution (5–10 megabases). Microarray is a new technol- • small-scale mutations that usually affect a single gene
ogy that can detect deletions and duplication that are • large-scale mutations that affect several or many genes.
below the resolution of conventional cytogenetics but It is also useful to divide mutations based on whether
above the single-gene level. Microarray is now com- they:
monly used in the assessment of children with devel- • primarily affect the structure of the gene(s); or
opmental disabilities (e.g. autism spectrum disorder, • primarily affect the function of the gene(s).
intellectual disability), and detects pathogenic CNVs In reality these distinctions are somewhat artificial;
in 15–20% of these children. nevertheless they provide a useful construct for under-
Although it provides a high-resolution scan of both standing the effects of various mutations. The different
non-pathogenic and pathogenic CNVs across the types of mutation are summarized in Table 10.2.1.

Table 10.2.1 Types of mutation

Scale and type of mutation Description and effect Disease examples*

Structural errors of genes

Deletion Loss of all or part of a gene resulting in little or no protein Duchenne muscular dystrophy
product

Duplication/insertion Duplication of all or part of a gene resulting in excess Charcot–Marie–Tooth disease

(or deficiency) of protein product

Nonsense (truncating) Mutation in one or more nucleotides preventing Hurler syndrome

generation of a complete RNA strand

Missense Mutation involving one codon that causes a critical Achondroplasia

alteration in the protein sequence

Splicing site mutation Mutation involving the nucleotides which identify the
junction between exons/introns leading to generation of
an abnormal RNA strand

Functional errors of genes

Regulatory Mutation in the regulatory region of a gene causing Thalassaemia
inappropriate activation or silencing of gene
295
Continued
 10.2 INHERITED AND METABOLIC PROBLEMS

Table 10.2.1 Types of mutation—Cont'd

Scale and type of mutation Description and effect Disease examples*

Abnormal imprint Reversal of the normal silencing or activation genes in Beckwith–Weidemann syndrome
the maternal or paternal germline

Unstable triplet repeat Increase in the number of copies of a repeated triplet Fragile X syndrome
of nucleotides causing abnormal function of a gene or
protein product

Structural errors of
chromosomes†
Monosomy (deletion) Loss of whole (or part) of a chromosome Turner syndrome

Trisomy (duplication) Excess of the whole (or part) of a chromosome Down syndrome

Triploidy Presence of an extra copy of each chromosome Miscarriage

Functional errors of
chromosomes
Uniparental disomy Both copies of all or part of a chromosome inherited from Prader–Willi syndrome
just one parent

*Note that different patients with the same genetic disorder may have different types of mutation in the same gene.
†
Structural errors of part of a chromosome are often called a copy number variation, or CNV.

Triplet repeat mutations • This tendency to expand means a genetic disorder

due to a triplet repeat mutation may become
Triplet repeat mutations are a special class of muta-
more severe when passed from parent to child, a
tion. Throughout the genome there are many loca-
phenomenon called anticipation.
tions where pairs or triplets of nucleotides are present
as multiple adjacent copies. Most of these nucleotide
• In some cases there is a parent-of-origin effect, and
large expansions are seen mainly in the gametes
repeats occur in non-coding DNA and are of no clini-
from the parent of one sex; this reflects a difference
cal consequence. However, some occur within genes or
in the survival of gametes with large expansions
within nearby regulatory regions.
(not a tendency to expand more in a sperm versus
• A number of genes contain the DNA sequence
an ovum, or vice versa).
CAG–CAG–CAG repeated many times.
• The codon CAG encodes the amino acid glutamine.
• The proteins synthesized from genes with runs of
CAG repeats contain regions of polyglutamine. Clinical example
• The number of CAG repeats in a gene varies within
Four-year-old Andrew has behavioural
a certain normal range in the general population.
problems, delayed language development and
• If the number of CAG repeats in an exon mild dysmorphic features (large everted ears,
increases outside this normal range, the length of an elongated face and hyperflexible joints). His
polyglutamine in the protein increases abnormally; mother had learning difficulties at school, particularly with
this usually interferes with protein function or mathematics. A maternal uncle has a moderate intellectual
degradation. disability. A molecular test for fragile X syndrome (FRAX)
• If the number of CAG repeats in a regulatory identified a full mutation in the FMR1 gene.
region expands outside this normal range, a gene Discussion
may be inactivated. FRAX is caused by a triplet repeat mutation in the FMR1 gene,
• Larger degrees of expansion tend to be associated which is located on the X chromosome. There are two forms
with more severe disruption of the normal function of the genetic error: a pre-mutation (55–200 CAG repeats,
rather than the normal 5–44) and a full mutation (more than
of the gene or protein.
200 repeats). Males with a full mutation have intellectual
One of the most striking features of these expanded impairment, usually in the moderate intellectual disability
triplet repeat mutations is that they tend to increase in range. Males with a pre-mutation do not have intellectual
296
size (expand) during cell division.
 Modern genetics 10.2
• A mutation on one X chromosome can result
disability, but are at risk of developing fragile X-related in patchy birth defects as the mutation will
tremor ataxia syndrome (FXTAS) as adults. Approximately interfere with the development of cells in which
50% of females with a full mutation have an intellectual
the mutant X chromosome is left active; cells that
disability, which is usually in the mild range. Females with
a pre-mutation do not have intellectual disability, but about inactivate the mutant X chromosome will develop
20% develop premature ovarian failure. normally.
• The cells giving rise to the female's ovaries will
also have the mutation, so the mutation may be
transmitted to her children.
Mutations that arise in an egg or sperm can be
transmitted to offspring
The majority of the mutations present at conception
Clinical example
are new mutations that occurred during the formation
of the individual ovum or sperm. The frequency of Osteogenesis imperfecta type II is a severe
new mutations in gametes accounts for much of the bone dysplasia that is usually fatal in the
high failure rate of human conception; three-quarters newborn period.
of all human conceptions fail to survive longer than • E ach affected baby has a new mutation that occurred
the first 6 weeks of a pregnancy (most of these mis- in one of the gamete cells from which the baby
carriages occur before a woman is aware that she is developed.
pregnant). • The parents are at a 5% risk of having a second
affected child.
• A sporadic (new) mutation that occurred during the • Familial cases are due to one parent having a mixture
formation of a gamete cell in one generation can be of mutant and normal gamete cells in their testes or
transmitted to the next generation, and become a ovaries (i.e. gonadal mosaicism).
familial mutation. • The mutant gamete cells are derived from a single
mutant precursor cell in the parent.

Mutations occurring during embryogenesis are

limited to specific lineages of cells
Mutations occurring after embryogenesis cause
Embryogenesis encompasses the first 12 weeks of
many of the features of ageing
a pregnancy. It is the period when the organs of the
body are formed. After embryogenesis is completed, new mutations
• A new mutation that occurs during embryogenesis continue to be generated and are transmitted to all the
may affect the structure, function or survival of progeny of a cell.
tissues derived from that cell lineage. • As a person ages, mutations accumulate within
• The other cells of the body that lack this mutation a cell's genetic code and eventually interfere with
function normally. cellular function.
• A mixture of normal cells and cells with a mutation • If the cellular dysfunction results in cell death, the
is called somatic mosaicism. loss of an individual cell will usually go unnoticed.
• If a mosaic mutation is not present in the gonads, • If a cell accumulates mutations in a number of
it will not be transmitted to the next generation and growth-limiting genes, the consequence will be
will not be familial. failure to regulate cell division; this is clinically
• If a new mutation occurs in a cell that contributes evident as cancer.
to the formation of an ovary or testis, the mature The progressive accumulation of mutations in the
gonad will contain a mixture of gamete cell nuclear DNA is compounded by a similar process
precursors, some that have and others that do not occurring in mitochondrial genes.
have the mutation; this situation is called gonadal • Mutations accumulate in mtDNA 10–20 times
mosaicism. faster than in nuclear genes.
• Gonadal mosaicism can result in a healthy person • A number of factors are responsible, including
having a number of children with the same ‘new’ the relatively high exposure of mtDNA to oxygen
mutation. radicals (a byproduct of ATP synthesis) and the
The focal effects of a mosaic mutation can be mim- lack of protective proteins and effective DNA
icked by X inactivation. repair mechanisms in mitochondria.
• Females inactivate one X chromosome in each cell • mtDNA is replicated independently of nuclear
of the body (lyonization). DNA and, as a result, mitochondrial mutations
• In healthy females there is little to distinguish cells accumulate in cells (such as neurons) that are not
297
that have inactivated different X chromosomes. actively dividing.
 10.2 INHERITED AND METABOLIC PROBLEMS

• As a person ages, mtDNA mutations may be so

widespread that energy production in many cells is Patterns of inheritance
compromised, which may result in problems such as Mendelian disorders are those that are explained
cardiac failure or dementia. by mutations in a single nuclear gene. There are five
basic patterns of mendelian inheritance (see below).
How are mutations inherited? However, most genetic or partially genetic disorders
The fact that an individual's genetic code is not static are not caused by mutations in a single gene; they are
but is accumulating mutations constantly from the caused by mutations in genes at multiple loci (oligo-
moment of conception has been highlighted above. genic and polygenic disorders). Environmental factors
• Mutations that are present only in somatic cells make an important contribution to the clinical expres-
may account for the development of clinical sion or phenotype of many polygenic disorders; thus
problems in an individual, but they are not passed they are often considered to be multifactorial.
to the next generation.
• Mutations that are present in the cells of the gonads Autosomal recessive inheritance
may be transmitted to a fertilized egg in the next
generation. If a mutation interferes with the function of one copy
• A mutation that is present at conception will of a gene, the presence of the other normal copy of
be present subsequently in the ovaries or testes the gene may be sufficient to prevent the development
of the developing child; if the child survives to of a condition. This type of mutation could be inher-
have children of their own, the mutation may be ited by many family members who remain healthy
transmitted again to the next generation. and are unaware that they are carrying the muta-
tion. This is called an autosomal recessive mutation
(Fig. 10.2.3).
Practical points
Autosomal dominant inheritance
• Inaccurate DNA copying generates new mutations that
are transmitted to all of a cell's progeny. For certain autosomal genes and mutations, the pres-
• New mutations account for many congenital abnormalities ence of one abnormal gene may be sufficient to cause
and disorders of ageing.
a clinical disorder. In this situation, most of the family
• Mutations that are present only in somatic cells are not
inherited. members who have the mutated gene will be affected.
• Mutations in the ovary or testis may be inherited. This type of mutation is called an autosomal domi-
nant mutation (Fig. 10.2.4).

Hallmarks of an autosomal recessive disorders

• often affect metabolic pathways Carrier parents
• affect both males and females (heterozygous)
• affected individuals are usually born to unaffected parents
• other members of the extended family are also unaffected
• vertical transmission (from an affected individual to the next
generation) is not usually seen
Gametes
• an affected individual carries a mutation in both copies of an
autosomal gene and is homozygous for the disorder
• a person who carries a mutation of one copy of a particular
gene is heterozygous; they are not affected by the disorder
• the frequency of the disorder is determined by the frequency
of carriers in the population
• the carrier frequency of some disorders is increased in certain
ethnic groups (e.g. Gaucher disease in Askenazi Jews; cystic
fibrosis in Caucasians)
Possible
• parental consanguinity increases the chance of having an
offspring
affected child
Affected Carrier Carrier Not a carrier
Examples
• congenital adrenal hyperplasia • phenylketonuria (PKU) 1/4 (25%) 2/4 (50%) 1/4 (25%)
• recessive congenital deafness • beta-thalassaemia
• spinal muscular atrophy (SMA) • cystic fibrosis
• hereditary haemochromatosis • sickle cell disease Key Gene with a mutation Normal gene
• Tay--Sachs disease • MCAD deficiency

298
Fig. 10.2.3 Autosomal recessive inheritance. MCAD, medium-chain acyl-CoA dehydrogenase.
 Modern genetics 10.2

Hallmarks of an autosomal dominant disorders One affected and one

• often affect genes coding for structural coding unaffected parent
• affect both males and females
• transmitted by males and females
• vertical transmission is seen; affected parents may have
affected children
• other members of the extended family may also be affected Gametes
• an affected individual carries a mutation in one copy of a
particular gene and is heterozygous

Complexities
• variable expression; different family members with the same
disease-causing mutation show different features of the disease
• non-penetrance; when an individual carries a disease-causing
mutation but is unaffected (phenotypically normal)
• gonadal mosaicism (see text) Possible
• lack of family history may be explained by a new mutation, offspring
non-penetrance or non-paternity
Affected Affected Not affected Not affected
Examples
• Marfan syndrome • neurofibromatosis type 1 2/4 (50%) 2/4 (50%)
• Huntington disease • achondroplasia
Key
• familial hypercholesterolaemia • long QT syndrome Gene with a mutation Normal gene
• hypertrophic cardiomyopathy • familial retinoblastoma

Fig. 10.2.4 Autosomal dominant inheritance.

X-linked recessive inheritance (Fig. 10.2.5). Recurrence risk counselling is a major

challenge in families with affected male members.
If a female has a recessive mutation on one X chro-
mosome, the presence of the normal gene on the
X-linked dominant inheritance
other X chromosome usually prevents the develop-
ment of a severe genetic disorder. A male has just This pattern of inheritance is usually characterized
one X ­chromosome and a mutation in a male's sin- by a similar disease frequency in males and females,
gle X ­chromo­some gene results in a genetic disorder although the female phenotype is often milder than

Hallmarks of an X-linked recessive disorders

• affects mainly males Carrier mother and
• females unaffected or have very mild disease unaffected father
• affected males never pass the disease to their sons, but pass
the mutated X to all their unaffected daughters, who are
obligate carriers
• female carriers pass the mutated X to half their sons (who are
Gametes
affected) and half their daughters (who are carriers)
• an affected male carries a mutation on his only copy of a
particular X-linked gene and is hemizygous
• a carrier female carries a mutation of one copy of a particular
X-linked gene and is heterozygous

Complexities
• transmission from an affected male to a carrier daughter to an
affected male grandchild (the ‘knight’s move’)
Possible
• skewed X-inactivation in affected females (see text)
offspring
• recurrence risk counselling in families with one affected male
is difficult Female carrier Male Female Male
Not affected Affected Not a carrier Not affected
Examples Not affected
• Duchenne muscular dystrophy • Haemophilia A
• red–green colour blindness • Lesch–Nyhan syndrome
• X-linked retinitis pigmentosa • Fabry disease Key X chromosome Normal X Normal Y
• X-linked mental retardation • Hunter disease with a mutation chromosome chromosome

299
Fig. 10.2.5 X-linked recessive inheritance.
 10.2 INHERITED AND METABOLIC PROBLEMS

the male phenotype (sex-dependent expression). Mitochondrial DNA mutations and maternal
The absence of male-to-male transmission distin- inheritance
guishes X-linked dominant disorders from autosomal
An abnormality of mitochondrial function due to a
dominant disorders. Regarding X-linked dominant
mutation in a nuclear gene demonstrates autosomal
disorders:
recessive, autosomal dominant or X-linked recessive
• if a male is affected, all of his daughters, but none
inheritance (see Figs 10.2.3–10.2.5). Because a nuclear
of his sons, are affected
gene mutation affects all the mitochondria in the body,
• if a female is affected, half of her daughters and
affected individuals in a family tend to have similar
half of her sons are affected
problems.
• X-linked dominant disorders are uncommon
Mitochondrial abnormalities due to a mutation in
• examples include X-linked dominant forms of
a mtDNA gene are maternally inherited (Fig. 10.2.6).
Alport syndrome and hypophosphataemic rickets
An affected individual may have a mixture of mutant
• Rett syndrome is a rare, progressive, X-linked
and non-mutant (wild-type) mitochondria, which is
dominant neurological disorder that almost
called heteroplasmy. Heteroplasmy leads to marked
exclusively affects females, being lethal in affected
variability in both the severity and the type of tissue
males.
involved within one family.

Y-linked inheritance Polygenic and multifactorial disorders

This pattern of inheritance is characterized by exclu- Many common genetic disorders cannot be attributed
sively male-to-male transmission of a disorder that to a mutation in a single gene. They result from the
only affects males. The Y chromosome has very few interaction of a number of genes, each of which has a
genes, most of which are involved in normal male sex- mutation or polymorphism that increases an individ-
ual development, so the phenotype of a Y-linked dis- ual's susceptibility to the disorder (Fig. 10.2.7). Even
order may include infertility. if an individual has inherited a number of mutations
• Y-linked inheritance is uncommon. that places them at increased risk of a polygenic dis-
• Affected males pass their Y chromosome to every order, non-genetic factors such as nutrition or chance
son, who will be affected. may ultimately determine whether the disorder occurs.
• Females inherit an X chromosome from their A disorder due to the interaction of multiple genes and
fathers, and are not affected by a Y-linked disorder. non-genetic factors is called a multifactorial ­disorder.

Hallmarks of disorders with mitochondrial inheritance

• affect males and females
• affected males never pass the disease to their sons or daughters
• demonstrate marked variability in clinical symptoms within
a single family
Unaffected mother Father
Complexities
• difficult to recognize because of clinical variability
– if the majority of a person’s mitochondria are normal they are
unaffected Possible
– if the majority of a person's mitochondria are mutant they offspring
are severely affected
– if a person has an intermediate proportion of normal and Unaffected Unaffected Affected Severely
mutant mitochondria the clinical symptoms depend on the child child child affected
proportion of mutant mitochondria in various tissues child
– usually the probabilities of each of these outcomes cannot
be predicted
• recurrence risk counselling in families is very complicated Open circles represent normal maternal
Key mitochondria
Examples Solid circles represent mutant maternal
• Leigh syndrome • MERRF syndrome mitochondria
• Leber’s hereditary optic neuropathy • MELAS syndrome As none of the father’s mitochondria is
• mitochondrial diabetes mellitus with deafness transmitted to his children, the paternal
mitochondria are not shown

300 Fig. 10.2.6 Mitochondrial inheritance. MERRF, myoclonic epilepsy with ragged red fibers; MELAS, mitochondrial encephalomyopathy,
lactic acidosis, and stroke-like episodes.
 Modern genetics 10.2
The threshold model for multifactorial disorders
Practical points
Distribution of susceptibility Average population
in the population susceptibility
• An autosomal recessive disorder is expressed in an
Threshold of individual who is homozygous for a mutation in the
susceptibility disease gene.
• An autosomal dominant disorder is expressed in an
individual who is heterozygous for a mutation in the
disease gene.
• An X-linked disorder is transmitted via the X chromosome;
it never displays male-to-male transmission.
Proportion
affected • A mitochondrial disorder can be caused by a mutation
in nuclear DNA or mtDNA; these disorders may display
autosomal dominant, autosomal recessive, X-linked or
maternal inheritance.
• Multifactorial disorders result from the interaction of
multiple susceptibility genes, environment and chance.
• The pattern of inheritance of a condition provides essential
Susceptibility (genetic + environmental) information regarding the recurrence risk among relatives.

Fig. 10.2.7 Threshold model for multifactorial disorders. Below

the threshold of susceptibility the disorder is not expressed.
Individuals above the threshold have the disorder. Clinical example

Over the last 5 years scientists have identified a num- Hereditary haemochromatosis (HH) is an
autosomal recessive condition caused by
ber of genes that confer susceptibility to polygenic
mutations in the HFE gene, and there are two
and multifactorial disorders. Identification of addi- common mutations in the Caucasian population.
tional susceptibility genes remains a major objective • HH is characterized by abnormal storage of iron in a
in genetic research. range of body tissues.
• One mutation or polymorphism is unlikely to cause • Iron overload causes progressive organ damage
the disorder on its own. and complications including cirrhosis of the liver,
cardiomyopathy, diabetes mellitus and arthritis.
• As the number of susceptibility genes a person
• The clinical features of HH are usually manifest in
inherits increases, the likelihood of the disorder
adulthood, and are more common in males.
occurring increases. • A significant proportion of people with two abnormal HFE
• If the number of genes reaches a critical value (the genes never develop signs of organ damage.
threshold), the susceptibility is so great that the • Iron overload can be easily prevented by regular phlebotomy.
disorder occurs. It has been proposed that all babies born in Caucasian
• Multifactorial disorders typically affect between communities be screened for the presence of the common
0.1% and 1% of the population. HFE mutations. The aim would be to:
• The recurrence risk among close relatives is usually • identify individuals with two mutations, and
10–20 times higher than the general population risk. • prevent the development of iron overload in adult life by
regular phlebotomy.
• Examples: some congenital malformations such as
Some arguments in favour are:
cleft lip and neural tube defects, and disorders of • HH is common, life-threatening, yet preventable if regular
later life such as asthma, diabetes and ischaemic phlebotomy is initiated before organ damage is established.
heart disease. • Inclusion of HFE gene screening in a newborn screening
programme would be straightforward.
• Identification of a single mutation in a baby would trigger
investigation of family members and might identify other
Clinical example relatives with two mutations prior to the development of iron
overload.
Neural tube defects are a group of related Some arguments against are:
congenital malformations caused by failure of • Neonatal diagnosis is not necessary as treatment is not
normal closure of the neural tube, and are seen needed until adult life.
in approximately 1 in 1000 live births. • A newborn infant cannot give consent for testing or retain
• Examples include spina bifida, anencephaly and privacy regarding the test result.
hydranencephaly. • There may be a risk of discrimination in the long term
• Deficiency of the vitamin folate and variations in genes (e.g. in relation to life or health insurance).
responsible for folate metabolism are associated with an • A significant and ill-defined proportion of those with two
increased risk of this group of major malformations. mutations never develop iron overload. 301
 10.2 INHERITED AND METABOLIC PROBLEMS

• For a couple with an affected child, should pre­

Genetics and ethics natal diagnosis in subsequent pregnancies be an
The ability to define a genetic condition, its pattern of option?
inheritance, the gene(s) and the mutation(s) responsible • Should a couple be able to terminate a pregnancy
for the condition raises many ethical questions including: affected by a genetic condition?
• DNA is ‘shared’ amongst a family, but who ‘owns’ • Should there be widespread screening for carriers
genetic information about an individual? of common autosomal recessive disorders?
• If a serious genetic condition is identified in a
family member, should at-risk relatives be informed
when that family member wishes to keep the
information private?
Acknowledgements
• Should children be tested to determine carrier The structure and content of this chapter draws
status at a young age so that they can grow up heavily from the previous versions written by my
mindful of this knowledge, or should genetic friend and colleague Dr Graeme Suthers – I thank
testing be deferred until a child can give informed and acknowledge him for his clarity of thought and
consent to have the DNA test performed? written word.

302
 The dysmorphic child
Elizabeth Thompson, Christopher Barnett
10.3
Dysmorphic, which literally means ‘abnormal form’, gene on chromosome 8; with this, CHARGE
refers to an unusual appearance, usually of the face. association became CHARGE syndrome.
A dysmorphic child may have an underlying diagnosis • Sequence. This refers to a group of abnormalities
that could have implications for the health not only of caused by a cascade of events beginning with
the child but also of other family members if the condi- one malformation. An example is the Potter
tion is inherited. With the advent of new genetic testing sequence, which can result from any cause of
options such as array comparative genomic hybridiza- severe oligohydramnios. For example, renal
tion (‘microarray’) and an upsurge in c­ommercially agenesis results in no fetal urine, leading to severe
available tests for single-gene d ­isorders, our under- oligohydramnios, with the consequence of lung
standing of the genetic basis underlying the dysmor- hypoplasia and intrauterine constraint, causing
phic child is improving all the time. The d ­ ysmorphic limb deformities, such as talipes, and a compressed
child may present as a neonate with one or more birth facial appearance.
defects (e.g. a missing hand), or later with developmen- • Developmental field defect. This refers to a group
tal delay or intellectual disability, failure to thrive or of malformations caused by a harmful influence in
obesity, short or tall stature, a behavioural d­ isturbance a particular region of the embryo. Abnormalities
or a metabolic problem. of blood flow are thought to underlie many of
Birth defects can be classified as deformations, disrup- these. An example is hemifacial microsomia with
tions, dysplasias or malformations (see Chapter 10.1). unilateral facial hypoplasia and ear anomalies
It is important to distinguish between abnormalities and relating to an abnormality in development of first
minor variants that are common in the general popu- and second branchial arch structures.
lation. These can, however, appear in syndromes. For Why is it necessary to recognize an underlying
example, a unilateral single transverse palmar crease is ­diagnosis? Some important reasons are:
seen in 4% of normal people but is more ­common in • avoiding unnecessary investigations
Down syndrome. Some physical traits, such as an unusu- • providing information about prognosis for doctors
ally shaped nose, are a harmless family ­variant but again and family
could be part of an undiagnosed syndrome in the family. • recognizing and treating complications that need to
Making an overall diagnosis relies on recognizing a be looked for prospectively
pattern of problems. The types of pattern include: • determining the pattern of inheritance and
• Syndrome. This is from the Greek ‘running together’ recurrence risk
and refers to a cluster of physical and other features • enabling support from other families. Individual
occurring in a consistent pattern, with an implied syndromes are rare and parents become the experts
common specific cause that may be unknown. The in day-to-day management of the child and can
word syndrome is often used loosely to describe any share this with other families.
of the other diagnostic patterns described below. Are there any pitfalls in making a diagnosis? Some
• Association. This is a group of physical features areas for consideration are:
that tends to occur together but the link is not • The diagnosis must be correct: the diagnosis may
consistent enough to allow the term syndrome to be based on clinical assessment alone with no
be used. An example is the VATER association (see confirmatory tests available; diagnosis must not be
below). The distinction between a syndrome and undertaken lightly as it can be difficult to remove
an association may be artificial and, increasingly, or alter a diagnosis once it has been made, with
associations are being redefined as syndromes as harmful consequences for the child and family.
their genetic basis is identified. For example, in • Parents do not wish their child to be labelled,
2004 CHARGE association (Coloboma, Heart especially if the child is young and they do not yet
defects, Atresia choanae, Retardation of growth perceive any problems themselves.
and development, Genital and Ear anomalies) was • Doctors may attribute all new problems to the
identified as being due to mutations in the CHD7 syndrome.
303
 10.3 INHERITED AND METABOLIC PROBLEMS

upper and lower body segment length) and any

Practical points asymmetry
• always plot measurements on standard normal
• Syndromes are individually rare but collectively common. charts. Charts are available for many different body
• Accurate syndrome diagnosis is important to give parts (e.g. hand measurements, foot and ear length).
information about prognosis, associated problems, Special charts are available for certain disorders
recurrence risk and support groups for families. (e.g. Down syndrome) and various bone dysplasias
• Diagnoses are made by thorough clinical assessment (e.g. achondroplasia)
followed by use of aids such as computerized syndrome
databases.
• facial features (Fig. 10.3.1) – careful assessment of
facial anatomy often provides clues to the diagnosis
• Even an experienced clinical geneticist may not make a
syndrome diagnosis in a child with dysmorphic features. • spacing of the eyes (hypertelorism or
• It is better to make no syndrome diagnosis than to make hypotelorism, i.e. wide or closely spaced); slant of
an incorrect diagnosis. the palpebral fissures (up or down)
• shape and size of the nose and mouth
• structure and position of the ears
• chest shape and spinal curvature
How to assess the dysmorphic • proportions of the limbs, muscle bulk and tone,
joint contractures and mobility
child • structure of hands and feet (shape, length, number
Instant recognition of digits, dermal ridges, nails)
• skin pigmentary or vascular markings
A ‘waiting room diagnosis’ based on the facial ‘gestalt’ • external genitalia
might be made if the doctor has seen a person with the • any birth defects? (e.g. cleft palate)
particular syndrome before, just as most people are able • auscultate the chest for any cardiac murmurs
to recognize whether a person in the street has Down • palpate the abdomen for organomegaly.
syndrome. Often, however, the diagnosis is not apparent A photograph (with parental consent) is useful for:
initially, and the following approach is recommended. • later comparison to see how the face has changed
• consulting colleagues.
History When examining the family of a child with unusual
Special points in the medical history include: facial features:
• Antenatal history: • parents and siblings should be examined to see
• teratogens, such as drugs, viruses, maternal whether this is a family characteristic
diabetes, maternal hyperthermia (see Chapter 10.1) • photographs of them at a younger age and of other
• fetal movements – a neuromuscular disorder family members may be helpful
may cause reduced fetal movements, resulting in • in the event of a syndrome being diagnosed, the
arthrogryposis (multiple fixed deformities of joints) family should also be examined for its specific
• prenatal screening and diagnostic tests. features.
• Perinatal history:
• weight, length, head circumference and Apgar Putting it all together
scores at birth
Growth and development, behaviour, sleep patterns. • Check textbooks of syndromes (e.g. Smith's
Family history – draw a three-generation family tree Recognizable Patterns of Human Malformation)
noting miscarriages, stillbirths and deaths of siblings, by trying to match the most important dysmorphic
any history of intellectual disability, congenital abnor- features and comparing the photographs with those
malities or consanguinity (i.e. are the parents related?), of the patient.
and enquire about other family members with the • Consultation:
same features. • Referral to a paediatrician is often appropriate
in the first instance for assessment of a potential
syndromic diagnosis.
Examination
• Referral to a clinical geneticist, who is a specialist
Observe the child before undressing or disturbing her or paediatrician, trained in clinical genetics, with
him. On the other hand, the examination is not complete experience in identifying many more syndromes.
until the child has been fully undressed. Especially note: Some have a special interest and expertise in
• behaviour and alertness syndrome diagnosis (dysmorphologists).
304 • height, weight, head circumference and shape, • It's not easy! A skilled dysmorphologist makes
body proportions (e.g. height to arm span ratio, a syndrome diagnosis in a dysmorphic child in
 The dysmorphic child 10.3

2 3
4

Fig. 10.3.1 Normal human face: list of common terms used in dysmorphology. (A) 1, Supraorbital ridge; 2, outer canthus; 3, inner
canthus; 4, palpebral fissure (line from inner canthus to outer canthus); 5, nasal root; 6, nasal bridge; 7, nasal tip; 8, naris/nares; 9,
columella; 10, philtrum; 11, nasolabial fold; 12, upper vermillion border of lip. (B) Lateral view: 13, line indicating normal ear height – the
superior attachment of the pinna should lie above an imaginary line drawn through both inner canthi and running posteriorly; ‘low-set’
ears are below this line; 14, lobule; 15, helix; 16, tragus; 17, antihelix.

about 30% of cases referred by an experienced • Examples of these databases are:

paediatrician. If an overall diagnosis is not made, • POSSUM (Pictures Of Standard Syndromes and
the recognized problems must still be managed. Undiagnosed Malformations), developed by the
• Review in 3–5 years’ time is often valuable and may Genetic Health Services, Victoria, Australia
allow a diagnosis to be made as the features of the • London Dysmorphology Database
syndrome evolve over time and new information or • London Neurogenetics Database.
laboratory techniques become available.
• Computerized databases:
Investigations
• Several thousand syndromes are published, and
many are individually rare Investigations are a necessary adjunct to the assess-
• Computerized databases combine pictures and ment of the dysmorphic child in most cases.
descriptions of syndromes A routine chromosome study (karyotype) on blood
• Searches are made using a few key dysmorphic lymphocytes remains an important test in some circum­
features and a number of possible diagnoses stances. It is still widely used prenatally and a karyo-
are suggested that can be compared with the type is done when there is a high level of clinical
patient suspicion about a known chromosomal disorder such
• Success is more likely if relatively rare features as Down syndrome. A karyotype will detect balanced
are used for the search; for example, a common chromosome arrangements such as balanced translo-
feature such as hypertelorism (widely spaced eyes) cations. Occasionally translocations interrupt genes
would give a long list of suggested syndromes, and result in syndromes. In the paediatric population,
whereas imperforate anus would give a more most applications of karyotype have been superseded
manageable list to consider by microarray.
• Training and experience are needed to use these Array comparative genomic hybridization (‘microar-
305
databases effectively. ray’) is a new technology that, in many circumstances,
 10.3 INHERITED AND METABOLIC PROBLEMS

has replaced the karyotype as the primary investiga- those at high risk, who may then opt for prenatal
tion of the dysmorphic child. In simple terms, micro- diagnosis by amniocentesis (see Chapter 10.1).
array is a blood test that allows detection of gains Features of Down syndrome include:
or losses of DNA, with much higher resolution than • flat midface, flat occiput, upward slanting eyes with
standard karyotyping. In addition to diagnosing well- medial epicanthic folds, Brushfield spots in the
known syndromes such as Down syndrome (trisomy iris, palpebrae ‘purse’ on laughing or crying, small,
21, a gain of chromosome 21) and Williams syn- downturned mouth and protruding tongue, small
drome (a deletion (loss) involving numerous genes on ears, excess nuchal skin in the neonatal period
­chromosome 7), microarray has resulted in the diag- • short fingers, clinodactyly of the fifth fingers (short
nosis of a new generation of previously undescribed middle phalanges lead to incurving), single palmar
microdeletions and microduplications, many with creases, widened gap between first and second toes
distinct facial dysmorphism. A microarray should be • birth defects may be present (e.g. congenital heart
done on all children with an intellectual disability or disease in 40–50%, duodenal atresia, anal atresia
autism, especially when dysmorphic features and birth and many others)
defects are present. A microarray abnormality is found • intellectual disability of varying degree, mean IQ
in 15–20% of such cases. Parental chromosomes may less than 50, up to about 70 and declines with age;
need to be examined if a structural alteration is found, all have neuropathological changes of Alzheimer
in order to clarify the abnormality and to facilitate disease by 35–40 years with clinical onset in the
genetic counselling in the family. early 50s; is an important cause of death in adults
• reduced lifespan (around 60 years if no organ
defects)
Other investigations
• follow-up is necessary for children with Down
Other investigations such as metabolic studies or radi- syndrome to monitor for cataracts, strabismus
ology should be done as clinically indicated. (30–40%), leukaemia, hypothyroidism, obesity,
infections, constipation, obstructive sleep apnoea,
dental problems and atlantoaxial instability,
although only a minority develop neurological
Practical points complications from this
• behaviour: often happy, affectionate, friendly, but
• Taking a good history is as important as physical anxiety and depression often occur with age.
examination in the assessment of a dysmorphic child.
• Genetics:
• Microarray technology has revolutionized syndrome
diagnosis and largely replaced karyotyping as the • 95% have trisomy for chromosome 21 with a low
investigation of choice. recurrence risk
• Examination of other family members (or their • the remainder have either a robertsonian
photographs) may be required in the assessment of the translocation (a chromosome 21 attached
dysmorphic child. to another similar chromosome, usually
chromosome 14) or mosaicism (some cells with
trisomy 21 and some with a normal karyotype)
• half of the translocation cases are inherited
Common chromosomal disorders from a parent, so parental chromosomes should
be checked only if there is a translocation. An
Children with chromosome disorders, particularly of
inherited translocation is associated with an
the autosomes (chromosomes 1–22), tend to be small,
increased risk of recurrence.
dysmorphic and have intellectual impairment.

Trisomy 18 (Edwards syndrome)

Numerical chromosome disorders
The birth incidence of trisomy 18 is about 1 in 8000
Trisomy 21 (Down syndrome)
live births:
Down syndrome is the commonest chromosome dis- • many have prenatal ultrasound abnormalities and
order in liveborn babies and is the commonest genetic are then detected at amniocentesis
cause of intellectual disability: • low birth weight, prominent occiput, dysplastic low-
• Birth incidence is about 1 in 1200 live births; set ears, micrognathia (small chin), short palpebral
the overall incidence rises after maternal age of fissures, small mouth
35 years. • characteristic clenched hand posture (fifth and
306 • Maternal serum screening and ultrasonography second fingers overlap fourth and third); prominent
can be offered to all pregnant women to identify heels
 The dysmorphic child 10.3
• malformations are common (e.g. heart, brain, • Genetics:
exomphalos, kidney) • 60% have 45,X; others have a structural defect
• behaviour: poor feeding and neurological in which one X chromosome is missing all or
development, about one-third die in the first part of the p (short) arm, or there is mosaicism
month, less than 10% live beyond 1 year. 46,XX/45,X
• Genetics: • not associated with advanced maternal age;
• most have trisomy for chromosome 18, which recurrence risk not increased.
is associated with advanced maternal age; a few
have translocations
Klinefelter syndrome
• recurrence risk for trisomy or non-inherited
translocation is low and prenatal diagnosis is Klinefelter syndrome is a disorder of males in which
available for the next pregnancy. there is an additional X chromosome:
• birth incidence is about 1 in 700 liveborn males
• many present as adolescents with delayed puberty,
Trisomy 13 (Patau syndrome)
or as adults with infertility
The birth incidence of trisomy 13 is about 1 in 30 000 • occasionally present in childhood with developmental
live births: delay, especially of speech or with learning disabilities,
• many have prenatal ultrasound abnormalities and often involving reading and mathematics
are then detected at amniocentesis • overall, IQ is reduced compared with that of
• low birth weight, microcephaly with sloping siblings, but usually in normal range.
forehead, scalp defects, cleft lip and palate, broad • features: tall stature, long limbs, small testes,
flat nose, polydactyly (extra digits) undescended testes, gynaecomastia and female fat
• birth defects such as holoprosencephaly and heart distribution with age, infertility, behaviour problems
defects are common • treatment with testosterone at puberty will bring
• very poor neurological status and 50% of babies die about a more normal virilization
within the first month. • early access to reproductive medicine services (i.e. in
• Genetics: teenage years) to store sperm enhance reproductive
• most have trisomy 13 associated with advanced chances.
maternal age; some have translocations • Genetics:
• recurrence risk for trisomy is low and prenatal • 47,XXY karyotype; extra X chromosome
diagnosis is available. inherited from either parent
• recurrence risk is low.
Turner syndrome
Triple X syndrome
Turner syndrome is one of the commonest chromo-
some defects at conception but the majority miscarry, This is a syndrome in which females have an extra X
usually at an early stage of pregnancy: chromosome:
• birth incidence is around 1 in 3000 liveborn girls • birth incidence is about 1 in 1500 liveborn females
• lymphoedema of the hands and feet, and redundant • features: tall stature, few dysmorphic features
nuchal skin are common in neonates • intellect: usually in normal range, but overall the IQ
• may present in childhood with short stature, or in is lower than that of siblings. Learning difficulties,
adolescence with failure of onset of puberty delayed speech and motor milestones, poor
• variable features, which include: webbed neck, coordination and behaviour problems are common
increased carrying angle of elbows, broad chest, • pubertal development and fertility are generally
pigmented naevi, narrow, deep-set hyperconvex normal.
nails, coarctation of the aorta, idiopathic • Genetics:
hypertension, renal anomalies • 46,XXX karyotype; extra X chromosome
• intelligence usually normal but specific learning inherited from mother
problems are common; 1 in 10 has a generalized • recurrence risk to siblings and offspring is low.
learning disability
• most are infertile because the ovaries are dysplastic Structural chromosome disorders
• pregnancy has been achieved by in vitro fertilization
Velocardiofacial syndrome
using donor eggs
• the mean untreated adult height is around 140 cm. The estimated birth incidence of the velocardio-
Refer early for assessment regarding growth facial syndrome (VCFS), also called 22q deletion
307
hormone treatment. (Fig. 10.3.2, 10.3.3) or DiGeorge syndrome, may be
 10.3 INHERITED AND METABOLIC PROBLEMS

• parents should be tested, as features can be mild

and risk to each child of a carrier is 50%.
• prenatal diagnosis is available.

Trinucleotide repeat sequence disorders

Fragile X syndrome is one of the commonest causes of
intellectual disability (1 in 4000 males and 1 in 10 000
females) and is one of a range of disorders caused by
‘unstable triplet repeats’ of DNA. In fragile X syn-
drome, an unstable triplet repeat of DNA next to the
FMR1 gene expands and switches off the FMR1 gene
on the X chromosome (see below).
The features of fragile X syndrome are:
• intellectual disability of varying degree, usually
more severe in males than females
• mild dysmorphism with macrocephaly, high
forehead, long face, large jaw, big ears, post-
pubertal macro-orchidism (large testes)
• soft skin, joint laxity
• shy personality, autistic features.
• Genetics:
• a normal FMR1 gene contains a sequence with
5–54 copies of a CCG triplet
• DNA testing can identify carriers of the pre-
mutation and full mutation
• a pre-mutation contains 55–200 CCG repeats.
Male and female carriers of this do not have
Fig. 10.3.2 22q microdeletion syndrome. Note small mouth fragile X syndrome, but females can have a
and broad nasal bridge with rounded nasal tip. child with fragile X and both males and females
are at risk of other health problems (see below)

as high as 1 in 2000. It is a very variable syndrome,

with more than 180 ­clinical features described. The
diagnosis should be suspected if a child has the fol-
lowing two features:
• palatal abnormality (cleft palate, bifid uvula, veloph­
aryngeal incompetence) – found in 70% of patients
with VCFS; 11% of patients have an overt cleft palate
• conotruncal congenital heart defects (tetralogy of
Fallot, aortic arch defects, ventricular septal defect,
pulmonary atresia/stenosis, and truncus arteriosus) –
found in 70% of patients with VCFS.
The facial appearance is variable but often there is a
prominent nasal bridge, narrow nostrils and a bulbous
nasal tip. Older children often have developmental
delay and learning disabilities, social immaturity, anxi-
ety and phobias. Up to 20% of adults with the syn-
drome have psychiatric illness:
• Genetics:
• deletion of 22q11, visible on karyotyping in 15% of
cases but detectable by microarray in the remainder
308 • up to 5% who clinically appear to have the Fig. 10.3.3 Velocardiofacial syndrome. Note long mid-face,
syndrome have no detectable deletion prominent nose with a squared-off nasal tip and notched nares.
 The dysmorphic child 10.3
• a full mutation contains more than 200 CCG
repeats. All males and about 60% of females Other common disorders
with a full mutation show clinical features of the VATER association
syndrome. The full mutation in males and some
females is associated with the appearance of a VATER is an acronym for Vertebral anomalies, Anal
‘fragile site’ on light microscopy when cells are malformations, Tracheo-(O)Esophageal fistula with
cultured in folate-deficient medium (o)esophageal atresia (American spelling), Radial and
• when the CCG repeat is passed from a carrier Renal anomalies.
mother to a child (but not from a carrier father), • Cardiac and non-radial Limb abnormalities are
it is unstable and tends to enlarge common and the association is sometimes enlarged
• intellectual impairment increases with CCG to VACTERL
repeat number • no particular facial appearance is associated and
• female carriers pass the abnormal gene to 50% mental development is usually normal
of their children but only males with the full • cause is unknown
mutation and 60% of females with the full • recurrence risk is low.
mutation will be affected with the syndrome
• male pre-mutation carriers pass the pre-mutation
Noonan syndrome
unchanged to their daughters
• male pre-mutation carriers (and to a lesser extent The birth incidence of Noonan syndrome (Fig. 10.3.4)
females) are at risk after their 50s of the fragile is 1 in 1000–2500 live births. It may present in utero
X tremor ataxia syndrome (FXTAS) with ataxia, with fetal nuchal oedema. The main features are:
parkinsonian features and cognitive defects • short stature – some have growth hormone deficiency
• female pre-mutation carriers are at risk of • short neck with webbing or redundancy of skin
premature ovarian failure (menopause before the • cardiac defect, especially pulmonary stenosis,
age of 40 years) atrial septal defect, ventricular septal defect, patent
• prenatal diagnosis on chorionic villus sampling ductus arteriosus, hypertrophic cardiomyopathy
or amniocentesis is available but is complicated • characteristic chest deformity with pectus carinatum
by the uncertainty of clinical outcome in a female superiorly and pectus excavatum inferiorly
fetus carrying a full mutation. • broad chest with widely spaced nipples
Another name for fragile X is fragile XA ­syndrome. • characteristic facial appearance that changes with age:
There is also a much less common fragile XE hypertelorism, broad forehead, ptosis, down-slanting
­syndrome, which is similar clinically and at the DNA eyes in infancy, epicanthic folds, posteriorly rotated
level but involves a CCG repeat in the FMR2 gene on ears; similar facial appearance to Turner syndrome,
the X chromosome. but affects both sexes and chromosomes are normal

309
Fig. 10.3.4A,B Noonan syndrome. Note droopy eyelids (ptosis), mild hypertelorism and posteriorly-rotated low-set ears.
 10.3 INHERITED AND METABOLIC PROBLEMS

• developmental delay is common and mild intellectual Achondroplasia

disability occurs in about one-third of cases.
This is the commonest and most widely recognized
• Look for: skeletal dysplasia, affecting about 1 in 26 000–28 000
• hearing loss (one-third of cases) newborns.
• a bleeding diathesis (one-third of cases)
• Main features:
• visual problems (in most children with the syndrome).
• short stature – mean adult height is 130 cm in
• Genetics: males and 125 cm in females
• many are sporadic but transmitted to offspring of
• short limbs, most marked in the upper segments
affected people as an autosomal dominant
of the limbs (rhizomelic shortening)
• mutations in five genes (PTPN11, SOS1, KRAS,
• short fingers with ‘trident’ hand shape
RAF1 and NRAS) have been identified in about
• relatively large head, depressed nasal bridge
75% of patients with Noonan syndrome (other
• small chest.
loci may be involved)
• Radiological features are also characteristic and
• prenatal diagnosis is possible but not available allow a firm diagnosis to be made soon after
routinely.
birth.
• Length can be within the normal range at birth.
Marfan syndrome
Occasionally the diagnosis is unrecognized for a few
This is a syndrome associated with tall stature and a months.
number of other features: • Guidelines for health supervision include regular
• incidence 1–2 in 10 000 individuals follow-up throughout childhood to monitor for
• connective tissue disorder caused by mutations in complications such as:
the fibrillin1 gene (at chromosome 15q21.1) • hydrocephalus
• diagnosis is clinical and is based on established • constriction of the cervicomedullary junction,
criteria (the Ghent criteria, 2010). mainly in the first 2 years
Features include: • upper airway obstruction, especially during sleep,
• musculoskeletal: due to small upper airway size
• tall stature, long limbs with significantly increased • middle ear dysfunction and hearing loss
arm span and reduced upper to lower body • kyphosis
segment ratio • lumbosacral spinal stenosis causing symptoms in
• long fingers (arachnodactyly) older children and adults
• joint laxity and flat feet • hypermobile joints, knee instability
• chest deformity and kyphoscoliosis • varus deformity (bow legs)
• long narrow face with deep set eyes, a high • dental crowding
narrow palate and dental crowding • adverse psychosocial impact of the disorder on
• cardiovascular: the child and family.
• mitral valve prolapse • Treatment:
• dilatation of the ascending aorta in 50% of • growth hormone transiently increases growth
children, which requires drug therapy to prevent or velocity but it is not known whether final adult
delay development of aortic dissection and rupture height is increased
• eye: • limb lengthening by cutting and stretching
• ectopia lentis (dislocation of the lens, often upward) the long bones with an external distractor
• myopia is controversial. A radio-operated internal
• retinal detachment distractor device has been developed with a
• mental development is normal. reduced risk of infection compared with the
Other problems such as spontaneous pneumothorax, external one. Many families believe it is better to
striae (stretch marks of the skin) and hernias can occur. modify the environment rather than the child.
• Genetics: • Genetics:
• autosomal dominant; 25% of cases are new • Autosomal dominant inheritance is usual, but
mutations (i.e. parents are normal) most cases result from a new mutation in the
• prenatal diagnosis is possible in some families in FGRF3 (fibroblast growth factor receptor 3)
which the fibrillin1 mutation has been identified. gene.

310
 Genetic Counselling
Zornitza Stark, Martin Delatycki
10.4
Genetic counselling involves a health professional As can be seen, it covers a wide age range of patients –
talking to an individual, a couple or a family about a from pre-conception to autopsy! Traditionally a paed­
medical condition or disease that is, or may be, genetic iatric specialty, the genetic specialist is increasingly
in origin. Genetic counselling is not always provided involved in diagnosis and counselling for adult-onset
by genetic specialists (clinical geneticists or genetic diseases as more and more genes are discovered for
counsellors). It is appropriate for paediatricians and these conditions.
disease-oriented specialists to counsel in their own
area of expertise. It may be difficult, however, for the
doctor who looks after a child with a genetic condition Indications for formal genetic
to challenge a family to look at their feelings in the
genetic counselling context. Even when another prac- counselling
titioner provides genetic counselling to the immediate Anybody who suspects they might be at increased
family, the genetic specialists will often be involved in risk of a genetic condition or producing a child with
counselling the broader family. a genetic condition or birth defect may wish to receive
The provider of counselling for any particular formal genetic counselling. This includes:
condition or situation tends to evolve with time. As • individuals who themselves have a genetic disorder
new technology arises it is often the genetic specialist • couples who have had a stillbirth
who will counsel the family, but with time this often • couples who have had a child with a birth defect
falls to the disease-oriented specialist and general • couples who have had a child with intellectual disability
practitioner. An example is counselling for advanced • family history of any of the above
maternal age and tests to diagnose Down syndrome • family history of known genetic disorders, such as
prenatally. In the 1980s medical geneticists and some Huntington disease, muscular dystrophy
specialized obstetricians largely undertook this. It • multiple miscarriages
is now usually done by obstetricians and general • exposure to radiation or drugs during pregnancy
practitioners. • advanced maternal age
• consanguinity
• chromosome anomalies, including translocations
Genetic specialists and inversions
• cancers, particularly where there are multiple
Clinical geneticists are medical practitioners who affected family members and/or where there is a
undertake specialist training in this discipline. Their very young age at disease onset.
primary training is usually in paediatrics or adult
internal medicine but can be in other areas, such as
obstetrics and gynaecology.
Genetic counsellors come from a range of differ-
Process of genetic counselling
ent backgrounds, such as science, nursing and teach- Genetic counselling is the process by which individuals
ing. They undertake a basic training programme in with or at risk of an inherited disorder are advised of:
both genetics and counselling, followed by on-the-job • the consequences and nature of the disorder
training. • the probability of developing or transmitting the
Areas that are covered by genetic specialist practice disorder, and
include: • the options open to them in management and
• dysmorphology family planning in order to prevent, avoid or
• prenatal counselling and testing ameliorate the disorder.
• neurogenetics This is a complex process that encompasses both diag-
• cancer genetics nostic and supportive aspects, and genetic s­pecialists
• bone dysplasias need to allow each family sufficient time in quiet sur-
311
• metabolic diseases. roundings for this to occur.
 10.4 INHERITED AND METABOLIC PROBLEMS

Diagnostic information is gathered by obtaining study, electron microscopy or histochemistry. When

detailed histories or records of probands (the affected death can be anticipated, it is best to raise the issue of
individual through whom a family with a genetic dis- an autopsy before death occurs. In practice this works
order is ascertained). Medical records and doctors' better than asking permission immediately after the
reports are best obtained before undertaking coun- death, when families are grieving deeply. When per-
selling, as this makes the consultation more efficient. mission for an autopsy has been granted, it is of the
A pedigree is drawn with a minimum of three gener- greatest importance that the parents return to discuss
ations (see below). Probands and other members of the autopsy findings fully.
the family are examined carefully and investigated as
necessary. Only then can counselling be undertaken
properly. Clinical example
Genetic counselling is generally non-directive. A
Thi and her partner Nam were planning to
genetic specialist will not tell the family what they start a family. They sought genetic counselling
should do, but will help them reach an informed and because Thi's sister had a son with muscular
reasoned decision based on the family's own values. dystrophy. They were told that it is usually an X-linked
Thus, when a family asks, ‘Should we have another condition, in which case there would be a significant risk that
child?’, rather than giving a direct answer the genet- they could have a son with the same condition. After gaining
icist might ask, ‘How would you feel about having permission from Thi's sister, a muscle biopsy from the
affected child revealed the diagnosis of limb-girdle muscular
another child with cystic fibrosis?’ In this way fami-
dystrophy 2B, an autosomal recessive condition. Thi and
lies are encouraged to explore their own feelings. For Nam were counselled that the risk for their own children
many families it is possible to be counselled in a sin- was low.
gle visit, but some families need to return for further
discussions.
It is excellent practice to write to all families seen Diagnostic precision may require the help of
for counselling, restating the advice given to them at s­pecialists who are expert in differentiating various
the time. This letter should be written in simple, clear ­neuromuscular diseases, retinal dystrophies and other
language and outline the discussion that has taken complex problems. Dysmorphic and intellectually dis-
place. A copy of this letter is sent to the family doctor abled children often require investigation before coun-
and other specialists so that everybody involved has selling can be given. An underlying chromosomal or
the same information. This document then serves as a metabolic basis should always be excluded and specific
valuable family record, can be shown to other profes- dysmorphic syndromes identified where possible (see
sionals and overcomes the problem of selective recall. Chapters 10.1, 10.3 and 10.5).
With advances in DNA technology it has become
essential to store samples of DNA from affected family
members who are likely to die, as well as from relatives
Diagnostic precision such as grandparents. This enables subsequent family
A critical element in genetic counselling is establish- members to benefit from advancing knowledge. Such
ing the correct diagnosis. A precise diagnosis may samples can also be obtained, with permission, at the
not influence treatment but may dramatically alter time of autopsy if not collected earlier. Appropriate
the genetic counselling given to the patient and fam- samples to allow DNA to be stored include blood and
ily. An example is muscular dystrophy. There are many fibroblasts from a small skin biopsy.
different forms of muscular dystrophy. The principles
of management are similar for these (e.g. appropriate
splints, physiotherapy and occupational therapy). The
risk for other family members, however, varies consid- Obtaining and recording a family
erably depending on whether the muscular dystrophy
is autosomal dominant, autosomal recessive, X-linked
history
recessive or mitochondrial (see Chapter 10.2). To The family history is an essential part of genetic con-
counsel a family appropriately, the exact diagnosis sultations, and is usually recorded graphically as a
must be known. pedigree (family tree) using a standard set of sym-
A post-mortem examination may be necessary to bols. The pedigree provides a concise record of both
establish a precise diagnosis. This can be of particular medical data and biological relationships between
importance in a child with malformations or retarda- family members. It serves as a tool in making a diag-
tion, and in adults with neurological disorders. Post- nosis and establishing the pattern of inheritance. It
mortem examinations need to be planned in advance, can be used to identify relatives at risk of a genetic
312
so that specific tissues can be obtained for biochemical disorder, calculate their risks, and decide on the most
 Genetic Counselling 10.4
Unaffected Affected
Clinical example male male

George died from Hunter syndrome at 10 years

of age in 1975. Hunter syndrome is a rare Unaffected Affected
X-linked recessive neurodegenerative disorder. female female
In 2010 his sister Eleni came for advice about her
risk of having a son with Hunter syndrome. Fibroblasts from
George had been stored. A gene mutation was found in DNA Carrier Carrier
extracted from the fibroblasts, even though the gene had female male
been cloned 15 years after George's death. Eleni was shown
not to carry the mutation. She could therefore be reassured
that her risk of having a son with Hunter syndrome was no
higher than that of any couple without a family history of the
condition.

Married couple Sibship of two brothers

effective cascade testing strategy. The process of tak- and a sister
ing a family history provides an excellent opportu-
nity to establish rapport with the patient, and can
give valuable insights about family dynamics and
life experiences that may be influencing decision-
making within the family. Reviewing the pedigree

Monozygous twins Dizygous twins

Clinical example

Giovanna (III:4) sought advice about the risk Deceased Pregnancy,

of having a child with Norrie disease, a rare female sex unknown
X-linked retinopathy. She was concerned
because her cousin Angelo (III:2) had been Fig. 10.4.2 Standard symbols used to record a pedigree.
born with the condition. The pedigree revealed that Angelo's
mother Maria (II:2) was Giovanna's paternal aunt. As
Giovanna's father (II:3) was unaffected, Giovanna was
not at increased risk of having a boy with Norrie disease with the patient can help explore their understand-
(Fig. 10.4.1).
ing of the condition and its inheritance, and clarify
misconceptions.
The pedigree should consist of at least three
generations. The individuals in each generation
are recorded on a single horizontal line. The pedi-
gree starts with the patient and their spouse(s) or
I:1 I:2
partner(s) if any in the middle of the page. Next
record their first-degree relatives (children, siblings
and parents). Extend the pedigree to include sec-
ond-degree relatives (nieces and nephews, aunts and
uncles, grandparents and grandchildren). Ask sys-
tematically about each person, noting their names,
dates of birth, dates of death and cause of death if
II:1 II:2 II:3 II:4
applicable, and any relevant clinical information.
Enquire specifically about miscarriages, stillbirths,
reproductive problems and consanguinity – informa-
tion that is not usually volunteered. Different shad-
ing or hatching patterns can be used to record the
clinical features of each individual, in which case it is
essential to include a key or legend with the pedigree.
III:1 III:2 III:3 III:4
Examples of standard symbols used in pedigrees are
313
Fig. 10.4.1 Pedigree for Norrie disease (see Clinical example box). provided in Fig. 10.4.2.
 10.4 INHERITED AND METABOLIC PROBLEMS

data. The following are examples of conditions that

Counselling for risk generally follow multifactorial inheritance:
Following diagnostic evaluation, an estimate of risk • congenital cardiac anomalies
can be made. Risk is a numerical estimate of the likeli- • asthma
hood of a particular disorder occurring in a current or • neural tube defects, such as spina bifida and
future pregnancy. anencephaly
• coronary artery disease
• cleft lip and cleft palate
Risk in specific situations • congenital dislocation of the hip
Mendelian disorders • pyloric stenosis.
These are conditions that are autosomal dominant,
autosomal recessive or X-linked. Some 6500 mende- Clinical example
lian disorders have been described in humans. They
are comprehensively catalogued in Online Mendelian Tatiana and her partner Boris had a child
Inheritance in Man (OMIM; http://www.ncbi.nlm.nih with anencephaly, a neural tube defect.
.gov/entrez/query.fcgi?db=OMIM). Where the disor- This is an invariably fatal condition where
der follows mendelian inheritance, risk calculation is the skull and brain do not form fully. They
sought counselling about the risk of recurrence and
based on the mode of inheritance and other factors,
what could be done to avoid this, and to detect it if it
such as carrier testing. DNA testing has improved the did recur. They were informed that the risk of a neural
precision of counselling in some cases. tube defect (anencephaly, spina bifida, encephalocele)
in Tatiana's next pregnancy was about 1 in 25. This risk
could be reduced by Tatiana taking folate 5 mg daily
for 3 months prior to conception and during the first
Clinical example 3 months of pregnancy. Tatiana and Boris were told that
detailed expert ultrasonography at about 11 and 18 weeks'
Lara's brother James had recently had a gestation are the best tests to detect a neural tube defect.
child, Craig, who was diagnosed with cystic
fibrosis by newborn screening. Lara and her
partner Ivan were planning a family and
sought advice about their risk of having a child with this Unknown diagnosis
condition. Based on a community carrier rate of 1 in 25,
Lara and Ivan were informed that their risk was 1 in 200. Of children presenting with intellectual disability or
Mutation testing of the CFTR gene revealed that Craig was dysmorphic features, approximately half will not have
homozygous for the p.F508del mutation, the commonest a precise diagnosis. There is a large body of empirical
mutation that leads to cystic fibrosis. Lara was tested and data that can be used for counselling in this group. The
was shown to carry this mutation. Ivan was then tested only caveat is that appropriate examination and inves-
and was shown to carry another cystic fibrosis mutation,
tigation should be done by an experienced clinician
p.G551D. This meant that they had a 1 in 4 risk of having
a child with cystic fibrosis and that it was possible for to exclude known disorders. Although an inability to
them to have prenatal or pre-implantation testing by DNA label a child with a specific diagnosis is disappointing
analysis for this condition. and frustrating for both parents and doctors, it should
not disadvantage the affected child, as management
can be based on periodic assessment and planning.
The evolution of knowledge and new techniques
Polygenic or multifactorial inheritance
makes it necessary to look again at old problems.
There are many common disorders in which there is Thus, patient review is of the greatest importance.
a genetic component and where the inheritance pat- For example, when the underlying chromosomal frag-
tern cannot be explained simply in terms of mende- ile site in fragile X syndrome became recognized as a
lian inheritance or chromosomal rearrangement. It major cause of intellectual disability, many families
appears that these disorders are due to the cumulative required further study using new chromosome tech-
action of a number of genes together with environmen- niques. This process was repeated again using DNA
tal influences. This is called polygenic or multifactorial studies when the triplet repeat abnormality was recog-
inheritance, and numerically is the commonest pattern nized as the cause. More recently, the advent of micro-
of inheritance responsible for the familial tendency or arrays for diagnosing subtle chromosomal deletions
predisposition to various disorders. The recurrence and duplications has improved the diagnostic yield for
risk of multifactorial disorders after a single affected individuals with intellectual disability and congenital
child or with a single affected parent depends on the anomalies from about 4% from a standard karyotype
314
condition and can often be estimated from empirical to about 10%.
 Genetic Counselling 10.4
Interpretation of risk
Predictive testing
Many families do not have a good grasp of probability,
and careful discussion is needed to give meaning to any Predictive or pre-symptomatic testing is defined as a test
risk estimate. It is important to emphasize to families on an asymptomatic person that allows that individual
that chance has no memory. Simple illustrations and to know whether or not they will go on to develop the
a concrete example such as tossing two coins are often condition in question. The test may be genetic (e.g. test-
helpful. Describing the risk in more than one way can ing for the CAG triplet repeat expansion in Huntington
also be helpful for some people. Thus, some may under- disease) or may involve other types of investigation (e.g.
stand a 25% recurrence risk more readily than 1 in 4. nerve conduction studies in an asymptomatic person at
It can be helpful to put risk into the perspective of how risk of Charcot–Marie–Tooth disease).
their risk compares with that of other families. There is Predictive testing is available mainly for neurodegen-
approximately a 1 in 30 risk that any child will be born erative diseases (e.g. Huntington disease, autosomal
with a major defect. This is the risk that any family either dominant spinocerebellar ataxia) and some cancers
accepts or ignores, and is a useful point of comparison. (familial breast/ovarian cancer, familial bowel cancer).
Although genetic counselling does not aim to tell a per- It is conducted in the setting of a counselling protocol
son what to do, it is important for a counsellor to see that to give those undertaking the testing the opportunity
parents understand the meaning of any numbers used. to understand what a gene-positive or -negative result
would mean for them. Where no preventative treat-
ment is available (e.g. Huntington disease), the major-
From the nuclear to the extended ity of those at risk choose not to be tested. Predictive
family testing for conditions where the onset is generally in
adulthood and where no preventative treatment is
Where a disorder is identified in a family that puts other available is not generally undertaken on minors for
family members at significant risk of either a problem ethical reasons (when they grow up, they might not
themselves or of having a child with a problem, the want to be tested), but minors might be tested ethi-
extended family needs to be offered the opportunity to cally if there are treatment implications.
discuss this and have testing. An example of this is the
clinical example of Lara and Ivan (above), where their
risk of having a child with cystic fibrosis came to light Clinical example
only because a child was born in the family with this
condition. This form of testing is called cascade test- Sue and David were 12-year-old twins and had
ing. Examples of conditions where the extended fam- a 50% risk of having familial polyposis coli (FAP).
FAP results in an affected individual having
ily may be at risk are: a chromosome translocation,
hundreds or thousands of bowel polyps, and,
an autosomal dominant disorder such as Marfan syn- if untreated, invariably leads to malignant change in one or
drome, common recessive disorders such as cystic fibro- more polyps. Sue and David's mother, uncle and grandfather,
sis and haemochromatosis, or sex-linked disorders such as well as a number of other relatives, had FAP. The causative
as Duchenne muscular dystrophy. Where members of mutation in the APC gene in Sue and David's family was
the extended family need to be informed that there is a known. Because polyposis and malignant change may occur
risk to them or their offspring of having a genetic disor- in the teens, it was recommended that surveillance by lower
gastrointestinal tract endoscopy begin in the early teens. Sue
der, a letter from the genetic specialist can be very help-
and David underwent predictive testing. It was found that Sue
ful in conveying this sensitive information. did not have the familial mutation but David did. David was
therefore recommended to have yearly colonoscopies, but
Sue did not need them. Prior to the availability of molecular
Clinical example diagnosis, Sue would have had yearly colonoscopies until she
reached her 30s before a confident diagnosis that she did not
Fergus had symptoms of lethargy, joint pain and have FAP could be made.
abdominal pain. Extensive medical evaluation
eventually revealed that the underlying cause
for this was iron overload due to hereditary
haemochromatosis. He was shown to be homozygous for
the common C282Y mutation in the HFE gene. Fergus had a
The burden
brother, Patrick. Patrick was found to be C282Y-homozygous, The burden of an actual or possible genetic diagnosis is
and iron studies showed a moderately raised ferritin and of great importance in genetic counselling. This can be
transferrin saturation. He had had no symptoms referable to
considered in two contexts: in prenatal diagnosis and
haemochromatosis. He had regular venesections to return
his iron indices to normal. By doing this, Patrick was avoiding diagnosis in a child. Where a diagnosis is made prena-
the risk of developing symptomatic haemochromatosis. tally, the couple needs to be fully informed about the
315
problems a child with that condition may face. This is
 10.4 INHERITED AND METABOLIC PROBLEMS

to allow an informed decision about pregnancy termi- • intrauterine diagnosis

nation, but it also allows couples who choose not to • donor gametes
terminate the pregnancy to prepare for the child's birth. • donor embryo
Where there is a strong family history of a condition, • pre-implantation genetic diagnosis.
the couple may be well aware of the burden. An exam-
ple is a pregnant woman who grew up with a brother Childless lifestyle
with Duchenne muscular dystrophy, and who has pre-
natal testing that reveals that the male she is carrying A family may choose not to have children where there
has this condition. More difficult is where a diagno- is a risk of a genetic condition or where a child has
sis is made that was not specifically being looked for. been born with a genetic condition.
An example is the diagnosis of Klinefelter syndrome
(47,XXY) on a prenatal chromosome test done to look Acceptance of risk
for Down syndrome. Here much time is often required
For some couples the risk of the disorder may be accept-
to help the couple understand what that diagnosis will
able compared with the burden of other alternatives. This
mean for their child and the rest of the family.
may relate to the perceived severity of the disorder. Thus,
Similar issues exist where a child is diagnosed with
prenatal diagnosis is requested much more often when
a particular condition. For example, parents of a baby
the disorder is fatal in childhood (e.g. Duchenne mus-
recently diagnosed as having cystic fibrosis or intellec-
cular dystrophy) than when it frequently leads to many
tual disability may have little idea of what lies ahead
years of health before its onset (e.g. Huntington disease)
for the child and themselves. It is necessary to give par-
or where its severity is unpredictable and it is often rela-
ents an understanding of what is going to be involved
tively mild (e.g. neurofibromatosis type I). Religious and
in the care of the child, including the life expectancy,
cultural factors may contribute to this decision.
quality of life, treatment and variability that exist for
that disorder. Just as importantly, it is vital that, in sit-
uations where the prognosis cannot be predicted, this Adoption
uncertainty is conveyed to the parents. For instance, The number of young babies available for adoption is very
an individual with a mutation in one of the two tuber- limited because of the increase in single-parent families
ous sclerosis genes may present with severe epilepsy and and termination of pregnancies. Thus, adoption is much
profound intellectual disability, he or she may be unaf- less common and less easily arranged than in the past.
fected or may have problems that fall between these two
extremes.
Intrauterine diagnosis
Intrauterine diagnosis provides an option for many
Practical points couples. This can be offered to families who feel that
termination of pregnancy is acceptable. The range of
• Accurate diagnosis is critical to enable the most accurate disorders that can be recognized by intrauterine diag-
advice to be provided. nosis is constantly increasing (see Chapter 10.2).
• Thorough assessment and investigation is essential to give
the best chance of a specific diagnosis.
• All reproductive options should be discussed so individuals Donor gametes
and couples can make an informed choice about the best
Artificial insemination by donor (AID) is of limited
option for them.
appeal. Although many couples and ethnic groups
• Sensitivity to the emotional impact of genetic disease
is critical and should be sought and addressed in all find it unacceptable, couples should be informed about
consultations. the option of AID to determine whether or not it is
acceptable to them. AID can provide an alternative
when the father has an autosomal dominant disorder,
carries a chromosome translocation, or is a carrier for
an autosomal recessive disorder.
Alternatives for families at risk In vitro fertilization (IVF) using donor ova can be
Where a couple have a child or know they are at risk offered when a woman is a carrier for an X-linked or
of having a child with a genetic condition, there are autosomal recessive disorder, has an autosomal domi-
a number of reproductive options available to them. nant disorder, carries a chromosome translocation, or
These include: has a mitochondrial DNA mutation. Parents may find
• childless lifestyle this more acceptable, as the mother still experiences
316
• acceptance of risk the pregnancy. However, this option is limited by the
• adoption shortage of donor ova available.
 Genetic Counselling 10.4
Donor embryo a ­neonatal death. People might be concerned about
details of their family history and worry that they
Donor embryos are usually donated by couples who
might be blamed for the problem that led them to
have utilized IVF and have stored residual embryos
seek genetic counselling. It is important to use sensi-
but do not require them as they have completed their
tive language to avoid perpetuating feelings of guilt,
family. Some couples prefer this to donor sperm or
shame and stigmatization. For example, a gene may
ova, because they feel uncomfortable about only one
be referred to as being ‘changed’ or ‘altered’, rather
partner being genetically related to their offspring.
than ‘bad’ or ‘faulty’. It is also important specifically
to reassure couples that a genetic condition is not any-
Pre-implantation genetic diagnosis one's fault, and has not been caused by anything they
have done before or during the pregnancy.
In pre-implantation genetic diagnosis (PGD), cells
In counselling, the emotional impact of a birth
from an embryo produced by IVF are tested for the
defect or the risk of producing a child with a birth
disorder in question. This may be through DNA anal-
defect is explored carefully. People need an opportu-
ysis or chromosome examination by fluorescence in
nity to vent their fears and anxieties. Discussions of
situ hybridization (FISH). Only unaffected embryos
emotional issues are of equal importance to discus-
are returned to the uterus. The advantage of PGD is
sions of risk, burden and alternatives. Families who
that termination of pregnancy is not required. The
have recently lost a child may need understanding and
disadvantages are that it is expensive, labour-­intensive
reassurance about the process of mourning, and may
and often subject to long delays. For each cycle of
need to allow time before they are ready for a further
IVF, the completed pregnancy rate is well below 50%,
pregnancy.
even in fertile couples.

Emotional impact of genetic Acknowledgements

We wish to thank Dr John Rogers for teaching us
counselling about the practice of genetic counselling. Dr Rogers
Patients often feel very vulnerable when referred was the author of this chapter in the first four editions
for genetic counselling. This may be because of the of Practical Paediatrics and the current chapter draws
recent birth of a child with a disability, a stillbirth or much from that work.

317
 10.5 Inborn errors of
metabolism
David Coman, Jim McGill

Inborn errors of metabolism (IEM), or metabolic

disorders, are clinical conditions that result from a Acute metabolic decompensation
block in one of the metabolic or biochemical pathways Acute metabolic decompensations can occur at any
in the body. Although individually uncommon, col- age and are generally a result of either accumulation
lectively metabolic disorders are frequent. The main of a specific toxin or an energy deficiency or both.
forms of presentation are:
• acute decompensations – at any age, usually triggered Neonatal presentations
by an intercurrent illness or dietary changes
• neurodegeneration Neonates have limited physiological repertoire to deal
• multisystem disorders with organ dysfunction. with stress, and an acutely unwell neonate with an
IEM, particularly in those presenting acutely, remain IEM will look similar to that of other neonatal emer-
underdiagnosed. Diagnostic clues such as: gencies (e.g. sepsis, duct-dependent cardiac lesion).
• hypoglycaemia The placenta acts as an excellent filtration device, so
• presence or inappropriate absence of ketosis the ‘toxin accumulation’ decompensations often occur
• metabolic acidosis (usually with a high anion gap) at day 2–5 of life.
• lactic acidosis The following can act as clues to prompt consider-
• respiratory alkalosis ation of an IEM in an acutely unwell neonate:
are often overlooked or are misinterpreted as being • Specific pattern of biochemical derangements
due to a precipitating infection or dehydration. (Table 10.5.1). (Note that ketosis in a neonate is
Investigations often have the highest yield during an always abnormal and must prompt consideration of
acute decompensation. Rapid diagnosis and insti- an IEM)
tution of appropriate therapy are essential to avoid • Multisystem organ involvement
death or permanent neurological damage. • Specific end-organ involvement
• hepatic failure
• cardiomyopathy
• seizures and aberrations in movement and tone
Practical points (especially peripheral hypertonia combined with
central hypotonia)
• Inborn errors of metabolism, particularly those presenting • Family history of neonatal deaths or sudden infant
acutely, remain significantly underdiagnosed. death syndrome
• Presence of hypoglycaemia, presence or inappropriate • Dietary triggers (e.g. galactose; see Table 10.5.1).
absence of ketoacidosis, metabolic or lactic acidosis, or
respiratory alkalosis should raise suspicion of a disorder of
metabolism. Older children
• In a child presenting acutely with a metabolic acidosis or
Acute metabolic presentations in children beyond the
hypoglycaemia, it is essential that the first urine passed is
analysed for organic acids, as the diagnostic metabolites neonatal period are normally precipitated by a viral
can clear quickly once intravenous glucose is given. illness associated with loss of appetite or vomiting.
• Plasma ammonium values increase markedly if the Ingestion of large amounts of protein or deliberately
specimen is allowed to sit around – collect the sample on fasting (e.g. for surgery) can also precipitate an acute
ice and analyse it quickly. decompensation in some disorders. Protein aversion in
• Abnormal liver function tests are not always indicative a child warrants consideration of an IEM, especially a
of hepatic pathology; for example, increased levels of
aspartate and alanine aminotransferase (AST and ALT)
urea cycle defect or an organic aciduria.
occur in muscle disease also warranting the need to check
creatine kinase levels. Decreased conscious state
• Pan-hypopituitarism can present in the neonatal
period with hypoglycaemia plus conjugated A decreased conscious state may be the result of:
318 hyperbilirubinaemia. • metabolic encephalopathy
• metabolic strokes
 INBORN ERRORS OF METABOLISM 10.5
Table 10.5.1 Biochemical approach to delineating an inborn error of metabolism in an acutely unwell neonate

Disease pH Ketones Lactate NH4 Glucose

Maple syrup urine disease − ++ − − −

Organic acidurias Acidosis ++ ↑/− ↑/↑↑ ↑↓

Mitochondrial disorders Acidosis ++ ↑↑ −/↑ ↑↓−

Urea cycle defects Alkalosis − − ↑↑ −

Fatty acid oxidation defects Acidosis −/+ ↑ ↑ ↓

Seizures − − − − −

• hypoglycaemia OTC deficiency is an X-linked disorder, so an extended

• hyperammonaemia family pedigree on the maternal side may be useful.
• aminoacidopathies (e.g. maple syrup urine disease). Females heterozygous for the gene may be symptom-
atic. Children with milder or partial deficiencies of
Hyperammonaemia urea cycle enzymes, including some females who are
heterozygous for OTC deficiency, present later in life,
usually after a high protein intake or with catabolism
with an intercurrent illness. Abdominal pain and vom-
Clinical example iting are early symptoms.
Joseph was born at term to non-consanguineous
parents. He fed well on the breast initially Hypoglycaemia
and was discharged to home on day 2 of life.
On day 3 he was noted by his mother to be
sleepy and feeding poorly. By that afternoon he could not Clinical example
be roused for feeds and he presented to the emergency
department. He was afebrile and a septic workup was Rebecca, aged 18 months, was noted to have a
negative. Blood gases revealed a respiratory alkalosis and protuberant abdomen. She had hepatomegaly,
the alert paediatric registrar ordered a plasma ammonium, but no splenomegaly. Liver function test results
which was 830 mmol/L (normal < 60) . He was treated with were normal. Four months later she was noted
peritoneal dialysis, sodium benzoate, sodium phenylbutyrate not to be using her left arm and further testing revealed a
(alternative pathways to excrete nitrogen) and arginine, and left hemiplegia. Investigations at that time revealed marked
his ammonium level gradually returned to normal. Plasma hyperlipidaemia and an appropriate diet was introduced.
amino acid analysis showed high glutamine and low citrulline A further 5 months later, she presented acutely with
concentrations, and his urine was positive for orotic acid. DNA anorexia due to an upper respiratory tract infection. She
studies confirmed ornithine transcarbamylase deficiency, and was tachypnoeic and sweating, but conscious. Her blood
testing showed his mother was a carrier. glucose level was 0.8 mmol/L and her bicarbonate level was
12 mmol/L (normal range 22–33) with a high anion gap.
Further testing showed a lactate of 15.0 mmol/L (normal
Hyperammonaemia often causes a respiratory alkalo- 0.7–2.5). With correction of the blood glucose, the lactate
sis. Findings and possible causes of hyperammonae- concentration returned to normal.
Glycogen storage disease was suspected and confirmed
mia may be:
by a liver biopsy, which showed glycogen accumulation
• normal anion gap: in the liver and a deficiency of glucose-6-phosphatase
• urea cycle disorders (e.g. ornithine (glycogen storage disease type 1b). Hyperlipidaemia is a
transcarbamylase (OTC) deficiency) feature of this disorder. The brain can learn to use lactate
• lysinuric protein intolerance as an alternate fuel and that is why Rebecca was conscious
• transient hyperammonaemia of newborn with such a low blood glucose value.
(premature babies with respiratory distress)
• increased anion gap:
• liver disease/failure Hypoglycaemia is a common issue in general pae-
• organic acidaemias (e.g. methylmalonic diatrics; it is always abnormal in children, and
319
acidaemia, propionic acidaemia). must be investigated and managed promptly. See
 10.5 INHERITED AND METABOLIC PROBLEMS

Figures 10.5.1–10.5.3 for an overview of the practi- Metabolic acidosis (excluding lactic acidosis)
cal approaches to refining a differential diagnosis of
Common disorders in this group are methylmalonic,
hypoglycaemia and an investigation pathway and the
propionic and isovaleric acidaemias. The clinical signs
Practical points box on hypoglycaemia, below.
in a child with a metabolic acidosis are non-specific;
Tests to be collected at the time of hypoglycaemia
for example, the associated tachypnoea can be mis-
are:
taken for respiratory disease. The metabolic acidosis
• Endocrine:
has a high anion gap (metabolic acidosis plus nor-
• glucose
mal anion gap can occur with renal tubular acidosis).
• insulin
Associated laboratory abnormalities can include neu-
• C-peptide
tropenia, thrombocytopenia, hypoglycaemia or hyper-
• growth hormone
glycaemia, hypocalcaemia and hyperammonaemia.
• cortisol
The diagnosis is reached by the examination of urine
• adrenocorticotrophic hormone (ACTH)
organic acids or plasma acylcarnitine profile, both of
• Metabolic:
which are most likely to be diagnostic if the specimen
• acylcarnitine profile
is collected during the acute decompensation.
• lactate
• ammonium Lactic acidosis
• plasma amino acids
• free fatty acids These patients have an energy deficiency. The main
• ketones (β-hydroxybutyrate, acetoacetate) symptoms are due to the high anion gap acidosis. In
• urine organic acids. neonates, ketosis is an important clue and increases

Hypoglycaemia

IEM Endocrinology General

Fatty acid Ketotic hypoglycaemia

oxidation defects Hypoadrenalism
of childhood

Glycogen Non-accidental
Hypopituitarism injury
storage defects

Gluconeogenic
Hyperinsulinism
defects

Organic acidurias

Ketone utilization
defects

320
Fig. 10.5.1 Overview of differential diagnosis associated with paediatric hypoglycaemia.
 INBORN ERRORS OF METABOLISM 10.5
Hypoglycaemia Hypoglycaemia
with hepatomegaly with inappropriately low ketones

IEM IEM Endocrinology

Fatty acid oxidation

Fatty acid oxidation
defects — may be Hyperinsulinism
defects
transient

Fig. 10.5.3 Differential diagnoses of hypoglycaemia associated

Glycogen storage with inappropriately low ketone levels.
defects

the likelihood of a metabolic disease as it is not usu-

ally present with hypoxia. Some of the disorders caus-
Gluconeogenic
defects — may be
ing lactic acidosis have associated dysmorphic features
transient and malformations. The most common cause for an
acutely raised lactate concentration is poor perfu-
Fig. 10.5.2 Differential diagnoses of hypoglycaemia with sion, for example cardiac decompensation or sepsis
hepatomegaly. (Fig. 10.5.4).

Lactic acidosis

Raised lactate : pyruvate Normal lactate : pyruvate Abnormal organic acids

ratio ratio

Respiratory chain Pyruvate dehydrogenase Organic aciduria,

defects deficiency e.g. MMA

Pyruvate carboxylase Pyruvate carboxylase Fatty acid oxidation

deficiency type B deficiency type A defect
(+ hyperammonaemia
and citrullinaemia

Glycogen storage disease

type 1 (hepatomegaly)

Fructose 1,6-
bisphosphatase deficiency
(hepatomegaly)
321
Fig. 10.5.4 Metabolic approach to lactic acidosis. MMA, methylmalonic aciduria.
 10.5 INHERITED AND METABOLIC PROBLEMS

Treatment
Clinical example
The basis of treatment in the disorders of fat and pro-
A 2-year-old boy, Gareth, presented with tein metabolism is to reverse the catabolism. This is
a 2-day history of vomiting and diarrhoea. usually achieved by intravenous 10–20% dextrose with
He had reduced consciousness and was maintenance salts. Sometimes it is necessary to remove
tachypnoeic. Blood gas analysis revealed the toxins by dialysis or haemoperfusion. Many of
a compensated metabolic acidosis. His urine had large the enzymes have vitamin co-factors, and in a small
amounts of ketones on standard urine dipstick testing, and
proportion pharmacological doses of the vitamin can
was positive for Phenistix, suggesting aspirin ingestion. His
parents denied giving him aspirin but were not believed overcome the defect (e.g. vitamin B12 for methylmalo-
and were warned of the dangers of aspirin in children. The nic acidaemia and biotin for biotinidase deficiency).
boy made a good recovery with intravenous fluids and was A secondary carnitine deficiency may develop in many
discharged. Six months later he re-presented after a more of these disorders and correction of that is essential.
severe vomiting illness and was again acidotic with a pH of In the long term, disorders of protein metabolism
7.1, and the anion gap was 28 mmol/L (normal range 4–13). require a low protein diet supplemented by amino acid
He required ventilation in the intensive care unit, and after
formulas lacking the amino acid or acids that accumu-
recovery was found to have dystonia. Magnetic resonance
imaging of his brain showed basal ganglia changes. Urine late proximal to the block and boosted in those amino
organic acids showed large amounts of methylmalonic acids that are deficient distal to the block.
acid. Gareth was not responsive to vitamin B12 injections. High-glucose infusions may exacerbate disorders
The positive Phenistix was due to methylmalonic acid, of the mitochondrial respiratory chain and pyruvate
not aspirin. An opportunity had been lost to diagnose dehydrogenase deficiency. In these disorders, a high
methylmalonic aciduria before it caused permanent
proportion of calories needs to come from fats.
disability.

Diagnosis and genetics

Seizures
The greatest impediment to diagnosing an IEM is sim-
Seizures are common in metabolic conditions, espe- ply not thinking of them in the first place. Collection of
cially neonatal seizures. The most common disorders appropriate samples during an acute decompensation
in the group are non-ketotic hyperglycinaemia (diag- can hone a diagnosis rapidly (e.g. urine organic acids,
nosed by a raised cerebrospinal fluid (CSF) : plasma plasma acylcarnitine profiles and amino acids). A secure
glycine ratio), sulphite oxidase deficiency (diagnosed formal diagnosis relies on biochemical clues, but also
by urine metabolic screen), disorders of the mito- confirmation at the enzymatic and molecular level. This
chondrial respiratory chain and peroxisomal disorders can be important for accurate genetic counselling for the
(diagnosed by plasma very long-chain fatty acids and family. IEM exhibit all modes of genetic transmission,
phytanic acid). This last group is usually dysmorphic with autosomal recessive being the most common.
and hypotonic.
Defects in pyridoxine metabolism are an impor-
tant differential diagnosis in the neonate with seizures.
Diagnostic clues to the precise block in pyridoxine Neurodegeneration
metabolism can be elucidated from CSF neu- Metabolic disorders are high in the differential diagnosis
rotransmitters and urine α-aminoadipic semi-aldehyde for children who have a loss of acquired skills following
measurements. A trial of pyridoxine and pyridoxal a period of normal development. This is termed regres-
phosphate should not be withheld while awaiting these sion and the disorders causing it are termed neurode-
results. The classical story of the EEG findings and generative disorders. Seizures are a frequent associated
seizures ceasing after administration of pyridoxine is symptom. Lysosomal storage disorders, peroxisomal
not universal in these conditions. disorders and disorders of the mitochondrial respira-
Glucose transporter 1 deficiency is an important tory chain can all be associated with neurodegeneration.
consideration in children with seizures, as it causes
reduced transport of glucose across the blood–brain
barrier. It is diagnosed by a low CSF : plasma glucose
ratio. A ketogenic diet is very effective in controlling Multisystem disease (Table 10.5.2)
the seizures in this disorder. Milder forms of this con-
Lysosomal storage disorders
dition can present with dystonia alone.
Metabolic disorders can cause underlying structural In these children, the lack of one of the lysosomal
brain malformations as part of their phenotype, for enzymes results in the accumulation of the substrate
322
example the peroxisomal biogenesis defects. in a variety of tissues. Presenting features include
 INBORN ERRORS OF METABOLISM 10.5
Table 10.5.2 Clinical clues prompting consideration of an inborn error of metabolism

Clinical feature Common metabolic causes

Cataract Galactosaemia, galactokinase deficiency, peroxisomal disorders, CDG, pentose pathway defects

Dislocated lenses Homocystinuria, sulphite oxidase deficiency

Eye movement disorders Upward gaze palsy: Gaucher disease, Neimann–Pick disease type C
Rotatory nystagmus: Pelizaeus–Merzbacher disease

Retinal haemorrhages Glutaric aciduria type 1

Retinitis pigmentosa Peroxisomal disorders, NARP, CDG, lysosomal storage defects (especially Batten disease)

Cherry red spots Multiple lysosomal storage diseases

Optic atrophy Panhypopituitarism, mitochondrial respiratory chain defects, organic acidurias

Cardiomyopathy Respiratory chain disorders, CDG, carnitine deficiency, disorders of fatty acid oxidation, Pompe
disease, glycogen storage disease, lysosomal storage disease (especially Danon disease), organic
acidurias

Cardiac arrhythmias Fatty acid oxidation defects, Pompe disease, Danon disease

Strokes Homocystinuria, CDG, MELAS

Movement disorders Mitochondrial respiratory chain, neurotransmitter disorders, purine and pyrimidine defects, glutaric
aciduria type I, iron metabolism defects

Brain malformations Perisylvian polymicrogyria: mitochondrial respiratory chain defects, peroxisomal biogenesis defects
Lissencephaly: peroxisomal biogenesis defects, O-glycosylation defects
Enlarged sylvian fissures: glutaric aciduria type 1
Cerebellar atrophy/hypoplasia: CDG
Midline defects: cholesterol biosynthesis defects
White matter abnormalities: mitochondrial respiratory chain defects, cerebral organic acidurias,
lysosomal disorders
Cerebral cysts: cerebral organic acidurias

Macrocephaly Glutaric aciduria, cerebral organic acidurias

Microcephaly Multiple causes

Myopathy Respiratory chain disorders, disorders of fatty acid oxidation, Pompe disease, glycogen storage
disease, lysosomal storage disease, channelopathies

Behaviour/psychiatry Autism: purine and pyrimidine defects (Lesh–Nyhan syndrome), cholesterol biosynthesis defects
Attention-deficit/hyperactivity disorder: MPSIII
Self-mutilation: purine and pyrimidine defects (Lesh–Nyhan syndrome)

Liver failure Galactosaemia, hereditary fructose intolerance, tyrosinaemia type 1, mitochondrial respiratory chain
disorders, neonatal haemochromatosis, bile acid synthesis defects, pentose pathway defects, CDG

Obstructive jaundice Panhypopituitarism, peroxisomal disorders, α1-antitrypsin deficiency, bile acid synthesis defects,
lysosomal storage disorders (especially Niemann–Pick disease type C), CDG

Intestine Protein-losing enteropathy: CDG

Diarrhoea: neurotransmitter defects
Motility disorders: mitochondrial defects

Respiration and sleep Respiratory failure: Pompe disease

Interstitial lung disease: lysosomal storage diseases
Disturbed sleep: MPSIII

Immune deficiencies Congenital disorders of glycosylation

323
 10.5 INHERITED AND METABOLIC PROBLEMS

Table 10.5.2 Clinical clues prompting consideration of an inborn error of metabolism­­—Cont'd

Clinical feature Common metabolic causes

Renal cysts Glutaric aciduria II, CDG, peroxisomal disorders, CPT-II

Dysmorphic face Smith–Lemli–Opitz syndrome, peroxisomal disorders, CDG

Skin Ichthyosis: peroxisomal biogenesis defect, cholesterol biosynthesis defect

Gaucher disease: collodian baby
Acrodermatitis enteropathicia: zinc deficiency, biotinidase deficiency
Fungal infections: organic acidurias (T-cell dysfunction)

Abnormal hair Menke syndrome, argininosuccinic aciduria, CDG, biotinidase deficiency (alopecia)

CDG, congenital disorders of glycosylation; CPT-II, carnitine palmitoyltransferase II; MELAS, mitochondrial encephalomyopathy, lactic
acidosis and stroke-like episodes; MPSIII, mucopolysaccharidosis III; NARP, neuropathy, ataxia and retinitis pigmentosa.

­ evelopmental regression, hepatomegaly, splenomeg-

d The diagnosis should be suspected in any child with a
aly, coarse facial features, corneal clouding and skeletal combination of symptoms, particularly if they are unre-
involvement (dysostosis multiplex). Not all types have lated (e.g. CNS and liver disease or renal tubular acidosis
central nervous system (CNS) involvement. Storage and a neurodegenerative disease). The basal ganglia are
bodies may be seen in white blood cells on a blood film. often seen to be involved on magnetic resonance imaging
Diagnosis is made by urine screens for mucopolysac- (MRI) and are a useful marker for this group of disorders.
charides and oligosaccharides and confirmed by white Mitochondria have their own DNA and mitochon-
cell, plasma or fibroblast lysosomal enzyme analysis. dria are inherited from the mother via the egg (mater-
Enzyme replacement therapy (ERT) is already com- nal inheritance). Some mitochondrial diseases are
mercially available for Gaucher disease types I and inherited as mutations in the mitochondrial DNA,
III, Fabry disease, mucopolysaccharidoses types I, II for example MELAS (mitochondrial encephalopa-
and VI, and Pompe disease (glycogen storage disease thy, lactic acidosis and stroke-like episodes), MERRF
type II). The ERT does not effectively cross the blood– (myoclonic epilepsy and ragged red fibres), NARP
brain barrier and so disorders that involve the CNS (neurogenic muscle weakness, ataxia and retinitis pig-
need different approaches (intrathecal injections of the mentosa) and Leigh disease. Others, such as complex
enzymes are being trialled). IV and polymerase γ (POLG) deficiencies (mitochon-
Cord blood stem cell transplantation is an effective drial depletion syndrome), are inherited from nuclear
treatment for several lysosomal disorders with CNS genes, mainly autosomal recessive. The latter form of
involvement. The outcome depends on the neurological inheritance is more common in childhood.
status at the time of transplant. The transplanted cells The diagnosis of mitochondrial diseases is difficult.
can cross the blood–brain barrier and can therefore sta- Screening tests include raised lactate levels in the blood
bilize brain pathology. Substrate inhibition therapy is or CSF, and histological changes on muscle biopsy
also being trialled for disorders with CNS involvement. including ragged red fibres. Mutations in nuclear genes
are more common than mutations of mitochondrial
Mitochondrial respiratory chain disorders DNA in affected children and may be present only in
some tissues, such as muscle. Enzyme complexes of the
Tissues that most depend on mitochondrial adenosine
respiratory chain can be measured in muscle, liver or
triphosphate (ATP) production, such as brain, skele-
skin, and may be tissue-specific. It is important to real-
tal muscle and heart, are more frequently affected in
ize that, at present, there is no test that can exclude a
disorders of the mitochondrial respiratory chain, but
disorder of the mitochondrial respiratory chain.
the clinical presentations are vast and can occur in any
A ‘cocktail’ of co-factors of the mitochondrial respira-
organ at any age. Common presentations in childhood
tory chain, including coenzyme Q10, thiamine, ribofla-
include seizures, developmental delay, regression,
vin, vitamin C and vitamin K, are usually trialled but are
strokes, lactic acidosis, myopathy, endocrine disor-
not often of significant benefit in the majority of patients.
ders, cardiomyopathy, liver failure, renal disorders,
ophthalmoplegia, retinitis pigmentosa and deafness.
Congenital disorders of glycosylation
There are mitochondrial mutations that predispose to
­aminoglycoside toxicity, and many of the patients who Glycoproteins are proteins that require the attachment
324 developed liver failure after sodium valproate therapy of specific carbohydrate residues for their function,
had a mitochondrial disease. protein folding, signalling pathways. and receptor and
 INBORN ERRORS OF METABOLISM 10.5
cell membrane integrity. Glycosylation is a biochemi- treatment of choice for XALD. The role of Lorenzo's
cal process called post-translational modification, and oil in the treatment of this group of disorders remains
many new disorders wait to be discovered in this field unclear.
over time. Clinical presentations include multiorgan
failure, neuropathies, strabismus, dysmorphic features
(facial changes, inverted nipples, fat pads), coagula-
tion disorders, cardiomyopathy, ataxia, psychomo- Newborn screening
tor retardation, stroke-like episodes, gastrointestinal Newborn screening is performed from a blood sample
symptoms and hormonal disorders. Cerebellar hypo- collected on to blotting paper at 2–3 days of age. Tests
plasia is found on cerebral imaging in the common are performed to identify disorders that are difficult to
type 1a form. Recently, mild forms have been identi- recognize clinically and for which early treatment is bene-
fied in individuals who are able to participate in the ficial. The first and most successful disorder so diagnosed
open workforce. is phenylketonuria (PKU). Prior to newborn screening,
Transferrin isoforms is an easily accessible screening children with PKU were not diagnosed until they pre-
tool for these disorders, but a negative test result does sented in childhood with intellectual impairment. With
not exclude them. A formal diagnosis is confirmed by treatment in the neonatal period, intelligence is normal.
enzyme analysis or DNA techniques. Therapy is symp- All Australian states and New Zealand screen for PKU,
tomatic for most forms. Mannose has been successful cystic fibrosis and hypothyroidism, and most screen for
in the treatment of type 1b. galactosaemia. A new form of screening based on tan-
dem mass spectroscopy has commenced in Australia and
Peroxisomal disorders New Zealand that allows the diagnosis of organic aci-
daemias (e.g. methylmalonic acidaemia), aminoacidop-
Peroxisomes are subcellular organelles involved in the athies (e.g. maple syrup urine disease) and disorders of
metabolism of many compounds including very long- fatty acid oxidation (e.g. medium-chain acyl-CoA dehy-
chain fatty acids, phytanic acid, ether lipids and bile drogenase deficiency; MCAD) in addition to the above
acids. Disorders in this pathway often involve assem- disorders. Lysosomal storage disorders and congenital
bly problems and therefore affect all the enzymes that adrenal hyperplasia are also likely to be added to new-
normally function within the peroxisomes. Children born screening protocols in the near future.
with these biogenesis defects usually present in infancy.
Profound hypotonia is a common problem but other
features include seizures, cataracts, retinitis pigmentosa,
liver disease, renal cysts and dysfunction, and dysmor-
phic features.
Peri-mortem protocol
X-linked adrenoleukodystrophy (XALD) is the If the possibility of a metabolic disorder is considered
most common peroxisomal disorder in older children. in an infant or child who has a terminal condition, it
It usually presents at 4–10 years of age with behav- is important to arrange to collect appropriate samples
ioural disturbances, motor problems, regression and either before or as soon as possible after death (within
adrenal insufficiency. It is rapidly progressive over a 1–2 hours, but the sooner the better). This should be dis-
few years. A milder disorder of the same gene, adre- cussed with the parents before death (see Chapter 10.4)
nomyeloneuropathy (AMN), occurs later in life with and the parents must be allowed some time with their
spasticity and peripheral neuropathy as well as adre- child after death before the procedure occurs.
nal insufficiency. The adrenal insufficiency, Addison Samples of blood (plasma and serum), CSF and
disease, may be the only symptom in some males. The urine should be collected and frozen. Muscle, liver,
different forms can all occur within the one family. skin for fibroblast culture and, if indicated, heart
Bone marrow or stem cell transplantation remains the ­tissue should be collected.

325
 10.5 INHERITED AND METABOLIC PROBLEMS

Practical points Clinical example

A 3-year-old girl, Roberta, presented to a

Hypoglycaemia general paediatrician because her mother
• Ketones are normal in a child with vomiting or starvation was concerned about her gait. She had seen
from other causes. Their presence in less than expected another paediatrician when she was aged
amounts is abnormal and warrants further investigation, 18 months. At that time an ataxic, broad-based gait had
especially considering a fatty acid oxidation defect or been noted but no cause had been found. Her gait had
hyperinsulinism. deteriorated and was associated with poor muscle bulk
• Glucometers are often unreliable for measuring and low tone. There were no fasciculations. MRI showed
hypoglycaemia; all children in whom there is a suspicion changes in the basal ganglia and posterior white matter.
of hypoglycaemia should have it confirmed by a formal Her plasma lactate level was 4.2 mmol/L (normal range
blood glucose measurement. 0.7–2.5), CSF lactate was 4 mmol/L (normal 0.7–2.5) and the
• The time elapsed from the last meal to the development lactate : pyruvate ratio was 24 (10–16).
of hypoglycaemia is an essential aspect of the history A disorder of the mitochondrial respiratory chain was
and fashions the differential diagnosis list; for example, confirmed by muscle and liver biopsies, which showed
hypoglycaemia 4 hours after a meal in a 2-year-old low complex IV activity. By the age of 3½ years Rebecca
infant would prompt consideration of a glycogen storage was unable to walk or crawl and was having swallowing
disease, whereas hypoglycaemia after 24 hours of difficulties. Following placement of a gastrostomy allowing
fasting in a 2-year-old child is more likely to be ketotic improved nutrition, she became stronger but still could
hypoglycaemia of childhood. not walk.
• Hyperinsulinism creates a voracious glucose requirement
to maintain glucose homeostasis at greater than 10 mg/
kg/min (normal value usually 3–4 mg/kg/min), and is
uncommon outside the neonatal period.
• Beyond the neonatal period, plasma cortisol and urine
organic acids at the time of hypoglycaemia are the most
useful diagnostic tests.
• Ketotic hypoglycaemia of childhood is a common self-
limiting condition (usually 6–8 years of age) of uncertain
aetiology, but is a diagnosis of exclusion. Every child
with this diagnosis requires an appropriate unwell
management plan to maintain glucose homeostasis
during intercurrent illness.

326
 11
PART

NEONATAL
PROBLEMS

327
 11.1 The newborn infant:
stabilization and examination
Brian Darlow

Dr Neil Campbell began this Chapter in the fifth c­ardiac output bypasses the lungs by flowing right-
­edition of this book, thus: to-left across the foramen ovale or through the ductus
arteriosus (Fig. 11.1.1). With the infant's first breath
‘Most babies are born at term gestation
the pulmonary vascular resistance falls and blood
(37–42 weeks), following normal pregnancy
flows to the lungs; with cord clamping the peripheral
and labour, and are healthy. Having a baby vascular resistance rises and the foramen ovale is kept
is for most people one of life's most joyous shut; and with the rise in partial pressure of oxygen
and ­enriching experiences. Health ­professionals (Pao2) and withdrawal of prostaglandins produced by
should keep these matters in mind and be as the fetoplacental unit, the ductus closes. In some babies
­unobtrusive as possible with medical i­nterventions, with persistent pulmonary hypertension, these changes
­remembering we are, in a way, p
­ rivileged to share do not occur and there continues to be a right-to-left
in this special experience.’ shunt at the atrium and ductus. Such infants are tachy-
pnoeic and remain cyanosed.

Introduction Respiration
Currently, annually, there are approximately
The fetal lungs are filled with fluid that has been
295 000 babies born in Australia and 64 000 born in
secreted by the pulmonary epithelium. There is a
New Zealand. In both countries the average age of a
net outward movement of this fluid into the amni-
mother having her first baby has been increasing in
otic fluid with breathing movements during fetal life.
recent years and is now around 30 years. Approximately
Hormonal changes, including a rise in catecholamines,
92% of all births are at term (at least 37 completed
occurring with the onset of labour, lead to the reab-
weeks of gestation). Around 25% of all births are now
sorption of some of this fluid from the alveolar sacs.
by ­caesarean section, although in many other coun-
Most remaining fluid is squeezed out of the lungs dur-
tries this figure is much lower.
ing passage of the chest through the birth canal (and
It is worth being aware that the outcome from
can be seen as clear fluid around the nose and mouth
pregnancy in developed countries does not always
­
at birth). With normal chest recoil the infant's lungs
conform to parental expectations:
fill with air, s­urfactant is released from the type II
• around 1 in 5 pregnancies ends in an early miscarriage pneumocytes, lowering surface tension in the alve-
• about 6%–8% of infants are born preterm (less than oli, and the residual lung volume is established with
37 completed weeks)
the first few breaths. Infants born by caesarean sec-
• 1% of infants still die around the time of birth tion, prior to labour, are more likely to have retained
• up to 5% of infants will have some form of birth defect. lung fluid (transient ­tachypnoea of the newborn; see
Chapter 11.3).

Neonatal transition
Temperature control
Much of the adaptation of the fetus to life ex utero
takes place over a few days and may bring to light Newborn infants have a larger surface area compared
congenital disorders. If the process is disrupted,
­ to their weight than do adults and can become cold
­serious disease may result. rapidly. They are wet at birth and lose heat through
water evaporation, as well as via radiation, conduction
and convection if not clothed. After birth, hormonal
Circulation
changes lead to heat production from ­non-shivering
In utero there is high pulmonary vascular resistance thermogenesis in the brown adipose tissue. Core
such that only 10–15% of the cardiac output goes temperature is normally maintained at 36.5–37°C.
328
through the pulmonary circulation. Most of the Hypothermia will increase oxygen consumption
 The newborn infant: stabilization and examination 11.1
Normal fetal circulation

Head and
upper extremities

Ductus arteriosus

Superior vena cava

Pul. A
Right Left

Aor ta
lung lung
V
Pul.

te ry
ar y
Left

nar
Foramen ovale atrium

Pulmo

ta
Descending aor
Right
atrium
Left
ventricle

Right
Liver ventricle
a cava
r ven

Umbilical vein
rio
Infe

Umbilical arteries

Trunk and
lower extremities
Placenta

Fig. 11.1.1 The normal fetal circulation. Pul. A, pulmonary artery; Pul.V, pulmonary vein.

required for basal metabolism and is a not uncommon Fluid balance

cause of tachypnoea (see Chapter 11.3). Hypothermia
Fetal urine contributes significantly to the amniotic
may also occur in conditions such as sepsis.
fluid volume. The fetal urine is dilute and the p­ lacenta
is responsible for fluid and electrolyte haemostasis.
After birth a transition is made to water and salt con-
Metabolism
servation by the kidneys. In the first 2–3 days there
The fetus is dependent on the maternal supply of is a negative sodium and fluid balance, contribut-
glucose via the placenta, and glycogen stores are ing to much of the infant's weight loss, as well as a
laid down in the liver, muscle and heart as gesta- shift in fluid from the extracellular to the intracellular
tion increases. At birth the maternal glucose supply compartments.
ceases and the infant's glucose levels fall over the next
1–2 hours before hormonal mechanisms bring about a
Gastrointestinal
rise from mobilized stores. Infants who have delay in
feeding, preterm, growth retarded and sick infants, as The fetus swallows amniotic fluid, which is rich in
well as infants of diabetic mothers, are all at increased growth factors. After birth, coordination of sucking
329
risk of significant hypoglycaemia (see Chapter 11.2). and swallowing is readily established on day 1, and
 11.1 NEONATAL PROBLEMS

healthy term infants demand to feed from the breast Primary Last Terminal
eight or more times a day. Meconium should be passed apnoea gasp apnoea

Respiratory
by all infants by 48 hours of age. Before birth, uncon-

effort
jugated bilirubin is excreted by the placenta. During
the transition to hepatic conjugation and excretion of
bilirubin, all infants have raised serum bilirubin levels 7.4
to some degree (see Chapter 11.2). All newborn infants

pH
7.0
have low levels of vitamin K-dependent clotting fac-
6.6
tors. Intrinsic vitamin K production follows bacterial
colonization of the gut. This occurs in the first few
days, but the vitamin K deficiency state ­carries with it

Heart rate (beats/min)

150
a risk of haemorrhage (see below).

100

Neonatal stabilization
and resuscitation 50

More than 5 million neonatal deaths occur worldwide

every year, with the World Health Organization esti-
mating that 19% of these are from birth asphyxia. In
80
developing countries, nearly 1 in 4 infants who fail
to initiate and sustain breathing at birth will die, yet
Blood pressure (mmHg)

­easily acquired skills and simple equipment can help

the majority of these babies.
It is estimated that 5–10% of newborns need some 40
stimulation to breathe at birth. However, population-
based surveys in developed countries suggest only 1–2%
of term or near-term infants need active resuscitation
with inflation breaths from a bag and mask. Only 20%
of these (2 per 1000 births) progress to intubation. 0
10 20
Resuscitation of the newborn infant follows the
same principles as resuscitation at other times (A, B, Onset of Time (min)
asphyxia Ventilation Cardiac
C, D: Airway, Breathing, Cardiac, Drugs). At the same
massage
time there are important differences resulting from
the unique physiological changes associated with the Fig. 11.1.2 Physiological changes after acute asphyxia in a
infant's transition from in utero to ex utero existence, newborn monkey.
as well as pathological states presenting at birth. In
most cases it is better to talk of neonatal stabilization Primary apnoea usually lasted for 1–2 min, with
rather than resuscitation, and delayed onset of respira- HR maintained at 80–120 bpm. It could be prolonged
tion rather than birth asphyxia. by commonly used obstetric analgesic or anaesthetic
Advanced resuscitation skills can be learned read- agents. Simple tactile stimulation shortened the time
ily with the aid of mannequins and teaching scenarios. to further gasping. In terminal apnoea, the time from
There are a number of different neonatal resuscitation the start of active resuscitation (ventilation) to further
guidelines and courses. Because neonatal resuscitation gasping and regular breathing reflected the degree of
demands a team approach, it is essential to be familiar acidosis from asphyxia.
with local equipment and protocols. In the human situation there is always a chance acute
Animal experiments carried out in the 1960s looked total asphyxia may occur, although it is uncommon,
at the effects of acute, total asphyxia on heart rate for example with shoulder dystocia and a tight cord
(HR) and breathing (Fig. 11.1.2). At delivery by cae- around the neck (nuchal cord), placental abruption or
sarean section (simply to control the situation), air cord accidents. However, most peripartum hypoxia is
breathing was prevented totally by occlusion of the in the context of prolonged, partial insults, and many
airway. There was an initial period of gasping ­followed of these can be predicted by the obstetric situation and
by c­essation of breathing (primary apnoea), then a fetal monitoring. At birth, most such infants will not
­further period of gasping and finally no b ­ reathing have progressed to terminal apnoea and will respond
330
­(terminal apnoea). promptly to resuscitation.
 The newborn infant: stabilization and examination 11.1
Because the extent of the asphyxial insult will be However, the 1-minute Apgar, if low, does ­indicate the
reflected by the pH and lactate in the arterial cord need for stimulation, and the 5-minute Apgar i­ ndicates
blood, resulting from anaerobic metabolism, a ­segment the response to earlier resuscitation.
of cord can be clamped at each end and sampled up to
20 min later. Which births to attend?
All births do need someone capable of looking after
Apgar scores the mother and a separate person capable of look-
ing after the infant. Anyone involved in the practice
Since the 1950s the Apgar score (Table 11.1.1) has
of childbirth has a duty to be competent in neonatal
been used to assess the infant's condition at birth and
resuscitation and a responsibility to see that the appro-
to differentiate those who are vigorous or depressed.
priate equipment is available and in working order.
Many health jurisdictions require the Apgar score at
Resuscitators should become familiar with their
1 and 5 minutes to be recorded.
equipment, or that provided in the health f­acility in
which they practise. The main tools to deliver p ­ ositive
pressure ventilation, short of intubation, are self-
Historical note inflating bags (Laerdal) or T-piece resuscitators
(Neopuff), and appropriately sized face masks. The
Virginia Apgar was an American obstetric anaesthetist. Her wearing of gloves is recommended.
score, based on the five signs typically used by anaesthetists
to monitor their patients, was first published in 1953 as a
method of assessing the effect of obstetrical and maternal Basic care and stabilization (Fig. 11.1.3)
anaesthetic management on the newborn. • Check the maternal and obstetric history.
• Anticipate problems.
• Check the equipment: infant overhead warmer, air
There are many problems with the Apgar score: and oxygen supply, suction apparatus, self-inflating
• Different observers will record slightly different scores. bag and appropriately sized masks and/or pressure
• There are clearly many routes to a score of 5 or 6 device and T-piece, intubation equipment, umbilical
(for example), and both this and the infant's catheter, drugs.
condition should be fully described. • Start stopwatch when infant's body is free from the
• Vigorous infants should not be suctioned (as this mother.
may lead to vagus-induced bradycardia or even • Assess the infant rapidly, particularly tone,
vocal cord occlusion) and so a score of 2 is awarded breathing and HR (use stethoscope on chest):
for ‘reflex irritability’ by inference. Such infants will 1. The infant is vigorous and crying. Leave alone (but
all have scores of 9–10. dry and wrap, or place in skin to skin contact with
• The score is much less satisfactory in very preterm mother).
or ventilated infants. 2. Infant cyanosed, irregular respirations, HR > 100.
• For an individual infant there is little correlation Gentle stimulation, check head in neutral position
between the Apgar score and pH or lactate values, (avoid neck flexion and hyperextension) to open
and unfortunately neither is good at predicting the the airway, gentle oropharyngeal suction if obvious
long-term outcome. obstruction. Most respond.

Table 11.1.1 The Apgar score

Score

0 1 2

A Appearance (colour) Pale or blue Body pink, extremities blue Pink

P Pulse rate Absent < 100 > 100

G Grimace (reflex irritability – the None Some, e.g. grimace Vigorous, cry
response to nasal suction)

A Activity (tone) Floppy Some flexion Good flexion

R Respiratory rate Apnoeic Irregular, weak Active crying 331

 11.1 NEONATAL PROBLEMS

Newborn life support

Term gestation? Yes Routine care:

Breathing or crying prevent heat loss
Good tone? Stay with Ongoing evaluation
mother
No

Prevent heat loss

Ensure open airway No
Stimulate

Heart rate below 100? No Laboured breathing or

Gasping or apnoea? persistent cyanosis?

Yes Yes
At all stages ask: do you need help?

Positive pressure Ensure open airway

ventilation SpO2 monitoring
SpO2 monitoring Consider CPAP

No
Heart rate below 100? Post-resuscitation
care

Yes

Ensure open airway

Reduce leaks
Considere increasing
pressure and oxygen

Heart rate below 60?

Yes

Chest compressions Targeted preductal

90/min SpO2 after birth
3 compressions to each
1 min 60–70%
breath
2 min 65–85%
100% oxygen
3 min 70–90%
Consider intubation
4 min 75–90%
or LMA
5 min 80–90%
10 min 85–90%

Heart rate below 60?

Yes

Venous access,
adrenaline
Adrenaline IV
Consider volume
10–30 µg/kg
expansion
332

Fig. 11.1.3 Newborn resuscitation algorithm. CPAP, continuous positive airway pressure; LMA, laryngeal mask airway; SpO2, peripheral
oxygen saturation Australian Resuscitation Council 2010.
 The newborn infant: stabilization and examination 11.1
3. Still inadequate respirations or apnoea, or • With the thumb and index finger apply even
HR <100: (30 seconds from birth). Three to five downward pressure on top of the mask (D).
slow (3 seconds) breaths then bag and mask • Do not let the fingers encroach on to the skirt of
at 40–60 per minute. Have pop-off valve or the mask.
manometer set at 30 cmH2O, but lower pressures • The other fingers perform a chin lift with upward
are probably adequate. Check the response: should pressure.
be visible chest movement and increase in HR.
4. HR < 60 and not increasing, inadequate respirations
Additional notes
or apnoea. Proceed to ADVANCED resuscitation.
Call for help. Intubate, if skilled. Otherwise continue The use of supplementary oxygen
with bag and mask, check head in neutral position in newborn resuscitation
with jaw thrust, check chest movement and air entry. The time-honoured practice of using 100% oxygen in
Give 3 cardiac compressions (see below) to 1 breath. neonatal resuscitation has recently been challenged in
Consider drugs: IV adrenaline (epinephrine). a number of ways, including trials comparing resuscita-
• Call for help at any time tion in air or 100% oxygen in term infants. Meta-analyses
• Assessment of colour is considered unreliable of these studies have resulted in the recommendation
so oxygenation should be assessed by pulse that, for term infants, room air should be used for initial
oximetry. Applying the probe to the right hand resuscitation with oxygen as backup if resuscitation fails.
or wrist before connecting to the instrument Ideally blended air and ­oxygen will be available with the
produces faster readings. concentration delivered guided by preductal (probe
placed on right hand or wrist) pulse oximetry. Note that
Studies have shown the appropriate technique to even in healthy term newborns it may take 5–10 minutes
achieve the most effective use of a face mask during for the preductal oxygen saturation to reach 90%.
neonatal resuscitation (Fig. 11.1.4).
• Hold the newborn head in a neutral position (A).
• Gently roll the mask on to the face from the tip of Chest compressions
the chin (B, C).
Newborn infants generally experience bradycardia
• Hold the mask with thumb and index finger at the
­secondary to respiratory problems rather than ­primary
top where the silicone is thickest (D).
cardiac arrest:
• It is essential that chest compressions follow
Practical points a period of adequate lung inflation – which is
generally the most effective.
Neonatal resuscitation • Chest compressions must not divert attention from
• It is essential to be familiar with the equipment in the ongoing lung inflation, or compromise adequate
birthing location and with the local resuscitation protocols. ventilation.
• The vast majority of term or near-term infants do not need • The correct method is with hands encircling the
active resuscitation. chest and thumbs on the lower third of the sternum,
• Apgar scores are useful to assess the infant's condition at compressing about one-third of the depth of the chest.
birth but do not predict long-term outcome or the cause of
any future disability.
• One large survey of over 30 000 births suggested
• Initial resuscitation with air is at least as good as 100%
that only around 1 per 1000 infants ‘need’ cardiac
oxygen for term or near-term infants. compressions. It is likely that chest compressions
are overused.

Fig. 11.1.4 Technique for using face mask in neonatal resuscitation. (From Schilleman K, Witlox RS, Lopriore E et al 2010 Leak and 333
obstruction with mask ventilation during simulated neonatal resuscitation. Arch Dis Child Fetal Neonatal Ed 2010;95:F398–F402, with
permission.)
 11.1 NEONATAL PROBLEMS

Practical points Newborn examination

It takes time to get to know the range of normality and
Umbilical vein cannulation to feel comfortable when examining newborn babies.
• When urgent venous access is required, placement of an New parents spend many hours looking at (examin-
umbilical vein catheter is easy to achieve.
ing) their offspring and may have concerns that are
• Place a cord tie around the cord and control any bleeding
by tying tight.
easily put to rest by a compassionate professional.
• Cut the cord 1 cm from the skin.
• The vein is oval and flush with the cord; the two arteries Purpose of newborn examination
usually project slightly from the surface.
• Have ready a sterile umbilical catheter, or other sterile • To check successful perinatal transition achieved
catheter, filled with 0.9% saline and attached to a syringe. and that the infant is healthy
• This is inserted 3–5 cm into the vein; there should be no • To screen for significant anomalies
obstruction. • To establish baseline for further assessments
(weight, length, head circumference)
• To address any parental concerns and provide
reassurance
Meconium exposure • To continue provision of health advice (e.g. supine
sleeping, breastfeeding, etc.).
Up to 10–20% of deliveries are accompanied by Excellent comprehensive guidelines are to be found in
­meconium-stained liquor. textbooks of neonatology.
• With delivery of the head it is possible to suction As in all medicine, the newborn examination must be
the oropharynx if the meconium is thick and seen in the context of medical history and family back-
particulate, but a well designed study found no ground. Some knowledge of family history, pre-pregnancy
benefit from this practice. maternal history, obstetric history, details of this preg-
• Following birth, if the infant is vigorous and crying, nancy (for instance, any antenatal scans) and birth must
no suctioning is required.
be elicited either from the notes and/or the mother.
• If the infant is floppy and has no or inadequate Patient-held obstetric notes greatly facilitate this process.
respirations, it is reasonable to aspirate the upper
airway under direct vision using a laryngoscope.
Who should do the examination?
Anyone with appropriate training can do the examina-
Caesarean sections
tion: midwife, nurse practitioner, general practitioner,
The Royal Australasian College of Physicians (RACP) paediatrician or junior doctor as part of the paediatric
recommends that paediatricians (or the designated team. Training will consist of some or all of: tutorials,
person for neonatal resuscitation, such as a trained visual aids that can be reviewed repeatedly, observation of
nurse practitioner) do not need to attend elective cae- an experienced practitioner and fully observed examina-
sarean sections under regional anaesthesia, although, tion by the student. It will still take some time to become
as for all births, there must be a person present whose completely familiar with the wide range of normality, and
role it is to care for the infant. people should not be shy of seeking another opinion and
telling the parents that this is being done and why.

When should it be done?

Clinical example The traditional and still the ideal, if possible, is a
­three-tiered approach:
Baby Aloisi was born at term following a
• a fairly quick examination at birth to establish the
ventouse-assisted delivery because of a delayed
second stage. He cried briefly at birth but at
sex, identify major anomalies and to check that the
30 seconds there was noted to be clear fluid infant is well and kept warm. Most newborns are
coming from both his nose and mouth, which was vigorously alert and responsive for some time after birth and
suctioned. The heart rate was then noted to fall to 80 bpm this is often a special time for new parents and their
and he was apnoeic. The senior midwife immediately infant to get to know each other
positioned the baby on his back with his head in a neutral • a full and thorough examination in the next
position and pushed the jaw forward to make sure his airway
48 hours, in the presence of one or both parents
was open. Baby Aloisi cried, his heart rate rose to 120 bpm
and he became fully pink. He was placed on his mother's • a repeat examination sometime later in the first week,
chest and covered to keep him warm. particularly to check on feeding, weight gain or loss,
334
jaundice and other aspects of the original examination.
 The newborn infant: stabilization and examination 11.1
This approach, however, is clearly tempered by early Well infants have a minor objection to being
discharge policies and will depend to some extent on undressed, but settle easily. Unwell infants are often
the place of birth and the domiciliary facilities, and either unduly irritable or lethargic. Most infants have
will often mean there is one main examination in the somewhat flexed limbs and spontaneous movements
first 24 hours. of all four limbs.
Check that the baby is not unduly pale. The hands
and feet are sometimes rather blue but the tongue and
Frequency of anomalies
mucous membranes should be pink. If there are any
Several series suggest as many as 10–20% of newborn doubts as to cyanosis, check with a saturation moni-
infants will have some anomaly, although the great tor: healthy term infants should normally have an arte-
majority are of no importance; 1–1.5% of all infants rial oxygen saturation (SaO2) of 95% or more.
have a more significant congenital anomaly. The dif- Most examiners then generally prefer to carry out
ference between a normal phenotypic variation (com- a top to toe method of review but take the opportu-
mon in the population and often familial, for example nity to examine out of sequence as it arises. For exam-
partial syndactyly of the second and third toes) and an ple, if the infant cries then look in the mouth. Various
anomaly occurring in less than 4% of the population reflexes can be elicited as the examination proceeds.
may be a matter of definition. The presence of three The Moro, or startle, reflex is when the infant's head is
or more minor anomalies greatly increases the risk of lifted a few centimetres off the bed and then allowed to
there also being a major malformation. fall back suddenly on to the examiner's hand. In a nor-
Whether born by vaginal delivery or caesarean sec- mal Moro reflex the infant cries, the arms extend and
tion, around 3% may have some form of birth trauma, then abduct across the chest. The Moro adds little to
such as bruising or a transient nerve palsy. Mostly, this the rest of the examination, is upsetting for the infant,
resolves quickly. and can usually be left out.

Outline of general examination Look for the presence of any skin lesions
Ideally, the examination should be when the infant is or rashes
quietly alert and the parents are present. Clarify that A majority of infants will have faint pink lesions over
the parents think their child is well or whether they the eyelids, temples, upper lip, nape of the neck, or
have concerns. Usually a review of feeding and passage elsewhere on the face. These capillary naevi, also called
of urine and bowel motions, plus enquiry into moth- salmon patches or stork marks, are benign and those
er's health, can establish rapport. The room should be on the front of the face nearly always fade completely.
warm and the lighting good. Many infants also have tiny white spots on the
Check that the infant has been weighed and the ­forehead, nose or cheeks. These are inclusion cysts
length and head circumference measured, and these in the epidermis called milia, and are of no conse-
values plotted on an appropriate centile chart. quence. Similar are small white to yellow papules from
­sebaceous hyperplasia on the nose and face.

Clinical example Head and scalp

Baby Jane was born at term following a • Caput is oedema over the presenting part of the
spontaneous vaginal delivery in a community scalp and will resolve in a day or two (Fig. 11.1.5).
hospital. Baby Jane's mother was 26 years old • A cephalhaematoma is a haemorrhage under the
and had been well in this first pregnancy, but periosteum of a skull bone, most commonly the
smoked 10 cigarettes a day. A 19-week ultrasound scan parietal, and so will not cross the suture lines. As
agreed with her dates and showed normal growth and
this large bruise will organize from the margins,
anatomy. The birth weight was 2780 g, length 48.5 cm and
head circumference 30.2 cm. The birth weight plotted on the it may feel firm at the edges with a soft, fluctuant
third centile on appropriate growth charts and the length centre before fully resolving.
on the 10th centile, but the head circumference was not • A subgaleal haemorrhage, bleeding into the scalp in
plotted. Baby Jane was thought to be well after birth with the subaponeurotic space, is much rarer and more
normoglycaemia, and went home on day 3. On day 7, she serious because significant hypovolaemia and anaemia
was seen at home when the domiciliary midwife plotted the can result. All of the scalp feels boggy and loose.
head circumference and found it to be 4 cm below the third
centile. Baby Jane was immediately referred for a paediatric
• There is often considerable moulding of the skull
opinion and MRI a few days later showed significant (i.e. movement of skull bones to allow passage
intracranial anomalies. through the birth canal), and sutures may be
335
overriding but should move separately.
 11.1 NEONATAL PROBLEMS

Caput
Cephalhaematoma
Subaponeurotic haemorrhage
Extradural haemorrhage
Skin
Epicranial aponeurosis
Loose areolar tissue
Periosteum
Skull

Fig. 11.1.5 Sites of extracranial and extradural haemorrhage in the newborn.

• A clear ridge over the suture, most commonly of • Subconjunctival haemorrhages are common and
the metopic (anterior part of the sagittal) suture, resolve without problems.
may indicate craniosynostosis or premature fusion • Elicit a normal red reflex with a small torch.
and will need neurosurgical referral. • An ophthalmoscope is needed to look for cataracts
• The anterior fontanelle may vary hugely in size but (most cannot be seen with the naked eye). Hold the
should move with respirations and not be tense ophthalmoscope about a foot away from the infant.
when the infant is quiet. • If there are sticky eyes and the conjunctiva are
red and swollen, urgent Gram stain and culture
are required to look for gonococcal ophthalmitis.
Face
Unilateral sticky eyes are more likely to be a
Many syndromes have several minor anomalies affect- bacterial infection, or blocked tear duct if no
ing the facies (e.g. Down syndrome, fetal alcohol redness or swelling is present. Bilateral mildly sticky
­syndrome) (see Chapter 10.3). eyes with no redness is often a chlamydial infection
• Facial asymmetry when the infant cries is most and requires special swabs and a course of oral
commonly a temporary facial palsy affecting eye erythromycin.
closure caused by pressure on the facial nerve • Pre-auricular skin tags and pits are common and,
during delivery. There is lack of creasing by the together with more major aural defects, such as
nose and side of the mouth, and lack of mouth microtia, should mean the infant has a formal
movement on the side affected with crying. hearing test (see below).
Function usually recovers within a few days but
in a few cases the defect is more protracted. There
Chest and heart
may also be a congenital nerve palsy as opposed
to trauma, or isolated congenital hypoplasia of the • The respiratory rate is normally 40–60 breaths
depressor anguli oris muscle. per minute and frequently somewhat irregular,
• Elicit a rooting reflex by stroking the infant's cheek. faster and slower with brief pauses. Infants with
The infant's suck can be assessed by letting him respiratory distress have rapid and often regular
or her suck on a clean finger, and the roof of the breathing, and may have subcostal recession and an
mouth can then be palpated for a submucous cleft. expiratory grunt (see Chapter 11.3).
• Cleft lips and palate may be isolated or syndromic. • Inspiratory stridor, more obvious when the infant is
• Pierre Robin sequence comprises micrognathia and crying, is common and self-limiting and should be
cleft palate, and requires careful assessment that the distinguished from inspiratory or expiratory stridor
infant can protect the airway. at rest or in the presence of other symptoms.
• Mucus retention cysts of the gums are common and • The heart rate varies from 90 to 160 bpm or more
benign. with crying. Sinus arrhythmia and occasional
• Occasionally an infant will be born with a (natal) ectopic beats are common.
tooth present. These are loose and easily dislodged, • Feel the brachial and femoral pulses.
so should be removed. • With coarctation of the aorta there may be absent
Many infants open their eyes when sucking or may femoral pulses – not always an easy thing to be
do so spontaneously. It should be easy to see that the sure about. If there are any doubts, check the
infant focuses on the examiner's face (about 50 cm blood pressure in the arm and leg, a difference of
336
away) and can follow movement visually. 20 mmHg being significant for possible coarctation.
 The newborn infant: stabilization and examination 11.1
• Listen for heart murmurs when the infant is quiet. investigations are required. The parents should be
The chance of detecting a murmur will depend clearly told that it is not possible to tell whether
upon the timing of this exam, up to 50% of infants their infant is a boy or a girl just now, and a phrase
having a precordial murmur within 6 hours of birth such as ‘because the genitalia are immaturely
from ductal or other flow. Later in the first week the formed’ may be useful.
incidence of murmurs is closer to 1–2%. Although • Hypospadias can be subtle and it may be necessary
there are reported features that increase the to see the infant micturate to detect the urethral
probability that a murmur is innocent in the newborn opening.
(soft, grade 1–2/6 systolic murmur at left sternal • Hydroceles, demonstrated by transillumination,
edge, normal pulses and no other abnormalities), are common and need no action. Other scrotal
it is recognized that significant heart disease can swellings and undescended or maldescended testes
occur with no or seemingly innocent murmurs. If require surgical referral (see Chapter 11.5).
the murmur persists at a second examination within • The foreskin is not retractile in the newborn. Tiny
24 hours, our policy, in common with others, is to epithelial pearls, white papules, are common here.
perform echocardiography; this is almost certainly • There is no medical indication for circumcision of
cost-effective and greatly reassuring for parents. the healthy male newborn.
• Checking for anal agenesis requires parting the
buttocks and fully examining the perineum. It is
Clinical example not uncommon to be fooled by observing some
Baby Jackie had her first full neonatal
meconium on the perineum or the nappy if there is
examination at 48 hours of age. The only an associated fistula connected to the bowel.
unusual finding was a loud systolic murmur at • Vaginal mucoid discharges are common, as is a small
the left sternal edge, which had not been noted vaginal bleed in the first few days of life, which
at birth. There was no family history of congenital heart needs no treatment (but check that vitamin K has
disease. Although there had been an antenatal anatomy been given – see below). Vaginal mucosa skin tags
scan at 21 weeks' gestation, views of the heart had not been
are also common and benign.
ideal. The resident doctor requested an echocardiogram,
which was carried out 2 hours later and showed a small,
mid-septal, muscular ventricular septal defect (VSD) with Limbs
no other problems. Baby Jackie's family were able to be
reassured this would cause no problems and that the defect • Extra digits may be parts of syndromes or isolated
was likely to close spontaneously by 1–2 years of age. and sometimes familial.
• Is there a grasp reflex on placing a finger in the
open palm? A similar plantar reflex can be found
Abdomen and genitalia
by placing a finger on the sole of the foot.
• There is often divarication of the rectus abdominis, • Erb's palsy occurs in 1–2 per 1000 births, being more
leading to a soft midline bulge above the umbilicus; common following shoulder dystocia or instrumental
this is normal. deliveries. It is the most common brachial plexus
• Check the umbilicus. The cord separates by a injury and the arm is flaccid by the side or in a
process of low-grade inflammation over several ‘waiter's tip’ position. Most are very transient
days. In the past, various regimens, including with improvement over a few days; otherwise
anointing the stump every 4 hours with antiseptic physiotherapy is indicated. Sometimes there is also
or alcohol, have been used to try to minimize a fractured clavicle, usually detected by crepitus over
bacterial colonization. It is doubtful whether such the bone, but no specific treatment is required.
practices are useful or necessary, and they may • Infants who have been in a breech presentation with
delay cord separation. extended legs may sometimes still prefer to lie in this
• Feel for any masses. The liver edge is usually position after birth for a few days. For examination
palpable 1–2 cm below the right costal margin. A for congenital dislocation of the hip see Chapter 8.1.
spleen tip may be felt in normal babies and the • Talipes calcaneovalgus, with the dorsum of the
lower pole of both kidneys felt on deep bimanual foot pressed against the front of the shin, is
palpation. A distended bladder, such as with nearly always positional and the ankle can be
posterior valves, can be felt up to the umbilicus. moved through a full range of movements. Talipes
• Bile-stained vomitus is always abnormal and urgent equinovarus, with the foot inverted, is more likely
investigations and possible surgical referral are to have restricted ankle movements and requires
required (see Chapter 11.5). orthopaedic referral (see Chapter 8.1.). There may
• Ambiguous genitalia should have been detected in be associated or isolated metatarsus varus in which
337
the labour ward. There are many causes, and urgent the forefoot is twisted relative to the heel.
 11.1 NEONATAL PROBLEMS

Other Tongue tie (ankyloglossia) describes a short frenulum

with relative tethering of the tongue, After many years
• Check the infant's tone. Placed prone, the infant of leaving such infants alone unless they have signifi-
will lie with flexed limbs and can just move the head
cant feeding difficulties or later speech problems, both
at least to the midline. On pulling the infant up by
uncommon, there has been a recent increase in recom-
the arms from supine there will be some flexion of
mendations that the tongue should be ‘released’. The
the elbows and resistance and tone in the shoulders,
change seems to stem from lactation consultants believ-
but quite marked head lag. On holding the infant
ing that the short frenulum may affect breastfeeding and
in ventral suspension, the hips and shoulders and
lead to maternal pain from poor latching, views that
head will raise up a little in contrast to the ‘rag doll’
have been supported by several small studies of vari-
feel if there is significant hypotonia.
able quality. If frenectomy is being considered, it must
• Check limb reflexes. One or two beats of clonus be performed by a properly trained health professional
at the ankle on sudden dorsiflexion of the foot is
and preferably with adequate analgesia. Side-effects,
normal.
­including haemorrhage, are rare but have been reported.
• The walking reflex consists of walking movements
of the legs stimulated by the soles of the feet
touching a surface when the baby is held vertical. Later examination
It is not necessary to elicit this reflex if the baby
otherwise appears normal, but it is often of great
• If there is a later examination at around 1 week or
beyond, the focus is a little different. It will include
interest to parents.
a history of feeding and bowel movements, and
• Gestational age scoring – a time-honoured
measurement of weight gain. The five ‘Hs’ are:
occupation of paediatricians has been estimation of
gestational age, but one that is now rarely indicated
• Head – congenital hydrocephalus may now
present with a full fontanelle, widened sutures and
(such as a concealed pregnancy):
abnormally increasing head circumference
• Many more pregnancies have early ultrasound
examinations that can confirm mother's dates.
• Heart – some murmurs may now be apparent, or
signs of heart failure (tachypnoea, hepatomegaly)
• The time of conception is not a fixed time from
the first day of the last menstrual period, so two
• Hepar – jaundice may need assessment (see
Chapter 11.2).
infants of the same gestation may not have the
same physiological maturity.
• Hips – another opportunity to examine for
congenital dislocation of the hips (see Chapter 8.1.)
• At best, a Dubowitz or Ballard score will estimate
the gestational age ±2 weeks.
• Hearing – does the baby hear, shown by a sudden
quieting to his/her mother's voice or a rattle shaken
• There is little point in the exercise, fun though it is!
out of view?

Common minor anomalies and debated

importance
Practice points
More recent series have confirmed earlier evidence
that simple sacral dimples or pits are not markers for Neonatal examination
occult spinal dysraphism (such as a tethered cord or • All infants must have a thorough examination within 48
dermal sinus). Simple sacral dimples are defined as less hours of birth.
than 5 mm and less than 2.5 cm from the anus in the • Clear and accurate records must be kept of all
gluteal fold. Lesions outside these limits, or when there examinations.
are two or more cutaneous markers, should be investi- • The findings will to some extent depend upon the timing of
the examination.
gated by ultrasonography (up to 2–3 months of age).
• Weight, length and head circumference must be
A single umbilical artery (SUA), detected antenatally accurately recorded on an appropriate centile chart.
or at the time of birth, occurs in about 1 in 200 infants
and 1 in 5 of these have an associated malformation,
which is often multiple and chromosomal. Recent
reviews suggests that, if the SUA occurs without obvi- Other issues
ous associated anomalies, there will be only a very
Analgesia
small yield from further investigation of the urinary
tract, with the majority of findings being self-limiting Newborn infants may be subjected to a number of
conditions such as minor degrees of vesicoureteric painful procedures, such as heel pricks, and have a
reflux. Despite this, other authors do recommend a right to effective analgesia. The RACP has issued
338
renal ultrasound scan if a SUA is detected. ­comprehensive guidelines on this topic.
 The newborn infant: stabilization and examination 11.1
Use of a pacifier with 0.5–1.0 mL 24% sucrose in life. Infection in early life is associated with a high risk
0.25-mL aliquots 2 min prior to venepuncture or heel of chronic hepatitis (see Chapter 20.5). In Australia, it
pricks reduces discomfort from these. Some mothers is recommended that all term infants receive hepatitis
may prefer to breastfeed and swaddle the baby during B vaccine at birth.
the procedure. Infants born to mothers who are hepatitis B carriers
should be given:
1. an early bath with 1% chlorhexidine obstetric
Vitamin K
cream to remove maternal blood and fluids.
Vitamin K deficiency bleeding is an uncommon but Within 12 hours of birth and as early as possible:
potentially fatal disorder which presents with spon- 2. hepatitis B immunoglobulin 100 IU i.m.
taneous bruising or internal, including intracranial, 3. hepatitis B vaccine i.m. (opposite thigh).
haemorrhage. There are three recognized forms:
• Early: This is very rare, occurs on the first day
Metabolic screening
of life, and is usually associated with maternal
medication such as anticonvulsants. Following informed parental consent, all infants
• Classical: Bleeding occurs from day 2–6 of life. should have a heel prick performed at 48 hours of age
Without vitamin K prophylaxis it may occur in 1 in for metabolic screening (commonly called the Guthrie
400 exclusively breastfed infants. card). Different diseases are screened for in the vari-
• Late: Between 1 week and 6 months of age, almost ous states of Australia and in New Zealand, but they
always in breastfed infants and often in association usually include phenylketonuria, hypothyroidism and
with unrecognized liver disease or malabsorption cystic fibrosis. The introduction of tandem mass spec-
syndrome. trophotometry has meant that a number of amino acid
In both Australia and New Zealand a mixed micelle and fatty acid oxidation disorders are also screened for
form of vitamin K is used (Konakion MM). The (see Chapter 10.5).
guidelines state that:
• the recommendations about vitamin K should be
discussed with parents before the infant's birth
• the preferred route is intramuscular, 1 mg, following Normal infant matters
birth
Weight
• should parents not agree to an intramuscular
injection (and most do), three oral doses of Normal infants lose up to 8% of their birth weight in
Konakion can be given over several weeks, although the first 3–5 days and regain birth weight by 7–10 days.
this may be a less effective prevention.
Micturition
Hearing screening
Normal infants often pass urine soon after birth,
In the past, referrals for hearing tests have been based then infrequently for the next 24 hours. As feeding is
on a number of factors conferring increased risk, established, urine is passed more often, usually every
including congenital deafness in a close relative, mal- 3–4 hours. Normal newborn urine is clear and colour-
formations of face or ear, very low birth weight, high less, although in the nappy there may be a pink colour
serum bilirubin level (> 340 μmol/L), hypoxic–isch- from the presence of urates exposed to the air.
aemic encephalopathy, bacterial meningitis, congenital
infection with rubella or cytomegalovirus, or exposure
Bowel actions
to aminoglycosides. However, such criteria detect only
a minority of affected infants and many countries, Some 20% of infants pass meconium before delivery
including Australia and New Zealand, are implement- or during the first 4 hours afterwards, 96% pass meco-
ing universal neonatal screening, with either oto- nium by 24 hours and 99.9% by 48 hours. Failure to
acoustic emissions or automated auditory brainstem pass meconium by 48 hours is almost always abnor-
responses, or a combination of these tests. mal and may indicate Hirschsprung disease, meco-
nium plug syndrome or other bowel obstruction.
Immunization
Vomiting
There is a high risk of vertical transmission of h
­ epatitis
B during delivery for mothers who are ­ hepatitis B Small-volume (< 5 mL) occasional vomits are ­common,
­carriers (HBsAg-positive). The risk of the infant acquir- as all infants have some degree of gastro-oesophageal
339
ing the virus remains high during the first 5 years of reflux in the first week of life. ‘Possets’ are tiny 1–2-mL
 11.1 NEONATAL PROBLEMS

vomits. Larger, more frequent, vomits may be a ­istinguish between several tastes. They move in
d
­normal variation but also may be the first signs of ill- ­characteristic ways to different rhythms of speech and
ness, for example a bacterial infection. Vomits contain- they mimic adult facial movements, including tongue
ing bile (which is green, not yellow) are almost always protrusion.
abnormal, strongly suggesting bowel obstruction, and We attribute many human experiences, emotions
should always be investigated even if other indicators and moods to newborn infants, and rightly so, but
of bowel obstruction (distension and constipation) are no one really knows what it is like to be a newborn.
absent. Health workers should strive to make this episode
in life as rewarding as possible for infants and their
­parents. The rewards for health workers who achieve
Waking, sleeping, crying
these goals are also great.
Normal infants are usually awake and active for
30 minutes or so after birth. Thereafter patterns of
List of (normal) newborn topics in other
sleep, wakefulness and crying are extremely variable.
chapters
On average, infants sleep for at least 18 hours a day in
the first week, with sleep evenly distributed through- • Breastfeeding and nutrition – Chapter 3.3
out the 24 hours. By 6 weeks of age most infants • General resuscitation – paediatric emergencies,
are sleeping more at night than during the day, and Chapter 5.2
by 12 weeks of age much more sleep occurs at night. • Congenital dislocation of the hip – Chapter 8.1
Acquisition of this circadian rhythm is clearly affected • Surgical issues (e.g. hydrocele) – Chapters 11.5 and
by various care practices as well as endogenous hor- 20.1
mone production. Newborn infants also may cry for • Birth defects – Chapter 10.1
an average of 4 hours or more per 24 hours. • Dysmorphic child – Chapter 10.3
Newborns infants will look at objects within a focal • Newborn (metabolic) screening – Chapter 10.5
distance of 20–45 cm and preferentially focus on the • Jaundice – Chapter 11.2
edges of objects, lines and shapes. They can distin- • Group B streptococcus and other infections
guish the human face from other objects. They can – Chapter 11.4
hear and distinguish their mother's voice from other • Antenatal pelvicalyceal dilatation – Chapter 18.1
sounds. They have a sense of smell and can distin- • Skin disorders – Chapter 21.1
guish their mother's smell from that of others. They • Hearing screening – Chapter 22.1

340
 Low birth weight, 11.2
prematurity and jaundice in
infancy
Jane Harding, Jane Alsweiler, Mariam Buksh

• Birth weight
Principles of care • low birth weight (LBW): < 2500 g
Care of the sick newborn is often complex, and • very low birth weight (VLBW): < 1500 g
requires specialized training and equipment. However, • extremely low birth weight (ELBW): < 1000 g
remembering the basic principles will allow you to pro- • Weight for gestational age
vide emergency care for the sick newborn, regardless • appropriate for gestation (AGA): birth weight
of diagnosis, until specialized help is available: between 10th and 90th centiles for gestation
• Keep the baby pink. Initial resuscitation should • small for gestational age (SGA): birth weight
follow the usual ABC guidelines (see Chapters 5.1, < 10th centile for gestation
5.2 and 11.1). After that, many babies will maintain • large for gestational age (LGA): birth weight
breathing with supplemental oxygen until more > 90th centile for gestation.
sophisticated respiratory support is available. If an
oxygen saturation monitor is available, give only
enough oxygen to keep a preterm baby's oxygen The premature infant
saturations between 86% and 94%, and a term Causes of preterm birth
baby's saturations above 95%.
• Keep the baby warm. Cooling increases the baby's Although there are many risk factors for preterm birth
oxygen and glucose requirements and is associated (Box 11.2.1), approximately half of preterm births
with increased mortality. Dry the baby and put a occur in the absence of recognized risk factors. Survival
hat on to reduce heat loss while you are assessing rates increase and the incidence and severity of com-
other problems. Use a radiant heater, electric plications all decrease with increasing gestational age
blanket or incubator if available. and birth weight (Figs 11.2.2, 11.2.3, Table 11.2.1).
• Keep the baby fed. Sick babies are at risk of
hypoglycaemia, which can cause brain damage.
If milk feeds are not possible, give intravenous Clinical example
10% dextrose 60 mL/kg daily (2.5 mL/kg hourly).
• Consider infection. Almost any signs and symptoms George is a 900-g (extremely low birth weight)
of illness in the newborn can be caused by baby born to a 16-year-old mother who received
infection, and untreated septicaemia can cause no prenatal care. His mother was admitted after
the membranes ruptured and she began to
death within hours. If specialized care is likely
have contractions. She did not remember the date of her last
to be delayed by more than an hour or two, take menstrual period and had not had any antenatal ultrasound
blood cultures if possible and give intravenous or scans. She smoked a pack of cigarettes per day during the
intramuscular antibiotics. pregnancy. At delivery, George had poor respiratory effort
and marked retractions so he was intubated in the delivery
room and brought to the neonatal intensive care unit. He
required moderate ventilator settings and 50% oxygen. Chest
Definitions X-ray showed a diffuse ground-glass appearance with air
bronchograms consistent with respiratory distress syndrome.
Babies are commonly classified into groups associated A dose of surfactant was given through the endotracheal
with different disease patterns and different outcomes tube. Gestational age was estimated at approximately 27
(Fig. 11.2.1). These include: weeks based on the Ballard examination, which assesses
physical and neuromuscular development. Based on
• Gestation this estimated gestation, the infant's weight, length and
• term: ≥ 37 completed weeks' gestation head circumference were all at the 25th centile, and were
• preterm: < 37 completed weeks' gestation appropriate for his gestational age.
• post-term: > 42 completed weeks' gestation 341
 11.2 NEONATAL PROBLEMS

5000 Short-term complications of prematurity

4500
Respiratory
Large for gestational age 90th centile
4000
A See also Chapter 11.3.
3500
Appropriate for
gestational age Respiratory distress syndrome
Weight (g)

3000
B 10th centile Respiratory distress syndrome is also called surfactant
2500 C
deficiency syndrome. Immaturity of the respiratory
2000 Low birth weight ­system with surfactant deficiency results in respiratory
Small for
1500 gestational age distress. This is managed with oxygen, nasal continu-
Very low birthweight ous positive airway pressure (NCPAP) or, when more
1000
severe, surfactant administration and mechanical ven-
500 tilation. Corticosteroids given to the mother before
preterm birth reduce the incidence and severity of
24 26 28 30 32 34 36 38 40 42 44
respiratory distress syndrome.
Gestation (weeks)

Post- Periodic breathing, apnoea of prematurity

Preterm Term
term Premature babies commonly experience periodic
breathing due to immaturity of the respiratory centres
Fig. 11.2.1 Common definitions of size at birth, illustrating the of the brain. Cessation of breathing persisting for more
difference between intrauterine growth restriction (IUGR) and
small for gestational age (SGA). Baby A is an appropriately
than 20 seconds, or less than 20 seconds if there is asso-
grown term baby. Baby B is also born with an appropriate size ciated bradycardia or desaturation, is termed apnoea.
for gestational age (AGA), but has suffered reduced intrauterine Premature babies require cardiorespiratory and pulse
growth compared with baby A and thus has IUGR. Baby C has oximetry monitoring to detect apnoea and associated
had normal intrauterine growth, but is born SGA. bradycardia or desaturation. Apnoea of prematurity
occurs in almost all extremely premature babies and
Box 11.2.1 Risk factors associated with preterm birth usually improves around 34–36 weeks' postmenstrual
age. Pharmacological treatment includes methylxan-
Maternal thines such as caffeine or theophylline, which improve
• Previous preterm birth diaphragmatic contraction and stimulate the respira-
• Extremes of maternal age
tory centres. NCPAP is also helpful, partly by reducing
• Low pre-pregnant weight
• Acute illness (e.g. pyelonephritis)
any obstructive component to the apnoea and reduc-
• Uterine anomalies ing the work of breathing. If apnoea is severe, the baby
• Cervical incompetence may have to be ventilated mechanically. Apnoea can
• Pre-eclampsia/eclampsia also be caused by many other complications of pre-
• Previous miscarriage or termination of pregnancy maturity, such as infection, neurological problems,
• History of infertility anaemia, hypoxia, patent ductus arteriosus and upper
• In vitro fertilization (IVF)
airway obstruction, so these need to be considered in
Fetal babies experiencing apnoea.
• Multiple gestation
• Fetal anomalies
• Polyhydramnios Cardiac
• Fetal demise
• First trimester threatened abortion Patent ductus arteriosus
Placenta and membranes Before birth, the ductus arteriosus diverts blood
• Placenta praevia from the right ventricle away from the lungs to the
• Abruptio placentae aorta. After birth it normally closes functionally
• Premature rupture of membranes within a few days. In premature babies, closure may
• Chorioamnionitis be delayed, leading to left-to-right shunting of blood
Social from the aorta through the ductus to the lungs. This
• Low socioeconomic status results in pulmonary congestion, worsening lung dis-
• Smoking ease and decreased blood flow to the gastrointestinal
• Alcohol abuse tract and brain. These changes have been impli-
• Illicit drug abuse
cated in the pathogenesis of necrotizing enterocoli-
• Heavy physical work
• Psychological stress
tis and intraventricular haemorrhage. A significant
patent ductus arteriosus (PDA) is often clinically
342
 Low birth weight, prematurity and jaundice in infancy   11.2
100

90

80

70

60

Survival (%)
50

40

30

20

10

9
00

9
9

9
24
74

99

49
49

99
<5

–1
0–

0–

–2
–1

–1
00
50

75

00
50

00
A
10

20
12

15
Birth weight group (g)

100

90

80

70

60
Survival (%)

50

40

30

20

10

0
23 24 25 26 27 28 29 30 31 32
B Gestational age (weeks)

Fig. 11.2.2 Survival of preterm infants admitted to neonatal units according to (A) birth weight and (B) gestational age. (Source of data:
Australian and New Zealand Neonatal Network (ANZNN) 2009 Report of the Australian and New Zealand Neonatal Network 2006.
ANZNN, Sydney.)

Neurological
silent, or there may be a continuous heart murmur,
hyperdynamic precordium, bounding pulses and
­ Intraventricular haemorrhage
widened pulse pressure. Diagnosis is made by echo- This is due to bleeding from the immature capil-
cardiography. A significant PDA may be treated by lary bed of the germinal matrix lining the ventricles,
giving prostaglandin inhibitors (indometacin or ibu- often within the first 48 hours after birth. Risk fac-
profen). If these are unsuccessful, surgical ligation tors include asphyxia and changes in cerebral blood
may be necessary. flow due to hypotension or rapid intravenous fluid
343
 11.2 NEONATAL PROBLEMS

80
Chronic lung disease
70
Retinopathy of prematurity — mild
Retinopathy of prematurity — severe
60
Intraventricular haemorrhage — mild
Intraventricular haemorrhage — severe
50
Percent
40

30

20

10

0
24 25 26 27 28 29 30 31 32

Gestational age (weeks)

Fig. 11.2.3 Frequency of complications of prematurity in babies admitted to neonatal units according to gestational age. (Source of
data: Australian and New Zealand Neonatal Network (ANZNN) 2009 Report of the Australian and New Zealand Neonatal Network 2006.
ANZNN, Sydney.)

Table 11.2.1 Complications of preterm birth

Common Rare except in very low birth weight

Early

Respiratory Respiratory distress syndrome

Apnoea

Cardiac Patent ductus arteriosus

Neurological Periventricular haemorrhage
Periventricular leukomalacia

Hepatic Hypoglycaemia Hyperglycaemia

Hyperbilirubinaemia
Renal Hyponatraemia Hyperkalaemia
Metabolic acidosis
Gastrointestinal Feeding problems Necrotizing enterocolitis
Other Anaemia
Infection
Poor thermoregulation

Late Delayed growth Retinopathy of prematurity

Chronic lung disease
Neurodevelopmental delay

infusion. Intraventricular haemorrhage is diagnosed and neurological abnormalities such as cerebral

by cranial ultrasonography and varies in severity palsy.
from grade I intraventricular haemorrhage (germinal
matrix haemorrhage) to grade IV (intraparenchymal Periventricular leukomalacia
haemorrhage). Although lower grades have a good This is an uncommon problem, characterized by isch-
prognosis, grades III and IV intraventricular haemor- aemic necrosis of the white matter surrounding the lat-
344
rhage are often associated with later ­hydrocephalus eral ventricles. Periventricular l­ eukomalacia is d
­ iagnosed
 Low birth weight, prematurity and jaundice in infancy   11.2
on head ultrasonography, usually at 4–6 weeks of age. It Gastrointestinal
often results in cerebral palsy.
Necrotizing enterocolitis
This is an uncommon inflammatory process in the
bowel wall that can lead to necrosis. Fluctuating gut
Clinical example blood flow, hypotension, hypoxia, infection and feed-
ing practices have all been implicated, but their exact
George improved significantly after the
contribution remains unclear. Exclusive breast milk
administration of surfactant. He was extubated
and was placed on nasal continuous positive feeding is partially protective against necrotizing
airway pressure (NCPAP) by age 36 hours. enterocolitis. Presentation of necrotizing enterocoli-
Caffeine was given before extubation in anticipation of tis can be non-specific, including apnoea, bradycar-
apnoea of prematurity. Small feedings of expressed breast dia and temperature instability, then with more focal
milk were started on day 1. Electrolytes were monitored abdominal signs such as distension, tenderness, feed
closely because of the potential of large insensible water intolerance, bloody stools and bilious gastric aspirates.
losses.
On day 4, George began to deteriorate with increasing
Occasionally there may be rapid progression to sepsis,
apnoeas and respiratory distress. A continuous murmur shock and death. Classical X-ray findings are air in the
was noted along the left sternal border. The pulses bowel wall (pneumatosis intestinalis) and perforation
were bounding and the precordium was very active. of the gut. Treatment is by withholding of feeds, anti-
Echocardiography confirmed the presence of a large biotics and, if necessary, surgery. There is emerging
patent ductus arteriosus and a course of indometacin was evidence that probiotics in the milk feeds may decrease
commenced.
the risk of developing necrotizing enterocolitis.
George did well during the next week. At 2 weeks of
age, he again developed worsening apnoea with feed Feeding problems
intolerance and temperature instability. A full blood count Premature babies have weak and uncoordinated
revealed anaemia and an increase in immature white cells.
Blood cultures, a lumbar puncture, chest X-ray and bladder
suck and swallow reflexes, delayed gastric empty-
tap were performed. George was treated with a blood ing and immature gut motility. Feed intolerance and
transfusion and antibiotics, with gradual improvement during gastro-oesophageal reflux are common. Parenteral
the next 2 days. nutrition is usually required initially in extremely pre-
mature babies, with gradually increasing volumes of
milk, preferably expressed breast milk, given by tube.
Supplemental vitamins, minerals, protein and calo-
Hepatic ries may also be required to allow adequate growth.
Sucking feeds are usually established at 34–36 weeks'
Hypoglycaemia is common because of decreased gly-
postmenstrual age.
cogen stores and increased glucose requirements in
premature babies.
Hyperglycaemia can also occur in VLBW babies Haematological
because of high glucose infusion rates, reduced insulin
Anaemia
secretion and impaired insulin sensitivity.
Anaemia of prematurity is almost universal, as a result
Hyperbilirubinaemia is common and due to hepatic
of low iron stores and red cell mass at birth, rapid
immaturity coupled with a shorter half-life of red blood
growth, reduced erythropoiesis and decreased survival
cells. Premature babies require treatment at lower bili-
of red blood cells, aggravated by repeated blood sam-
rubin levels than term babies because their low albumin
pling. Treatment is supportive with transfusion in the
levels and immaturity of the blood–brain barrier place
early period and iron supplementation.
them at greater risk of bilirubin encephalopathy.

Immunological
Renal
Infection
Immaturity of the kidneys results in a poor ability to Premature babies have increased susceptibility to
concentrate or dilute the urine. This may be aggravated infection due to impaired cell-mediated i­mmunity and
by immature skin leading to high insensible water reduced concentrations of complement and immuno-
losses, contributing to: globulins, together with exposure to i­nvasive ­procedures
• dehydration and monitoring. Signs of sepsis are extremely non-­
• hypernatraemia and hyponatraemia specific, including lethargy, temperature instability,
• hyperkalaemia apnoea, tachypnoea, feed intolerance and jaundice.
• metabolic acidosis due to inability to conserve Investigation usually requires a full blood count, blood 345
bicarbonate. culture, chest X-ray, bladder tap urine and l­umbar
 11.2 NEONATAL PROBLEMS

puncture. Because deterioration can be rapid, early radical-mediated lung injury. Babies with chronic lung
treatment with antibiotics is essential pending culture disease may require supplemental oxygen for months or
results. even years, and are at increased risk of respiratory infec-
tions in the first year and adverse developmental outcome.

Thermoregulation
Growth
This is a significant problem in the premature baby
Because premature babies often do not grow for
due to a relatively large body surface area, thin skin
2–3 weeks after birth, most are still below birth centiles
and subcutaneous tissues, and lack of a keratinized
at discharge; however, steady catch-up growth is usual
epidermal barrier. Nursing preterm infants in an incu-
during the first 2 years of life. Permanent growth fail-
bator, with humidification if necessary, maintains a
ure is more likely in premature babies who were also
stable temperature.
small for gestational age.

Clinical example Neurodevelopmental impairments

Severe impairments (cerebral palsy, mental retarda-
George did well throughout the remainder of
his hospitalization. He began to suck
tion, blindness, deafness) occur in 10–15% of VLBW
some feeds by 34 weeks' corrected age, babies. More subtle delays in language, attention defi-
and by 37 weeks he was fully breastfed. His cits and social/behavioural difficulties are common.
eyes were examined for retinopathy of prematurity (ROP) Regular developmental assessment is recommended
at 6 weeks of age and were found to be immature but for all VLBW babies.
with no evidence of ROP. He would be followed every
2–3 weeks until his retinas were fully mature. His head
ultrasound scans were normal at 5 and 28 days of age. Growth and developmental expectations
He continued to have occasional episodes of desaturation
until 36 weeks' corrected age and required oxygen Growth according to centiles and developmental
100 mL/min by nasal cannula to maintain adequate achievements are usually corrected for prematurity up
oxygenation. He received his first vaccinations until the end of the second year of life.
before discharge. He was discharged at 38 weeks'
postmenstrual age with an appointment to be seen in
the high-risk follow-up clinic 6 weeks later. He was also Immunizations
followed by home health nurses while on oxygen.
Immunizations should be administered according to
the baby's chronological age and the timing should not
be adjusted for prematurity.
Late-onset complications of prematurity
Retinopathy of prematurity The late preterm baby
ROP results from disruption of the normal process of Babies born at 34–36 weeks' gestational age make
vascularization of the retina, with new vessel forma- up the largest proportion of preterm births. These
tion and fibrous scarring. Although ROP can result babies are often managed in a similar fashion to term
from excessive oxygen exposure, most cases occur in babies owing to their relatively large size and func-
extremely premature babies with multiple other prob- tional maturity. However, late preterm babies have an
lems even when oxygen monitoring has been meticu- increased incidence of neonatal mortality and mor-
lous. Severity is classified on the basis of the location bidity, and in later life have a higher rate of behav-
and extent of ROP, from grade 1 (mild changes) to ioural and developmental problems compared with
grade 4 (retinal detachment). Most mild ROP regresses term babies.
spontaneously; however, regular eye e­ xaminations are
required to detect progressive ROP requiring laser
therapy to reduce the chances of myopia and blindness. Practical points

Low birth weight

Chronic lung disease • May be due to a number of underlying causes.
This is usually defined as the need for supplemental • Consider whether appropriately grown preterm infant or
small-for-gestational-age (SGA) infant.
oxygen at 36 weeks' postmenstrual age. It results from • Monitor for hypoglycaemia and hypothermia.
a combination of lung immaturity, oxygen toxicity, • Prognosis will depend on the underlying cause.
346
ventilator-induced lung injury, inflammatory and free
­
 Low birth weight, prematurity and jaundice in infancy   11.2
Box 11.2.2 Causes of being small for gestational age
Practical points
Intrinsic: altered growth potential
Prematurity • Chromosomal
• Antenatal corticosteroids given to a mother at risk of • Congenital anomalies
preterm delivery decrease mortality and morbidity in • Dysmorphic syndromes
preterm babies. • Congenital infections
• Keep a preterm baby pink, warm and fed until specialized
help is available. Extrinsic: reduced fetal nutrient supply
• The more preterm the baby, the greater the likelihood • Reduced substrates in maternal blood (e.g. severe
of complications of prematurity and decreasing maternal undernutrition, eating disorders, chronic
survival. illness)
• Complications of prematurity can affect every organ • Reduced uterine blood flow (e.g. hypertension,
system and can have lifelong effects. renovascular disease, vigorous exercise)
• Reduced placental transfer of substrates to the fetus (e.g.
placental infarcts, abruption)
• Factors acting at all of these points (e.g. drugs, smoking,
alcohol)
Small for gestational age
Causes and complications
It is useful to think of the causes and complications of
Clinical example SGA in two main groups (Box 11.2.2):
Rachel was born at 36 weeks' gestation to
• Intrinsic fetal problems: altered fetal potential
a 30-year-old mother in her first pregnancy. for growth, such as chromosomal anomalies,
Labour was induced because of poor intrauterine infection and congenital anomalies.
growth and maternal pregnancy-induced Management and outcome in this group depend on
hypertension. Delivery was by emergency caesarean the underlying cause.
section for fetal distress. Rachel was vigorous at birth • Extrinsic problems in fetal supply: the baby is
with a birth weight of 1800 g, which was less than the 3rd undernourished in utero as a result of factors
centile. Her length was 45 cm, on the 10th centile, and her
head circumference was 33 cm, on the 50th centile. Apart
limiting nutrient supply at one or more places
from her small size, no abnormalities were detected on along the fetal supply line. Complications and
initial examination. In particular, there were no dysmorphic outcome can be thought of as those of intrauterine
features or signs of congenital infection. She was initially starvation (Table 11.2.2).
nursed in an incubator because of poor temperature However, in a large proportion of cases (perhaps 30%),
maintenance in a cot. Blood glucose concentrations were no cause is identified.
monitored because of her small size. Despite early milk
feeds, Rachel required an intravenous glucose infusion
for the first 24 hours to maintain adequate blood glucose
Treatment
concentrations. She also became jaundiced and required No specific treatments have been shown to improve
phototherapy for days 3–6 after birth.
growth before or after birth. Treatment is directed to pre-
venting and managing complications (see Table 11.2.1).

Terminology Clinical example

Smallness for gestational age (SGA) is usually defined
Clinically Rachel did well. She fed vigorously,
as birth weight below 10th centile for gestation. The lost little weight after birth, and by 12 days she
distinction between SGA babies and those with intra- was weaned from the incubator to the cot.
uterine growth restriction (IUGR) would be useful Her weight at that time was 1900 g. She was
but is difficult to make clinically (see Fig. 11.2.1). discharged home at 2 weeks of age. On follow-up at age
SGA is measured by birth weight because this is easy 2 years, all of her measurements were at the 10th percentile
and accurate, but babies with IUGR suffer a vari- and she had normal developmental milestones.
ety of complications even when birth weight is in
the normal range. Similarly, some SGA babies are
Prognosis
small normal babies, for example the small infant of
a small mother in some ethnic groups. This problem • General. Prognosis depends on the cause of growth
is reduced by the use of centile charts specific for the restriction. For the intrinsic group, outcome is that
347
relevant population. of the underlying problem. For the extrinsic group,
 11.2 NEONATAL PROBLEMS

Table 11.2.2 Pathophysiology of intrauterine growth restriction

Possible clinical consequences

Fetal nutrient limitation Consequences for the fetus for the newborn Long-term consequences

Reduced supply of glucose Reduced body fat Hypothermia Increased mortality

Reduced glycogen stores Hypoglycaemia Neurological damage

Reduced supply of oxygen Stillbirth Meconium aspiration Neurological damage

Asphyxia Hypoxic ischaemic encephalopathy
Increased haematopoiesis Coagulopathy
Polycythaemia
Jaundice
Redistributed cardiac output Relatively big head (head-sparing)
Cardiac failure Pulmonary haemorrhage

Reduced supply of amino acids Impaired immune function Infection Poor growth
Delayed bone maturation Hypocalcaemia
Reduced muscle mass Insulin resistance

outcome depends on severity and time of onset of Bilirubin synthesis

the growth restriction. In general, the earlier the
Bilirubin is derived from haemoglobin, and to a lesser
onset in gestation and the more severe the growth
degree from myoglobin and the cytochromes. These haem
restriction, the greater the likelihood of permanent
proteins are oxidized in the reticuloendothelial system to
growth and developmental problems.
form biliverdin and then unconjugated bilirubin. Because
• Growth. Most SGA babies catch up in the first
unconjugated bilirubin is not water-soluble, most of it cir-
6 months after birth. However, babies born
culates bound to albumin. Circulating bilirubin is taken
short tend to remain short, and account for
up by the liver, and conjugated in the endoplasmic retic-
approximately 20% of short adults.
ulum by the enzyme glucuronyl transferase to form bili-
• Neurodevelopment. If growth restriction is of late
rubin monoglucuronides and diglucuronides. Conjugated
onset and head size is normal, outcome may be good.
bilirubin is excreted via the biliary tree into the gastrointes-
However, many of the complications of growth
tinal tract and then into the faeces. However, some of the
restriction impair developmental outcome, and on
conjugated bilirubin is converted back to unconjugated
average performance is reduced (see Table 11.2.1).
bilirubin and is reabsorbed into the circulation by a pro-
• Adult disease. Babies born small are at increased
cess known as enterohepatic circulation.
risk of a number of chronic diseases in
adulthood, particularly coronary heart disease,
stroke, hypertension and non-insulin-dependent Evaluation of jaundice
diabetes. This is thought to be because fetal
Jaundice usually becomes visible at serum bilirubin
adaptations to undernutrition in utero result in
levels of 85–120 μmol/L; however, the depth of jaun-
both small size at birth and permanent resetting
dice is an extremely unreliable guide to the bilirubin
of homeostatic mechanisms (programming) that
level. Jaundice progresses in a cephalocaudal fashion
increase risk of later disease (the developmental
and is more likely to be significant if it affects the arms
origins of health and disease or Barker
or lower legs. Unconjugated hyperbilirubinaemia is the
hypothesis).
most common type and can be physiological or path-
ological. Conjugated hyperbilirubinaemia, defined as
a serum conjugated bilirubin above 35 μmol/L, always
requires urgent evaluation (see Chapter 20.5).
Jaundice The extent of evaluation required in a jaundiced baby
depends on the wellness of the baby and the pattern
See also Chapter 20.5.
of jaundice (Fig. 11.2.4). As a minimum, all jaundiced
Jaundice is the visible yellow coloration of the skin
babies should have a history taken, physical examina-
due to raised bilirubin levels. It is extremely common,
tion and measurement of the serum bilirubin level.
affecting approximately 50% of all newborns. In most
babies jaundice is physiological. However, it should
History
always be taken seriously, as it is a common sign of
348
­illness, and at high levels bilirubin can cause perma- • Family history: previous sibling, other family
nent brain damage (kernicterus). members with jaundice (hereditary causes?)
 Low birth weight, prematurity and jaundice in infancy   11.2
500
Early jaundice
Physiological
400 Persistent

Serum bilirubin (mmol/L)

Late jaundice

300

200

100

0
1 2 3 4 5 6 7 8 9 10 11 12 13 14

Age (days)

Fig. 11.2.4 Trends in serum bilirubin levels in common types of jaundice: early-onset haemolytic jaundice, physiological jaundice,
prolonged jaundice and late-onset jaundice.

• Maternal history: history of splenectomy, • Coombs test

haemolytic anaemia, gallstones, blood type • assess risk for hereditary haemolytic diseases
• Pregnancy history: gestational diabetes, illnesses • consider cultures for infection.
(polycythaemia, infections?)
• Delivery history: type of delivery (forceps, vacuum Jaundice at more than 24 hours of age
extraction, trauma?), medications, length of rupture
of membranes (sepsis?), delay in cord clamping Is it physiological? (Normal history and examination,
(polycythaemia?), Apgar score (asphyxia?) normal pattern of jaundice)
• Newborn history: feeding history (dehydration, • Monitor, no further investigations.
starvation?), stool pattern (Hirschsprung disease?), Not definitely physiological?
vomiting (intestinal obstruction, pyloric stenosis?). • Assess for haemolysis and sepsis as above.
• Assess feeding and weight gain/loss.
Physical examination • Assess for gastrointestinal obstruction.
• Urinalysis for reducing substances
• Measurements: small for gestational age or infant (galactosaemia).
of a diabetic mother (polycythaemia?)
• Colour: plethora (polycythaemia?), pallor
(anaemia?) Persistent or late jaundice (> 2 weeks in term
• Wellness: activity, tone, cry (sepsis?) baby, > 3 weeks in preterm baby)
• Presence of bruising, petechiae, cephalhaematoma • Total and conjugated bilirubin (conjugated requires
• Umbilical cord: infection or umbilical hernia immediate investigation)
(hypothyroidism?)
• Breast milk jaundice?
• Hepatosplenomegaly (haemolysis, intrauterine • Full blood count
infection?)
• Thyroid function tests
• Neurological examination: evidence of bilirubin • Liver function tests.
encephalopathy.

Physiological jaundice
Laboratory evaluation
Physiological jaundice begins after 24 hours of age, peaks
Early jaundice (< 24 hours of age)
on approximately day 3 and resolves around the end of
Always pathological. the first week (see Fig. 11.2.4). It is unconjugated and
• Evaluate for haemolysis and sepsis: caused by a number of factors, including increased bil-
• serum bilirubin irubin load and impaired excretion (Box 11.2.3). The
349
• full blood count infant is healthy with a relatively slow rise in serum
• maternal and infant blood type bilirubin (< 85 μmol/L daily), which does not generally
 11.2 NEONATAL PROBLEMS

Box 11.2.3 Causes of physiological jaundice Box 11.2.4 Causes of haemolytic jaundice

Increased bilirubin load Immune-mediated

• Increased red blood cell volume • ABO incompatibility
• Decreased red blood cell survival • Rhesus disease
• Increased enterohepatic circulation • Minor blood group incompatibilities
• Drug-induced
Defective hepatic uptake • Maternal autoimmune haemolysis
• Relative hepatic uptake deficiency
Acquired, non-immune
Defective bilirubin conjugation • Congenital intrauterine infection
• Decreased synthesis and activity of glucuronyl • Bacterial sepsis
transferase
Hereditary
Defective bilirubin excretion • Membrane defects: hereditary spherocytosis,
• Higher concentration of β-glucuronidase in intestinal elliptocytosis, and others
mucosa increasing bilirubin breakdown • Enzyme abnormalities: glucose-6-phosphate dehydrogenase
• More alkaline pH in proximal small intestine causing (G6PD) deficiency, pyruvate kinase deficiency
breakdown of conjugated bilirubin
• Lack of intestinal flora Haemoglobinopathies

exceed 250 μmol/L. In the premature baby, the bilirubin g­ lucose-6-phosphate dehydrogenase (G6PD) deficiency,
peaks towards the end of the first week and resolves in an X-linked disorder seen in Mediterranean and Asian
the second week. ethnic groups, or hereditary spherocytosis, an autosomal
Physiological jaundice is a diagnosis of exclusion. In dominant disorder affecting the cell membrane.
a well baby whose jaundice is following the predicted
course, no further investigation or treatment is required; Non-haemolytic jaundice
however, any signs of illness in the baby or alterations in
Unconjugated hyperbilirubinaemia can be caused by
the pattern of jaundice require immediate investigation.
increased production or decreased clearance of biliru-
bin, or sometimes by a combination of these factors
Breast milk jaundice (Box 11.2.5).
Breast milk jaundice is a prolonged unconjugated
hyperbilirubinaemia common in breastfed babies. The Complications of jaundice
jaundice peaks in the second week but resolves only very Unconjugated bilirubin is lipid-soluble, so can cross
slowly and may last up to 3 months (see Fig. 11.2.4). cell membranes and is toxic to cells, especially the
The infant is healthy and thriving. Breast milk jaundice brain. Kernicterus is a term used to describe the y­ ellow
is thought to be due to factors in breast milk that cause
increased enteric absorption of bilirubin.
Diagnosis is based on the pattern of jaundice and Clinical example
wellness of the baby. As for any prolonged jaundice,
conjugated hyperbilirubinaemia must be excluded. Jaundice
The diagnosis can be confirmed by improvement of David is a term male infant born to a 33-year-
the jaundice on temporary interruption of breastfeed- old G2P1 blood group O+ serology-negative
ing, but this is rarely required. mother by normal vaginal delivery. Jaundice was noted
at 18 hours of life, with an unconjugated bilirubin of
220 mmol/L.
A full blood count showed a normal haemoglobin level.
Pathological unconjugated jaundice
The peripheral smear showed occasional spherocytes and
Haemolysis some fragmented red blood cells, and the reticulocyte count
was significantly raised. The baby was found to be blood
The onset of jaundice before 24 hours of life is always type A+ with a positive direct Coombs test. A diagnosis for
pathological and usually caused by haemolysis ABO incompatibility jaundice was made. Phototherapy was
(Box 11.2.4). Haemolytic jaundice is most commonly started and the serum bilirubin was monitored. The bilirubin
immune-mediated and due to blood group incompat- rose to near exchange transfusion levels on day 2 before
stabilizing. On day 7 a full blood count showed a slightly
ibilities, such as ABO and rhesus incompatibility. If
low haemoglobin level due to haemolysis. Phototherapy
investigations for immune-mediated haemolysis are neg-
350 was stopped on day 14. Blood counts were monitored after
ative, further investigations are necessary to ­determine discharge to look for worsening anaemia.
whether haemolysis is due to other causes such as
 Low birth weight, prematurity and jaundice in infancy   11.2
550
Box 11.2.5 Other causes of unconjugated Exchange transfusion
hyperbilirubinaemia and phototherapy
500
Increased haem load
• Haemorrhage Exchange transfusion
450 if phototherapy fails
• Haematoma (especially cephalhaematoma),

Serum bilirubin (µmol/L)

pulmonary haemorrhage, cerebral haemorrhage, birth
trauma, occult 400
• Polycythaemia Suspect
haemolysis
• Swallowed blood
350 Phototherapy

Increased enterohepatic circulation

• Bowel obstruction or ileus
300
• Pyloric stenosis

Impaired hepatic uptake and conjugation 250

• Inborn errors of bilirubin metabolism
• Non-haemolytic inherited disorders: type I, type II,
Gilbert disease 200
0 24 48 72 96
• Metabolic disease: galactosaemia, tyrosinosis,
hypermethionaemia Time after birth (h)
• Endocrine
Fig. 11.2.5 Example of a nomogram for the treatment of
• Hypothyroidism, hypopituitarism, drugs
jaundice in healthy term infants.
• Inhibitors
• Lucey–Driscoll syndrome, breast milk

Mixed
bilirubin near the skin into a water-soluble form
• Asphyxia through photo-isomerization. Bilirubin can then
• Prematurity be excreted in the bile and urine. This is a safe,
• Sepsis simple treatment, designed to avoid exchange
• Infants of diabetic mothers transfusion.
• Exchange transfusion. The baby's blood is replaced
with donor blood in order to decrease the bilirubin
s­ taining of the brain and the associated neuronal death level rapidly. The procedure carries a small risk
seen on histology. The cerebellum, basal ganglia and of morbidity and mortality, and is now rarely
cranial nerve nuclei tend to be most severely affected. undertaken.
Bilirubin encephalopathy refers to the clinical manifesta- The levels at which phototherapy and exchange trans-
tions of bilirubin injury to the central nervous system. fusion are performed are usually determined using
These can include abnormalities of muscle tone, leth- standard hospital nomograms. An example is illus-
argy, seizures, opisthotonus (arching of back), cerebral trated in Figure 11.2.5. The threshold for treatment
palsy and deafness. The risk of brain damage can be is lower if the infant is premature, asphyxiated, ill or
increased by: haemolysing.
• high serum unconjugated bilirubin concentration Intravenous immunoglobulin may be helpful in the
• reduced binding of bilirubin to albumin, due to treatment of immune-mediated haemolytic disease,
prematurity with low serum albumin concentrations, probably by blocking the Fc receptors on the red blood
acidosis and displacement of bilirubin by fatty acids cells and thereby inhibiting haemolysis.
(e.g. intralipid) or certain drugs
• impairment of the blood–brain barrier due to
prematurity, asphyxia, meningitis.
Practical points
Treatment of jaundice
Jaundice
The aim of treatment is to prevent encephalopathy by • History and physical examination – is the baby well and
reducing bilirubin levels. feeding?
• General. Ensure adequate calorie and fluid • Jaundice on day 1 is not physiological – think haemolysis,
intake and adequate stool production to reduce sepsis.
enterohepatic circulation. Treat with antibiotics if • Jaundice in the first week– baby well? Pattern of jaundice
appropriate? – think physiological jaundice.
sepsis is suspected.
• Late jaundice – conjugated or unconjugated? Conjugated 351
• Phototherapy. The baby is nursed under blue light always requires investigation.
at wavelengths of 450–460 nm. This transforms
 11.3 Breathing problems
in the newborn
Luke Jardine, Mark Davies

• Nasal flare – the alae nasi flare during inspiration

Introduction and this decreases airway resistance.
The establishment and maintenance of breathing is • Central cyanosis – almost invariably some alveoli
vital for the newborn infant. Problems with b
­ reathing that are not ventilated remain perfused. The
are common and dealing with them forms the bulk resultant ventilation/perfusion mismatch leads to
of neonatal care. The establishment of lung func- cyanosis. It is important to remember that babies
tion is dealt with in Chapter 11.1. Respiratory prob- who are relatively polycythaemic will have cyanosis
lems beyond the immediate post-birth period include at relatively high oxygen saturation, and babies with
respiratory distress (from a myriad of causes), airway low haemoglobin will not appear cyanosed until
obstruction and hypoventilation (including apnoea their saturation is extremely low.
and various neuromuscular problems). Not all babies with respiratory distress have all of the
signs listed above. For example, an infant may have
significant respiratory distress and yet have a respira-
tory rate of 40 breaths per minute. Often, the some-
what more subjective impression that the baby has
Respiratory distress increased respiratory effort or is ‘working hard’ is just
Respiratory distress is a broad term that refers to a as important.
constellation of signs seen in the neonate who has dif-
ficulty breathing and has increased respiratory effort.
The signs that the infant with respiratory distress
exhibits include the following: General principles of
• Tachypnoea – is defined as a respiratory rate of management of respiratory
more than 60 breaths per minute. In order to
clear more carbon dioxide, the infant increases
distress
the respiratory rate and therefore the minute The general principles of management apply no mat-
ventilation. ter what the diagnosis or gestational age. The causes
• Expiratory grunt – this sound is produced by the of respiratory distress are many, and some are imme-
exhalation of gas from the lungs through a partially diately life-threatening. As always, you must attend to
closed glottis; this helps with the maintenance of the any need for resuscitation and ensure that the infant is
functional residual capacity. It can be misinterpreted physiologically stable.
by the inexperienced observer as the baby crying or • Put the baby somewhere you can watch it. This is
moaning. best achieved by admission to a neonatal nursery
• Recession – with increased inspiratory effort the with the baby nursed in an incubator, unclothed
baby generates more negative intrapleural pressure. initially (this allows frequent observation and the
This increases the gradient between the atmosphere status of the baby's breathing and colour can be
and the intrapleural space. This gradient occurs assessed instantly upon looking in the incubator).
across the chest wall, and the softer or more The incubator should also keep the baby warm.
compliant parts of the chest wall are sucked in • Monitor the vital signs including heart rate, respiratory
during inspiration – usually the intercostal spaces rate and pre-ductal oxygen saturations (put the
and the sternum (the lower part is especially oximeter probe on the right hand). These should be
mobile and can be sucked in considerably during noted frequently so that any changes over time can be
inspiration). There is also indrawing of the lower determined with a glance at the observation record.
costal margin during inspiration, but this occurs • Assume the baby is infected until the results of
owing to a different mechanism, namely contraction investigations confirm or exclude this. Take cultures:
of the diaphragm, and is sometimes erroneously a blood culture is best, with or without surface
352 called subcostal recession. swabs and a gastric aspirate. Then start antibiotics.
 BREATHING PROBLEMS IN THE NEWBORN 11.3
• Start intravenous fluids. If you are struggling to with respiratory distress is at least breathing and
breathe you do not need a stomach full of milk. achieving some gas exchange – you don't want to
If a peripheral venous cannula cannot be readily convert that situation into something worse with
inserted then insert an umbilical venous line. multiple unsuccessful attempts at intubation.
Infusing 10% dextrose at 60 mL/kg daily is more • Generally accepted criteria for the need for
than adequate in the first couple of days of life. ventilation are unresponsive, severe or frequent
• Get a chest X-ray. There are some conditions that apnoea; acidosis (arterial pH < 7.25 with an
require an immediate change in management, such arterial partial pressure of carbon dioxide (PaCO2)
as a pneumothorax, congenital diaphragmatic > 60 mmHg or pH < 7.25 with base excess below
hernia or intrapleural fluid. Although many −10 not corrected by bicarbonate or volume
conditions have characteristic appearances on loading), requiring a FiO2 > 50% to maintain
chest X-ray, none of the findings is definitive. You oxygen saturation above 88%.
can never exclude infection by looking at a chest • Exogenous surfactant is usually given via an
X-ray. endotracheal tube to any intubated baby with
• Get advice. If you are not in a neonatal unit that hyaline membrane disease. Natural, animal-derived
has a paediatrician or neonatologist then you surfactants are usually used, including Survanta (a
should ring your local neonatal unit. Do this after calf lung extract), Curosurf (a porcine product) and
attending to any requirements for resuscitation and BLES (bovine lipid extract surfactant). It is also
after you have started antibiotics. used before the diagnosis is made in infants of less
The baby may require respiratory support for the than 26 weeks' gestational age, as soon as they are
respiratory failure that accompanies the respiratory intubated.
distress. This may include oxygen therapy, continu- Once any necessary resuscitation has been attended
ous positive airway pressure (CPAP) or intubation and to, the management principles above applied and any
mechanical ventilation. Some specific lung diseases respiratory support given, you can think about work-
will also require exogenous surfactant treatment. ing out a cause for the respiratory distress.
• Oxygen treatment. Remember that oxygen is a • Take a history. Get details of the pregnancy,
toxic substance, so use only the minimum amount labour and delivery: results of antenatal screening
necessary. If pre-ductal oxygen saturations are including ultrasound findings, poly- or oligo-
below 90%, it is reasonable to increase the fraction hydramnios, gestational age, risk factors for
of inspired oxygen (FiO2). In infants who do not infection, meconium-stained liquor, need for
require any other form of respiratory support this is resuscitation after birth.
best achieved by running oxygen into the incubator. • Examine the baby: be gentle. Look for any obvious
Start with a flow of 2 L/min and increase or congenital abnormalities.
decrease to keep the pre-ductal oxygen saturations • Get a chest X-ray if you haven't already done
in the low 90s. so. Take blood for a full blood count and film
• Blood gas monitoring. Usually, if an infant requires examination. A blood culture should already have
an FiO2 of more than about 0.4 on CPAP or is been taken. Send a gastric aspirate and surface
intubated and ventilated, they should have an swabs (include groin and ear) for bacterial
arterial line. This is best achieved by inserting an culture.
umbilical arterial catheter, but this should be done • If an airway problem is suspected, make sure
by someone who is experienced in doing it. Get the nares and oesophagus are patent. The
advice. successful passing of a nasogastric tube should
• Continuous positive airway pressure (CPAP). confirm this.
This is usually delivered with some form of nasal
or nasopharyngeal tube. The aim is to provide
a continuous positive background pressure
to the infant's airway to help keep the airway
Causes of respiratory distress
open, maintain good lung volume and treat any A wide variety of congenital and acquired disorders
atelectasis. Usually, a pressure of around 7 cmH2O can present in the newborn period as respiratory dis-
is used. This will help to minimize any ventilation/ tress (Box 11.3.1). A systematic approach, which
perfusion mismatch. includes taking a thorough history, performing a com-
• Intubation and mechanical ventilation. The plete physical examination and undertaking ancillary
decision to ventilate a baby with respiratory investigations, will readily determine most of these.
distress needs to be taken in discussion with the The most common causes are explained in greater
relevant paediatrician or neonatologist. A baby detail below. 353
 11.3 NEONATAL PROBLEMS

conditions listed below will have an element of lung

Box 11.3.1 Causes of respiratory distress
atelectasis. Atelectasis decreases respiratory com-
• Infection (e.g. congenital infection, acquired infection)
pliance and therefore increased pressure is required
• Retained fetal lung fluid, also known as transient to achieve adequate tidal volumes. Atelectasis also
tachypnoea of the newborn or ‘wet lung’ leads to ventilation/perfusion mismatch and cyano-
• Infant respiratory distress syndrome, also known as sis. These features in turn lead to a need for increased
hyaline membrane disease ventilation and therefore respiratory distress.
• Pulmonary air leak (e.g. pneumothorax,
pneumomediastinum, pneumopericardium, pulmonary
interstitial emphysema) Infection
• Aspiration (including meconium aspiration syndrome,
blood, liquor amnii and milk) It can be impossible to differentiate infection from
• Surgical conditions (congenital diaphragmatic other causes of respiratory distress such as respiratory
hernia, cystic hygroma, haemangioma, congenital distress syndrome, retained fetal lung fluid or meco-
lobar emphysema, congenital cystic adenomatoid nium aspiration syndrome. Therefore, in all babies
malformation, sequestration of lung, lung cysts)
with respiratory distress, there should be a high index
• Pulmonary hypoplasia (e.g. oligohydramnios from
prolonged premature rupture of membranes or decreased
of suspicion for infection and a low threshold for sep-
fetal urine output, space-occupying thoracic lesions, fetal tic workup and commencement of antibiotic therapy.
dyskinesia) Infection may be contracted in utero (congenital) and
• Chronic neonatal lung disease present at birth or soon afterwards (usually during the
• Airway obstruction (e.g. choanal atresia, oesophageal first 48 hours of life), or acquired and present later
atresia with tracheo-oesophageal fistula, micrognathia, (this is often nosocomial). Maternal risk factors for
laryngomalacia, tracheomalacia, vascular ring, subglottic
congenital infection include known colonization with
stenosis)
• Cardiac disease (e.g. pulmonary hypertension, a pathogenic organism (e.g. group B streptococcus);
transposition of the great arteries with intact septum, previous infant with early-onset neonatal septicaemia;
total anomalous pulmonary venous return, patent ductus prolonged rupture of membranes (≥ 18 hours); multi-
arteriosus, large ventriculoseptal defect, atrioventricular ple vaginal examinations; intrapartum or postpartum
canal) temperature ≥ 38°C; and preterm labour (< 37 com-
• Other respiratory causes (pulmonary haemorrhage, pleted weeks of gestation).
pulmonary lymphangiectasia, pleural/chylous effusions,
Signs of infection in the baby are non-specific and
hydrops fetalis, eventration of the diaphragm)
• Abdominal distension (e.g. bowel obstruction, necrotizing include respiratory distress, an unexpected need for
enterocolitis, massive ascites) resuscitation, lethargy, apnoea, hypoglycaemia, hyper-
• Other – severe anaemia, polycythaemia, ischaemia, glycaemia, bradycardia, poor perfusion, hypotension,
metabolic disease, increased metabolic demand such increased respiratory tract secretions, temperature
as hyperthermia, acidaemia, decreased chest wall instability (especially hypothermia) and feed intoler-
compliance (e.g. severe oedema or skeletal dysplasia)
ance. Infection may be found in any normally ster-
ile or non-sterile site, but is most commonly seen in
the blood (septicaemia), respiratory tract, urinary
It is important to remember that not all cases of tract or cerebrospinal fluid. A large number of organ-
respiratory distress are caused by respiratory disease. isms including bacteria, viruses and fungi have been
One of the most common non-respiratory causes reported to cause congenital and nosocomial infection
is metabolic acidosis (as seen in hypoxic ischaemic in neonates.
encephalopathy); the baby compensates for the aci- Unless you are absolutely certain that the baby does
dosis by increasing the respiratory effort in order to not have a bacterial infection (and this is rarely the
clear more carbon dioxide. Some of the other non- case in a baby with respiratory distress), you should
respiratory causes of respiratory distress are listed in start antibiotics. Antibiotic regimens vary according
(Box 11.3.1.) to local patterns of disease, the age of the baby and
previous organisms isolated (from mother or baby).
Generally speaking, initial antibiotic choices should
be broad-spectrum and then tailored once an organ-
Respiratory causes of respiratory ism and its antibiotic sensitivities have been identified.
For early infection, a penicillin and aminoglycoside
distress are usually used. Antibiotic choice for late infection
Regardless of the lung disease that causes the respi- is very much driven by the type of bacteria prevalent
ratory distress, the single most important aspect of in the neonatal unit at the time and known c­ olonizing
354 its pathophysiology is atelectasis. Almost all of the bacteria.
 BREATHING PROBLEMS IN THE NEWBORN 11.3

Clinical example

Baby Caleb was born via vaginal delivery at

41 weeks and 5 days' gestation. His 30-year-
old primigravida mother had undergone
induction for being post dates and had received
two doses of dinoprostone (Prostin). An artificial rupture of
membranes was performed 19 hours prior to delivery and no
intrapartum antibiotics had been administered. Caleb was
unexpectedly flat at delivery but responded well to 60 seconds
of intermittent positive-pressure ventilation via bag and
mask for resuscitation. His birth weight was 3200 g and the
Apgar score was 4 and 8 at 1 and 5 minutes respectively. At
60 minutes of age he was noted to have grunting respirations,
poor perfusion and seemed lethargic. Caleb was admitted to
the nursery, had a full blood count and blood culture collected, Fig. 11.3.1 Chest X-ray of retained fetal lung fluid.
and was commenced on intravenous antibiotics and a 10%
dextrose infusion at a rate of 8 mL/h. He proceeded to have
major apnoea, which required intubation and mechanical
ventilation. Umbilical venous and arterial catheters were
deficiency in the alveoli. Surfactant is produced by
placed. Caleb continued to deteriorate with increasing oxygen
requirements, hypotension and hypoglycaemia. At 14 hours of the type 2 pneumocytes and is a surface tension low-
age the laboratory called to inform that the blood culture was ering agent that allows alveoli to expand more eas-
positive and growing Gram-positive cocci. Despite intravenous ily and helps to prevent their collapse. The incidence
antibiotics, inotropic support and mechanical ventilation, Caleb is directly related to gestational age (Fig. 11.3.2) and
died at 20 hours of age. The culture subsequently revealed can be prevented by administering antenatal corti-
group B streptococcus, which was sensitive to penicillin. costeroids or treated with surfactant replacement
therapy (either prophylactic or rescue). The natu-
ral history of RDS is that it presents at or shortly
Retained fetal lung fluid or transient
after birth, increases in severity for 24–72 hours, the
tachypnoea of the newborn
baby then starts to diurese and recovery subsequently
Retained fetal lung fluid (RFLF), also commonly occurs over the next 48–72 hours. This is often abbre-
known as transient tachypnoea of the newborn (TTN) viated by the administration of exogenous surfac-
or ‘wet lung’, occurs when either there is an excess of tant but can be prolonged in the extremely preterm
lung fluid or clearance mechanisms are inefficient. It infant. Treatment of RDS with exogenous surfactant
is generally a benign, self-limiting disorder and occurs decreases mortality and the incidence of pulmonary
in 1–2% of term newborn infants. Risk factors include air leak.
caesarean section without labour, breech delivery, male
sex, birth asphyxia and heavy maternal analgesia. Babies
present with respiratory distress and are sometimes
described as ‘mucusy’ owing to the increased nasal and 100
oral secretions. Infection should always be considered as 90
a possible cause. A chest X-ray should be performed to 80
rule out other causes of respiratory distress (e.g. pneu-
70
mothorax, congenital diaphragmatic hernia). The lung
% with RDS

60
fields on a chest X-ray show coarse streaking with fluid
in fissures, giving a ‘wet lung’ appearance (Fig. 11.3.1). 50
Most babies will settle with minimal handling in 24–48 40
hours and cot oxygen, but occasionally require respira- 30
tory support (e.g. CPAP, rarely ventilation). 20
30
Respiratory distress syndrome or hyaline 0
membrane disease 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37
Gestational age (completed weeks)
Respiratory distress syndrome (RDS), also known
as hyaline membrane disease (HMD), is a specific Fig. 11.3.2 Incidence of respiratory distress syndrome (RDS)
entity in preterm infants; it is caused by surfactant with gestational age.
355
 11.3 NEONATAL PROBLEMS

• pulmonary interstitial emphysema (PIE): air in the

interstitial lung spaces
• pneumoperitoneum: air in the peritoneal cavity
(although this is more often secondary to a
perforated abdominal viscus).
The pathophysiology of these conditions is similar, in
that the alveoli become hyperinflated and rupture. Air
escapes into the lung interstitium (PIE) or tracks along
the perivascular spaces and ruptures into the medias-
tinum (pneumomediastinum), through the visceral
pleura (pneumothorax) or rarely into the pericardial
space (pneumopericardium).
Predisposing factors include the administration
of positive-pressure breaths (including during active
resuscitation at birth) and lung disease (especially
Fig. 11.3.3 Chest X-ray of respiratory distress syndrome. hypoplastic lungs, meconium aspiration syndrome,
RDS and RFLF). Spontaneous pneumothorax occurs
in 1% of vaginal and 1.5% of caesarean section deliv-
RDS has a characteristic clinical picture and chest eries, but is usually asymptomatic.
X-ray shows hypoaeration, a diffuse granuloreticu- Signs of a pulmonary air leak are non-specific
lar pattern (ground-glass appearance), air broncho- and include respiratory distress, chest asymmetry,
grams and, in its most severe form, a diffuse ‘white out’ decreased air entry on auscultation on the affected
(Fig. 11.3.3). side, trachea deviated away from the affected side,
increased transillumination on the affected side,
increasing ventilatory or oxygen requirements, and
sudden deterioration with cardiorespiratory collapse.
If the baby is stable, pulmonary air leak can be con-
Clinical example firmed by chest X-ray. If the baby with a pneumotho-
rax is unstable, emergency ‘needle’ aspiration and then
Baby Kate was born at 29 weeks' gestation via drainage with an intercostal catheter may be required.
emergency caesarean section to a 31-year- A pneumomediastinum rarely needs to be drained.
old G2P1 mother who presented with a blood
pressure of 150/100 mmHg, abnormal liver
function test results and hyperreflexia, presumably secondary
to pregnancy-induced hypertension. Her mother was given
one dose of betamethasone only 1 hour prior to delivery.
Kate weighed 1100 g and had Apgar scores of 3 and 6 at 1 Clinical example
and 5 minutes of age. She was commenced on nasal CPAP
shortly after birth, but over the next 4 hours had increasing Baby Isabelle was born via elective lower-
work of breathing and oxygen requirements, which increased segment caesarean section at 38 weeks'
to 35%. Umbilical and venous catheters were inserted. gestation to a 27-year-old primigravida mother.
After a premedication she was intubated with a 3.0-mm Her birth weight was 3000 g and her Apgar
endotracheal tube, given a dose of exogenous surfactant and score was 9 and 9 at 1 and 5 minutes respectively. She
ventilated with synchronous intermittent positive-pressure developed early respiratory distress with a respiratory rate
ventilation. Her ventilatory requirements weaned rapidly and of 70 breaths per minute, expiratory grunting, intercostal
she was subsequently extubated to CPAP 12 hours later. She recession and cyanosis. She was found to have oxygen
remained CPAP dependent for a further 16 days. saturations in the low 80s, which improved with oxygen. She
was commenced on nasal CPAP and seemed to settle until
4 hours of age when her oxygen requirement and work of
breathing suddenly increased and she became bradycardic.
Clinical examination revealed decreased air entry on the
right, the trachea deviated to the left, an asymmetrical chest
Pulmonary air leaks
wall with the right side appearing full compared with
Pulmonary air leaks are more common in the neonatal the left, and the right chest bright on transillumination.
period than at any other time of life. There are several A tension pneumothorax was suspected and an emergency
needle aspiration was performed. Some 80 mL air was
types:
removed, with an immediate improvement in her condition.
• pneumothorax: air in the pleural cavity An intercostal catheter was placed on the right side and she
356 • pneumomediastinum: air in the mediastinum was commenced on a morphine infusion for analgesia.
• pneumopericardium: air in the pericardial space
 BREATHING PROBLEMS IN THE NEWBORN 11.3
Aspiration
Any liquid or solid that enters into the respiratory tract
can lead to obstruction, atelectasis and an inflamma-
tory response. In newborn babies, the most commonly
aspirated agents are meconium, liquor amnii, blood,
milk and gastric contents.
Meconium staining of liquor occurs in 10–20%
of births, especially breech, post-term and where
there is fetal distress. Staining of the amniotic fluid
may range from thin green/brown-stained fluid to
thick particulate matter. Meconium aspiration syn-
drome (MAS) occurs in only about 5% of infants
born through meconium-stained amniotic fluid.
Aspiration probably occurs in utero as the fetus
starts to gasp with hypoxia. Suction of the airway
under direct vision at birth of an infant with meco-
nium-stained liquor is recommended only if the Fig. 11.3.4 Chest X-ray of meconium aspiration.
infant is non-vigorous and has not yet established
respiration. A vigorous baby is one that has strong
breathing efforts, a heart rate greater than 100 beats
Abdominal contents herniate through a muscu-
per min and good tone.
lar defect in the diaphragm into the chest. The inci-
dence is 1 in 3800 births, with 60% isolated and
Meconium aspiration syndrome
40% associated with other anomalies or chromo-
MAS has a constellation of features, which usually somal defects. The hernia is usually a posterolateral
include the following: (Bochdalek) type, with 85% occurring on the left
• birth asphyxia requiring resuscitation side. The defect in the diaphragm permits bowel or
• infant covered in meconium with staining of cord, liver to herniate into the thorax with lung compression
skin and nails and pulmonary hypoplasia (worse on the side of the
• meconium in the airway hernia but also present on the opposite side). Most
• early-onset respiratory distress that may increase in cases are diagnosed by routine obstetric ultrasonog-
severity as inflammatory response develops raphy at 17–19 weeks' gestation or following investi-
• pulmonary hypertension gation for polyhydramnios. If not diagnosed in the
• surfactant dysfunction antenatal period, an infant may present immedi-
• secondary bacterial infection (occurs late but ately after birth with respiratory distress, dextrocar-
always consider congenital infection as a potential dia (if a left-sided hernia) and a scaphoid abdomen.
cause). Diagnosis is confirmed by demonstration of abdom-
Chest X-ray can show widespread, coarse, pulmonary inal contents (especially bowel loops) in the thorax
infiltrate and atelectasis, areas of hyperinflation, and on chest X-ray.
often both (Fig. 11.3.4).
Management
Management
Management involves gastric decompression and car-
Morbidity and mortality from MAS can be prevented
diorespiratory support. Surgical repair is typically
or minimized by optimal perinatal management.
delayed for 3–7 days to enable maximum stabilization.
Treatment for established MAS is as for respiratory
Prognosis depends on age at presentation, coexisting
distress, with emphasis on humidification of inspired
problems, degree of pulmonary hypoplasia, presence
gases, postural drainage and airway suction, and
of polyhydramnios and the severity of pulmonary
antibiotics. Other management strategies include
hypertension. Overall only 30–60% of children with
mechanical ventilation optimizing lung expansion,
an isolated lesion survive.
surfactant, inhaled nitric oxide, high-frequency oscil-
lator ventilation and, possibly, extracorporeal mem-
brane oxygenation. Pulmonary hypoplasia
Normal fetal lung development requires adequate
Congenital diaphragmatic hernia
amniotic fluid volume and fetal breathing move-
357
See also Chapter 11.5. ments. Although unilateral lung hypoplasia may be an
 11.3 NEONATAL PROBLEMS

i­solated developmental anomaly, bilateral hypoplasia • type 1 (70%) – single or multiple large cysts in one
is secondary to other factors, such as: lobe
• oligohydramnios (e.g. prolonged membrane • type 2 (18%) – multiple medium-sized cysts
rupture and liquor leak, or severe renal disease • type 3 (10%) – large cysts containing smaller cysts.
with little fetal urine output). The baby with renal Differential diagnosis is from lobar emphysema,
agenesis may exhibit additional features of Potter sequestration of lung and pulmonary lymphangiecta-
deformation sequence with facial dysmorphism, sia. Surgical resection is usually curative.
joint contractures and amnion nodosum of the
placenta Neonatal chronic lung disease
• a space-occupying lesion in the thorax (e.g.
diaphragmatic hernia, pleural effusion, cystic Neonatal chronic lung disease (CLD) usually fol-
adenomatoid malformation of the lung) lows acute lung disease (most often RDS) in babies
• chest wall deformities (e.g. skeletal dysplasia) at high risk – the extremely preterm and those requir-
• fetal dyskinesia causing a decrease in fetal breathing ing mechanical ventilation with high pressures and
patterns. large tidal volumes. The lung disease is characterized
Infants with pulmonary hypoplasia present with by chronic inflammation of the alveoli and airways
progressive respiratory failure from birth, with with small airway narrowing, areas of atelectasis and
marked hypoxia, hypercarbia and metabolic acidosis. hyper-expansion, increased airway secretions and, in
Pneumothorax is common, due to the increased ven- the extremely preterm, altered lung architecture with
tilatory pressures used to try to achieve adequate gas decreased numbers of distorted alveoli. For research
exchange. Death, ventilator dependence or broncho- and audit purposes, neonatal CLD in ex-preterm
pulmonary dysplasia may result. infants is best defined as infants who require respiratory
support or oxygen beyond 36 weeks' postmenstrual age.
CLD may also complicate other lung diseases, such as
Pulmonary haemorrhage meconium aspiration or pulmonary hypoplasia.
Pulmonary haemorrhage most commonly presents in Infants with neonatal CLD have persistent chest
very preterm infants with haemorrhagic pulmonary recession, increased work of breathing, episodes of
oedema (with blood welling up the endotracheal tube), cyanosis and crackles/wheeze on auscultation of
which will compromise ventilation and lead to cardio- the chest. They are prone to lung infections, gastro-
vascular collapse. It may be seen in a large patent duc- oesophageal reflux, aspiration, systemic hypertension,
tus arteriosus, severe perinatal asphyxia, coagulation bronchospasm, progressive pulmonary hypertension
disturbances, severe intrauterine growth restriction, with or without cor pulmonale, poor growth, develop-
hypothermia or congenital heart disease, and occa- mental delay and sensorineural disability.
sionally following exogenous surfactant therapy for
RDS. Treatment consists of positive-pressure venti- Other lung diseases
lation with high positive end-expiratory pressure to Other disorders presenting in the newborn include
keep the lungs open and management of any coexist- sequestration of lung, pulmonary lymphangiectasia,
ing shock, coagulation disturbance or patent ductus lung cysts (especially bronchogenic), pleural/chylous
arteriosus. effusions and eventration of the diaphragm.

Congenital lobar emphysema

This is a rare anomaly due to cartilaginous deficiency Airway obstruction
in lobar bronchus (left upper lobe 50%, right middle
Any form of obstruction to the upper airway or lower
lobe 24%, right upper lobe 18%). It may present as an
airway can cause respiratory distress. The normal anat-
insidious onset of respiratory distress over 2–3 weeks.
omy of the upper airway is shown in Figure 11.3.5.
It is associated with congenital heart disease in 30%
Babies with severe airway obstruction from birth usu-
of cases. On chest X-ray there is a hyperinflated lobe
ally present with respiratory distress immediately after
with surrounding pulmonary collapse and mediastinal
birth with rapid onset of cyanosis, bradycardia and
displacement. Surgical lobectomy is usually curative.
eventually apnoea.

Cystic adenomatoid malformation Nasal obstruction

This is often diagnosed on antenatal ultrasonography. As newborn infants are obligatory nose-breath-
Polyhydramnios, hydrops fetalis, prematurity or still- ers, choanal atresia (caused by a bony obstruction
358
birth may result. There are three types: of the nasopharyngeal meatus) can present with
 BREATHING PROBLEMS IN THE NEWBORN 11.3

Palate

Nasopharyngeal
Tongue meatus

Epiglottis

Oesophagus
Trachea

Fig. 11.3.5 Normal upper airway anatomy.

Pharyngeal obstruction
obstructed breathing and apnoea. The atresia can
be confirmed by failure to pass a nasogastric tube Micrognathia (as seen in the Pierre Robin sequence)
through either nare. This can be managed tempo- causes a backward displacement of the tongue which
rarily by the insertion of an oropharyngeal airway obstructs the pharynx. This can be managed tem-
(Fig. 11.3.6). porarily by insertion of a nasopharyngeal airway

Bony obstruction of
the nasopharyngeal
meatus
Oropharyngeal
airway

359
Fig. 11.3.6 Choanal atresia and oropharyngeal airway.
 11.3 NEONATAL PROBLEMS

Nasopharyngeal
airway

Fig. 11.3.7 Micrognathia and nasopharyngeal airway.

(Fig. 11.3.7). Severe macroglossia (as seen in trisomy

21 and Beckwith–Weidemann syndrome) can be man- Hypoventilation
aged in a similar fashion. Rare causes of upper airway The physiology of breathing requires more than a pair
obstruction include tumours and cysts of the tongue of lungs with a functional gas-exchanging surface and
or floor of the mouth, as well as cystic hygromas. matching circulation. It also requires an intact mecha-
nism to enable the mechanics of breathing (i.e. moving
Laryngeal and/or tracheal obstruction a bulk volume of air in and out of the lungs with each
breath). A clear airway is essential, as is an intact path-
Laryngomalacia, due to a large floppy larynx (sec- way from the respiratory signals in the brainstem to the
ondary to decreased cartilage) that narrows on inspi- muscles of breathing. Any malfunction of the neuro-
ration, may rarely present in the newborn period as muscular pathway (Fig. 11.3.8), from brain to respira-
respiratory distress (most commonly as inspiratory tory muscles, can lead to hypoventilation and inadequate
stridor when crying). Most cases are benign. However, gas exchange, especially carbon dioxide clearance.
if severe, consult with an ENT surgeon as surgical
laser excision of the aryepiglottic folds may be cura-
Apnoea
tive. Other causes of upper airway obstruction include
subglottic stenosis (often due to repeated or trau- The ultimate form of hypoventilation is apnoea.
matic intubations), laryngeal webs, laryngeal oedema/ Apnoea is defined as a cessation or absence of air flow
inflammation (due to prolonged/traumatic intubation) in and out of the lungs. In a practical sense, neonates
or haemangiomas. Unilateral vocal cord paralysis will are said to have had an apnoea when either there is: (1)
partially obstruct the larynx; bilateral paralysis causes no air flow for 20 seconds or more, or (2) no air flow
complete obstruction. Other causes of obstruction for 10 seconds or more if it is accompanied by brady-
in the lower airway include tumours, haemangiomas cardia or desaturation.
of the airway (can be in the lumen, in the wall of the Apnoea does not necessarily mean there is no respira-
larynx or trachea, or compressing from outside the air- tory effort. Complete airway obstruction will not allow
way), vascular rings, broncho/tracheomalacia, and any airflow, but, at least initially, there will be respira-
tracheal stenosis or webs. Examination of the airway tory effort – this is the case with obstructive apnoea.
under direct vision (laryngoscopy and/or bronchos- The most common cause of apnoea in neonates is
copy) is often required to define the cause and extent apnoea of prematurity. The immature respiratory centres
360
of the airway obstruction. in the brainstem regulate breathing poorly until around
 BREATHING PROBLEMS IN THE NEWBORN 11.3
Modified by: Spontaneous rhythmic discharge
• alteration in PaO2, of neurons in the respiratory • Immaturity
PaCO2 and pH centres of the brain stem • Hypoxic–ischaemic injury
• neural input from (pons and medulla)
vagus and various
receptors

White matter tracts

in brain stem and • Spinal cord injury
spinal cord

Anterior horn cells

• Spinal muscular atrophy

Respiratory motor
neurons
(phrenic and
thoracic nerves)

Neuromuscular • Maternal myasthenia gravis

junction • Infant botulism

Respiratory muscles • Congenital myopathies and

(diaphragm, intercostal muscular dystrophies
muscles) including myotonic dystrophy

Fig. 11.3.8 Flow diagram showing control of respiration.

34 weeks' gestational age. Breathing patterns will • infection – generalized or focal; bacterial or viral
vary from regular, irregular and periodic; all may be • intracranial haemorrhage
­accompanied by apnoea in a well preterm infant. Periodic • polycythaemia with hyperviscosity
respirations refer to a cyclical pattern of changes in the • necrotizing enterocolitis
size of the infant's breaths – usually alternating periods • patent ductus arteriosus
of normal breathing with hypoventilation. • seizures
Apnoeas commonly occur in otherwise well preterm • temperature instability (e.g. incubator temperature too
infants. They often resolve spontaneously or gentle high, hypothermia, too rapid warming or cooling).
stimulation is required to restart breathing. Any previously well preterm infant who develops
Because of preterm infants' immature respiratory apnoea or has an increase in the frequency or sever-
centres, they are prone to developing apnoea (or more ity of their apnoea warrants investigation for a cause.
severe or more frequent apnoea) from a variety of This must include a blood culture (with or without
causes. These include: cerebrospinal fluid culture), a full blood count and
• lung disease blood film examination, and then commencement of
• hypoxia antibiotics.
• acidaemia Apnoea in a term infant is always abnormal and
• drugs (e.g. narcotics (including those given to the a cause must be sought. Cover with antibiotics until
mother), dinoprostone, magnesium sulphate) bacterial infection is ruled out. Consider covering for
• metabolic disturbance (e.g. hypoglycaemia, treatable viral infections such as herpes.
hypocalcaemia, hypomagnesaemia, It is sometimes useful to classify apnoea as central, 361
hypermagnesaemia) obstructive, mixed or reflex:
 11.3 NEONATAL PROBLEMS

• Central apnoea – apnoea secondary to factors Hypoxic–ischaemic encephalopathy can interfere

affecting the respiratory centres in the brainstem. It with respiratory centre function secondary to direct
is characterized by an absence of respiratory effort. neuronal injury. Any accompanying seizures are
• Obstructive apnoea – complete obstruction of the more likely to cause apnoea. Spinal cord injury is a
central airways will cause obstructive apnoea. Nasal rare complication of traumatic delivery (e.g. follow-
obstruction can also cause obstructive apnoea ing rotational forceps delivery). In congenital spi-
because newborn infants are obligatory nose- nal muscular atrophy the anterior horn cells of the
breathers. Causes of airway obstruction have been motor neurons degenerate, leading to generalized
discussed above. Transient causes include milk muscle weakness that includes the respiratory mus-
and mucus, or foreign bodies lodged in the airway. cles. Blockage of the neuromuscular junction can
Obstructive apnoea is characterized initially by occur with infant botulism (rare in the developed
increased respiratory efforts. world but not infrequent in the developing world)
• Mixed apnoea – a mixture of central and or maternal myasthenia gravis (maternal anti-acetyl-
obstructive types; seen especially in the preterm choline receptor antibodies block the neuromuscular
infant where an obstruction can trigger central junction). Any weakness of the respiratory muscles
apnoea. This is difficult to diagnose clinically. from congenital myopathies and muscular dystro-
• Reflex apnoea – reflex or vagally mediated apnoea phies (including myotonic dystrophy) will also lead
can occur after suction of the pharynx, larynx or to hypoventilation.
stomach, secondary to passage of a nasogastric
tube, or even in response to defaecation. Apnoea
associated with gastro-oesophageal reflux may be Practical points
reflex and/or obstructive.
• The signs of respiratory distress may include any of the
following: tachypnoea, expiratory grunt, recession, nasal
Neuromuscular causes flare and central cyanosis.
Sometimes hypoventilation presents without overt • A baby with respiratory distress should be monitored
closely for signs of respiratory failure.
apnoea. Any interruption of the pathway shown in • Infection should always be considered as a possible cause
Figure 11.3.8 can decrease ventilation; this usually of respiratory distress. Unless you are absolutely certain
causes carbon dioxide retention initially, with or with- that the baby does not have a bacterial infection (and
out hypoxia. Often babies with neuromuscular causes this is rarely the case in a baby with respiratory distress),
for their hypoventilation will have a high PaCO2 in the you should collect a blood culture and start intravenous
antibiotics.
absence of any increased respiration. If the respira-
tory neuromuscular pathway is intact, a high PaCO2 • A chest X-ray is useful to exclude causes of respiratory
distress such as pulmonary air leak and congenital
will usually cause dramatically increased respiratory diaphragmatic hernia.
efforts.

362
 Congenital and perinatal 11.4
infections
Mike Starr

Many organisms can cause infection in the fetus and

Introduction newborn. Box 11.4.1 lists some of the more common
Infections in the fetus and newborn (perinatal infec- or clinically significant.
tions) may be acquired in utero (congenital infec-
tion), around the time of delivery or in the neonatal Risk assessment
period.
The risk of fetal damage can be estimated, based on:
• the likelihood of maternal exposure and infection
Modes of acquisition of infection • the likelihood of transmission to the fetus
• In utero • the stage in gestation at which infection occurs –
this influences the risk of vertical transmission and/
• haematogenous – placental infection and/or
transplacental transmission or the fetal or perinatal consequences.
Only a small number of exposed infants are infected
• ascent from the maternal genital tract – across
intact membranes, or after the membranes and, of these, a minority will have adverse effects.
rupture Many infections that can damage the fetus are mild
or asymptomatic in the mother, and diagnosis may
• During delivery
• from maternal genital secretions depend on routine antenatal screening. Whether this is
• from maternal blood appropriate depends on the frequency and severity of
• After birth fetal or neonatal disease and the availability of a suit-
• from breast milk able screening test and effective intervention.
• by conventional (horizontal) routes from mother
or other contacts.
The route by which the fetus or newborn acquires the Practical points
infection has important implications for management
during pregnancy and the neonatal period, and for the Congenital infections
development of appropriate intervention strategies to • Some common viral infections (e.g. cytomegalovirus,
prevent mother-to-child transmission. parvovirus, rubella, varicella-zoster virus) can cause fetal
The outcome of perinatal infection may include infection with severe consequences if acquired during
pregnancy by a non-immune woman.
particular constellations of congenital abnormali-
• Ensuring that a woman has antenatal testing and
ties, spontaneous abortion or stillbirth, or acute is immunized with all recommended vaccines is an
neonatal infection. Common clinical manifestations important part of care during pregnancy.
include: • Management of a pregnant woman exposed to relevant
• growth retardation viral infections depends on a careful risk assessment,
• prematurity which includes knowledge of the woman's immune status,
history of the exposure, stage in the pregnancy, and
• hepatitis, thrombocytopenia
clinical presentation in the woman.
• meningoencephalitis
• microcephaly
• intracerebral calcifications
• rash
• chorioretinitis Organisms associated
• deafness with perinatal infection
• neurological defects.
Cytomegalovirus
For some congenital infections, there may be no symp-
toms or signs in the neonatal period and it may be Primary cytomegalovirus (CMV) infection is usually
weeks, months or even years before the effects first asymptomatic or causes a non-specific illness with
become evident. fever, atypical lymphocytosis and mild hepatitis. The 363
 11.4 NEONATAL PROBLEMS

Box 11.4.1 Organisms commonly associated with

• 1% of women seroconvert during pregnancy.
perinatal infection • 30% of fetuses of women with primary infection
are infected.
Associated with congenital abnormalities • The risk of congenital CMV infection after primary
• Cytomegalovirus maternal CMV infection remains increased for up
• Parvovirus B19 to 4 years after seroconversion, with the highest risk
• Rubella being in the first 2 years.
• Toxoplasma gondii
• Treponema pallidum (syphilis)
• Infection is transplacental; severe fetal damage is
• Varicella zoster virus more likely early in gestation.
• 10% of infants infected during primary maternal
Associated with acute neonatal infection infection are symptomatic at birth: of these, 90%
• Chlamydia trachomatis have significant long-term handicap.
• Escherichia coli • 90% of infants infected during primary maternal
• Enterovirus infection are asymptomatic at birth: of these,
• Herpes simplex virus
• Listeria monocytogenes
10% go on to develop deafness or intellectual
• Group B streptococcus handicap.
• The overall incidence of congenital infection due to
Associated with chronic infection primary maternal infection is 1 in 1000.
• Hepatitis B virus
• Hepatitis C virus
• Human immunodeficiency virus Reactivation
• 20–30% of seropositive women reactivate latent
infection during pregnancy.
virus remains in a latent state with periodic asymp- • 2–5% of their infants are infected in utero but
tomatic reactivation and excretion in urine, saliva or significant CMV disease is rare; mild sequelae
genital secretions. Primary maternal infection or reac- (unilateral deafness) occur infrequently (< 10%).
tivation can result in fetal CMV infection, although • The overall incidence of congenital infection is
fetal damage is more likely to be associated with pri- 1–2% – the majority are unaffected.
mary infection. CMV can infect the fetus transplacen-
tally to cause congenital infection.
Clinical features
Cytomegalovirus can also be transmitted d ­uring
or after delivery when the neonate comes in contact The clinical features of severe intrauterine CMV infec-
with maternal genital secretions or with breast milk. tion include:
However, it appears that there are no hearing or • intrauterine growth restriction
neurodevelopmental sequelae. • hepatosplenomegaly, hepatitis
Congenital CMV affects approximately 3–12 per • anaemia, thrombocytopenia
1000 births and causes 10–30% of childhood sensori- • pneumonitis
neural hearing loss (SNHL). Infants with asymptom- • microcephaly, encephalitis, cerebral calcification
atic congenital CMV have a risk of developing hearing and chorioretinitis
loss or intellectual disability. Early intervention can • SNHL in congenital CMV affects 50% of
minimize the impact of SNHL on language devel- symptomatic infants and 10% of asymptomatic
opment. Moreover, antiviral treatment may improve infants. It is the most common long-term
outcome. consequence. It ranges from mild unilateral to
The best evidence for primary maternal infection profound bilateral hearing loss. In asymptomatic
is seroconversion but this may not be demonstrable infants it may be underdiagnosed because the
if investigation is delayed. Specific immunoglobulin SNHL is detected too late to prove congenital
(Ig) M may indicate recent infection but is unreliable: infection
it may be detectable for months, can rise after reacti- • cerebral palsy, intellectual disability, epilepsy and
vation, and false-positive results are not uncommon. visual impairment.

Primary infection Diagnosis

• 50% of young women are seronegative (susceptible). If primary maternal infection is suspected or can-
In developing countries and lower socioeconomic not be excluded, fetal infection can be diagnosed
groups, primary infection occurs at a younger age by culture and/or polymerase chain reaction (PCR)
364
and fewer women are susceptible. analysis of amniotic fluid at 18 weeks’ gestation.
 Congenital and perinatal infections   11.4
Depending on when maternal infection occurred, Parvovirus B19
the risk of fetal damage may justify termination of
Most cases of parvovirus B19 infection are asymp-
pregnancy.
tomatic. The most common clinical presentation of
Congenital CMV infection is diagnosed by a posi-
infection is erythema infectiosum, or ‘slapped cheek
tive culture of urine or saliva collected in the first
disease’ in children.
3 weeks of life; after that it is difficult to distin-
Parvovirus B19 can also cause:
guish congenital from postnatal infection. Testing
for CMV IgM in the infant's serum is less sensitive
• asymptomatic infection
and specific. Congenital infection may be confirmed
• mild respiratory tract illness without rash
by PCR analysis of dried blood spots (e.g. Guthrie
• petechial or purpuric rash
card).
• arthritis in adults
• chronic bone marrow failure in immunodeficient
patients
Treatment • transient aplastic crisis in patients with haemolytic
anaemia (e.g. sickle cell disease).
Antiviral drugs active against CMV are contraindi-
Approximately 60% of adult women are immune.
cated during pregnancy but have been used with limited
The risk of infection in seronegative women is great-
success in congenitally infected infants. Intravenous
est in women exposed to an infected child at home
ganciclovir and oral valganciclovir have been shown
(approximately 50%). The risk for childcare and pri-
to reduce hearing deterioration in infants with symp-
mary school teachers exposed is 20–30%, and the risk
tomatic congenital CMV and central nervous system
overall depends on exposure to children but is approxi-
involvement. However, use of these medications is lim-
mately 10–20%.
ited by their side-effects. There is currently no indi-
cation for systemic antiviral therapy for infants with
asymptomatic infection at birth. Fetal risks following maternal infection
In 50% of cases of maternal infection, the fetus is unaf-
fected. Fetal damage occurs only if maternal infection
occurs before 20 weeks’ gestation. The complications
Clinical example include:
• fetal loss in the first 20 weeks of pregnancy (15%
A 32-year-old woman delivered a small-
for-gestational-age baby boy weighing
compared with 5% in controls, i.e. 10% excess fetal
2400 g at 38 weeks’ gestation. His head loss)
circumference was smaller than expected for • congenital abnormalities: < 1% (anecdotal reports
his weight and he had hepatosplenomegaly. He also had only)
thrombocytopenia. • hydrops fetalis: following maternal infections at
Rubella, CMV, Toxoplasma and syphilis serology were 9–20 weeks’ gestation (incidence is approximately
performed on the baby and compared with the mother's
3%); may result in:
antenatal serological results. The baby had urine collected
for viral culture. The baby had CMV IgG and IgM present, • spontaneous resolution (one-third of cases)
and CMV was cultured from the urine, confirming congenital • fetal death (usually without intrauterine
CMV infection. transfusion; occasionally despite it)
The potential side-effects of 6 weeks of intravenous • resolution after intrauterine transfusion (most
ganciclovir therapy in this child must be weighed against cases in which it is attempted)
a possible small benefit in terms of reduction of hearing • long-term sequelae: chronic congenital anaemia
deterioration. Affected neonates should have baseline
after intrauterine transfusion is rare.
audiology testing, and this should be repeated in the
first 6 months of life. They should also be monitored for See also Table 11.4.1.
developmental delay. There are no specific congenital abnormalities asso-
ciated with maternal parvovirus infection.

Table 11.4.1 Risk assessment – parvovirus B19

Any pregnant woman Pregnant woman with

exposed to parvovirus (%) proven recent infection (%)

Excess fetal loss in first 20 weeks 0.4–1 (1 in 100–250) 5 (1 in 20)

Death from hydrops or its treatment 0.05–0.1 (1 in 850–2000) 0.6 (1 in 170) 365
 11.4 NEONATAL PROBLEMS

Diagnosis v­ accination programmes. However, in many develop-

ing countries, congenital rubella syndrome remains a
Diagnosis in children is mainly clinical. In potentially
major cause of developmental anomalies, particularly
infected women, serology and PCR can be performed.
blindness and deafness.
IgM is detectable within 1–3 weeks of exposure and
usually remains detectable for 2–3 months. Specific
IgG may rise 2–3 weeks following infection. Parvovirus Clinical features
DNA can be detected in serum for up to 9 months The risk of fetal infection and damage is greatest
after the acute viraemic phase in some patients, so it during the first 8 weeks of pregnancy and damage
does not necessarily indicate acute infection. is rare after 16 weeks. Congenital rubella syndrome
(Fig. 11.4.1) may include a number of clinical features,
Management some of which may not present until adolescence or
adulthood:
Pregnant school teachers or childcare workers do not
• intrauterine growth restriction
need to be excluded from work, even during an epi-
• neonatal purpuric rash and hepatosplenomegaly
demic (nor do infected children). It is certainly not
• microcephaly and developmental delay
practicable to prevent exposure at home. Pregnant
• cardiac: pulmonary artery hypoplasia, patent
women who have been exposed to parvovirus, and
ductus arteriosus
those with an illness consistent with parvovirus,
• eye: cataract, retinopathy; microphthalmia
should be tested serologically. If maternal infection is
• deafness – develops later
confirmed, the pregnancy should be monitored with
• diabetes mellitus – develops later.
serial ultrasonography.
Diagnosis
Clinical example Congenital rubella is confirmed by:
• isolation of rubella virus from saliva, tears, urine,
A 24-year-old primary school teacher is
cerebrospinal fluid (CSF) or tissue during the first
12 weeks’ pregnant. She has a 3-year-old who is
well at the moment. She is concerned because 3 months of life
there is a boy in her class with ‘slapped cheek • demonstration of specific IgM antibody or
disease’. What advice should be given to her? persistence of IgG antibody beyond 6 months of age.
The likelihood is that she is immune – 60% of women of
child-bearing age are seropositive. She should have her
serology done to check. Even if she is not immune, there
is no point in her staying away from school. The boy with
slapped cheek disease is probably no longer infectious –
once the rash is apparent children are not infectious,
and there may well have been others in the class with
asymptomatic infection. If there have been many cases of
parvovirus infection around, her 3-year-old may have had it
too, and the greatest risk of infection for a pregnant mother
is from her own children.
If the woman is seronegative when checked, she should
be offered repeat serology in 2 weeks. If the serology is
negative at this time, nothing further needs to be done. If she
has evidence of seroconversion, there is a 50% chance that
the fetus will be infected and a very small risk that she will
lose the pregnancy or that the fetus will develop hydrops.
She should have ultrasonography at 1–2-week intervals
for the next 8 weeks, checking for the development of fetal
hydrops. Even if this develops, at least 60% of fetuses will
have a good outcome.

Rubella
The teratogenic effects of rubella were first noted in
1941 by an Australian ophthalmologist, who recog-
nized several cases of congenital cataract following
a large outbreak of rubella. Maternal rubella is now Fig. 11.4.1 Characteristic purpuric (‘blueberry muffin’) rash of
366
rare in many industrialized countries with rubella congenital rubella.
 Congenital and perinatal infections   11.4
Prevention • central nervous system damage – intracranial
calcification, hydrocephalus and microcephaly
Congenital rubella is preventable by immunization
in childhood (see Chapter 3.5). Routine antenatal
• neurological and/or visual impairment in most
survivors.
screening and postpartum immunization of suscepti-
ble women provides additional protection. If rubella
infection or contact is suspected during pregnancy,
Diagnosis and management
investigation to detect or exclude infection (specific
IgM or IgG seroconversion) should be done, even in Toxoplasmosis during pregnancy is ideally diagnosed
women with known past immunity, as re-infection by demonstrating seroconversion. More commonly,
occasionally occurs. Termination of pregnancy may be it is suspected because specific IgM is detected in
recommended after proven infection during the first serum by antenatal screening. IgM can remain detect-
trimester. able for many months and, in the absence of symp-
toms, further testing is needed. Tests for the avidity
of IgG antibodies can discriminate between recently
Toxoplasma gondii
acquired and previous infection. If recent infection
Toxoplasma gondii is a protozoan parasite that is confirmed or cannot be excluded, treatment of the
infects up to a third of the world's population. mother with spiramycin can reduce the risk of verti-
Infection is acquired mainly by ingestion of food or cal transmission.
water that is contaminated with oocysts shed by cats Appropriate management depends on diagnosis of
or by eating undercooked or raw meat containing intrauterine infection by amniotic fluid PCR at about
tissue cysts. Primary infection is usually subclinical 18 weeks’ gestation. If fetal infection occurs during
but may cause lymphadenopathy or ocular disease. the first trimester, termination of pregnancy is often
Infection acquired during pregnancy may cause recommended. If infection occurs during the sec-
severe damage to the fetus. The risk of fetal infec- ond or third trimester, treatment of the mother with
tion increases, but that of fetal damage decreases a combination of pyrimethamine and a sulphon-
with advancing gestation (Table 11.4.2). There is amide is likely to reduce sequelae of the disease in
geographical variation in the incidence of congeni- the newborn.
tal infection; in Australia it is estimated to be less Specific IgM in the infant's serum or persistence
than 1 in 1000 births. of IgG beyond the first few months of life is evi-
dence of congenital toxoplasmosis. T. gondii may
Clinical features be detected in tissue by histological examination or
PCR, or in CSF by PCR. Treatment of a congeni-
• Most congenitally infected infants are tally infected infant with spiramycin, pyrimethamine
asymptomatic at birth. and a sulphonamide can reduce progressive damage
• Many later develop signs and sometimes symptoms after birth.
of chorioretinitis (up to 80%, with some visual
impairment in about half).
• Some 10% develop neurological sequelae and/or Treponema pallidum (syphilis)
hearing deficit.
Syphilis is a sexually transmitted infection caused
• Signs of severe symptomatic congenital
by Treponema pallidum. Congenital syphilis is now a
toxoplasmosis include:
rare disease in most countries but it remains a severe
• anaemia, hepatosplenomegaly, jaundice,
adverse outcome of pregnancy in many less devel-
lymphadenopathy
oped countries. Untreated syphilis in pregnancy can
• thrombocytopenia, petechial rash
cause stillbirth, preterm labour and intrauterine
growth restriction. Later in life, a range of neuro-
logical disorders can occur, including paretic neuro-
syphilis; all of these manifestations respond poorly
Table 11.4.2 Risk assessment – Toxoplasma gondii to treatment.
Fetal infection (%) Fetal damage (%)
Fetal infection is a result of haematogenous spread
from an infected mother, although transmission at the
First trimester 5–15 60–80 time of delivery can occur from direct contact with
infectious genital lesions. Transmission from mother
Second trimester 25–40 15–25
to fetus can occur at any stage of pregnancy, particu-
larly during early (primary, secondary or early latent)
Third trimester 30–75 2–10 367
syphilis. Maternal syphilis is often asymptomatic and
 11.4 NEONATAL PROBLEMS

recognized only because of a positive routine ante-

natal serological test. Early antenatal screening and Clinical example
treatment of maternal syphilis can prevent most cases
of congenital infection. A 19-year-old intravenous drug user has a past
history of a stillbirth at 36 weeks’ gestation,
The fetal outcome of untreated maternal syphilis
for which no cause was found. She is known
depends on the stage of the disease: to be hepatitis C positive, but her human
• primary or secondary: premature delivery or immunodeficiency virus (HIV) status is unknown. She is now
perinatal death, 50%; congenital syphilis, 50% pregnant and presents at term, having had no antenatal
(few normal infants) care. She delivers a baby boy who is noted to have
• early latent syphilis (or indeterminate): at least 50% hepatosplenomegaly. What tests should be done?
normal, 20–40% congenital syphilis; increased risk With no antenatal care and a baby with
hepatosplenomegaly, the concern is that the baby may
of perinatal death and preterm birth.
have a congenital infection. Given the history that she
was an intravenous drug user and hepatitis C positive,
particular concerns would include syphilis, hepatitis C,
Clinical features hepatitis B and HIV.
Mother and baby should have serological tests for
At least 50% of infants with congenital syphilis syphilis: rapid plasma reagin test (RPR) and Treponema
are asymptomatic, so diagnosis may rely on serol- pallidum haemagglutination test (TPHA). If the neonatal
ogy. Clinical features typical of congenital syphilis antibody titres are significantly higher than the mother's,
include: the baby's IgM should be tested. A lumbar puncture should
• an abnormally bulky placenta – histological also be performed on the baby. Neurosyphilis is suggested
examination should be done by CSF pleocytosis, raised protein level and positive CSF
serology.
• hydrops fetalis due to severe anaemia and/or severe The mother should have other serological testing: HIV
liver disease antibodies, hepatitis B surface antigen and hepatitis C
• lymphadenopathy, hepatosplenomegaly, jaundice antibody, and viral load. The baby should have hepatitis C
• osteochondritis with typical radiological changes; antibody testing no earlier than 12 months, and preferably at
arthropathy or pseudoparalysis 18 months of age. If performed earlier, a positive result may
• rhinitis (‘snuffles’) simply reflect the mother's antibody.
• vesiculobullous rash on back, legs, palms and soles,
followed by desquamation
• condylomata lata – fleshy lesions in moist areas of Varicella-zoster virus
skin.
At least 90% of adults are immune to varicella, but
The diagnosis is confirmed by serological tests on the
exposure during pregnancy is common. Fetal out-
mother and infant: neonatal IgG antibody titres that
comes following maternal infection early in pregnancy
are significantly higher than the mother's and/or the
include:
presence of specific IgM in the infant. A lumbar punc-
• uncomplicated self-limiting infection (10%)
ture should be performed on the infant. Neurosyphilis
• herpes zoster (shingles) in the first year of life
is suggested by CSF pleocytosis, raised protein level
(2–3%)
and positive CSF serology.
• fetal varicella syndrome (2–3% of cases),
manifestations of which include:
• growth restriction
Treatment
• skin scarring over a dermatomal distribution
Congenital syphilis is treated with parenteral peni- (Fig. 11.4.2)
cillin. Serological and clinical follow-up is needed • ipsilateral limb or other skeletal hypoplasia
to confirm successful treatment and exclude neu- • encephalopathy and abnormalities of various
rological or ophthalmological abnormality or organs.
deafness. The risk of fetal varicella syndrome in children
Congenital syphilis may present in a variety of exposed to varicella-zoster virus (VZV) in utero is
ways. It is important to screen for maternal syphilis around 0.5% after maternal infection at 2–12 weeks of
following stillbirth or if an unusual lesion or condi- pregnancy, 1.4% after infection at 12–28 weeks, and
tion consistent with syphilis is present in the new- does not occur after infection from 28 weeks onwards.
born infant. Routine antenatal screening for syphilis It occurs in around 1.6 per 100 000 births in the popu-
is cost-effective and still recommended, although the lation. Shingles in the mother does not carry a risk of
prevalence in Australia is low. Adequate treatment fetal varicella syndrome.
of an infected mother during pregnancy will prevent VZV infection of the newborn results from trans-
368
fetal damage. mission from a mother with chickenpox to her infant
 Congenital and perinatal infections   11.4

Clinical example

A 30-year-old mother of two has just had her

third baby. The day after delivery, her 2-year-
old developed chickenpox. She had cuddled
and kissed her mother and the new baby.
The 4-year-old has not had chickenpox and the mother
is not sure whether she has had it herself. The father had
chickenpox as a child. What should be done for this family?
The mother should have her VZV serology checked
immediately. If she is seronegative, the baby should be given
ZIG within 96 hours of exposure. ZIG may not abrogate the
risk of fetal infection, so the baby should be watched for
development of vesicles, and aciclovir should be given if he
Fig. 11.4.2 Skin scarring from congenital varicella-zoster virus
develops chickenpox.
infection.
The mother and 4-year-old should be offered VZV vaccine,
as post-exposure administration of the vaccine within 5 days
of exposure can prevent or limit severity of disease.
around the time of delivery, where the infant lacks the If the mother is found to be seropositive, nothing needs to
be done for her or the baby.
protection of maternal antibodies. The likelihood of
infection depends on the timing of delivery in relation
to when the mother develops the chickenpox rash. If
the rash develops more than 7 days before delivery, this
generally allows time for the development and trans- Neonatal sepsis
fer of protective maternal antibodies. However, as Neonatal sepsis is generally divided into early and late-
transfer of antibodies from the mother to the infant onset sepsis (EOS and LOS). The cut-off for these def-
is limited before 26–28 weeks of gestation, maternal initions is variable throughout the literature. EOS is
immunity to VZV does not usually protect preterm often defined as sepsis occurring within the first 7 days
infants delivered before 28 weeks’ gestational age. after birth, and LOS after 7 days. EOS is associated
If maternal VZV infection occurs during the week with maternal risk factors and acquisition of patho-
from 5 days before delivery until 2 days afterwards, gens from the birth canal, whereas LOS is associated
infection of the infant may be complicated by pneu- with infection by pathogens acquired at delivery but
monia, hepatitis or encephalitis, and high mortality. invading later, acquired at home or in hospital.
When maternal infection occurs more than 5 days The bacterial pathogens that classically cause EOS
before delivery, infection in the infant is usually mild. are:
Infants exposed to varicella after the first few days of • Streptococcus agalactiae (group B streptococcus,
life also usually have mild disease, although this is vari- GBS) – the most common in industrialized
able and depends, amongst other factors, on the moth- countries
er's immune status. • Escherichia coli
• Listeria monocytogenes – uncommon but often
Prophylaxis and treatment occurring in clusters.
Numerous bacteria can cause LOS, including coagulase-
Zoster immune globulin (ZIG) can prevent or modify negative staphylococci, Gram-negative bacilli, strep-
varicella if given within 4 days (preferably 48 hours) of tococci, anaerobes, Staphylococcus aureus, Chlamydia
exposure to: trachomatis and genital mycoplasmas.
• pregnant women with no past history of Neonatal infection with herpes simplex virus and
chickenpox who are seronegative or whose immune enterovirus may mimic bacterial sepsis.
status is unknown Risk factors for neonatal sepsis include premature
• newborn infants of women who develop varicella rupture of the membranes, chorioamnionitis and
within 5 days before to 2 days after delivery. maternal fever.
Severe varicella in mother or infant should be treated
with intravenous aciclovir.
Clinical features
Varicella vaccine is now a component of the rou-
tine immunization schedule (see Chapter 3.5). Intrauterine infection can cause premature labour or
Immunization of susceptible women of child-bearing fetal distress with or without maternal fever. The clini-
age will protect the fetus from the risk of congenital cal manifestations of neonatal sepsis are non-specific:
369
varicella. • respiratory distress, tachypnoea, apnoea
 11.4 NEONATAL PROBLEMS

• temperature instability, irritability infection, which manifests principally as ophthalmia

• feeding difficulty, vomiting, diarrhoea and neonatorum or pneumonia, is a significant cause of
jaundice neonatal morbidity. C. trachomatis is the most com-
• haematological changes – neutrophilia mon infectious cause of ophthalmia neonatorum in
or neutropenia, increased proportion of industrialized countries and is a significant cause of
immature neutrophils, thrombocytopenia and neonatal conjunctivitis in developing countries.
coagulopathy. The incidence of chlamydial infection varies widely
Focal disease such as pneumonia, meningitis, or uri- according to geography and socioeconomic group.
nary tract, bone, soft tissue or middle ear infections The incidence is relatively high in young, single women
may complicate disseminated sepsis or occur alone, with multiple sexual partners, in socially disadvan-
often with only non-specific systemic symptoms. taged groups and in developing countries. Additional
risk factors include presence of another sexually trans-
mitted infection or a partner with urethritis.
Diagnosis
Most infants of infected women are normal at
Investigations for suspected neonatal sepsis may delivery, but about 60% of those exposed are infected
include: and, of these, about half develop symptoms: 18–50%
• full blood examination and acute phase reactants develop conjunctivitis, 15–20% nasopharyngeal colo-
such as C-reactive protein nization and 5–20% pneumonia.
• culture of blood, CSF or urine (preferably collected
by suprapubic bladder aspiration)
Clinical features
• CSF examination (if indicated): typical findings
in bacterial meningitis are pleocytosis, with a • Conjunctivitis:
predominance of polymorphonuclear leukocytes, a • may develop a few days to several weeks
raised protein and decreased glucose level; in viral postpartum, typically between 5 and 14 days after
meningoencephalitis the cell counts are usually delivery
lower, mononuclear cells usually predominate and • severity ranges from mild conjunctival injection
glucose levels are normal to severe conjunctivitis with purulent discharge
• chest X-ray. • usually begins in one eye with progressive
involvement of the other eye after 2–7 days
• symptoms are often persistent but are eventually
self-limiting.
Practical points • Pneumonia:
• usually occurs between 2 and 19 weeks
Neonatal sepsis postpartum, typically around 6 weeks of age
• Newborn infants can develop bacterial sepsis from the • is associated with conjunctivitis in only half of all
same postnatally acquired infections as older infants
(e.g. Streptococcus pneumoniae, Staphylococcus aureus,
cases
Haemophilus influenzae), but in addition, are at risk of • subacute onset and insidious course
infection from perinatally acquired organisms. • paroxysmal cough, vomiting and weight loss;
• These organisms include group B streptococcus, often misdiagnosed as pertussis
Escherichia coli and Listeria monocytogenes. • systemic symptoms are minimal and fever absent
• Herpes simplex virus and enterovirus infection in the • prolonged but eventually self-limiting course.
newborn can mimic bacterial sepsis.
• Investigations and empiric antibiotic treatment for sepsis
in the neonatal period must take account of these Diagnosis
organisms.
Diagnosis involves culture, immunofluorescence or
PCR analysis of conjunctival scrapings or nasopha-
ryngeal aspirate.
Organisms associated
Treatment
with acute neonatal infection
Infection in an infant is a marker of maternal infec-
Chlamydia trachomatis
tion; if untreated, a woman may develop postpartum
Chlamydia trachomatis is a sexually transmitted organ- salpingitis with a risk of secondary infertility. Thus, it
ism that causes cervicitis, pregnancy complications is important for both mother and infant that a specific
and secondary infertility in women, and can be trans- diagnosis be made, even if mild conjunctivitis is the
370
mitted vertically during delivery. Neonatal chlamydial only symptom. The mother and her sexual partner(s)
 Congenital and perinatal infections   11.4
should be treated. Treatment of chlamydial pneumo- • peripartum – maternal genital tract during delivery
nia should reduce the duration of illness. (HSV-1 or HSV-2) – 85%
Conjunctivitis or pneumonia should be treated • postpartum (postnatal) – contact after birth with
with azithromycin. Topical therapy does not eradi- cold sores, infected saliva or hands (usually
cate C. trachomatis from the nasopharynx or prevent HSV-1) – 10%.
pneumonia. Primary maternal HSV infection can cause fever,
systemic symptoms and severe mucocutaneous
lesions, but is often asymptomatic (and diagnosed
Escherichia coli by seroconversion). Transplacental infection is rare,
Escherichia coli causes bacteraemia, urinary tract but spontaneous abortion or preterm labour can
infection and meningitis in the first week of life. occur.
However, there is a continued risk up to 2 months of
age. Premature infants are more commonly affected.
Treatment is with intravenous antibiotics for 3 weeks. Risk factors for vertical transmission
• Type of maternal infection – recurrent genital
Enterovirus herpes infections are the most common form of
genital HSV during pregnancy. However, women
Enteroviruses, which include Coxsackie A, B and with primary genital HSV infections who are
echoviruses, cause hand, foot and mouth disease, gas- shedding HSV at delivery are 10–30 times more
troenteritis and meningitis. Neonatal infection may be likely to transmit the virus to their babies than
acquired from maternal infection in the 2 weeks prior women with a recurrent infection. The difficulty
to delivery or postnatal exposure. In newborn infants, is that approximately 66% of women who
enteroviral disease may be particularly severe and is acquire genital herpes during pregnancy remain
associated with high morbidity and mortality. During asymptomatic.
summer and autumn, neonatal enteroviral disease may • Maternal (and neonatal) antibody status –
be more common than diseases caused by GBS or her- transplacental passage of anti-HSV-neutralizing
pes simplex virus. Despite this, it is frequently unrecog- antibodies reduces the risk of transmission and of
nized as a cause of neonatal sepsis. disseminated disease.
• Prolonged rupture of membranes.
Clinical features • Poor integrity of mucocutaneous barriers (e.g. use
of fetal scalp electrodes).
• Meningoencephalitis • Mode of delivery – caesarean section reduces risk
• Thrombocytopenia of HSV transmission in women shedding HSV
• Disseminated intravascular coagulopathy at the time of birth, particularly in women with
• Cardiomyopathy first-time infections who are HSV type-specific
• Hepatitis. antibody-negative.

Diagnosis Clinical features

Viral culture or PCR analysis of CSF, stool or throat Perinatal HSV infections can be classified as:
swab. • Disseminated disease
• involving multiple visceral organs, including lung,
Treatment liver, adrenal glands, skin, eye and the brain
• 25% of perinatal HSV disease (with early
There are no readily available antiviral agents for treat- treatment)
ing enteroviral infection. Intravenous immunoglobulin • usually presents at 10–12 days of life
has been used to treat neonatal disease, but there is • fever, disseminated intravascular coagulation,
limited evidence. shock, hepatitis, pneumonia, encephalitis
• 80% mortality rate untreated
• high incidence of sequelae in survivors.
Herpes simplex virus
• CNS disease
Perinatal herpes simplex virus (HSV) infection can be • meningoencephalitis
acquired in one of three ways: • one-third of perinatal HSV disease
• in utero – maternal viraemia during primary • usually presents at 16–19 days of life 371
infection (HSV-1 or HSV-2) – 5% • 60% have skin lesions at some point
 11.4 NEONATAL PROBLEMS

• seizures, lethargy, irritability, poor feeding Prevention

• presentation may be indistinguishable from
• Caesarean delivery in a woman with active genital
neonatal sepsis.
lesions can reduce the risk of perinatal HSV
• Skin, eye, mouth (SEM) disease infection.
• disease limited to the skin, eyes and/or mouth
• Prophylactic aciclovir beginning at 36 weeks’
• 45% of perinatal HSV disease (with early gestation reduces the risk of clinical HSV
treatment)
recurrence at delivery, caesarean delivery for
• usually presents at 10–12 days of life recurrent genital herpes and the risk of HSV
• infants with apparently localized mucocutaneous viral shedding at delivery. However, it is not clear
HSV infection may have neurological sequelae
whether there is a reduction in perinatal disease.
from unrecognized encephalitis.
• There may be a role for the use of condoms and
See Figure 11.4.3.
oral antivirals in a seronegative woman with a
seropositive sexual partner.
Diagnosis
Neonatal HSV infection is diagnosed by isolation or Listeria monocytogenes
detection of HSV by immunofluorescence or PCR • Listeriosis is usually acquired from contaminated
in skin lesions, blood, CSF, saliva, urine or tissue food such as dairy products and processed meats.
biopsy. • Pregnant women, neonates, the elderly and the
immunocompromised are most at risk.
• Maternal infection is often asymptomatic or mild.
Treatment • Spontaneous abortion, stillbirth or premature
Early treatment with high-dose intravenous aciclovir delivery, and neonatal sepsis or meningitis can
reduces mortality and morbidity, and should be given occur.
for suspected neonatal HSV infection. Treatment must
be continued for 3 weeks if HSV is proved (or cannot Diagnosis
be excluded).
Culture of blood and CSF.

Treatment
High-dose intravenous benzylpenicillin.

Group B streptococcus
The burden of EOS due to Streptococcus agalactiae or
GBS has declined substantially over the past 20 years
as a result of widespread use of intrapartum antibi-
otic prophylaxis. However, it remains the most com-
mon cause of neonatal sepsis overall. GBS is carried in
the vaginal flora of 25% of healthy women. Less than
1% of the infants of carriers are infected. The overall
incidence of neonatal GBS sepsis in Australia is 0.4
per 1000 live births.

Clinical features
• GBS can cause neonatal sepsis, pneumonia,
meningitis and, less frequently, focal infections such
as osteomyelitis, septic arthritis or cellulitis.
• Early-onset disease occurs within the first week of life;
most occur on the day of birth or within 72 hours.
• Late-onset disease occurs after the first week, and
cases are relatively evenly distributed over the first
372
Fig. 11.4.3 Localized herpes simplex virus skin lesions. 3 months of life.
 Congenital and perinatal infections   11.4
• Some 50% of infections begin in utero; associated Diagnosis
with preterm labour, prolonged rupture of
Culture of blood and CSF, plus chest X-ray if indicated.
membranes and chorioamnionitis.
• The mortality rate varies with gestational age at
infection: Treatment
• 2% after 37 weeks High-dose intravenous Benzylpenicillin plus synergis-
• 10% for neonates aged 34–36 weeks tic gentamicin.
• 30% for neonates aged less than 33 weeks.

Risk factors for early-onset disease

• Maternal GBS colonization
Organisms associated
• Prolonged rupture of membranes with chronic infection
• Preterm delivery
Hepatitis B virus
• GBS bacteriuria during pregnancy
• Previous GBS-infected baby Women who are chronic carriers of hepatitis B virus
• Maternal chorioamnionitis (HBV) (i.e. have persistently detectable hepatitis B sur-
• Young maternal age face antigen (HBsAg) in serum), or who have acute
• Low levels of serotype-specific IgG antibody hepatitis B late in pregnancy, often transmit the virus
against GBS. to their infants. The three main modes of transmission
These factors often coexist, but maternal age and ges- from the mother to the infant are:
tational age have been shown to be independent pre- • in utero infection – unusual except in the setting
dictors of early-onset disease risk. of acute hepatitis B infection during the third
trimester
• direct inoculation during delivery – most common
Risk factors for late-onset disease
mode of transmission. As the fetus passes through
• Preterm gestation the vaginal canal, maternal blood may be swallowed
• Young maternal age by the fetus. Up to 95% of infants born to mothers
• Maternal GBS colonization. who are HbsAg-positive have the antigen in their
gastric fluid
• postnatal (horizontal) transmission.
Intrapartum antibiotic prophylaxis
The risk and the outcome depend on the amount of
Intrapartum penicillin given to carrier mothers has live virus in maternal serum. A relatively high level of
been shown to decrease early-onset neonatal GBS infectivity is indicated by the presence in serum of the
sepsis. Two strategies have been used to identify hepatitis B e antigen (HBeAg) or DNA polymerase,
which women should receive intrapartum chemo- both of which are associated with active viral replica-
prophylaxis; routine antenatal screening for vaginal tion. About 90% of infants of HbeAg-positive carriers
GBS carriage and identification of clinical risk fac- are infected during delivery and will become chronic
tors during labour. Recent data suggest that screen- carriers; they are at risk from chronic liver disease, cir-
ing programmes for the detection of GBS carriage rhosis and hepatocellular carcinoma, which does not
may be more effective than risk-based strategies to usually occur before early adulthood. Children who
prevent early-onset neonatal GBS sepsis. Combined are HBsAg carriers are a potential source of horizon-
vaginal and rectal swabs, collected between 35 and tal transmission of HBV to other young children.
37 weeks’ gestation, either by a health-care worker The risk of becoming a carrier is much lower
or by the patient herself, and inoculated on to selec- (approximately 10%) for infants of HBsAg carriers
tive media after enrichment, provide the optimum with antibody to HBeAg (indicating lower infectivity),
conditions to detect carriage. Increasingly, erythro- but these infants may develop acute HBV infection.
mycin and clindamycin resistance is being described The risk of chronic infection and subsequent liver
overseas; this may influence the choice of antibiotics disease is inversely proportional to age at the time of
used in those allergic to penicillin. Widespread anti- infection:
biotic use, particularly with broad-spectrum agents, • 90–95% of HBV infections under 1 year of age
may lead to increasing neonatal sepsis with ampicil- result in chronic liver disease
lin-resistant organisms. Although rates of non-GBS • 25–50% of HBV infections in 1–5-year-olds result
neonatal sepsis are generally stable, there is evidence in chronic liver disease
suggesting that E. coli sepsis in premature infants is • 6–10% of HBV infections in adults result in chronic 373
increasing. liver disease.
 11.4 NEONATAL PROBLEMS

Prevention but not before 1 month of age, as the sensitivity of the

test is low (22%). A positive PCR result should always
Universal HBV immunization is the most effec-
be confirmed on a separate occasion.
tive means of preventing HBV transmission (see
There is no evidence that HCV transmission occurs
Chapter 3.5). Routine antenatal screening and immu-
during breastfeeding, nor that caesarean delivery
nization of infants of HBsAg carriers can prevent
reduces the risk of transmission.
neonatal HBV infection. The infant should be given
hepatitis B immune globulin (HBIG) as soon as pos-
sible after birth (no later than 48 hours) and a course Human immunodeficiency virus
of HBV vaccine starting in the first week. Three fur-
The rate of mother-to-child transmission of HIV
ther doses should be given at 2, 4, and 6 or 12 months
around the world varies according to availability of
(the timing depends on the combination vaccine used).
antenatal care, antiretroviral drugs and background
This prevents HBV infection in more than 95% of
prevalence rates. In the absence of antiviral and
infants at risk.
obstetric interventions, the risk overall of mother-to-
Lamivudine has been used to prevent the transmis-
child transmission is reported as 20–40%.
sion of HBV to neonates in mothers with high viral
There are three routes of vertical transmission of
load.
HIV:
• in utero
• during labour and delivery – 70%
Hepatitis C virus
• breastfeeding – transmission risk is highest in the
Approximately 1% of pregnant women are infected first few months of life.
with hepatitis C virus (HCV). Perinatal transmission Perinatal transmission risk can be reduced to less than
has been shown to be the leading cause of HCV infec- 1% with measures including:
tion among infants and children. However, the risk of • antiretroviral therapy (for the mother during
vertical transmission is low (approximately 5%). There pregnancy and labour) and to the infant for the first
is an increased risk with high maternal viral load and 6 weeks of life
maternal co-infection with HIV. • elective caesarean section (it is generally thought
Perinatally-acquired HCV infection has a slower, that interventions to minimize infant contact with
more indolent course than infection in older children maternal vaginal secretions and infected blood
and adults. Approximately 20% of children appear to during passage through the birth canal is important
clear the infection, 50% develop chronic asymptomatic to reduce the risk of vertical transmission)
infection and 30% develop chronic active infection. • avoidance of invasive obstetric procedures
The general recommendation for testing a well child • avoidance of breastfeeding.
with perinatal HCV exposure is to test for HCV anti- The Royal Australian and New Zealand College of
bodies at ≥ 18 months of age, as passively transferred Obstetricians and Gynaecologists recommends that all
maternal HCV antibodies will have cleared by then. pregnant women should be assessed for risk of HIV
When follow-up cannot be guaranteed, however, test- infection and should be offered HIV antibody testing
ing by HCV RNA PCR should be performed earlier, following appropriate counselling.

374
 Surgical conditions 11.5
in the newborn
Sebastian K. King, Spencer W. Beasley

The majority of the conditions discussed in this chapter In duodenal atresia there may be other abnormalities,
will present initially to the paediatrician, general practi- such as Down syndrome and imperforate anus (see
tioner or obstetrician as emergencies. Delay in diagno- Chapter 10.3). In the absence of birth asphyxia these
sis may seriously compromise recovery and will almost infants are usually alert and feed well, but they vomit
certainly increase morbidity. Disorders that are obvious bile-stained material almost immediately. There may
at birth but do not require urgent surgical referral have be epigastric distension. The diagnosis of duodenal
not been included in this chapter. For information on atresia is made on plain X-ray of the abdomen, which
these, the reader is referred to paediatric surgical texts. reveals a characteristic ‘double bubble’ due to gas in
the stomach and proximal duodenum (Fig. 11.5.1).
Little or no gas will be visible distal to the obstruction.
Duodenoduodenostomy is performed after resuscitation
Oesophageal atresia and correction of any fluid or electrolyte disturbance.
Any newborn infant who appears to salivate exces- Bile-stained vomiting may also be an indication of
sively (drooling) at birth should be suspected of having malrotation complicated by volvulus. The small bowel
oesophageal atresia. This is a congenital abnormality mesentery has a narrow attachment to the posterior
where the mid-portion of the oesophagus is missing. abdominal wall, the so-called ‘universal mesentery’,
In most there is an abnormal communication between which allows the midgut to twist around the superior
the trachea and the lower oesophageal segment, called mesenteric vessels. This is a true surgical emergency as
a distal tracheo-oesophageal fistula. the blood supply to the midgut may be cut off as the
The diagnosis is confirmed by passing a large, firm midgut twists around this axis. The diagnosis can be
catheter, for example a 10-French gauge orogastric confirmed with an urgent barium meal or by ultraso-
tube, through the mouth and finding that it cannot nography. If signs of peritonitis with abdominal dis-
be passed more than about 10 cm from the gums. The tension and guarding are already present, the infant
child must not be fed; otherwise, aspiration of feeds should be taken immediately to theatre.
into the lungs is likely to occur. A plain X-ray of the
torso will show gas in the bowel, confirming the pres-
ence of a distal tracheo-oesophageal fistula. About
50% of these infants have other congenital abnormali-
Distal bowel obstruction
ties, most of which form part of the VACTERL asso- In more distal bowel obstructions, vomiting remains a
ciation (vertebral, anorectal, cardiac, renal and limb major feature but tends to occur later and is associated
abnormalities; see Chapter 10.3). Major chromosomal with abdominal distension. The more distal the obstruc-
abnormalities are seen in 5%, of which trisomy 18 and tion, the later the vomiting and the more pronounced
trisomy 21 are the most frequent. Many are premature the distension (Fig. 11.5.2). The vomitus may become
and a history of maternal polyhydramnios is common. faeculent. An erect film of the abdomen will show dis-
Initial management involves regular suctioning of tended loops of bowel and fluid levels (Fig. 11.5.3). The
the upper oesophageal pouch to prevent aspiration number of loops is dependent on the level of obstruc-
until the tracheo-oesophageal fistula has been divided. tion. The radiological appearances of Hirschsprung
The oesophageal ends are anastomosed at the time of disease, meconium ileus and ileal atresia may be similar,
surgery to close the fistula. and a contrast study, rectal biopsy or laparotomy may
be required to make the definitive diagnosis.

Duodenal obstruction Hirschsprung disease

Bile-stained vomiting starts soon after birth. The Hirschsprung disease (congenital megacolon) is the
obstruction may be: most common cause of neonatal bowel obstruction.
• intrinsic (e.g. duodenal atresia, duodenal web) There is an absence of ganglion cells for a variable
375
• extrinsic (e.g. malrotation with volvulus). distance proximal to the anus. Peristalsis is abnormal
 11.5 NEONATAL PROBLEMS

Fig. 11.5.1 X-ray of the abdomen in a neonate demonstrating Fig. 11.5.3 Erect X-ray of the abdomen, showing marked
the ‘double bubble’ sign. Note the absence of gas in the bowel dilatation of multiple loops of bowel and several fluid levels. The
distal to the second bubble. This child had duodenal atresia. most likely diagnoses include Hirschsprung disease, meconium
ileus and ileal atresia.

It is often performed as a single-stage procedure at

diagnosis in the neonate, but in certain circumstances
requires a staged approach.

Meconium ileus
Meconium ileus occurs in infants with cystic fibrosis.
In this condition meconium becomes excessively thick
and tenacious, causing obstruction, and the distal
ileum is jammed with hard pellets of inspissated meco-
nium. The colon is empty and no meconium is passed
after birth. The infant has a distended abdomen and
commences vomiting shortly after birth. A contrast
enema will demonstrate a microcolon.
Fig. 11.5.2 Distal bowel obstruction in a neonate. Gross Sometimes the impacted pellets can be dislodged with
abdominal distension was evident and associated with vomiting
of faeculent material.
a Gastrografin enema, but usually surgery is required.
A temporary ileostomy allows the bowel to be irrigated
to clear the inspissated meconium. The diagnosis of cys-
in the aganglionic segment and results in an incom- tic fibrosis is confirmed subsequently (see Chapter 14.6).
plete lower intestinal obstruction with severe constipa-
tion. The bowel proximal to the aganglionic segment
Small bowel atresias
becomes dilated and hypertrophied. The diagnosis
is confirmed on suction rectal biopsy. Most of these Atresias of the jejunum are often multiple (Fig. 11.5.4).
infants present at 3 or 4 days of age with increasing There is gross distension of the proximal jejunum
abdominal distension and delay in the passage of proximal to the first atresia, followed by multiple
meconium. Surgical correction involves: short segments of jejunum and collapsed normal
376 • excision of the aganglionic segment bowel distally. Ileal atresia tends to be an isolated
• anastomosing ganglionated bowel to the anus. lesion. Colonic atresia is extremely rare.
 Surgical conditions in the newborn 11.5
• high lesions – the rectum stops at or above the
pelvic levator ani musculature (Fig. 11.5.5A).
Low lesions usually have a fistulous communica­
t­ion with the skin as an anocutaneous fistula, for
which a cutback anoplasty is performed as a neonate
(Fig. 11.5.5B). High lesions tend to be more compli-
cated and are more likely to be associated with other
congenital abnormalities, particularly of the urinary
tract. In the male with a high lesion there is either no
opening at all or the rectum communicates with the
urinary tract via a rectourethral or rectovesical fistula
(Fig. 11.5.5C). In the female with a high lesion the rec-
Fig. 11.5.4 Intraoperative photograph showing multiple areas tum usually communicates with the vestibule or vagina
of jejunal atresia in a neonate who presented with vomiting after as a rectovestibular or rectovaginal fistula respectively
the first two feeds after birth. (Fig. 11.5.5D). High lesions require an anorectoplasty – a
considerably more complicated procedure, performed
either at birth or as a staged procedure later. In addi-
Neonatal necrotizing enterocolitis
tion, a rare and even more severe group of abnor-
Neonatal necrotizing enterocolitis (NEC) is an malities may occur in the female; in these cloacal
acquired condition that predominantly afflicts the pre- malformations there is only one opening for the rec-
mature neonate who has undergone severe perinatal tum, vagina and urinary tract.
stress (see Chapter 11.2). The neonate becomes lethar-
gic and unwell, usually between 2 days and 2 weeks after
birth. There is bile-stained vomiting and the abdomen Clinical example
becomes distended. Loose stools are passed, which
may contain blood. As the disease progresses, signs of Thomas was born normally after an uneventful
peritonitis develop: there is redness and oedema of the pregnancy and labour. Meconium was first
abdominal wall and increasing abdominal tenderness. passed at 36 hours. At the age of 4 days
Both small and large bowel may be involved. Plain he was noted to be feeding poorly and his
abdomen was becoming increasingly distended but no mass
X-rays of the abdomen show:
was palpable. He vomited twice. On rectal examination a
• dilated loops of bowel ‘squirt’ of meconium was passed. A plain upright film of
• intramural gas (pneumotosis intestinalis) – this is a the abdomen revealed several fluid levels suggestive of
pathognomic sign on radiology intestinal obstruction. A provisional diagnosis of Hirschsprung
• portal venous gas – this is a sign of severe disease and disease was made. This was confirmed on suction rectal
poor prognosis in which surgery is usually required biopsy, which demonstrated the absence of ganglion cells
in the submucosa. A primary pull-through procedure via the
• pneumoperitoneum – results from full-thickness
perineum was performed, with the transition zone being
perforation and surgery is almost always determined by intraoperative frozen sections.
required.
Initial management involves cessation of all enteral
feeds, decompression of the gastrointestinal tract by
nasogastric aspiration, fluid resuscitation and antibi-
otics. Where there is continued clinical deterioration
Abdominal wall defects
despite appropriate resuscitation, or there is evidence The two main major abdominal wall defects are:
of full-thickness bowel necrosis (e.g. free intraperito- • exomphalos (omphalocele)
neal gas on X-ray), surgery is indicated. Necrotic bowel • gastroschisis.
is excised and a defunctioning stoma may be required. Frequently, a diagnosis of exomphalos or gastroschi-
Malabsorption, short gut syndrome and colonic stric- sis is made on antenatal ultrasonography. This may
tures may complicate the condition. influence the location and timing of delivery, but does
not influence the mode of delivery. It also provides an
opportunity for antenatal counselling.
Anorectal malformations
These include a spectrum of abnormalities that affect
Exomphalos
the anorectum, loosely called ‘imperforate anus’
(Fig. 11.5.5). They fall into two main groups: This is a large defect at the umbilicus with herniation
• low lesions – the rectum continues beyond the of bowel and liver into a sac covered by fused amni-
377
pelvic levator ani musculature otic membrane and peritoneum (Fig. 11.5.6). The sac
 11.5 NEONATAL PROBLEMS

A B

C D

Fig. 11.5.5 Anorectal anomalies presenting as imperforate anus in the neonatal period. (A) High imperforate anus, the lesion being
above the levator ani musculature. (B) Imperforate anus due to a low lesion. Meconium is visible behind the distended skin of the
median raphe. (C) Passage of meconium from the urethra. This has occurred in a neonate with a high imperforate anus and an
associated rectourethral fistula. (D) Anorectal anomaly in a newborn girl. The catheter has been passed into the rectum.

is translucent at birth but quickly becomes opaque as loss. A nasogastric tube keeps the stomach empty, aid-
it desiccates. Coexisting abnormalities are common ing subsequent closure of the defect. The defect can
and usually involve the heart and kidneys. Beckwith– usually be repaired at birth but the largest defects, par-
Wiedemann syndrome may also be present and must ticularly those that contain liver, may require a period
be recognized as it is associated with severe hypogly- of external compression or staged procedures.
caemia that requires immediate correction at birth (see
Chapter 10.3).
Gastroschisis
The early management of exomphalos involves plac-
ing the neonate in a warm Humidicrib incubator and In gastroschisis there is a small defect immediately to
wrapping the entire torso, including the exposed vis- the right of the umbilicus through which bowel (and
378
cera, in clear plastic wrap to prevent evaporative heat sometimes the gonads) herniate (Fig. 11.5.7). There is
 Surgical conditions in the newborn 11.5
the left posterolateral part of the diaphragm that
allows the contents of the abdomen to herniate into
the left thoracic cavity. This limits the space available
for the lungs to develop in utero. The resulting pulmo-
nary hypoplasia results in severe respiratory distress
within minutes of birth and in some neonates is not
compatible with long-term survival. The more severe
the lung hypoplasia, the earlier the neonate becomes
symptomatic and the poorer the prognosis. Diagnosis
of the condition may be made antenatally on routine
ultrasonography.
The diagnosis is confirmed after birth by a chest
X-ray, which shows loops of bowel in the left tho-
racic cavity. The heart is displaced to the contra-
Fig. 11.5.6 Exomphalos, showing the site of the defect at the lateral side and there is little room available for the
umbilicus. In some affected neonates the lesion is much larger
lungs. Right-sided diaphragmatic hernias account
and may contain most of the bowel and liver.
for only 15% of such lesions. Early treatment
involves aggressive cardiorespiratory support and
decompression of the bowel with a nasogastric tube.
When the child is stable, operative repair of the dia-
phragm is undertaken.

Sacrococcygeal teratoma
This is a rare tumour that is usually evident at birth;
the baby is born with a large mass protruding from
the lower back and arising from the tip of the coccyx
or sacrum. In other infants it may expand predomi-
nantly into the pelvis. It may be extremely large and
cause obstetric difficulties. The tumour is removed
Fig. 11.5.7 Gastroschisis, with herniation of abdominal contents
soon after birth. Malignant change is possible and is
through an abdominal wall defect lateral to the umbilicus.
more likely if surgery is delayed or where the tumour
is uniformly solid and devoid of cysts.
no covering sac, and the eviscerated small and large
bowel is thickened and densely matted with exudate as a
result of amniotic peritonitis before birth. These infants
have a significant risk of hypothermia, and exposed vis-
cera should be wrapped in clear plastic wrap to prevent Practical points
evaporative heat loss. Surgery is directed at returning
the bowel to the peritoneal cavity and repairing the • Oesophageal atresia is often associated with other
defect. Where the peritoneal cavity is too small to accom- congenital anomalies (e.g. VACTERL association) and
presents with excessive salivation at birth.
modate the bowel, it may be necessary to create a tem-
• Bile-stained vomiting may have a serious underlying
porary prosthetic silo that contains the remaining bowel. cause, such as malrotation with volvulus, which must
After surgical repair the bowel may take many weeks be excluded with an upper gastrointestinal contrast
to function normally. Coexisting abnormalities are nor- study.
mally confined to the gastrointestinal tract. • The most common cause of neonatal bowel obstruction is
Hirschsprung disease.
• Necrotizing enterocolitis most commonly affects
premature neonates who have suffered perinatal stress.
• Exomphalos is a midline defect where bowel and liver
Diaphragmatic hernia protrude from beneath the umbilicus, whereas the defect
in gastroschisis is typically to the right of the umbilicus and
In the most common type of congenital diaphrag- the bowel has no covering sac. 379
matic hernia (Bochdalek hernia) there is a defect of
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 12
PART

INFECTIONS

381
 12.1 Infectious diseases David Burgner, David Isaacs

bloodstream and the rash may evolve very quickly. A

Infectious diseases presenting non-blanching petechial rash is not specific for menin-
with fever and rash gococcal infection; only about 10% of ­children with
a petechial rash have meningococcal disease and the
Infectious diseases of childhood are a significant cause remainder have viral infections, other bacterial infec-
of illness in children, especially in the first years of tions, or have suffered minor trauma. Early treatment
life. Globally, infection is responsible for the m ­ ajority is potentially life-­saving; intravenous or intramuscular
of the more than 10 million childhood deaths that antibiotics should be given immediately if the diagno-
occur each year. Many of these infections are prevent- sis is suspected and prior to urgent transfer to hospital
able by immunization and the high mortality rate is (Fig. 12.1.1).
compounded by malnutrition and low birth weight The terminology used to describe infections causing
(see Chapter 11.2). In resource-rich countries such as fever and rash can be confusing and some terms are
Australia, infectious diseases are the commonest cause largely of historical interest. An exanthem (from the
of admission to hospital and amongst the common- Greek exanthema, ‘a breaking out’) usually refers to
est reasons for a child to consult a general practitio- a widespread rash, often of viral origin. An enanthem
ner. The burden of infectious diseases falls mainly on refers to small spots on the mucous membranes, such
infants and the preschool child and disproportionately as Koplik's spots seen in measles. In the early 20th cen-
on Indigenous children. tury, prior to immunization, six common exanthems
Many infections and related conditions manifest of childhood were categorized. Historically these were
as fever and rash, and a timely and accurate diagno- known as ‘the six diseases of childhood’ (Table 12.1.1).
sis is important. This chapter discusses some of the This numerical terminology is still used occasion-
more important and common of these conditions, ally, although the existence of the ‘fourth disease’ is
­highlighting the epidemiological and clinical features questionable.
that may point to a specific diagnosis, as well as the
complications, treatment and prevention. Other causes
of fever and rash include drug reactions, toxins and
autoimmune diseases and these are discussed in related
chapters (see Chapters 13 and 21).
Measles (rubeola, morbilli)
The child with rash and fever needs careful assess- Measles is a leading cause of childhood ­mortality,
ment. The most important aspect is identifying poten- and in 2008 caused an estimated 164 000 deaths glob-
tially life-threatening conditions, of which meningo­coccal ally, or nearly 18 deaths per hour. Malnourished
septicaemia (also known as meningococcaemia; see and vitamin A-deficient children are at increased
Chapter 12.3) is the most c­ommon and important. risk. More than 95% of measles deaths occur in
Meningococcal septicaemia may occur in isolation or low-income countries and there are over 20 million
together with meningococcal meningitis. It progresses measles cases per year. There is a highly effective vac-
rapidly, has a high mortality, and requires prompt iden- cine and increased measles immunization c­overage
tification and aggressive treatment. Meningococcal has resulted in a decline by over 75% in total deaths
­disease should be considered in any febrile child with between 2000 and 2008. Most deaths result from bac-
signs of shock even ­if there is no rash. Other indica- terial complications. Even in resource-rich countries,
tors of severe illness include ­pallor, meningism, abnor- measles has a significant mortality rate, approaching
mal cry, lack of eye contact and failure to respond to 1 in 25 000. From 1978 to 1992, about 10 Australian
­normal social clues. Early in the illness, the typical children died from measles each year, as a result of
­non-blanching rash may be absent in up to a third of acute encephalitis or pneumonia. With increasing
cases, may be difficult to find (so undress the child fully immunization coverage, the number of deaths fell
and remember to look at the conjunctivae and palate), to 1–2 per year from 1992, and there have been no
or initially may be ­maculopapular with subtle petechial deaths since 1995, when a second preschool dose of
382
elements. The meningococcus replicates rapidly in the measles vaccine was introduced.
 Infectious diseases 12.1

Meningococcal disease
Yes
Dengue fever - take travel Hx

Unwell
Petichial/non-blanching Shocked
Toxic Enteroviral infection
Rubella (unimmunised)
No
EBV
HSP

Early meningococcal disease

Yes
Other rarer diagnoses – take travel Hx

Unwell
Macular and/or papular Shocked
Toxic Measles (unimmunised)
Erythema infectosum
No Roseola infantum
Adenoviral infection
EBV

Toxic shock syndrome

Invasive Group A streptococcal infection
Yes
Scarlet fever
Kawasaki disease
Unwell
Diffuse erythematous Shocked
Toxic
Staphylococcal slapped cheek syndrome
No
Enteroviral infection

Varicella zoster infection

Vesicular/bullous Herpes simplex infection
Staphylococcal infection

Fig. 12.1.1 An approach to the patient with rash and fever.

Table 12.1.1 The ‘six diseases’ or ‘six exanthems’ of childhood

Historical name Name Synonym(s) Aetiological agent

First disease Measles Rubeola, morbilli Measles virus (= morbillivirus)

Second disease Scarlet fever Scarlatina (milder form) Streptococcus pyogenes (= Lancefield
group A streptococcus)

Third disease Rubella German measles Rubella virus (= rubivirus)

Fourth disease Filatow–Dukes' disease The existence of Fourth disease as a separate entity is controversial – term
not widely used

Fifth disease Erythema infectiosum Slapped cheek disease Parvovirus B19

Sixth disease Roseola infantum Exanthem subitum Human herpesvirus 6 (HHV-6) and
less commonly HHV-7 383
 12.1 INFECTIONS

In resource-rich countries, most cases are imported

or occur in unimmunized children. Measles is caused
by measles or morbillivirus, an RNA virus with high
infectivity and virulence that is thought to have evolved
from the virus that causes rinderpest in cattle. However,
humans are the only hosts of measles virus. Infection
results in significant suppression of T-cell immune
responses, with increased susceptibility to diarrhoea
and respiratory illness, and an increased overall
­infection-related mortality for up to a year following
measles. Measles can be a life-threatening infection in
the immunocompromised (e.g. oncology patients) and
suspected cases require strict infection control.

Epidemiology
• Humans are the only known host.
• Infants and young children are the most susceptible
to severe infection.
• Respiratory droplet or airborne spread, highly
infectious, causing outbreaks every 2 years in
unimmunized populations.
Fig. 12.1.2 Measles: blotchy, raised rash.
• Incubation period is 8–14 days from the exposure to
onset of symptoms.
• Measles is highly contagious and over 98%
of adults in unimmunized communities are
Day of illness 1 2 3 4 5 6 7 8 9 10
seropositive.
40.0
• Infected individuals are infectious for 4 days
39.4
Temperature

before until 4 days after the rash appears (but 38.8

immunocompromised patients are infectious for the 38.3
duration of the illness). 37.7
• Measles virus may survive in air and on inanimate 37.2
surfaces for some hours. 36.6
• In developing countries, the high mortality rate Rash
is due mainly to pneumonia, often with bacterial Kopliks spots
(staphylococcal or pneumococcal) superinfection.
Conjunctivitis

Coryza
Clinical features (Figs 12.1.2, 12.1.3)
Cough
• Prodromal period (symptoms before rash)
3–5 days, with sudden onset of high fever, Fig. 12.1.3 The development of measles.
irritability, brassy or hacking cough, exudative
conjunctivitis, rhinorrhoea, otitis media, and
a characteristic enanthem on buccal mucosa
Complications
(Koplik's spots).
• Rash starts behind ears and spreads caudally. It is • Acute complications reflect the intense
a blotchy, raised rash, confluent in places. The more inflammatory response to measles infection,
confluent the rash, the more severe the illness. possibly with associated immune suppression.
• Child is miserable and febrile when rash is present but • Otitis media is the commonest acute
fever resolves rapidly after a few days; persistent complication, followed by lower respiratory tract
fever suggests bacterial superinfection. infection.
• Immunocompromised patients may have minimal • Encephalitis is a rarer but more serious
rash (showing that T cells are important in the complication, possibly related to the host immune
aetiology of measles rash) and may develop response. It may be fatal (15%) or result in
384 fulminant giant cell pneumonia. neurological sequelae (25%).
 Infectious diseases 12.1
• In resource-poor countries, mastoiditis and significant maternal measles IgG antibodies
diarrhoea are common and life-threatening are present or if children have received recent
complications. intravenous immunoglobulin.
• Subacute sclerosing panencephalitis (SSPE) • In Australia, measles–mumps–rubella (MMR)
is a rare (1 in 100000), devastating, invariably vaccine is given at 1 year of age and a second dose
fatal, neurological condition that occurs about at 4–5 years of age (note that maternal antibody
7–8 years after wild-type measles infection (but is generally protective before 1 year and interferes
not vaccination), especially in children infected with immunogenicity if vaccine is given earlier).
in infancy. It is characterized by developmental • Live vaccines are generally contraindicated in
regression with deteriorating intellectual function, those with significant immunodeficiency. If
seizures, coma and death. exposed to measles, intramuscular or intravenous
immunoglobulin gives ‘passive’ protection.
Differential diagnosis
• In roseola infantum (see below) the rash may Clinical example
be identical to measles but appears as the fever
subsides, and the child looks well when the rash Harriet, 3 years old, was in preschool with a
appears, in contrast to children with measles who friend who, 10 days earlier (1), had a cough
are unwell with the rash. and fever (2) and later came out in a rash.
Neither had been immunized against measles
• Other viruses causing morbilliform (measles-like)
(3). Harriet developed a high fever, runny nose and cough
rash on occasions: enteroviruses, Epstein–Barr virus (4) and was irritable. Her eyes became red and weepy
(EBV), adenoviruses, influenza and parainfluenza (5) and her ears were sore (6). After 3 days (2) her doctor
viruses. found bilateral otitis media (6) and white spots on a red
• Antibiotics, especially amoxicillin or ampicillin, background on her buccal mucosa (7). Next day she
may cause a rash, particularly if given to a child remained miserable and hot, and developed a rash behind
her ears, which spread over the next 2 days to her face,
with EBV infection.
trunk and limbs, and was pink to red and blotchy (8). In
• Kawasaki disease. some areas the rash joined up and was raised (8). She
• Scarlet fever. had scattered wheezes bilaterally (4). She remained febrile
and unwell for 3 days, when the rash faded leaving brown
Laboratory diagnosis discoloration of the skin with desquamation of the fingers
and toes (9).
• Rapid antigen detection: immunofluorescent or The following are features typical of measles infection:
PCR staining of nasopharyngeal secretions. • Incubation period 8–14 days (1)
• Infectious during the prodromal period, which lasts
• Serology: measles-specific immunoglobulin (Ig) M
3–5 days (2)
or 4-fold rise or greater in IgG titre – less helpful in
• Immunization over 95% protective (3)
making a rapid diagnosis. • Bronchitis (4), exudative conjunctivitis (5) and otitis media
(6) are almost invariable features
Treatment • Enanthem called Koplik's spots (7)
• Rash is classically descending, blotchy to confluent (8),
• Mainly symptomatic in industrialized may be papular (raised) and may desquamate, often
countries. more marked in children from developing countries (9).
• Vitamin A therapy recommended for severe cases
and malnourished children more than 6 months of
age, as reduces severity and mortality.
• Antibiotics for bacterial complications, particularly Roseola infantum (exanthem
pneumonia.
subitum, sixth disease)
Prevention Epidemiology
• Measles is a vaccine-preventable disease; it should • Caused by infection with human herpesvirus
be possible to eradicate measles from the world by 6 (HHV-6) and occasionally HHV-7, both DNA
immunization, because humans are the only host. viruses.
• Measles vaccine is a live, attenuated vaccine, that • Many HHV-6 and HHV-7 infections are
can be given alone (monovalent) or in combination asymptomatic or have non-specific symptoms (e.g.
with mumps and rubella (MMR) and also varicella fever).
vaccines (MMRV). It is not immunogenic if • Mainly affects infants aged 3–18 months. 385
 12.1 INFECTIONS

• Infants usually infected by asymptomatic shedding Epidemiology

of virus from family member.
• RNA virus; humans are the only host.
• Incubation for HHV-6 is about 10 days; unknown • Respiratory droplet spread; patients are infectious for
for HHV-7.
about 5 days before and after development of the rash.
• Incubation period is 2–3 weeks.
Clinical features and complications
• Spring and summer epidemics in non-immunized
• High fever, irritability, lymphadenopathy, upper populations.
respiratory tract signs with inflamed tympanic • Mainly affects children aged 5–10 years, but also
membranes and diarrhoea are common but non-immune pregnant women.
non-specific features. • Less infectious than measles: 15–20% of adults in
• Morbilliform (measles-like) rash appears as high unimmunized populations are non-immune.
fever subsides in classical roseola infantum, although
pattern is less predictable in many HHV infections. Clinical features (Figs 12.1.4, 12.1.5)
• Bulging fontanelle and febrile convulsions in acute • Rubella is usually a mild or subclinical disease in
phase are more common than with other viral children.
infections. • Rash much fainter and less florid than measles, not
• Virus persists in host (herpesvirus latency) and may raised.
reactivate, especially if immunocompromised.

Prevention and treatment

There is no vaccine and no specific antiviral treat-
ment for HHV-6 and HHV-7 infections (aciclovir is
Rash relatively
ineffective). profuse on trunk

Clinical example

Mark, a previously well 9-month-old baby,

developed a runny nose, fever and irritability (1)
and went off his feeds. After 2 days of fever, he
had a generalized tonic–clonic seizure (2), which
Rash
stopped after 2 minutes. He was admitted to hospital, sparse distally
where he was found to have a fever of 40 °C and cervical
lymphadenopathy (3) but no rash or enanthem (4). A lumbar
puncture was normal. After 24 hours' observation in hospital
his fever subsided but he developed a diffuse maculopapular
rash on his trunk, thought at first to be measles (5). He was
well and was discharged home. Serology for HHV-6 revealed
positive specific IgM.
The following are features typical of classical roseola Fig. 12.1.4 The distribution of rash in rubella.
infantum:
• Usual presenting features, lasting 2–3 days (1), (3)
Day of illness 1 2 3 4 5 6 7 8 9 10
• Febrile convulsion (2) is a recognized complication
40.0
• No enanthem (4)
39.4
Temperature

• Rash often misdiagnosed as measles but, unlike measles,

the child with roseola becomes afebrile as the rash 38.8
appears and looks well (5). 38.3
37.7
37.2
36.6

Rubella (German measles, Rash

third disease) Lymph nodes

Malaise
Rubella is a rare infection in resource-rich countries
where vaccination is widespread. Its main importance Conjunctivitis
is congenital infection, which can cause miscarriage, Coryza
fetal death or a constellation of teratogenic effects on
386
the fetus, called ‘congenital rubella syndrome’. Fig. 12.1.5 The development of rubella.
 Infectious diseases 12.1
• Rash often starts on face in young children, spreads
to neck, trunk and extremities.
• Lymphadenopathy common, particularly
suboccipital, postauricular and cervical.
• Adolescents and adults often have constitutional
symptoms: conjunctivitis, arthralgia or arthritis,
malaise and fever.
• Encephalitis and purpura are rare complications.
• Congenital rubella syndrome results from first-
trimester rubella infection (see Chapter 11.4).
• There is no specific therapy.

Diagnosis
In non-immune pregnant woman exposed to possible
rubella, send serum for rubella-specific IgM and repeat
2–4 weeks later for rising IgG titre. If baby or cord
blood has positive rubella IgM (which does not cross
placenta), this indicates recent or congenital infection.

Differential diagnosis
Fig. 12.1.6 Fifth disease: slapped cheeks and lacy rash
• Many other viruses cause rubelliform rashes. (with permission of Bernard Cohen, DermAtlas: http://www.
• Clinical diagnosis of rubella is notoriously dermatlas.org).
unreliable.
• Rubella is very rare in infancy: other viruses
(e.g. enteroviruses, HHV-6) are much more likely
Day of illness 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
to cause infantile rashes.
40.0
39.4
Temperature

Prevention 38.8
• Live attenuated rubella vaccine is usually given 38.3
37.7
universally as MMR in resource-rich countries.
37.2
• Congenital rubella syndrome is rare in 36.6
industrialized countries such as Australia, but more
Rash
common in developing countries.
Malaise

Myalgia

Erythema infectiosum (slapped Headache

cheek disease, fifth disease) Arthralgia or

Arthritis
• Caused by human parvovirus B19 (parvo = small),
a DNA virus. Fig. 12.1.7 The development of erythema infectiosum (fifth
• Spread by respiratory route or vertical transmission disease).
from mother to fetus.
• Incubation period 4–14 days. anaemia but with severe anaemia in those with
• May cause epidemics in school-aged children and shortened red cell survival (e.g. children with
household contacts. haemoglobinopathies or fetuses).
• Initial presentation is mild, with fever in only • In sickle cell disease and other hereditary anaemias,
15–30%, cervical lymphadenopathy and an infection may cause a severe but transient aplastic
intensely red, ‘slapped cheek’ rash often with crisis due to red cell aplasia.
circumoral pallor (viraemic phase). • Infection during the second trimester of pregnancy
• Subsequently develop lacy, reticular rash on limbs may result in fetal hydrops due to fetal anaemia,
and trunk, sometimes with arthralgia or arthritis with a mortality rate of about 5%.
(immune complex-mediated) (Figs 12.1.6, 12.1.7). • There is no specific treatment. Aplastic crises may
• The virus infects red cell precursors in the bone require transfusion and severe fetal hydrops may
387
marrow, usually with mild, non-significant necessitate intrauterine transfusion.
 12.1 INFECTIONS

• Humans are only host.

Varicella (chickenpox) • Effective live attenuated vaccine available.
Chickenpox (Figs 12.1.8, 12.1.9) is a highly infectious
Clinical features
disease causing a bullous (pox-like) rash. The DNA
virus responsible, varicella-zoster virus (VZV), is a • Typically causes 250 to 500 intensely pruritic skin/
herpesvirus and has the ability to remain dormant in palatal lesions that are initially vesicular or bullous
the dorsal root ganglia and reactivate as herpes zoster and then crust.
(shingles, discussed below). • Skin lesions may scar.
• Illness is more severe in adolescents and adults.
Epidemiology • May result in severe congenital syndrome if maternal
infection occurs at less than 20 weeks' gestation.
• Occurs worldwide, although spreads less readily in
tropical countries. • If infection occurs just before delivery,
transplacental transfer of virus before protective
• Highly infectious, spread by respiratory route, due
antiviral antibodies can cross the placenta may
to infectious particles from burst vesicles and from
result in severe and potentially fatal infection in the
respiratory tract.
newborn (neonatal varicella).
• Incubation period 10–21 days, short prodromal period
of 1–2 days, which is the most infectious period. Complications
• Infectivity persists until the last skin lesion has crusted.
• Peak age incidence is 2–8 years. • Bacterial superinfection of skin.
• Pneumonia/pneumonitis:
• varicella pneumonitis particularly affects
immunocompromised children, but also pregnant
women and normal adults
• bacterial pneumonia (pneumococcal or
staphylococcal) can rarely complicate varicella
pneumonitis.
• Encephalitis:
• incidence about 1 in 1000 cases
• most common form is pure cerebellar ataxia, with
complete recovery over days to weeks
• severe form is acute disseminated
encephalomyelitis (ADEM), a post-infectious
demyelinating illness.
• Haemorrhagic chickenpox – severe illness in those
with cellular immune deficiency (e.g. oncology
patients), indicating importance of T cells in
recovery from VZV infection.
• Streptococcal toxic shock syndrome, due to
Streptococcus pyogenes superinfection.

Diagnosis

Fig. 12.1.8 Chickenpox: vesicles and pustules on trunk • Usually clinical.

and scalp. • PCR of virus from blister fluid in tissue culture or
detect antigen by PCR or immunofluorescence on
vesicle fluid.
Day of illness 1 2 3 4 5 6 7 8 9 10 11 12 13 14
• Can use serology (IgM).
40.0
39.4
Prevention
Temperature

38.8
38.3 • Live attenuated VZV vaccines are highly protective,
37.7 but contraindicated in pregnancy and in those with
37.2 impaired immunity.
36.6
• Given early, vaccines are effective in preventing
Rash infection following exposure.
388 Crops Scabs • Varicella-zoster immune globulin (ZIG or VZIG)
is an immunoglobulin preparation with a high titre
Fig. 12.1.9 The development of chickenpox. of anti-VZV IgG antibodies. It is used for passive
 Infectious diseases 12.1
prophylaxis of immunocompromised patients
(e.g. oncology patients, neonates) exposed to VZV.

Treatment
Aciclovir is used to treat children with, or at risk of,
severe varicella. It is not indicated in uncomplicated
primary varicella in an immunocompetent child.

Clinical example

Charles, aged 6, had been in contact with a

school friend who was off school 2 weeks ago
with chickenpox (1). Charles had a sore throat and
fever of 38 °C but no spots. Next day, a few small
red spots like mosquito stings appeared on his trunk and limbs
(2) and on his scalp under the hair (3). These became raised,
then developed into small, fluid-filled blisters surrounded by a
small area of erythema (4). They were intensely itchy and when
scratched readily became superinfected and left a scar (5). These
spots crusted over within hours, but fresh crops of vesicles kept
appearing on Charles' face, trunk and limbs (6). He had difficulty
swallowing and his eyes were red and sore. He was miserable
but not unwell and was troubled by the intense pruritus. On
the fifth day he became febrile again and a lesion on his leg
developed surrounding erythema, diagnosed as cellulitis (7). He
recovered after a course of intravenous antibiotics in hospital.
The following are features typical of varicella:
• Incubation period 10–21 days (1) Fig. 12.1.10 Ophthalmic zoster: zoster affecting the ophthalmic
• Short 1–2-day prodrome during which infectious (not division of the Vth nerve. Needs urgent admission and treatment
infectious during the incubation period) (2) as potentially sight-threatening.
• Spots under hairline characteristic and distinguish varicella
from insect bites (3) in early childhood; if a young child gets zoster, ask
• Start as macules, then progress to papules, vesicles or
about chickenpox in pregnancy.
pustules (4)
• If scratched they may become infected, the commonest • Immunocompromised children are at increased risk
complication, and leave a scar or pockmark (5) of zoster, which may disseminate.
• They come in crops, and can infect the pharynx, palate • Neuralgia before, during and after zoster is very
and conjunctivae of the lids. The child is infectious until the uncommon in children, in contrast to adults.
last spot crusts (6) • Most childhood zoster does not need specific
• Children are usually febrile only during the initial
treatment but intravenous aciclovir is indicated
viraemic phase. Prolonged or recurrence of
fever suggests bacterial superinfection or other
for ophthalmic zoster (to prevent eye damage;
complications (7). Fig. 12.1.10) or if the child is immunocompromised
(to prevent life-threatening disseminated infection).

Zoster (herpes zoster, shingles) Scarlet fever and scarlatina

• VZV remains dormant in the dorsal root ganglia • Group A streptococcus causes a range of infections,
of sensory nerves after primary infection and can most commonly pharyngitis and scarlet fever, but also
reactivate many years later as zoster. Zoster follows toxic shock and necrotizing fasciitis (see Chapter 21).
a dermatomal distribution that does not cross the • Post-infectious complications include acute
midline. Historically the distribution of the sensory rheumatic fever (see Chapter 12.2) and
nerves was mapped by areas affected by zoster glomerulonephritis (see Chapter 18.2).
infection, which may occur on the trunk and limbs • Scarlet fever (Fig. 12.1.11) is a toxin-mediated
or follow cranial nerves. disease caused by exotoxins from group
• Zoster infection in a previously well child is almost A streptococcus (S. pyogenes).
always benign and not suggestive of underlying • It is commonest at age 5–10 years.
immune deficiency. • Toxins act as ‘superantigens’, causing widespread 389
• About 10% of children whose mothers developed T-cell activation by bypassing the usually
chickenpox during pregnancy will develop zoster highly specific human leukocyte antigen (HLA)
 12.1 INFECTIONS

Day of illness 1 2 3 4 5 6 7 8 9 10
40.0
Infectious mononucleosis
39.4 (glandular fever)
Temperature

38.8
38.3 Epidemiology
37.7
• Infectious mononucleosis is caused by Epstein–Barr
37.2
36.6
virus (EBV), a DNA herpesvirus; humans are the
only host.
Rash
• Typically a disease of adolescence.
Sore throat
• Transmission from infected saliva by the oral route
(known as the ‘kissing disease’).
Fig. 12.1.11 The development of scarlet fever.
• Asymptomatic secretion of the virus is common.
• A similar clinical syndrome may be caused by
infection with cytomegalovirus (CMV) and
presentation of antigens to T cells. Analogous
Toxoplasma gondii (toxoplasmosis).
superantigen-mediated diseases include toxic shock
syndrome and possibly Kawasaki disease.
Clinical features
• The primary site of group A streptococcal infection
is the throat, causing exudative tonsillitis and/or • Fever, exudative pharyngitis, lymphadenopathy and
pharyngitis. splenomegaly.
• Scarlatina is a mild form of scarlet fever, usually • Palatal petechiae may be present.
affecting preschool-aged children. • Rash may be subtle but typically becomes more
florid if amoxicillin is given.
Clinical features • Infections in younger children may be subclinical or
cause severe enlargement of the tonsils.
• Usually occurs in association with pharyngitis, • Severe disseminated infection may occur in the
rarely with pyoderma or wound infection. immunocompromised.
• Confluent sandpaper-like rash, which may be pruritic.
• Strawberry tongue and circumoral pallor may occur. Diagnosis
• Treatment is with oral penicillin.
• Specific IgM or rising IgG titre to EBV. The Paul–
Bunnell test and monospot test detect non-specific
Diagnosis (heterophil) antibodies produced because of the
Positive throat swab (although asymptomatic carriage polyclonal B cell proliferation caused by EBV. They
of S. pyogenes is common in school-aged children) or have low sensitivity in preschool children. False-
positive serology: high or rising titre to streptolysin O positive EBV serology may occur in other febrile
(anti-streptolysin O titre; ASOT) or ­deoxyribonuclease illnesses.
B (anti-DNAase B). ASOT and anti-DNAase B are • The blood film is often suggestive, showing many
generally higher in Australian Aboriginal children. atypical mononuclear cells. PCR of blood may be
helpful in immunocompromised patients.

Treatment
Clinical example • Contact sports should be avoided until the spleen is
no longer palpable, as there is a risk of rupture.
Anna, 7 years old, presented with fever and sore
throat for 2 days, followed by a rash. Her tonsils
• Corticosteroids may be considered if airway
were red and covered in spots of white exudate. obstruction is developing due to tonsillar hypertrophy.
Her tongue had prominent red papillae. Her face
looked red but was white around the mouth, like a clown's.
The rash was red, patchy and rough to the touch, and covered
her whole body. In the axillae and groins there were lines of Clinical example
petechiae. Her cervical lymph nodes were enlarged and tender.
She was treated with penicillin and rapidly improved. Two Beth, 6 years old, presented with fever, sore
weeks later she had extensive peeling of her hands and feet. throat and malaise. She was treated with
The following are features typical of scarlet fever: amoxicillin for exudative tonsillitis. Two days
exudative tonsillitis; strawberry tongue; circumoral pallor; later, she developed a florid rash. When
sandpaper rash; Pastia's lines; tender cervical lymphadenitis; reviewed, she had marked tonsillar enlargement and large
390 peripheral desquamation. matted nodes in the neck, which were moderately tender.
 Infectious diseases 12.1
Diagnosis
She had petechiae on the soft palate. Her eyelids were puffy
and her spleen was palpable 2 cm below the costal margin. Rapid diagnosis by immunofluorescence of blister
Pulse oximetry, performed overnight to exclude significant fluid or polymerase chain reaction (PCR) of blister
upper airway obstruction, was normal, so dexamethasone fluid and/or cerebrospinal fluid is preferred to culture
was withheld and Beth was sent home. or serology (IgM).
‘Purulent’ exudative tonsillitis may be due to group A
streptococcus or EBV at this age. Ampicillin or amoxicillin Treatment
causes a dramatic rash in EBV infection. Tender lymphadenitis
occurs in both infections, but palatal petechiae, puffy eyelids Aciclovir is effective against HSV and may be given
and splenomegaly are typical features of EBV infection. There topically (e.g. for keratitis), orally (for mild disease) or
is no specific treatment, although steroids are sometimes intravenously (for severe or neonatal infection).
used to reduce upper airway obstruction.

Enteroviruses
Herpes simplex virus • The enteroviruses, as the name suggests, are gut
viruses, usually transmitted faecal–orally, although
Epidemiology and clinical features respiratory spread can occur.
• Herpes simplex virus (HSV) is a DNA herpesvirus, • Commonly spread in swimming pools.
with two serotypes, HSV-1 and HSV-2. • Faecal shedding may continue for months, often
• HSV-1 is primarily oropharyngeal, whereas HSV-2 asymptomatically; respiratory shedding is for less
is primarily genital. than 1 week.
• Neonates may acquire HSV around delivery, • Spring and summer peaks.
usually (about 90%) HSV-2. • They are picornaviruses (from pico = small + RNA).
• HSV infection can disseminate in the skin of children • They can affect the central nervous system, causing
with eczema (eczema herpeticum, Kaposi varicelliform a variety of syndromes.
eruption) if not treated promptly with aciclovir. • The major groups of enteroviruses are:
• Neonatal HSV infection may be localized to skin, • coxsackieviruses
eye (conjunctivitis) and/or mouth, may cause • echoviruses
isolated encephalitis or isolated pneumonitis or, if • enterovirus types (somewhat confusingly).
not treated with aciclovir, will usually disseminate • Polioviruses are usually considered separately from
to cause hepatitis, disseminated intravascular non-polio enteroviruses.
coagulation, encephalitis and death.
Clinical features
• Neonatal HSV encephalitis (see Chapter 11.4) is
usually due to primary maternal genital infection Enteroviral infection may result in a broad range of
and more rarely following reactivation of maternal clinical infections.
genital herpes. • Fever: common cause of isolated fever in infancy.
• Most post-neonatal infections are symptomatic. • Rashes:
• The commonest primary HSV infection in • hand, foot and mouth disease – blistering rash on
childhood is gingivostomatitis; it causes nasty palms, soles and palate caused by coxsackievirus
ulceration of the gums (gingivae), buccal mucosa A16 and other enteroviruses, including
(stoma = mouth) and pharynx. enterovirus (EV) 71
• In primary infection, HSV is shed for about 1 week; • various non-specific rashes – macular, papular,
in recurrent infection for 3–4 days. papulo-urticarial, vesicular, morbilliform,
• Incubation period beyond the neonatal period is rubelliform, etc.
from 2 days to 2 weeks. • Enanthem: herpangina (= ulcerative pharyngitis)
• Herpes encephalitis can occur at any age, may be due to coxsackievirus A.
primary or secondary, due to HSV-1 or HSV-2, and • Neurological:
has a poor prognosis, even if treated with aciclovir. • paralytic – poliomyelitis due to infection of
• As a herpesvirus, local recurrences of HSV are anterior horn cells by poliovirus, but similar
common, often at the mucocutaneous junction syndrome can be caused by other enteroviruses
of the lip (‘cold sores’), but can be on the finger • monoplegia – EV 71, other enteroviruses
(‘whitlow’) or on the skin elsewhere. They may be • ‘aseptic’ meningitis and encephalitis –
exacerbated by sunlight exposure. coxsackieviruses, echoviruses, EV 71.
• Try to avoid the child inoculating virus into the • Cardiac: myocarditis – mainly coxsackievirus B.
391
genital area. • Liver: hepatitis – mainly echoviruses.
 12.1 INFECTIONS

• Eyes: epidemic haemorrhagic conjunctivitis – EV 71. • changes to the extremities (swollen erythematous
• Gastrointestinal: vomiting, diarrhoea, abdominal hands and feet, desquamation especially around
pain and hepatitis. nail-beds in subacute phase)
• Musculoskeletal: Bornholm disease (epidemic • non-purulent bilateral conjunctival injection
pleurodynia) due to coxsackie virus B. • lymphadenopathy (unilateral, > 1 cm, largely in
older children).
Diagnosis • Clinical features appear sequentially and are rarely
PCR or PCR from throat and rectal swabs, stool and present at same time.
CSF. Serology is not possible. • Children are usually very irritable and often have
white cells (but no pathogens) in CSF and urine.
Treatment • C-reactive protein (CRP) and neutrophil count
The antiviral drug pleconaril has activity against usually high acutely; platelets rise in subacute phase.
enteroviruses, but is not widely available. • Coronary artery damage may occur in those with
fewer than four features (‘incomplete Kawasaki
Prevention disease’); consider the diagnosis in any child with
prolonged unexplained fever unresponsive to
Immunization against polio with oral polio vaccine (live,
antibiotics.
attenuated) or inactivated polio vaccine (injected, killed).
• Treatment with intravenous immunoglobulin given
before day 10 reduces coronary artery damage.
Usually given with low-dose aspirin.
Adenoviruses
• Multiple serotypes.
• In infancy, adenoviruses are an important cause Clinical example
of exudative tonsillitis with high fever (at this age,
group A streptococcal infection is rare). Josh, an 18-month-old child of Japanese and
• Can cause epidemics of conjunctivitis, often with Australian parents, presents with a 4-day
red throat (pharyngoconjunctival fever). history of fever, unresponsive to antipyretics and
oral amoxicillin, given by his general practitioner
• Can cause disseminated infection with pneumonia, for a red throat. Josh has had red eyes, which have largely
hepatitis and encephalitis (particularly adenovirus resolved, and an erythematous rash with target lesions.
7 and 21); rare, but may be fatal. His mother noticed very red lips (‘as though he had put on
• Enteric adenoviruses can cause gastroenteritis. my lipstick’), swollen feet and a reluctance to walk. He was
extremely irritable.
Diagnosis Following admission to hospital, examination of blood,
urine and CSF showed inflammatory changes, but cultures
Viral culture or immunofluorescence on throat swab. were sterile and there was no response to intravenous
broad-spectrum antibiotics. The diagnosis of Kawasaki
disease was made on day 7, and Josh defervesced following
Kawasaki disease intravenous immunoglobulin. An echocardiogram at
diagnosis showed mild coronary artery dilatation, which was
(mucocutaneous lymph found to have resolved after 6 weeks, when low-dose aspirin
node syndrome) therapy was ceased.

• Kawasaki disease is an important but poorly

understood cause of prolonged fever, rash and
other features.
• Results in coronary artery damage in 25% of Practical points
untreated and 5% of treated children.
• The cause is unknown; probably an abnormal • Measles is a severe vaccine-preventable childhood
infection.
immune response to an infectious trigger.
• Children with measles are sick when the rash appears;
• Predominantly affecting those between 6 months and children with roseola infantum are sick until the rash
4 years, but can occur at any age. Commoner in boys. appears.
• Much more common in north-eastern Asians • Rubella is usually mild but can cross the placenta in the
(Japanese, Koreans) but seen in all ethnic groups. first trimester to cause congenital rubella syndrome.
• Diagnosis is made clinically with fever of at least 5 days • Chickenpox and measles can be devastating in children
and classically at least four other diagnostic criteria: with impaired cell-mediated (T cell) immunity.
• polymorphous rash (petechiae and vesicles do not • Scarlet fever is a toxin-mediated disease caused by an
exotoxin produced by group A streptococci.
392 occur)
• Consider Kawasaki disease in a child with fever persisting
• changes to mucous membranes (red lips, for more than 5 days and no clear diagnosis.
strawberry tongue, red pharynx, no exudates)
 Bone and joint infections
Jonathan Carapetis, Andrew Steer
12.2
Sequestra and Brodie abscesses are sometimes found
Introduction in chronic osteomyelitis. Most cases of chronic
Infections of bones (osteomyelitis) and joints (­septic osteomyelitis, like acute osteomyelitis, are caused
arthritis) can occur at any age but are much more by Staphylococcus aureus, but chronic presentations
common in children than adults. They are often
­ increase the likelihood of unusual organisms, includ-
­difficult to diagnose, can be difficult to treat and, if not ing Mycobacterium tuberculosis, fungi and Kingella
­diagnosed and treated promptly, can lead to permanent kingae.
disability. Many children and adults have shortened Septic arthritis may occur de novo, as a result of
or deformed limbs, fused joints or even amputations deposition of bacteria in the joint. Alternatively there
because ­ osteomyelitis or septic arthritis was diag- may be extension from adjacent osteomyelitis, which
nosed too late or treated inadequately. Almost all these is more common in children than adults, possibly
poor outcomes need not have happened; with careful because of transport of bacteria through blood ves-
­history-taking and examination, prudent use of investi- sels that cross the epiphyseal plate. In some joints, the
gations – particularly imaging – and close observation, metaphysis is intra-articular, which means that osteo-
virtually all bone and joint infections can be diagnosed myelitis can transform directly into septic arthritis.
and treated before permanent damage ensues. These joints are:
• proximal femur → hip joint
• proximal humerus → shoulder joint
• proximal radius → elbow joint
Pathogenesis • distal lateral tibia → ankle joint.
Synovial joints are poor at clearing infection and the
The area around the growth plates of children's connective tissue may be damaged by enzymes released
bones is particularly prone to infection. Although the by bacteria. Initially, the inflammation results in a
metaphysis has a plentiful blood supply from nutrient joint effusion, which may be purulent; if left untreated,
arteries, blood flow through capillary loops and sinu- the articular and growth cartilage can be destroyed.
soidal veins at the metaphyseal–epiphyseal junction is Longer-term complications may include dislocation,
slow, which allows bloodborne bacteria to deposit in avascular necrosis of intra-articular epiphyses and
this region (Fig. 12.2.1). This area also has poor pen- joint destruction.
etration of white blood cells and other immune media-
tors, so deposited bacteria are relatively protected. As
the infection progresses, pus accumulates under pres-
sure, further limiting the blood supply to the region.
Increased stasis and activity of cytokines encourages
Microbiology
clots to form in blood vessels, leading to ischaemic Although occasionally caused by fungi, and rarely by
bone necrosis. Infection then spreads to the cortex parasites or viruses, osteomyelitis and septic arthri-
through the Volkmann canals and haversian system, tis are predominantly bacterial infections, most often
and subsequently into the subperiosteal space. caused by S. aureus. The major bacterial pathogens are:
If the infection remains untreated, bone necrosis • Staphylococcus aureus (80–90% of culture positive
may lead to development of a sequestrum – an area cases) – usually methicillin-susceptible but
of dead cortical bone separated from normal bone. community-acquired methicillin-resistant S. aureus
Sometimes the infection becomes walled off by granu- (CA-MRSA) is on the rise in many places.
lation tissue that forms a fibrous capsule, the so-called • Kingella kingae – recent studies using polymerase
Brodie abscess, usually located in the metaphysis and chain reaction (PCR) diagnosis suggest that this
presenting subacutely with pain and tenderness, but organism is a common cause of osteomyelitis and
rarely fever. septic arthritis in young children (usually under
Chronic osteomyelitis is usually the result of 2 years), but is often not identified using standard 393
untreated or inadequately treated acute ­osteomyelitis. laboratory cultures.
 12.2 INFECTIONS

1. Sluggish flow through 2. Poor penetration 3. Bacteria seed the 4. Pus under 5. Infection spreads
capillary loops and of white blood cells metaphyseal pressure further to the subperiosteal
sinusoidal veins –epiphyseal junction limits blood supply space

Epiphysis

Metaphysis

Diaphysis Periosteum
Nutrient artery
and vein

Fig. 12.2.1 Anatomical evolution of osteomyelitis. (Adapted with permission from Krogstad P, Smith AL 2004 Osteomyelitis and
septic arthritis. In: Feigin RD, Cherry JD, Demmler GJ, Kaplan SL (eds) Textbook of pediatric infectious diseases, 5th edn. WB Saunders,
Philadelphia, PA, pp 683–703.)

• Streptococcus pyogenes (group A streptococcus) – have been present for 2–3 days prior to presentation.
sometimes associated with varicella infection. Early in the illness, when bacteraemia is present, the
• Streptococcus pneumoniae – mainly in children aged child may be unwell with fever and malaise. Later, as
less than 2 years. the infection establishes itself, the symptoms relate to
• Pseudomonas aeruginosa – immunocompromised the main site of infection. Both diseases usually pres-
patients or traumatic (classical cause is a ent with fever and limb pain; in younger children this
nail through a tennis shoe causing calcaneal will most often manifest as a limp, or disuse of a limb
osteomyelitis). or other body part. Septic arthritis is more likely than
• Group B streptococcus or Escherichia coli – osteomyelitis to have obvious localized clinical signs.
especially in neonates.
• Haemophilus influenzae type b – in unimmunized Osteomyelitis
populations (mainly in developing countries).
• Mycobacterium tuberculosis – mainly in children In osteomyelitis, there is pain, which may be poorly
from developing countries or immigrant localized, especially in young children. Neonates may
populations; 50% of cases affect the spine. Often present with a generalized febrile illness, ­ without
subacute presentation. any localizing features. The precise location of the
• Salmonella spp – particularly in people with sickle infection can often be elicited with careful physical
cell anaemia. examination, looking particularly for metaphyseal
• Neisseria gonorrhoeae – mainly in developing tenderness. Erythema and swelling are signs of abscess
countries; may cause multifocal septic arthritis in formation, which occurs late in the illness. In one-third
neonates or sexually active adolescents. of cases there is a history of mild preceding trauma
to the affected area so such a history should increase
rather than reduce the suspicion of osteomyelitis.
Osteomyelitis most commonly affects, in order:
1. femur
Clinical presentation 2. tibia
Although osteomyelitis and septic arthritis are usu- 3. humerus
ally considered distinct entities, in paediatric practice 4. calcaneus.
they are sometimes difficult to distinguish and may The pelvis and vertebrae are less commonly affected
occur together. Children with septic arthritis are more but more likely to present with advanced disease
likely than adults to have osteomyelitis in the adjacent because of delayed presentation (in vertebral osteo-
bone. In neonates and infants, osteomyelitis and septic myelitis) or delayed diagnosis (in pelvic osteomyelitis).
arthritis coexist so commonly that the preferred term The diagnosis of osteomyelitis in long bones may also
is ‘osteoarticular infection’. be delayed – and hence become subacute or chronic –
The typical child with osteomyelitis or septic arthri- because of ­formation of a Brodie abscess or the pres-
tis is aged less than 5 years: approximately 50% of ence of ­low-grade infection, sometimes due to unusual
394 cases occur under the age of 5 years and of these 25% ­organisms. In these cases, diffuse pain or tenderness is
are under the age of 1 year. Usually the symptoms prominent and fever may be absent.
 Bone and joint infections 12.2
Septic arthritis empirically with antibiotics without first obtaining a
diagnostic specimen.
Differentiating septic arthritis from osteomyelitis can
Acute joint swelling may be caused by inflammatory
be difficult. Children with osteomyelitis may not want
arthritis (e.g. juvenile chronic arthritis, inflammatory
to move the adjacent joint because of either pain or
bowel disease, other connective tissue diseases), reac-
muscle spasm. In addition to fever and limb pain, the
tive arthritis (which may occur in association with a
hallmark of septic arthritis is a warm, tender joint with
wide range of pathogens including Mycoplasma, cyto-
a dramatically restricted range of movement and an
megalovirus, Epstein–Barr virus, parvovirus, hepati-
effusion. However, these signs are not always present.
tis, rubella, Yersinia, Salmonella and Shigella species),
Septic arthritis of the shoulder or hip is very ­difficult
rheumatic fever and Henoch–Schönlein purpura.
to diagnose early, because of the lack of visible joint
Rarely, osteomyelitis or septic arthritis may affect
swelling in the early stages.
multiple bones or joints at the same time. This should
The following features should raise suspicion that
raise the suspicion of a distant source of persistent
there is coexistent osteomyelitis and septic arthritis:
bacteraemia such as endocarditis or occult abscess,
• osteomyelitis in a bone with an intra-articular and should lead to a thorough investigation for other
metaphysis (proximal femur, proximal humerus,
sites of infection (e.g. heart, liver, spleen, brain, eyes).
proximal radius, distal lateral fibula)
It should also raise suspicion of unusual organisms
• slow clinical response to therapy (e.g. N. gonorrhoeae) as a cause of multifocal septic
• slow response of inflammatory markers (e.g. arthritis or an alternative diagnosis if an organism
C-reactive protein) to therapy
cannot be identified (e.g. CRMO, inflammatory or
• age less than 18 months reactive arthritis, or rheumatic fever).
• delayed presentation
• previous antibiotic therapy.

Confirming the diagnosis

Differential diagnosis As a minimum, all patients with suspected bone or
The most important diagnosis to exclude in possible joint infections should have a blood culture, blood
osteomyelitis is malignancy. Bone tumours can cause count and film, C-reactive protein (CRP) measure-
local bone destruction, and leukaemia may pres- ment and plain radiography. Other investigations are
ent with fever and bone pain. Cellulitis may mimic tailored to the likelihood of bone or joint infection
the focal tenderness and erythema of late-presenting (Fig. 12.2.2).
osteomyelitis. Patients with sickle cell disease may
develop bone infarction, which can be difficult to dif-
Osteomyelitis
ferentiate from osteomyelitis.
Chronic recurrent multifocal osteomyelitis (CRMO) Diagnosis depends upon the presence of two of the
is a rare, non-infectious, inflammatory syndrome of following:
unknown pathogenesis that affects children and young • clinical signs (fever, localized tenderness, erythema,
adults and is most common in girls. Affected chil- oedema)
dren have prolonged symptoms of pain and swelling • pus aspirated from bone
that relapse and recur. The clavicle is a classical site • positive blood or bone culture
of involvement. Treatment with antibiotics does not • evidence of osteomyelitis on plain radiography,
alter the course of the disease but steroids and anti- bone scan or magnetic resonance imaging (MRI).
inflammatory medication may provide symptomatic Other laboratory tests can provide supportive evidence
relief. CRMO usually resolves, although it may relapse for the diagnosis:
and recur over a prolonged period (up to 15 years), • The peripheral white cell count (WCC) is normal in
and there is a danger of premature epiphyseal closure. half or more of osteomyelitis cases. However, WCC
Septic arthritis of the hip can present similarly to and blood film examination should be performed to
transient synovitis (‘irritable hip’), which usually occurs exclude leukaemia.
following minor injury or a viral illness. Children with • Erythrocyte sedimentation rate (ESR) and CRP
transient synovitis are usually not unwell and their are raised at presentation in more than 90% of
joint signs are not as severe as those in children with cases. CRP is preferred to ESR to monitor response
septic arthritis, but in the early stages of either ill- to therapy because it rises faster (within 6 hours,
ness the diagnoses can be confused. Sometimes the compared with 24 hours for ESR) and responds more
only way to be sure of the diagnosis is to aspirate the quickly to treatment (returning to normal in 2 weeks,
395
joint and observe the child. It is important not to treat compared with 3–4 weeks for ESR in typical cases).
 12.2 INFECTIONS

Suspected uncomplicated osteomyelitis or septic arthritis

(typical history and examination, not a neonate,
immunocompromised, or sickle cell anaemia patient)

Initial investigations (Blood culture, WCC, CRP,

ESR and plain AP and lateral radiograph)

Well localized Poorly localized

Well localized
clinical signs clinical signs
clinical signs Signs suspicious
Suspected No abnormality of tumour – biopsy*
Suspected
subperiosteal or soft tissue
septic arthritis
abscess signs only on X-ray

Arthrotomy or MRI if available.

Ultrasound. Aspirate*, Bone scan
arthroscopic
biopsy* and IV (or MRI if
washout*.
antibiotics as indicated. localized infection
IV antibiotics.
Proceed to scintigraphy and MRI available)
Investigate for bone
infection if suspicion if any suspicion of
of concurrent multifocal disease
osteomyelitis

Negative scan but strongly suspicious Positive scan Cold scan – consider MRI. Surgery
clinical findings – start antibiotics (MRI or hot bone scan) for drainage of abscess*.
and consider aspiration*, MRI, gallium Start IV antibiotics Start antibiotics if
scan, repeat bone scan investigation/surgery delayed

Poor response to therapy or deterioration

(persistent fever, clinical signs, rising CRP)

Further imaging – MRI, ultrasound. Surgery – open drainage

of abscess*, decompression of intramedullary collection

*All specimens obtained from aspiration, abscess drainage, joint washout or bone biopsy should be sent fresh (not in preservative)
to the microbiology laboratory for Gram stain and culture, in addition to any histological examination. Antibiotic therapy can be
adjusted once formal culture and susceptibility results are known.

Fig. 12.2.2 Approach to the management of osteomyelitis and septic arthritis in children. AP, anteroposterior; CRP, C-reactive
protein; ESR, erythrocyte sedimentation rate; IV, intravenous; MRI, magnetic resonance imaging; WCC, white cell count. (Adapted with
permission from Steer AC, Carapetis JR 2004 Acute hematogenous osteomyelitis in children: recognition and management. Pediatric
Drugs 6:333–346.)

• delayed presentation
Pus aspirated from bone
• a child with any predisposing condition (e.g.
Although some advocate diagnostic bone aspiration immune compromise, sickle cell disease, other
or biopsy as a routine, the majority of children do not haemoglobinopathies)
396
need these invasive tests. A diagnostic specimen should • unusual radiographic findings (e.g. lucency on plain
be obtained in any of the following situations: radiography at presentation)
 Bone and joint infections 12.2
• geographical region where there is a high likelihood
of CA-MRSA
• reason to suspect a complication such as an abscess
• reason to suspect an alternative diagnosis such as
malignancy
• delayed response to antibiotics.

Positive blood or bone culture

Cultures from bone aspiration or biopsy are positive
at admission in 50–70% of osteomyelitis cases, and
culture-negative cases may have a positive Gram stain
or typical histological features of acute osteomyelitis.
However, as stated above, this procedure is usually not
needed. Blood cultures are positive in 30–50% of cases.

Imaging
Plain radiography
Plain radiography should be performed routinely
to exclude a fracture or malignancy. There are no
changes of osteomyelitis in the first 3 days. From days
3–10 there may be non-specific, deep, soft tissue swell-
ing followed by poor distinction of muscular planes.
From days 10–21 periosteal elevation or lytic lesions Fig. 12.2.3 Osteomyelitis in a 3-year-old girl who presented
may be seen (Fig. 12.2.3). Because these changes indi- with pseudoparalysis. Radiographs at presentation were normal.
cate longer-standing disease, if they are seen on radi- This radiograph, taken 2 weeks after presentation, shows
ography at presentation the child should not be treated early abscess formation in the distal radius with erosion of the
as having acute, uncomplicated osteomyelitis (i.e. the radial metaphysis and loss of fat plane definition. (Courtesy
child requires more prolonged courses of antibiotics, of Professor Kerr Graham; reproduced with permission from
Steer AC, Carapetis JR 2004 Acute hematogenous osteomyelitis
initially intravenous and subsequently oral).
in children: recognition and management. Pediatric Drugs
Bone scan 6:333–346.)
The typical bone scan uses technetium-99 m-labelled
phosphates or phosphonates, which bind to hydroxy-
apatite crystal as they flow through bone. Uptake is Clinical example
increased with increased blood flow, inflammation and
increased osteoblastic activity. The sensitivity of bone Michael, aged 15 months, was noted by his
parents to be reluctant to bear weight on his
scans in the diagnosis of osteomyelitis is more than
right leg and had a low-grade fever. He was
90%, but a negative bone scan does not exclude the seen by his general practitioner and referred
diagnosis. False-negative bone scans in osteomyelitis immediately to the emergency department, from where
can be caused by focal ischaemia due to compression he was admitted with ‘possible osteomyelitis’ of the right
from abscess formation, leading to a ‘cold’ rather than distal femur because of mild metaphyseal tenderness and
the typical ‘hot’ scan. There is a 5–30% false-positive refusal to bear weight. Osteomyelitis was confirmed by
rate of bone scans, usually due to difficulty in differenti- positive blood culture (S. aureus) and a positive bone scan.
Plain radiographs were normal. Michael was managed
ating infection in surrounding soft tissue or joints from
with intravenous flucloxacillin for 3 days, followed by oral
bone. Bone scans are considered the investigation of flucloxacillin for 3 weeks. He was followed for 6 months and
choice by many people for osteomyelitis because they had no long-term sequelae.
are sensitive, cheap, usually positive within 48 hours of
onset of symptoms, rarely require sedation and allow
for the detection of multifocal disease (because the
whole skeleton is visualized). However, bone scans give Ultrasonography
a relatively high radiation dose (equivalent to 100 chest Ultrasonography is used mainly to guide aspiration
X-rays, or half that for computed tomography (CT) of of subperiosteal fluid collections. There may be other
the chest) and do not give detailed anatomical informa- changes that suggest osteomyelitis (e.g. cortical
397
tion, particularly relating to collections of pus. breaches and soft tissue swelling), but u
­ ltrasonography
 12.2 INFECTIONS

is rarely used by itself for diagnosing osteomyelitis. osteomyelitis because of the risk of epidural abscess, and
It may also detect fluid collections in adjacent joints in the pelvis, where there is a higher risk of abscess for-
­suggestive of septic arthritis. mation. However, it is often difficult to obtain an MRI
scan at short notice, scans are expensive and younger
Magnetic resonance imaging
children may need to be anaesthetized for a scan. MRI
MRI is the best test for osteomyelitis in cases where
may also be useful in cases where there is high clinical
symptoms and signs are localized (Fig. 12.2.4). A find-
suspicion of localized osteomyelitis but a negative (and
ing of dark bone marrow intensity on T1-weighted
therefore possibly false-­negative) bone scan.
images has almost 100% sensitivity. The specificity is
not quite so high, although the use of fat-suppressed
contrast-enhanced imaging improves specificity. The Septic arthritis
other advantages of MRI are that it will show abscesses Septic arthritis can usually be diagnosed more easily
and sinus tracts, and is particularly useful in planning than osteomyelitis because the signs are more obvi-
surgery in complex cases. MRI is often used in vertebral ous and a diagnostic specimen is obtained more easily.
Traditional teaching is that any child with a possibly
infected joint requires urgent surgical intervention,
usually a formal arthroscopic washout or arthrotomy
in the operating theatre under general anaesthesia. In
general, joint aspiration should be performed to obtain
a specimen only when the diagnosis is in doubt – with
the intention of proceeding to the operating theatre if
the diagnosis is confirmed – or if there is an unavoid-
able delay before getting the child to the operating
theatre. However, recent published experience from
Finland suggests that diagnostic joint aspiration may
be the procedure of choice; more research is needed in
this area before firm recommendations can be made.
Joint fluid should be sent immediately to the labora-
tory for Gram staining and culture. The Gram stain
is not a reliable method of microbiological diagnosis,
so Gram staining results should not be used as a rea-
A son to cease anti-staphylococcal antibiotics in favour
of other antimicrobials. Instead, Gram staining sug-
gesting other organisms (e.g. Gram-negative bacilli)
is an indication to add broader-spectrum cover to
the a­ nti-staphylococcal antibiotic. The antimicrobial
treatment can be rationalized when definitive culture
and susceptibility results are known.
Occasionally, pus from an obviously infected joint
may not grow organisms on culture, even if a child has
not received prior antibiotics. This is probably because
of the high levels of natural cytokines and other anti-
bacterial agents in the effusion, although sometimes
it may be because the infection is caused by an organ-
ism, such as K. kingae, that is not easily identified
using standard culture techniques. Microbiological
yield from joint fluid can be increased by inoculating
B
the fluid directly into a blood culture. Most culture-
Fig. 12.2.4 An 18-month-old child who presented with fever negative cases can be managed as S. aureus infections,
and limp. (A) Magnetic resonance image shows an abscess but sometimes the negative culture result is because
that originates in the metaphysis of the right proximal femur the joint is not actually infected. A number of patients
crossing the physeal cartilage to the epiphysis. (B) Plain with juvenile chronic arthritis and rheumatic fever
radiograph shows an abscess in the proximal femur. (Courtesy
present initially with culture-negative ‘septic arthritis’.
of Professor Kerr Graham; reproduced with permission from
Steer AC, Carapetis JR 2004 Acute hematogenous osteomyelitis Therefore, a negative culture of synovial fluid should
in children: recognition and management. Pediatric Drugs lead to a thorough re-evaluation of the patient and
398
6:333–346.) exclusion of other diagnoses.
 Bone and joint infections 12.2
Duration of antibiotic therapy
Treatment
Adult patients are usually treated for osteomyelitis
The choice of empirical antimicrobial therapy is or septic arthritis with 4–6 weeks of intravenous anti-
similar for septic arthritis and osteomyelitis. The
­ biotics. By contrast, children can often be treated for
duration of treatment is identical for uncomplicated a shorter time and most of the treatment course can
cases. Osteomyelitis is more likely than septic arthritis be given orally. The typical child with acute, uncom-
to be complicated and then to require longer courses plicated osteomyelitis or septic arthritis who responds
of ­initial parenteral and subsequent oral therapy. quickly to initial therapy can be treated with 3 days
Surgery is always required for septic arthritis, but only of intravenous antibiotics followed by 3 weeks of oral
­occasionally required for osteomyelitis. antibiotics. However, this regimen should be used only
in otherwise healthy children with classical acute pre-
sentations, no evidence of chronicity on initial radiog-
Antibiotic choice raphy and a rapid response to treatment. Children with
atypical presentations, underlying illness, evidence of
S. aureus is the most common cause of bone and
chronicity, complications or delayed response to treat-
joint infections in all age groups, and in most parts
ment should all be treated with longer initial courses
of Australia CA-MRSA rates are low (< 10% of all
of intravenous antibiotics and longer total duration
community-acquired S. aureus infections). In these
of therapy. When the switch is made from parenteral
regions, empirical antibiotic therapy should always
to oral antibiotics, they should be used at two to three
contain an anti-staphylococcal antibiotic such as a
times higher doses than normally given to achieve ade-
β-lactamase-resistant penicillin (e.g. flucloxacillin)
quate serum and bone c­ oncentrations. Children usually
or first-generation cephalosporin (e.g. cephalothin
tolerate this well, with few ­side-effects. Recent evidence
or cefazolin). Where rates of CA-MRSA infection
suggests that even shorter courses may be possible – a
are high, either clindamycin or vancomycin should
total of 10 days (including an initial 3-day intravenous
be used empirically (in some regions, clindamycin
course) for septic arthritis, or a total of 20 days (with
resistance is also rising, in which case vancomycin
an initial 4-day intravenous course) for acute haemat­
is the best choice) until microbiological diagnosis is
ogenous osteomyelitis with or without adjacent septic
confirmed and antibiotics can be tailored accord-
arthritis. However, such abbreviated courses should be
ing to susceptibility testing. Note that K. kingae is
considered only in uncomplicated cases that show a
usually susceptible to most antibiotics used empir-
rapid and sustained response of signs, symptoms and
ically, including penicillins and c­ephalosporins,
CRP to intravenous treatment, in whom close follow-
but is commonly resistant to clindamycin and
up is assured, and when the ­carers appreciate the pos-
vancomycin.
sibility that the treatment failure rate may be greater
The following patients should have other antibiotics
than after more prolonged ­treatment courses.
added to (not substituted for) the anti-staphylococcal
antibiotic regimen:
• neonates: add gentamicin or a third-generation Surgical management
cephalosporin (e.g. cefotaxime, ceftriaxone)
• sickle cell anaemia: add a third-generation As mentioned above, the current recommendation is
cephalosporin (e.g. cefotaxime, ceftriaxone) that all children with septic arthritis require a formal
• puncture wounds to the feet: add an anti- arthroscopic washout or arthrotomy as a diagnostic and
pseudomonal antibiotic (e.g. ceftazidime, therapeutic procedure. Recent data suggesting that diag-
piperacillin, ticarcillin) nostic aspiration alone may be preferable require confir-
• immunocompromise: add an anti-pseudomonal mation before a change to routine management can be
antibiotic, as above. If there is no response, recommended. Splinting an infected joint may be useful
consider also adding an antifungal (e.g. to reduce pain in the first few days, but joint mobility
amphotericin or voriconazole) should be encouraged once the acute signs have settled.
• children aged less than 5 years and not immunized An infected hip may require abduction bracing to pre-
against H. influenzae type b (Hib): add a third- vent or treat septic d
­ islocation in the younger child.
generation cephalosporin (e.g. cefotaxime, The main place for surgery in osteomyelitis is to
ceftriaxone). confirm the diagnosis or manage complications such
Following identification of the organism, antibiotic as abscesses, chronic osteomyelitis, sequestra, pseud-
choice is dictated by susceptibility testing. If unable to arthroses or growth defects. In chronic osteomyelitis,
obtain cultures or if cultures are negative, the i­nitial both long-term antibiotics and surgical debridement
empirical choice should be continued provided the are needed. Deformities that result from chronic
399
clinical response is adequate. osteomyelitis or growth plate damage may require
 12.2 INFECTIONS

limb reconstruction techniques. Destruction to artic- c­ omplications include pathological fractures and bone
ular cartilage causes lifelong problems that are not deformities, including growth arrest, and leg-length
­correctable by surgery. discrepancy. The outcome of septic arthritis is also
usually good but delayed or inadequate treatment can
Adjunctive treatment lead to joint damage or destruction, with long-term
problems of poor function and osteoarthritis. All of
A recent placebo-controlled randomized controlled
these complications are more common in children
trial found that 4 days of intravenous dexamethasone
whose diagnosis is not made sufficiently early or who
in addition to antibiotic and surgical management
receive inadequate initial treatment.
led to a significant reduction in residual dysfunction,
from 26% in the control group to 2% in the treatment
group, 12 months later. However, because the baseline Clinical example
rate of dysfunction in that study was much higher than
would be normal in Australia, adjunctive corticoste- Jennifer, aged 6 months, was admitted to
roids ­cannot be routinely recommended until further hospital with a diagnosis of ‘pyrexia of unknown
evidence of their efficacy is available. origin’. She was investigated extensively.
Eventually she was treated with oral antibiotics
for a ‘possible urinary tract infection’. This made her afebrile,
Monitoring therapy and follow-up but the fever returned within 2 days of completing the
The child should be followed clinically to ensure that antibiotic course. Septic arthritis of the right hip and proximal
femoral osteomyelitis was diagnosed 3 weeks after the onset
pain, tenderness, mobility and systemic symptoms all
of fever. Jennifer progressed to develop septic dislocation
respond quickly and do not relapse on or after anti- of the right hip, avascular necrosis of the femoral capital
biotic treatment. Inflammatory markers are usually epiphysis and growth arrest. She required more than 20
also followed. The CRP is the best marker in bone and hospital admissions for orthopaedic operations throughout
joint infections – it is almost always raised initially, childhood. At the age of 15 years, she is a very troubled
unlike the WCC, and responds more quickly to treat- teenager with a painful hip, short leg and severe limp.
ment than the ESR. It is not necessary to wait for the
ESR to normalize before ceasing antibiotic treatment,
provided the child has fully responded clinically and
the CRP has normalized or dramatically improved.
Discitis and vertebral osteomyelitis
A rise in CRP after antibiotics have been started may Musculoskeletal infection of the spine is uncommon
indicate the presence of complications or septic arthri- but does occur in children. There are two distinct enti-
tis in addition to osteomyelitis. ties of spinal infection: vertebral osteomyelitis and
If there is persistent fever or local symptoms and/ discitis (or diskitis). In their initial phases, both pres-
or the CRP has not begun to fall 2–3 days after ent with poorly localized back pain and absent or only
commencing intravenous antibiotics, there may be
­ low-grade fever.
a ­complication such as an abscess, coexistent septic Children with vertebral osteomyelitis are usually
arthritis or a sequestrum. In these cases, re-imaging older (> 8 years) and eventually become febrile and toxic,
is usually needed with MRI or ultrasonography. Any developing localized back pain that may affect any part
collection should be drained and, if no collection is of the spine. The cause is usually S. aureus ­infection
present, aspiration at the site of infection should be and, because of delayed presentation, complications
undertaken for histology and culture/Gram staining. such as paraspinal abscesses are often found. These
Typical cases that respond well to initial treatment children require prolonged antibiotics and frequently
and can be switched to oral treatment in the first week also surgical drainage of abscesses to prevent spinal
can be discharged from hospital shortly after com- cord or nerve compression.
mencing oral antibiotics. They should be assessed Discitis tends to occur in the lower lumbar spine
clinically and with CRP measurement for 3 weeks and and in younger children (< 5 years) who present with
reviewed occasionally (e.g. every 6 months) for the next non-specific symptoms such as a limp or refusal to
2 years to monitor for relapse. bear weight. The ESR is usually raised and by 4 weeks,
plain radiography of the spine reveals narrowing of
one or more disc spaces. MRI may provide further
detailed anatomical information. In many cases of dis-
Prognosis citis no clear evidence of infection can be found, and
In affluent countries, children almost never die from surgery is usually not recommended when the diagno-
osteomyelitis but some children develop r­ecurrent sis is clear from history, examination and imaging. It
400 infection (which may occur many months or even is generally accepted that the treatment is prolonged
years later) or chronic osteomyelitis. Other rare ­anti-staphylococcal antibiotics such as flucloxacillin.
 Bone and joint infections 12.2

Practical points Practical points

Osteomyelitis Septic arthritis

• Fever and limb pain is a common presentation of • Most cases of uncomplicated acute septic arthritis are due
osteomyelitis in older children, with the femur and the tibia to Staphylococcus aureus.
being the most commonly affected bones. • Gram stain result of aspirated fluid that suggests
• Osteomyelitis in neonates and infants presents non- organisms other than S. aureus is an indication to add
specifically with fever – neonates are more likely to have broader-spectrum antibiotic therapy.
multifocal disease and Gram-negative organisms. • Septic arthritis is more likely to coexist with osteomyelitis
• Bone malignancy is an important differential diagnosis when the joint involved has a metaphysis that is intra-
and must be excluded (usually by X-ray at presentation). articular (hip, shoulder, elbow and ankle), when there has
• A bone scan or MRI is indicated in the investigation of been slow response to therapy, in infants, and when there
suspected osteomyelitis – MRI is the best test where is delayed presentation.
symptoms are clearly localized, because of the detailed • Every child with septic arthritis requires urgent surgical
information it provides. intervention – this means a washout of the joint.
• Treatment of simple, uncomplicated cases is with an anti- • Treatment of uncomplicated cases following joint
staphylococcal antibiotic (tailored according to local rates washout is with an anti-staphylococcal antibiotic
of CA-MRSA) given intravenously for 3–5 days followed by (tailored according to local rates of CA-MRSA) given
a high-dose oral anti-staphylococcal antibiotic for 3 weeks, intravenously for 3 days followed by a high-dose oral anti-
or even as little as 20 days' total treatment for simple and staphylococcal antibiotic for 3 weeks, although simple
very responsive cases. cases that respond very quickly may be treated with
• In cases that are not simple or have a delayed response courses for as little as 10 days.
to treatment, further investigation, obtaining a surgical • In cases that are not simple or have a delayed response
specimen, and longer and broader-spectrum antibiotic to treatment, prolonged antibiotic therapy and possibly
therapy are indicated. surgical intervention may be indicated.

401
 12.3 Meningitis and
encephalitis
Robert Booy, Cheryl Jones

Meningitis and encephalitis are both life-threatening The environment

infections that require rapid recognition and treatment
The incidence of bacterial meningitis is higher in the
for a child to survive without sequelae. They are on the
Indigenous and the poor, the two all too often occur-
differential diagnosis for all febrile ill children, particu-
ring together. Prior viral respiratory infection and
larly those with altered consciousness.
crowding (including school and daycare attendance)
increase risk and perhaps explain why disease peaks
during late winter and spring. Exposure to smokers
and close personal contact is also important.
Bacterial meningitis
The improving control of leading causes of bacterial
meningitis has reduced both mortality and m ­ orbidity; Microbe: polysaccharide capsule
both vaccination and improved quality of life have A key virulence determinant is the microbe's polysac-
contributed to dramatic declines in the incidence of charide capsule. Specific human antibody to each
the big three causes: Haemophilus ­influenzae type b, ­capsule is protective.
Neisseria meningitidis and Streptococcus pneumoniae.
Consequently, the reduced familiarity of doctors with
disease must be balanced by better training in the early Human genetic factors
recognition and treatment of these deadly infections. Human genetic factors predisposing to disease are
Knowledge of local epidemiology should direct increasingly recognized, although so far they account
antibiotic use. Appropriate adjustments in antibiotics for only a small proportion of cases. Our understand-
rely heavily on culture and sensitivity results. Improved ing in this area is growing rapidly.
supportive and resuscitative measures in recent • Defects in the various complement pathways
decades have reduced the range of case fatality rates predispose to meningococcal disease. First
from 5–25% (pneumococcal meningitis and menin- recognized were mutations of terminal complement
gococcal sepsis being the most deadly) to 2%–8%. components, then properdin.
What has made the difference, at least in developed • More recently, variants in mannose-binding
­countries, includes paying close attention to: protein and factor H binding protein have been
• fluid resuscitation for circulatory compromise identified as increasing the risk of meningococcal
• elective intubation before respiratory failure infection.
• management of convulsions • For Hib, genetic variation in Toll-like receptor-4
• control of cerebral oedema and associated pathways are linked to increased
• electrolyte and glucose balance. risk.
• The risk of pneumococcal disease is increased
by an inherited defect in interleukin-1 receptor-
Epidemiology
associated kinase-4 (IRAK-4), leading to a
The annual incidence of bacterial meningitis is about failure to make cytokines following stimulation
10–20 cases per 100 000 children aged 0–5 years, with Toll-like receptor agonists such as
highest in infants. In Australia, the pneumococ- interleukin-1β.
cus bacteria is now the commonest cause, and Hib • Congenital absence of the spleen may have a
immunization means that there are only a few spo- genetic basis and predisposes to infection with
radic Hib cases. Pneumococcal and meningococcal encapsulated organisms.
cases are sporadic too, except for occasional out- • Immunoglobulin deficiencies (X-linked or
breaks of meningococcal disease. As with other seri- recessive) predispose to meningitis generally,
ous infections, the risk of disease and its severity are whereas recurrent meningococcal disease may
determined by factors to do with the e­ nvironment, be associated with immunoglobulin (Ig) M
402
the microbe and the host. deficiency.
 MENINGITIS AND ENCEPHALITIS 12.3
Other factors that increase the risk of • Children older than 5 years:
meningitis: • N. meningitidis
• Acquired impaired immunity (e.g. human • S. pneumoniae.
immunodeficiency virus infection) and splenectomy
• Congenital or acquired neuroanatomical defects Pathogenesis
(e.g. base of skull fracture)
The development of bacterial meningitis usually follows:
• Penetrating head injuries, neurosurgical procedures
(1) colonization of the nasopharynx by encapsulated
• Cerebrospinal fluid (CSF) leak
bacteria; (2) invasion of the host causing bacteraemia
• Congenital dural defect (dermal sinus or
and then invasion of the meninges; (3) bacterial multi-
myelomeningocele)
plication and induction of inflammation within the sub-
• Cochlear implants.
arachnoid space; and (4) neuronal injury (Fig. 12.3.1).
Aetiology
The most common pathogens in each age group are: Clinical presentations
• Neonates and infants aged under 3 months:
Infants
• Escherichia coli
• Streptococcus agalactiae Many symptoms and signs within this age group are
• Listeria monocytogenes non-specific:
• Infants and children: • poor feeding, vomiting
• Streptococcus pneumoniae (pneumococcus) • fever, irritability, drowsiness.
• Neisseria meningitidis (meningococcus) Neck stiffness or a bulging fontanelle are more
• Haemophilus influenzae type b (Hib) ­specific but may be absent, especially early in the illness.

Microbial Host and

factors environmental factors

Adhesins, proteases Bacterial colonization Viral infection, crowding,

and local invasion tobacco smoke exposure

Polysaccharide capsule Bacteraemia and Absence of complement

meningeal invasion and/or specific anticapsular
antibodies

Multiplication within
Bacterial cell wall products the subarachnoid Inflammatory cytokines
space and induction and chemotaxins
of inflammation

Meningeal inflammation,
Bacterial cell wall products, altered microvascular Neutrophil infiltration,
polysaccharide capsule endothelium and inflammatory cascade
cerebral vasculitis

Ischaemia, cerebral oedema,

Neuronal injury oxygen radicals, NO, cytokines,
excitory amino acids
403
Fig. 12.3.1 The pathophysiological cascade of meningitis.
 12.3 INFECTIONS

Children aged at least 3 years • Full blood count, including white blood cell
differential, C-reactive protein or procalcitonin may
Symptoms and signs are more obvious:
all point to the seriousness of infection.
• severe headache, vomiting, photophobia
• Serum electrolytes, glucose and creatinine should be
• fever, neck stiffness, delirium or deteriorating
monitored and managed.
consciousness.
Lumbar puncture is delayed for patients with any of the
Convulsions are a presenting feature in 20–30% of
following:
infants and children with bacterial meningitis. Those
with meningococcal meningitis or septicaemia may
• absent or non-purposeful responses to pain
have a petechial and/or purpuric rash over the trunk,
• focal neurological signs (or a false localizing sixth
nerve palsy)
limbs and, in extremis, the face. Initially the rash may
be blanching, but within hours become non-blanching
• abnormal pupil size or reaction
purpuric lesions that may progress through dermal
• decerebrate or decorticate posturing
vascular necrosis to peripheral gangrene (Fig. 12.3.2).
• irregular breathing, rising blood pressure and
falling pulse (despite peripheral vasoconstriction)
• papilloedema
Diagnosis • continuous fitting.
Such patients require intensive care management,
Lumbar puncture (LP) helps to establish and localize
including measures to reduce intracranial pressure.
the infection through obtaining a sample for micros-
LP should still be performed, but only when the child
copy, culture, biochemistry and molecular ­diagnostic
is stable, usually within 2–3 days. Cerebral herniation
testing. Unless the child is already treated with
occurs in about 5% of cases, with or without LP, and
­antibiotics, LP has a very high sensitivity. Molecular
may account for 30% of the deaths.
diagnostic testing using polymerase chain reaction
The typical CSF changes in bacterial meningi-
(PCR) on blood or CSF can identify the cause of men-
tis are outlined in Table 12.3.1. Organisms are often
ingitis in patients pretreated with antibiotics.
seen on Gram stain of the CSF, making a presumptive
Owing to concern over the dangers of cerebral her-
­diagnosis possible.
niation, circulatory compromise or disseminated intra-
CSF examination may be difficult to interpret, espe-
vascular coagulation, in recent years LP has often been
cially when prior antibiotics have been given.
postponed; immediate collection of peripheral blood
Parameningeal foci, such as brain abscess or sub-
samples for diagnosis (culture, PCR) is helpful but
dural empyema, and tuberculous meningitis can
diagnostic sensitivity may be reduced by up to 50%.
have a similar CSF profile to partially treated bac-
The suspicion of bacterial meningitis should prompt
terial ­meningitis, so should be in the differential
rapid commencement of antibiotics; this is ultimately
diagnosis.
a clinical decision.
Cerebral imaging, by either computed tomogra-
Paired serology is helpful, but only in retrospect.
phy (CT) or magnetic resonance imaging (MRI),
• Needle aspirate from skin lesions for Gram stain
is not recommended routinely and is not useful
and culture is useful for diagnosis in meningococcal
for determining whether there is raised intracra-
disease.
nial pressure. It has a role when there is concern
• Suprapubic aspirate or catheter urine specimen,
that conditions that may mimic meningitis are pres-
if less than 6 months old, may reveal dual sites
ent, such as intracranial mass lesions, and LP is
of infection.
contraindicated.

Antibiotic treatment
The antibiotics selected should cover the commonly
encountered causative bacteria. As strains of S. pneu-
moniae resistant to penicillin and cephalosporin are
relatively common in many settings, vancomycin may
be used with a third-generation cephalosporin as ini-
tial empirical therapy, except in infants aged less than
3 months for whom amoxicillin should be given in
­addition to cover Listeria.
Subsequent adjustments depend on culture and
­sensitivity results.
Fig. 12.3.2 Meningococcal infection with purpura and Dosage and duration of antibiotic treatment are
404
ecchymoses. outlined in Table 12.3.2.
 MENINGITIS AND ENCEPHALITIS 12.3
Table 12.3.1 Cerebrospinal fluid: normal values and typical changes in some pathological conditions

Total WCC (× 106/L)* Predominant cell type Glucose (mmol/L) Protein (g/L)

Normal <5 Lymphocytes 2.5 < 0.4

Normal neonate < 20 (<3 neutrophils) Lymphocytes Normal Mildly increased

Bacterial meningitis 1000s Neutrophils Reduced or Moderately raised

undetectable

Partially treated 100–1000s Neutrophils Reduced or Moderately raised

bacterial undetectable
meningitis†

Tuberculous meningitis 50–100s Neutrophils/mononuclear Reduced or Moderately to

cells undetectable markedly increased

Viral meningitis < 10–100s Lymphocytes‡ Usually normal Normal to < 1

Encephalitis < 10–100s Lymphocytes Usually normal Mildly to moderately

raised

Brain abscess Normal to mild increase Variable neutrophils Normal Normal to mildly
and other mass raised
lesions§

*A traumatic tap is the commonest cause of blood-stained cerebrospinal fluid; for every 1000 × 106/L red blood cells, add 2 × 106/L
white blood cells and 0.01 g/L protein to normal values, but can also be seen in HSV encephalitis.
†
Partially treated meningitis is seen when children receive oral antibiotics before the diagnosis of meningitis has been made.
‡
Neutrophil predominance may be present in enterovirus meningitis.
§
Lumbar puncture is not done if a mass lesion is suspected. CSF changes depend on the site of the lesion; for example, if near the
cerebral surface pleocytosis occurs.
WCC, white cell count.

Table 12.3.2 Antibiotic therapy for bacterial meningitis

Pathogen Antibiotic Dose (mg/kg) Duration (days)

Streptococcus pneumoniae
Penicillin susceptible Penicillin G 60 IV 4-hourly 7–10
Penicillin non-susceptible Cefotaxime* 50 IV 6-hourly 7–10
 Penicillin + third-generation Vancomycin + 15 IV 6-hourly 10–14
cephalosporin non-susceptible Cefotaxime* 75 IV 6-hourly

Neisseria meningitidis Penicillin G 60 IV 4-hourly 4–7

Haemophilus influenzae b and non-b species

Non-β-lactamase-producing Amoxicillin 50 IV 4-hourly 7
β-Lactamase-producing Cefotaxime* 50 IV 6-hourly 7

Unknown pathogen Cefotaxime* ± 50 IV 6-hourly 7

Vancomycin 15 IV 6-hourly

Maximum doses: penicillin G, 2.4 g; amoxicillin, 2 g; cefotaxime, 3 g; ceftriaxone, 2 g; vancomycin, 500 mg.
*Ceftriaxone 50 mg/kg 12-hourly can be substituted for cefotaxime. 405
 12.3 INFECTIONS

Supportive treatment Convulsions

Clinical observations About 30% of children with bacterial meningitis
have convulsions, more commonly with pneumococ-
Keeping a regular record of heart and respiratory
cal or Hib meningitis than meningococcal meningi-
rates, blood pressure, temperature and conscious state
tis. Benzodiazepines such as diazepam or midazolam
can detect important trends such as falling heart rate
will control most convulsions, but if these recur or are
and rising blood pressure with rising intracranial
prolonged they may raise intracranial pressure and
pressure. The head circumference in infants should be
worsen the cerebral ischaemic injury. Administration
measured daily.
of ­phenytoin or phenobarbital, and mechanical ven-
tilation may be necessary. Consider aberrations in
sodium, calcium or glucose levels.
Fluid therapy
Intravenous fluids are administered initially to restore
Cerebral oedema
circulating blood volume, to correct glucose or electro-
lyte disturbance, and to minimize the need to swallow, Careful observation for signs of increased intra-
with its attendant risk of aspiration. cranial pressure (IIP) is essential. These are listed
In contradiction to past recommendations, recent above under reasons for delaying a LP. Refer also
studies have shown that fluid restriction is not helpful above to section on fluid therapy. The child with sus-
for children with bacterial meningitis and, indeed, the pected raised IIP should be nursed head-up and in
use of maintenance fluid is associated with fewer neu- ­midline, be sedated, intubated and ventilated, and
rological complications. Fluid administration should given boluses of ­hypertonic saline or mannitol to
be adjusted according to vital signs and adequacy of reduce pressure. Regular oral glycerol (with or with-
circulation. The low serum sodium levels and reduced out dexamethasone) may reduce both mortality and
urine output that may occur in bacterial meningitis are neurological sequelae, ­especially in cases caused
due to fluid depletion rather than inappropriate antid- by Hib.
iuretic hormone secretion.
Circulatory shock
Corticosteroids Approximately 5–10% of children with bacterial men-
ingitis present in shock and initially require large-­
Dexamethasone for treating bacterial meningitis is
volume fluid resuscitation in 10–20-mL/kg boluses.
controversial and depends on the cause. Children
If a second bolus is required, strong consideration
with Hib meningitis have a reduced risk of deafness if
should be given to elective intubation and ventila-
dexamethasone is given prior to antibiotics. Benefit,
tion, but in a third-world setting without ventilator
or detriment, in children with either pneumococ-
support research suggests fluids be given more slowly
cal or meningococcal meningitis remains unproven;
(i.e. not by bolus).
however, a recent Cochrane review showed a lower
Inotropic agents may be needed to help support the
case-fatality rate and fewer long-term sequelae in
circulation.
a combined adult/child group of bacterial meningi-
tis cases. A ­reasonable approach for bacterial menin-
gitis of, as yet, uncertain aetiology might be to give Neurological lesions
dexamethasone 0.15 mg/kg just before the first dose
Hard neurological deficits (central, cranial and/or
of empirical antibiotics and to continue 6 hourly for
peripheral) are present in 10–20% of children ­during
4 days, but to cease if N. meningitidis becomes the
the acute illness, although some may be r­eversible.
principal diagnosis.
Long-term follow-up studies suggest an average
IQ diminution of 5 points and significantly more
­psychological, social and educational impediments.
Acute complications
During meningitis, complications from central
Subdural effusion
­nervous system infection or systemic effects of infec-
tion are common. Children with recurrent or pro- This is a fluid accumulation in the subdural space
tracted convulsions, circulatory instability or signs that is usually sterile but needs to be differenti-
of cerebral oedema should be managed in an inten- ated from subdural empyema (see below). An effu-
sive care unit. sion is quite a common complication of bacterial
406
 MENINGITIS AND ENCEPHALITIS 12.3
­ eningitis, ­usually asymptomatic and occasionally
m Cerebral imaging
associated with:
Cranial CT or MRI is useful in identifying:
• persistent or recurring high fever
• subdural collections
• focal or generalized convulsions
• brain abscess
• persistent vomiting
• cerebral vascular thrombosis
• increasing head circumference or fontanelle tension
• hydrocephalus.
• development of a focal neurological deficit.
These investigations are considered for patients with:
Most resolve spontaneously. Subdural empyema is
uncommon but should be suspected when the above
• prolonged coma
features are accompanied by ongoing irritability
• sustained irritability or convulsions
and raised erythrocyte sedimentation rate (ESR)/C-
• persistent focal neurological deficits
reactive protein levels. Cerebral CT (Fig. 12.3.3) or
• enlarging head circumference
MRI establishes the diagnosis of subdural effusion or
• recurrent disease.
empyema.

Outcome
Persistent (> 7 days) or secondary fever
• Mortality rate 2–8% (industrialized countries),
Differential diagnosis: lowest in meningococcal and highest in
• viral nosocomial infection pneumococcal meningitis.
• subdural effusion • Intellectual disability, spasticity, convulsions,
• thrombophlebitis hydrocephalus, deafness 5–15%.
• other suppurative lesions • Later learning and behaviour disorders 25–40%
• immune-mediated disease – reactive arthritis or (may be subtle).
pericarditis. Independent risk factors for severe neurological or
Uncommonly, fever may also result from: intellectual disability are meningitis in infancy, delayed
• inadequately treated meningitis diagnosis, persistent or late-onset convulsions and
• a parameningeal focus (e.g. abscess or subdural focal neurological signs.
empyema) All children should have their hearing tested fol-
• drugs (e.g. penicillin, co-trimoxazole) lowing meningitis, by brainstem (auditory) evoked
• Munchausen by proxy syndrome (parent infecting potentials or formal audiometry. Regular review
child deliberately). should be continued in children, particularly for
those with persisting auditory and neurological
abnormalities. Even in first-world settings, up to
50% of children and adolescents discharged after
bacterial meningitis are not assessed routinely in
outpatients.

Primary prevention
Antibodies directed against the capsular compo-
nents of Hib, S. pneumoniae and N. meningitidis are
especially important for protection. Polysaccharide–­
protein conjugate vaccines are commercially available
against:
• Hib
• S. pneumoniae
• N. meningitidis A, C, Y and W135.
Cases of Hib, pneumococcal and meningococcal sero-
group C meningitis have substantially decreased in
countries where routine implementation has occurred,
Fig. 12.3.3 Cranial computed tomogram of a 5-month-old boy
with pneumococcal meningitis who developed secondary fever
but following use of the 7-valent pneumococcal con-
and generalized convulsions on his seventh day in hospital. It jugate vaccine there has been evidence of replacement
shows subdural effusions over both frontal lobes. He received disease with non-vaccine serotypes (e.g. 19A) in some
anticonvulsant therapy and the effusion resolved spontaneously. countries (see Chapter 3.5).
407
 12.3 INFECTIONS

Chemoprophylaxis
Clinical example
Transmission of Hib and the meningococcus bacteria is
Mousaka, a 7-month-old female infant, by oral and respiratory secretions. Those at increased
presented after a 15-minute right-sided focal risk of infection are:
convulsion. She had been unwell for 12 hours • household members
with poor feeding. Her past medical history, • childcare contacts
growth and development were normal. Her primary • persons intimately exposed to oral secretions.
immunizations were up to date for age. There was no family
At-risk contacts of a case of meningococcal meningi­
history of convulsions. Her temperature was 39.3°C. She was
pale and very irritable when handled. There was no neck
tis should immediately receive oral rifampicin, 10 mg/kg
stiffness, bulging fontanelle or rash. No focal neurological (neonates 5 mg/kg) to a maximum of 600 mg, twice
signs were present. daily for 2 days. Alternatively a single dose of intra-
A lumbar puncture revealed turbid CSF. Numerous ­ muscular ceftriaxone (125 mg for children under 12
Gram-negative coccobacilli were seen in the CSF, and non- years of age, 250 mg for older children and adults) is
typeable H. influenzae was isolated. Mousaka's clinical given, or adults may receive 500 mg oral ciprofloxacin.
course was complicated by a secondary fever, a tense
The index case does not require further prophylaxis if
fontanelle with increasing head circumference, recurrent
focal convulsions, right hemiplegia, and persistently raised treatment has included a third-generation cephalospo-
peripheral white blood cell counts and C-reactive protein rin. Parents must be warned that if they, or their chil-
concentrations. Subdural pus was surgically drained after dren, are unwell immediate medical attention should
MRI demonstrated a left-sided subdural empyema. This was be sought.
followed by rapid clinical improvement. Subsequent testing Because of the increased risk of Hib infection
found no signs of underlying immunodeficiency. in young contacts, rifampicin 20 mg/kg (maximum
600 mg) as a single daily dose for 4 days is prescribed
for the index case of Hib meningitis and all household
contacts, if the child is aged less than 2 years or the
Less than 1% of children with febrile convulsions
household contacts include unimmunized children
have meningitis. Infants and those with complex
aged younger than 4 years of age. Unlike N. menin-
febrile convulsions are more likely to have bacterial
gitidis, single doses of ceftriaxone do not eradicate
meningitis. It is important that, following a febrile con-
Hib from the nasopharynx. Chemoprophylaxis is not
vulsion, children are evaluated carefully for signs of
required in cases of pneumococcal meningitis.
meningitis. The impact of conjugate vaccines means
that rarer causes of bacterial meningitis are relatively
more important. Although the incidence of non-­ Special circumstances
typeable H. influenzae meningitis has hardly changed,
Neonatal meningitis
in fully immunized children it has become a more
common cause of meningitis than Hib. Such children Neonates, particularly if premature, are at increased
often have an underlying medical condition and, com- risk of meningitis. The responsible pathogens are
pared with Hib infection, they have a more severe illness mainly:
with greater mortality. • S. agalactiae (group B streptococcus)
The monovalent C meningococcal conjugate vaccine • Escherichia coli and other Gram-negative bacilli
has dramatically reduced the incidence of C disease • L. monocytogenes.
in children and adolescents. The newer quadrivalent As in infants, the symptoms and signs of meningitis
conjugate, which also incorporates protection against are often non-specific. Approximately 5–15% of septic
serogroups A, Y and W135, is offered routinely in the neonates have concomitant meningitis. Initial therapy
USA and soon, perhaps, in other countries. It provides is with amoxicillin and cefotaxime until culture and
especial benefits when travelling to meningitis-prone antibiotic sensitivities are available. Antibiotic treat-
areas such as the sub-Saharan region. The success of ment should be for at least 2 weeks for Gram-positive
conjugate vaccines rests not only on inducing immu- meningitis, and 3 weeks for Gram-negative bacillary
nity in young children and establishing immunologi- cases.
cal memory but also on engendering herd immunity.
Challenges remain over the cost and delivery of these
Infants aged 1–3 months and the
vaccines to children in developing nations where they
immunocompromised
are most needed. The poorly immunogenic meningo-
coccal B capsular polysaccharide has necessitated a dif- These patients may have meningitis from pathogens
ferent approach; various outer membrane proteins have common to both neonates and older children. Empirical
been incorporated in new candidate meningococcal B therapy (usually with amoxicillin and cefotaxime) must
408
­vaccines based on ‘reverse vaccinology’ techniques. cover a wide range of pathogens. When the clinical
 MENINGITIS AND ENCEPHALITIS 12.3
c­ ircumstances (e.g. asplenia), CSF Gram stain and/or be in an intensive care unit (preferably paediatric) and
PCR testing suggest that S. pneumoniae is the causative includes aggressive fluid resuscitation to restore the
agent, vancomycin should replace amoxicillin. circulating blood volume, cardiac and respiratory sup-
port, and careful management of blood electrolyte
and glucose levels. Short-term corticosteroids may
Meningococcaemia
benefit those in septic shock. The use of other adjunc-
Although N. meningitidis serogroup A is associated tive therapies, such as recombinant human activated
with epidemics in sub-Saharan Africa, in industrial- protein C and monoclonal antibody to endotoxin, is
ized countries serogroups B, C and Y (at least in the not supported by results of clinical trials. Although
USA) are endemic, but serogroup B causes most spo- prehospital treatment with penicillin has reduced the
radic meningococcal disease. Large increases in disease proportion of culture-confirmed cases, the use of PCR
caused by meningococcal clones have been observed to detect meningococcal DNA in normally sterile flu-
over recent decades. ids has improved the sensitivity of diagnosis without
The majority of invasive meningococcal disease is materially affecting the specificity.
acute meningococcaemia, which is almost always sep-
ticaemic. Although about two-thirds have concomi-
Tuberculous meningitis
tant meningitis, signs of sepsis dominate the clinical
presentation and the necessary management. Half of This is most common in children younger than 5 years.
cases occur in children aged less than 5 years in whom The onset is gradual, with headache, malaise, fever and
serogroup B strains predominate. Cases may deterio- irritability, progressing over 1–2 weeks to drowsiness,
rate rapidly within a few hours, initially with: neck stiffness, convulsions, cranial nerve palsies and
• fevers, rigors coma. Typical CSF changes are listed in Table 12.3.1.
• severe pain in the limbs, abdomen or back There may be no history of infectious contact.
• vomiting, plus or minus headache Tuberculin skin testing (Mantoux) is often nega-
• mottled or pale skin, with cool extremities. tive and a chest X-ray abnormality is present in only
Additional non-specific signs in infants include: half of cases. Gastric aspirates, urine and CSF should
• fever, irritability or drowsiness be sent for culture and PCR, and some experts also
• grunting or moaning respirations. ­recommend that a sample of sputum be induced with
A rash is present, or develops during illness, in most hypertonic saline, usually performed by a physiother-
cases irrespective of age. Initially it may be a blanching apist wearing mask, gown and gloves. Cranial CT or
macular or maculopapular rash before evolving into the MRI may detect hydrocephalus and basilar meningeal
characteristic petechial or purpuric rash of meningococ- inflammation; basal ganglia infarction is a late radio-
caemia (Fig. 12.3.2). The clinical course can be rapidly graphic sign. Initial treatment is with isoniazid, rifam-
progressive, with the time from onset of fever until death picin and pyrazinamide. A fourth drug is added if there
as short as 12 hours. The overall mortality rate for inva- are concerns over potential drug resistance. High-dose
sive meningococcal disease is 10%, but the case fatality steroids are also used during the first weeks of therapy.
rate reaches 20% for fulminant forms of the disease.
Many of the clinical features of meningococcaemia
are provoked by antibiotics causing the release of cell
Clinical example
wall products which, in turn, activate proinflamma-
tory cytokines and complement; this leads to endothe- Tom, aged 14 years, had developed chills on
lial injury with capillary leak and loss of vasomotor the day of presentation and complained of
tone. The major cause of death in meningococcaemia pain in his head, neck and limbs. He rapidly
is circulatory collapse from capillary leak, intravascu- became confused, agitated and started to
lar volume depletion, vasodilatation and myocardial vomit. When seen by his family doctor, Tom was pale and
a faint red macular rash had appeared over his buttocks
failure. Haemodynamic collapse in combination with
and legs. A diagnosis of possible meningococcaemia was
disseminated intravascular coagulation (DIC) leads to made and Tom received 1.2 g penicillin intramuscularly
multiorgan dysfunction. before immediate transfer to hospital. On arrival he was
Treatment is urgent and is commenced immediately pale and shocked, was difficult to arouse, and had an
(preferably by the intravenous (IV) route, but intra- evolving purpuric rash. He received cefotaxime, aggressive
muscular acceptable) the diagnosis is suspected, and fluid resuscitation, inotropes and assisted ventilation. He
ideally after taking blood cultures. Penicillin G is the gradually improved and a lumbar puncture 2 days later
showed 150 white blood cells ×106/ L only. Although cultures
drug of choice, the recommended dose being 60 mg/kg
were sterile, PCR testing of whole blood collected upon
IV given 4-hourly. The patient is managed in respira- arrival at hospital confirmed meningococcal infection and
tory isolation during the first 24 hours of treatment. Tom completed a 5-day course of intravenous penicillin G. 409
Management of those with signs of septic shock should
 12.3 INFECTIONS

Recurrent meningitis cause 80–90% of identifiable cases. The onset is often

acute with:
This is uncommon and an underlying cause should be
• fever
sought:
• headache
• immunodeficiency (see Chapter 13.2)
• vomiting
• neuroanatomical defects: intracranial or
• neck or spine stiffness.
lumbosacral.
Abdominal pain and diarrhoea are common and
Consider neuroanatomical defects when enteric
occasionally a macular rash appears, suggesting an
­bacteria or Staphylococcus aureus are cultured from
enterovirus as the causative agent. The illness may be
the CSF. Cranial and spinal MRI, or high-­resolution
biphasic, with return of fever and neurological man-
CT of the temporal and frontal bones, may be
ifestations after an interlude. Signs of meningism
indicated.
indicate the need for LP. Typically, there is a CSF
­pleocytosis with normal to mildly raised protein and
normal glucose levels (see Table 12.3.1).
PCR testing of CSF specimens for enterovirus or
Aseptic and viral meningitis, and herpes simplex virus DNA have become important
infectious encephalitis diagnostic tools. Other disorders that may present in a
similar fashion include:
‘Aseptic’ meningitis is inflammation of the meninges, • partially treated bacterial meningitis
as shown by leukocytes in the CSF, in the absence of • tuberculous meningitis
bacteria. Viruses are the commonest cause of aseptic • cryptococcal meningitis
meningitis. Encephalitis is inflammation of the brain • Mycoplasma meningitis
with associated neurological symptoms. It is usually • cerebral abscess
due to infection, most commonly viruses, although • cerebral tumour.
an aetiological agent is not identified in many cases. A repeat LP or cerebral imaging may also be required
Immune-mediated encephalitides are also being rec- to clarify the diagnosis.
ognized increasingly in children. Box 12.3.1 lists Viral meningitis is usually a benign disease, and
common causes of infectious encephalitis and viral requires symptomatic treatment only. Complete recovery
meningitis. without sequelae is expected within a few days to weeks.

Viral meningitis Infectious encephalitis and myelitis

The absence of an altered sensorium and focal neu- Infectious agents may cause encephalitis directly, by
rological findings generally helps to distinguish viral invading the central nervous system, or indirectly,
meningitis from encephalitis. Non-polio enteroviruses by inducing proinflammatory responses or v­ asculitis

Box 12.3.1 Viruses and non-bacterial infecting agents that may commonly cause meningitis and encephalitis

Para- or post-infectious encephalitis without direct invasion • Other viruses – adenoviruses, measles, rubella, rotaviruses,
of the CNS rabies viruses, lyssavirus
• Measles, influenza, Mycoplasma pneumoniae, RSV, • Arbovirus (arthropod-borne virus) – e.g. flaviviruses and
parainfluenza viruses, Rickettsia, rubella, varicella, EBV, alphaviruses, such as Japanese encephalitis, West Nile
mumps, post-immunization encephalitis, Murray Valley encephalitis, Dengue virus,
Nipah virus
Meningitis and/or encephalitis with direct CNS infection • Bacteria – Haemophilus influenzae, Streptococcus
• Enteroviruses – ECHO, Coxsackie, enteroviruses and polio pneumomiae, Neisseria meningitidis, Listeria
viruses. These usually cause meningitis but can occasionally monocytogenes
cause encephalitis. EV71 is associated with demyelinating • Other agents – Toxoplasmosis gondii, Coxiella burnetii
disease
• HSV type 1 can cause focal (usually temporoparietal) Progressive encephalitis
encephalitis (HSV-1 or -2 can cause encephalitis in neonates) • For example, subacute sclerosing panencephalitis due to
• Mumps – usually meningitis, less often meningoencephalitis measles virus infection, HIV, or human prion disease
• Other herpes group viruses – human herpesvirus 6/7, EBV,
varicella, cytomegalovirus (neonates, immunocompromised)

CNS, central nervous system; EBV, Epstein–Barr virus; ECHO, Enteric Cytopathic Human Orphan; EV, enterovirus; HIV, human
410 immunodeficiency virus; HSV, herpes simplex virus; RSV, respiratory syncytial virus.
 MENINGITIS AND ENCEPHALITIS 12.3
in the brain during or after infection at other sites.
Viruses are the major known cause of infectious
encephalitis, although a confirmed aetiology is not
identified in many cases. Worldwide, vector-borne
viruses are becoming an important cause of infec-
tious encephalitis. Acute disseminated encephalomy-
elitis (ADEM) is a neurological syndrome associated
with white matter demyelination that is thought to
be immune-­ mediated after a variety of viral and
bacterial infections, or rarely immunization (see
Box 12.3.1). It is subacute in onset and usually pres-
ents without fever after a non-specific respiratory or
gastrointestinal illness. Fig. 12.3.4 T2-weighted axial magnetic resonance images.
Infectious encephalitis presents with an array of (A) A 6-year-old girl with HSV encephalitis (see text for clinical
details), which shows an increased signal in the right temporal
neurological signs:
lobe. (B) A 4-year-old boy with focal convulsions and dysphasia
• altered conscious state following a respiratory illness. The bilateral and asymmetrical
• confusion and disorientation multifocal increased signal in the white–grey junction and
• behaviour, personality or speech disturbance subcortical white matter is characteristic of acute disseminated
• generalized or focal convulsions encephalomyelitis.
• ataxia or other movement disorders
• headache, vomiting involvement of the basal ganglia, brainstem and cer-
• focal neurological deficits ebellum to a lesser extent. In contrast, ADEM is char-
• fever, or history of fever. acterized by multiple asymmetrical areas of increased
Meningism is frequently absent. The involvement of focal signal in the white matter of both hemispheres,
the spinal cord (transverse myelitis) may develop in basal ganglia, cerebellum and, on occasions, the spinal
isolation and can lead to flaccid paralysis, loss of ten- cord. Other treatable causes of acute encephalopathy
don reflexes, neurogenic bladder and a definable sen- should also be sought.
sory level. When it occurs, acute cord compression Initially, aciclovir is given in all cases of suspected
from a spinal epidural abscess or some other cause encephalitis until a diagnosis of HSV encephalitis can
must also be considered and excluded urgently by be excluded on clinical, radiological and PCR criteria.
MRI or CT myelography. Early initiation of appropriate antiviral therapy (e.g.
Causes of acute encephalitis may be suggested by: oseltamivir) should be also considered if influenza is
• the season suspected. Treatment of viral encephalitis and ADEM
• recent travel history is otherwise supportive, involving:
• prior personal or family illness • careful fluid and electrolyte management
• animal exposures or insect bites • control of convulsions
• drug and immunization history • monitoring for signs of raised intracranial pressure
• presence of lymphadenopathy, parotitis, rash or • circulatory support to maintain cerebral perfusion
pneumonia. • assisted ventilation for respiratory failure
Investigations to identify the aetiological agent include: • maintenance of nutrition.
• PCR of CSF, blood, respiratory secretions Corticosteroids should be considered when MRI
• viral culture of CSF, blood, respiratory secretions, shows striking enhancement of multifocal white mat-
faeces and urine ter lesions consistent with ADEM.
• serology. Almost 10% of children with encephalitis die, and
The CSF profile of encephalitis is outlined in long-term studies suggest that nearly half of the survivors
Table 12.3.1, although patients may have normal have neurological or educational disabilities. Young age,
CSF parameters. PCR analysis provides a rapid and coma, delayed presentation, high CSF protein and infec-
accurate diagnosis for a wide range of pathogens. tion with HSV or Mycoplasma pneumoniae are associated
Electroencephalographic (EEG) abnormalities are with a poor prognosis. However, patients can also make
seldom specific but may be helpful in herpes sim- an excellent recovery, even after prolonged coma.
plex virus (HSV) encephalitis. MRI is more sensitive
than cranial CT and helps differentiate encephalitis
Herpes simplex encephalitis
from ADEM (Fig. 12.3.4). MRI T2-weighted images
in viral encephalitis demonstrate one or more diffuse Herpes simplex virus causes a severe, sporadic focal
areas of hyperintensity involving the grey matter of the encephalitis. Outside the newborn period, individuals
411
cerebral cortex and the underlying white matter, with with defects in innate immunity such as a ­deficiency
 12.3 INFECTIONS

of signalling protein Unc-93B, are at increased risk of severe with fever, headache, vomiting, altered con-
HSV encephalitis. Treatment with the antiviral agent sciousness, ­convulsions, tremor and dystonia. Both
aciclovir reduces the mortality rate to below 20%. Japanese encephalitis and West Nile encephalitis
However, most survivors still have severe neurologi- may present with acute flaccid paralysis. The mor-
cal or behavioural sequelae. Neonatal herpes simplex tality rate for Japanese and Australian encephalitis is
encephalitis can be due to either HSV-1 or HSV-2, 20–30%, with 50% of survivors experiencing severe
whereas cases outside the neonatal period are almost neurological and intellectual sequelae. Vector control
exclusively caused by HSV-1. One-third of cases programmes and personal p ­ rotection are i­mportant
in older infants and children result from a p ­ rimary preventative measures, and there is a vaccine for
infection. Japanese encephalitis.
CSF PCR for HSV DNA is the diagnostic test of
choice. Although frontal and temporal lobe local-
Slow virus infection
ization is characteristic, PCR and MRI have shown
that the disease can be diffuse in neonates and young Some viruses can cause a subacute or chronic neurode-
­children. The course described in the clinical example generative disorder. The major example in ­childhood
is typical of HSV encephalitis. is subacute sclerosing panencephalitis, a rare late
­complication of measles, especially if measles occurs
early in life. Rubella is a less common cause. The ­disorder
is manifest by:
Clinical example • deterioration of behaviour, personality and intellect
• myoclonic convulsions
Rachael, aged 6 years, was hospitalized with
a 3-day history of fever, headache, intermittent
• motor disturbance.
confusion and progressive lethargy. On The onset is usually several years after measles. As
presentation she had several left-sided focal the disease progresses, spastic paresis, tremors, ath-
convulsions. Her temperature was 40.1°C; she was drowsy etosis and ataxia develop. The disease runs a vari-
with mild neck stiffness and left hemiparesis. able but progressive course and is usually fatal
Her CSF had 100 × 106/L lymphocytes. The protein content within 2 years. Initially, the EEG shows a typical
of the CSF was mildly raised and the glucose concentration ‘suppression-burst pattern’. The typical clinical
was normal. HSV encephalitis was suspected and aciclovir
­picture and high-titre CSF measles antibody estab-
(500 mg/m2 IV 8-hourly) was started. Phenytoin controlled
Rachael's convulsions. An EEG demonstrated periodic lish the diagnosis.
discharges localized to the right temporal lobe, and MRI
showed increased signal in T2-weighted images of this
region (see Fig. 12.3.4A). PCR of the CSF was positive for
HSV-1 DNA. Practical points
Rachael gradually improved over several days, but was
still febrile after 2 weeks of treatment. A repeat lumbar
puncture at 3 weeks revealed persisting HSV-1 DNA. Aciclovir • Meningitis and encephalitis should always be considered
was continued for a total of 4 weeks. Her fever settled, but in ill-appearing infants and children but impaired conscious
the hemiparesis remained and she was left with major state or altered behaviour especially suggests encephalitis.
behaviour and learning disabilities. • Unless contraindicated by signs of raised intracranial
pressure, haemodynamic instability or DIC, lumbar
puncture should be performed as part of the diagnostic
work-up to establish the diagnosis and to help identify the
causative organism.
Arthropod-borne encephalitis viruses
• Control of infection, shock, electrolyte imbalance and
Viruses transmitted to humans by biting arthropods convulsions are the immediate treatment goals for
(mainly mosquitoes and ticks) are a major cause bacterial meningitis. Steroids at disease onset are often
indicated.
of encephalitis. Flaviviruses are the most common
• Bacterial meningitis that is recurrent, caused by an
and include Japanese encephalitis (Asia), West Nile unusual pathogen or the consequence of vaccine failure
encephalitis (Africa, Middle East, North America) in a fully vaccinated child raises the possibility of an
and Australian encephalitis (Australia). West Nile underlying disorder, including immunodeficiency or a
encephalitis has recently become established in North neuroanatomical defect.
America following its introduction into New York • The absence of an altered sensorium and focal
in 1999, and Japanese encephalitis has expanded neurological findings helps distinguish viral meningitis
from acute encephalitis.
throughout Asia and into Australia.
• Antiviral therapy with aciclovir should be commenced if
Most infections are mild or subclinical, with there are clinical signs of encephalitis until herpes simplex
less than 1% developing neurological symptoms. virus can be excluded.
412
However, when symptomatic, the disease is often
 Infections in tropical and 12.4
developing countries
Stephen Graham, David Brewster

Most of the world's population lives in the tropics and • MDG 4: Reduce by two-thirds the mortality rate
subtropics in developing countries where health out- among children under 5 years of age
comes are much poorer than in developed countries such • MDG 6: Halt and begin to reverse the spread of
as Australia or New Zealand. Infections are a major cause HIV/AIDS and the incidence of malaria and other
of childhood disease in these settings and an important diseases
contributor to overall child mortality. Rather than geog- • MDG 7: Reduce by half the proportion of people
raphy and climate, however, it is socioeconomic factors without sustainable access to safe drinking water
that have most influence on susceptibility to infections, and basic sanitation.
leading to high mortality. These factors are highlighted Although these MDGs are unlikely to be achieved in
in Chapter 1.2: Child health in a global context. They many high-mortality settings, they have provided an
include low levels of female literacy, lack of access to important focus and substantial progress has been
clean water, poor sanitation and hygiene, nutritional made in the last decade. Important child health pro-
insecurity, and inadequate health-care resources, includ- grammes that reduce the burden of infectious disease
ing human resources. The main causes of ­morbidity and include the Expanded Programme on Immunization
mortality are not exotic tropical diseases but common (EPI), breastfeeding promotion and infectious disease
conditions such as pneumonia, malaria, diarrhoea, sep- control programmes. Immunization against measles
sis and human immunodeficiency virus (HIV) infection and polio, for example, has been highly effective and
caused by common pathogens. highly cost-effective. EPI continues to be expanded
The main seasonal influences in the tropics are with the addition of Haemophilus influenzae type b
the rainy season, when there is increased exposure to (Hib) conjugate vaccine and hepatitis B vaccine to
pathogens (e.g. malaria and diarrhoea), and the hun- the schedules of many low-income countries in recent
gry season, when there is food insecurity. These sea- years. Vaccines against Streptococcus pneumoniae
sons tend to coincide resulting in a strong seasonal (pneumococcus) and rotavirus are the likely next
influence on the prevalence of childhood malnutri- candidates for wider implementation in low-income
tion. Poor nutrition is an important contributor to the countries.
high childhood mortality rate from infectious diseases Gains are also being made by disease control pro-
in the developing world, including intrauterine growth grammes using a combination of reducing transmis-
retardation resulting in low birth weight. Over half sion of infections and more effective treatment. Three
of child deaths are due to the potentiating effect of infections that have received particular attention and
malnutrition on infections. Malnutrition can also be a funding support to national control programmes are
consequence of recurrent or chronic infections. HIV, tuberculosis (TB) and malaria. HIV has had a
The purpose of this chapter is to give an overview profound impact on child morbidity and mortality
of common infections in tropical regions, including in high HIV-endemic countries. Strategies that lead
Australia, and developing countries. It is not possi- to a reduction in antenatal HIV prevalence and pre-
ble to discuss in detail the many disorders endemic to vent mother-to-child transmission of HIV will reduce
these areas. The focus of the chapter is on the common HIV-related child mortality as well as reduce the bur-
infectious causes of childhood disease, with an empha- den on child health-care services. Antiretroviral treat-
sis on public health and prevention. ment of the mother during and after pregnancy can
reduce the risk of HIV transmission to the newborn
to less than 1%, and make breastfeeding a feasible
option. The HIV epidemic has also increased the
An overview prevalence of TB, including drug-resistant infection.
In malaria-endemic settings, children and pregnant
Prevention and disease control
women are particularly susceptible to severe disease.
Three of the seven Millennium Development Goals Malaria control is being improved with increased
(MDGs) set in 2000 for 2015 have direct relevance to usage of insecticide-treated bed-nets and more effec-
413
childhood infections: tive first-line therapy.
 12.4 INFECTIONS

Integrating and improving clinical horizontal approach aims to avoid the limitations of
case management a vertical single-disease approach. This will hopefully
provide improved patient care as well as recognition
The usual clinical presentations of infections in trop-
of the importance of integration between national
ical and developing countries are as one or more of
disease control programmes. Evaluation studies of
typical clinical scenarios (e.g. respiratory distress,
the quality of care at hospitals and health centres in
diarrhoea with dehydration, sepsis, anaemia or febrile
the developing world consistently report major defi-
seizures). There is clinical overlap between disease
­
ciencies in triage, emergency care, monitoring, drug
groups, a range of possible causes including the pos-
availability, staffing levels and the use of protocols for
sibility of co-infections with more than one pathogen,
clinical care. On the other hand, implementation stud-
and the need for health workers to assess and promptly
ies show what can be achieved when such deficiencies
treat the most likely infectious causes, often empiri-
are addressed, even with limited resources. In 2005,
cally on the basis of clinical assessment alone. Further,
WHO published a pocketbook of guidelines for the
these challenges are particularly common in those at
management of common illnesses in health facilities
greatest risk of death, such as the young infant, the
with limited resources.
malnourished or the HIV-infected.
The World Health Organization (WHO) has devel-
oped treatment protocols for the common diseases,
Travel bug
based upon simple clinical indicators, that can be
assessed by health workers with minimal training. The The ease of air travel and the frequency of people of
Integrated Management of Childhood Illness (IMCI) all ages visiting the tropics have made it essential for
initiative aims to reduce child morbidity and mortal- the student and practising doctor to have an appre-
ity in developing countries by improved management ciation of tropical medicine. Migration, includ-
of common illnesses (Box 12.4.1). This integrated ing for humanitarian reasons (refugees), makes it
almost certain that some will carry disease unde-
tected by the medical screening process. The major-
Box 12.4.1 Diagnostic classifications and clinical signs
for referral to hospital ity of children with TB infection or disease identified
in Australia have recently immigrated from or spent
Young infants (0–2 months) time in TB-endemic countries. It is of the greatest
1. Possible serious bacterial infection – seizures, tachypnoea importance that a history of overseas travel is sought
(≥ 60 breaths/min), severe chest indrawing, nasal in any unusual disease presentation, particularly a
flaring, grunting, bulging fontanel, perforated eardrum, febrile illness.
omphalitis, fever or hypothermia (≥ 38°C or < 30°C), many
or severe skin pustules, difficult to wake up or cannot be
calmed within 1 hour
2. Diarrhoea with severe dehydration – lethargic or
unconscious, sunken eyes and skin pinch goes back very Invasive bacterial disease
slowly
3. Severe persistent diarrhoea (≥ 14 days) Serious bacterial infections are much more common in
4. Not able to feed children in tropical and developing countries than in
temperate and developed countries, and 25% or more
Children (2 months to 5 years) of children dying in hospital have bacteraemia. Studies
1. General danger signs – not able to drink or breastfeed, from tropical Africa in infants and children hospital-
vomits everything, convulsions, or lethargic or unconscious
ized with a wide range of presentations, including
2. Severe febrile disease – fever (rectal temperature ≥ 38°C)
and any general danger sign, or stiff neck
severe malaria, have documented that invasive bacte-
3. Severe pneumonia – cough or difficult breathing and rial infections are common and associated with a high
any general danger sign, chest indrawing, or stridor case-fatality rate.
when calm Common clinical presentations include:
4. Diarrhoea with severe dehydration – abnormally sleepy • pneumonia
or difficult to wake up, sunken eyes, not able to drink or • septicaemia with or without focus
drinking poorly, skin pinch goes back very slowly
5. Severe persistent diarrhoea (≥ 14 days) with dehydration –
• meningitis
restless/irritable, sunken eyes and skin pinch goes back • bone and joint sepsis
slowly • soft tissue sepsis (e.g. abscess, cellulitis, pyomyositis).
6. Severe malnutrition or severe anaemia – visible severe Important risk factors for disease incidence and/or
wasting, oedema of both feet, or severe palmar pallor poor outcome include:
• Age: particularly common in infants and young
Adapted from World Health Organization Integrated children. Neonatal sepsis is a major contributor to
414 Management of Childhood Illness.
the high neonatal mortality in developing countries.
 Infections in tropical and developing countries 12.4
• Co-morbidities: such as malnutrition, HIV Salmonella in Africa. This poses a management chal-
infection, measles or sickle cell disease. lenge in settings where availability and choice of anti-
• Late presentation to health services: common in biotics is limited. Third-generation cephalosporins
resource-limited settings. (e.g. ceftriaxone) or quinolones (e.g. ciprofloxacin)
Pneumococcus and Hib have been the commonest are usually effective alternatives, although quinolone
causes of invasive bacterial disease in children beyond resistance is increasing in Asia.
the neonatal age group. The increasing uptake of Hib Group A streptococcus is also important in devel-
conjugate vaccine into EPI schedules has resulted in a oping countries, not as a major cause of invasive dis-
dramatic reduction in the burden of invasive disease ease in children, but more as a cause of pharyngitis
due to Hib, including meningitis. Pneumococcus is the and skin sepsis in communities where rheumatic heart
commonest cause of bacterial pneumonia and menin- disease and acute glomerulonephritis are common and
gitis in developing countries. Uptake of the pneumo- cause significant morbidity.
coccal conjugate vaccine has been limited in low- and
middle-income countries due to cost constraints.
However, wider implementation of a vaccine that cov-
ers the majority of the serotypes causing disease is Viruses
high on the global public health agenda, such as the Finally, it is important to recognize that viruses are
GAVI Alliance. a common cause of lower respiratory tract infection
Other causes of invasive bacterial disease include and diarrhoea in developing countries. The causes
the Gram-negative enteric pathogens (e.g. Salmonella are similar to those in developed countries, but with
spp, Escherichia coli, Klebsiella pneumoniae) and less marked seasonal variation in the tropics. With
Staphylococcus aureus. They are important causes in improved socioeconomic conditions in communi-
the young including neonates, the malnourished and ties in the Asia–Pacific region, viruses are responsible
HIV-infected. Resistance of Gram-negative bacilli to for a larger proportion of disease than bacteria, and
multiple antibiotics is common. S. aureus is an impor- virus-induced airway disease (e.g. acute bronchiolitis,
tant cause of bone, joint and soft tissue sepsis, as well asthma) is increasingly common. This has important
as of pneumonia in association with measles and HIV implications for clinical management guidelines such
infection. as IMCI protocols, and appropriate use of antibiotics.
Salmonella infections occur worldwide but are par-
ticularly important in tropical and developing coun-
tries. Enteric or typhoid fever is due to Salmonella
Practical points
typhi and S. paratyphi. Typhoid fever is confined to
humans, and occurs where standards of hygiene, water
Bacterial infections
supply and sanitation are poor. The typical presenta-
• Serious bacterial infections are common in children in
tion is fever, malaise, headache, abdominal discom- developing countries and associated with a high case-
fort, and sometimes vomiting and diarrhoea. In severe fatality rate.
disease, toxaemia is profound and complications such • Important causes include pneumococcus, Haemophilus
as small bowel perforation can occur in older chil- influenzae type b, multiresistant Enterobacteriaceae (e.g.
dren. This typical presentation of typhoid fever is Salmonella, E. coli ) and Staphylococcus aureus.
mainly in children of school age. In younger children, • IMCI guidelines aim to help primary care health workers to
identify children needing antibiotic treatment.
S. typhi often presents with a non-specific febrile ill-
ness. Invasive disease due to S. typhi is particularly
common in Asia and some Pacific Islands.
There are over 2000 serotypes of non-typhoidal sal-
monellae. In developed countries, the usual presen-
tation is acute gastroenteritis due to food poisoning.
Tuberculosis
In malaria-endemic regions of Africa, non-typhoidal It is estimated that a third of the world's population is
salmonellae commonly cause severe invasive disease infected with Mycobacterium tuberculosis and almost
in children, including meningitis in infants, especially all live in developing countries. Most of these people
during the rainy season, presenting as a non-specific have latent TB infection and will not develop TB dis-
febrile illness with a high case-fatality rate of 20–25%. ease. However, many do develop disease, most com-
Consistent clinical associations include young age, monly pulmonary tuberculosis (PTB), and infection
malaria, anaemia, malnutrition and HIV infection. is readily transmitted through coughing. Children are
Antibiotic resistance to ampicillin, co-trimoxazole usually infected by contact with an adult or older child
and chloramphenicol (multidrug resistance) is now with sputum smear-positive PTB. Generally, children
415
common for S. typhi in Asia and for non-typhoidal under 8–10 years of age do not develop pulmonary
 12.4 INFECTIONS

cavities; thus they have pauci-bacillary disease which Children with TB receive similar regimens to
is not considered contagious, and do not require adults depending on the type of disease, but at
isolation. higher dosages in milligrams per kilogram (mg/kg).
If a child is infected, the risk of developing symp- Children tolerate anti-TB therapy very well and seri-
tomatic TB disease depends on: ous adverse events are rare. HIV-infected children
• Age: infants and children aged less than 3 years with TB require co-trimoxazole preventative therapy
have a much higher risk of disease than older and antiretroviral therapy (ART) in addition to anti-
children, and a high risk of severe disseminated TB therapy. ART improves outcome in HIV-infected
forms of disease such as TB meningitis. children treated for TB disease, and is generally
• HIV co-infection: HIV-infected children are at commenced as soon as TB treatment is tolerated.
increased risk of exposure/infection because they Although there is a risk of immune reconstitution
live in families with TB/HIV, and at much higher inflammatory syndrome (IRIS) in the severely immuno-
risk of disease than HIV-uninfected. Antiretroviral suppressed child, early HIV treatment appears not to
therapy (ART) reduces the risk of developing increase mortality.
disease following infection in HIV-infected children. Children who are close household contacts of
• Other co-morbidities: severe malnutrition, recent source cases with TB, especially those with sputum
measles or other conditions associated with smear-positive disease, should be screened. Those with
immunosuppression. symptoms suggestive of TB disease should be assessed
• Bacille Calmette–Guérin (BCG) vaccination: and investigated as appropriate for possible TB dis-
given to newborns in TB-endemic countries, this ease. Asymptomatic children at risk of developing
provides some protection against severe forms of disease after exposure: any child contact aged less than
TB in young children, such as TB meningitis and 5 years, or an HIV-infected child of any age, should
miliary TB. It is recommended that BCG is not be given preventative therapy following exclusion of
given to HIV-infected infants because of the risk of active disease.
disseminated BCG infection.
The commonest form of TB in children is PTB (about
75% of cases) and most cases present in young chil- Practical points
dren, as do TB meningitis and miliary TB. Other
forms of extrapulmonary TB that tend to present in Tuberculosis
older children include TB adenitis (cervical TB is com- • Childhood TB is common in countries with a high incidence
monest), TB pleural effusion, TB ascites or spinal TB. of sputum smear-positive TB in the community.
Common clinical features associated with a diagno- • Diagnosis is usually clinical, and important features in
sis of TB include a persistent cough not responding children include persistence of symptoms, history of
contact with a source case, age and nutritional status of
to broad-spectrum antibiotics, weight loss or failure
the child, and HIV infection status.
to thrive, persistent fever, and fatigue or reduced play-
fulness. A history of contact with an infectious case
should be carefully sought, and is often positive in
young children. The diagnosis of PTB is usually based
on clinical and radiological features because young
children have pauci-bacillary disease and have dif-
Malaria
ficulty in providing sputum for microscopy. Sputum Malaria is a major global health problem, with an
smear-positive disease is not unusual in older children estimated 50% of the world's population in 88 coun-
and adolescents, but the yield from gastric aspirates or tries in 2010 exposed to various degrees of risk, almost
induced sputum in young children is very low. Thus, exclusively in tropical regions. In holo-endemic set-
TB diagnosis in young children remains one of the tings, children are the most vulnerable group for severe
most challenging issues in paediatric practice in tropi- disease and death due to malaria. Immunity to severe
cal and developing countries with HIV and malnutri- disease is acquired with age. Pregnant women are also
tion, and diagnostic algorithms perform poorly. vulnerable in the third trimester of pregnancy and
An HIV test should be routine in assessment of chil- malaria in pregnancy is an important cause of low
dren with suspected TB. This is because HIV infection birth weight babies.
increases risk of TB disease and is associated with a Severe malaria in children:
poorer outcome. Further, the diagnosis of TB in chil- • is caused mainly by Plasmodium falciparum
dren with chronic respiratory symptoms can be more infection
challenging in HIV-infected children because there are • is most common during the rainy season
416 other forms of HIV-related lung disease to consider such • presents mainly as cerebral malaria or severe
as lymphoid interstitial pneumonitis and bronchiectasis. anaemia, or as a combination of both.
 Infections in tropical and developing countries 12.4
Thick blood film microscopy remains the ‘gold stan- • Supportive care: management of hypoglycaemia
dard’ for malaria diagnosis. However, parasitaemia is and seizures.
not necessarily synonymous with disease. In 1000 chil- • Blood transfusion: the decision to transfuse is
dren bitten by an infected mosquito there might be 400 based on severity of anaemia, evidence of cardiac
asymptomatic infections, 200 cases of clinical malaria failure and degree of parasitaemia.
(febrile illness), 12 cases of severe malaria and 1 death. • Antibiotics should be considered in severe cases
Rapid diagnostic tests that detect Plasmodium-specific as bacteraemia is common and associated with
antigens are now available, but are expensive and not a worse outcome. Severe malarial anaemia is
species specific. associated with invasive disease due to non-
Cerebral malaria is characterized by acute encepha- typhoidal Salmonella.
lopathy with coma (Table 12.4.1) and often with seizures, The most effective malaria control measures available
and presents in older children (mean age 3–4 years) to clinicians are insecticide-treated bed-nets (ITNs)
in areas with seasonal and moderate transmission. In (e.g. permethrin), personal protection with mosquito
Africa, cerebral malaria has a mortality of around repellents (e.g. DEET – N,N-diethyl-meta-toluamide)
10% and significant neurological sequelae can occur and effective malaria treatment. In systematic reviews,
in survivors. The main features of severe disease with the protective efficacy of ITNs and indoor-residual
poor outcome are prolonged unresponsive coma, deep spraying on reducing the malaria-attributable mortal-
breathing, decerebrate posturing and hypoglycaemia. ity rate in children aged under 5 years in P. falciparum
Severe malarial anaemia is most frequent in younger settings is 55% (range of 49–61%). WHO has formu-
children (mean 1–2 years) in regions with high malar- lated a global strategic plan (2005–2015) called Roll
ial transmission. Severe malarial anaemia presents to Back Malaria. Its priorities include:
hospital with severe pallor and often respiratory dis- • locally appropriate vector control methods
tress due to lactic acidosis and/or heart failure from an (e.g. ITNs)
abrupt drop in haemoglobin levels. • prompt diagnosis and treatment with effective
Treatment for malaria depends on severity and may anti-malarial medicines (e.g. ACT)
include: • pregnant women receive intermittent preventative
• Anti-malarial therapy: treatment.
• non-severe disease: the most widely recommended Although there have been major international efforts
treatment is currently artemether combination to develop malaria vaccines, an effective, affordable
therapy (ACT), because resistance to chloroquine vaccine is at least a decade away from implementation.
and sulfadoxine–pyrimethamine has emerged in
many parts of the world
• severe disease: parenteral quinine or artesunate (in Practical points
south-east Asia where there is quinine resistance).
• Exclude other diagnoses: for example, meningitis, Malaria
because there is overlap with the clinical diagnosis • Malaria affects 50% of the world's population in 88
of cerebral malaria. countries.
• Important malaria control activities include the use
of insecticide-treated bed-nets and effective first-line
treatment.
Table 12.4.1 Modified Blantyre Coma Score as used • Clinical algorithms for malaria diagnosis perform poorly,
for cerebral malaria so thick blood film or rapid diagnostic tests are important
diagnostic tools.
Score Responses to painful fingernail
• Cerebral malaria and malarial anaemia are the two forms
and sternal pressure of severe falciparum malaria in children.
0 No response or decerebrate/decorticate • Parenteral artesunate or quinine is the drug of choice for
or opisthotonic postures severe malaria.

1 Non-specific response (e.g. moans or moves)

2 Withdraws the limb Dengue virus infection

3 Localizes the painful stimulus A number of viruses are capable of producing
haemorrhagic disease in humans. They are mainly
­
4 Responds and cries momentarily but relapses arthropod-borne, the most common vectors being
into coma
ticks and mosquitoes. Dengue is the most widespread,
vector-borne, viral infection in humans, with 50–100
5 Normal or fully conscious 417
million cases annually, being particularly common in
 12.4 INFECTIONS

tropical countries where the mosquito vector Aedes immune response in the pathogenesis of severe disease
aegypti is present. Dengue is a leading cause of child- and complicating vaccine development. Epidemics can
hood mortality in Asia and South America, and is be contained only by vector control until a vaccine is
the most rapidly spreading and important arbovi- available, hopefully in the near future.
ral disease in the world with a geographical distribu-
tion of more than 100 countries. Most dengue cases
are sporadic, but dengue is endemic in south-east
Asia and recent epidemics have occurred in the Asia-
Diarrhoeal disease
Pacific region (e.g. East Timor, Fiji, New Caledonia). Diarrhoea is a major cause of morbidity and mortal-
The incubation period is 2–7 days and asymptomatic ity in children in developing countries. Important envi-
infections are common. ronmental, socioeconomic and host risk factors for
The clinical features are abrupt onset of high fever infection and severe disease are well known, and have
with generalized aches and pains, and a macular skin already been mentioned in the introduction. Similar
eruption. The influenza-like illness lasts 2–6 days and to child pneumonia, there is a wide range of possible
then may relapse a day or two later with fever and aetiological agents that include bacteria, viruses and
rash, followed by fatigue for several weeks. Severe den- protozoa, and the relative importance of each of these
gue is characterized by the two syndromes: varies between regions and populations. The princi-
• Dengue haemorrhagic fever (DHF): a petechial ples of management are similar to those outlined in
rash appears on about the third day, with bleeding Chapter 20.2. This chapter will briefly highlight a few
from the gums, nose, gastrointestinal tract and issues that are particularly relevant to management of
venepuncture sites. After the initial phase as fever children with diarrhoea in developing countries.
begins to subside, signs of circulatory failure Diarrhoea is generally divided into three categories
appear, with restlessness, pallor, diaphoresis and for clinical management purposes:
cool peripheries. T-cell activation with a rapid • Acute watery: the commonest form, often seasonal.
increase in cytokines and chemical mediators Cholera and enterotoxigenic E. coli are important
leads to malfunction of vascular endothelial and causes of severe dehydrating diarrhoea in some
haemocoagulation systems. Typical laboratory regions. Viruses also important worldwide,
findings include thrombocytopenia, raised especially rotavirus. Effective fluid management
haematocrit, increased liver enzymes and abnormal of dehydration and maintenance is critical. The
coagulation test results. widespread use of pre-packaged oral rehydration
• Dengue shock syndrome (DSS): shock results from solution has had a major impact in reducing
marked plasma leakage due to a diffuse vasculitis diarrhoea-related mortality in children, particularly
often with features of disseminated intravascular from dehydration and hypokalaemia.
coagulation (DIC). It usually progresses from • Acute bloody (or dysentery): usually due to invasive
haemorrhagic fever, but some develop signs of bacterial pathogens such as Shigella dysenteriae.
shock earlier in the illness. Antibiotics are indicated in the acute phase, in
The management of dengue fever is symptomatic and addition to fluid management.
supportive: • Persistent diarrhoea: may follow the presentation
• circulatory support – adequate fluid intake, the use of either of the above. More common in
of plasma expanders malnourished or HIV-infected children – and may
• replacement of coagulation factors lead to malnutrition by persistent malabsorption.
• careful clinical monitoring. Nutritional support is very important to promote
Most children will recover and proper management of catch-up growth.
severe disease is crucial for reducing case-fatality rates, Nutrition is important for recovery from acute diar-
but a mortality rate of 2% persists, even in sophisti- rhoea. Children with diarrhoea should continue to
cated centres. feed with normal diet to facilitate recovery. Zinc sup-
It is still not clear why some children with dengue plementation for 10–14 days significantly reduces the
progress to shock or haemorrhagic syndromes, but the duration of diarrhoea and time to recovery.
key immunopathological mechanisms are viral strain No particular pathogen is associated with persis-
virulence and host immune responses, which augment tent diarrhoea in children under 5 years in low- and
the severity of infection. A notable risk factor for ­middle-income countries, although enteropathogenic
DHF is the existence of heterotypic dengue virus anti- E. coli is the only organism found in over 10% of cases.
bodies, present because the host has previously been Pathogens detected in children with persistent diar-
infected with a different strain of dengue virus. These rhoea may not necessarily be the cause of the illness,
antibodies are associated with increased viraemia in as up to 43% of non-diarrhoeal controls have at least
418
second infections, indicating the importance of the one organism isolated from stool. There is therefore
 Infections in tropical and developing countries 12.4
no evidence to justify routine antimicrobial use for stool microscopy on 1.5 million people, found a preva-
children with persistent diarrhoea of unknown cause. lence of 63%, of whom 43% had multiple parasites.
Dietary management of carbohydrate intolerance is The five most common parasites were Ascaris lumbri­
important, particularly in poor hygiene settings and coides (47%), Enterobius vermicularis (26%), Trichuris
with HIV-infected infants. trichiura (19%), Giardia lamblia (2.5%) and Entamoeba
In terms of diarrhoeal disease control, the key inter- histolytica (0.9%). This compares to prevalence esti-
ventions of proven effectiveness are handwashing with mates in sub-Saharan African schoolchildren of 32%
soap and water, improved water quality and access, for hookworms, 30% for Ascaris and Trichuris, and
and breastfeeding promotion. Children living in poor 14% for Schistosoma mansoni.
hygiene circumstances or with HIV infection are likely
to be affected by tropical or environmental enteropa-
Giardiasis
thy with partial villous atrophy of the small intestinal
mucosa, mucosal T-cell activation and crypt hyperpla- G. lamblia is one of the most common parasitic infections
sia. Indigenous Australians living in remote communi- in humans, with a prevalence of 20–30% in many devel-
ties have particularly high rates of enteropathy, and a oping countries, although it is also common in developed
superimposed enteric infection with E. coli, rotavirus, countries. The clinical manifestations of Giardia vary
Cryptosporidium or Strongyloides results in complete from asymptomatic passage of cysts to chronic diar-
villous atrophy with lactose intolerance, hypokalaemia, rhoea with malabsorption and weight loss. The usual
acidosis and dehydration. Tropical enteropathy also clinical syndrome is characterized by watery diarrhoea,
appears to contribute significantly to growth failure in foul-smelling stools, bloating and abdominal cramps.
young children unresponsive to dietary interventions, Only about half of patients develop symptoms following
and may also contribute to iron deficiency anaemia. ingestion of cysts. The course is frequently prolonged and
some go on to develop syndromes of chronic diarrhoea
or frequent relapses. Children in the developing world
Practical points with chronic diarrhoea and malnutrition often have giar-
diasis but are also co-infected with other enteric patho-
gens. The diagnosis relies upon stool microscopy finding
Diarrhoea
trophozoites or cysts. Presumptive treatment with tinida-
• Acute diarrhoea is very common and, due to a wide range
of pathogens, variable between regions. zole or metronidazole for children with persistent diar-
• Effective management of dehydration is extremely rhoea is common practice. Giardia is waterborne and
important to avoid deaths, irrespective of the cause. cysts are highly resistant to chlorine and ozone, so filtra-
• Acute bloody diarrhoea or dysentery is usually due to tion provides the best protection against transmission.
invasive bacteria and antibiotics are indicated.
• Continued feeding and zinc supplementation improves
recovery from acute diarrhoea. Amoebiasis
• The management of persistent diarrhoea can be
complicated and nutritional support is important in Although this organism is commonly found in stools
recovery. in children in the tropics, recent molecular and immu-
nological techniques have demonstrated two distinct
species of Entamoeba that are morphologically identi-
cal. E. histolytica is pathogenic, causing symptomatic
disease in 10% of infections, whereas E. dispar causes
Parasitic infections only asymptomatic colonization. Abdominal discom-
Human parasites are classified into five major fort may be the only symptom of amoebiasis, but an
divisions: acute attack may provoke severe diarrhoea, cramps,
• Protozoa (e.g. amoebae, sporozoans) tenesmus and toxaemia, with stools containing blood
• Platyhelminths (cestodes, trematodes) and mucus but little pus. Amoebic liver abscess, a well-
• Acanthocephala (thorny-headed worms) known complication in adults, is rare in childhood.
• Nematodes (roundworms) Risk factors for invasive disease are interaction with
• Arthropods (spiders, ticks). bacterial flora, host genetic susceptibility, malnutri-
Geohelminths are a subgroup of soil-transmitted tion, male sex, young age and immunodeficiency.
intestinal nematodes such as Strongyloides, hook-
worm, Ascaris and Trichuris (Table 12.4.2). The WHO
Schistosomiasis (bilharzia)
estimates that some 3.5 billion people are infected by
intestinal parasitic and protozoan infections, and that There are seven human species of this trematode,
450 million have disease, the majority being children. including Schistosoma haematobium, which affects
419
In China, for example, a nationwide survey, including the renal tract, and S. mansoni, which affects the
420

12.4
INFECTIONS
Table 12.4.2 Common intestinal parasites

Infection Other name Symptoms Transmission Treatment of choice Alternative treatments

1. Protozoa
Entamoeba histolytica Amoebiasis Dysentery Faecal–oral Metronidazole
Entamoeba dispar – Asymptomatic Faecal–oral Nil
Giardia lamblia Giardiasis Chronic diarrhoea, or malabsorption Faecal–oral Tinidazole Metronidazole or nitazoxanide
Cryptosporidium parvum Cryptosporidiosis Persistent diarrhoea Faecal–oral Nitazoxanide*
Cyclospora cayetanensis Cyclosporiasis Diarrhoea Faecal–oral Co-trimoxazole
Isospora belli Isosporiasis Diarrhoea with AIDS Faecal–oral Co-trimoxazole

2. Nematodes
Ascaris lumbricoides Roundworm Intestinal obstruction Faecal–oral Albendazole† Levamisole, pyrantel
Enterobius vermicularis Pinworm/threadworm Nocturnal anal pruritus Faecal–oral Albendazole Levamisole, pyrantel
Ancylostoma duodenale Hookworm Iron deficiency anaemia Percutaneous Albendazole Levamisole, pyrantel
Necator americanus Hookworm Iron deficiency anaemia Percutaneous Albendazole Levamisole, pyrantel
Strongyloides stercoralis Strongyloidiasis Diarrhoea Percutaneous Ivermectin Albendazole
Trichuris trichiura Whipworm/trichuriasis Dysentery, rectal prolapse Faecal–oral Albendazole Levamisole, pyrantel

3. Cestodes
Hymenolepis nana Dwarf tapeworm Asymptomatic Faecal–oral Nitazoxanide* Praziquantel

4. Trematodes
Schistosoma mansoni Bilharzia Melaena/portal hypertension Percutaneous Praziquantel Oxamniquine
Fasciolopsis buski Giant intestinal fluke Percutaneous Praziquantel

* Where treatment is indicated. Note that nitazoxanide has not been found to be effective in human immunodeficieny virus (HIV)-infected children with cryptosporidiosis.
†
Or mebendazole.
 Infections in tropical and developing countries 12.4
g­ astrointestinal tract. It has been estimated that 220 The most common clinical feature of ascariasis is
million people are infected by schistosomiasis in 74 intestinal obstruction from a bolus of worms, which
countries and that 20 million have severe disease. Eggs occurs in 0.2% of infections in children but accounts
of S. mansoni or S. haematobium are passed in the fae- for 72% of all complications of Ascaris infection.
ces or urine respectively. They hatch in warm water Surgical management can invariably be avoided with
and the ciliated larvae penetrate freshwater snails, pro- experience with this syndrome, using daily nasogas-
ducing thousands of tiny cercariae. These penetrate tric administration of anthelminthics with support-
human skin in water, enter peripheral lymphatics or ive therapy until the bolus is passed. Worms are often
veins, and are carried via the lung to mature in portal vomited or passed in stools on presentation of sick
or vesical vessels. Adult worms may survive 5 years or children. The diagnosis is based upon identification of
longer, producing eggs that cause granuloma forma- the characteristic eggs on microscopy of stool or iden-
tion in bowel, liver or bladder. Most infections are light tification of the adult worm passed spontaneously or
and asymptomatic. However, the host's inflammatory after treatment. Eggs are plentiful in faeces, as each
reaction to eggs carried to the liver can lead to portal female produces a mean of 200 000 eggs daily. A lack
hypertension. Severe disease with hepatosplenomeg- of latrines and soap for handwashing are risk factors
aly affects about 10% of S. mansoni cases in endemic for infection.
areas, taking 5–15 years to develop. Normally the con-
dition presents with blood in stools, abdominal dis-
Hookworm
comfort, tiredness and weight loss in children The key
early feature of S. haematobium infection is terminal The two major species of hookworm are Ancylostoma
haematuria which, untreated, may progress over years duodenale and Necator americanus, which have similar
of heavy exposure to obstructive uropathy, hydrone- life cycles and disease. The gravid female hookworm
phrosis and pyelonephritis. produces about 5000–30 000 eggs per day in faeces.
Diagnosis is based on finding eggs in the faeces, but The eggs hatch into rhabditiform larvae that grow
stool concentration methods and numerous immu- into infective larvae and enter the host, usually by bor-
nological techniques (e.g. enzyzme-linked immuno- ing through bare feet, and reach venules or lymphat-
sorbent assay; ELISA) are more sensitive for milder ics. The larvae then migrate into the lungs, ascend the
infections. Treatment is with praziquantel 40 mg/kg as respiratory tract and descend to the small intestine,
a single dose. Prevention involves avoidance of water where they attach and mature in the jejunum.
sources containing cercariae and promotion of latrine Hookworms are probably the second most prev-
use. Control programmes for schistosomiasis involve alent intestinal parasite after ascariasis, with 1200
mass chemotherapy, destruction of snails, environ- million people infected worldwide (two-thirds by
mental sanitation, prevention of water contact and Necator), including 90–130 million with morbidity.
health education. Necator predominates in Central and South America,
and Ancylostoma in India, China, North Africa and
tropical Australia, but mixed infections occur in many
Ascariasis
regions. Unlike Ascaris and Trichuris, hookworm
Ascariasis is one of the most prevalent infections in transmission is associated with rural rather than urban
the world, affecting approximately 1400 million peo- settings. There are several other species of dog and cat
ple (23% of the world's population), with 59 million, helminth (e.g. Toxocara spp) that can cause eosino-
mostly children, at risk of morbidity. The highest philic enteritis, cutaneous larva migrans or viscera
prevalence is in countries where sanitation is deficient. larva migrans in humans.
Curiously, ascariasis was never common in tropical Hookworm larvae entering the skin can result in a
Australia, unlike other intestinal parasites. Morbidity papulovesicular rash at the site of entry, or cutane-
is directly related to worm load. Geophagy (eating ous larvae migrans for animal hookworms. Although
soil) is a significant risk factor for ascariasis and trich- eosinophilia accompanies the larval migration phase,
uriasis. Ascaris infection is not associated with muco- pneumonitis is mild and is rarely recognized in chil-
sal damage, and 85% of infected individuals have light dren. The main morbidity from hookworm is iron
infections that remain asymptomatic. Heavy infection deficiency anaemia, particularly with heavy infections.
may induce a pneumonitis from migrating pulmonary The diagnosis of hookworm is based upon identifying
larvae, with cough, wheeze, eosinophilia and transient hookworm eggs on microscopy of faeces. Eosinophilic
patchy infiltrates, which may be difficult to differenti- enteritis due to animal hookworm may require endos-
ate from pneumonia, asthma or bronchitis. This syn- copy for definitive diagnosis, as stool microscopy will
drome of tropical pulmonary eosinophilia (Loeffler), be negative. Charcot–Leyden crystals in the stools
common in adults, is rarely recognized clinically in reflect breakdown of eosinophils, which is a non-specific
421
children with Ascaris or hookworm. feature of early infection.
 12.4 INFECTIONS

Measures to prevent hookworm include ceasing the Among Aboriginal children in Darwin, Cryptos­
use of human faeces as fertilizer, use of toilets, wearing poridium was found in the stool of 7.4% of admissions
shoes and generally improving living standards. In high- with diarrhoeal disease, with a mean age of 12 months
prevalence areas of hookworm and schistosomiasis, and mean admission serum potassium of 2.7 mmol/L.
regular mass de-worming campaigns using albendazole It was associated with severe and prolonged mucosal
or praziquantel are effective in reducing anaemia rates. damage and inflammation.
Cryptosporidiosis is diagnosed by finding oocysts in
stool using an acid-fast stain, which is sensitive only in diar-
Whipworm
rhoeal cases. Immunofluorescent and ELISA techniques
A mature Trichuris trichiura female worm produces are more sensitive, and polymerase chain reaction (PCR)
up to 20 000 eggs/day, which are not infectious over may be even more sensitive for detecting low numbers of
2–4 weeks. Once ingested, larvae penetrate the epithe- oocysts in stool specimens. The high infectivity and ubiq-
lium of the mucosal crypt in the caecum, where they uitous oocysts in the environment make prevention by
moult and the hairlike worm remains attached while water, hygiene and sanitation programmes very difficult –
the broader distal end extends into the lumen. The adult indeed impossible in the developing world, where up to
worm is 4 cm long and survives 1–2 years in the host. 95% of children in some areas have positive serology by
Trichuriasis is a very common infestation with an esti- the age of 2 years. Precautions for travellers include hand-
mated 1049 million cases worldwide, including 114 mil- washing, boiling water, avoiding animals, proper cooking
lion preschool- and 233 million school-aged children. of food, peeling fruit and avoiding uncooked food in con-
Most infections in children are light (< 20 adult worms) tact with unboiled water (e.g. salads).
and asymptomatic, with symptoms developing in less
than 10% of infected children. Light infections incite a
Strongyloidiasis
local inflammatory response involving eosinophils and
neutrophils in the colon. With heavy infestations, fre- Although not a major cause of morbidity worldwide,
quent watery or mucous stools occur, sometimes with the nematode Strongyloides stercoralis is unique in its
frank blood. Rectal prolapse can occur with heavy ability to persist indefinitely within the host through
infestations, and occasionally heavily infected children autoinfection and to cause disseminated disease asso-
develop a dysentery syndrome characterized by chronic ciated with prolonged use of corticosteroids or other
dysentery, stunting, anaemia and finger clubbing. causes of immunosuppression.
The diagnosis is based on finding eggs on stool S. stercoralis is present in tropical and subtropical
microscopy. The use of proper latrines, good hygiene regions, but estimates of worldwide prevalence vary
with handwashing, and washing vegetables will inter- widely (3–100 million), with the best estimate that
rupt the life cycle. Overcrowded urban slums with lim- of 30 million people in 70 countries. Strongyloidiasis
ited water supply and heavily faecally contaminated accounts for about 8% of acute diarrhoeal admissions
soil for growing vegetables place children at particu- in Australian Aboriginal children in Darwin, with a
lar risk. Mass chemotherapy is highly effective but re- mean age of 23 months, this group being significantly
infection occurs rapidly in high-exposure settings. older than for other children with diarrhoeal admis-
sions. Prevalence rates vary with climate, geographical
region, soil characteristics and socioeconomic status,
Cryptosporidiosis
such as quality of housing, hygiene standards and
The protozoa Cryptosporidium parvum, Isospora belli, crowded population density.
Cyclospora cayetanensis and Sarcocystis hominis all Malabsorption and small-bowel bacterial over-
belong to the group of intestinal coccidial infections, growth occur with strongyloidiasis, and symptoms of
which cause diarrhoea. They have come into promi- abdominal pain, diarrhoea and weight loss. As with
nence in recent years through causing severe and pro- hookworm, larval migration may affect the lungs
tracted diarrhoea in people with acquired immune (eosinophilic pneumonitis) or skin (‘ground itch’ on
deficiency syndrome (AIDS) and infecting piped the foot or ‘larva currens’ on the buttocks) but these
water supplies as a result of the chlorine resistance of are not usually recognized in children. The common-
oocysts. However, Cryptosporidium can also cause per- est manifestation of S. stercoralis infection in children
sistent diarrhoea and proximal small intestinal enter- is an acute diarrhoeal illness with foul stools with a
opathy in children with normal immune function. typical musty odour. Severe dehydration is uncom-
Transmission is from person to person and from mon, but hypokalaemia and malabsorption occur
animals to people by ingestion of faecally contami- commonly. Eosinophilia (5–15% of total white blood
nated food or water. Cryptosporidial infection causes cell count) is a common but not universal finding.
watery diarrhoea with low-grade fever, vomiting and A syndrome of partial intestinal obstruction with stron-
422
often cramps, severe dehydration and h ­ ypokalaemia. gyloidiasis has been described in Aboriginal c­hildren
 Infections in tropical and developing countries 12.4
in the Northern Territory. Strongyloides fulleborni is
a more virulent infection affecting young children in Practical points
Papua New Guinea, which may be transmitted via
breast milk, and is characterized by abdominal swell- Intestinal parasites
ing, ascites, pleural effusions and a high mortality rate. • Intestinal parasitic and protozoan infections are highly
Disseminated strongyloidiasis (hyperinfection) occurs prevalent, with 3.5 billion people infected and 450 million
with impaired cell-mediated immunity, such as children having disease.
treated with prolonged courses of steroids or children with • Roundworms, whipworms and protozoa are transmitted
faecally–orally (poor hygiene), hookworms and
malignancy (e.g. lymphoma, leukaemia) on immunosup- Strongyloides percutaneously (walking barefoot), and
pressive drugs. Eradication of Strongyloides is essen- schistosomiasis from water (bathing, wading).
tial before immunosuppressive therapy is commenced. • Amoebic organisms in stool are most likely to be
Dissemi­nated infection is always a serious complication Entamoeba dispar, which is not pathogenic.
with high mortality, usually affecting bowel, lungs and • Only Cryptosporidium and Strongyloides are significantly
central nervous system, and often accompanied by sepsis. associated with diarrhoea; Giardia can cause chronic
diarrhoea but is found more commonly in stools of
The diagnosis is established by identification of larvae
children without diarrhoea.
on stool microscopy, which is very reliable in acute diar-
• Control of intestinal parasites in high-prevalence
rhoea but less reliable in chronic or asymptomatic infec- communities is best achieved through integrated
tion because larvae excretion is irregular and the parasite health interventions including periodic anthelminthic
load is often low, so a single stool examination may administration and improved water and sanitation.
detect larvae in only 30% of cases of latent infection.
The stool culture technique is more sensitive. Various
serological tests are also available. Disposal of human
excreta, wearing shoes, treatment of cases and improved
hygiene reduce the risk of transmission of strongyloidi- Specific infections
asis in communities. Regular mass chemotherapy pro-
grammes have a modest impact on strongyloidiasis.
of the Australian tropics
Box 12.4.2 lists the common infections in hospitalized
children in the Top End of Australia. Murray Valley
Drug treatments for parasitic diseases
encephalitis is endemic in north-west Australia, with
The benzimidazoles albendazole and mebendazole have significant rates of exposure but a low clinical attack
broad-spectrum activity against roundworm, whipworm, rate of about 0.1% of those infected. However, those
hookworm, pinworm and wireworm species. Pyrantel with clinical illness develop devastating encephali-
pamoate is active against Ascaris and Enterobius. tis with fever, coma, seizures and neurological signs
Levamisole is an immune stimulant that is effective of cerebellar, spinal cord and brainstem involvement,
against intestinal infection caused by Ascaris and hook- with a mortality rate of 20% and neurological sequelae
worm. Ivermectin has broad-spectrum activity against in up to 40% of survivors. Although more common
helminths and filariasis but is the drug of choice against in the tropical north of Australia, Ross River and
strongyloidiasis. Metronidazole and tinidazole are used Barmah Forest viruses can cause outbreaks through-
for giardiasis and amoebiasis. Nitazoxanide is a new out Australia. Infection in children is usually asymp-
broad-spectrum antimicrobial agent with activity against tomatic and it is likely that infection in childhood
nematodes, trematodes, anaerobic bacteria and proto- accounts for the very low incidence of clinical dis-
zoal parasites such as Cryptosporidium. However, it does ease in Aboriginal communities in northern Australia
not appear to be effective in HIV-infected children with despite high rates of seropositivity.
cryptosporidiosis. Melioidosis is caused by the bacterium Burkholderia
The results of systematic reviews of preventative pseudomallei, which is ubiquitous in soil and water
programmes show the public health benefits of com- in northern Australia and is even more common in
bining health interventions such as integrated school Thailand. Disease in children is relatively uncom-
health packages, which may include deworming, iron mon compared with adults (only 4% of cases at Royal
supplementation, school feeding and malaria con- Darwin Hospital are in children), who often have pre-
trol. The impact of anthelmintic treatment is greatest disposing chronic disease risk factors, such as diabetes
when albendazole is co-administered with praziquan- and alcoholism. Although pneumonia is the common-
tel. Although there are strong theoretical reasons to be est presentation of melioidosis, there is a wide spec-
concerned about the effect of iron on predisposing to trum of manifestations, from mild cutaneous lesions
infection, including malaria, prevention of iron defi- to fulminant disease with multiple visceral abscesses.
ciency is clearly beneficial, so the benefits outweigh the Prolonged treatment is required, usually with the anti-
423
risks even in sub-Saharan Africa. biotics ceftazidime or imipenem and co-trimoxazole.
 12.4 INFECTIONS

Box 12.4.2 Common infections in Aboriginal community children in tropical Australia

Respiratory infections • *Strongyloides, which causes diarrhoea and occasionally

• Otitis media – especially chronic suppurative otitis media disseminated infection
(CSOM) • *Hookworm – Ancylostoma duodenale (less common now
• Airway disease – acute bronchiolitis, chronic mucopurulent because of widespread use of albendazole)
bronchitis progressing to *bronchiectasis
• Bacterial pneumonia (N.B. pneumococcal and Hib Skin infections
infections now uncommon because of the use of • Impetigo and cellulitis – usually Streptococcus pyogenes
conjugate vaccines) • Boils and abscesses – usually Staphylococcus aureus
• *Scabies, often with pyoderma
Infectious diarrhoea • Tinea corporis – usually Trichophyton rubrum
• *Enteropathogenic Escherichia coli (EPEC) and
enteroaggregative E. coli (EAEC) Bone, joint and muscle infections
• Rotavirus (*complicated by metabolic acidosis and • Septic arthritis, osteomyelitis and *pyomyositis, usually
secondary lactose intolerance) S. aureus
• *Strongyloides stercoralis
• *Cryptosporidium parvum Other
• Salmonella (N.B. clinical dysentery uncommon) • *Rheumatic fever (group A streptococcus)
• *Acute post-streptococcal glomerulonephritis (group A)
Intestinal nematodes • *Epidemic gonococcal conjunctivitis (occasionally)
• *Whipworm – Trichuris trichiura (N.B. Ascaris or roundworm • *Trachoma (Chlamydia trachomatis)
is very rare) • Hepatitis A (usually anicteric)

* Occurs predominantly in Aboriginal children.

424
 13
PART

ALLERGY, IMMUNITY
AND INFLAMMATION

425
 13.1 Atopy Mike Gold

Pathogenesis
General principles
Although atopy is defined by an excessive p ­ roduction
Definition, prevalence and burden of disease of IgE, this is only one of many immunological changes
Atopy is defined as the ability of an individual to that characterize the allergic diseases, as these are also
form specific immunoglobulin (Ig) E antibodies to associated with a complex dysregulation of the humoral
one or more common inhaled aeroallergens such as and cellular immune systems (Fig. 13.1.1). For this pro-
animal dander, pollen, mould or house dust mite. An cess to occur, both a genetic predisposition and early life
­allergen is defined as an antigen (usually a protein) that environmental exposure are important. During early
is r­ecognized by the immune system, is usually harm- life, naive T-helper lymphocytes respond in a particular
less, and induces an allergic inflammatory response. The way to environmental allergen e­ xposure as well as a host
atopic or allergic diseases include eczema, asthma and of other non-allergen immunomodulatory factors (such
allergic rhinoconjunctivitis. These are complex inflam- as endotoxin). T-regulatory cell function and the pat-
matory conditions that are associated with immune tern of cytokine secretion are ­central to the factors that
dysregulation. Not all atopic individuals express clini- result in the production of antibodies, including IgE.
cal disease, but the majority of children who have these
diseases are atopic. For example, 30–40% of individuals
in developed countries can be shown to be atopic (have
detectable allergen-specific IgE antibodies), yet only Approach to diagnosis,
5–20% may manifest an atopic disease. The reasons for investigation and management
this variable disease expression are not known.
History and examination
There is a marked variation in the global and regional
prevalence of the atopic diseases, with the highest dis- The history and examination should cover the follow-
ease burden in industrialized countries and urbanized ing aspects:
communities. In these countries, atopic diseases are now • Specific symptoms
the commonest ailments of ­childhood, and Australian • nature, timing (seasonal, perennial, episodic),
and New Zealand children have the fifth highest global situational (specific site or circumstance)
rates of atopic d ­ isease (Table 13.1.1). Since the indus- • Severity of symptoms and degree of disability
trial revolution, the prevalence of atopic diseases has • medication required to control symptoms, medical
been increasing in most communities, for reasons visits and hospitalization, school absenteeism,
that are not yet apparent. Environmental factors are interference with sleep, sport or play
thought to account for the variable and increasing prev- • Use of medication
alence of atopic disease. A commonly cited hypothesis, • current and past medications, efficacy,
the ‘hygiene hypothesis’, proposes that the lack of early compliance, technique of use and side-effects
childhood exposure to infections and/or other envi- • Environmental history – identification of triggers
ronmental ­factors (such as bacterial endotoxin) may • exposure to common allergens (Box 13.1.1) and
predispose to atopic disease in g­ enetically susceptible non-allergen (e.g. cigarette smoke) triggers should
individuals. Such a hypothesis can be supported by epi- be considered
demiological and possibly immunological evidence. • a trigger may be identified easily if the onset
Because atopic diseases are common, often chronic and of symptoms is acute and occurs soon after
usually begin in early childhood, the burden to the com- exposure, if symptoms occur in a specific
munity, family and individual is considerable. The cost of geographical location, are seasonal, or occur
allergic disease to the Australian community is estimated repeatedly following similar exposures
to be $7 billion per annum. Importantly, the impact of • a trigger may be difficult to identify when
severe atopic disease such as atopic ­dermatitis on a ­family continuous exposure results in chronic symptoms
426 may exceed that of other chronic childhood disorders • identification of possible triggers requires knowledge
such as diabetes mellitus or juvenile rheumatoid arthritis. of the likely circumstances of allergen exposure.
 Atopy 13.1
Table 13.1.1 Prevalence of atopic disorders among
On examination, atopic children may have a typical
Australian children appearance (Table 13.1.2).

Disorder 6–7-year-olds (%) 13–14-year-olds (%)

Assessment
Eczema ever 23 (11) 16 (10)
Once the history and examination are completed,
Asthma ever 27 (25) 28 (29) there is seldom difficulty in diagnosing the present-
ing atopic disease. However, as many children mani-
Hayfever ever 18 (12) 43 (20) fest more than one atopic disease, it is important
Values in parentheses show the percentage that currently have
to consider whether any other atopic condition is
the condition. Data obtained from the International Study of ­present. A ­differential diagnosis should be considered,
Asthma and Allergy in Childhood questionnaire-based survey as uncommon disorders may present similarly to an
of 10 914 children in Melbourne, Sydney, Adelaide and Perth. atopic ­disease (Table 13.1.3).

Genetic predisposition Early life environmental exposure

• Polygenic inheritance • Allergens – ingested or inhaled
• Atopy gene not identified – candidate • Non-allergens – infection, diet,
genes at 5q, 11q and 12q pollution, use of antibiotics

Immune dysregulation
• Induction of Th2 lymphocyte phenotype
• Production of Th2 cytokines (IL-4, -5, -13)

Sensitization
• Production of allergen-specific IgE by
gene transcription and recombination

Allergen exposure

Allergy cascade

Early phase – immediate Late phase – delayed

• IgE and allergen binding on mast cells • Allergens – ingested or inhaled
• Mast cell degranulation • Non-allergens – infection, diet,
• Mediator release – histamine, pollution, use of antibiotics
leukotrienes, etc.

Atopic disease
• Atopic dermatitis
• Asthma
• Allergic rhinoconjunctivitis

427
Fig. 13.1.1 Pathogenesis of atopic disease. Ig, immunoglobulin; IL, interleukin; Th2, T-helper type 2.
 13.1 ALLERGY, IMMUNITY AND INFLAMMATION

(Table 13.1.4). Measurement of ASE may be ­helpful

Clinical example in identifying a specific allergen trigger. However,
­interpretation of the skin test or ASE result is critical:
Michaela, aged 10 years, had severe, persistent • The presence of specific IgE to an allergen is only
asthma. She presented for follow-up after a one factor in establishing whether the allergen is a
recent admission to the intensive care unit
for acute respiratory symptoms diagnosed
clinically significant trigger.
as status asthmaticus. In passing, her mother mentioned • The result should always be correlated with the
that immediately prior to her most recent episode she had history and/or a trial of allergen avoidance with or
inadvertently eaten a chocolate containing peanuts. She did without subsequent challenge.
not usually eat peanuts because she said that they made • The predictive value of a negative result is higher
her mouth ‘feel funny’. Her mother recalled that as an infant than the predictive value of a positive result.
Michaela experienced two episodes of generalized skin rash
immediately following peanut ingestion.
• The skin test or ASE result should always be
The history is suggestive of an IgE-mediated peanut
discussed with the parent or caregiver to avoid
anaphylaxis. Children with asthma are at increased risk of misinterpretation.
death from anaphylaxis. Additional questions in the history • Failure to discuss often leads to inappropriate
should ascertain whether Michaela had experienced any avoidance measures such as excluding foods from
urticaria, angio-oedema, abdominal pain or vomiting with the diets of children solely on the basis of a positive
the most recent episode, as this would suggest the recent skin test or ASE result.
presentation was due to anaphylaxis rather than status
asthmaticus. An assessment of allergen specific IgE (skin or
serological test) to peanut should be obtained. Management Management
of severe peanut allergy should include the complete dietary
exclusion of peanut, an anaphylaxis action plan, adrenaline The aims of management in atopic disease may vary
(epinephrine) for first aid use (EpiPen or Anapen) and a MedicAlert depending on the clinical context.
bracelet. Michaela's parents and other carers (including
those at school) should be trained to use the anaphylaxis
action plan. At this age, nut allergy is likely to be lifelong. Primary prevention of atopic disease
The most useful predictor for the development of an
atopic disease is the family history. If one or both par-
Investigations ents are affected, the risk to an infant of developing an
atopic disease is 40–60%. With no positive family his-
Investigations in the atopic child are limited. Total IgE
tory, the risk of developing an atopic disease is 10%.
concentration is raised in the majority of children with
General primary prevention advice should be to avoid
atopic disease but there is substantial overlap with val-
exposure to tobacco smoke and promotion of breast-
ues in non-atopic children. Measurement of total IgE
feeding, although the evidence concerning the pro-
levels is seldom indicated. Allergen-specific IgE (ASE)
tective effects of breastfeeding for allergy prevention
is more useful and can be determined using both
remains variable. Maternal allergen avoidance during
in vivo (skin testing) and in vitro (serological) methods
pregnancy is not thought to be effective. Still under
current investigation is maternal intake of omega-3 fish
oils and probiotics during pregnancy. There is evidence
Box 13.1.1 Allergens that may trigger symptoms in atopic that use of a partially hydrolysed cow's milk formula
children (if breastfeeding is not possible) may be of benefit in
high-risk infants, and also under investigation is the use
Inhaled allergens
• Animal dander – cat, dog, horse, rabbit of infant formulae containing prebiotics and probiot-
• Pollen – grass (rye, couch, timothy), weed (plantain), tree ics. The timing of the introduction of ‘allergenic foods’
(olive, plane) (e.g. cow's milk, egg and nuts) and the association with
• Mould – Alternaria, Aspergillus, Cladosporium, Penicillium spp the development of food allergy is under investigation.
• House dust mite – Dermatophagoides pteronyssinus, However, there is currently no evidence to ­ support
Dermatophagoides farinae prolonged empirical avoidance of allergenic foods
­
• Cockroach
beyond 6 months of age, even in high-risk infants.
Ingested allergens
• Food – cow's milk, egg, nuts, fish, shellfish, soy, wheat, fruit
Management of symptomatic atopic disease
• Medication – antibiotics (penicillin) and non-antibiotic
medication Once the child has developed symptomatic atopic
­disease, management involves allergen ­identification and
Miscellaneous
avoidance, and symptomatic treatment. Immunotherapy
428 • Latex contained in balloons and surgical gloves
may be appropriate for selected children.
Table 13.1.2 Examination of the atopic child

System Clinical findings

Growth Weight
Height

Facies Facial pallor

Allergic shiners – infraorbital dark circles due to venous congestion
Dennie–Morgan lines – wrinkles under both eyes
Mouth breathing
Dental malocclusion – from long-standing upper airway obstruction
Sinus tenderness

Skin Atopic dermatitis

White dermatographism – white discoloration of skin after scratching
Xerosis – dry skin
Urticaria and/or angio-oedema

Nose Horizontal nasal crease

Inferior nasal turbinates – pale and swollen
Clear nasal discharge

Respiratory Chest deformity – Harrison sulcus, increase in anteroposterior diameter

Respiratory distress
Wheeze and/or stridor

Eyes Conjunctivitis
Subcapsular cataracts associated with conjunctivitis

Ears Tympanic membrane dull and retracted

Throat Tonsillar enlargement

Postpharyngeal secretions and cobblestoning of mucosa

Cardiovascular Blood pressure

Table 13.1.3 Differential diagnosis of atopic disease

Atopic disease Differential diagnosis

Atopic dermatitis Seborrheic dermatitis

Psoriasis
Wiskott–Aldrich syndrome*
Hyper-IgE syndrome*

Asthma Infection – viral, bacterial, mycobacterial

Congenital anomaly (e.g. vascular ring)
Cystic fibrosis
Immunodeficiency disease
Aspiration syndrome secondary to gastro-oesophageal reflux, incoordinate swallowing or
tracheo-oesophageal fistula
Inhaled foreign body
Cardiac failure

Allergic rhinitis Infective rhinitis

Non-allergic rhinitis
Vasomotor rhinitis
Rhinitis medicamentosa
Sinusitis
Adenoidal hyperatrophy
Nasal polyps
Nasal foreign body
Choanal atresia (unilateral, bilateral)

*These immunodeficiency diseases may have atopic dermatitis as a component. 429

 13.1 ALLERGY, IMMUNITY AND INFLAMMATION

Table 13.1.4 Determination of allergen-specific IgE

• other indoor allergens (cat, cockroach, mould)
and outdoor allergens are less easily avoided and
Skin testing Serology alternative forms of therapy may be required.
Method Skin puncture test UniCAP Symptomatic treatment
When allergen avoidance is difficult, the response is par-
Availability Limited Widely tial or the allergen cannot be identified, s­ymptomatic
treatment is indicated. A number of medications are
Expense Cheap Expensive
available, including antihistamines, sympathomimet-
Results Immediate Delayed ics, mast cell stabilizers, corticosteroids and ­leukotriene
antagonists (Table 13.1.5).
Risk of Rare Nil
anaphylaxis Induction of tolerance: immunotherapy
Allergen immunotherapy was first used for grass
Interference Antihistamines High total IgE pollen-induced allergic rhinitis almost 100 years ago
Extensive atopic dermatitis and is effective only for IgE-mediated inhalant or venom
Dermatographism (bee, wasp, jumper ant) allergic disease. Although the
exact mechanism is not known, the induced state of tol-
Sensitivity ++++ ++
erance to an allergen is associated with the production of
Specific ++++ ++ blocking antibodies, downregulation of T-helper type
2 (Th2) lymphocytes and a decrease in ASE.
Ig, immunoglobulin; UniCAP, radioallergosorbent test. Immunotherapy should be initiated and supervised
by an experienced allergist. Pollen-induced allergic
rhinoconjunctivitis remains the main indication for
Allergen identification and avoidance
immunotherapy and should be considered in ­children
When possible, this remains an important component of
who have intractable and disabling symptoms that
management. Avoidance measures may involve consid-
have failed to respond to allergen avoidance and to
erable parental education, effort and expense. Note that:
symptomatic treatment. Immunotherapy for children
• with ingested allergens identification and avoidance are who present primarily with asthma is controversial.
particularly important when atopic disease is associated
Not only is the risk of an adverse reaction higher in
with a food allergy, as this is the only means of therapy
these children, but they are often sensitized to both
• with inhalant allergens, methods have been seasonal and perennial allergens. No form of immu-
evaluated to reduce exposure to indoor allergens,
notherapy is currently available for atopic dermatitis.
most importantly house dust mite (Box 13.1.2).
A number of studies in sensitized individuals have
demonstrated improvements in atopic dermatitis
and allergic rhinitis following house dust mite Specific atopic disorders
reduction measures. The benefit of house dust mite The majority of children who develop atopic dermati-
avoidance in asthma is much more controversial tis (eczema) or asthma present by 6 years of age, with
most individuals manifesting symptoms of allergic
rhinoconjunctivitis by age 20 years. However, there is
Box 13.1.2 Methods to reduce house dust mite exposure a predictable pattern of disease expression, which is
called the ‘allergic march’:
Definitely useful
• Encase bedding in impermeable covers (dust mite covers): • Expression of atopy usually starts with atopic
most important measure, because the bed is the major dermatitis, which presents in the first 6 months of
source life and often improves in the second year of life.
• Hot water washing of bedding and clothes (> 56°C): will • Approximately 50% of children with atopic dermatitis
destroy house dust mite and remove allergens will then develop asthma in early childhood.
• With resolution of asthma in late childhood some
Probably useful
• Replacement of fitted carpets with smooth flooring
children then develop allergic rhinitis, which may be
• Hard-surface cleaning with a damp cloth, at least once a week lifelong.
• Importantly, in a number of children all forms
Possibly useful of atopic disease may be expressed concurrently.
• Air filtration, ionizers and air conditioning For this reason, although one atopic disease
may be predominant at a particular age, it is
Unlikely to be useful
always important to consider which other atopic
430 • Acaricides (dust mite sprays) for the carpet and mattress
conditions may be present.
 Atopy 13.1
Table 13.1.5 Medications for the symptomatic treatment of allergic disease

Important mechanisms of action in allergic disease Examples

Antihistamines
   First and second generation H1-receptor antagonism Diphenhydramine
Promethazine
Hydroxyzine
  Second generation Above plus antiallergic effects Cetirizine
Decrease mediator release Loratadine
Decreased migration and activation of inflammatory cells Terfenadine
Reduced adhesion molecule expression

Sympathomimetics
  β-agonists Bronchial smooth muscle relaxation Salbutamol
Reduce mast cell secretion Albuterol
Terbutaline
  α- and β-agonists Bronchial smooth muscle relaxation Adrenaline (epinephrine)
Vasoconstriction – skin and gut
Inotropic and chronotropic effects
Reduce mast cell secretions
Glycogenolysis

Cromolyn Mast cell stabilizer Cromolyn sodium

Inhibits chemotaxis of eosinophils Nedocromil sodium
Inhibits pulmonary neuronal reflexes

Corticosteroids Reduce T-cell cytokine production Hydrocortisone

Reduce eosinophil adhesion, chemotaxis Beclomethasone
Reduce mast cell proliferation Budesonide
Reduce vascular permeability Fluticasone/flunisolide
Reverse adrenoreceptor downregulation Triamcinolone acetonide

Leukotriene antagonists 5-Lipo-oxygenase enzyme inhibition, or LTD4 receptor Montelukast

antagonist

LT, leukotriene.

Atopic dermatitis • other atopic diseases and atopic facies (see

Table 13.1.4)
See also Chapter 21.1.
• food allergy and intolerance.

Definition and clinical presentation

Atopic dermatitis is a chronic inflammatory skin disor- Clinical example
der that is associated with overproduction of IgE and
eosinophils due to a systemic Th2 cytokine response. Hannah, aged 8 months, had severe atopic
dermatitis. Her skin was permanently excoriated
Histamine, neuropeptides, proinflammatory cytokines,
and erythematous. She had been breastfed and
mast cells, eosinophils and antigen-presenting cells are was on solids, which included rice, vegetables
all increased in skin affected by atopic dermatitis. The and wheat. A dietary history revealed that she also had food
cardinal features of atopic dermatitis include: that contained small amounts of egg and cow's milk protein.
• intense pruritus A UniCAP performed by her general practitioner showed specific
• a relapsing course IgE antibodies to egg of more than 100 U/L (very high) and
to cow's milk of 30 U/L (moderate). No specific IgE had been
• a typical distribution of skin rash
detected to wheat and rice.
• a personal or family history of an atopic disease The treatment of atopic dermatitis involves avoidance
• additional features that may be present: of skin irritants, use of skin moisturization, topical
• dry skin (xerosis), skin infection, white anti-inflammatories and the identification and avoidance of
431
dermatographism
 13.1 ALLERGY, IMMUNITY AND INFLAMMATION

• food allergens
triggers. Approximately 50% of infants with atopic dermatitis • allergens such as house dust mite, animal dander,
have IgE sensitization to one or more of the common food mould and pollen
proteins. Some of these infants may have an IgE-mediated
food allergy, and in some ingestion of these food proteins
• bacterial (Staphylococcus aureus) or viral (herpes
may trigger atopic dermatitis. This infant should have dietary simplex virus) skin infection
exclusion of egg and cow's milk protein, and the effect on • stress.
her atopic dermatitis should be assessed. It is important The aim of management is to reduce as many of these
not to continue a prolonged exclusion diet unless there is a triggers as possible and to provide symptomatic relief
significant clinical improvement in the eczema as a result. until the disorder improves, which fortunately occurs
Therefore, if possible, this should occur under the supervision in most children.
of a dietitian and alternative sources of protein and calcium
The majority of children respond to general mea-
should be included in the diet. Egg and cow's milk allergy
usually resolve by 5 years of age, so regular review of the sures of skin care, which include:
diet and other management is mandatory. • avoidance of skin irritants – soaps, shampoo,
woollen clothing, hot baths
• frequent use of topical moisturizers (at least twice
daily)
The main symptom of atopic dermatitis is intense
• antiseptic measures – antiseptic bath oil, topical
pruritus, which when severe may be associated with
antiseptic cream (intermittent)
disruption of sleep, school and social interactions, and
• wet wraps – wet dressings (bandages) applied to the
can profoundly affect the quality of life. In older chil-
affected skin.
dren and adolescents, disfigurement and teasing may
If symptoms persist despite these general measures
be important. The appearance of the skin in atopic
then medication should be considered:
dermatitis may be variable:
• Topical corticosteroids are used commonly:
• In infants with an acute presentation the lesions are
• The least potent steroid should always be used for
erythematous, papulovesicular and occur mostly on
maintenance therapy.
the face, scalp, extensor surfaces of the limbs and
• If possible, steroids should be used intermittently.
trunk.
• Potent steroids must be avoided on the face.
• With increasing age the lesions localize to the hands,
• Antihistamines may be useful for skin itch.
feet, and the antecubital and popliteal flexures.
Non-sedating antihistamines may be useful during
• Chronic changes include lichenification of the skin, the day and sedating antihistamines may be used
which is a skin thickening resulting from persistent
intermittently, particularly for night-time itch in
rubbing and scratching.
children older than 2 years of age.
• The skin is almost invariably dry and its appearance
• Antibiotics may also be useful for secondary
may be altered by intense excoriation and
bacterial infection of the skin.
secondary bacterial infection.
If symptoms persist and are severe despite general
measures of skin care and topical steroids, an allergy
Investigations review would be appropriate; the aim would be to
Determination of specific IgE to inhaled or ingested identify allergens that could be significant triggers.
allergens by skin test or UniCAP should be consid- Allergen avoidance is particularly important in infants
ered if the atopic dermatitis is extensive and has not and children who have associated food allergies and
responded to measures of general skin care and symp- those who have been sensitized to house dust mite.
tomatic treatment. Unfortunately, a small number of children have
Most affected children above 2 years of age have a severe and disabling atopic dermatitis despite all of
raised total IgE concentration and have measurable spe- these measures and may require intermittent hospital-
cific IgE to common inhaled and ingested allergens. This ization for intensive topical therapy, phototherapy and
is a marker of atopic status rather than indicating that a immunosuppressive medication.
specific allergen may be a trigger for atopic dermatitis.
Response to withdrawal of the allergen is currently the Asthma
only way to determine the significance of these results.
See also Chapter 14.3.
Management
Definition and clinical presentation
A number of triggers may exacerbate atopic dermati-
tis, including: Asthma is defined as a chronic inflammatory lung dis-
432 • skin irritants (e.g. soap, heat) order usually associated with bronchial hyperactivity,
• viral infection and presents as a symptom complex of cough, wheeze
 Atopy 13.1
and shortness of breath. As asthma is discussed Management
­elsewhere (see Chapter 14.3), this section will review
The management of asthma depends on the frequency
asthma in the context of the atopic child.
and severity of the condition. Episodic asthma may
Although the exact cause of asthma is not known,
require intermittent treatment, whereas persistent asthma
the two most significant risk factors are a family history
may require continuous treatment (see Chapter 14.3).
and atopy. Specifically, 60–80% of asthmatic children
Asthma education is critical and includes an explana-
are atopic. Furthermore, sensitization to indoor aller-
tion of the disease, education about techniques of using
gens (house dust mite and cockroach) combined with
the inhalers and spacers, home monitoring, an explana-
exposure to high levels of these allergens is an impor-
tion of the side-effects of medications, an action plan for
tant risk factor associated with symptomatic asthma.
home treatment, and education about allergen avoidance.
The implication is that exposure to indoor allergens
may contribute to the development of asthma and that
Allergen identification and avoidance in asthma
ongoing exposure or intermittent exposure may be a
trigger factor for asthma. Studies of house dust mite reduction in atopic asth-
matics with persistent asthma have had variable results.
Allergen triggers and asthma It is clear that studies that have markedly reduced the
Asthma has multiple triggers, the most important of exposure of asthmatics to house dust mite (e.g. by hos-
these being viral infections and physical factors such pitalization) have shown an improvement in asthma.
as cold air and exercise. However, in individuals who However, clinical trials that have aimed to reduce dust
have become sensitized to inhaled allergens, further mite exposure in patients’ homes have had more vari-
allergen exposure may act as a trigger for asthma: able results, which probably correlate with the effective-
• Bronchial challenge studies show that acute ness of dust mite reduction methods. Although effective
bronchospasm can be induced in atopic asthmatics
methods have been evaluated to reduce house dust
by inhalation of aeroallergens.
mite levels, these are expensive and time-consuming
• Epidemics of asthma have been documented in and often not adhered to by patients (see Box 13.1.2).
association with airborne allergens. Removal of pets from the homes of ­sensitized asthmat-
• The level of exposure to indoor allergens has ics should be recommended, but occurs uncommonly.
been correlated with the extent of asthma Ingested allergens rarely trigger asthma as a sole
severity. manifestation. Other features of ingested allergens in
• In controlled settings asthmatic symptoms, relation to asthma are:
peak expiratory flow rate and bronchial
• acute bronchospasm – may be part of anaphylaxis
hyperresponsiveness improve when individuals in asthmatic children, but usually occurs with other
avoid allergens to which they are allergic. manifestations of anaphylaxis, such as skin rash or
vomiting
• a history from parents that cow's milk appears
Investigations
to cause respiratory tract symptoms, including
Demonstration of ASE (positive skin tests or UniCAP) asthma; however, empirical removal of cow's milk
may be useful in children who: from the diet of children with asthma without such
• present with the symptom complex of cough and/or a history is not justified
wheeze and in whom the diagnosis of asthma may • in some asthmatics, ingestion of metabisulphite can
not be clear, because atopy is commonly associated result in immediate bronchospasm. This is because
with asthma of a pharmacological intolerance to metabisulphite,
• have persistent asthma in association with possibly as a result of direct irritation of the airway.
allergic rhinitis. Determination of ASE to inhaled Metabisulphite is a commonly used preservative in
allergens could be considered part of routine a number of food substances including meat, dried
asthma management in children with persistent fruit, fruit juices and hot chips.
asthma. Identification of those individuals
sensitized to animal dander and house dust mite Allergic rhinoconjunctivitis
may be useful because allergen avoidance would
See also Chapter 22.1.
be important for control of allergic rhinitis.
Treatment of allergic rhinitis usually results in
Definition and clinical presentation
improvement of asthma.
Determination of ASE is not indicated in episodic Allergic rhinoconjunctivitis is rare in infants under
asthma because viral infection is the most frequent 6 months old. Perennial allergic rhinoconjunctivitis
trigger. However, if a specific inhaled allergen trigger may occur at any age in childhood, and seasonal aller-
433
is suspected from the history, ASE may be helpful. gic rhinoconjunctivitis often develops in older children.
 13.1 ALLERGY, IMMUNITY AND INFLAMMATION

The primary functions of the nose are olfaction and Management

air filtration and humidification. This is achieved by
In children sensitized to indoor allergens a trial of
the nasal structure, which ensures that inhaled air is in
avoidance measures should be instituted. The choice of
contact with an extensive and highly vascular m ­ ucosal
symptomatic treatment depends on the nature, severity
membrane. In sensitized individuals, mucosal c­ ontact
and timing of symptoms. Intermittent and infrequent
with inhaled allergens in the nose and conjunctiva
symptoms can be treated with antihistamines. Prolonged
elicits IgE-mediated mast cell degranulation and a
­
symptoms are best treated with topical steroids com-
chronic inflammatory response.
bined with antihistamines if control is inadequate. For
The history should determine the specific symp-
seasonal allergic rhinoconjunctivitis, treatment should
toms, as the presentation is quite variable, with either
be commenced before the onset of spring:
rhinitis or conjunctival symptoms predominating:
• Topical nasal corticosteroids are most effective
• The symptoms of allergic rhinitis are nasal
for nasal obstructive symptoms but also reduce
obstruction, itch, sneezing and clear rhinorrhoea.
rhinorrhoea, sneezing and conjunctival symptoms.
• Conjunctival symptoms include itching and an
Steroids may take up to a week to work and
increase in tear fluid.
may require prior use of a decongestant to allow
The timing of symptoms provides important informa-
adequate nasal delivery. In general, nasal steroids
tion concerning possible triggers. Symptoms may be
have been shown to be safe in children but epistaxis
seasonal, perennial, a combination of perennial and
may be a problem in some children. This can be
seasonal, or episodic:
reduced by directing the nasal spray away from the
• Symptoms during spring, summer or autumn indicate
nasal septum.
seasonal allergic rhinoconjunctivitis, which may be
triggered by pollen (grass, weed or tree) or mould.
• Antihistamines (oral or topical) are useful for
symptoms of rhinorrhoea, nasal or eye itch,
• Perennial symptoms may be due to indoor allergens
and watery eyes, but are not effective for nasal
(house dust mite, animal dander, cockroach).
obstruction. When given orally, non-sedating and
• Episodic symptoms are most often due to exposure
long-acting antihistamines are preferred but often
to animal dander but may occur in response to
are more expensive.
other allergens.
Examination of the nose and eyes is important (see
• Use of nasal decongestants (vasoconstrictors),
either topical or oral, for longer than 5 days should
Table 13.1.4):
be discouraged.
• The inferior nasal turbinates can be visualized
with a light source (using an otoscope), with the
• Conjunctival symptoms can be controlled with
mast cell stabilizers or, if severe, short-term topical
diagnostic features being pallor and swelling. When
ocular steroid drops.
severe, the swollen nasal turbinates may extend to
Immunotherapy should be considered in children with
the nasal septum and may be mistaken for nasal
aero-allergen-induced seasonal allergic rhinoconjunc-
polyps, which are uncommon in children. Typical
tivitis who have failed to respond to symptomatic
findings may not be present.
treatment, provided the selection criteria have been
• Conjunctival injection and oedema affect both
fulfilled.
the bulbar and tarsal conjunctiva, and appear as
redness and swelling.
Rhinitis symptoms may occur without evidence of an
allergic cause (see Table 13.1.4). If nasal obstruction is
the main symptom, it is important to exclude an ana- Complications of atopic disease
tomical cause. If symptoms such as sneezing, mucoid and important associated
rhinorrhoea and/or obstruction are predominant,
alternative diagnoses such as vasomotor or infective
conditions
rhinitis need to be considered. A number of important conditions occur more com-
monly in children with atopic disease. The exceptions
are medication and insect venom allergy, which are not
Investigations
more common in atopic children.
Determination of ASE is not indicated in seasonal
allergic rhinitis unless symptoms are intractable and
immunotherapy is being contemplated. ASE is indi-
Food allergy and intolerances
cated in perennial allergic rhinitis if symptoms are Adverse reactions to food are often reported in children
troublesome because, if specific IgE to an indoor with atopic disease. The important ­reactions to ­consider
allergen(s) can be demonstrated, a trial of allergen are food allergies and intolerances, ­particularly in infants
434
avoidance measures would be justified. and young children with atopic ­dermatitis (Table 13.1.6).
 Atopy 13.1
Table 13.1.6 Food allergy versus food intolerance

Food allergy Food intolerance

Mechanism Immune-mediated: Non-immune-mediated:

• IgE-mediated • Pharmacological
• Non-IgE-mediated – cell-mediated

Food triggers Food proteins Food chemicals

• Cow's milk Food additives:
• Egg • Preservatives
• Nuts • Food colourings
• Fish and shellfish • Monosodium glutamate
• Soy Natural constituents:
• Wheat • Salicylates
• Fruits • Amines
• Monosodium glutamate

Conversely, food is an uncommon t­ rigger for asthma and Up to 60% of children who have an IgE-mediated
allergic rhinitis. Food allergy and intolerance may occur allergy to one food protein are allergic to another
in children without any atopic disease. food, mainly cow's milk, egg, nuts, soy, fish and wheat.
Hence, if an infant presents with a reaction to one
food, it is always important to exclude others.
Food allergy
IgE-mediated food allergy
It is important to recognize IgE-mediated food allergy
Clinical example
in children with atopic disease:
• The condition is more common in infants and John, aged 12 years, had asthma. While
children with atopic dermatitis. In some studies of swimming he was stung by a bee on his hand.
children presenting with atopic dermatitis up to one Within 5 minutes he developed generalized
third may have an IgE-mediated food allergy. urticaria, facial angio-oedema, cough, wheeze
• Those children who have asthma and IgE-mediated and difficulty breathing. An ambulance was called and
intramuscular adrenaline (epinephrine) was administered,
food allergy are at greater risk of experiencing more
with resolution of John's symptoms.
severe reactions, and rarely death from anaphylaxis Anaphylaxis is defined as a multisystem and generalized
may occur in this group of children. allergic reaction with involvement of the cardiorespiratory
Diagnosis. The diagnostic hallmark of IgE-mediated system. The emergency treatment is adrenaline, which
food allergy is that symptoms usually occur immedi- initially is easily administered by the intramuscular route.
ately (minutes to hours) after ingestion of the food. The incidence of bee venom anaphylaxis is not increased in
Although the most severe manifestation of IgE- asthmatics. However, asthma is a risk factor for more severe
episodes of anaphylaxis in anyone with a food, medication
mediated food allergy is anaphylaxis, a generalized or insect venom allergy. For this reason, in someone who has
or facial skin rash may be the sole manifestation. asthma and anaphylaxis, first aid measures should be in
Anaphylaxis is a multisystem disorder characterized place, including access to an adrenaline auto-injector device,
by respiratory and/or cardiac involvement, usually which should be prescribed together with an anaphylaxis
in combination with involvement of another system, action plan. Immunotherapy is recommended for the long-
most often the skin. The following symptoms and/or term treatment of bee venom anaphylaxis.
signs may occur with a generalized allergic reaction,
including anaphylaxis:
• skin – generalized skin erythema, urticaria or Non-IgE-mediated food allergies
angio-oedema Non-IgE-mediated food allergies are thought to be
• respiratory system – rhinorrhoea, sneezing, cough, mediated by cellular mechanisms, probably involving
wheeze, stridor, respiratory distress T lymphocytes. Cow or soy milk protein is the usual
• gastrointestinal system – abdominal pain, vomiting, trigger, but other food proteins may be involved:
diarrhoea • Exacerbation of underlying atopic dermatitis,
• cardiovascular system – hypotension (if severe, which usually presents as a delayed reaction hours
435
collapse with loss of consciousness). after exposure to the offending food
 13.1 ALLERGY, IMMUNITY AND INFLAMMATION

• A number of gastrointestinal manifestations of be instituted for more than 4 weeks and should be
non-IgE-mediated food allergy may occur: used as a diagnostic trial. If the child responds, this
• cow's milk protein-induced colitis presents as a should be followed by appropriate challenges to
well infant with fresh blood in the stools, which identify specific food triggers.
resolves once cow's milk is excluded from the • Unsubstantiated tests (e.g. Vega or cytotoxic tests)
infant's diet or from the diet of the mother if should never be used to diagnose food allergy or
breastfeeding intolerance.
• food protein-induced enterocolitis may present as
sudden vomiting, dehydration and collapse, which Management
may be mistaken for a gastroenteritis or bowel
obstruction and occurs within hours of exposure The only management available for food allergy or
to the food trigger intolerance is exclusion of these foods from the child's
• other manifestations include an enteropathy, diet. Additionally:
which may present as failure to thrive, • education of the parents and other carers,
irritability, chronic diarrhoea and anaemia, particularly when young children attend childcare
or eosinophilic eosophagitis, which presents and kindergarten, is essential and may require the
with abdominal pain, recurrent vomiting and advice of a dietitian
dysphagia and may be mistaken for gastro- • in breastfed infants with atopic dermatitis and food
oesophageal reflux. allergy, exclusion of food triggers from the maternal
diet may also be tried, although this is best done
with the support of a dietitian and may not be
Food intolerances beneficial in all infants
Food intolerances are thought to be pharmacological • with any exclusion diet it is important to ensure
in nature. Important food intolerances in atopic chil- that the diet is nutritionally adequate. This is
dren include: particularly important as regards calcium intake
• metabisulphite, a common food preservative, which when milk products are excluded.
may trigger acute wheeze in a small minority of • In atopic children who have had food anaphylaxis
children with asthma the following points are important:
• facial skin rashes, due to contact irritation from • anaphylaxis is a medical emergency and requires
foods such as tomato and citrus, common in prompt recognition and treatment (Box 13.1.3)
children with atopic dermatitis • all children should undergo subsequent specialist
• generalized exacerbations of eczema due to food review
intolerance have been proposed in children with • appropriate dietary advice is essential to avoid
atopic dermatitis, but the evidence is poor and this recurrent episodes
remains a controversial area. • adrenaline (epinephrine) for first aid use by
parents and other carers should be considered.
This is prescribed most conveniently in the form
Investigation of food allergy and intolerance
of an auto-injector device. Appropriate training
The investigation of food allergy and intolerance is and documentation in the form of an anaphylaxis
limited: action plan is essential.
• If an adverse food reaction is thought to be IgE-
mediated, determination of ASE is indicated.
However, foods should not be excluded from the Box 13.1.3 Emergency management of anaphylaxis
diet solely on the basis of a skin test or UniCAP.
• There are no validated tests for non-IgE-mediated 1. Remove the trigger.
food allergy or food intolerances. The only 2. Administer adrenaline (epinephrine) by deep
investigation is to demonstrate an improvement intramuscular injection: 0.01 mL/kg 1 : 1000 adrenaline
(maximum dose 0.5 mL).
of symptoms following withdrawal of the
3. Establish an airway if required and administer oxygen.
food trigger and recurrence of symptoms with 4. Assess circulation. If hypotensive: administer IV fluids,
rechallenge. Double-blind and placebo-controlled normal saline 10–20 mL/kg as a bolus.
challenges are preferable but are seldom available 5. Repeat doses of intramuscular adrenaline can be
except in specialized facilities. An open and administered every 5 min until clinical improvement occurs.
non-blind challenge is more practical but is less Consider intravenous adrenaline if hypotension and poor
accurate. response to IV fluids and intramuscular adrenaline.
6. Antihistamines and steroids are not administered for the
436 • Empirical use of a diet that eliminates a number of initial management but should be given as second-line therapy.
naturally occurring food substances should never
 Atopy 13.1
whether allergic rhinitis is a significant underlying
Clinical example factor because of eustachian tube obstruction. If
indicated, allergic rhinitis should be treated in such
Justine was 12 months old and was known to children, but this may not improve the secretory
have atopic dermatitis. She had been otherwise
otitis media.
well and her weight was 10 kg. She was
breastfed and, because her mother was about
to return to work, Justine was offered her first bottle-feed
containing a cow's milk protein formula. Immediately after Practical points
drinking a small amount she became irritable, vomited and
then developed generalized urticaria, a persistent cough, • The atopic diseases of childhood are eczema, asthma and
difficulty breathing and stridor. allergic rhinitis. The majority of children who have these
Justine had experienced an anaphylactic reaction to cow's conditions will be atopic – have allergen-specific IgE (ASE)
milk protein. Although this was the first apparent exposure, to one or more common allergens.
she was likely to have been exposed to cow's milk protein in • The presence of ASE does not always indicate an allergen
maternal breast milk. trigger, and should be interpreted together with the
Adrenaline (epinephrine) is required for the emergency history and/or a trial of allergen avoidance with or without
management and is most easily administered by deep subsequent challenges.
intramuscular injection (0.01 mL/kg of 1 : 1000 (i.e. 0.1 mL at • The management of atopic disease includes identification
Justine's weight of 10.0 kg). The response is usually rapid but and avoidance of allergens (if possible), symptomatic
the dose can be repeated until a clinical response is obtained. treatment and immunotherapy for selected children.
It was important to ensure that the family was educated • Anaphylaxis is a generalized multisystem allergic reaction,
regarding subsequent exclusion of cows’ milk from Justine's which includes cardiorespiratory involvement.
diet. Tolerance to cow's milk develops by school age in the • The emergency treatment of anaphylaxis is adrenaline
majority of children. Approximately 60% of children with a (epinephrine), which, unless hypotension is present, can
cow's milk allergy may have an allergy to other foods – most be administered via the intramuscular route.
commonly egg and nuts. Therefore, a careful history should • All children with anaphylaxis should undergo a specialist
be taken to ensure that these foods have been ingested review so that the trigger can be identified, avoidance
and tolerated. If there has been no ingestion (for example strategies implemented and first aid measures
of nuts), the options of determining IgE to these foods (by a established, including use of injectable adrenaline.
skin prick test or UniCAP) or a graded home introduction can
be discussed with the family.
Obstructive sleep apnoea in allergic rhinitis
Prognosis Nasopharyngeal obstruction in children may present
with snoring and, if severe, obstructive sleep apnoea
The natural history of food allergy and intolerances
(OSA). OSA may present in children with early morn-
is to improve with increasing age. Therefore, care-
ing headache, daytime sleepiness and poor concentra-
fully supervised challenge with the implicated food at
tion. Children who present with allergic rhinitis should
12-month intervals is recommended. Determination
be questioned about these symptoms, and those chil-
of ASE may predict when it is appropriate to consider
dren presenting with upper airway obstruction should
a challenge. IgE-mediated nut, fish and shellfish aller-
be evaluated and, if needed, treated for allergic rhinitis.
gies may require a challenge less frequently because
these allergies may be lifelong, although tolerance may
develop in up to 10% of children. Skin infection in atopic dermatitis
Bacterial, viral and fungal skin infection is an impor-
Recurrent or chronic sinusitis in allergic rhinitis tant complication of atopic dermatitis:
Allergic rhinitis should be considered as a possible pre- • Staphylococcus aureus is detected almost universally
disposing factor in children who: in atopic dermatitis. The organism produces
• have recurrent or chronic sinusitis. The orifices of the exotoxins, which may potentiate the inflammatory
frontal, ethmoid and maxillary sinuses are located in process. Topical antiseptic measures are important
close proximity to the nasal turbinates, and rhinitis but oral antibiotics may be required.
may predispose to ostial obstruction. Symptoms • Herpes simplex virus (HSV) type I may infect
of sinusitis in older children and adults are typical, lesions and present as vesicular lesions, which
and include facial pain, toothache, headache and soon ulcerate. Generalized HSV skin infection
fever (see Chapter 22.1). However, young children may be severe and would be an indication for
may present with rhinorrhoea, cough, post-nasal hospitalization and parenteral aciclovir.
discharge, periorbital swelling and otitis media • Dermatophyte infections may occur in atopic
• have secretory otitis media, in whom the incidence dermatitis and should be considered in resistant
437
of atopy is increased. However, it remains unclear lesions.
 13.1 ALLERGY, IMMUNITY AND INFLAMMATION

Spasmodic croup
laryngotracheobronchitis such as fever or coryza.
Spasmodic croup is a condition of recurrent s­udden Approximately 50% of these children have an atopic
upper airway obstruction that presents as stridor disease. The condition is managed symptomatically
and cough, usually in the early hours of the morning and there is no evidence to suggest that measures such
(see Chapter 14.2). Typically, the condition is short- as allergen avoidance or symptomatic treatment with
lived and there are no features to suggest an ­infective antihistamines are useful.

438
 Immunodeficiency and its 13.2
investigation
Melanie Wong

Recurrent infections, especially in the small child, are • normal microbial flora: gastrointestinal, genital tract
common. It can be challenging, but important, to deter- • phagocytic cells: neutrophils, macrophages
mine which children warrant investigation to exclude • natural killer cells
an underlying immunodeficiency, and which tests are • proteins: complement, mannose-binding lectin,
most appropriate. Primary immunodeficiencies (PID) antimicrobial peptides
are rare, but with increasing physician and community • pattern recognition receptors: toll-like receptors
awareness and rapid technological advances, the num- and the associated transcription pathways.
ber of recognized genetic defects predisposing to infec- 2. Adaptive, antigen-specific immune responses are the
tion risk is increasing exponentially. Some defects are basis of immunological memory and are essential
essential to diagnose early, with appropriate treatment for maturation of protective immune responses and
influencing morbidity and mortality. Others contribute efficacy of vaccination. The components are:
to our understanding of the complexity of the immune • T cells: cellular immunity
response, allow tailoring of treatment and provide an • B cells and antibody: humoral immunity.
explanation to concerned families. Deficiencies or disruption of any of these c­ omponents
Susceptibility to infection varies, influenced by age, can predispose to infection. These defects may be the
genetic and environmental factors, including atopy, sib- result of immaturity, primary or acquired ­deficiency,
lings, daycare, exposure to cigarette smoke, drug thera- influencing age and severity of presentation as well as
pies and anatomical variations, all secondary factors management and prognosis. Some disorders will result in
that may be the sole cause of increased manifestations localized disease, whereas others predispose to infection
of infection, or contribute to the severity of an under- with specific microorganisms, as shown in Figure 13.2.1.
lying primary immune defect. Despite the emphasis on
primary disease, the clinical significance of secondary
The influence of atopy
immunodeficiencies cannot be underestimated.
The aim of this chapter is to provide an approach for When recurrent respiratory infections are the sole
differentiating primary immunodeficiency from other infectious manifestation, allergy must be considered.
factors predisposing to a real or apparent increased Features that suggest an allergic or atopic condition may
risk of infection, based on history, examination and be responsible include absence of fever, clear non-puru-
appropriate initial investigation. A selection of PIDs lent discharge, personal and/or family history of atopic
will be highlighted but it is beyond the scope of this conditions such as eczema, food allergies, asthma and
chapter to discuss in depth the pathophysiology and allergic rhinitis, seasonal or exposure-related pattern,
specialized treatment of these disorders, or specifically variable response to antibiotics, and good response to
to cover all potential PIDs. A list of recent references antihistamines, bronchodilators and/or topical steroids.
is provided for further reading. In addition, atopic tendencies can prolong and adversely
modify the severity of otherwise minor, often viral,
infections for which antibiotics may be prescribed, con-
tributing to the perception of frequent severe infection.
Host factors and resistance
to infection Acquisition of immunological memory
Immune defence is provided by multiple well-orches- The adaptive immune response develops with recur-
trated components, which can be categorized into two rent exposure to infection. Primary exposure often
main groups: resulting in clinical infection occurs most frequently
1. Innate, non-antigen-specific responses are in infancy and early childhood. Secondary exposure
initiated early. There are an increasing number of in the presence of an intact adaptive immune system,
recognized components, including: results in a more rapid and efficient response, and
• barriers: epithelial surfaces, mucosal barriers avoidance of subsequent infection in older children
439
• secretions: saliva, respiratory secretions, tears, urine and adults. In association with increasing exposure,
 13.2 ALLERGY, IMMUNITY AND INFLAMMATION

Specific immunity Non-specific immunity

Antibody Cellular Complement Phagocytes

Defence mainly Intracellular

Bacteria + protozoa Bacteria +fungi
against: organisms

Usual
microorganisms: Pyogenic bacteria: Viruses: Pyogenic bacteria: Bacteria:
Staphylococci Cytomegalovirus Staphylococci Staphylococci
Streptococci Vaccinia Streptococci Gram negative
Haemophilus Herpes Haemophilus
Measles Fungi:
Some viruses: Neisseria Candida
Enteroviruses, e.g. Fungi: Aspergillus
polio, ECHO virus Candida Some viruses
Aspergillus

Bacteria:
Mycobacteria
Listeria

Protozoa:
Pneumocystis

Fig. 13.2.1 Common infections associated with immunodeficiency.

this results in the peak number of infections between or identifiable infection, the possibility of an autoin-
the ages of 2 and 4 years, with an average of six infec- flammatory syndrome should be considered. Many
tions a year. Existence of siblings, daycare attendance primary immunodeficiencies present in infancy with
and exposure to cigarette smoke further increase this dermatological manifestations such as severe or atyp-
number. Children attending daycare or preschool can ical eczema, thrombocytopenic purpura, recalci-
experience 10 to 12 upper respiratory tract infections trant candidiasis and abscesses. Some are diagnosed
and 1 to 2 gastrointestinal tract infections per year. in association with other conditions such as cardiac,
The induction of immunological memory is the prin- endocrine and neurological anomalies (e.g. DiGeorge
ciple underlying vaccination. Not only does ­vaccination syndrome, ataxia telangiectasia). Conditions such as
enable protection from and/or attenuation of the ­severity common variable immunodeficiency, natural killer cell
of t­argeted infections, measurement of specific antibody and complement deficiencies can present at a range of
levels after vaccination provides a means by which the ages, from late infancy to young adulthood.
function of the immune system can be assessed.

Age of presentation, infective complications Defects associated with

and diagnosis
prematurity and delays in
Deficiencies of humoral immunity typically present
after the age of 4–5 months, when maternally-derived
immunological development
antibody has waned. Significant deficiencies of T-cell In the absence of intrauterine infection, the fetus exists
function present earlier, within the first months. The in a sterile environment until birth, at which time
type of infection(s) as well as associated clinical fea- specific immune responses begin to develop. Active
tures may provide clues to the deficient immune com- ­transplacental transport of immunoglobulin (Ig) G
440
ponent (see Fig. 13.2.1, Table 13.2.1). In children (but not IgA, IgM or IgE) occurs during the third tri-
presenting with recurrent fever without obvious and/ mester, providing humoral protection to the newborn.
 Immunodeficiency and its investigation 13.2
Table 13.2.1 Clinical features suggestive of some immune defects

Clinical feature Immunodeficiency

Recurrent sinopulmonary infections/chronic diarrhoea and failure to thrive (and, less commonly, Humoral
cytopenias, arthritis, hepatitis, coeliac disease, inflammatory bowel disease, granuloma formation,
malignancy)

Recurrent fungal, opportunistic infections/chronic diarrhoea, failure to thrive, neonatal hypocalcaemia Cellular

Recurrent periodontal disease, gingivitis, skin and deep abscesses, fungal pneumonia, osteomyelitis Phagocytic

Recurrent or severe meningococcal or pneumococcal infection Complement

Physiological hypogammaglobulinaemia of infancy a trial of cessation of intravenous immunoglobulin

occurs between 3 and 6 months of life at the nadir of (IVIG) should be undertaken after a period free of
waning maternal IgG balanced by increasing infant significant infection. A small number of these chil-
production of IgG (Fig. 13.2.2). This can be accentu- dren continue to have immune abnormalities and
ated and prolonged in premature infants by a reduced require ongoing IVIG, the diagnosis evolving to com-
store of maternally derived IgG, or alternatively by mon variable immunodeficiency (CVID). This diag-
delay in IgG production, the latter termed transient nosis cannot be made definitively before the age of
hypogammaglobulinaemia of infancy. 2 years.
In most cases, these measurable abnormalities are T cell-independent antibody responses, for example
asymptomatic and resolve completely, usually by to polysaccharide antigens, which are important for
9–15 months of age, but in some cases low levels of humoral protection from encapsulated microorgan-
IgG, and sometimes also IgA and IgM, may persist isms such as pneumococcus, Haemophilus and menin-
for longer. With more sophisticated follow-up, spon- gococcus, are poor in infants aged less than 2 years.
taneous resolution has been documented up to the Protein-conjugated vaccines induce T ­cell-dependent
end of the first decade. Immunoglobulin replacement antibody production in younger infants, enabling vac-
therapy may rarely be required in affected infants cination from 2 months of age.
experiencing significant infections despite prophylac- Neonates have relatively low levels of complement
tic antibiotics, such as co-trimoxazole. If commenced, and impairment of neutrophil chemotaxis, both of

Evolution of serum IgG, IgA and IgM levels in utero and during the first year
following birth, illustrating the contribution of maternal and neonatal IgG

12
Maternal IgG
Total IgG
10 Neonatal IgG
IgM
IgA
8

60% of adult
g/L 6 IgG level

75% of adult
2 IgM level
20% of adult
IgA level
0
–8 –6 –4 –2 0 2 4 6 8 10 12

Months pre and post birth

Fig. 13.2.2 Evolution of serum immunoglobulin (Ig)G, IgA and IgM levels in utero and during the first year after birth, illustrating the 441
contribution of maternal and neonatal IgG. Levels of IgM reach adult equivalents by approximately 3 years of age, IgG by 5–6 years
and IgA by 9–12 years.
 13.2 ALLERGY, IMMUNITY AND INFLAMMATION

which mature rapidly during early infancy. T-cell c­ ategories of immune function and thus collectively
proliferative responses are reasonable but c­ytokine
­ are not uncommon. Table 13.2.2 lists these conditions
production, particularly of proinflammatory (T-helper as categorized by IUIS and, where known, the mode
type 1, Th1) cytokines such as interferon (IFN)-γ, is of inheritance.
immature, which may compromise T-cell help. This An underlying PID may be suggested by the frequency,
immaturity may persist in some infants with an atopic severity and type of infection, the response or lack of
tendency, potentially contributing to infection risk. response to antimicrobial therapy, associated fail-
ure to thrive and existence of significant family history
(Box 13.2.1).
Secondary immunodeficiency, usually as a result of
Clinical example suppression, reduced production or loss of c­ omponents
of the immune system, is much more common.
Thomas presented at 12 months of age with a Important causes, listed in Box 13.2.2, include
history of six episodes of otitis media associated prematurity, metabolic diseases, infiltrative diseases
­
with green nasal discharge since the age of and their treatment, malnutrition, infection, trauma,
6 months. Each responded to antibiotics with immunosuppressive therapy and ageing.
recurrence soon after cessation. There was discharge from
the left ear on two occasions from which Streptococcus
pneumoniae and non-typeable Haemophilus influenzae
were isolated. Thomas was thriving and had no other Investigations
symptoms. He was an only child, his immunizations were
The proportion of PIDs in each of the categories listed
up to date, and he did not attend daycare. There was no
significant family history.
in Table 13.2.2 has been calculated from data derived
Examination revealed a perforated left tympanic from four major international PID registries: European
membrane. Tonsillar tissue was present. Full blood count Society for Immunodeficiencies (ESID), Latin
was unremarkable. Serum IgG (2.5 g/L, normal range American Group for Primary Immunodeficiencies
3.4–11.6 g/L) and IgA (0.1 g/L, normal range 0.2–1.2 g/L) were (LAGID), Australia and New Zealand, and Iranian
moderately reduced but IgM level was normal for age. Both registries. Predominantly antibody deficiencies
IgG1 and IgG2 levels were slightly below the normal range.
accounted for 56%, combined antibody and cellu-
T-and B-cell numbers were normal. Levels of antibodies
to vaccine antigens (tetanus, diphtheria, and conjugated lar deficiencies for 8.4%, other well defined immuno-
Haemophilus influenzae B and pneumococcal vaccines) deficiencies 18.3%, diseases of immune dysregulation
were acceptable. 2.7%, disorders of phagocytic cells 11.2%, defects of
A provisional diagnosis of transient hypogammaglobuli­ innate immunity 0.4%, and complement defects for
naemia of infancy was made. A trial of prophylactic, daily, 2.5% of all reported cases. As most of the first three
low-dose co-trimoxazole successfully prevented further categories affect humoral immune responses, screen-
recurrences of ear infection, until an attempt to cease
therapy after a year. Antibiotic prophylaxis was ceased
ing of antibody levels will detect a large proportion
uneventfully at 3 years of age. Serum IgG and IgA levels rose of cases. Blood count and film will identify patients
gradually into the lower end of the normal range by the age with asplenia, ­neutropenia, neutrophil granule abnor-
of 2 and 5 years respectively. malities and thrombocytopenia associated with
small platelet size, the latter features pathognomic of
Wiskott–Aldrich syndrome. Second-tier investigations
(Table 13.2.3), some of which are available only from
specialized laboratories, will depend on clinical suspi-
Primary and secondary cion of either humoral, cellular, phagocytic or comple-
ment abnormalities. Genetic testing may be available to
immunodeficiencies confirm some PIDs and/or used for genetic counselling
More than 150 primary immunodeficiencies (PID) and future prenatal testing.
have been identified and characterized, and the Consideration of age-related reference ranges are
number is growing constantly. An expert interna- essential for interpretation of serum immunoglobulin
tional committee of the International Union of levels (particularly the IgG subclass), lymphocyte num-
Immunological Societies (IUIS) meets regularly to bers and subset analyses. However, there is significant
update continually the known primary immunodefi- variability in the rate of rise in levels as well as biologi-
ciencies and, where identified, the underlying genetic cal fluctuations over time. The division of age groups
cause. The publication by Notarangelo and co-work- for each reference range is arbitrary, such that children
ers, summarizing the most recent meeting in 2009, at the boundaries of age groups may be erroneously
contains detailed tables summarizing clinical features, affected. This may not be obvious to the requesting
442 laboratory findings, genetics and relative frequency of clinician because reference ranges are usually reported
known PIDs. Although, individually, most are rare without information regarding the actual age range or
or extremely rare, many affect similar pathways or the reference range of adjacent age groups. Thus normal
 Immunodeficiency and its investigation 13.2
Table 13.2.2 International Union of Immunological Societies (IUIS) classification of primary immunodeficiencies

Disease Inheritance Disease Inheritance

Combined T- and B-cell Isolated IgG subclass deficiency Variable

immunodeficiency IgA with IgG subclass deficiency Variable
T− B+ SCID Selective IgA deficiency Variable
γc deficiency XL Specific antibody deficiency with normal Ig Variable
JAK3 deficiency AR concentrations and normal B cell numbers
IL-7 receptor α deficiency AR Transient hypogammaglobulinaemia of Variable
CD45 deficiency AR infancy with normal B-cell numbers
CD3δ/CD3ε/CD3ζ deficiency AR Other well-defined
Coronin-1A deficiency AR immunodeficiency syndromes
T− B− SCID Wiskott-Aldrich syndrome XL
RAG1/RAG2 deficiency AR DNA repair defects
DCLREIC (Artemis) deficiency AR Ataxia telangectasia AR
DNA PKcs deficiency AR Ataxia telangectasia-like disease AR
Adenosine deaminase (ADA) deficiency AR Nijmegen breakage syndrome AR
Reticular dysgenesis AR Bloom syndrome AR
Omenn syndrome AR (most) Immunodeficiency with centromeric AR
DNA ligase IV deficiency AR instability and facial anomalies (ICF)
Cernunnos deficiency AR PMS2 deficiency AR
CD40 ligand deficiency XL Thymic defects
CD40 deficiency AR DiGeorge anomaly De novo/AD
Purine nucleoside phosphorylase deficiency AR Immune osseous dysplasias
CD3γ deficiency AR Cartilage hair hypoplasia AR
CD8 deficiency AR Schimke syndrome AR
ZAP-70 deficiency AR Comel–Netherton syndrome AR
Ca2+ channel deficiency AR Hyper-IgE syndromes (HIES)
MHC class I deficiency AR AD-HIES AD
MHC class II deficiency AR AR-HIES AR
Winged helix deficiency (nude) AR Chronic mucocutaneous candidiasis AD/AR/sporadic
CD25 deficiency AR Hepatic veno-occlusive disease with AR
STAT5b deficiency AR immunodeficiency
Itk deficiency AR XL dyskeratosis congenita XL
DOCK8 deficiency AR Diseases of immune dysregulation
Predominantly antibody deficiencies Immunodeficiency with hypopigmentation
Severe reduction in all serum Ig isotypes with Chediak–Higashi syndrome AR
profoundly decreased or absent B cells Griscelli syndrome, type 2 AR
Btk deficiency XL Hermansky–Pudlak syndrome, type 2 AR
μ heavy chain deficiency AR Familial haemophagocytic
λ5 deficiency AR lymphohistiocytosis
Igα deficiency AR Perforin deficiency AR
Igβ deficiency AR UNC13-D deficiency AR
BLNK deficiency AR Syntaxin 11 deficiency AR
Thymoma with immunodeficiency None Lymphoproliferative syndromes
Severe reduction in at least 2 serum Ig isotypes XLP1, SH2D1A deficiency XL
with normal or low numbers of B cells XLP2, XIAP deficiency XL
 Common variable immunodeficiency Variable Itk deficiency AR
disorders Syndromes with autoimmunity
ICOS deficiency AR Autoimmune lymphoproliferative
CD19 deficiency AR syndrome (ALPS)
TACI deficiency AD or AR CD95 (Fas) defects, ALPS type 1a AD
BAFF receptor deficiency AR CD95L (Fas ligand) defects, ALPS
Severe reduction in serum IgG and IgA with type 1b AR
normal/raised IgM and normal B-cell numbers Caspase 10 deficiency, ALPS type 2a AR
CD40L deficiency XL Caspase 8 deficiency, ALPS type 2b AR
CD40 deficiency AR Activating N-ras, N-ras-dependent ALPS AD
AID deficiency AR APECED (autoimmune polyendocrinopathy with AR
UNG deficiency AR candidiasis and ectodermal dystrophy)
Isotype or light chain deficiencies with normal IPEX (immune dysregulation, XL
numbers of B cells polyendocrinopathy, enteropathy,
Ig heavy chain mutations or deletions AR X-linked)
443
κ chain deficiency AR CD25 deficiency AR

(Continued )
 13.2 ALLERGY, IMMUNITY AND INFLAMMATION

Table 13.2.2 International Union of Immunological Societies (IUIS) classification of primary immunodeficiencies—cont'd

Disease Inheritance Disease Inheritance

Congenital defects of phagocyte number, Autoinflammatory disorders

function or both Familial Mediterranean fever AR
Severe congenital neutropenias AD TNF receptor-associated periodic fever AD
Kostman disease AR syndrome (TRAPS)
Neutropenia with cardiac and urogenital AR Hyper-IgD syndrome AR
malformations Muckle–Wells syndrome AD
Glycogen storage disease type 1b AR Familial cold autoinflammatory syndrome AD
Cyclic neutropenia AD NOMID/CINCA AD
X-linked neutropenia/myelodysplasia XL Pyogenic sterile arthritis, pyoderma AD
P14 deficiency AR gangrenosum, acne (PAPA) syndrome
Leukocyte adhesion deficiency type 1 AR Blau syndrome AD
Leukocyte adhesion deficiency type 2 AR Chronic recurrent multifocal osteomyelitis AR
Leukocyte adhesion deficiency type 3 AR and congenital dyserythropoietic
Rac2 deficiency AD anaemia (Majeed)
β-Actin deficiency AD DIRA (deficiency of IL-1 receptor antagonist) AR
Localized juvenile periodontitis AR Complement deficiencies
Papillon–Lefèvre syndrome AR C1q deficiency AR
Specific granule deficiency AR C1r deficiency AR
Schwachman–Diamond syndrome AR C1s deficiency AR
X-linked chronic granulomatous disease XL C4 deficiency AR
Autosomal chronic granulomatous diseases AR C2 deficiency AR
IL-12 and IL-23 receptor β1-chain deficiency AR C3 deficiency AR
IL-12p40 deficiency AR C5 deficiency AR
IFN-γ receptor 1 deficiency AR, AD C6 deficiency AR
IFN-γ receptor 2 deficiency AR C7 deficiency AR
STAT1 deficiency AR C8 deficiency AR
AR hyper-IgE syndrome AR C9 deficiency AR
AD hyper-IgE syndrome AD C1 inhibitor deficiency AD
Pulmonary alveolar proteinosis Bi-allelic Factor I deficiency AR
Defects in innate immunity Factor H deficiency AR
Anhidrotic ectodermal dysplasia with XL Factor D deficiency AR
immunodeficiency (EDA-ID) Properdin deficiency AR
AD EDA-ID AD Mannose-binding lectin deficiency AR
IL-1 receptor-associated kinase 4 (IRAK4) AR MASP2 deficiency AR
deficiency AR Complement receptor 3 (CR3) deficiency AR
MyD88 deficiency AD Membrane cofactor protein (CD46) AD
WHIM (warts, hypogammaglobulinaemia, deficiency
infections, myelokathexis syndrome) Membrane attack complex inhibitor (CD59) AR
Epidermodysplasia verruciformis AR deficiency
Herpes simplex encephalitis (HSE) – UNC93B1 AR Paroxysmal nocturnal haemoglobinuria Acquired
HSE – TLR3 AD Immunodeficiency associated with ficolin-3 AR
Chronic mucocutaneous candidiasis – CARD9 AR deficiency
Trypanosomiasis AD

AD, autosomal dominant; AR, autosomal recessive; IFN, interferon; Ig, immunoglobulin; IL, interleukin; XL, X-linked.
Modified from: Notarangelo LD, Fischer A, Geha RS et al 2009 Primary immunodeficiencies: 2009 update. Journal of Allergy and
Clinical Immunology 124:1161–1178.

screening tests, particularly at the lower end of the ref- exposure to excess radiation should be avoided. The indi-
erence range, in the presence of a suspicious clinical cation for each chest X-ray and computed tomography
picture, should not prevent specialist referral. scan, especially repeated high-resolution scans to assess
Many primary immunodeficiencies are associated with the presence of bronchiectasis, should be considered
an increased risk of malignancy. Thus, where possible, carefully.
444
 Immunodeficiency and its investigation 13.2
Box 13.2.1 Warning signs of primary immunodeficiency
• immunoglobulin replacement therapy, mostly as
a monthly intravenous infusion in hospital, but
Patients are advised to seek medical review if affected increasingly via subcutaneous infusion at home
by 2 or more of the following 10 warning signs of primary • avoidance of live vaccinations where a T-cell
immunodeficiency (Jeffrey Modell Foundation, New York): defect is suspected and live polio vaccination in
1. Eight or more new ear infections within 1 year hypogammaglobulinaemia. Routine immunization
2. Two or more serious sinus infections within 1 year is unnecessary when receiving immunoglobulin
3. Two or more months on antibiotics with little effect
replacement therapy and any potential response may
4. Two or more pneumonias within 1 year
5. Failure of an infant to gain weight or grow normally be inhibited. However, influenza vaccination may be
6. Recurrent, deep skin or organ abscesses of benefit in some patients, such as those with CVID
7. Persistent thrush in the mouth or on the skin, after age 1 year • bone marrow transplantation, for example in SCID
8. Need for intravenous antibiotics to clear infections or WAS
9. Two or more deep-seated infections such as meningitis, • gene therapy for some rare PIDs – gene therapy
osteomyelitis, cellulitis or sepsis for X-linked SCID has been the most successful to
10. A family history of primary immunodeficiency
date, but remains experimental in view of ongoing
safety and technical concerns.
Treatment
Management will depend on the diagnosis but may
include: Specific primary
• awareness of types of infection most likely for that PID immunodeficiency disorders
• early, appropriate antibiotic treatment
Examples of some important primary immunodefi-
• prophylactic therapy – for example, co-trimoxazole
ciency disorders are discussed.
for chronic granulomatous disease (CGD) and severe
combined immunodeficiency (SCID), antifungals
for CGD and mucocutaneous candidiasis (MCC), Predominantly antibody deficiencies
IFN-γ for CGD
X-linked agammaglobulinaemia/Btk deficiency
• awareness and management of autoimmune
and atopic disease complications, for example in Affected boys have a defect in BTK (Bruton tyrosine
common variable immunodeficiency (CVID) and kinase) gene on the X chromosome. The gene prod-
Wiskott–Aldrich syndrome (WAS) uct, Btk, has a major role in activated B-cell receptor

Box 13.2.2 Secondary immunodeficiency

Premature and newborn Infectious diseases

• Congenital rubella
Hereditary and metabolic diseases • Viral exanthema – measles, varicella
• Chromosomal abnormalities (e.g. Down syndrome) • HIV infection, AIDS
• Uraemia • Cytomegalovirus
• Diabetes mellitus • Infectious mononucleosis
• Malnutrition • Bacterial infections
• Vitamin and mineral deficiencies • Mycobacterial, fungal or parasitic diseases
• Protein-losing enteropathies
• Nephrotic dystrophy
• Myotonic dystrophy Infiltrative and haematological diseases
• Sickle cell disease • Histiocytosis
• Sarcoidosis
Immunosuppressive agents • Hodgkin's disease and lymphoma
• Radiation • Leukaemia
• Immunosuppressive drugs • Myeloma
• Corticosteroids • Agranulocytosis and aplastic anaemia
• Anti-lymphocyte or anti-thymocyte globulin • Lymphoma in immunocompromised transplant recipients
• Anti-T- or B-cell monoclonal antibodies

Surgery and trauma Miscellaneous

• Burns • Lupus erythematosus
• Splenectomy • Chronic active hepatitis
• Anaesthesia • Alcoholic cirrhosis
• Head injury • Ageing
445
 13.2 ALLERGY, IMMUNITY AND INFLAMMATION

Table 13.2.3 Investigations for immunodeficiency

Test Suspected deficiency

Screening
Blood count and film
Immunoglobulin G, A and M levels

Second tier dependent on clinical suspicions

Immunoglobulin G subclass titres (IgG 1, 2, 3, 4) H, Com
Immunoglobulin E H, Com, N
Isohaemagglutinins H, Com
Specific antibody titres H, Com
• After routine vaccinations – tetanus, diphtheria, Hib, pneumococcal
• After pneumococcal polysaccharide vaccine – non-conjugate vaccine serotypes
Lymphocyte subsets (T, B and NK cell) H, C, Com
Check chest X-ray for thymus (neonates and young infants) C, Com
Lymphocyte proliferation to mitogens (e.g. PHA, ConA) (non-specific) C, Com
Lymphocyte proliferation to specific antigens (e.g. Candida) C, Com
Adenosine deaminase and purine nucleotide phosphorylase measurements C, Com
Neutrophil function testing N
• Nitroblue tetrozolium (NBT)/equivalent dihydrorhodamine (DHR)-based assay
• More extensive testing of chemiluminescence, chemotaxis
• Surface expression of CD11 and CD18
NK cell cytotoxicity NK
Complement testing Complement
C3, C4, CH50 (AH50, specific complement components)
C1 esterase inhibitor and function C1-INH
HIV testing C, Com
Genetic studies

C, cellular; Com, combined humoral and cellular; ConA, concanavalin A; H, humoral; HIV, human immunodeficiency virus; INH,
inhibitor; N, neutrophil/phagocyte; NK, natural killer cell; PHA, phytohaemagglutinin.

signalling and is required for normal B-cell develop- The most useful clinical feature is absent or mark-
ment. In X-linked agammaglobulinaemia (XLA), pre- edly hypoplastic tonsils. Serum IgG levels are mark-
cursor cells in the marrow fail to develop into mature edly reduced with undetectable IgA and IgM. There
circulating B cells. Absence of peripheral mature B is an absence of circulating B cells and no functional/
cells is also a feature of several rarer autosomal reces- specific antibody response to common antigens such
sive forms of early-onset hypogammaglobulinaemia as tetanus and diphtheria vaccination. Absent Btk
with clinical features similar to XLA, but also affect- expression can be demonstrated on flow cytome-
ing girls (see Table 13.2.2). try and BTK mutations on genetic testing, both of
Most boys with XLA are asymptomatic for the which detect female carrier status. If prenatal diag-
first 4–6 months of life. Nearly all develop symptoms nosis is not undertaken, newborn males with a fam-
by 18 months of age, and the diagnosis is usually ily history can be screened non-invasively for absent
made within the first 3 years of life. The common- cord blood B cells. Early diagnosis allows institu-
est manifestations are recurrent mucopurulent otitis tion of therapy before the development of infective
media, upper and lower respiratory tract infections complications.
with common respiratory tract organisms, in par- Early commencement of lifelong immunoglobulin
ticular Streptococcus pneumoniae and Haemophilus replacement therapy will minimize complications, sig-
influenzae type b, despite vaccination, as well as nificantly reducing the incidence of chronic lung dis-
Staphylococcus aureus infections. Resolution is often ease and prolonging life expectancy. However, as these
slow and incomplete, eventually leading to bronchi- infusions replace only IgG, recurrent conjunctivitis and
ectasis in the absence of intervention. Meningitis, diarrhoea may not be eliminated because ­secretory IgA
septicaemia, diarrhoea, aseptic mono- or oligo-artic- function is not restored. The usual dose is 400 mg/kg
ular arthritis, septic arthritis, osteomyelitis, chronic intravenously every 4 weeks, but varies to maintain
or recurrent conjunctivitis, and chronic or dissemi- adequate trough IgG levels and to prevention infection.
446
nated enteroviral infection occur more frequently. This 4-week interval between infusions is based on a
 Immunodeficiency and its investigation 13.2
half-life of IgG in normal individuals of 21–28 days, shared by other well-defined i­mmunodeficiencies such
but some individuals require more frequent infusions. as mutations in genes for Btk in XLA, CD40 ligand in
Alternatively immunoglobulin replacement can be hyper-IgM syndrome, and SLAM-associated protein
given by subcutaneous infusions once to three times (SAP) in X-linked lymphoproliferative disease. In recent
a week, facilitating administration at home. Specific years, mutations in a number of novel genes have been
infections are treated with appropriate antibiotics. identified, including BAFF-receptor, TACI, CD20,
CD81, Toll-like receptors and CD21, which all result
in a failure to produce an adequate humoral immune
Hyper-IgM syndrome
response. Despite these advances, however, many of
Most cases of hyper-IgM syndrome are X-linked, and the defects underlying CVID are not yet known. The
are secondary to mutations in the CD40 ligand gene. majority of individuals with CVID have no family his-
Hyper-IgM syndrome is characterized by defective tory of CVID. However, 10–20% may have a relative
B-cell switching from IgM to IgG and IgA produc- with selective IgA deficiency.
tion, as well as abnormalities of T-cell function. An CVID is an acquired hypogammaglobulinaemia,
autosomal recessive form secondary to mutations in with onset usually in the second and third decades
the CD40 gene has similar clinical features, whereas but sometimes in childhood. The spectrum of respi-
there is no T-cell dysfunction in the other known reces- ratory infections is similar to that observed in XLA,
sive forms, AID and UNG deficiency. Raised IgM lev- but onset of the symptoms may be more insidious.
els can also be found in other immunodeficiencies such Uncommonly pneumonia has been associated with
as CVID and anhidrotic ectodermal dysplasia with Pseudomonas aeruginosa or Pneumocystis jiroveci
immunodeficiency (NEMO deficiency). (previously P. carinii). Occasionally, lymphoid inter-
The spectrum of respiratory infections is similar to stitial pneumonitis develops, presenting with cough,
that observed in XLA, but Pneumocystis pneumonia dyspnoea, weight loss and an interstitial infiltrate,
is a frequent presentation. Intermittent or persistent causing a restrictive lung disease pattern. Diarrhoea
neutropenia commonly causes oral and upper gas- due to Campylobacter jejuni or Giardia lamblia is
trointestinal tract ulceration. Haemolytic anaemia, common. Other manifestations include hepato-
thrombocytopenia, nephritis and arthritis also occur. splenomegaly, autoimmune haemolytic anaemia,
Infection with Cryptosporidium is common and may thrombocytopenia, neutropenia, non-caseating gran-
lead to sclerosing cholangitis. ulomas of lungs, spleen, skin and liver, and atypical
Serum IgA and IgG levels are low with a normal lymphoid hyperplasia. There is an increased inci-
or raised IgM concentration. B- and T-cell numbers dence of lymphoma.
are normal. However, there is an absence of switched The diagnosis of CVID depends on exclusion of
memory B cells. Primary and secondary antibody other well-defined syndromes on the background
responses are reduced and limited to IgM. Hyper-IgM of significantly reduced serum IgG levels (usually
syndrome must be considered when there is a history not as low as in XLA) and reduced IgA and/or IgM
of proven Pneumocystis pneumonia and a normal with defective specific antibody responses. T- and
mitogen-induced T-cell proliferative response, mak- B-cell numbers are variable, as are T-cell prolifera-
ing SCID unlikely. X-linked hyper-IgM syndrome tive responses. A diagnosis of CVID cannot be made
can be confirmed by absent CD40 ligand expression in children less than 2 years of age, although a small
on activated T cells or identification of mutations in number of children with presumed transient hypogam-
the CD40 ligand gene. CD40 deficiency can be identi- maglobulinaemia, selective antibody, IgA or IgG sub-
fied by absence of CD40 expression on B cells. class deficiency may subsequently develop definitive
Treatment consists of intravenous immunoglobulin features of CVID. Measurement of switched memory
replacement therapy, appropriate antibiotic treatment B cells may prove helpful in determination of diagno-
of specific infections, and prophylaxis for Pneumocystis sis, prognosis and therapeutic decisions. The subset of
infection. Granulocyte–macrophage colony-stimulat- children and adults with CVID who have low numbers
ing factor (GM-CSF) may be required if neutropenia of switched memory B cells tends to have more infec-
is severe. Measures to avoid Cryptosporidium infection tions, as well as autoimmune, granulomatous and lym-
may prevent liver disease. phoproliferative complications.
Treatment consists of intravenous ­immunoglobulin
replacement therapy and appropriate antibiotic
­
Common variable immunodeficiency
treatment of specific infections. Autoimmune phe-
CVID is a heterogeneous group of disorders due to either nomena may need corticosteroid and immunomod-
an intrinsic B-cell defect or a B-cell dysfunction second- ulatory therapy, and those considered at risk of
ary to abnormal T cell–B cell i­nteraction. Underlying Pneumocystis infection should receive co-trimoxa-
447
genetic defects are being identified increasingly, some zole prophylaxis.
 13.2 ALLERGY, IMMUNITY AND INFLAMMATION

Selective IgA deficiency relevance, particularly specific antibody responses to

polysaccharide antigens, such as unconjugated pneu-
Selective IgA deficiency is defined as a serum IgA
mococcal vaccine, in children older than 2 years.
level of less than 0.05–0.07 g/L (the lower limit of
Maturational delay of T cell-independent antibody
detection of most commercial assays) with normal
responses may prolong susceptibility to infections
IgG and IgM levels, probably secondary to impaired
­(particularly sinopulmonary infections) with encapsu-
switching from IgM to IgA production. No underly-
lated bacteria in children over the age of 2 years, even
ing genetic defect has been identified and there is usu-
in the presence of quantitatively ‘normal’ levels of IgG,
ally no family history. It is the commonest primary
IgA and IgM. Defective antibody responses associated
immunodeficiency, with reported prevalence ranging
with quantitatively normal IgG and IgG subclass lev-
from 1 in 200 to 1 in 1000 of the normal population.
els is referred to as specific antibody deficiency (SAD).
Most are asymptomatic but there is an increased inci-
Many children with SAD also do not respond to conju-
dence of recurrent infections, particularly bronchitis
gated pneumococcal vaccination. However, conjugated
and otitis media. More severe suppurative sinopul-
vaccine will benefit those children who do respond.
monary disease is less common and is often associ-
Clinical features of SAD and IgG subclass defi-
ated with reduced IgG2 subclass levels and specific
ciency with defective antibody responses include
antibody deficiency. Secretory IgM is thought to
chronic otitis media with discharge, bronchitis, sinus-
compensate for IgA deficiency in asymptomatic
itis and pneumonia. Affected individuals usually pres-
individuals.
ent in the first 7 years of life. The range and severity of
Serum IgA levels are low in normal infants, reaching
infections may be similar to those in other antibody
adult equivalents by 9–12 years of age. IgA deficiency
deficiencies such as XLA and CVID.
may be transient, reflecting a maturational delay. The
Management of symptomatic children with defec-
detection of salivary IgA may help distinguish this
tive antibody responses with or without IgG sub-
group, as salivary IgA levels reach normal adult lev-
class deficiency includes ready access to antibiotic
els by 6 months of age. However, this test is not rou-
therapy, a trial of antibiotic prophylaxis and, in a
tinely available. The clinical significance of detectable
small subset, intravenous immunoglobulin ther-
serum IgA but at a level below the normal reference
apy with periodic reassessment of ongoing require-
limit is uncertain, but in most children IgA levels
ment. In many, the defect will resolve with age, but
are likely eventually to increase to the normal range.
in a smaller proportion the defect is permanent or
Transient IgA deficiency in infants and young chil-
evolves into CVID.
dren is unlikely to predispose to increased frequency
or severity of infections.
IgA deficiency is associated with an increased inci-
Combined T- and B-cell immunodeficiency
dence of autoimmune diseases, allergic disorders and
malignancy. Acute reactions, including anaphylaxis, Severe combined immunodeficiency
to residual IgA in blood transfusions and intravenous
SCID encompasses a heterogeneous group of condi-
immunoglobulin can occur due to the development of
tions associated with a profound deficiency of both
anti-IgA antibodies.
T- and B-cell function, the genetic basis of which is
being increasingly identified (see Table 13.2.2). X-linked
IgG subclass deficiency and specific
SCID, secondary to a mutation in the common γ chain
antibody deficiency
of the interleukin (IL)-2 receptor, accounts for over half
There are four subclasses of IgG. IgG1 accounts for of all cases. Autosomal recessive forms include defects
65% of total serum IgG, IgG2 for 25%, IgG3 for 7% of recombinase activating genes (RAG-1 and RAG-
and IgG4 for less than 5%. Antibody responses to 2), IL-7 receptor, signalling components after T-cell
peptides are predominantly IgG1 and IgG3, whereas receptor activation such as ZAP-70 and Jak3, enzymes
responses to polysaccharides are predominantly IgG2 essential for lymphocyte metabolism such as adenosine
and, to a lesser extent, IgG1. Deficiency may occur deaminase (ADA) and purine nucleoside phosphorylase
in one or more subclasses. However, the diagnosis is (PNP), and DNA repair mechanisms such as Artemis.
hampered by the significant individual variation in SCID usually presents within the first 6 months
IgG subclass levels with age, and the logistic difficul- of life. There is often a history of diarrhoea, lower
ties in establishment of age-related normal ranges. respiratory tract infections, failure to thrive, candi-
There is poor correlation between the diagno- diasis and rash. Pneumocystis pneumonia is com-
sis of IgG subclass deficiency and susceptibility to mon and its occurrence should always prompt
infection, resulting in controversy regarding whether investigation to exclude SCID. It is often insidious
IgG subclass deficiency is a true immunodeficiency. in onset with cough and pulmonary infiltrates that
448
Coexistence of a functional antibody deficit is of more progress over several weeks (Fig. 13.2.3). Children
 Immunodeficiency and its investigation 13.2

Clinical example

Daniel presented to the emergency department

of his local hospital at 4 months of age with
a 2-week history of increasing cough and
respiratory distress. He also had persistent
oral and napkin-area thrush associated with chronic loose
stools, irritability and poor weight gain over the preceding
couple of months. He had received his routine vaccinations
at 2 months of age. There was no known family history of
immunodeficiency.
On physical examination, he had evidence of failure
to thrive, with reduced subcutaneous fat and his weight
was significantly below the third percentile for age. Lymph
nodes were not palpable and no tonsils were seen. He was
tachypnoeic and had generally reduced air entry. Chest
X-ray revealed hyperinflated lungs with a diffuse interstitial
infiltrate. There was no thymic shadow.
Daniel was found to be lymphopenic (0.2 × 109/L) on
full blood count. Serum IgG was very low (0.4 g/L, normal
Fig. 13.2.3 Chest X-ray of a 6-month-old child with range 1.6–7.8 g/L) and IgA undetectable, whereas IgM
Pneumocystis pneumonia associated with severe combined was mildly reduced (0.26 g/L, normal range 0.33–1.05 g/L).
immunodeficiency. The mediastinum is narrowed by absence Isohaemagglutinins were not detected. Lymphocyte subsets
of the thymic shadow. The lungs are hyperinflated and there is demonstrated absence of T and natural killer (NK) cells, but
bilateral diffuse pulmonary infiltrate. the presence of some B cells. There were no detectable
antibodies to his routine vaccinations and no T-cell
proliferative response to the mitogen, phytohaemagglutinin
(PHA). Stool culture detected vaccine associated poliovirus.
Pneumocystis jiroveci was isolated from bronchoalveolar
with SCID are extremely susceptible to bacterial, lavage (BAL) sampling.
viral and fungal infection. Without bone marrow The diagnosis of X-linked severe combined
transplantation, death usually occurs within the first immunodeficiency was made. Daniel commenced treatment
2 years of life. for Pneumocystis pneumonia with high-dose intravenous
Immune abnormalities vary but usually include co-trimoxazole and corticosteroids, and started replacement
lymphopenia with markedly reduced T-cell num- with monthly intravenous immunoglobulin (IVIG). On recovery
from his respiratory illness, the co-trimoxazole was reduced
bers and reduced serum IgG, IgA and IgM levels.
to a prophylactic dose to prevent recurrence of Pneumocystis
The presence or absence of normal B-cell num- infection. Daniel underwent a successful HLA-matched
bers may help to identify the underlying genetic unrelated bone marrow transplant from cord blood 3 months
defect (see Table 13.2.2). T-cell proliferative response later, having no suitable HLA-matched relatives. Daniel is
to mitogens is abnormal, and specific antibody now well with no detectable immune abnormality.
responses, including isohaemagglutinins, are absent. Genetic testing confirmed the diagnosis of X-SCID and
Daniel's mother's carrier status. This enabled prenatal
Molecular diagnosis should be undertaken where
diagnosis in subsequent pregnancies.
available to aid genetic counselling and future pre-
natal diagnosis.
Supportive treatment involves protective isolation,
specific antimicrobial therapy, intravenous immu-
noglobulin replacement and prophylaxis against Other well-defined immunodeficiency
Pneumocystis. Live virus vaccines should be avoided syndromes
and blood products must be irradiated to prevent
Wiskott–Aldrich syndrome
graft-versus-host disease from transferred T cells.
Definitive therapy is bone marrow transplantation. Wiskott–Aldrich syndrome is an X-linked condition
Early transplantation from a human leukocyte anti- that usually presents with refractory atopic dermati-
gen (­ HLA)-identical sibling has a success rate of over tis and thrombocytopenic purpura. Otitis media and
90%, but is lower with matched unrelated donors. pneumonia are common and associated with defec-
ADA deficiency can be treated with ADA replace- tive antibody response to polysaccharide antigens.
ment. Patients with X-SCID and ADA deficiency There is a variable T-cell defect and children with
have been treated successfully with gene therapy, but WAS are at risk of Pneumocystis infection. Serum
this remains experimental owing to technical and IgA and IgE levels are usually high, with low or nor-
449
safety concerns. mal IgG and IgM levels. There is a ­variable reduction
 13.2 ALLERGY, IMMUNITY AND INFLAMMATION

in T-cell number and function, which deteriorates facies with palatal dysfunction leading to feed-
with age. Platelets are ­typically small. Definitive diag- ing difficulties, speech delay and ­aspiration, behav-
nosis can be made by demonstrating a mutation in ioural and ­ developmental problems, and thymic
the WASP gene. absence or hypoplasia resulting in T cell-­mediated
Treatment consists of IVIG for demonstrated anti- immunodeficiency.
body deficiency, appropriate antibiotic treatment of Complete absence of the thymus resulting in a SCID
specific infections, and prophylaxis for Pneumocystis phenotype is rare. Most patients have mild immune
infection. Life expectancy is reduced by infection, impairment. Susceptibility to otitis media and sinusitis
haemorrhage and a high incidence of malignancy, often is usually more a result of anatomical and functional
B-cell lymphoma, in early adult life. Splenectomy can airway compromise than of systemic immunodefi-
reduce the risk of life-threatening haemorrhage but ciency. The commonest finding is a mild reduction in
increases the risk of serious infection with encapsu- total T-cell numbers (CD3), particularly of the CD4
lated organisms. Definitive treatment is bone marrow subset, which is usually of no clinical significance.
transplantation, although the preliminary results of Occasionally there is an associated specific antibody
gene therapy in children with WAS appear promising. deficiency that requires immunoglobulin replacement
therapy. Live vaccines should not be given until the
degree of immune impairment has been determined.
Ataxia telangectasia
Ataxia telangectasia (AT) is an autosomal recessive
Chronic mucocutaneous candidiasis
chromosomal breakage syndrome, resulting from a
defect in DNA repair. Most patients present with ataxia Chronic mucocutaneous candidiasis (CMC) is charac-
in infancy or early childhood, then develop telangiecta- terized by persistent or recurrent Candida infections of
sia of the skin and bulbar conjunctivae associated with the skin, mucous membranes and nails. In most, iso-
hyperpigmented and depigmented cutaneous patches. lated defects in cell-mediated immunity to Candida can
The degree of immune dysfunction is variable. be demonstrated by delayed hypersensitivity skin tests
Suppurative sinopulmonary infections occur in half or in vitro techniques.
of the patients. Aspiration may contribute, the sever- There are several distinct clinical syndromes. The
ity of respiratory tract disease usually correlating with classical autosomal recessive form, secondary to muta-
the severity of neurological impairment. Pneumonia tions in the AIRE gene, is associated with autoimmune
is a major cause of death. There is a high incidence of polyendocrinopathies (APECED). An autosomal
lymphoreticular malignancy. dominant form is associated with thyroid disease.
IgA deficiency, often with associated IgG2 subclass Although candidiasis usually manifests before the age
deficiency, is common. IgE is often absent. Defects of 5 years, endocrine dysfunction may present at any
in T-cell function and number are variable. Serum age. Deficiencies of CARD-9 and Dectin-1 have been
α-fetoprotein levels are raised in virtually all cases. identified in CMC without endocrinopathy. CMC
Defects in DNA repair lead to an increased incidence is also a prominent feature of hyper-IgE syndrome.
of chromosome breaks in cytogenetic studies. Defects in the Th17/IL-17 pathway, involving either
Infections should be treated early with appropriate Th17 cell numbers, ligand binding, signalling path-
antibiotics, whereas IVIG may be indicated if a signifi- ways, IL-17 and/or IL-22 production or neutralizing
cant antibody defect is demonstrated. antibodies to these cytokines, appear to be the unify-
ing aetiology of CMC in these diverse conditions.
Long-term oral antifungal therapy is usually
DiGeorge syndrome (velocardiofacial
required to prevent recurrence.
syndrome, Sprintzen syndrome)
DiGeorge syndrome is the result of interrupted
Hyper-IgE syndrome
embryonic development of the third and fourth pha-
ryngeal pouches. Deletions of chromosome 22q11.2, Hyper-IgE syndrome is characterized by recur-
detectable by fluorescence in situ hybridization rent infections and eczematous or vesicular rash
(FISH), are found in over 85% of cases, whereas dele- from infancy. There is progressive development of
tions of chromosome 10p13-14 are found in a smaller coarse facial features, osteopenia, retained primary
number. ­dentition and skeletal abnormalities. Subcutaneous
There is a significant phenotypic variability, but cold abscesses and suppurative lower respiratory tract
the syndrome is characterized by conotruncal car- disease caused by staphylococcus, Haemophilus influ-
diac defects (e.g. interrupted aortic arch or truncus enzae, pneumococcus, Candida and Pseudomonas are
arteriosus), symptomatic neonatal hypocalcaemia common. Persistent pneumatoceles (Fig. 13.2.4) fol-
450
secondary to parathyroid hypoplasia, c­ haracteristic lowing infection occur in most patients.
 Immunodeficiency and its investigation 13.2

Practical points

• Recurrent infections are common in early childhood.

• Resistance to infection is provided by non-specific
mechanisms and through the adaptive immune response.
• A small number of children with recurrent infections will
have a primary immunodeficiency disorder.
• Some components of the immune response are immature
at birth.
• A blood count, blood film and measurement of serum
immunoglobulin concentrations can be a useful screen for
primary immunodeficiency disorders.

Surgical intervention may be required and IVIG may

reduce the incidence of infection if a functional antibody
deficiency is demonstrated.

Phagocytic cell disorders

Chronic granulomatous disease
CGD is caused by a defect of one of the four subunits
of phagocyte NADPH oxidase (phox), required to
produce the respiratory burst that generates r­eactive
Fig. 13.2.4 Staphylococcal pneumonia with pneumatocele in oxygen intermediates, such as superoxide and hydro-
hyper-IgE syndrome. gen peroxide, which are used to kill phagocytosed
pathogens. The majority (60–70%) of cases are due
to an X-linked mutation of the gp91phox gene; the
Serum IgE levels are usually markedly raised, but remainder are due to autosomal recessive mutations
may be near normal in infancy. Extremely high IgE of p22phox, p47phox or p67phox.
levels can also be detected in infants with severe Failure to thrive, bacterial adenitis, abscesses
atopic dermatitis, but this can be differentiated from or osteomyelitis may occur within the first year of
hyper-IgE syndrome by the localization of infection life. Pneumonia and lymphadenitis due to catalase-­
to superficial skin and by the distribution and char- positive organisms such as Staphylococcus and
acteristics of the rash. Levels IgG, IgA and IgM are Serratia, or fungi such as Candida and Aspergillus
also typically increased. There are variable defects in are the most common infections. Intestinal or uri-
neutrophil chemotaxis. Some subjects have a defec- nary tract obstruction can be caused by granuloma
tive functional antibody response to polysaccharide formation. Gingivitis (Fig. 13.2.5), inflammatory
antigens.
Most cases of hyper-IgE syndrome are autosomal
dominant or sporadic. These are secondary to muta-
tions in the STAT3 gene which causes deficiency
of Th17 cells and, as a consequence, of cytokines
such as IL-17 and IL-22, which have important roles
in humoral immune responses and defence against
mucocutaneous candidiasis. The mechanism by
which STAT3 mutations cause the musculoskeletal
associations is yet to be fully elucidated. Mutations
in Tyk2 and DOCK-8 are causes of autosomal reces-
sive hyper-IgE syndrome. Patients with autoso-
mal recessive hyper-IgE syndrome typically do not
develop the musculoskeletal abnormalities, and have
a higher incidence of viral infections and malig-
nancy than those with autosomal dominant disease. Fig. 13.2.5 Gingival inflammation secondary to infection in an
Management consists of long-term anti-­staphylococcal individual with cyclic neutropenia. Symptoms included halitosis 451
antibiotic prophylaxis and treatment of acute infections. and bleeding gums with minor trauma.
 13.2 ALLERGY, IMMUNITY AND INFLAMMATION

bowel disease, hepatosplenomegaly and lymphade- molecules (CD11a, CD11b and CD11c) on stimulated
nopathy are other features. neutrophils.
The diagnosis is made by demonstrating absence
of an oxidative burst in activated neutrophils on
Defects of the interleukin-12/interferon-γ axis
nitroblue tetrazolium (NBT) testing or an equiva-
lent flow cytometric assay. These tests can detect A number of gene defects affecting the IL-12/IFN-γ
female carriers of X-linked CGD, but not autoso- axis have been identified (see Table 13.2.2) that pre-
mal recessive carriers. CGD can be confirmed on dispose affected individuals to atypical mycobacterial
formal neutrophil function testing and/or by molec- and salmonella infections.
ular testing.
Early diagnosis and co-trimoxazole prophylaxis
has dramatically reduced the incidence of infections
and improved survival. Additional antifungal and/or Practical points
IFN-γ prophylaxis is also beneficial. Development of
invasive fungal infections is associated with poorer • Primary immunodeficiency disorders may present with
severe or unusual infections.
prognosis. Bone marrow transplantation is gener-
• Many of the primary immunodeficiency disorders are
ally limited to patients with more severe disease, associated with specific gene mutations.
preferably where there is a related HLA-matched • Treatment of a primary immunodeficiency disorder
donor, and is associated with significant mortality. depends on a specific diagnosis, treatment and
Promising results had been reported in preliminary prevention of a variety of infections, and therapies such
trials of gene therapy, but the response proved short- as intravenous immunoglobulin and bone marrow
lived owing to lack of a selective advantage in gene- transplantation.
modified cells. • Demonstration of a specific genetic defect is important
information for genetic counselling.

Leukocyte adhesion deficiency Complement disorders

These rare conditions are secondary to abnormalities Deficiencies of early classical complement components
of cell surface expression of proteins responsible for are associated with an increased incidence of immune
the adhesion, activation and movement of phagocytes complex-mediated autoimmune disease, ­ particularly
out of blood vessels into areas of inflammation. The systemic lupus erythematosus (SLE). Patients with
most common defect, leukocyte adhesin deficiency deficiency of terminal complement components are at
(LAD) type I, is due to an autosomal recessive defi- increased risk of recurrent neisserial infections, whereas
ciency of β-integrins (CD18). deficiency of some components of the a­ lternative path-
Affected children suffer from recurrent severe infec- way (e.g. properdin) predispose to overwhelming/fatal
tions and usually die in the first few years of life neisserial and pneumococcal infection. C3 deficiency
without bone marrow transplantation. Severe gingi- predisposes to severe recurrent bacterial infection and
vitis and periodontitis, and impaired healing of trau- is associated with a high mortality rate.
matic or surgical wounds are major features among all Integrity of the classical and alternate complement
patients who survive infancy. pathways is tested by the classical (CH50) and alternate
The characteristic features are delayed separation (AH50) haemolytic complement assays, respectively.
of the umbilical cord, a significantly raised peripheral Although CH50 and the complement components C3
blood neutrophil count, and paucity of neutrophils and C4 are readily available, AH50 and assays of other
in areas of infection. Diagnosis is confirmed by flow individual components are often available only from
cytometry showing absence of CD18 and associated specialized laboratories.

452
 Arthritis and connective 13.3
tissue disorders
Kevin Murray, Navid Adib

Chronic inflammatory arthritis and connective t­issue may also result from bleeding into the joint in haemo-
disorders are associated with immune dysregulation philia (see Chapter 16.2), from chloroma associated
and may affect many systems, involving joints, skin and with neoplastic disease, or rarely from foreign-body
internal organs. Although the exact aetiology of most penetration.
of these disorders remains unknown, it is believed that
they may be the result of interaction between genetic
and environmental factors.
Box 13.3.1 lists some of the important forms of Juvenile idiopathic arthritis
chronic arthritis and connective tissue disorders of
childhood. Persistent or chronic arthritis in the absence of any other
associated diagnosis or disorder, in a young ­person under
16 years of age, is diagnosed as JIA. The term ‘juve-
nile’ refers to the onset of this disorder, and arthritis
Frequency commonly persists into adulthood.
In 1996, efforts to harmonize research and clinical
The chronic arthritis and connective tissue disorders care in juvenile forms of chronic arthritis resulted in the
in childhood are generally uncommon. The most development of an international classification s­ ystem,
­common type of chronic arthritis is juvenile idiopathic which is now widely recognized. The most recent revi-
arthritis (JIA). The prevalence is estimated to be 1 in sion of this classification is detailed in Box 13.3.1. The
1000, although the condition may be even more com- three main broad clinical presentations are:
mon. Other causes of arthralgia or musculoskeletal
• oligoarthritis
pains are seen far more often, such as pain related
• polyarthritis
to mechanical disorders, ligamentous laxity or joint
• systemic arthritis.
hypermobility.

Oligoarthritis
Oligoarthritis, defined as four or fewer joints involved
Arthritis in children during the first 6 months after onset of symptoms,
Arthritis is inflammation of, or related to, a joint and is the commonest form of JIA, accounting for over
symptoms of arthritis may include: 60% of cases. Most children present between 1 and
• pain 4 years of age, girls twice as frequently as boys. Knees
• heat are affected most commonly, followed by ankle (and
• swelling subtalar) joints, wrists and elbows. Hip disease is rare,
• deformity or loss of range of motion and a child presenting with isolated hip involvement
• stiffness, particularly early morning must be investigated carefully for disorders such as
• loss of function septic arthritis or osteomyelitis and, in the appropri-
• occasionally erythema. ate age groups, avascular necrosis of the femoral head
In the evaluation of the acute onset of joint inflamma- (Perthes disease) and slipped femoral capital epiphysis
tion, infection or trauma must be considered. Infection (see Chapter 8.1).
may occur as primary septic arthritis or extension of There is usually no systemic disturbance in oligo-
infection from a nearby focus of osteomyelitis into the arthritis. Radiographs may show soft tissue swelling,
joint space (see Chapter 12.2). Meningococcal septi- effusions and widening of the joint space, but erosions
caemia and Haemophilus influenzae type b meningi- are rare. Where treatment has been delayed, epiphy-
tis may be complicated by septic arthritis, or by sterile seal overgrowth and lengthening of the involved limb
reactive arthritis. Where trauma is suspected with joint is common. Untreated children ultimately develop
swelling, both accidental and non-accidental injury erosive disease, whereas growth plate involvement may
must always be considered. Inflammation in a joint result in arrest of linear growth and limb d ­ eformity 453
 13.3 ALLERGY, IMMUNITY AND INFLAMMATION

Box 13.3.1 Chronic inflammatory arthritis and

connective tissue disorders of childhood, including
Clinical example
the new International League of Associations for
Tianna, 2  years old, had an 8-week history of
Rheumatology (ILAR) classification system for juvenile
a painful left knee that was stiff in the mornings
idiopathic arthritis
and became progressively more swollen. The
orthopaedic team performed arthroscopic
• Juvenile idiopathic arthritis
drainage of the knee joint and gave antibiotics with little
1. Systemic arthritis
improvement in her knee. The synovial fluid showed more
2. Oligoarthritis
than 20 000 white blood cells but was negative on culture.
a) persistent oligoarthritis
The histopathology report of a synovial biopsy showed
b) extended oligoarthritis
synovial hypertrophy with ‘non-specific’ inflammation.
3. Rheumatoid factor-negative polyarthritis
Rheumatology review noted a knee effusion, synovial
4. Rheumatoid factor-positive polyarthritis
thickening and 15° flexion deformity with significant
5. Psoriatic arthritis
quadriceps wasting. Tianna also had mild (asymptomatic)
6. Enthesitis-related arthritis
swelling of her left ankle that had gone unnoticed.
7. Undifferentiated arthritis
Investigations revealed an erythrocyte sedimentation
• Systemic lupus erythematosus
rate (ESR) of 41 mm/h and a positive ANA titre of 1 : 160.
• Juvenile dermatomyositis
Ophthalmological review revealed evidence of cells and flare
• Scleroderma
in the anterior chamber of Tianna's left eye, consistent with
• Overlap syndromes
chronic iridocyclitis. The diagnosis was juvenile idiopathic
• Primary vasculitic disorders
arthritis of the oligoarthritis type with uveitis.
Tianna was treated with a non-steroidal anti-inflammatory
drug (NSAID), aspiration of involved joints, with intra-articular
(Fig. 13.3.1A,B). More than 70% have a positive injection of long-acting corticosteroid (triamcinolone) and
serological test for antinuclear antibody (ANA), and regular physiotherapy. Within 3 weeks all signs of her arthritis
rheumatoid factor is usually negative. Oligoarthritis had resolved and her range of motion was near normal.
onset has the greatest association with anterior uveitis Her eye disease responded rapidly to topical steroids and
(see below), which if untreated can cause blindness. mydriatics, although it recurred several times over the next
2 years. The arthritis recurred twice in the following few years,
Approximately 25% of patients with oligoarthri-
requiring further corticosteroid injections with further excellent
tis will develop progressive polyarthritis after the response. By 10 years of age, Tianna's arthritis and uveitis had
first 6 months, and are classified as having extended been in remission off all treatment for over 2 years.
oligoarthritis.

A B

Fig. 13.3.1 A 15-year-old girl with oligoarthritis-onset form of juvenile idiopathic arthritis from age 5 years, largely untreated. (A) Marked
454 flexion deformity and overgrowth of the left leg. (B) Response to multiple joint injections, methotrexate and intensive physiotherapy for
12 months.
 Arthritis and connective tissue disorders 13.3
Polyarthritis
Polyarthritis, defined as involvement of five or more
joints in the first 6 months of disease, accounts for
about 25% of JIA cases. Girls are affected twice as
often as boys. Onset is most common between the ages
of 2 and 4 years, but can be at any age.
Asymmetrical large and small joint involvement is
usual. Hip disease may occur, particularly later. Untreated
polyarthritis may cause severe disability, joint deformi-
ties, asymmetrical overgrowth (particularly knees) and
undergrowth (temporomandibular joint and mandible;
Fig. 13.3.2), destruction, ankylosis (especially the wrist
and cervical spine) and considerable muscle wasting.
Only a small subgroup is rheumatoid factor-positive,
usually adolescent females with a symmetrical small Fig. 13.3.3 Typical salmon-pink macular rash of systemic onset
and large joint arthritis (see below). Tests for ANA are form of juvenile idiopathic arthritis in a 10-year-old boy.
positive in 30–40%, and uveitis may also occur, man-
dating screening, although not as c­ommonly as with occur on the upper trunk, arms and thighs associated
oligoarthritis. Radiographs are similar to those in oligo- with fever, a warm bath or scratching the skin (Koebner
arthritis, but radiological progression is more frequent. phenomenon) (Fig. 13.3.3). Notably, in some individu-
als, particularly darker-skinned ­children, the rash may
Systemic arthritis be more urticarial and papular.
Other features include generalized lymphadenopathy,
Systemic arthritis (formerly called Still's disease) may
hepatosplenomegaly, serositis causing abdominal pain
present at any age in childhood, although rarely in the
(peritonitis), pleuritis and pericarditis. Pericardial effu-
first year. Adults may rarely develop a similar ‘adult-onset
sions may result in cardiogenic shock in young children.
Still's disease’. Presentation is classically with ­systemic
Early systemic arthritis mimics infection and malig-
symptoms and extra-articular manifestations, and
nancy, and diagnosis may be difficult, especially when
affected children may not develop joint disease for
there is no joint involvement. Haematological features
many months, making diagnosis difficult.
include anaemia, leukocytosis, thrombocytosis, and
Systemic arthritis affects both sexes equally and
markedly raised acute-phase reactants.
accounts for about 10% of cases of JIA. The initial pre-
Both large and small joint involvement occurs. About
sentation is often with daily or twice-daily spiking fevers,
half of children with arthritis respond relatively well to
usually above 39 °C, returning to normal between spikes.
treatment and eventually remit within a few years. In oth-
Affected children are very irritable and movement appears
ers, the course is of relentless polyarthritis, often initially
painful, although joints may not appear inflamed. A clas-
with persistent fever and rash. Occasionally children die
sical evanescent rash, usually salmon-pink macules, may
from infections or macrophage activation syndrome. In
the era before methotrexate and other cytotoxics, sys-
temic amyloidosis could cause fatal multisystem failure.
In recent years, biological agents that inhibit interleukin
(IL)-1, IL-6 or tumour necrosis factor (TNF)-α have
been used increasingly in severe disease.

Clinical example

Andrew, aged 3 years, had been unwell for

4 weeks with a daily high-spiking fever and a
widespread rash that was worse with fever or if
he scratched himself. He had not responded to
several courses of antibiotics. He presented to the emergency
department with chest pain and difficulty breathing. He was
unwell, dyspnoeic, febrile to 39.5 °C and had a widespread,
erythematous, macular rash. He had generalized
Fig. 13.3.2 A 14-year-old girl with severe mandibular deformity lymphadenopathy and mild hepatosplenomegaly. His heart
due to asymmetrical right-sided temporomandibular joint sounds were muffled and his peripheral pulses weak. 455
involvement causing failure of growth of the right ramus.
 13.3 ALLERGY, IMMUNITY AND INFLAMMATION

and ­ plantar fascia insertions. ERA was previously

Andrew's haemoglobin was 89 g/L, white cell count
called juvenile spondyloarthropathy or HLA-B27-
29 000/mm3, platelets 829 000/mm3 and ESR 131 mm/h.
Tests for ANA and rheumatoid factor were negative, as were associated arthritis. HLA-B27 antigen is present in
multiple blood cultures. He had cardiomegaly on chest X-ray about 60–90% of affected patients. Boys aged 6 years
and a moderate pericardial effusion on echocardiography. or older typically present with lower-limb asymmetri-
A diagnosis was made of JIA of the systemic arthritis cal arthritis (similar to the oligoarthritis pattern) with a
type. Andrew had minimal response to NSAIDs and predilection for the tarsus and great toe. Unlike oligo-
developed a widespread polyarthritis of both small and
arthritis, hips may be the first (or only) joints involved.
large joints. He was given intravenous pulse (high-dose)
methylprednisolone for 3 days followed by oral steroids, with
In later adolescence, sacroiliac and lumbar spine
a dramatic improvement in his fever, rash and joint swelling. inflammation is typical, although peripheral joints
­
His pericarditis resolved within a week. He was commenced are usually involved also. In some (< 10%) the arthritis
on low-dose methotrexate (15 mg/m2) as a ‘steroid-sparing persists into adulthood, resembling ankylosing spon-
agent’, but relapsed whenever steroids were tapered. dylitis. Early-onset cases often remit later, although if
Six months later Andrew's polyarthritis deteriorated, HLA-B27-positive may develop acute anterior uveitis
with only a transient response to methylprednisolone. He
or inflammatory bowel disease.
was started on the biological agent etanercept (anti-TNF)
subcutaneously twice weekly, with a moderate improvement
over 6 months. The etanercept therapy was switched to Arthritis in association with other connective
anakinra (an IL-1 receptor antagonist), used for several
tissue diseases or conditions associated with
years with methotrexate. He improved markedly and was
eventually weaned successfully off all medication. immune dysregulation
Chronic or episodic arthritis may be seen in other con-
nective tissue disorders such as systemic lupus erythe-
Other forms of juvenile idiopathic arthritis matosus (SLE), juvenile dermatomyositis, sarcoidosis,
vasculitides (e.g. polyarteritis nodosa), and s­ cleroderma
Rheumatoid factor-positive polyarthritis (both localized and systemic). Furthermore, velocar-
Rheumatoid factor-positive polyarthritis usually pres- diofacial and Down syndrome, as well as some ­specific
ents in later childhood or adolescence with a symmet- immune deficiency disorders, may feature chronic
rical arthritis involving predominantly small joints inflammatory arthritis. Cystic fibrosis and other suppu-
initially, but in time large joints equally. Erosions rative lung diseases may develop ­inflammatory arthrop-
occur early in untreated disease, and the course is often athy, possibly due to immune complex deposition.
severe and deforming. Early, aggressive treatment with Hypertrophic pulmonary osteoarthropathy (HPOA)
disease-modifying antirheumatic drugs and newer associated with congenital cyanotic heart d ­ isease or
biological agents is usually needed. This disorder severe cystic fibrosis involves large joints symmetrically,
resembles adult-onset rheumatoid arthritis, although closely resembling inflammatory arthritis.
complications of vasculitis, Felty syndrome and car-
diopulmonary disease are not common.
Eye disease in juvenile arthritis
Inflammatory disease of the uveal tract (uveitis or iri-
Psoriatic arthritis (PsA)
docyclitis) can complicate most forms of JIA, and is
Some children with oligoarthritis or polyarthritis have an important cause of acquired paediatric eye disease
nail dystrophy and skin rash consistent with psoria- and blindness in developed countries. Young girls with
sis, although the rash may not appear for many years. oligoarthritis who are ANA-positive are at highest
Dactylitis (sausage-like swelling of one or more fingers risk, whereas young boys may be more refractory to
or toes) and distal interphalangeal (DIP) arthritis are treatment (Fig. 13.3.4).
features. Skin involvement may be subtle, for instance Acute anterior uveitis presents as unilateral painful
umbilical, scalp, external auditory meatus, or behind red eye with photophobia and reduced vision. Chronic
the ears. The severe form, arthritis mutilans, is very rare anterior uveitis, however, is painless and usually goes
in childhood. A family history of psoriasis is typical. unnoticed, so slit-lamp examination by an ophthal-
Treatment is as for other forms of JIA. Skin disease may mologist at diagnosis and in follow-up is essential.
also respond to methotrexate and anti-TNF therapy. Treatment is with mydriatics and topical steroid prepa-
rations. Untreated eye disease may lead to severe impair-
ment of vision due to band keratopathy and adhesions
Enthesitis-related arthritis (ERA)
of the iris (synechiae). Glaucoma and ­cataracts may
Enthesitis refers to inflammation of tendons, liga­ also occur due to persistent inflammation.
ments or fascia at their points of insertion into the A granulomatous pan-uveitis or posterior uveitis
456
bone, particularly the Achilles tendon, patellar tendon may occur in paediatric sarcoidosis, which is rare.
 Arthritis and connective tissue disorders 13.3
dysplasia, bone or synovial tumours, unsuspected
fractures and radio-opaque foreign bodies) and serve
as baseline measurements. Later changes include loss
of joint space, bone overgrowth (e.g. fusion of spi-
nous processes in cervical spine), joint damage and
ultimately joint ankylosis, (usually cervical spine
or wrist), or subluxation. Erosive disease occurs in
aggressive disease, such as rheumatoid factor-positive
­enthesitis-related and psoriatic arthritis. Magnetic res-
onance imaging (MRI) is used increasingly for diffi-
cult diagnoses, to assess deep joints such as the hip, for
enthesitis, and with gadolinium to show the presence
Fig. 13.3.4 Abnormal right eye of a 5-year-old boy with juvenile
idiopathic arthritis and chronic silent anterior uveitis, showing an
and extent of synovitis. High-frequency ultrasound
irregular fixed pupil and early cataract formation. ­imaging shows promise in assessing synovial pathol-
ogy, although is operator-dependent and requires
patient cooperation.

Investigation of chronic arthritis

in childhood Management of idiopathic
Pathology and laboratory findings arthritis
Useful initial investigations are listed in Box 13.3.2. Management of JIA has been revolutionized in the
Common findings on investigation in a child with one last few decades with vastly improved drug regimens
of the arthritis or connective tissue disorders are: and the evolvement of multidisciplinary centres with
• hypochromic microcytic anaemia allied health professionals. The overall aim of such
• raised erythrocyte sedimentation rate (ESR) and therapy is to normalize major outcomes such as
C-reactive protein (CRP) level health-related quality of life (HRQOL) and p ­ revent
• autoantibodies, for example antinuclear antibody structural ­damage. A concerted and integrated
(ANA) and, less commonly, rheumatoid factor approach will ensure that the psychosocial wellbe-
(RF+ polyarthritis) or anti-cyclic citrullinated ing of the young person, in relation to their environ-
peptide (anti-CCP) antibodies ment (family, friends, school), has been optimally
• HLA-B27 antigen in ERA promoted.
• inflammatory synovial fluid (white cell count >
2000/mm3, and protein)
• histological evidence of chronic inflammation in Relief of pain
synovium.
Persisting pain in the involved joints is a major b
­ urden
for children and their families. Pain in any joint can
Radiology lead to poor sleeping, irritability and depressed mood,
Plain radiographs are often normal in early arthritis, as well as decreased appetite. Inability to do simple
or show only periarticular osteopenia or soft tissue activities because of pain has a marked effect on
changes, but can rule out other diagnoses (e.g. bone the child and family. Pain in the joints of the lower
limbs interferes with walking and mobility, and chil-
dren with painful wrists and fingers may no longer be
able to dress or feed themselves. Splinting may reduce
Box 13.3.2 Initial investigations in suspected juvenile pain, but prolonged disuse may accelerate osteope-
arthritis nia and irreversible loss of range of movements. Heat
application may relieve stiff joints, whereas the hot
• Full blood count (FBC) and film
• Erythrocyte sedimentation rate and/or C-reactive protein
inflamed joint may be more comfortable with cold
• Rheumatoid factor packs. Simple analgesics such as paracetamol and
• Antinuclear antibody non-steroidal anti-inflammatory agents (NSAIDs)
• HLA-B27 (children aged ≥ 6 years, especially males) can help with pain control and inflammation. Early
• Liver function, coagulation profile, iron studies and renal intervention with intensive medical therapy, including
function tests in those who are systemically unwell intra-articular corticosteroids and disease-modifying
• Radiography of major involved joints (may X-ray
antirheumatic drugs (DMARDs), has improved pain
contralateral joints for comparison) 457
control in JIA.
 13.3 ALLERGY, IMMUNITY AND INFLAMMATION

Children with severe disease with significant d

­ isability
Practical points or pain need ongoing psychological support. Many
children, particularly adolescents, who face challenges
• In an acutely swollen joint with marked pain, limitation of altered body image and threats to their indepen-
of motion or associated fever, septic arthritis should be dence, benefit from appropriate counselling. Parents
considered, and should be ruled out by aspiration and often require supportive therapy, particularly soon
culture. after diagnosis. Social work involvement is often
• Swelling of a joint or joints, lasting longer than 6 weeks, required for children with severe arthritis. For exam-
and with other causes excluded, is highly likely to be
ple, disabled parking access, health-care cards and dis-
juvenile idiopathic arthritis (JIA).
All children diagnosed or suspected as having JIA should ability support allowances are an important part of
•
be seen by an ophthalmologist to screen for uveitis. The assistance for parents to provide the extra care needed.
risk is highest in young females with oligoarthritis and a Patient travel allowances and specific pharmaceuti-
positive antinuclear antibody (ANA) test result. cal benefits for children with chronic diseases and
• Chronic arthritis in the lower limbs in an older high drug costs are also available. Parent and patient
boy who is HLA-B27-positive, associated with painful/ ­support groups (such as the Arthritis Foundation) are
swollen entheses, is likely to be enthesitis-related
­valued greatly by families with affected children.
arthritis (ERA).
• For any joint with persistent chronic synovitis unresponsive
to NSAIDs, injection with a long-acting steroid is usually
very efficacious
• For any polyarthritis unresponsive to simple therapies, Management of associated
use of a disease-modifying drug such as methotrexate is
mandated.
abnormalities
• Most forms of JIA are treatable, with an excellent outcome The management of uveitis has been described above.
expected for most, although some require treatment into Growth may be impaired in any chronic inflamma-
their adult years. tory state, and nutritional assessment and advice is
important. Growth hormone has been used in selected
patients to help restore growth velocity, particularly
during less active phases of disease. Osteoporosis is a
Maintenance of joint function and prevention well-recognized complication of severe JIA through
of disability persistent inflammation and reduced activities, and is
exacerbated by steroid use. Attention to calcium and
Physiotherapy limited by pain is ineffective, so medi-
vitamin D intake is important. Bone densitometry is
cal treatment to relieve pain is needed first. As inflam-
indicated in severe cases and with long-term corticoste-
mation improves, an active exercise programme can
roid use. For children at risk of pathological f­ ractures,
be introduced to improve the range of joint move-
bisphosphonates (e.g. pamidronate) may be necessary.
ment and to strengthen muscles around the involved
joint. Joint function is maintained by active and pas-
sive physiotherapy and occupational therapy, and
attention to overall fitness and stamina facilitates
other aspects of treatment. Occasionally night-time
Outcomes of juvenile arthritis
or functional splinting may be required to restore There has been rapid progress in management. Long-
range of movement, but regular physiotherapy is term outcome studies relate to patients treated in the
needed to ­prevent osteopenia and loss of movement previous 20–30 years and are biased towards more
in other joints. Hydrotherapy in a heated pool is espe- severe cases, but suggest that most children with
cially ­ helpful for lower limb joints. Home exercise significant joint involvement are still affected by
­
­programmes and guidance with sporting activities are ­disability and pain in adulthood. Milder cases and
essential. Appropriate ergonomic seating at home and those with oligoarthritis undoubtedly fare better,
at school, encouragement and assistance with activi- although eye complications are usually more severe in
ties of daily living, and information for schoolteachers the latter. Long-term disability is most frequent with
and peers are all important. severe polyarticular-onset disease and with systemic
Surgical intervention is rarely needed in JIA, unless disease that progresses rapidly to widespread poly-
joints have become severely deformed, causing func- articular involvement. The biological therapies have
tional impairment, or cause severe pain. Severe long- improved outcomes, but treatment may be needed
standing hip disease may benefit from muscle/tendon long into adulthood. Physical function, level of educa-
release or joint replacement, for example. Adults tion and employment prospects may be impaired even
whose disease ‘burned out’ in childhood may require with moderate disease if multidisciplinary input was
458
surgery for accelerated degenerative disease. not provided.
 Arthritis and connective tissue disorders 13.3
Other disorders associated with Box 13.3.3 Miscellaneous conditions that may be
associated with joint pain or dysfunction in childhood
arthritis in childhood
• Legg–Calvé–Perthes disease
Arthritis due to viral infections may be due to viral inva- • Slipped upper femoral epiphysis
sion of the synovium or immune complex deposition. • Transient synovitis (e.g. irritable hip)
The viruses most commonly associated with arthritis • Chronic recurrent multifocal osteomyelitis
or arthralgia are rubella, parvovirus B19, Epstein–Barr • Foreign-body synovitis (e.g. plant-thorn synovitis)
virus, hepatitis B virus and, in Australia, Ross River • Chondromalacia patellae and anterior knee pain syndromes
• Unrecognized trauma
virus. Post-infectious inflammatory arthritis is usually
• Metabolic and inherited disorders and syndromes
of less than 6 weeks’ duration. Transient synovitis of • Malignancy, including acute lymphoblastic leukaemia
the hip or ‘irritable hip’ is probably post-viral, typically • Dysplastic bone/cartilage disorders
occurs in early childhood and is self-limiting. • Conditions with joint hypermobility as clinical feature
Bacteria can also cause inflammation. Rheumatic • Overuse conditions, especially in elite child athletes and
fever (see Chapter 15.2) is well known. Post-streptococcal gymnasts
arthritis and post-Mycoplasma arthritis are increasingly • Reflex sympathetic dystrophy (complex regional pain
syndrome II)
recognized clinical entities, and arthritis is common with
• Chronic pain and fatigue syndromes (‘fibromyalgia’)
gastrointestinal bacteria such as Shigella, Salmonella, • Conversion symptoms and hysterical gait abnormalities
Yersinia and Campylobacter. Treatment with NSAIDs
is usually effective, but o­ ccasionally a short course of
steroids is beneficial. deposition. Autoantibodies are seen in serum and
Some bacterial infections may cause a persistent tissue biopsy samples, but their specific role in the
arthritis; tuberculosis is still an important cause of ­manifestations of disease remains speculative.
chronic joint infection in some countries and may also SLE is uncommon in childhood, but 10–20% of all
be associated with a reactive arthritis (Poncet disease). cases of SLE have onset at less than 18 years of age,
Lyme disease does not occur in Australia unless although rarely under age 5 years. Disease in children
contracted overseas, but is a very important cause of may be severe. Females are more commonly affected.
arthritis in some parts of the world. Infection with SLE is seen both with higher frequency and severity
tickborne Borrelia species leads to a rash known as in some populations (e.g. South-East Asia or Africa,
erythema chronicum migrans, neurological signs and a including after migration). In Australia, SLE is up
relapsing arthritis, usually of one or more large joints. to four times more common in Indigenous than non-
Henoch–Schönlein purpura (see Chapters 16.2, 18.2) Indigenous children.
is associated with transient arthritis. Haemophilia SLE often presents with non-specific symptoms of
(see Chapter 16.2) with recurrent intra-articular joint lethargy, low-grade fever, loss of appetite and oral
bleeding leads to chronic synovitis and destructive ulceration. Raynaud's phenomenon may be present,
changes in joints often indistinguishable from inflam- and patchy alopecia or scalp ulceration may occur.
matory arthritis, particularly in the knee and the ankle. The typical lupus rash, a photosensitive vasculitis rash
Polyarthritis due to chloromatous involvement of with clear demarcation and associated scaling and ery-
joints in leukaemia may be difficult to distinguish from thema over the malar area of the face, is present in
JIA; severe night pain and complete refusal to mobili- 70% of cases. Vasculitic lesions may be present on the
zation and a low platelet count are suggestive. pulp of the digits, extensor surfaces of the arms and
legs, and the palate. Purpura or ecchymoses may result
from thrombocytopenia or associated coagulopathy.
Other disorders that may present There may be arthralgia or symmetrical painful
arthritis with some swelling (Jaccoud's arthropathy).
as joint pain or dysfunction in Joint symptoms often resolve rapidly when treatment
childhood is commenced. Myositis may contribute to weak-
Other conditions that may present with joint pain or ness. Renal involvement can cause microscopic or
dysfunction are listed in Box 13.3.3. frank haematuria, proteinuria may be mild or in the
nephrotic range, and children may present with a
mixed nephritic–nephrotic picture with oliguria and
hypertension. Rarer manifestations are autoimmune
Systemic lupus erythematosus hepatitis and pancreatitis.
SLE is a chronic multisystem disorder. Polyclonal acti- Neurological manifestations from cerebral lupus
vation of B cells is associated with excessive antibody include severe headache, mood disorder and cognitive
459
formation, and disease results from immune complex dysfunction. Seizures, psychosis, chorea, ­polyneuropathy
 13.3 ALLERGY, IMMUNITY AND INFLAMMATION

or transverse myelitis are less common, but are associ- To minimize the long-term and undesirable side-
ated with poorer disease outcome. Lung and cardiac effects of systemic steroids, steroid-sparing or
abnormalities may also occur. disease-modifying immunosuppressive agents should
­
be used in most patients. Methotrexate or azathioprine
are often the first agents used. Hydroxychloroquine
Laboratory findings
has long-term cardiovascular protective effects and
Common laboratory findings are: may help severe skin rash. Cyclophosphamide is usu-
• Coombs-positive haemolytic anaemia or anaemia ally used for severe nephritis, cerebral vasculitis, or
of chronic disease severe pulmonary interstitial disease. Mycophenolate
• raised ESR but normal CRP levels mofetil may be used, but evidence less emphatic.
• leukopenia (specifically lymphopenia) Plasmaphaeresis is sometimes used in refractory cases.
• thrombocytopenia Autologous stem cell transplantation has induced
• low C3 and/or C4 levels remission in some severe, treatment-resistant cases.
• microscopic haematuria, proteinuria, cellular casts Rituximab, an anti-B-cell (CD20) monoclonal anti-
and altered renal function body, may be effective, especially in patients with severe
• ANA-positive (often homogeneous pattern) in haematological manifestations, although because of its
almost all cases, with anti-double-stranded DNA anti-B cell properties there is a risk of life-­threatening
present in only 30% of cases initially. infections.
Important diagnostic immunological findings in Multidisciplinary involvement of medical special-
SLE are the presence of autoantibodies. ANA is ists, dietitians, psychologists and physiotherapists is
present universally, often in very high titre. The often needed. Most children with SLE will require
ANA may be directed against specific identifiable ­steroid use for some or all of their disease, and many
extractable nuclear antigens (ENA) such as anti-Sm will develop significant dyslipidaemia with risk of ath-
(Smith), which is diagnostic for SLE, anti-Ro (SSA) erosclerotic complications in adult life, which thus
and anti-La (SSB). Antibody to double-stranded needs to be monitored and treated.
(native) DNA in high concentrations is almost spe- The outcome for children with SLE has improved
cific for SLE, and is associated with more severe markedly in recent decades with earlier intensive and
renal disease and central nervous system disease. successful therapies. With careful therapy, renal func-
Anti-cardiolipin antibody may be present and may tion is usually maintained. Side-effects of steroid
be associated with lupus anticoagulant. The associ- therapy and persistently active disease, including avas-
ated risk of thrombosis with such antibodies seems cular necrosis of the femoral heads, decreased spinal
to be rarer in children than in adults, but may be a mineralization and growth suppression, remain diffi-
severe complication. cult areas of management. For many children, how-
Biopsy of involved tissues such as skin and kidney ever, the aim should be a near normal life expectancy
shows evidence of characteristic inflammation, and and preservation of fertility, with m ­ inimal ­disease
immunoglobulin and complement deposition in blood and minimal treatment morbidity.
vessels and tissues. The staging of renal disease by
biopsy is important for guiding therapy and determin-
Neonatal lupus syndrome
ing outcomes. Diffuse proliferative glomerulonephri-
tis (grade IV), the most severe form, is the commonest Some infants born to mothers with serological evi-
finding in children with kidney disease. dence of SLE-type antibodies will have transient
manifestations of SLE. The mothers rarely have
a diagnosed rheumatic disorder (such as SLE or
Management
Sjögren disease) but may go on to do so in later
Treatment of SLE requires careful and expert super- life. The neonatal manifestations are due to trans-
vision, often by multiple specialists. Steroids are the placental passage of maternal IgG autoantibody,
mainstay of initial management of SLE, and admin- particularly anti-Ro and anti-La antibodies. The
istration of high doses by oral or intravenous route is most common abnormality is a discoid lupus-like
often required. Prednisolone (2 mg/kg daily) may be skin rash (Fig. 13.3.5), mild thrombocytopenia and
needed, and in very severe disease pulsed intravenous transaminitis, which gradually improve as mater-
methylprednisolone. High-dose steroids may lead to nally-acquired antibody titres decrease. Usually no
significant side-effects, such as weight gain, osteopo- treatment is required. The most important compli-
rosis and an increased risk of infections. Because SLE cation is ­isolated congenital heart block, which may
itself increases susceptibility to infection and immu- be ­diagnosed ­antenatally, can cause fetal or n
­ eonatal
nosuppressives may mask symptoms, a high index of death, and may require cardiac ­pacemaker for its
460
suspicion regarding infections is critical. treatment.
 Arthritis and connective tissue disorders 13.3
(anasarca), as well as ulcerative skin disease around
the face and ears, may predict a severe disease course.
A scaly erythematous rash over the dorsum of the small
joints of the hands (Gottron's papules) and elbows and
knees is common. Occasionally other patterns such as
a ‘shawl’ or ‘V’ neck photosensitive distribution may
be seen. Extensive subcutaneous calcification may be
seen, usually associated with severe treatment-­resistant
disease. Muscle enzyme levels in serum are usually
raised (creatine kinase, lactate dehydrogenase, trans-
aminases). Diagnostic imaging using MRI is useful.
Electromyography shows myopathic features with mus-
cle irritability, short duration and low-amplitude poten-
tials. Muscle biopsy is useful for atypical or severe cases
when treatment with immunosuppressive regimens (e.g.
cyclophosphamide) is contemplated early.
Treatment is initially with high-dose corticosteroids
(oral or intravenous), reduced gradually. Early cyto-
toxic treatment with methotrexate or ciclosporin has a
steroid-sparing effect, although some children require
steroids for many years. Few children are able to have
treatment withdrawn in less than 2 years.
Fig. 13.3.5 A 6-week-old boy with neonatal lupus
erythematosus showing facial rash (‘racoon facies’); his
mother was well but had passed 52-kDa anti-Ro antibodies
transplacentally. The baby was well, had mild transaminitis, and
all features resolved without treatment in 3 months.
Clinical example

Joshua, aged 6 years, developed a scaly,

erythematous rash over his face after sun
Sjögren disease exposure that persisted for several months
despite topical allergy treatments. He became
Primary Sjögren syndrome is very rare in childhood, pre- very fatigued, often sleeping on return from school for
several hours. He stopped playing sport and riding his bike,
senting with constitutional symptoms, rash, recurrent or
and complained of painful legs. Over several weeks his rash
chronic parotitis and conjunctivitis. Xerostomia and the worsened and spread to his elbows, knees and the back
sicca complex are rarely seen in isolation, although more of his hands. He had lost 2 kg in weight, and had difficulty
commonly in association with mixed connective tis- getting up on to the family doctor's examination couch.
sue disease (MCTD) or overlap syndromes. Serological Examination revealed a thin boy with a scaly, red rash
markers may be similar to those of SLE, with a promi- over the small joints of his hands, knees and elbows. He had
nence of anti-Ro and anti-La antibodies. a macular erythematous rash on his face, and his eyelids had
a violaceous hue. He had marked weakness in his proximal
leg muscles, shoulders and trunk, was unable to get up from
lying unaided, and was unable to raise his arms above his
Juvenile dermatomyositis head for more than a few seconds.
Joshua had a normal blood count, ESR of 25 mm/h, normal
Dermatomyositis in children is seen most commonly renal function, an aspartate transaminase level of 145 IU/L
between the ages of 4 and 10 years. Weakness and pain (normal < 50) and alanine transaminase 109 IU/L (normal < 50)
in the proximal muscle groups of the limbs are univer- with normal bilirubin and albumin levels. His creatine kinase
concentration was 2988 IU/L (normal < 200) and lactate
sal. Gait abnormality or difficulty walking are common
dehydrogenase 1468 IU/L (normal < 200). He was diagnosed
presenting features. Weakness of muscles may progress to with an inflammatory myositis. MRI of his thighs showed
involve the trunk and respiratory muscles, and pharyngeal typical widespread but patchy signal changes in the muscle
muscle weakness may increase the risk for aspiration. In and fascial tissues of the gluteal region and thighs. A biopsy
some children, onset may be rapid and life-­threatening, of the lateral thigh confirmed the inflammatory nature of the
whereas in others progression may be insidious. myositis. His specific diagnosis was juvenile dermatomyositis
The typical rash of dermatomyositis is a heliotrope based on the clinical picture (facial rash, Gottron's papules
and muscle weakness) and investigations (raised muscle
(purplish) discoloration around the eyes and involving enzymes, MRI and histological findings). By this stage, Joshua
the eyelids. There is commonly an associated erythem- was having difficulty walking any distance and getting up out
atous facial rash without clear demarcation as seen of a chair, and had considerable muscle pain. 461
with SLE, and oedema is common. Extreme oedema
 13.3 ALLERGY, IMMUNITY AND INFLAMMATION

severe constipation. Treatment remains difficult, with

Treatment was commenced with pulse intravenous ­ ethotrexate and cyclophosphamide offering some
m
methylprednisolone for 3 days followed by 1 mg/kg benefit. Symptomatic treatment with antihyperten-
oral steroids and oral methotrexate 20 mg/m2. Joshua
sives (e.g. angiotensin-converting enzyme (ACE)
started a graduated physiotherapy programme in the
hydrotherapy pool. During the first week he gradually
inhibitors) and pulmonary vasodilators contribute
improved, and after a second course of intravenous to management and a reduction in the early mortal-
methylprednisolone was discharged with marked ity rate. Autologous stem cell transplantation has also
improvement in his skin rash and muscle strength. He been used successfully in a number of patients.
could walk and started to use stairs. Over the subsequent Localized scleroderma, although uncommon, is
3 months his steroids were slowly weaned, he had seen 10–20 times more frequently than systemic sclero-
progressive improvement in his muscle strength and was
sis in childhood. It occurs as either morphea (isolated
able to start junior soccer training. His parents had noticed
several small lumps on Joshua's knees and inner thighs, patches) or linear scleroderma, or as combinations
which proved to be calcinosis on X-ray. These gradually of the two lesions, and may be very widespread. The
reduced in size and disappeared over the next 12 months. involved skin becomes shiny and thickened, deeply
Joshua was kept on methotrexate for 2 years and, never tethered, and has patches of depigmentation, which
having experienced a major relapse, was weaned off this may evolve into areas of excess pigmentation. The
medication and discharged after another year in long- involved areas with active disease feel warmer than the
term remission.
surrounding skin. Major joint contractures occur when
it crosses joints, and linear growth in the limb may be
arrested. A form occurring on the head (known as en
Some children have persistent chronic disease activ-
coup de sabre) may be severe enough to cause hemifa-
ity or multiple relapses despite intensive therapy for
cial atrophy (Parry–Romberg syndrome), occasionally
many years. Other treatments used or added in these
with uveitis and central nervous system involvement
situations are azathioprine, ciclosporin and cyclo-
(Fig. 13.3.6). There are usually no associated systemic
phosphamide (particularly in ulcerative disease).
features, although inflammatory polyarthritis may be
Intravenous immunoglobulin (IVIG) may be useful
coexistent.
early in the disease course. Complications include mus-
Evidence now indicates that early treatment with
cle wasting, joint contractures, a form of progressive
steroids and maintenance with methotrexate for more
chronic arthritis, c­ alcinosis of areas of skin and sub-
severe lesions over a number of years may benefit
cutaneous tissue with u ­ lceration of the overlying skin,
many patients. Such treatment may reverse the severe
and, rarely, a lipodystrophy syndrome. However, many
children have a very good outcome after a number
of years with appropriate intensive ­multidisciplinary
treatment.

Scleroderma
The major feature of scleroderma is induration or
sclerosis of skin and subcutaneous tissue with sub-
sequent atrophy of sweat and sebaceous glands and
of underlying muscle and bone. This may occur in
several forms. Systemic sclerosis occurs in a diffuse
or limited form (the latter being known formerly as
CREST syndrome). It is very rare in childhood, but
occasionally seen in adolescents. A typical wide-
spread, symmetrical, waxy, tightened, indurated skin
with atrophy of muscles is seen, and is associated
with anti-PM/Scl antibody in some. The associated
vasculopathy causes serious renal and cardiopulmo-
nary disease, and major gut involvement with reflux
and malabsorption is seen. Oesophageal dysmotility
may cause dysphagia and decreased oral intake with
severe weight loss. Contrast studies or upper gastro-
intestinal endoscopy may reveal achalasia. Intestinal Fig. 13.3.6 A 12-year-old girl with left facial localized scleroderma
462
transit time is often increased, with moderate to and associated atrophy of the tongue.
 Arthritis and connective tissue disorders 13.3
and disfiguring fibrosis if commenced in the inflam-
Box 13.3.4 Primary vasculitic disorders in childhood
matory stage of the disease. Topical treatments have based on predominant size of vessel involved
been largely unsuccessful, and cosmetic and corrective
surgery may be required. Classification of childhood vasculitis (International
Consensus Conference, Vienna, 2005)
I. Predominantly large vessel vasculitis
• Takayasu arteritis
Overlap syndromes II. Predominantly medium-sized vessel vasculitis
• Childhood polyarteritis nodosa
Some children appear to have features of several of • Cutaneous polyarteritis
the disorders described above, or some features with- • Kawasaki disease
III. Predominantly small-vessel vasculitis
out having any complete disorder. One specific type of A) Granulomatous
‘overlap syndrome’ disorder is called mixed connective • Wegener's granulomatosis
tissue disease (MCTD), in which there is Raynaud's • Churg–Strauss syndrome
phenomenon, skin nodules, arthralgia or arthritis, B) Non-granulomatous
sclerodactyly and sometimes myositis. Patients with • Microscopic polyangiitis
MCTD characteristically have a speckled-pattern • Henoch–Schönlein purpura
• Isolated cutaneous leukocytoclastic vasculitis
high-titre ANA with specificity for U1RNP. Some
• Hypocomplementaemic urticarial vasculitis
children with MCTD later develop major manifesta- IV. Other vasculitides
tions of SLE or scleroderma. Other children may pres- • Behçet's disease
ent with what is termed undifferentiated connective • Vasculitis secondary to infection (including hepatitis
tissue disease, where they may have a positive ANA B-associated PAN), malignancy and drugs including
and phenomena such as Raynaud's and mild, small hypersensitivity vasculitis
vessel vasculitis. They may rarely develop connective • Isolated vasculitis of the central nervous system
• Cogan syndrome
tissue disorder in later life.
• Unclassified

Vasculitis syndromes
Box 13.3.4 provides a classification of primary vas-
culitic disorders occurring in childhood according
to the predominant vessels involved. The common-
est are Henoch–Schönlein purpura (see Chapter 16.2,
18.2) and Kawasaki disease (see Chapter 12.1).
Acute secondary vasculitis of the skin may be asso-
ciated with acute infectious syndromes such as with
streptoccocal or Mycoplasma infection (Fig. 13.3.7)
and rarely meningoccocal and gonococcal infection.
The other vasculitic disorders are rare in childhood,
often ­presenting with constitutional symptoms, fever,
weight loss and rash. They may evolve later into more
organ-specific features, such as nephritis and hyper-
tension in polyarteritis nodosa, or respiratory symp-
toms in Wegener granulomatosis. Biopsy of affected Fig. 13.3.7 An 11-year-old girl with peripheral vasculitis
tissues or angiography is usually required to establish secondary to Mycoplasma infection and cold agglutinins which
the diagnosis. Therapy usually involves corticosteroids resolved in 4 weeks.
and immunosuppressive or cytotoxic medications for
long periods, with significant risk of morbidity and
mortality.
of major arteries, particularly the coronary arteries,
which can be prevented in most cases by early treatment
Kawasaki disease
with IVIG (see Chapter 12.1). Criteria were developed for
Kawasaki disease is a systemic vasculitis that occurs diagnostic and e­ pidemiological ­purposes, but some chil-
worldwide but is more common in children of Japanese dren will be considered a­ typical or have an incomplete
descent. It is most common under 4 years of age. The aeti- version of the disorder, and the diagnosis should still be a
463
ology is unknown. The major c­ omplication is aneurysms clinical one.
 13.3 ALLERGY, IMMUNITY AND INFLAMMATION

distal tibia or femur, vertebrae or mandible. Mult­

Practical points iple lesions may be associated with some consti-
tutional symptoms and increased inflammatory
• When more than one system appears to be involved in markers. Some children have features of psoriasis
an inflammatory disorder, suspect a connective tissue or a family history of psoriatic arthritis, or features
disorder or vasculitis. of the same arthritis themselves such as dactylitis
• Autoantibodies such as ANA may be useful in a child (Fig. 13.3.9).
suspected of a connective tissue disorder and are more The constellation of synovitis, acne, pustulosis,
specific if found in high titre or with specific antibodies
hyperostosis and osteitis (so-called SAPHO s­ yndrome)
such as double-stranded DNA or extractable nuclear
antigens such as anti-Ro, anti-La and anti-Sm. is rare in childhood. Biopsy reveals non-­specific chronic
• In children with an acute illness comprising high inflammatory changes and is always negative on cul-
fever, rash, lymphadenopathy and oral mucosal ture. Affected children often received recurrent antibi-
changes, Kawasaki disease should be considered, and otics without benefit. Treatment is with NSAIDs, or
echocardiography and IVIG treatment considered. even with steroids or DMARDs (e.g. methotrexate) for
• When steroid therapy is required, the minimal effective severe cases.
dose should be used and steroid-sparing agents should be
introduced as soon as practical if prolonged use is expected.
• All children who require any prolonged steroid therapy
should have calcium and vitamin D supplementation and
bone mineral density studies to help treat and prevent
osteoporosis.

Chronic recurrent multifocal

osteomyelitis
Chronic recurrent multifocal osteomyelitis (CRMO)
is a chronic inflammatory condition that usually pres-
ents in older children and mimics pyogenic osteomy-
elitis. The disease causes inflammatory, painful, bony
swelling and arthritis if near a joint, or occasionally
atypical pain in a limb or in the back. Radiology reveals
characteristic lesions with bone lysis and new bone for- Fig. 13.3.9 A 10-year-old boy with a history of pustulosis and
mation, and nuclear bone scans may reveal (usually) bony osteolysis with acute dactylitis of the hand. Prominent distal
multiple areas of increased uptake. The most common interphalangeal (DIP) joint involvement is seen with overlying
site is the medial third of the clavicle (Fig. 13.3.8A,B), erythema as part of his SAPHO syndrome.

A B

464 Fig. 13.3.8 (A) A 12-year-old girl with left clavicular enlargement as part of chronic recurrent multifocal osteomyelitis (CRMO). (B) Computed
tomogram of the same girl with bony lysis and new bone formation typical of CRMO.
 Arthritis and connective tissue disorders 13.3
tender or trigger points in the musculature. Another
Non-inflammatory form of chronic pain disorder is often localized to
musculoskeletal disorders an extremity and is known as reflex sympathetic
­dystrophy or complex regional pain syndrome. This
General practitioners and paediatricians see many chil- takes the form of a limb or joint that becomes painful
dren with joint symptoms, the majority of whom will after minor injury and is immobilized to control the
not have an inflammatory arthritis or connective tissue pain. Subsequent sensory and vasomotor disturbance
disorder. The history for these children is often shorter may follow with discoloration, altered sweating and
or more episodic, and usually the joint discomfort is eventually atrophy of tissue if untreated (Fig. 13.3.10).
associated with activities and relieved by rest. These Patients are typically pre-adolescent or early-­adolescent
symptoms are mechanical in origin and are related to females who are often highly disabled by their symp-
underlying factors such as ligamentous laxity (hyper- toms, with cessation of their physical activities and fre-
mobility), overuse, poor fitness or specific inherited quent school absenteeism.
physiques (such as pes planus or genu valgus). These disorders are considered by most practi-
tioners to have a major psychogenic component,
Hypermobility disorders although physical deconditioning and tissue changes
may become established. Hence, physical treatment
Marked ligamentous (and soft tissue) laxity is often seen is an important part of rehabilitation. Psychological
in specific genetic disorders such as Ehlers–Danlos and treatment of the young person and their family, and
Marfan syndromes, but also occurs in Down syndrome counselling, are usually required to ensure a timely
and Stickler disease. Far commoner is so called benign and complete recovery.
joint hypermobility, where inherited ligamentous laxity
is associated with musculoskeletal symptoms such as
‘growing pains’, recurrent lower-limb arthralgia, pain-
ful flat feet, anterior knee pain syndrome and adoles-
cent mechanical back pain. Bursitis and tendonitis can
also be seen, particularly in older children. Mechanical
spinal pain disorders in adolescence are becoming more
common and appear to be associated with increasing
sedentary lifestyle and obesity. It is possible that these
may predispose to p ­ remature degenerative spinal dis-
ease and osteoarthritis in later life.

Chronic pain disorders

In some children, musculoskeletal symptoms develop in
the absence of any definable cuastive organic pathology. Fig 13.3.10 A 13-year-old girl with a swollen left foot after cold
Fibromyalgia or chronic widespread pain disorder is a immersion and mild chilblains with associated hypersensitivity to
symptom complex of chronic muscle and joint pain, touch and prolonged immobilization typical of reflex sympathetic
marked sleep disturbance, and the presence of typical dystrophy.

465
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 14
PART

RESPIRATORY
DISORDERS

467
 14.1 Acute upper respiratory
infections
Craig Mellis

Because of their frequency, upper respiratory tract of wheeze and asthma in young children, resulting in
infections (URTIs) are a major burden for young chil- high rates of attendance at emergency departments
dren and their parents. Although the common cold is and hospitalization. Viral URTIs can also trigger vas-
the most common ailment in humans, it is particularly cular syndromes, such as Henoch–Schönlein purpura.
frequent in preschool-aged children, who average six Further, it is difficult clinically to differentiate viral
to eight episodes per year. The timing and frequency pharyngitis (very common – and relatively harmless)
of these infections depends on the level of exposure, from streptococcal pharyngitis (uncommon – but can
occurring earlier and more often in those with older result in serious complications such as acute glomeru-
siblings, and those who attend daycare (Fig. 14.1.1). lonephritis or rheumatic fever).
The vast majority of URTIs are viral in origin, mild,
and of short duration (5–7 days), and usually described
as a ‘common cold’. Numerous different viruses are
responsible, and the age of the child and the specific Incubation period of viral
respiratory virus are the major predictors of the symp-
toms, severity and extent of respiratory tract involve-
respiratory infections
ment (Tables 14.1.1, 14.1.2). Knowledge of the incubation period of these respi-
ratory viruses is useful when considering the likely
timing of infection, the source and quarantine deci-
sions. A systematic review of over 400 publications
Respiratory complications described the median incubation period (and 95%
The importance of these recurring infections of early confidence intervals) for the respiratory viruses
childhood should not be underestimated. A signifi- of public health importance; these are listed in
cant percentage of children will suffer from local Table 14.1.2. Most have a short incubation period,
complications of viral URTIs, especially acute oti- with symptoms generally developing within 2–3 days
tis media and acute sinusitis (Fig. 14.1.2). Moreover, of exposure.
progression of the infection into the lower respira-
tory tract is a risk, particularly in the very young.
This is especially likely with the more potent respira-
tory viruses, such as respiratory syncytial virus (RSV Identifiable URTI syndromes
– the usual cause of acute viral bronchiolitis), para- Arbitrary definitions are used to describe the many
influenza (the usual cause of viral ‘croup’), influenza ‘URTI syndromes’, such as rhinitis, rhinosinusitis, sto-
virus (A and B) and the recently recognized human matitis, pharyngitis (tonsillitis) and otitis media. These
metapneumovirus (HMP – a close relative of RSV). descriptive terms signify the site of predominant symp-
Some children are particularly vulnerable to these toms – nose, sinuses, mouth, throat and ear (earache)
lower respiratory tract complications, suggesting respectively. Clearly there is substantial overlap with
additional important host and environmental factors these syndromes, as viral infections ignore anatomical
(Fig. 14.1.3). boundaries. Indeed, as a general rule, viral inflamma-
tion of the respiratory tract is usually diffuse rather
than focal, whereas bacterial infections of the respira-
tory tract (such as streptococcal tonsillitis) are often
Systemic complications more localized anatomically.
As well as their direct respiratory morbidity, viral The two most common forms of URTI are the ‘com-
URTIs can cause serious indirect or systemic compli- mon cold’ (with predominant symptoms being nasal)
cations. For example, respiratory viruses are by far the and pharyngitis (predominant symptom being sore
most common trigger of severe acute exacerbations throat), which are discussed in detail below.
468
 Acute upper respiratory infections 14.1
10
Mean no. of URTIs per annum

Table 14.1.2 Incubation period of viral respiratory

8 infections

Virus Median incubation period

6
(95% confidence interval)
4 Influenza A 0.6 (0.5 to 0.6) days

2 Rhinovirus 1.9 (1.4 to 2.4) days

0 Parainfluenza 2.6 (2.6 to 3.1) days

1 2 3 4 5
Age in years Adenovirus 3.2 (2.8 to 3.7) days

Daycare Homecare Respiratory syncytial virus 4.4 (3.9 to 4.9) days

Fig. 14.1.1 Number of respiratory tract infections per year in Influenza B 12.5 (11.8 to 13.3) days
infants and preschoolers (daycare versus homecare). (From data
in Isaacs D, Moxon ER 1996.)

infectious and spread via both droplets (particu-

Common cold (uncomplicated viral URTI or
larly by sneezing) and nasal secretions on hands
‘head cold’)
and fomites (clothing, handkerchiefs, toys, cot
This is defined as an acute illness where the major sides). Viral shedding is maximal in the 7 days
symptoms are: after inoculation and most have a short incuba-
• nasal (snuffliness, sneezing and rhinorrhoea) tion period (2–3 days). Therefore, close proximity
• mild sore throat such as household contacts with older school-aged
• conjunctival irritation (red, watery eyes). siblings, daycare attendance, overcrowding, lower
The symptoms are mild, fever is often minimal or socioeconomic status and poor personal hygiene
absent, and all symptoms resolve between 5 and are all associated with higher rates of URTI (see
7 days. The usual pathogen responsible for an Fig. 14.1.3).
uncomplicated viral URTI is rhinovirus, which Local ENT complications of the common cold
has over 100 types. However, there are many other include otitis media and acute rhinosinusitis (see
respiratory viruses that can produce this syn- Fig. 14.1.2), and a small proportion progress to involve
drome (see Table 14.1.2). These viruses are highly the lower respiratory tract.

Table 14.1.1 Age of child and type of respiratory tract infection

Age Type of infection

Newborn Risk of acute, generalized systemic illness with respiratory syncytial virus (looks ‘septic’)

Infant High risk of lower respiratory tract involvement with respiratory viruses (particularly acute viral
bronchiolitis from respiratory syncytial virus)

Toddler/preschooler Very frequent viral respiratory tract infections, mostly confined to upper respiratory tract
High risk of viral laryngotracheobronchitis (‘croup’) from parainfluenza viruses

School age (5–15 years) Lower rates of viral respiratory tract infection
Suspect:
• bacterial (streptococcal) tonsillitis
• Epstein–Barr viral pharyngitis/tonsillitis
• Mycoplasma pneumoniae if lower respiratory tract involvement (bronchitis and
bronchopneumonia)

469
 14.1 RESPIRATORY DISORDERS

All viral URTIs

Uncomplicated URTIs
(’common colds’)
(90%)

Local ENT Spread to lower Triggers an

Complications respiratory tract exacerbation of asthma
(10%) (5%) (common)

(5%) (5%) Viral bronchitis

Viral ‘croup’
Viral bronchiolitis
Viral bronchopneumonia
Acute Acute
sinusitis otitis
media
Bacterial
superinfection
(uncommon)

Fig. 14.1.2 Complications of viral upper respiratory tract infections (URTIs).

Pharyngitis (oropharyngitis/tonsillitis)
VIRUS
Pharyngitis is a clinical syndrome in which the major
• Type complaint is acute sore throat and/or discomfort on
• Potency swallowing (dysphagia). The illness is common, gen-
• Infectivity erally mild and self-limiting, with three-quarters of
• Dosage patients free of pain within 2–3 days of onset, whether
due to a respiratory virus or to β-haemolytic strepto-
coccus. Many respiratory viral infections begin with a
HOST ENVIRONMENTAL sore throat, before the development of the more obvi-
ous symptoms and signs such as rhinorrhoea/sneezing.
However, there are a number of specific, recognizable
• Age • Exposure syndromes of oropharyngitis/tonsillitis, which are
• Gender - older siblings described briefly below.
• Birth weight - daycare
• Gestational age - overcrowding
Ulcerative pharyngotonsillitis
• Family history • ETS/air quality
(e.g. atopy) • Socioeconomic status This is usually due to an adenovirus infection and
• Diet/nutrition • Quality of homecare typically occurs in infants and toddlers. It produces
• Race (e.g. ATSI) an isolated exudative tonsillitis resembling strepto-
Fig. 14.1.3 The frequency and severity of viral upper respiratory
coccal tonsillitis or Epstein–Barr virus pharyngitis.
tract infections depend on a complex interaction between virus, Adenoviruses (types 3, 4, 7, 14 and 21) also produce the
host and environment. ATSI, Aboriginal or Torres Strait Islander; very specific ‘pharyngoconjunctival fever’. The entero-
ETS, environmental tobacco smoke. viruses (Coxsackie virus and echovirus) and herpes
470
 Acute upper respiratory infections 14.1
simplex virus can also produce ulcerative pharyngoton-
sillitis. Other respiratory viruses (including RSV and Jennifer was difficult to examine, but had submental and
parainfluenza) usually cause a more diffuse nasophar- cervical lymphadenopathy. With gentle persuasion, she was
encouraged to open her mouth. The gingivae and anterior
yngitis rather than this focal tonsillar inflammation.
oropharynx were bright red, and there were many small
ulcers on her gums, tongue and hard palate.
Epstein–Barr virus pharyngitis/tonsillitis Jennifer had acute gingivostomatitis, almost certainly due
to herpes simplex virus. She was given small frequent sips
Although this typically occurs in older, school-aged chil- of water and milk to maintain her hydration. She could not
dren, it can also cause an exudative tonsillitis in the very take paracetamol because she had difficulty swallowing
young. The tonsillitis is associated with a membrane in the first 24 hours, and it was difficult to apply a topical
and marked cervical lymphadenopathy. Generalized analgesic gel because of pain. The first night, a paracetamol
symptoms, including fever, lethargy, anorexia and head- suppository was used to provide some analgesia. The ulcers
healed after 4 days and did not leave any scars.
ache, can also occur, especially in older children and
adolescents, and the condition is usually referred to as
infectious mononucleosis, or ‘glandular fever’.
The virus may result in persistent dormant infec-
Primary herpes simplex virus stomatitis tion in the oral region, with recrudescent orolabial
infections (‘cold sores’). These episodes may be trig-
Primary infection with herpes simplex virus (HSV), gered by intercurrent viral infections, stress, menstru-
usually HSV type 1, typically causes multiple dis- ation, and exposure to cold or ultraviolet radiation.
crete ulcers on the anterior regions of the orophar-
ynx – tongue, gums and palate (gingivostomatitis),
most commonly in children aged 1–3 years. Other Herpangina
characteristic features are vesicles on the lips or cir-
cumoral region, significant fever and lymphadenopa- Herpangina typically occurs in preschool-aged chil-
thy (especially submental and anterior cervical lymph dren, due to enteroviruses (Coxsackievirus A or B, or
glands). The ulcers persist for 5–7 days and can cause echoviruses). It results in a number of discrete mouth
considerable pain, feeding difficulty and irritability. ulcers, localized to the back of the oropharynx: tonsil-
Asymptomatic oral shedding of HSV henceforth is lar pillars, pharyngeal wall, uvula and palate. This dis-
common and can transmit the virus. Infection may be tribution contrasts with the anterior ulcers due to HSV.
widespread in children with eczema and severe in the
immunocompromised.
Hand, foot and mouth disease
The usual treatment is analgesics, such as
paracetamol. Local anaesthetic gels are commonly Hand, foot and mouth disease affects young children
tried but are often poorly tolerated because they sting and is also due to enteroviruses (mainly Coxsackie
and the child already has a painful mouth. There have A and enterovirus 71), causing oral ulcers similar to
also been adverse effects reported, including aspiration those of HSV. The usual symptoms are sore throat
from pharyngeal numbness and seizures from excessive and refusal to eat and drink. There is often an asso-
absorption. Aciclovir is generally reserved for immu- ciated vesicular or papular rash on the hands, feet,
nocompromised children. A study has shown benefit buttocks or trunk. The mouth ulcers are generally
from aciclovir in HSV stomatitis in normal hosts, but around the mouth (circumoral), tongue, palate and
it is effective only when given within 72 hours of onset, buccal mucosa. The illness classically occurs in mini-
which is often before presentation to medical care. epidemics, is moderately contagious, has an incuba-
tion period of 3–7 days, and clinical recognition is
relatively simple.

Acute bacterial tonsillitis (‘streptococcal

Clinical example
pharyngitis’)
At the age of 18 months, Jennifer developed Group A β-haemolytic streptococcus is the usual bac-
a high fever and irritability. She cried loudly
terial cause of acute pharyngitis (Box 14.1.1) and is
when given cordial to drink and spat it out. She
could not swallow her saliva and was dribbling
more common in school-aged children. Although it is
constantly. Her mouth looked red and inflamed, and her important to distinguish viral pharyngitis from strep-
mother took her immediately to see her family doctor. tococcal pharyngitis, unfortunately this is not easy
on clinical grounds. However, if three or more of the
471
 14.1 RESPIRATORY DISORDERS

Box 14.1.1 Clinical features of group A b-haemolytic prescribed at this time as Adam was considered to be
streptococcal tonsillitis at low risk of suppurative or rheumatic complications of
streptococcal infection. He re-presented several days later
History because of ongoing fever and the development of a clear
• Age 3–15 years nasal discharge and watery eyes. He had a mild dry cough
• Abrupt onset but was now drinking well and not complaining of a sore
• Severe sore throat (pain and difficulty swallowing) throat. His throat culture was sterile. The illness was almost
• Systemic symptoms certainly due to a respiratory virus (probably an adenovirus).
• headache Several days later Adam's mother rang to say that he
• abdominal pain/nausea/vomiting was now virtually back to his normal self. This case clearly
• No cough or coryzal/nasal symptoms demonstrates the major clinical difficulty in distinguishing a
bacterial from a viral tonsillitis/pharyngitis.
Examination
• Tonsillar exudates, purulent and patchy (rather than a
membrane); marked inflammation of throat and tonsils
• Enlarged, tender bilateral anterior cervical lymph nodes Mumps (epidemic parotitis)
• No nasal discharge
Mumps is primarily a disease of childhood; 90% of cases
occur before adolescence. It is preventable by immuniza-
following characteristics are present then it is more tion with live attenuated virus vaccine (usually given
likely that the child has a streptococcal infection: with measles and rubella vaccines as MMR vaccine).
• age 3–14 years Mumps classically causes swelling, pain and tenderness
• high fever of the parotid glands. It can rarely be unilateral, but
• tonsillar exudate unilateral neck swelling is more suggestive of alterna-
• tender, enlarged anterior cervical lymph nodes tive diagnoses (e.g. lymphadenopathy, Kawasaki dis-
• absence of cough and/or coryzal symptoms. ease, recurrent benign parotitis of childhood). Other
Although this clinical dilemma can be overcome by use salivary glands, sublingual and submandibular, may be
of rapid laboratory (antigen detection) tests, a throat involved in mumps. Complications include viral men-
culture remains the ‘gold standard’ for confirming the ingitis (symptomatic in 10% of children with mumps,
presence of streptococcal pharyngitis and rational use asymptomatic in over 50%), encephalitis, orchitis,
of antibiotics. oophoritis, pancreatitis, thyroiditis, deafness and rarely
It would appear logical to give antibiotics in the pres- ophthalmitis, arthritis, myocarditis and nephritis.
ence of streptococcal pharyngitis, but current evidence
casts doubts on efficacy. A Cochrane review of random- Acute sinusitis (rhinosinusitis)
ized controlled trials concluded that antibiotics confer Bacterial infection of the paranasal sinuses occurs as a
little benefit (in terms of pain relief) in the treatment complication of approximately 5–10% of viral URTIs
of sore throat, irrespective of whether the infection is and generally involves the maxillary sinuses. The usual
due to a virus or to streptococcus. However, in children manifestation is a profuse, mucopurulent nasal discharge
known to be at high risk of complications of strepto- with nasal obstruction. Uncomplicated acute viral rhi-
coccal infection (post-streptococcal glomerulonephri- nosinusitis normally resolves without specific treatment
tis and/or rheumatic fever), the threshold for giving in 7–10 days. Thus, if the child has a purulent nasal dis-
antibiotics should be considerably lower. Populations charge continuing beyond 10 days, the possibility of sec-
at particular risk include Aboriginal and Torres Strait ondary bacterial sinusitis needs to be considered.
Islanders, Maori and Pacific Islander children. A Cochrane review of randomized controlled tri-
als concluded that antibiotics have a small beneficial
effect in uncomplicated acute sinusitis, which needs to
Clinical example be weighed against the potential for adverse effects due
Adam is a 5-year-old Caucasian child who to the antibiotics. However, as complications of acute
presented with fever, sore throat and difficulty bacterial sinusitis can be serious, the sicker the child
swallowing over the previous 24 hours. When (high fever, toxic or constitutionally ill), or the more
first seen he had an axillary temperature prolonged the symptoms (more than 10–14 days), the
of 38.2 °C and both tonsils were swollen and inflamed, more prudent it is to prescribe antibiotics. The usual
with a visible yellow exudate scattered over both tonsils. organisms responsible for acute bacterial sinusitis are
There was bilateral enlargement of the lymph nodes in
the anterior cervical chain. A clinical diagnosis of acute
Streptococcus pneumoniae, non-typeable Haemophilus
streptococcal tonsillitis was made, and a throat swab was influenzae and Moraxella catarrhalis. Amoxicillin plus
taken for culture. Oral penicillin was considered, but not clavulanic acid is, therefore, generally considered the
472 antibiotic of choice.
 Acute upper respiratory infections 14.1
Acute otitis media Journal of Australia in 2009, and includes the man-
agement of otitis media with effusion (glue ear) and
See also Chapter 22.1.
chronic suppurative otitis media.
Acute otitis media is characterized by earache, fever,
reduced hearing, and non-specific discomfort and irri-
tability in the very young child. Examination shows a
red tympanic membrane, loss of the normal anatomi- Approach to management of
cal landmarks on the tympanic membrane, the pres- respiratory tract infections
ence of a middle ear fluid, and the eardrum may be
visibly bulging. However, because not all of these signs Prevention and treatment
may be observed easily, the diagnosis of acute otitis Provided they are uncomplicated, URTIs are self-lim-
media is often made with a degree of uncertainty, par- iting and require no specific pharmacological interven-
ticularly in infants and very young children. tion. An extraordinary number of therapeutic agents
Acute otitis media is the most frequent complication has been studied in an attempt either to prevent or to
of viral URTI, particularly in the very young (from treat the common cold, an indicator that there is prob-
6 months to 2 years of age). Virtually all children will ably nothing that makes any real difference. Indeed,
have at least one episode of otitis media and some are there are currently 16 Cochrane systematic reviews of
particularly prone to this complication. Viral inflam- various interventions, most of which conclude either
mation of the nasopharynx disrupts the function of the ‘no difference from placebo’, or that the studies are
eustachian tubes, impairing ventilation, thus rendering of such poor quality that ‘no firm recommendation
the middle ear liable to infection. The microbiology of can be made’. Interventions studied include garlic,
otitis media has been well documented. In a Finnish Echinacea, vitamin C, Chinese medicinal herbs, zinc
study, middle ear fluid was obtained (by myringotomy) and antibiotics. Although NSAIDs improve symp-
in over 90% of 2500 episodes of clinical acute otitis toms of pain (e.g. earache, headache, joint pain), they
media during the first 2 years of life, and a bacterial have no impact on respiratory symptoms. However,
pathogen, particularly S. pneumoniae, M. catarrhalis the transmission of respiratory viruses can be largely
and H. influenzae, was cultured from over 80%. prevented by hygienic measures such as simple hand-
Although this suggests that young children with washing, face masks and isolation (Box 14.1.2).
acute otitis media should be treated with an antibiotic,
the evidence is unimpressive. A Cochrane review found
no reduction in earache at 24 hours between antibiot- Box 14.1.2 Prevention of upper respiratory tract
ics and placebo, and only a small (6%) absolute reduc- infections (URTIs)
tion in pain at 2–7 days. Approximately 80% of all
children with acute otitis media, irrespective of treat- Reduction of exposure in daycare
• Cohorting (both by age and if symptomatic of respiratory
ment, will be pain-free by 2–7 days. This small benefit
tract infection)
of antibiotics is possibly outweighed by the 5% risk of • Reducing overcrowding
adverse effects (rash, diarrhoea and/or vomiting). The • Improving ventilation
duration of antibiotic administration has also been • Individual use of personal items (e.g. toothbrushes and
addressed in a Cochrane review, which concluded that facecloths)
5 days of antibiotics is adequate for uncomplicated ear • Strict handwashing by both staff and children
infections in children. Education of parents about spread of respiratory viruses
Consequently, simple oral or topical analgesics and appropriate care
(anaesthetic ear-drops) are the mainstay of ther- • Similar issues to those outlined above for daycare
apy. However, as with streptococcal pharyngitis, in • Education concerning no antibiotics for URTIs
patients considered at increased risk of complications • Symptomatic treatment should be minimal (e.g. oral
analgesics)
of otitis media (particularly Aboriginals, Torres Strait
Islanders, Maoris and Pacific Islanders) the thresh- Reduced exposure to environmental tobacco smoke,
old for prescribing antibiotics should be substantially especially in homes and cars
lower. Vaccination
S. pneumoniae is the most common reported bacte- • Influenza vaccine
rial cause of acute otitis media (between one-third and • to prevent serious influenza A and B infections in young
one-half of all cases) and initial trials of multivalent children
conjugate vaccines against the serotypes responsible • to reduce the pool of infection to protect the elderly
for otitis media have been shown to be effective. An community
• Pneumococcal conjugate vaccine (to reduce rates of acute
updated summary of the primary care management of
otitis media)
otitis media in Australia was published in the Medical 473
 14.1 RESPIRATORY DISORDERS

Reduced exposure to environmental tobacco

smoke Summary
Although the evidence concerning respiratory infec- The vast majority of respiratory tract infections in
tions and passive smoking relates predominantly to young children are uncomplicated ‘common colds’
lower respiratory tract infections, there is also evidence that require no specific treatment. Although local ENT
that URTIs in young children are increased in those complications are not uncommon, antibiotic treat-
exposed to environmental tobacco smoke. ment for acute otitis media and acute sinusitis offers
limited benefit and can cause adverse effects (partic-
ularly rashes and gastrointestinal symptoms). A very
Immunization small proportion of URTIs are bacterial. Streptococcal
Immunization with pneumococcal conjugate vac- tonsillitis resolves quickly without complication in the
cines reduces the incidence of pneumococcal otitis majority of children without antibiotics. When treating
media due to serotypes in the vaccine, but there is populations known to be at high risk of suppurative
often replacement by non-vaccine serotypes, so that complications, and/or high rates of post-streptococcal
the overall incidence of otitis media is only slightly glomerulonephritis or rheumatic fever, there must be a
lower. New pneumococcal conjugate vaccines incor- substantially lower threshold for antibiotic treatment.
porating increasing numbers of serotypes are being
introduced.
Although often recommended, the use of influ- Practical points
enza vaccine in infants and young children remains
controversial. During years when influenza viruses • Young children experience six to eight viral URTIs per year.
predominate, the rates of hospitalization with acute The vast majority are mild, self-limiting ‘common colds’,
respiratory disease in children under 2 years of age that require no treatment.
(without specific risk factors) can be as high as 2% • Local ENT complications of viral URTIs (e.g. acute sinusitis,
acute otitis media) occur in approximately 10% of URTIs.
per annum. Studies have also found that routine Although these may benefit from symptomatic therapy
immunization of schoolchildren results in a reduc- (such as analgesics), antibiotics are not generally necessary.
tion in mortality from influenza in the elderly. This • A very small proportion of URTIs are bacterial (and may
confirms that children are the major disseminators benefit slightly from antibiotics). The most common is
of influenza, and routine annual influenza immuni- streptococcal pharyngitis (‘tonsillitis’), especially in school-
zation for children should be considered in all young aged children.
children. • Spread of the viral infection into the lower respiratory tract
and secondary bacterial infection are both uncommon
In children over the age of 1 year, it is possible to complications.
use neuraminidase inhibitors, which are potent, safe • The age of the child, the specific infective agent, and other
agents effective against both influenza A and B viruses. host and environmental factors have a major bearing
A Cochrane review concluded that both inhaled zana- on the nature of the respiratory infections, including the
mivir and oral oseltamivir were effective in shortening timing, frequency, severity and likelihood of either local or
illness duration (by 1.0–1.5 days) and hastening return distant complications.
to normal activity in previously healthy children with • A number of recognizable viral oropharyngeal syndromes
occur in young children, including herpes gingivostomatitis
influenza. Efficacy in ‘at risk’ children remains to be and the enteroviral syndromes – herpangina, and hand,
proved. Emergence of drug-resistant strains of viruses foot and mouth disease.
is a potential problem.

474
 Stridor
Sadasivam Suresh, Peter Sly
14.2
Stridor is a symptom of airway obstruction that the extrathoracic airways and to dilate the intratho-
­predominantly involves the upper and larger airway. racic airways (Fig. 14.2.1A). During ­expiration, the
Croup is the commonest cause of stridor in children. direction of the forces is opposite, resulting in a ten-
dency to narrow intrathoracic airways and dilate
extrathoracic airways (Fig. 14.2.1B).
As stridor is an inspiratory noise, the predomi-
Stridor nant site of obstruction (the site responsible for the
flow ­limitation) is generally in the extrathoracic air-
Physiological principles ways. Stridor with an expiratory component, that is,
Stridor is defined in Dorland's Illustrated Medical where the noise can also be heard at the beginning of
Dictionary (28th edition) as ‘a harsh, high-pitched expiration, can result either from a severe obstruction
respiratory sound such as the inspiratory sound often producing flow limitation during expiration as well,
heard in acute laryngeal obstruction’. Although this or from a lesion that extends into the intrathoracic
definition is strictly correct, it is not all that helpful and airways.
gives no information about how and why stridor comes
about. Stridor is a harsh, high-pitched noise heard
Differential diagnosis
predominantly during inspiration. Consideration of
the physiological principles underlying this fact gives When considering the differential diagnosis, several
some clue as to the site of the lesion causing the stri- factors need to be taken into consideration. These
dor. The presence of an added respiratory sound include:
implies an obstruction to the free flow of gas through • Age of onset. A stridor present from the first few
the airway tree. This obstruction is usually known as days of life suggests a congenital or structural
flow limitation. Flow limitation in a compliant tube, cause.
such as the airways, is accompanied by fluttering of • Speed of onset of symptoms. Infective causes such
the walls, which occurs to conserve energy when driv- as croup tend to come on quickly; however, most
ing pressure exceeds the pressure required to produce cases of congenital or structural stridor commonly
the maximal flow. The fluttering of the walls produces first present following a viral upper respiratory
a respiratory noise. When this phenomenon occurs illness.
during inspiration the resultant noise is known as • Progression of stridor. Stridor increasing in severity
stridor, and when it occurs during expiration the noise over weeks to months suggests a progressive lesion,
is known as wheeze. such as subglottic haemangioma.
During breathing, there are pressure gradients • Effect of body position. Stridor that is worse
between the airway opening and the alveoli. Inspiration when lying supine is seen commonly with
occurs when alveolar pressure is lowered below atmo- laryngomalacia.
spheric pressure and air flows in to equalize the pres- • Presence of an expiratory component. This suggests
sures. At the onset of expiration, alveolar pressure a more severe obstruction that limits flow during
exceeds atmospheric pressure and air flows out. There expiration as well as during inspiration.
are also pressure gradients across the airway wall and • Quality of voice. Although the voice is frequently
these tend to alter airway calibre. The pressure around normal, a hoarse voice would suggest a vocal cord
the extrathoracic airways, that is, those above the lesion.
thoracic inlet, is atmospheric, whereas the pressure • Other medical conditions that could contribute
around the intrathoracic airways essentially is equal to to the pathogenesis or presentation: febrile
the pleural pressure. As illustrated in Figure 14.2.1, the illness, ex-premature infant, gastro-oesophageal
pressure gradients across the airway wall during inspi- reflux, cutaneous haemangiomas, Möbius
ration means that there is a net force tending to narrow syndrome (a very rare syndrome characterized
475
 14.2 RESPIRATORY DISORDERS

A 0 • acute epiglottitis (typically a low-pitched rumbling

noise coming from the supraglottic area)
-1 • diphtheria.

-4
-2 2. Persistent stridor
a. Common causes:
-3 • laryngomalacia (infantile larynx)
• congenital subglottic stenosis
-4
• acquired subglottic stenosis in a premature
infant who required intubation
b. Uncommon causes:
-4
• subglottic haemangioma
• vocal cord palsy (unilateral or bilateral)
• laryngeal webs
B 0 • cysts of the posterior tongue or aryepiglottic
folds
+1 • subglottic mucus retention cysts in a premature
infant who required intubation
+4 • vascular ring (note that this usually presents with
+2
a predominantly expiratory noise)
c. Rare causes:
+3
• laryngocele
• laryngeal cleft
+4 • tracheal stenosis (note that this usually presents
with a predominantly expiratory noise).
+4

Characteristics of the more important causes

Fig. 14.2.1 The distribution of pressures throughout the of stridor
respiratory system during (A) inspiration and (B) expiration.
Atmospheric pressure is shown as zero. During inspiration, the Laryngomalacia
expansion of the thorax results in pleural pressure falling below
Laryngomalacia, which is sometimes known as
atmospheric. This relatively negative pressure is transmitted to
the alveoli and a pressure gradient is established between the
infantile larynx, is the most common cause of per-
airway opening and the alveoli. Gas flows into the lungs along sistent stridor. The supraglottic tissues appear as if
this pressure gradient. The pressure outside the airways is they are too large for the size of the glottis and nar-
essentially pleural pressure, and results in net forces that tend to row the glottic aperture during inspiration instead of
expand intrathoracic airways and to collapse the extrathoracic the more normal widening during inspiration. This
trachea. As shown in B, the pressure gradients are opposite can occur in a number of ways, the most common
during expiration.
being:
• a long, curled (sometimes called omega-shaped)
epiglottis collapsing during inspiration so that the
by congenital palsy of the external rectus and
lateral walls touch, restricting the free passage of
facial muscles, usually bilateral, associated with
air (Fig. 14.2.2A)
paralysis of the sixth and seventh nerves).
• floppy arytenoid processes prolapsing into the
glottic aperture during inspiration (Fig. 14.2.2B)
Classification • a long epiglottis collapsing against the posterior
pharyngeal wall during inspiration.
1. Acute stridor
In more severe cases, combinations of these mech-
a. Common causes: anisms may be responsible for the inspiratory
• laryngotracheobronchitis (croup) obstruction.
b. Rare causes (in developed countries): Laryngomalacia classically produces a cog-wheel
• laryngeal trauma stridor, with no expiratory component. The cog-wheel
• acute angioneurotic oedema nature to the stridor is likely to come from vibrations
476 • retropharyngeal abscess of the supraglottic tissues as the degree of obstruc-
• peritonsillar abscess (quinsy) tion varies during the inspiratory effort. The stridor
 Stridor 14.2

Clinical example

Tran was a 3-month-old infant who had been

referred to the respiratory medicine clinic for
assessment of persistent stridor. She was
born at term following an uneventful antenatal
course and normal vaginal delivery. The stridor was not
present at birth and was noticed for the first time at the age
of 2 months when she caught a cold from her older brother.
Her mother was extremely concerned that something was
seriously wrong with her baby as several relatives had told
her it is not normal for a baby to make this type of noise.
Since that time the stridor had been present on most days
but was heard less commonly when Tran was sleeping. Her
mother was concerned that the stridor was becoming louder
and, on questioning, reported that sometimes an expiratory
component could be heard. The stridor was typically worse
when Tran was crying or when lying supine for nappy changes.
Examination revealed a female infant who looked
scrawny. Her height was on the 50% percentile but her
weight was just below the 10% percentile. She had two
typical strawberry naevi on her trunk. While being held in
her mother's arms, a cog-wheel stridor with no expiratory
component could be heard clearly. When she was lying
supine, the stridor was associated with a soft but definite
expiratory component and mild suprasternal retraction.

Discussion points
• What is the most likely diagnosis?
• What investigations are warranted?
A flexible bronchoscopy was performed under general
anaesthesia and revealed laryngomalacia, with a tightly
coiled epiglottis and prolapsing arytenoid processes. The
subglottic area and lower airways were normal.

Discussion points
• Is any treatment warranted?
• Is the fact that Tran's weight percentile is lower than her
height percentile of concern?
• Is the laryngomalacia likely to be responsible for her
relative failure to thrive (lower weight percentile than
Fig. 14.2.2 Flexible bronchoscopy images showing (A) omega- height percentile)?
shaped epiglottis and (B) prolapse of the arytenoids into the • How could this come about?
glottic aperture. The bronchoscopic findings are diagnostic of laryngomalacia
and one can be confident that the symptoms will resolve
spontaneously with time. The relative failure to thrive may
be related to the increased work of breathing required to
may be worse when the infant is lying supine, although overcome the obstruction. However, a dietary assessment
this feature is not always seen. More severe obstruc- is warranted before attributing the failure to thrive to this
tion may be associated with suprasternal and sternal mechanism. As the obstruction decreases with time, Tran's
retraction during inspiration. work of breathing will also decrease and the failure to thrive
Laryngomalacia is usually a benign condition that should resolve.
does not require any treatment, except to ­ reassure
the parents that this is the case. Severe laryngoma-
Subglottic stenosis
lacia may be associated with failure to thrive and
­gastro-oesophageal reflux. The importance of paren- Subglottic stenosis refers to a narrowing in the upper
tal ­
reassurance should not be underestimated, as part of the trachea, immediately below the glottis. This
the stridor is likely to last for 2–3 years. Frequently, narrowing may be congenital or acquired. Congenital
parents find the most distressing part of having a
­ subglottic stenosis occurs typically at the level of, and
child with laryngomalacia are the looks from people involves, the cricoid cartilage. The tracheal epithelium
when they take the child out in public and the well- typically appears normal but the cross-sectional area
477
intentioned advice received from relatives. of the lumen is reduced and typically does not vary
 14.2 RESPIRATORY DISORDERS

with respiration. Acquired subglottic stenosis usu- ous haemangiomas, although the converse association
ally results from trauma and is most commonly seen is much less frequent.
in premature infants who required intubation. Older The earlier a subglottic haemangioma presents,
infants and children who require prolonged intubation the more likely that surgical treatment will be neces-
are also at risk. Here the tracheal epithelium is more sary. Tracheostomy remains the definitive treatment if
likely to be replaced by scar tissue. ­airway obstruction is marked. Medical management is
Subglottic stenosis may present soon after birth or also shown to be of benefit in a subgroup of patients.
the presentation may be delayed. The stenosis, either Commonly used agents are propranolol, corticoste-
congenital or acquired, is usually not progressive but roids or interferon. The milder forms of haemangioma
the degree of obstruction may increase, for example regress, not needing further intervention.
as the child's activity levels increase or at times of
respiratory infection. The typical presentation is with Investigations
stridor, particularly at times of respiratory infection. The most important investigations in elucidating the
If the obstruction is severe enough, the stridor may cause of a stridor are a thorough history and physical
have an expiratory component and be associated with examination. As discussed above, the characteristics
­suprasternal and sternal retractions. of the stridor, the time of onset, the progression, and
Many cases of subglottic stenosis do not require whether or not an expiratory component is p ­ resent
treatment and most will improve with growth. Laser will clarify the cause of the stridor on many occasions.
and dilatation treatments are generally disappointing. The definitive investigation for stridor is bronchos-
More severe obstruction may require surgery, usually copy, preferably performed with a flexible, fibreoptic
involving a procedure in which the cricoid cartilage is bronchoscope. Laryngoscopy is not sufficient as the
split and reconstructed. subglottic area and lower trachea cannot be assessed
safely and adequately. Frequently the trachea can be
Subglottic haemangioma visualized on penetrated radiography of the chest and
The subglottic area can also be narrowed by a hae- lateral neck; however, these X-rays rarely replace the
mangioma occurring in this area. These are typical need for bronchoscopy.
haemangiomas occurring in the submucosal layer of
the tracheal wall (Fig. 14.2.3). As with other haeman-
giomas, they enlarge during the first year of life and Clinical example
­typically present with increasing stridor and inspira-
tory obstruction. The stridor is rarely present at birth Jane was a 4-year-old girl who was brought to
and most come to attention around 4–6 months of age. the emergency department by her mother, who
As the obstruction becomes worse, the stridor ­develops reported increased wheezing over the past day,
an expiratory component and is associated with ­sternal associated with a cold. Jane had a history of
troublesome episodes of asthma for the past 3 years. She was
and suprasternal retractions. Approximately 50% of reasonably well between episodes but, since starting preschool,
subglottic haemangiomas are associated with cutane- her mother had noticed that Jane wheezed when running
and appeared to tire more easily. Jane's mother reported
that the wheeze was not really helped by bronchodilators
and that inhaled steroids did not help prevent the attacks.
On examination, Jane had an expiratory wheeze but had a
prominent inspiratory component to her wheeze. She was not
particularly distressed and her oxygen saturation was normal.

Discussion points
• What is the most likely diagnosis?
• What investigations are warranted?
A chest X-ray showed an odd appearance to the upper
mediastinum but was otherwise normal. A barium swallow
was performed which demonstrated a well-defined indentation
at the upper half of the oesophagus (Fig. 14.2.4). This confirmed
the clinical diagnosis made by the emergency department
consultant that the stridor was due to a vascular ring.

Discussion points
A vascular ring causes an obstruction to the intrathoracic
portion of the trachea. Using the distribution of pressures
throughout the respiratory system shown in Figure 14.2.1,
478 Fig. 14.2.3 Flexible bronchoscopic image showing subglottic explain the physical signs Jane presented with.
haemangioma at the 5–7 o'clock position.
 Stridor 14.2
infection and progress to typical croup over 1–2 days.
Practical points The most common viruses ­isolated from ­children with
croup are parainfluenza virus type 1 (up to 50% in
• A careful history of the age of onset, features of preceding some series), parainfluenza virus type 3 (up to 20%) and
viral infection, nature and respiratory timing of the stridor respiratory syncytial virus (approximately 10%).
are important for diagnosis.
• Many children with stridor need no investigations.
• Persistent stridor with an expiratory component always Clinical manifestations
warrants further investigation.
As mentioned above, croup usually begins with signs and
symptoms of an upper respiratory infection, including
fever and rhinitis. A cough may be present. The typical
barking, croupy cough usually begins during the night
or the early hours of the morning. As the disease pro-
gresses, stridor may be heard on e­ xertion initially. If the
subglottic obstruction progresses ­further, stridor may
be heard at rest and an expiratory component may be
heard. The typical cough continues to be heard.
If the degree of obstruction continues to worsen,
the stridor may become more difficult to hear and
the child may become distressed and restless. Cough
may be absent at this stage. The lack of stridor comes
about because the amount of air moving through the
obstructed airway is not sufficient to generate the noise
(see above). The distress and restlessness are most likely
to be due to hypoxia and signal impending complete
respiratory obstruction.
The viral illness generally lasts 7–10 days, but the
typical croupy cough usually only occurs on the first
2–3 nights.

Investigations
Fig. 14.2.4 Barium swallow demonstrating extrinsic compression
of the oesophagus by the vascular ring. Most children with croup do not warrant any inves-
tigations. Viral diagnosis on nasal secretions, usually
obtained by per nasal aspiration, can be helpful from
an epidemiological point of view but will not alter
Croup (laryngotracheobronchitis) management. Chest X-rays are not helpful for children
Croup is usually considered to exist in two forms: with typical croup.
• acute viral croup Children less than 6 months old who present with croup
• recurrent (or spasmodic) croup. or those whose croup runs an atypical course warrant
Although these two conditions have a number of simi- investigation. The most useful investigations are likely to
larities, they are likely to be distinct entities. They have be a lateral neck X-ray and flexible bronchoscopy.
in common that they involve the larynx, trachea and
bronchi, and present with a typically barking cough. Management
The cough is so typical it is usually referred to as a
‘croupy’ cough. The majority of children with croup do not require any
treatment. Symptomatic treatment for fever and cold
symptoms may be warranted. Children with a croupy
Acute viral croup
cough and stridor on exertion (but not at rest) can usu-
Acute viral croup is typically a disease of toddlers, being ally be managed with supportive treatment only. There
rare in the first 6 months of life and reaching a peak is a widespread belief that exposing these children to
incidence of 5 cases per 100 children per year during the steam, especially by steaming up the home bathroom,
second year of life. Boys are affected more commonly helps relieve stridor. There is no evidence to support
than girls. Most children who get acute viral croup will this treatment. The only benefit that is likely to come
only ever have one or two episodes. These episodes typi- from sitting with the child in a steamy bathroom is from
479
cally begin with the symptoms of an upper respiratory sitting quietly with the child and not from the steam.
 14.2 RESPIRATORY DISORDERS

Children with stridor at rest warrant medical assess- Recurrent (spasmodic) croup
ment. The most useful treatment for croup that has
Some children suffer recurrent episodes of croup,
reached this severity is corticosteroids. These can be
­frequently without the preceding viral prodrome usu-
giving orally in syrup form or inhaled (nebulizer or
ally seen in acute viral croup. Typically these children
metered-dose inhaler and spacer). The mechanism of
are well when they go to bed and wake in the early
action is not known but is likely to be via a topical
hours of the morning with a barking cough and stri-
action. A single dose of steroids decreases the risk of
dor. Fever is unusual in this form of croup. The same
hospitalization dramatically.
viruses as found in acute viral croup may be found in
More severe obstruction can be relieved by nebu-
the upper airways of children with spasmodic croup,
lized adrenaline (epinephrine). Traditionally this has
although the relationship between the viruses and
been given as a 50 : 50 mix of the l- and d-isoforms
the symptoms is less clear. Frequently children with
(known as racemic adrenaline), but the l-isoform (as
­recurrent croup have a family history of atopy and
found in standard ampoules of intravenous adrena-
asthma, or have asthma themselves. This, together
line) is as effective and is now commonly used. This
with the uncertain relationship between the clinical
relieves obstruction by causing a topical vasoconstric-
symptoms and the presence of a virus, have led to the
tion, which wears off in 1–4 hours, depending on the
concept that spasmodic croup may be a manifestation
severity of the underlying obstruction.
of upper airway hyperresponsiveness. There are no
Severe obstruction may require intubation or even
direct data to support or refute this hypothesis. The
tracheostomy, although the need for these types of
viral isolates from these patients are similar to those
treatment has become much less with the widespread
found in children with acute croup. There is some
use of oral corticosteroids in the emergency depart-
­literature supporting the association between gastro-
ments of paediatric hospitals in Australia.
oesophageal reflux disease and episodes of recurrent
A management flowchart from a recent review
croup.
article summarizes acute outpatient management of
Spasmodic croup may be severe enough to require
croup (Fig. 14.2.5).
treatment with oral corticosteroids, nebulized a­ drenaline
or even intubation; however, the episodes are ­frequently
short-lived and often settle by the time the child
Practical points ­presents to the emergency department.
Although controlled trials have not been carried out,
• Use of corticosteroids can favourably modify the course there is a substantial body of anecdotal evidence that
of acute viral croup.
frequent bouts of recurrent croup can be prevented by
• Severe croup can lead to complete airway obstruction and
death. maintenance therapy with inhaled corticosteroids via
a spacer.

480
 Stridor 14.2
Mild Moderate Severe

Give oral or Give oral or Minimize situations that may

intramuscular intramuscular cause distress in child, such
dexamethasone, dexamethasone, as separation from parents
0.6 mg/kg 0.6 mg/kg and unnecessary examination
Discuss with parents Minimize situations Provid ‘blow-by’ oxygen if
likely course of that may cause cyanosis present
illness and when to distress in child, Give oral or intramuscular
seek additional such as separation dexamethasone, 0.6 mg/kg
care if further from parents and Administer epinephrine by
respiratory unnecessary nebulization, either racemic
distress occurs examination epinephrine 2.25%, 0.5 ml in
Observe for 2.5 ml of saline, or L-
improvement for epinephrine, 1:1000 dilution
1–4 hr in 5 ml of saline
DIscharge home

If patient improves — If no or minimal If good response to If poor response,

as evidenced by no improvement after epinephrine, observe repeat nebulized
stridor at rest and no 4 hr, consider for 2 hr epinephrine; if poor
chest-wall hospitalization response to second
indrawing — then treatment, admit
discuss with child for ICU care
parents likely course and probable
of illness and when workup for LTB,
to seek additional LTBP, and secondary
care bacterial infection

If only mild symptoms If severe respiratory

DIscharge home persist (i.e. croupy distress recurs,
cough) and there is no repeat nebulized
recurrence of stridor epinephrine
at rest or of chest-wall
indrawing then discuss
with parents when to
seek additional care
If good response, If poor response to
observe for 2 hr; if only second treatment
mild symptoms persist with nebulized
DIscharge home and there is no epinephrine, admit
recurrence of stridor child for ICU care
at rest or of chest-wall and probable
indrawing, then workup for LTB,
discuss with parents LTBP, and secondary
when to seek bacterial infection
additional care

DIscharge home

Fig. 14.2.5 Outpatient management flow chart. ICU, intensive care unit; LTB, laryngotracheobronchitis; LTBP, laryngotracheo­
bronchopneumonitis. (Source: Cherry JD 2008 Clinical practice. Croup. N Engl J Med 358:384–389.)

481
 14.3 Asthma Adam Jaffé

is likely to be caused by the spread of viruses such as

Definition rhinovirus in the classroom.
The word ‘asthma’ is a derivative of the Greek verb
aazein , meaning ‘to pant’. In an attempt to describe
it more precisely, the Global Initiative for Asthma
(GINA) has defined asthma as ‘a chronic inflamma- Age of onset
tory disorder of the airways in which many cells and The onset of asthma can occur at any age, including
cellular elements play a role. The chronic inflamma- within the first few years of life; children under 4 years
tion is associated with airway hyper-responsiveness of age are more likely to be hospitalized or to seek medi-
that leads to recurrent episodes of wheezing, breath- cal attention. However, the diagnosis of asthma is par-
lessness, chest tightness, and coughing, particularly at ticularly difficult in the preschool child as there are many
night or in the early morning. These episodes are usu- different wheezing phenotypes in this age group (see
ally associated with widespread, but variable, airflow Chapter 14.4). It is often difficult to distinguish young
obstruction within the lung that is often reversible children who wheeze with upper respiratory tract viral
either spontaneously or with treatment’. Although infections from those with intermittent asthma. The
this is a complex definition and is of limited practi- importance of this distinction is that those with virus-
cal value in making the diagnosis in an individual, it induced wheeze will usually get better by 6 years of age.
highlights the interplay between inflammation, air- The Asthma Predictive Index is a helpful guide
way hyper-responsiveness, obstruction and clinical in the clinical setting for predicting whether chil-
symptoms. dren under 3 years of age with recurrent wheeze will
develop asthma when older. Children are at a high risk
of developing asthma if they have either:
one of:
• parental history of asthma (particularly
Burden of asthma maternal)
Asthma is estimated to affect 300 million people • eczema
worldwide. Although the burden of asthma contin- • sensitization to aeroallergens
ues to increase in some countries, its prevalence is sta- or two of:
bilizing and even declining in others. In the UK the • allergic rhinitis
prevalence of asthma is 1 in 11, and in Australia it is • > 4% eosinophilia
1 in 9 children. The International Study of Asthma • food allergies
and Allergies in Childhood (ISAAC) has identified • wheezing in circumstances not related to upper
Australia, along with the UK, New Zealand and the respiratory tract infections.
Republic of Ireland, as having a relatively high prev-
alence of asthma in children compared with other
countries. It is one of the commonest presentations
to the primary physician and emergency depart- Pathogenesis
ment. In most developed countries the mortality rate
Genes
remains low, but death still occurs in childhood. Like
many respiratory diseases, the prevalence of asthma The cause of asthma is multifactorial and complicated,
is higher in Indigenous children. and involves an interaction between genetic deter-
The return to school after the summer holidays is minants and environmental stimuli (Table 14.3.1).
associated with a peak in hospital admissions; this Although asthma has been known to run in fami-
occurs in February in the southern hemisphere, and in lies, the inheritance pattern remains unclear. Asthma
October in countries in the northern hemisphere, and is polygenic and, although many potential candidate
482
 ASTHMA 14.3
Table 14.3.1 Factors involved in the pathogenesis of asthma

Host Environment

Innate immunity Allergens

• Hygiene hypothesis • Aeroallergens (house dust mite, cockroaches, Alternaria)

Genetic candidates Respiratory infections

• β2-adrenoreceptor • Viruses (e.g. RSV) (association but causation not yet proven)
• Tumour necrosis factor α Environmental tobacco smoke
• Interleukin-4 • In utero causes smaller airways and increased wheeze in
• Interleukin-4 receptor early life
• Clara cell protein • Continued exposure associated with increased asthma severity
• CD14
Air pollution (association but causation not fully proven)
• β-chain of IgE receptor
• RANTES (a chemokine) promoter polymorphism Low intake of antioxidants (association but causation not yet proven)
• ADAM33 (a disintegrin and matrix metalloproteinase Low intake of omega-3 fatty acids (association but causation not yet
domain-containing protein 33) proven)
Sex Obesity (via inflammatory mediators)
• More prevalent in boys
• From puberty, more prevalent in females Chlorinated swimming pools in infancy (association but causation not yet
proven)
Paracetamol (controversial – association in utero and first 12 months of
life but causation not proven)

Ig, immunoglobulin; RANTES, regulated upon activation, normal T cell expressed and secreted; RSV, respiratory syncytial virus

genes have been discovered, no single gene accounts immune system to develop along the Th1 pathway
for more than 10% of the susceptibility of an indi- with expression of IL-2 and interferon-γ. Having older
vidual for developing asthma. Boys generally have siblings or living in a rural environment also favours
smaller airways than girls and tend to suffer more from the expression of the Th1 phenotype; these children
asthma. However, after adolescence the prevalence is generally do not develop an allergic phenotype.
higher in females.
Viruses
Allergy
Although viruses such as human rhinovirus C cause
The role of allergy in asthma is very important and asthma exacerbations, it is increasingly recognized
more than 80% of people with asthma have an allergy. that exposure to viruses may lead to the development
Sensitization and chronic exposure to aeroallergens such of asthma. Some researchers have demonstrated that
as house dust mite, cockroach and animal dander are babies exposed to winter viruses are more likely to
implicated in the development of asthma; however, this develop asthma later in life. The role of respiratory
research area remains confusing as there is evidence that syncytial virus (RSV) is important but controversial.
early exposure to animals such as dogs may be protective. Infection with RSV is certainly associated with the
development of asthma, but whether it causes asthma
directly or is simply a marker for those likely to develop
Hygiene hypothesis
asthma remains to be elucidated.
This is another explanation for why children develop
asthma. At birth, there is an overexpression of the Most children with asthma have an underly-
T-helper cell type 2 (Th2) pathway. Th2 cells produce ing immunoglobulin (Ig) E-mediated eosinophilic
cytokines (interleukin (IL)-4, -5, -6, -9 and -13) that response, but it is increasingly being recognized that
mediate allergic inflammation, and this pathway is there are other phenotypes such as neutrophilic
associated with the development of atopy and asthma. asthma. This has potential implications with regard
Factors that favour the Th2 phenotype include anti- to therapy, as children with neutrophilic asthma may
biotic use, diet, urban environment and lifestyle, and benefit from medications such as macrolides. Future
sensitization to allergens. Exposure to environmen- research will help to define better the different pheno-
tal stimuli such as lipopolysaccharide stimulates the types and causes of asthma in children.
483
 14.3 RESPIRATORY DISORDERS

Clinical features Clinical example

The diagnosis of asthma is likely in children with the
John was a 12-year-old boy who presented with
following symptoms, particularly if they occur at night a history of breathlessness and chest pain that
or early in the morning or have identified triggers: occurred towards the end of an 800-metre run.
• Wheeze – the main symptom is wheeze which is a Neither cough nor wheeze was present. He had
musical note caused by turbulent air flow and is received bronchodilators and sodium cromoglycate before
usually, but not always, present in children with exercise, without benefit. A trial of inhaled corticosteroids for
6  weeks followed by a leukotriene receptor antagonist had
asthma. Parents often mistake wheeze for other
also been ineffective. His parents were both keen athletes
sounds such as stertor or rattle, so it is important and hoped that John would become a champion athlete.
to ensure that parents understand what is meant by Physical examination was normal. FEV1 was normal and
the term ‘wheeze’ (see Chapter 14.4) a mannitol challenge test was negative, with no evidence
• Cough of airway hyper-responsiveness. John was non-atopic on
• Difficulty breathing allergen skin testing. After an explanation to John and
• Chest tightness. his parents that he did not have asthma, John indicated
that he was not interested in competitive athletics. He
The likelihood of asthma is increased if there is a per-
was discharged on no treatment. One year later he was
sonal history of atopy or a family history of atopy or completely well. He could play regular sport with no
asthma. A clinical or lung function bronchodilator difficulties. The tests used were helpful in confirming that
response to β-agonists further supports the diagnosis of John did not have asthma.
asthma. It is a myth that asthma cannot be diagnosed
under 2 years of age, although it is often difficult to do
so in the absence of confirmatory lung function testing.

Classification
A useful way to classify asthma is according to symp-
History tom pattern, which helps to determine the need for a
controller medication (Table 14.3.2). Infrequent ­inter-
The key points to concentrate on are:
mittent asthma occurs in 70–75% of all childhood
• antenatal history: smoking (causes smaller airways) asthmatics. Frequent intermittent asthma occurs in
• birth history: prematurity, need for ventilator 20% of asthmatic children, and only 5% of children
support (premature babies may wheeze for other
have persistent asthma.
reasons such as bronchomalacia)
Questions that are particularly helpful in clarifying
• atopy: development of food intolerance, eczema, the pattern of asthma include:
hay fever
• Are there nocturnal symptoms?
• triggers: viruses, exercise, allergen exposure,
• Are there symptoms on waking in the morning?
cold air, emotions such as laughter,
• Is there normal exercise tolerance?
thunderstorms
• How much school is missed because of asthma?
• symptom pattern: this helps classify the type and
• How frequent is the use of bronchodilator
severity of asthma
medication?
• family history: asthma, eczema, hay fever, atopy
• How frequent are asthma symptoms?
(particularly parental)
• social history: exposure to environmental tobacco smoke
(parental smoking outside still results in exposure to
the child), pets, mould, cockroaches, house dust mite.
Clinical example

Jane presented with her first episode of wheeze

at 8  months of age. She responded well to a
Examination bronchodilator. She did not have eczema and
there was no history of asthma or hay fever
The key signs on examination in both acute and in the family. She continued to become wheezy when she
chronic asthma are summarized in Figure 14.3.1. caught a viral upper respiratory tract infection. The episodes
An alternative diagnosis should be sought in chil- occurred approximately every 3  months and she was treated
with inhaled salbutamol via a spacer only. When she started
dren who are clubbed, have a history of a moist cough,
school, her symptoms disappeared. Her case is typical of those
have cough as their only symptom, have normal clini- children with infrequent intermittent asthma where a preventer
cal signs and spirometry when symptomatic, and do is not necessary; most children grow out of it by 6  years of age.
484
not respond to asthma treatment.
 ASTHMA 14.3

Acute signs of asthma Growth Chronic signs of asthma

Cyanosis in
Allergic shiners
severe asthma

Transverse nasal crease

Tracheal tug Swollen turbinates
Rhinitis

Pulsus paradoxus Mouth breather

Prolonged expiratory
phase/wheeze (may be Pectus carinatum/
absent in severe asthma) hyperexpansion

Use of accessory muscles

Intercostal/subcostal Excema
recession

Increased respiratory
rate (may be decreased Never clubbed
in severe asthma)

Abdominal breathing
Harrison’s sulci
prominent in babies

Fig. 14.3.1 Key examination findings in acute and chronic asthma.

the administration of a β-agonist indicates a

Investigations significant positive bronchodilator response and
• Chest X-ray: there is no role for a routine chest X-ray. supports the diagnosis of asthma.
This should be done only if the diagnosis is uncertain. • Bronchial provocation tests help in assessing whether
• Skin prick tests to common aeroallergens in the child has bronchial h
­ yper-responsiveness. There
children of all ages are usually helpful but may are different techniques available but they all rely
change over time in the very young child whose on the principle of inhaling increasing doses of
immune system is developing. a stimulus that causes bronchoconstriction and
• Spirometry: typically children from age 5 years measuring the fall in FEV1:
onward can perform reproducible spirometry, • Direct challenge of bronchial smooth muscle cells:
although children from 31⁄2 years may be able to methacholine; histamine. Although responsiveness
do this with incentive software on lung function correlates well with asthma severity, a response is
testing equipment. Typically the flow volume loop not necessarily specific to asthma diagnosis.
will show an obstructive picture with classical • Indirect challenge by the action of inflammatory
‘scooping’ of the expiratory flow volume loop mediators released from intermediary cells
(Fig. 14.3.2) with a reduced forced expiratory such as mast cells in response to a stimulus to:
volume in 1 second (FEV1) to forced vital capacity adenosine; hypertonic saline; cold air; eucapnic
(FVC) ratio of less than 0.70. voluntary hyperpnoea (hyperventilating with
• Bronchodilator response: an increase in FEV1 or a dry gas); exercise; mannitol (useful for the
485
FVC of ≥ 12% or ≥ 200 mL 10–15 minutes following diagnosis of exercise-induced asthma).
 14.3 RESPIRATORY DISORDERS

Table 14.3.2 Classification of asthma by symptom pattern in children

Intermittent Persistent

Infrequent Frequent Mild Moderate Severe

Symptoms None None > 1 per week but < 1 Daily Continual
per day

Exacerbations Brief, mild, occur > 2 per month May affect activity and ≥ 2 per week Frequent
< 4–6 weeks sleep Affects activity and Restricts activity
sleep
Nocturnal None None > 2 per month > 1 per week Frequent
symptoms

FEV1 or PEF (in > 80% predicted > 80% predicted > 80% predicted 60–80% ≤ 60%
children over
5  years of age)

Variability of FEV1 < 20% < 20% 20–30% 30% >30%

and PEF (in children
over 5  years of age)

FEV1, forced expiratory volume in 1  second; PEF, peak expiratory flow.

Adapted with permission from: Global Initiative for Asthma (GINA) 2008 Global strategy for asthma management and prevention,
Bethesda, and National Asthma Council Australia 2006 Asthma management handbook 2006, South Melbourne.

16

Spirometry Ref Pre %Ref Post %Ref %Chg

FVC Litres 4.71 4.01 85 4.19 89 5
FEV1 Litres 4.06 2.97 73 3.38 83 14
12
FEV1/FVC L/sec 86 74 81
FEF25–75% L/sec 4.50 2.32 52 3.18 71 37
PEF L/sec 8.22 6.59 80 7.02 85 7
PIF L/sec 3.72 4.17 12
8
Flow (L/sec)

PRED
4
PRE
POST

8
0
6
Volume

2
–4
0
–1 0 1 2 3 4 5 6 7 8
Time

Fig. 14.3.2 Spirometry demonstrating a scooped flow volume loop seen in obstructive disease in asthma. Following bronchodilator
486 use (PRED, predicted) there is a positive bronchodilator response of > 12% in forced expiratory volume in 1 second (FEV1). FEF, forced
expiratory flow rate; FVC, forced vital capacity; PEF, peak expiratory flow rate; PIF, peak inspiratory flow rate.
 ASTHMA 14.3
• Exhaled nitric oxide is a marker of lower airway should be avoided in those taking oral theophyl-
eosinophilic inflammation and may have a role in line owing to its potentially cardiotoxic nature. In
helping make the diagnosis of asthma and assessing deteriorating severe cases, intravenous magnesium
the impact of therapy. It is often raised in children sulphate may avoid intubation. Any child requir-
with allergies. ing 3-hourly or more frequent β2-agonists should be
admitted to hospital.
The resolution of an acute attack of asthma is
not the end of treatment and should be used as an
Management opportunity to consider the background control
and educate the child and parents in the ongoing
Acute asthma
management.
The focus of management of acute attacks is the
assessment of severity of the episode and treatment to
Chronic asthma
restore to normal baseline lung function. The initial
assessment identifies children whose asthma is mild All children should have an asthma action plan
and may be managed at home and those who require reviewed at least 6-monthly. The school should be
admission to hospital and may require management in aware of the child's medical condition and have a copy
an intensive care unit. The key signs on examination of the plan.
in acute asthma are displayed in Figure 14.3.1. The • Preventative strategies:
assessment of a child with acute asthma is outlined in • environmental tobacco smoke avoidance
Table 14.3.3. • aeroallergen avoidance (such as pets)
Initial management consists of oxygen and • Pharmacological management. There are two
repeated doses of an inhaled β2-agonist, preferably principal classes of medication used in the chronic
by a spacer device. A nebulizer driven by oxygen may management of asthma:
be required in severe asthma. Ipratropium may be • Relievers – short-acting bronchodilators have a
considered in moderate to severe cases for its addi- rapid onset and are used as required. Rapidly
tive effect. Systemic steroids should be given either acting inhaled β2-agonists are generally more
by the oral route or intravenously in severe cases. effective than ipratropium bromide. Children
In deteriorating cases, salbutamol may be given with infrequent intermittent asthma require
intravenously with regular monitoring of potas- treatment only during exacerbations and do not
sium. Intravenous aminophylline may also be used need controller medications. Those who have
in severe asthma, although its popularity in various more regular symptoms require a controller
paediatric departments fluctuates. A loading dose medication.

Table 14.3.3 Assessment of a child with acute asthma

Symptoms Mild Moderate Severe and life-threatening

Saturations in air > 94% 90–94%* < 90%*

Central cyanosis None None Present

Heart rate Normal range for age Mild–moderate tachycardia Marked tachycardia for age (bradycardia
for age suggests imminent arrest)

Ability to talk Sentences/long cry Phrases/shortened cry Words/weak cry/unable to vocalize

Use of accessory muscles None Mild to moderate Moderate to severe

Presence of wheeze Variable Moderate to loud Quiet/absent

Consciousness Alert Easily engaged Agitated, drowsy, confused

*Inhaled β-agonists can cause an increase in ventilation perfusion mismatch and a decrease in oxygen saturations. A low reading
should be interpreted in the context of other clinical symptoms.
Adapted with permission from: National Asthma Council Australia 2006 Asthma management handbook 2006, South Melbourne. 487
 14.3 RESPIRATORY DISORDERS

• Controllers – inhaled steroids; leukotriene Unified airway hypothesis

receptor antagonists; cromones; combination
The nose is that part of the airway accessible to the
therapy of inhaled steroid and long-acting β ­ 2-
finger. Nasal inflammation is likely to exert effects on
agonist; theophylline.
the lower airway through a, yet to be proven, ‘naso-
Children with frequent intermittent asthma may ben-
bronchial reflex’. It is essential that allergic rhinitis is
efit from a controller, particularly over the winter
treated appropriately as this can improve asthma con-
months. Controller medications are required in those
trol and lung function with a reduction in lower airway
with persistent asthma. Although there are ­subtle dif-
inflammation. The most effective treatment is with
ferences in the stepwise management in various guide-
topical steroids, but leukotriene receptor antagonists,
lines worldwide (Figs 14.3.3 & 14.3.4), the ­principal aim
inhaled cromones and antihistamines (oral or inhaled)
is to start at the most appropriate level and step up or
are alternative strategies.
down depending on the level of control (Table 14.3.4).

Drug side-effects
Clinical example
Steroids
Craig was an 8-year-old boy who had eczema
The growth of children on long-term inhaled ste-
and rubbed his nose. He coughed most nights
and when tickled. He wheezed with exercise.
roids may be affected. Although final adult height is
His mother had severe asthma and smoked. attained, it may be delayed. Use of high-dose inhaled
There were two cats at home. Craig demonstrated a steroids (> 500 μg fluticasone, > 800 μg beclomethasone
bronchodilator response of 21% FEV1. Skin-prick testing was diproprionate, > 800 μg budesonide per day) is associ-
positive to house dust mite, cat and grasses. Think about ated with adrenal suppression and has resulted in death
how you would classify his pattern of asthma and develop due to adrenal crisis. These overall potential risks are
an asthma management plan. Remember to address
well balanced by their benefits. Children on inhaled
environmental factors, treat the nose, assess the level of
control and choose an appropriate step to commence a corticosteroids at these doses should have their adrenal
controller medication. function tested; they may require steroid replacement
in times of stress if they have adrenal insufficiency.

Step 4
Refer to respiratory
paediatrician

Step 3
BTS – LTRA if on low dose
– If children < 2 years consider moving
to Step 4
Aus – low dose inhaled steroid (200-400
mcg/day)* if on LTRA
– If on low dose inhaled steroid then
double to (400–800 mcg/day)* BTS = British Thoracic Society
GINA – Double inhaled steroid (400–800 Aus = National Asthma Council, Australia
mcg/day)* or GINA = Global Initiative for Asthma
– add LTRA
LTRA = Leukotriene receptor antagonist
Step 2
BTS – Inhaled steroid
– LTRA if inhaled steroid cannot be used * Budesonide equivalence
Aus – Inhaled steroid or
– LTRA or At all steps check:
– cromones
GINA – inhaled steroid • Level of control
• Diagnosis
Steroid dose is low dose (200-400 mcg/day)* • Aherence
• Technique
Step 1 • Nasal Symptoms
Short acting β agonist as required • Modifiable environmental factors
• Consider stepping down

Fig. 14.3.3 Stepwise pharmacological management of asthma in children aged 5 years and younger, incorporating Australian
488 National Asthma Council (Aus), British Thoracic Society (BTS) and Global Initiative for Asthma (GINA) guidelines. *Budesonide
equivalence. LTRA, leukotriene receptor antagonist. LABA, long acting β agonist.
 ASTHMA 14.3
Refer to repiratory paediatrician
Step 5
BTS – Daily oral steroid
Aus – Add LABA and then increase to
800 mcg/day* if not controlled
GINA – Oral steroids
– consider anti-IgE

Step 4
BTS – Increase inhaled steroids to 800
mcg/day*
Aus – Increase inhaled steroids to 800
mcg/day*
GINA – Oral steroids
– consider anti-IgE

Step 3
BTS – add LABA; if still not controlled either
– increase steroid to 400mcg/day* or
– stop LABA and increase steroid to
400 mcg/day*. If still not controlled
then add LTRA or slow release
theophylline
Aus – Low dose inhaled steroid if on LTRA
– If on low dose inhaled steroid then
double to 400–800 mcg/day* or add
LTRA if exercise related symptoms
GINA – Add LABA or
– Increase to medium dose of inhaled
steroids or
– Add LTRA or slow release theophylline BTS = British Thoracic Society
Aus = National Asthma Council, Australia
GINA = Global Initiative for Asthma
Step 2 LABA = long acting β agonist
BTS – Inhaled steroid LTRA = Leukotriene receptor antagonist
– other preventer if inhaled steroid
cannot be used * Budesonide equivalence
Aus – Inhaled steroid or
– LTRA or
– cromones At all steps check:
GINA – inhaled steroid (preferred) or
– LTRA • Level of control
• Diagnosis
Steroid dose is low dose (200-400 mcg/day)* • Aherence
• Technique
Step 1 • Nasal Symptoms
Short acting β agonist as required • Modifiable environmental factors
• Consider stepping down

Fig. 14.3.4 Stepwise pharmacological management of asthma in children aged over 5  years, incorporating Australian National
Asthma Council (Aus), British Thoracic Society (BTS) and Global Initiative for Asthma (GINA) guidelines. *Budesonide equivalence.
Ig, immunoglobulin; LABA, long-acting β-agonist; LTRA, leukotriene receptor antagonist.

Long-acting β-agonists
The use of long-acting β-agonists (LABAs) alone has Practical points
been associated with an increase in death in adults and
should never be used without an inhaled steroid in
• The severity pattern of asthma indicates whether a
­combination. Some children with the Arg/Arg muta- controller medication should be used.
tion at position 16 of the β2-adrenoreceptor gene • All children should have an asthma action plan that is
treated with LABAs may develop tachyphylaxis/toler- reviewed regularly.
ance to β-agonists, resulting in worsening of asthma • Aeroallergens and exposure to environmental tobacco
control and poor response to short-acting β-agonists. smoke should be avoided.
Given these potential problems, LABAs should be • Treatment is aimed at controlling symptoms.
• Regularly check the level of control, diagnosis, inhaler
used only in children with severe uncontrolled persis- technique, response to treatment and adherence.
tent asthma (approximately 5% of all children with • Allergic rhinitis should be treated. 489
asthma).
 14.3 RESPIRATORY DISORDERS

Table 14.3.4 Assessment of asthma control in children of all ages

Uncontrolled
Controlled Partly controlled (3 or more features of partly
Characteristic (all of the below) (any measure in a week) controlled in any week)

Daytime symptoms None (≤ 2 per week) > 2 per week > 2 per week

Limitations of activities None (≤ 2 per week) Any Any

Nocturnal symptoms None Any Any

Need for reliever None (≤ 2 per week) > 2 per week Any

Exacerbations None ≥ 1 per year 1 in any week

Lung function (over Normal < 80% predicted or best < 80% predicted or best
5  years only)

Adapted with permission from: Global Initiative for Asthma (GINA) 2008 Global strategy for asthma management and prevention,
Bethesda, and GINA 2009 Global strategy for the diagnosis of management of asthma in children 5  years and younger, Bethesda.

Inhaler devices Prognosis

The most effective way for delivering an inhaled med- Most children who have wheezed in childhood will grow out
ication at any age is by a metered-dose inhaler and of it by adulthood. The rates vary from 58% (Melbourne
valved spacer device. Children should use a spacer study) to approximately 75% (UK and Tasmanian stud-
with mask until 3 years of age, and after that use ies). The discrepancies may be due to the classification of
a spacer with mouthpiece. One actuation at a time asthma in these studies. The long-term prognosis depends
should be used to ensure optimal delivery. Owing to on the pattern of asthma in childhood. Some 60% of those
the impracticality of carrying around a spacer device, with intermittent (previously called episodic) asthma will
particularly for short-acting β−agonists, a dry-­powder have grown out of it, but as many as 90% of those chil-
device may be used in older children. Irrespective of dren with severe persistent asthma will continue to have
which device the child uses, it is essential that it is age- symptoms in adulthood and have reduced lung function.
appropriate and that inhaler ­technique is assessed However, with appropriate therapies, asthma should be
regularly. well controlled, ensuring a normal quality of life.

490
 Wheezing disorders 14.4
other than asthma
Hiran Selvadurai

The previous chapter discussed the diagnosis and extrathoracic compartment, wheezing may be heard in
management of asthma. An important feature of
­ the inspiratory phase of the respiratory cycle. Other
asthma is wheeze. Although asthma is the most sounds such as stridor, snoring and nasopharyngeal
common cause of recurrent wheeze in childhood,
­ congestion may all be erroneously reported to the
there are several other causes of wheezing that need ­clinician as a ‘wheeze’. Unlike a typical wheeze, these
to be considered. The non-asthmatic causes of wheeze sounds tend to be low-pitched and guttural in nature.
in childhood are frequently seen by general practi- The aetiology of non-asthmatic wheeze can be
tioners and may provide a diagnostic conundrum. ­categorized according to the age of presentation. As
The purpose of this chapter is to present some of the such, non-asthmatic wheeze in infants and preschool
more common causes of wheezing that are not due to ­children will be presented separately to non-asthmatic
asthma. Although space precludes an exhaustive and wheeze in school-aged children.
detailed list of non-asthmatic causes of wheeze, it is
hoped that when the typical signs and symptoms of
asthma do not ‘fit’, the clinician is prepared to ­consider
other causes of wheeze. Causes of non-asthmatic wheeze
in infancy and preschool children
Transient infantile wheeze
Definition and pathophysiology Transient infantile wheeze is typified by wheeze that
It is important to have a clear definition of a wheeze is associated with an intercurrent respiratory tract ill-
in order to obtain an accurate history from the child's ness within the first 3 years of life. Unlike in children
parent. A ‘wheeze’ can be defined as a high-pitched with asthma, children with transient infantile wheeze
whistling noise that occurs during the respiratory are non-atopic and generally do not have a family
cycle. The high-pitched whistle is caused by air flowing ­history of asthma. There is no hypoxia or significant
rapidly through compressed or partially obstructed morbidity with this condition. The children are gener-
airways. Although a wheeze can occur in either the ally thriving. After the age of 3 years, children with
inspiratory or the expiratory phases of the respiratory transient infantile wheeze become less symptomatic
cycle, the latter is significantly more common in child- and generally are symptom-free by the age of 6 years.
hood. The reason is that, owing to the small size, par- The pathophysiology of this condition is thought to
tially obstructed flow most commonly occurs in the be congenitally small, poorly developed, airways.
bronchioles. The bronchioles lay in the intrathoracic Although the aetiology is uncertain, there is an associ-
section of the respiratory system. During inspiration, ation with maternal smoking. Bronchodilators are not
the highly negative intrapleural pressures relative to usually effective in treating the wheeze in children with
the intraluminal pressures keep the bronchioles patent. transient infantile wheeze.
However, during expiration, the intrapleural pressures
relative to intraluminal pressure are positive. Hence,
Infections
the lumen of the bronchioles and other intrathoracic
structures may be compromised. Consequently, partial The common viruses that can infect the respiratory
obstruction of the bronchioles tends to occur during tract of infants and preschool children are respira-
the expiratory phase of the respiratory cycle. tory syncytial virus (RSV), metapneumovirus, influ-
Although it is correct that partial obstruction can enza, parainfluenza and rhinovirus. Children with
occur in the larger airways and turbulent flow can acute bronchiolitis may present with a short history of
cause a wheeze to occur, this is less common as plates coryza, cough and wheeze, together with tachypnoea
of cartilage that are present in the trachea serve to and a mild fever. On auscultation, coarse crackles are a
keep it firm and less likely to be compressed. If there is more common finding than wheeze. See Chapter 14.5
partial obstruction in the larger airways that lay in the for a detailed review of this topic. 491
 14.4 RESPIRATORY DISORDERS

Most children with Mycobacterium tuberculosis

infection do not develop clinical disease. Uncommonly,
young children with tuberculosis may present with
cough, fever, weight loss and wheeze as the constella-
tion of symptoms. These symptoms are more typical
of adulthood. Tuberculosis in the young child dif-
fers to that in adolescence or adulthood in that it is
unlikely to be infective to contacts. The diagnosis can
be made with a tuberculin skin test (Mantoux test).
Three-quarters of children with a positive tuberculin
test have a normal chest radiograph.

Bronchopulmonary dysplasia
Children who are born prematurely with a history of
hyaline membrane disease are at risk of developing
Fig. 14.4.1 Child with cystic fibrosis demonstrating classical
bronchopulmonary dysplasia (BPD). BPD is defined
upper lobe bronchiectasis.
by the need for supplemental oxygen therapy beyond
28 days of life and is associated with chronic radiologi-
X-linked hypogammaglobulinaemia and immotile cilia
cal changes. The radiological changes associated with
syndrome. The latter, also called primary ciliary dyski-
BPD are characterized by areas of fibrotic, thickened
nesia, is due to absent or abnormally functioning cilia
markings with cystic changes. Children with BPD may
that line the respiratory tract. Children with this condi-
present with an acute viral infection that precipitates a
tion typically have other upper airway manifestations
respiratory decompensation. On examination, they may
such as recurrent middle ear infections and sinusitis.
demonstrate signs of increased work of breathing (such
In approximately half the children with primary cili-
as tachypnoea, nasal flare, intercostal muscle recessions
ary dyskinesia, there is associated dextrocardia. This
and use of accessory muscles of respiration). On auscul-
constellation is referred to as Kartagener s­yndrome
tation, widespread expiratory wheeze may be present.
(Fig. 14.4.2). Management is aimed at achieving good
The long-term prognosis for children with BPD is good
airway clearance with physiotherapy and antibiotics to
in terms of lung function but there is growing evidence
treat infective exacerbations.
of ongoing exercise limitation into adulthood.

Aspiration pneumonia
Cystic fibrosis
Aspiration pneumonia could occur from below the
Cystic fibrosis (CF) is a cause of chronic suppurative
diaphragm due to gastro-oesophageal reflux of gastric
lung disease with an estimated carrier rate of 1 in 20
contents. It can also occur if a child has a d
­ iscoordinate
in the Caucasian population and an incidence of 1 in
2500 live births. More than 1700 genes are associated
with CF. Although newborn screening is now widely
performed, a small proportion of infants may fail to
be diagnosed if they have uncommon mutations. If
symptoms of failure to thrive, recurrent chest infec-
tions, cough and wheeze are noted, the clinician should
consider CF as a diagnosis. If the child has associ-
ated pancreatic insufficiency, steatorrhoea may be
­present. Chest radiographs may be normal or demon-
strate upper lobe bronchiectasis (Fig. 14.4.1). A sweat
test may aid in making the diagnosis and should be
­performed after consultation with a paediatrician.

Non-cystic fibrosis suppurative lung disease

Recurrent wheeze can be a presenting feature in chil-
dren with other non-CF causes of suppurative lung
disease. Causes of generalized wheeze and crackles Fig. 14.4.2 Child with primary ciliary dyskinesia with
492
would include underlying immune deficiency such as dextrocardia (Kartagener syndrome).
 Wheezing disorders other than asthma 14.4

Fig. 14.4.4 High-resolution computed tomogram of a child with

bronchiolitis obliterans. Note the areas of hyperlucency, traction
bronchiectasis and peripheral bronchial pruning.

Fig. 14.4.3 Child with neurological impairment and chronic Bronchiolitis obliterans has also been reported as a
pulmonary aspiration. long-term sequela of Mycoplasma pneumoniae and
influenza virus infection.
Management is based on treating hypoxia and any
oral swallow and aspirates non-particulate matter. The intercurrent infection. Systemic steroids and macro-
latter presentation is more common in children with lide antibiotics have been used to manage this condi-
neurological impairment. Figure 14.4.3 depicts a child tion, with variable benefit.
with chronic aspiration who, due to a poor swallow-
ing coordination, had no oral intake and was fed via
Structural airway abnormalities
a gastrostomy button. Underlying anatomical abnor-
malities such as a tracheo-oesophageal fistula may A variety of structural abnormalities can present with
result in aspiration pneumonia. Clinical presenta- wheeze as one of the signs. Generally, however, there
tions may vary, and recurrent wheeze may be a feature. are other clues to the diagnosis.
Bronchoscopy, barium studies, pH studies and milk
scans may all be needed to confirm this diagnosis, as
Subglottic haemangiomas
each of these investigative tools has limitations when
used in isolation. Subglottic haemangiomas may present with stridor
in infancy. The stridor is described as biphasic, as
it may be heard in both inspiration and expiration.
Bronchiolitis obliterans
Expiratory wheeze may be another presenting sign.
Bronchiolitis obliterans is a chronic form of bronchiol- The diagnosis may be considered in children between
itis where the child presents with a waxing and waning the ages of 6 weeks and 6 months. Haemangiomas
history of wheeze, episodes of atelectasis and tachy- of the skin may occur concurrently, especially along
pnoea. Radiographic findings are variable, with areas the neck and jaw, but their absence should not
of atelectasis as well as areas of hyperinflation with ­dissuade the clinician from considering this diagnosis.
peribronchial thickening. High-resolution computed Bronchoscopy is ­usually required to make the diagno-
tomography may reveal pruning of the bronchial tree. sis and, if the obstruction is significant, laser therapy
There may be some evidence of traction bronchiectasis may be considered.
(Fig. 14.4.4).
Bronchiolitis obliterans may be a long-term sequela
Airway ‘malacia’
to significant respiratory tract infection. Long-term
follow-up studies demonstrate that the majority of Bronchomalacia may present with tachypnoea and
children who are infected with adenovirus types 7 and cough. On auscultation, a localized wheeze may be
21 have pulmonary function and radiological find- heard. Radiological evidence of atelectasis, recur-
ings that are consistent with a diagnosis of bronchi- rent localized pneumonia or even gas trapping may
olitis obliterans. More common viruses such as RSV be noted. The pathophysiology of bronchomalacia
have been associated with bronchiolitis obliterans is thought to be due to an absence or deficiency of
if the child has other predisposing factors such as functioning cartilage. Bronchomalacia may occur in 493
immunodeficiency or if they are immunosuppressed. isolation or be associated with congenital pulmonary
 14.4 RESPIRATORY DISORDERS

malformations such as lobar emphysema. One-third Other causes of wheeze in infancy and
of children with congenital lobar emphysema have preschool children (Box 14.4.1)
localized bronchomalacia to the affected lobe.
Cardiac causes of wheeze
Children may have a deficiency of effective cartilage
in the tracheal wall that will result in tracheomalacia. A child with an underlying cardiac defect may p ­ resent
Children with tracheomalacia have a typical ‘brassy’ with wheeze and shortness of breath. The large and
cough. If the condition is severe enough, these chil- small airways may be compressed in a variety of
dren may have episodes of acute respiratory collapse. ­cardiac defects. The large airways may be compressed
Airway ‘malacia’ is best diagnosed using a flexible by an enlarged left atrium or large pulmonary vessels.
fibreoptic bronchoscope. The small airways may be compressed by engorged pul-
monary vasculature, which may be due to a large left
to right shunt. The wheeze is caused by the t­urbulent
Airway stenosis
air flow through partially compressed airways.
Congenital tracheal stenosis is rare, and the signs and Children with a history of cardiac surgery (espe-
symptoms will depend on the locality and extent of cially the Fontan procedure) may present with an
the defect. Stridor is the predominant feature but these acute severe bronchitis with wheeze. This condition
children may present with a wheeze. is referred to as ‘plastic bronchitis’. Unlike the plastic
bronchitis that can occur with asthma, those with prior
cardiac disease have bronchial casts that are devoid of
Congenital vascular ring
eosinophilic inflammation and Curschmann's spirals.
A congenital vascular ring may be formed when the Figure 14.4.6 demonstrates a bronchial cast that was
usual attachments of the large vessels to the heart
are misplaced. For example, a right-sided aortic arch Box 14.4.1 Causes of non-asthma wheeze in infants and
with a ligamentum arteriosum, or a double aortic preschool children
arch, or an aberrant right subclavian artery, or an
anomalous innominate artery may each entrap the Obstruction of small airways
trachea and the oesophagus, and cause compression. • Transient infantile wheeze
Although this may cause a wheeze, the infant will gen- • Acute infection (e.g. bronchiolitis)
• Suppurative lung disease
erally have other signs such as failure to thrive and
• Chronic lung disease of prematurity
feeding difficulties. The diagnosis may be considered • Secondary to cardiac causes
with a barium study that demonstrates a posterior or
lateral indentation on the oesophagus (Fig. 14.4.5). Obstruction of large airways
Computed tomography with angiography will help • Inhaled foreign body
make the definitive diagnosis, and surgical treatment • Structural abnormalities
is considered. • Mediastinal masses

494 Fig. 14.4.5 Barium study in a child with a vascular ring Fig. 14.4.6 Bronchial cast from a 5-year-old boy in acute
demonstrating an oesophageal indentation. respiratory distress who had a history of cardiac disease.
 Wheezing disorders other than asthma 14.4
removed during emergency bronchoscopy in a child Enlarged hilar lymph nodes may compress the main
who presented in acute severe respiratory distress with bronchi and may uncommonly present with cough,
a history of known cardiac disease. ­dyspnoea and wheeze. This may occur in primary tuber-
culosis. Endobronchial tuberculosis may also occur by
compromising the patency of the airway, resulting in
Inhaled foreign body
radiographic evidence of atelectasis. A detailed history
An inhaled foreign body may present with localized is important and may reveal other symptoms such as
wheeze, cough and shortness of breath. Clinicians should fever, night sweats and weight loss. Sarcoidosis is a
be aware that the typical history of choking soon after rare cause of hilar lymphadenopathy, and may mimic
the child was playing with a toy or food is uncommon. tuberculosis clinically and radiologically.
Children are capable of inhaling a variety of objects such Lymphomas may present with non-tender swell-
as nuts, seeds and components of plastic toys. For ana- ing of the cervical or supraclavicular region, of short
tomical reasons, the most common area for the object to duration. If the anterior mediastinum is affected, the
get lodged is the right main stem bronchus. On examina- child may present with cough, dyspnoea and wheeze.
tion, asymmetrical air entry may be noted. Although the Case reports of the use of systemic steroids to treat
inspiratory film of a chest radiograph may be relatively the wheeze resulting in catastrophic acute tumour lysis
unremarkable, gas trapping may become evident on the syndrome are well documented.
expiratory film (Fig. 14.4.7). This is due to the ball-valve Oesophageal duplication cysts may lay in the mid-
effect of the foreign body. If the foreign body has been dle mediastinum and cause airway compression.
lodged for a prolonged period of time, atelectasis, rather Figure 14.4.8 demonstrates the barium study of a
than gas trapping, will be noted in the affected region. 4-year-old boy who presented with a provisional
This is due to reabsorption of the trapped gas. If the clin- diagnosis of difficult-to-treat asthma that was not
ical examination is suggestive, a normal chest radiograph responsive to asthma medication. A barium study
should not dissuade the clinician from requesting a bron- demonstrated that the child had achalasia that caused
choscopy in search of a foreign body. It is reported that airway obstruction by the mass effect. When the acha-
one-third of children with inhaled foreign bodies have lasia was treated with oesophageal myotomy, the child's
unremarkable chest radiographs. wheeze and respiratory symptoms also regressed.

Mediastinal masses
Posterior mediastinal masses such as neuroblastomas Causes of non-asthmatic wheeze
and neuroenteric cysts are less likely to compress the in school-aged children (Box 14.4.2)
airways and cause wheeze.
Masses in the anterior and middle mediastinum may Infection
cause airway compression. Teratomas and dermoid Many of the infective causes of wheeze that were dis-
cysts may present with wheeze as one of the constel- cussed in the preschool age group may also present
lation of symptoms. in the school-aged group. However, infections such

A B
Fig. 14.4.7 The inspiratory film (A) appears normal, whereas the expiratory film (B) shows gas trapping in left lung. The left lung
remains fully inflated while the right lung partially deflates, as is normal in expiration. At bronchoscopy, a small plastic toy building brick 495
was found in the left main bronchus. (Image reprinted with permission of radRounds Radiology Network – http://www.radrounds.com).
 14.4 RESPIRATORY DISORDERS

the condition (see Chapter 13.3). Uncommonly, in

school-aged children, wheeze may be part of the clinical
spectrum either as part of the ­primary disease process or
secondary to evolving bronchiolitis obliterans.

Mediastinal masses and malignancy

As in the preschool group, school-aged children may
develop extrinsic airway compression due to medias-
tinal masses and present with wheeze. Malignancies
such as lymphomas may present with non-specific
malaise, weight loss and fever. They may also present
more insidiously with a non-specific wheeze that the
clinician is tempted to treat as asthma. Endobronchial
lesions due to tuberculosis and malignancy, such as
bronchial adenomas, may present with a unilateral
wheeze and tachypnoea. Occasionally, there may be a
Fig. 14.4.8 Barium study demonstrating oesophageal achalasia. history of haemoptysis. Partial ball-valve effect may
occur and cause hyperinflation in the manner of an
inhaled foreign body.
Box 14.4.2 Causes of non-asthmatic wheeze in
school-aged children
Uncommon causes of wheeze in school-aged
Obstruction of small airways children
• Infection (e.g. Mycoplasma pneumoniae)
• Suppurative lung disease A variety of hypersensitive pneumonitis due to ­exposure
• Mixed connective tissue diseases to an array of triggers such as bird droppings, mould
and even medications such as paracetamol (acetamin-
Obstruction of large airways ophen) may result in a clinical presentation of tachy-
• Inhaled foreign body pnoea and wheeze. The diagnosis is suggested by the
• Mediastinal masses
rapid improvement in symptoms when the child is
• Endobronchial lesions (e.g. tuberculosis, bronchial adenomas)
removed from the offending environment.
Vocal cord dysfunction A condition that may mimic the clinical presenta-
tion of asthma is Churg–Strauss syndrome. This is
a systemic vasculitis that differs from asthma by the
as M. pneumoniae are more common in school-aged concurrent presence of gastrointestinal symptoms
­
children. Infection with M. pneumoniae may present such as diarrhoea and abdominal pains.
in a variety of ways and should be considered in a α1-Antitrypsin deficiency typically presents with
child with cough and fever who, on auscultation of the gastrointestinal symptoms in childhood. Respiratory
chest, may demonstrate mild crackles or wheeze but symptoms due to restrictive lung disease usually ­present
on chest radiography has diffuse and extensive paren- in adulthood but there are sporadic case reports of
chymal disease. Infection with Chlamydia pneumoniae ­children presenting with wheeze, cough and tachypnoea.
may cause wheeze, either by the primary infection or
by acting as an inflammatory trigger for asthma. The
Vocal cord dysfunction
presentation is non-specific and similar to that of
M. pneumonia. The diagnosis is made by isolation of The pathophysiology of vocal cord dysfunction is not
the organism from nasopharyngeal or throat swabs. clear. Children may present with symptoms suggestive
Infections due to tuberculosis should be considered of exercise-induced asthma. Unlike typical exercise-
in this age group. The presentation may be with non- induced asthma, where maximal b ­ ronchoconstriction
specific symptoms of malaise, cough and fever. Wheeze occurs on completion of exertion, children with vocal
may occur if there is compression of the a­ irways by cord dysfunction may report wheeze early in the course
hilar nodes or endobronchial extravasation. of exercise. On auscultation, the wheeze is heard max-
imally in the neck and there is no evidence of lung
hyperinflation. Figure 14.4.9 shows the exercise flow
Mixed connective tissue disorders
volume loop of a child with vocal cord dysfunction.
Mixed connective tissue disorders, such as systemic lupus The wavering inspiratory loop is typical of vocal cord
erythematosus and scleroderma, typically have other dysfunction. Counselling and psychological support
496
symptoms and signs, such as rash and a­ rthralgia, ­suggesting have been beneficial in children with this condition.
 Wheezing disorders other than asthma 14.4
8
Practical points

• All infants and children who wheeze do not necessarily

4 have asthma.
• Be prepared to consider other causes of wheeze in
children if the history is suggestive.
Flow (L/sec)

• The aetiology of non-asthma wheeze differs according to

0 the age group.
0 2 4 6 • Referral to a paediatrician is needed when the diagnosis
or management is not clear.

–4

–8
Volume (L)

Fig. 14.4.9 Exercise flow volume loop demonstrating variable

inspiratory flow obstruction (Dashed lines denote predicted
normal flow. Solid lines denote actual measured flow).

497
 14.5 Lower respiratory
tract infections and
abnormalities
Peter LeSouëf

Pneumonia should be suspected in any child with an

Lower respiratory tract infections unexplained tachypnoea. Cyanosis is rare, but low
Lower respiratory tract infections (LRTIs) are a major levels of oxygen saturation are common. Clinical
cause of morbidity in developed and ­ developing signs are less reliable in younger children and can be
­countries and the greatest cause of mortality in ­children ­virtually absent in the presence of obvious radiologi-
under 5 years of age in developing countries, with cal changes.
more than 2 million deaths from pneumonia in this However, none of the symptoms or signs is s­pecific
age group annually. Respiratory tract infections often for pneumonia, and the clinical diagnosis should
involve both the upper and lower respiratory tracts, be s­uspected when the history and examination are
particularly those due to viruses. For respiratory tract consistent. Signs of complications of pneumonia
­
infections that appear to involve mainly the upper include those related to:
­airway, involvement of the lower respiratory tract is • pleural effusion – shifting of mediastinum or
usually present to some degree. Over the last few years, trachea, dullness to percussion (stony dullness with
acute asthma has been shown to be caused mainly by large effusions), reduced or absent breath sounds,
respiratory viral infection of the lower a­ irway, and this and bronchial breathing above the effusion
is now recognized as the most ­common form of LRTI. • pneumothorax – uncommon, shifting of
However, this form of LRTI is discussed in the chapter mediastinum or trachea, reduced breath sounds.
on asthma (see Chapter 14.3).

Investigations
Pneumonia
Chest radiography is the most reliable investigation
Pneumonia is a common cause of morbidity and to confirm the presence of pneumonia. If the chest
morta­lity in children and is characterized by infection, radiograph is normal, pneumonia can be reasonably
inflammation and consolidation of the lung. There excluded at that time, but if the X-ray is taken very
are many different causes of pneumonia. Viruses are early in the disease process this does not p
­ reclude radio-
the most common cause. Bacteria cause fewer cases of logical changes developing later. In general, patchy or
pneumonia, but the morbidity and mortality is several peripheral consolidation may be more in keeping with
times higher than for viral pneumonia. Atypical infec- a viral infection, lobar opacification is suggestive of
tious agents cause fewer cases of pneumonia, except in bacterial pneumonia, and a more central peribron-
the increasing number of children with human immu- chial infiltrate may indicate Mycoplasma infection,
nodeficiency virus (HIV) infection. but the specificity of these changes is r­ elatively poor.
Symptoms of acute infective pneumonia include Importantly, all of these radiological features can be
dyspnoea, fever and malaise. Cough may be dry or found with asthma.
moist, but is not always present. Pleuritic chest pain Repeat X-ray to establish resolution of the p­ neumonia
is often present. If the pneumonia involves the apices, is important to reduce the risk of missing an unrec-
neck pain may be present and can be confused with ognized, underlying or unresolved pathology, parti­
the neck stiffness of meningism. If the diaphragmatic cularly those related to mechanical obstruction of
pleural surface is involved, pain can be referred to the the airway. Preferably this should be done at least
abdomen or shoulder tip. 4–6 weeks after the acute illness has settled down, as
Signs include tachypnoea and respiratory dis- the radiological abnormalities of pneumonia can be
tress, dullness to percussion, and, on auscultation, slow to resolve and may still be present if the repeat
localized crackles and bronchial breathing. Of these X-ray is done too early.
signs, tachypnoea is the most consistent and reliable, Blood culture may be performed if clinically indicated.
498
and may be the only sign pointing to this diagnosis. Bacteraemia is not common in bacterial pneumonia.
 LOWER RESPIRATORY TRACT INFECTIONS AND ABNORMALITIES 14.5
A nasal aspirate should be taken if the diagnosis the area involved. Dullness to percussion may indicate
is unclear or viral aetiology is suspected. The aspi- the presence of an empyema. If the upper lobes are
rate should be subjected to polymerase chain reac- involved, neck stiffness may be present and lead to the
tion (PCR) analysis to detect the presence of causative misdiagnosis of meningitis.
respiratory viruses, but care is needed in interpreting Chest X-ray findings vary widely, but the most
results as positive results for respiratory viruses are common and classic finding is lobar involvement
common in asymptomatic children, and the presence (Fig. 14.5.1). A well-defined round opacification is not
of a virus in a nasal aspirate does not exclude the pos- uncommon and patchy changes can occur. Empyema,
sibility of a bacterial pneumonia. Human r­hinovirus abscesses and pneumatoceles are less common than
detection should be included in the PCR detection in staphylococcal pneumonia. Increases in white cell
panel as increasing recent evidence suggests that this count and indices of inflammation are commonly
virus is responsible for many LRTIs in hospitalized found in peripheral blood, and blood culture may be
children. Rhinovirus typing may also be included positive.
in the near future, as even more recent evidence has The diagnosis should be made as early as pos-
shown that the newly discovered human rhinovirus sible and treatment commenced with penicillin and
group C is the most common virus group causing a third-generation cephalosporin. The response to
LRTI in hospitalized children, and also causes more treatment is usually rapid and complete recovery can
pathology than previously known rhinovirus groups, be expected.
as well as the majority of acute asthma admissions in
children.
Sputum is often difficult to obtain and of limited
usefulness due to contamination by upper airway Clinical example
bacteria.
Pleural fluid specimen. In more serious cases where Jack, a 3-year-old boy, presented with a 4-day
a pleural effusion of sufficient size is present, obtain- history of cough and fever. He was noted to
ing pleural fluid should be considered, as it provides a be mildly unwell, to have a respiratory rate of
60 breaths per minute and bronchial breathing
more reliable possibility of obtaining a bacteriological
over the left base posteriorly. A chest X-ray showed
diagnosis. Ultrasonography may be employed to guide opacification confined to the left lower lobe. He was treated
the aspiration. with parenteral then oral penicillin, and was afebrile within
Bacterial antigen detection in the peripheral blood is 8 hours. The bronchial breathing had disappeared the next
also of limited use. day and Jack was back to normal health within a week.
Immune function. In recurrent or atypical pneumo- A repeat X-ray 1 month later was normal.
nia, consideration should be given to the possibil-
ity of immunodeficiency. Initial investigations may
include assessment of serum immunoglobulins and
tests for HIV.

Pneumococcal pneumonia
Streptococcus pneumoniae is the most common
cause of bacterial pneumonia in children at any age.
Pneumococcal pneumonia is most common in chil-
dren under 3 years of age. Risk factors include male
sex, Indigenous ethnicity and pre-term delivery.
Pneumococcal pneumonia may be preceded by
symptoms suggestive of a mild upper respiratory
tract infection, and typical symptoms and signs of
pneumonia may then appear. Although these can be
­non-specific, compared with viral pneumonia, symp-
toms are likely to include fever, dyspnoea, pleuritic
chest pain and cough. Cough can, however, be absent
and sputum production is less likely in younger chil-
dren. Signs are more likely to include tachypnoea,
grunting, nasal flaring, reduced movement of the
chest wall on the affected side, dullness to percussion, Fig. 14.5.1 Pneumococcal pneumonia in a 5-year-old girl, 499
reduced breath sounds and bronchial breathing over showing opacification in the midzone of the right lung.
 14.5 RESPIRATORY DISORDERS

Staphylococcal pneumonia
Pneumonia due to Staphylococcus aureus is important
as it is usually more severe than pneumonia due to
other infective agents and is more common in younger
children, especially those under 1–2 years of age.
However, even in this younger age group, pneumococ-
cal pneumonia is more common. Another important
risk factor for staphylococcal pneumonia is a socially
disadvantaged or Indigenous background.
Compared with other forms of pneumonia, the
child with staphylococcal pneumonia is more likely to
have a shorter acute history, to appear more unwell,
and to have a high fever, marked tachypnoea and sig-
nificant respiratory distress. The onset is usually acute
and the course more rapid. Chest signs are often non-
specific. The chest X-ray may be normal early in the
disease, but later is more likely to show severe involve-
ment. The early radiological features may be similar to
those of other forms of bacterial pneumonia, includ-
ing lobar consolidation, patchy shadowing and a small
pleural effusion. However, more serious complications
are common and these can develop quickly within the
first few days; they include:
• widespread opacifications, displaced intrathoracic
structures and pleural effusions
• more specific to staphylococcal pneumonia:
• large or encysted pleural effusions with thick
Fig. 14.5.2 (A) Chest X-ray and (B) a single slice from
walls
thoracic high-resolution computed tomography in an
• empyema immunocompromised 15-year-old with staphylococcal
• abscesses, either single or multiple pneumonia and bronchopleural fistulae. There is diffuse air
• air leaks are common, occurring in around space opacification with several pneumatoceles and a left-sided
half of cases and include pneumothorax, pneumothorax.
pneumomediastinum, pneumopericardium and,
in particular, pneumatoceles (Fig. 14.5.2A).
during the acute phase of the illness. Deterioration can
Although highly specific to staphylococcal
be rapid, and air leaks can occur and require imme-
pneumonia, these complications are not
diate treatment. Broad-spectrum antibiotics should
pathognomonic of this condition, as air leaks
be used until an accurate diagnosis can be made. The
including pneumatoceles can very occasionally
combination of a β-lactamase-resistant penicillin such
be found in bacterial pneumonias caused by
as flucloxacillin and a third-generation cephalosporin,
pneumococci, Escherichia coli, Klebsiella,
both given intravenously, is useful in this situation, as
Pseudomonas and group A streptococci.
it combines direct treatment of staphylococci as well
High-resolution computed tomography (HRCT) of
as coverage of other common respiratory pathogens.
the chest (Fig. 14.5.2B) is often useful in defining the
In any child under 2 years of age with clinically sig-
nature and extent of these complications.
nificant pneumonia, flucloxacillin should be included
Investigations in the treatment regimen because of the much higher
Blood cultures are positive in the acute phase of the ill- prevalence of staphylococcal pneumonia in this age
ness. Pleural effusions should be aspirated, when large group.
enough, to assist with diagnosis, but the fluid from an Resistance to β-lactamase-resistant penicillins
empyema may be sterile if sufficient antibiotic treat- ­(methicillin-resistant Staphylococcus aureus (MRSA))
ment has been given. is now common in staphylococcal pneumonia caused
by community-acquired organisms, and multire-
Management sistant organisms have become more common in
Owing to the increased risks from staphylococcal pneu- ­nosocomially acquired cases. Hence, from a therapeu-
monia, infants in whom this diagnosis is suspected tic viewpoint, nosocomial staphylococcal infections
500
should be hospitalized to allow adequate observation are more likely to show multiple drug resistance than
 LOWER RESPIRATORY TRACT INFECTIONS AND ABNORMALITIES 14.5
community-acquired MRSA infections. Treatment Haemophilus influenzae type b pneumonia
needs to be ­tailored to the prevailing local situation,
Pneumonia due to Haemophilus influenzae is now
but other drugs such as clindamycin should be con-
uncommon in countries with efficient immuniza-
sidered. Given the high risk of relapse, the duration
tion programmes against this organism. In countries
of antibiotic treatment is often extended to around
without effective immunization policies, it remains
6 weeks, particularly in more severe cases or those
a common and important cause of pneumonia. The
with complications.
organism colonizes the upper respiratory tract of the
Surgical intervention majority of normal, non-immunized children, but does
Staphylococcus is the more common cause of so less commonly in those who have been immunized.
­empyema in Western society, and whether or not Risks factors for H. influenzae infection include age
to undertake drainage of effusions or empyema less than 5 years, Indigenous ethnicity, lower socioeco-
depends on their size and the severity of the case. nomic group, male sex, and congenital and acquired
In appropriate cases, drainage may be undertaken immunodeficiency.
early in the course of the illness to assist in diag- The signs, symptoms and radiological features of
nosis or to reduce the mechanical effects of large H. influenzae pneumonia are not specific or distin-
effusions. The use of video-assisted thoracoscopic guishable from those found in other pneumonias.
surgery (VATS) to drain empyemas depends on the Other foci of infection including the meninges and the
availability of an appropriately trained and skilled ­epiglottis are common in children with Haemophilus
surgeon. Whether or not drainage reduces the ­pneumonia. For children in whom H. influenzae pneu-
total duration of illness is less clear, but the need monia is suspected who are either under 12 months
to reduce the space-occupying and pressure effects of age or significantly unwell, treatment with a paren-
of a large effusion, as well as reducing the recovery teral third-generation cephalosporin is recommended,
time, should be considered. and for children who are less unwell, oral amoxicillin–­
clavulanic acid is appropriate. Other children in the
Long-term outcome family do not require prophylactic treatment if they
Clinical recovery from staphylococcal pneumo- are adequately immunized.
nia is usually good, with a very high likelihood of a
­complete return to normality. Radiological recovery
is usually also complete, as children examined radio- Mycoplasma pneumonia
logically some years after recovery generally show no
­evidence of previous problems, despite extensive, seri- Mycoplasma pneumoniae is a frequent cause of
ous abnormalities on chest X-ray at the time of the community-acquired pneumonia in children, partic-
­
illness. However, a strong risk factor for more severe ularly those over 5 years of age, as it is most common
staphylococcal pneumonia, necrotizing pneumonia, in young school-aged children. The clinical course is
and a higher morbi­ dity and mortality is the pres- characterized by the gradual development over several
ence of the Panton–Valentine leukocidin (PVL) toxin, days of fever, malaise, upper respiratory symptoms and
which is common in c­ommunity-acquired staphylo- cough. The cough tends to be non-productive initially
coccal pneumonia. and may become productive and troublesome. In chil-
dren with a tendency to asthma, wheeze is commonly
present, but wheeze can occur in children with no prior
history of asthma. Signs also often include widespread
Clinical example sparse fine or coarse crackles. Both clinical signs and
chest X-ray changes are typically more striking than
Jayda, a 9-month-old girl, was brought to the expected for the degree of clinical illness. The radiologi-
local doctor by her mother. She had been unwell cal findings themselves are usually n ­ on-specific, but can
for 12 hours, with increasing fever, lethargy
include perihilar opacification, and consolidation of one
and difficulty feeding. The doctor noticed
that she was pale, listless and tachypnoeic, and scattered or more lobes (Fig. 14.5.3). The diagnosis is supported by
coarse inspiratory and expiratory crackles were heard on positive serology.
auscultation of her chest. She was transferred by ambulance Treatment with a macrolide is indicated as M. pneu-
to hospital where a chest X-ray showed opacification in the moniae is usually susceptible to this group of antibiotics.
right upper and left lower lobes. Jayda was treated with However, the response to treatment may be restricted to
oxygen and intravenous flucloxacillin and cefotaxime. Blood a reduction in general symptoms, as the clinical course of
culture was positive for Staphylococcus aureus, and treatment
the pneumonia itself may not be affected by treatment
with flucloxacillin was continued for 6 weeks. Jayda slowly
improved and she was fully recovered when seen after the unless this is started within the first few days of symp-
antibiotic treatment had been completed. toms. The anti-inflammatory effects of ­macrolides could
501
also contribute to the modest efficacy of treatment.
 14.5 RESPIRATORY DISORDERS

pneumonia, but the complications of lung abscess and

pneumatocele may occur and, without appropriate
treatment, the mortality rate is high. Recommended
treatment depends on individual resistance patterns,
but is likely to include an aminoglycoside and a third-
generation cephalosporin.
Other bacteria
Other bacterial organisms that are rare causes of pneu-
monia in immunocompetent children include anthrax,
Bordetella pertussis, Brucella, Burkholderia cepacia,
Citrobacter spp., Corynebacterium spp., Coxiella bur-
netii, E. coli, Listeria monocytogenes, Mycobacterium
spp., Neisseria meningitidis, Pasteurella spp., Proteus spp.,
Pseudomonas aeruginosa, Salmonella spp. and Yersinia spp.

Fig. 14.5.3 Mycoplasma pneumonia in a 7-year-old girl Viral pneumonia

presenting with cough and fever. There is extensive consolidation Viruses are the most common cause of lower respira-
in the left lung with air bronchogram formation and focal
tory illnesses in children, and viral pneumonia is the
consolidation in the lateral basal segment of the right lower lobe.
most common form of pneumonia in childhood. The
spectrum of disease varies widely, but viruses are the
greatest contributor to the 3–5 million children who
Other less frequent causes of bacterial pneumonia
die worldwide each year from an acute respiratory
Group A b-haemolytic streptococci (Streptococcus ­illness. Risk factors for viral pneumonia include:
pyogenes) • Age – children under 5 years of age are at greatest
This organism is a common cause of bacterial pharyn- risk of viral pneumonia, but the risk remains high
gitis, but a rare cause of pneumonia. When it does cause throughout the first decade of life.
pneumonia, it tends to be in children over 5 years of • Season – peak incidence is in winter.
age, and the clinical course is rapid, severe and poorly • Passive smoke exposure – maternal smoking
responsive to antibiotic treatment compared with other increases the risk, especially in the first year of life.
causes of bacterial pneumonia. Fever, chest pain and Exposure during pregnancy is a much greater risk
haemoptysis are more common than with other forms factor than exposure thereafter.
of pneumonia, and the necrotizing nature of the infec- • Poor socioeconomic status – a risk factor in both
tion means that serious complications such as air leaks, developing and developed countries.
large pleural effusions and empyema are more likely to • Pre-existing chronic problems – the risk is increased
occur. Once the organism has been isolated, treatment with chronic problems such as cystic fibrosis, post-
is with high-dose intravenous penicillin G. neonatal lung disease, congenital heart disease and
immunodeficiency.
Other streptococci
The most important causative viruses are parain-
Group B β-haemolytic streptococci are a common and
fluenza virus, influenza virus, respiratory syncytial
important cause of neonatal pneumonia, which occurs
virus (RSV), human metapneumovirus (HMV), ade-
within hours of birth, has a rapidly progressive course,
novirus and human rhinovirus (HRV). All of these
can mimic respiratory distress of prematurity and has a
viruses can cause other respiratory illnesses apart
high mortality rate. After the neonatal period, it rarely
from pneumonia, including acute upper respiratory
causes pneumonia and, when it does, the disease course
tract infection, acute laryngotracheitis, bronchitis and
is usually less acute. Group C streptococci are also a
bronchiolitis. Symptoms of these illnesses can coexist
rare cause of pneumonia in children and, as for group
with those of pneumonia. Rhinoviruses, cytomega-
A, the clinical picture can be severe and protracted.
lovirus and ­measles virus can also cause pneumonia.
Klebsiella pneumoniae In recent years, HRV has been identified as the most
This organism typically causes pneumonia in neonates common cause of exacerbations of acute asthma in
and immunocompromised hosts. Klebsiella pneumo- both c­ hildren and adults, so care is needed to avoid
nia is rare in children, and when Klebsiella infection misdiagnosing pneumonia in children with X-ray
is present bacteraemia is more common than pneu- changes due to ­HRV-induced asthma. The radiologi-
monia. The clinical picture of Klebsiella pneumonia cal features of viral pneumonias are non-specific, but
502
initially is not distinguishable from other forms of patchy, widespread ­infiltrates are more characteristic
 LOWER RESPIRATORY TRACT INFECTIONS AND ABNORMALITIES 14.5

Practical points

Pneumonia
• Tachypnoea is the most useful clinical sign.
• Pneumococcal pneumonia is the most common cause of
bacterial pneumonia at all ages, including the first year
of life.
• Staphylococcal pneumonia is uncommon, but occurs most
commonly in the first year or two of life.
• Follow-up X-rays should be taken to ensure that there is
no significant underlying pathology.
• Follow-up X-ray timing: leave for at least 4–6 weeks
to allow enough time for complete clearing of the
abnormalities.
Fig. 14.5.4 Viral pneumonia in a 15-month-old child, with typical
non-specific, patchy widespread opacifications in both lung fields.

Acute viral bronchiolitis

than lobar involvement (Fig. 14.5.4). Treatment with
antiviral agents is of limited efficacy and rarely indi- Bronchiolitis is the most common significant LRTI in
cated in normal children, but supportive measures are the first year of life and is also common in the second
­commonly required. year. It is the most common cause of hospital admis-
sion in the first year and a common cause of mortal-
ity globally. Bronchiolitis follows a seasonal pattern
Clinical example with the highest rates occurring during winter in most
locations, but in more tropical or subtropical latitudes
Emily, a 4-year-old girl, was brought to her
the highest rates are during the rainy season. The rea-
general practitioner with a 3-day history of
fever, increasing dry cough and loss of appetite. son for these seasonal patterns is unknown. Maternal
Her 6-year-old brother had also been unwell smoking is a major risk factor, related mostly to
with a cough and a fever. On examination, her doctor noted smoking during pregnancy rather than by inhalation
a temperature of 37.8 °C, a respiratory rate of 36 breaths during infancy. Other risk factors include p ­ re-term
per minute, mild soft tissue recession, and the presence of delivery and chronic lung disease of prematurity,
sparse, coarse crackles bilaterally on auscultation. A chest
allergy, chronic cardiorespiratory diseases (includ-
X-ray showed scattered areas of patchy opacification. She was
diagnosed as having viral pneumonia, treated symptomatically
ing congenital heart disease and cystic fibrosis) and
and recovered uneventfully over the next few days. immunodeficiency.
Classically, acute viral bronchiolitis has been consid-
ered to be a disease mainly caused by the respiratory
Fungal pneumonia syncytial virus (RSV), as RSV is the most common
virus detected in children who are hospitalized with this
Fungal causes of pneumonia or pneumonia-like ill-
condition. However, in recent years c­ommunity stud-
nesses occur most commonly in immunocompro-
ies have shown that milder cases that do not present
mised children, and include Actinomyces, Aspergillus,
to hospital are more likely to be due to infection with
Candida, Coccidiomycosis, Cryptococcus, Histoplasma
human rhinovirus (HRV) and that, overall, HRV causes
and Nocardia spp. Some fungi are endemic in certain
more cases of bronchiolitis than RSV. Dual infection
areas. For example, Coccidiomycosis is endemic in
with RSV and HRV is also common. In ­ addition,
places in the Americas, including the south-west of the
most other respiratory viruses can cause bronchiolitis,
USA, and histoplasmosis is endemic in the mid-west-
including parainfluenza viruses 1–3, influenza virus A
ern USA. Fungal respiratory infections in non-immu-
and B, adenovirus and HMV. Bronchiolitis is rarely
nocompromised children are usually mild and do not
due to ­bacteria, and secondary infection with bacteria
require specific treatment.
is also rare.
The clinical course of bronchiolitis tends to be of
Protozoal pneumonia
symptoms gradually increasing over 2–3 days, and
Protozoa that cause pneumonia or pneumonia-like consisting of mild or no fever, tachypnoea, a mild
illnesses also occur most commonly in immuno- dry cough and expiratory wheezing. With increasing
compromised children and include Cryptosporidium severity, dyspnoea becomes more marked and feed-
spp., Pneumocystis jiroveci (formerly carinii) and ing is impaired. Clinical signs typically include soft 503
Toxoplasma spp. tissue recession on inspiration, the appearance of
 14.5 RESPIRATORY DISORDERS

increased work of breathing, hyperinflation of the

chest, fine inspiratory crackles and wheeze. After Practical points
2–3 days the symptoms gradually resolve and the
child should have recovered within a week. Slow or Bronchiolitis
prolonged recovery is more common if an under- • Bronchiolitis is the most common cause of wheeze in
lying predisposing chronic problem is present; if early life.
recovery has not been achieved within 2 weeks, fur- • Rhinovirus is the most common cause of mild
ther investigations such as a sweat test should be bronchiolitis, RSV is the most common cause of severe
bronchiolitis.
considered.
• Clinical features include low-grade fever, cough, wheeze,
The main differential diagnosis is early asthma hyperinflation and fine inspiratory crackles.
(now more commonly called ‘virus-induced wheeze • Differentiation of some cases of bronchiolitis from early
of infancy’). Hyperinflation and fine inspiratory asthma or ‘virus-induced wheeze’ is often not possible.
crackles are classical for bronchiolitis, but many • Treatment is supportive only – oxygenation, hydration,
infants have a mixture of these signs and those nutrition.
more consistent with asthma, including expiratory
wheeze. As the two conditions are caused by the
same viruses and overlap so much, in many cases
Pertussis (whooping cough)
there is no reasonable way to s­eparate these two
diagnoses. This serious respiratory illness is caused by the bacte-
Investigations are not needed in mild cases, but in rium Bordetella pertussis. It can occur at any age but
hospitalized children a nasal fluid specimen should infants, particularly those aged less than 6 months,
be obtained to allow viral detection by PCR and ade- are at greatest risk of complications, which include
quate isolation of infectious cases. If a chest X-ray is apnoea, severe pneumonia, encephalopathy and
indicated clinically, the usual findings are of hyperin- death.
flation with few other changes in mild cases and more Immunity from the natural infection is not com-
widespread, but non-specific, opacifications in more plete, and reinfection can occur in children and
severe cases. The level of oxygen saturation is a good adults. However, the incidence and severity of pertus-
guide to the severity of the illness, and oxygen should sis is greatly reduced by pertussis vaccine, originally a
be given accordingly. whole-cell vaccine and now an acellular pertussis vac-
Treatment is supportive and consists of ensuring cine. A major value in immunization is the increased
adequate oxygenation and care with fluid intake to herd immunity that reduces transmission to young
avoid aspiration. Particular care needs to be taken babies from older siblings and adults. This is impor-
with infants who are reluctant to feed, as aspiration tant, as those most at risk from pertussis are those too
can occur if oral fluids are pushed too hard or admin- young to be immunized.
istration of nasogastric fluids is accompanied by vom- Pertussis is most infectious in the prodromal phase
iting. In marked respiratory distress where the infant's and continues to be infectious for up to 3 weeks.
ability to cough or maintain an airway is impaired,
intravenous fluids should be given. No drugs have
Clinical features
been proven to be effective in treating bronchiolitis.
Despite this, many infants receive bronchodilators The incubation period is usually 7–10 days, and has
even though there is evidence that they increase the a prodromal phase with nasal discharge and a mild
need for additional oxygen. Specific treatments tar- non-productive cough that lasts for a few days. This
geting the virus have not found their way into rou- precedes the phase when cough becomes pronounced.
tine practice. Anti-RSV immunoglobulins are not In most, but not all, cases prolonged paroxysms of
indicated for regular use owing to poor efficiency and coughing are followed by a characteristic ‘whoop’.
high expense. The cough is often accompanied by vomiting and may
The great majority of cases of bronchiolitis resolve be so severe that subconjunctival haemorrhages occur.
without sequelae, but longitudinal studies have shown Apnoea is common in very young infants. Less com-
that the risk of further wheezing is increased. Whether monly, young infants can develop severe pneumonia
this is due to pre-existing variations of immune func- or encephalopathy, both of which can be fatal.
tion or to changes induced by the infections that
cause bronchiolitis has not been resolved completely.
Investigations
However, the presence of relative deficiencies in innate
immunity that predate bronchiolitis in children des- A nasopharyngeal specimen is used to detect pertus-
tined to become atopic and asthmatic suggests that the sis using immunofluorescent antibodies or culture.
504
former is more likely. Serology is less reliable.
 LOWER RESPIRATORY TRACT INFECTIONS AND ABNORMALITIES 14.5
Management weight loss, malaise, fever, and a dry cough and wheeze
if an airway is obstructed.
Infants less than 6 months of age are more likely to
Diagnosis is established by:
require hospital admission for supportive therapy.
• a positive tuberculin skin test (> 15 mm skin
Macrolide antibiotics reduce the period of infectivity
induration from 5 tuberculin units (TU) of purified
and can alter the course of the illness, but only if com-
protein derivative (PPD)-S is taken as evidence
menced before the paroxysmal phase. Thus, they are
of disease; 10–15 mm suggests that infection has
indicated in those seen very early in the course of the
occurred, but disease may not be present; false-
illness or those with severe symptoms. Household con-
negatives can occur in early or severe disease)
tacts are usually also treated to reduce spread of infec-
• culture of the organism from early-morning gastric
tion. Infected individuals should avoid contact with
lavage
other children until they have had at least 5 days of
• radiological findings that include hilar or mediastinal
antibiotics or have had the illness for at least 3 weeks.
lymphadenopathy, lobar hyperinflation or atelectasis
if an airway is obstructed, consolidation, effusions
and empyema. Cavitation is uncommon in young
Pulmonary tuberculosis
children. Miliary TB has a widespread ‘snowstorm’
Tuberculosis (TB) is the most common chronic infec- appearance. HRCT is often useful if characterizing
tion in the world and is caused by infection with the anatomy and extent of the findings.
Mycobacterium tuberculosis. Pulmonary TB is an • light microscopic identification of bacilli from
important cause of morbidity and mortality in chil- sputum, bronchoalveolar lavage fluid or pleural fluid.
dren worldwide. The tubercle bacillus was discovered Treatment has traditionally been with triple therapy,
by Koch in 1822, and in the 20th century the incidence which consists of 6 months’ treatment with rifampi-
of the disease was reduced in developed countries by cin, isoniazid and pyrazinamide, but World Health
effective public health and therapeutic approaches. In Organization recommendations for therapy are fre-
recent years, the TB incidence rates have been stable or quently updated and the latest of these should be
falling in many regions, but in other regions the inci- ­consulted. Patients with a positive skin test without
dence has been slowly increasing. This increase is likely any evidence of pulmonary disease are treated with
to be due to the presence of large numbers of people isoniazid alone for 6–9 months.
with HIV infection who are highly susceptible to TB,
and who are responsible for the subsequent increase in Atypical mycobacterial infection
the global pool of infective organisms. In developed
Atypical mycobacteria (M. avium, M. intracellulare,
countries that accept large numbers of refugees from
M. scrofulaceum) can, on rare occasions, cause
developing countries, high rates have been found in
­pulmonary disease in immunocompetent children, par-
those emigrating, and this has also increased the circu-
ticularly in Australia. Presentation with symptoms and
lation of the organism.
signs of airway obstruction secondary to pulmonary
Children usually acquire the infective agent from an
lymphadenopathy is typical in these cases. Diagnosis
adult or adolescent rather than from other children.
is made by specific skin testing and by identification
TB in children is most common under 5 years of age,
of bacilli from fluid or tissue. Response to treatment
with a lower incidence between 5 and 15 years. Other
is slow, and therapy may need to be continued for
risk factors are low socioeconomic conditions, an
12–24 months, but prognosis for full recovery appears
Indigenous ethnic background and immunodeficiency.
to be excellent.
The organism is transmitted mainly by inhalation in
the indoor environment, and only a small proportion
of those infected will develop disease.
After exposure, signs of pulmonary TB do not Congenital disorders of the lower
appear for weeks, months or years. The initial lesion is respiratory tract
often subpleural, occurring with an associated lymph
Congenital lung abnormalities
node response that comprises a primary complex.
Early symptoms are often absent or few, in which case These are rare and may go undetected for life. They
a dry cough and mild dyspnoea may be noted. The often present well into childhood with non-specific
disease does not progress further in most patients but, symptoms. Most can be detected on chest X-ray.
when it does, effusions may occur, lymph nodes may Lung cysts can vary from being simple and solitary
enlarge and obstruct major airways, and the lung may to multiple and complex. Cysts can become infected
be damaged by extensive caseation. The disease may if they communicate with the airway. They can also
then disseminate and produce miliary, meningeal or cause symptoms if they become enlarged and ­compress 505
renal tuberculosis. Hence, later symptoms may include ­surrounding structures.
 14.5 RESPIRATORY DISORDERS

Unilateral pulmonary agenesis may present with neo- Congenital chest wall abnormalities
natal respiratory distress or with non-specific symp-
Pectus excavatum is a common midline concave depres-
toms later in life. Careful radiological investigation
sion of the lower sternum and is not usually associated
including HRCT is needed to confirm the diagnosis.
with any underlying respiratory abnormality or effect
Congenital cystic adenomatoid malformation
on rib cage or lung function. Cosmetic correction can
(CCAM) is caused by either hamartomatous growth
impair lung function.
of the bronchial tree or a localized arrest in develop-
Thoracic dystrophies are characterized by impaired
ment of the fetal bronchial tree. CCAM generally con-
development of the chest wall and are associated with
sists of multiple cysts and abnormal proliferation of
pulmonary hypoplasia.
lung elements. It can present at birth and, if sufficient
Scoliosis can cause a restrictive functional defect in
lung is involved, cause chronic respiratory insuffi-
chest wall function if the angle of the curve is great
ciency. Surgery may be needed to remove troublesome
enough.
cysts. The associated small increase in risk of malig-
Congenital eventration of the diaphragm is a malfor-
nancy requires careful consideration regarding the rel-
mation of the diaphragm in which the diaphragmatic
ative risks of surgery or continued observation.
muscle is incomplete and replaced by thin fibroelastic
Congenital lobar emphysema is characterized by
tissue that allows the dysfunctional hemidiaphragm
overinflation of a lung lobe and commonly presents
to be displaced upwards. It occurs more in males and
before 6 months of age with respiratory distress or
can be difficult to differentiate from diaphragmatic
tachypnoea. Surgical intervention may be required if
hernia. More severe cases may present neonatally
the emphysematous lobe causes significant compres-
and require surgery, but minor cases can be found
sion of neighbouring lung.
incidentally.
Sequestration of the lung is likely to be the result
Congenital diaphragmatic hernia: see Chapter 11.5.
of a small independent accessory lung bud develop-
ing from the foregut. Sequestration is characterized by
Congenital lower airway abnormalities
part of the lung being discontinuous with the rest of
the lung, and this can be intrapulmonary or extrapul- • Tracheomalacia and bronchomalacia: see
monary. The former is much more common, and more Chapter 14.4.
likely to become infected and require surgical removal. • Oesophageal atresia and tracheo-oesophageal
The latter is most frequently left-sided, with an a­ berrant fistula: see Chapter 11.5.
systemic blood supply, and is asymptomatic. • Bronchogenic cysts: see Chapter 14.4.

506
 An approach to chronic 14.6
cough and cystic fibrosis
Anne Chang, Nitin Kapur

• Many cough treatments are not based on the results

Introduction of randomized controlled trials.
Cough is the most common symptom of respiratory • As the aetiology and management of cough in
disease for which parents seek medical attention in childhood are quite different to that in adults,
young children. The presence of cough can indicate extrapolation of the adult cough literature to
the entire spectrum of cardiorespiratory childhood children can be harmful.
illness, ranging from a symptom of the ‘common
­
cold’ to a symptom of a severe, life-limiting disorder
such as cystic fibrosis (CF). Most cough in children is Approach to diagnosis and
acute and resolves promptly. Chronic cough is defined
as cough lasting longer than 4 weeks. It is abnormal
management
and deserves careful consideration of the cause. In the Figure 14.6.1 outlines a schematic approach to the
evaluation of children with chronic cough, determin- diagnosis and management of chronic cough. The key
ing which children require further investigations and/ questions are presented in Box 14.6.1. Initial catego-
or treatment is a key management issue. rization of cough into acute, subacute and chronic
cough according to duration is helpful. There is, how-
ever, no strict definition of chronic cough. Most acute
cough arises from respiratory viruses and settles within
Pathophysiology 2 weeks. Subacute cough commonly lasts from 2 to 4
weeks, whereas chronic cough can be defined as cough
Cough is generally considered a reflex, but also can be lasting longer than 4 weeks.
voluntarily generated (or suppressed). Cough is com-
prised of three phases – inspiratory, compressive and
expiratory – and serves as a vital defence mechanism
Clinical example
for lung health. The forceful expiration occurs after a
build-up of pressure in the thorax (up to 300 mmHg) Adrienne, a 13-year-old girl, was referred to a
by contraction of expiratory muscles against a closed respiratory physician for a chronic cough. She
glottis. This leads to expulsion of air at high velocity had been managed incorrectly as an asthmatic
and sweeps material within airways towards the mouth. for more than 10 years. On specific questioning,
Inspiration of a variable volume of air occurs when Adrienne said she had been coughing for as long as she
could remember and indicated that her cough was worse
cough is stimulated. Successive coughs may or may in the mornings and that she often expectorated sputum.
not be preceded by inspiration. Cough is an important Her cough had been stable and she had not noticed any
component of normal respiratory function through exertional dyspnoea. She had no growth failure and did not
two mechanisms. Firstly, mechanical stimulation of the have digital clubbing. Given that she had some features of
larynx causes immediate expiratory efforts through the bronchiectasis, high-resolution computed tomography of her
expiratory reflex, a primary defence mechanism that is chest was performed and revealed focal changes in the right
basal segment (Fig. 14.6.2). Her serum immunoglobulin levels
stimulated when foreign objects (such as food or fluid)
were normal and she was Mantoux and sweat test negative.
are inhaled. Secondly, cough enhances ­ mucociliary On flexible bronchoscopy, a retained foreign body (piece
clearance. The absence of a forceful cough (e.g. gen- of shell) was visualized and removed from the right medial
eralized muscular weakness) has ­ important clinical segment of her right lower lobe. The foreign body had caused
repercussions, such as ­ difficulty clearing secretions, prolonged partial bronchial obstruction and was the cause of
atelectasis, lobar collapse and recurrent pneumonia. Adrienne's localized bronchiectasis.
Issues to keep in mind when the presenting symp- It is important to define the aetiology of any child's
chronic cough. This child had features listed in Box 14.6.1
tom is cough:
that indicate ‘specific cough’ and further investigations were
• Cough usually resolves spontaneously (called indicated. For children, it is best for investigations to be
the period effect), which makes evaluation of performed in a children's facility. 507
therapeutic interventions difficult.
 14.6 RESPIRATORY DISORDERS

Chronic/ persistent cough (>4 weeks)

CXR Consider early

Spirometry Either abnormal consultation
Both normal
(if >6 years old) with paediatric
pulmonologist
for assessment

Absence of ‘other features’, Reversible airway

wheeze and productive/ obstruction?
wet cough?

Asthma Yes No
Yes No
if cough does
not settle consider

Non specific cough ‘Other Features’ Assess risk factors for

Consider: present?
• post viral
• increased CRS
• asthma No
• GOR Yes
• UA problems
• functional disorders
(habit cough, tics,
psychogenic)

Bronchiectasis Aspiration Chronic or Interstitial Cardiac

Purulent productive or recurrent • primary and less common lung • pulmonary
or moist/wet cough pneumonia secondary infections disease hypertension
and without wheeze • cystic fibrosis • neurologically • TB • rheumatic • cardiac
• ciliary dyskinesia abnormal • non diseases oedema
• previous severe • altered swallow tuberculous • cytotoxics
pneumonia • weak cough mycobacteria • drugs
Yes No • immunodeficiency reflex • mycoses • radiation
• structural airway • neuromuscular • pertussis • etc.
lesions disease • atypical
• congenital lung • laryngeal pneumonia
lesions abnormalities • mycoplasma
Subacute Asthma • missed foreign • tonsil adenoid
bronchitis: but review body hypertrophy Paediatric
needs for other • TOF/ H fistula • TOF/ H fistula cardiologist
follow-up; if causes of • severe GOR
recurrent or wheezing
persistent,
needs
investigation
• sweat test • ba swallow • mantoux • autoimmune Echo
• bronchoscopy • bronchoscopy • bronchoscopy markers cardiac
• cilia biopsy and lavage and lavage • HRCT chest catheter
• immune workup • video • HRCT chest • lung biopsy
• HRCT chest fluoroscopy
• ba swallow • pH monitor
Review and if • lung milk scan/
‘other features’ present salivagram

Fig. 14.6.1 Guide for approaching a child with a persistent cough. Symptoms and signs vary according to age and illness severity.
Ba, barium; CRS, cough receptor sensitivity; CXR, chest X-ray; GOR, gastro-oesophageal reflux; HRCT, high-resolution computed
tomography; TOF, tracheo-oesophageal fistula, TB, tuberculosis; UA, upper airway.

A key point in the assessment of chronic cough is c­hildren and adults manifests as a moist or ‘rattly’
whether it is specific or non-specific, according to the cough in younger children. The presence of any of these
presence or absence of particular features (Box 14.6.2). symptoms or signs raises the possibility of an underly-
Children aged less than 6 years do not generally expec- ing disorder. Certain cough characteristics are associ-
508
torate sputum. Thus the productive cough of older ated with particular illness types (see Table 14.6.1).
 An approach to chronic cough and cystic fibrosis 14.6
Box 14.6.1 Key questions to consider Table 14.6.1 Classical recognizable cough in children

• Is the cough representative of an underlying respiratory Cough characteristic Associated illness type
disorder?
Barking or brassy cough Croup, tracheomalacia, habit
• Are any of the symptoms and signs in Box 14.6.2 present?
cough
• Are exacerbating environmental factors present (passive
or active tobacco smoking, other lung toxicants)
Honking Psychogenic
• Should the child be referred promptly?
Paroxysmal (with/ Pertussis and paratussis
without whoop)

Staccato Chlamydia in infants

Cough productive of Plastic bronchitis

casts

aspiration lung disease, atypical respiratory infections,

cardiac anomalies and interstitial lung disease. If basic
investigations are not helpful, referral to a general
or respiratory paediatrician is indicated rather than
­further investigations.

Fig. 14.6.2 High-resolution computed tomogram of Adrienne,

as described in Clinical example – a 13-year-old girl with a moist Management of non-specific
cough for more than 10 years. This child had been incorrectly
managed as an asthmatic for 10 years until referred for another
cough
opinion. The scan shows focal bronchiectasis of the right basal The majority of children with non-specific cough
segment. Flexible bronchoscopy revealed a foreign body (piece
have post-viral cough and/or increased cough recep-
of shell) in the right basal medial bronchus.
tor sensitivity. There is no serious underlying cause of
non-specific cough and reassurance is a large part of
Box 14.6.2 Symptoms and signs alerting to the presence management. Understanding and listening to paren-
of an underlying disorder tal concerns and expectations is important. There is
no evidence that ‘over the counter’ (non-prescription)
• Auscultatory findings medications reduce cough in young children.
• Cough characteristics, for example cough with choking,
Identification of exposure to environmental
cough quality (see Table 14.6.1), cough starting from birth
• Cardiac abnormalities (including murmurs) tobacco smoke (ETS) in children and active smok-
• Chest pain ing in adolescents is an important part of respiratory
• Chest wall deformity history-taking. ETS exposure can cause non-specific
• Chronic dyspnoea cough and exacerbate a variety of respiratory disor-
• Daily moist or productive cough ders. If ­smoking cessation cannot be achieved, aim
• Digital clubbing to reduce smoking in enclosed spaces (e.g. house
• Exertional dyspnoea
and car).
• Failure to thrive
• Feeding difficulties Habit cough is a cause of non-specific cough. The
• Haemoptysis age of diagnosis is broad, but is commonly 4–15 years.
• Immune deficiency Severe cases are more common in adolescents than in
• Neurodevelopmental abnormality children. The cough is classically ‘honking’. It is gen-
• Sinopulmonary infections erally absent in sleep and worse at times where atten-
tion is focused on the cough. Habit cough generally
settles promptly once parents are aware that there is
The choice of investigation depends on the clini- no underlying respiratory problem. Mental health
cal findings. Minimum investigation of chronic cough expertise is required for those with more severe or
in children is chest radiography and lung spirometry prolonged symptoms, especially if there are other
(if aged above 6 years). Diagnoses to be considered features of somatization or concerns of underlying
509
include bronchiectasis, asthma, retained foreign body, psychopathology.
 14.6 RESPIRATORY DISORDERS

A longitudinal population study of cough in in-

Cough, asthma and allergy fants and children revealed that recurrent cough
There is little doubt that children with asthma can (rather than chronic cough) presenting in the first year
­present with cough. However, most children with non- of life resolves over time in the majority of children.
specific chronic cough do not have asthma. Furthermore, The group of children with recurrent cough with-
although nocturnal cough is a feature of children with out wheeze had neither airway hyper-responsiveness
asthma, nocturnal cough alone is uncommonly due nor atopy, and significantly differed from those with
to asthma. If asthma ‘preventer’ medication is used, it ­classical asthma, with or without cough, in the per-
should be introduced on a trial basis with early review sistence of symptoms over time. It is believed that
(2–4 weeks) and cessation of medication if the cough infants with recurrent cough without wheeze may
does not respond to asthma therapy. Failure to do so have more narrow airways. This group of infants is
will result in escalation of medication dose with the risk hard to ­differentiate clinically from those who con-
of significant side-effects (see Clinical example below). tinue to have recurrent cough from asthma, making
predictions of future illness difficult in infancy.

Clinical example

Gino was first seen by a paediatric respiratory Cough, gastro-oesophageal

physician when aged 8 years. He had been
receiving 2000 μg/day inhaled corticosteroids for
reflux and aspiration
the last 6 years for a chronic dry cough; he had lung disease
been managed as an ‘asthmatic’ and his medications were
escalated when his cough did not respond to the steroids. Gastro-oesophageal reflux (GOR) can be associ-
When seen, his chest X-ray findings and spirometry were ated with cough. However, although GOR can cause
normal, and he was cushingoid (Fig. 14.6.3). Earlier pictures of cough, cough can also cause GOR. GOR is neither
him showed a normal-sized 3-year-old boy and his 6-year-old a specific nor a frequent cause of chronic cough in
brother's body habitus was normal. Gino had been exposed
young children. As cough is very common in children
to tobacco smoke and had an element of habitual cough. His
asthma medications were subsequently withdrawn and his
and respiratory symptoms may exacerbate GOR, it is
cough eventually subsided when he was no longer exposed difficult to delineate cause and effect. Infants regularly
to tobacco smoke and received appropriate counselling. regurgitate, yet few if any well infants cough with these
This example illustrates the importance of obtaining episodes.
a history of smoke exposure. Also, it is crucial not to Aspiration lung disease can result from severe GOR
‘overdiagnose’ asthma based on the presence of isolated or discoordinated swallowing. These children pres-
cough. In children, when cough is representative of asthma,
ent with chronic cough but usually in the context of
the cough should subside within 2 weeks of appropriate
asthma treatment. If the cough does not subside, the asthma developmental or neurological disturbance. The inves-
therapy should be withdrawn and not escalated. tigatory evidence for aspiration lung disease can be
difficult. Ambulatory oesophageal pH studies can

Fig. 14.6.3 (A) This previously normal child had a chronic dry cough that had been treated incorrectly with escalating doses of inhaled
510 corticosteroids. (B) Two years later, he was cushingoid in appearance without any change in cough. Children with isolated cough
should not be treated with increasing doses of asthma therapy.
 An approach to chronic cough and cystic fibrosis 14.6
identify acid GOR, but a positive result does not Bronchiectasis can be the end result of various dis-
confirm that aspiration has occurred and a negative orders, and may be diffuse or focal. Diffuse disease
result indicates only the absence of reflux related to usually develops secondary to an underlying disorder
acid. Similarly primary aspiration (from swallowing such as cystic fibrosis, immunodeficiency or primary
discoordination) is also difficult to confirm because ciliary dyskinesia, although it can be idiopathic. In
current standard tests, such as nuclear medicine milk Indigenous Australians, bronchiectasis is not uncom-
scan or modified barium swallow, provide only a ‘sin- mon and is thought to result from respiratory infec-
gle moment’ test that may not be representative of the tions. Focal bronchiectasis more commonly reflects
child's routine feeding pattern. airway narrowing, either congenital (e.g. bronchial
stenosis) or acquired (e.g. retained foreign body).
Congenital forms of bronchiectasis (e.g. Williams–
Campbell syndrome) are rare.
Cough, sinusitis and post-nasal The spectrum of bronchiectasis varies from mild to
drip severe. Symptoms and signs reflect the extent of the
disease. Children with bronchiectasis have a chronic
Although it is widely stated that sinusitis/post-nasal moist or productive cough, characteristically worse
drip is a common cause of cough, there is little sup- in the mornings. Physical findings are non-specific:
portive evidence in children. There are no cough recep- clubbing, chest wall abnormality (hyperinflation or
­
tors in the pharynx or post-nasal space. Although rarely pectus carinatum; Fig. 14.6.4) and inspiratory
sinusitis is common in childhood, it is not associated crepitations. Absence of these signs does not imply
with asthma or cough once allergic rhinitis, a common absence of disease (see Clinical example below) and
association, has been treated. The relationship between most children diagnosed early do not have features
nasal secretions and cough is more likely linked by associated with more advanced bronchiectasis. Plain
common aetiology (infection and/or inflammation radiography may show suggestive features in severe
causing both) or due to throat clearing of secretions disease (dilated and thickened bronchi may appear
reaching the larynx. as ‘tram-tracks’), but are insensitive. Confirmation
is by high-resolution computed tomography (CT)
of the chest (routine CT provides insufficient detail)
with a lower threshold of bronchoarterial ratio used
Protracted bacterial bronchitis in children.
The entity of protracted bacterial bronchitis (PBB) A child with suspected bronchiectasis should be
was recently described in children where a wet cough referred for investigation of a specific cause and spe-
resolves completely following antibiotic treatment. cific treatment instituted when indicated (e.g. immu-
PBB, sometimes truncated to protracted ­ bronchitis nodeficiency). Australian and New Zealand guidelines
(PB), is clinically defined as: (a) the presence of advocate early diagnosis and appropriate management
­isolated chronic (> 4 weeks) wet/moist cough, (b) res- to improve quality of life and reduce lung function
olution of cough with antibiotic treatment, and (c) decline. The general approach to managing children
absence of pointers suggestive of an alternative spe- with bronchiectasis is similar to (but not exactly the
cific cause of cough. Many of these children were
previously misdiagnosed with asthma, and in some
settings they would have been classified as having ‘dif-
ficult or severe asthma’. PBB is clearly differentiated
from acute bronchitis: cough is of shorter duration
(≤ 2 weeks) in paediatric acute bronchitis, and antibi-
otics are not indicated in acute bronchitis. Some chil-
dren with PBB go on to have chronic suppurative lung
disease or bronchiectasis, and thus should be followed
up to ensure the cough resolves.

Bronchiectasis
Bronchiectasis is now less common compared with Fig. 14.6.4 Severe pectus carinatum. This can be present in
its incidence in the mid-20th century. However, in children with any chronic lung disease. Gross pectus carinatum, 511
the last decade it has been diagnosed increasingly. as shown in this figure, is now rarely seen.
 14.6 RESPIRATORY DISORDERS

other organ diseases such as the eye (retinitis pigmen-

Clinical example tosa), the ear (hearing loss) and kidneys (polycystic
diseases).
Deanna was hospitalized on several occasions The severity of pulmonary manifestations of PCD
for pneumonia, initially at 2 months of age.
varies widely. Presentation can be early in life with
She was first referred at 2.5 years of age and
had a prolonged moist cough. She had a
neonatal respiratory illness. In infants and older
hyperinflated chest wall, early digital clubbing and growth children, the diagnosis should be considered in those
failure. Her weight was below the third percentile and height with chronic cough, bronchiectasis, recurrent pneu-
was at the third percentile. Chest high-resolution CT showed monia, atypical asthma, recurrent rhinosinusitis
post-infectious bronchiolitis obliterans and bronchiectasis. and chronic secretory otitis media. Specific investi-
Other investigations were normal. Deanna's parents were gations for PCD include assessment of mucociliary
taught home physiotherapy and Deanna was admitted for
clearance, measurement of ciliary beat frequency,
a prolonged course of intravenous antibiotics. Following
discharge she remained on maintenance antibiotics. Her and electronic microscopic identification of cilial
daily moist cough disappeared when her bronchiectasis was ultrastructure.
treated aggressively with antibiotics and physiotherapy.

Cystic fibrosis
same as) that described for CF (see Key elements of CF is the most common life-threatening autosomal
respiratory management, below). In addition, children recessive disorder in Australians, affecting approxi-
aged above 2 years should receive pneumococcal vac- mately 1 in every 2500 births. It is caused by a defect
cine. Pooled immunoglobulin replacement is indicated in the CF transmembrane conductance regulator
for those with identified immunoglobulin deficiency gene (CFTR). The CFTR gene encodes a protein
­syndromes. Surgery is very rarely indicated, and only for a cyclic adenosine monophosphate (cAMP)-
for those with focal disease. regulated chloride channel present on many epithe-
lial cells, including those of the conducting airways,
gut and genital tract. The commonest mutation,
delta508, accounts for approximately 70% of
Primary ciliary dyskinesia mutant alleles, and more than 1300 mutations have
Primary ciliary dyskinesia (PCD) syndromes encom- been described.
pass several congenital disorders, all of which affect
the ciliary function of several organs, including the
Diagnosis
upper and lower respiratory tracts and genitourinary
tract. The term includes Kartagener syndrome (situs All infants in Australia are now screened at birth for
inversus associated with bronchiectasis), immotile CF. A two-stage screening procedure is widely used.
cilia syndrome, ciliary dysmotility and primary ori- Initially, immunoreactive trypsin (IRT) is measured
entation defects of ciliary components. PCD has in Guthrie blood spot samples. Samples with an IRT
a prevalence of 1 in 20 000, is mostly autosomal level above the 99th percentile are then tested for the
recessive in inheritance and probably genetically common mutation (additional mutations are tested in
heterogeneous. some states).
Cilial ultrastructure consists of a 9 + 2 arrangement: Most Australian children with CF are identified
the axoneme consists of 9 peripheral microtubular by neonatal screening, with the diagnosis confirmed
doublets surrounding a central pair of microtubules. using a sweat test (pilocarpine iontophoresis) at 6–10
Abnormalities in cilial function are due to alteration weeks. Newborn screening does not detect all children
of its ultrastructure or its function, the ciliary beat with CF. A sweat test should be arranged if there are
frequency. Secondary abnormalities in both ultra- phenotypic features suggestive of CF. A raised sweat
structure and function can also occur as a result of chloride level (> 40 mmol/L) is diagnostic (some cen-
infection, smoking or pollutants. Cilial dysfunction tres use a higher cut-off). To minimize the multiple
markedly reduces mucociliary clearance and results errors that can occur (especially false-negatives), sweat
in recurrent infections of both the upper and lower testing should be undertaken in a laboratory that rou-
respiratory tract (middle ear infections, bronchitis, tinely does sweat tests. Very infrequently, patients have
bronchiectasis). In the genitourinary tract, ciliary dys- been identified with an abnormal CF genotype yet
function can lead to infertility in males and to ectopic have a normal sweat test result. A borderline sweat test
pregnancies in females. Increasingly structural cil- result is more commonly seen in those with retained
512
ial abnormality has been found to be associated with pancreatic function.
 An approach to chronic cough and cystic fibrosis 14.6
Some 15–20% of Australian infants with CF pres-
ent before the results of screening with meconium
ileus, a form of neonatal intestinal obstruction.
Antenatal diagnosis for CF is available when both
parents are known carriers of the CF gene owing
to the birth of a previous child with CF or a ­family
history.
Fig. 14.6.5 Digital clubbing in a boy with bronchiectasis. Digital
clubbing is non-specific and may or may not be present in
Clinical children with suppurative lung disease.
CF affects multiple organ systems, causing a range of
clinical problems of varying severity (Table 14.6.2). It
is a severe disorder, although the occasional child has
mild disease. Rarely, it is so mild that it is not diag- Additionally, there are various degrees of gastric and
nosed until adult life, following a presentation of duodenal hyperacidity, impaired bile salt activity and
Pseudomonas pneumonia or male infertility. CF has a mucosal dysfunction. Stools are abnormal, being typ-
major impact on the lungs, where the altered physico- ically frequent and bulky. Growth failure may result
chemical properties of the airway epithelium result in from many reasons, including inadequate energy
abnormally viscid mucus and bacterial colonization of intake, malabsorption and chronic bacterial infection.
the respiratory tract. The lungs of a child with CF are Long-term retention of pancreatic function is associ-
normal at birth, but over time chronic airway infec- ated with better survival.
tion develops that causes progressive obstructive lung As survival of patients with CF improves, a range
disease. Clinically, chronic productive cough develops of CF-related diseases becomes more important. This
as bronchiectasis progresses and lung function deterio- includes growth and nutrition; diabetes mellitus and
rates. Clubbing is a feature in later stages of the disease liver disease (both seen in approximately 15–20% of
(Fig. 14.6.5). adolescents and adults); arthropathy and arthritis;
Malabsorption is present in approximately 90% of and osteoporosis. Men are generally infertile owing to
children with CF, due to failure of the exocrine pancreas. bilateral absence of the vas deferens. Women are fer-
tile, although pregnancy presents a range of health
risks to both the fetus and the mother. Women have
increased rates of vaginal yeast infections and stress
Table 14.6.2 Common manifestations of cystic fibrosis incontinence.
disease

System Manifestation

Respiratory Chronic productive or moist cough Principles of management of a child with

Features of bronchiectasis
Clubbing
cystic fibrosis
The median age of survival has dramatically improved
Ear, nose and throat Nasal polyps as a range of clinical improvements has developed
Sinusitis
over time. Four decades ago, median survival was
Gastrointestinal Meconium ileus less than 10 years. Current median survival is into the
Features of malabsorption mid-40s, although males survive longer than females.
Distal intestinal obstruction A range of improvements has contributed to these
syndrome improved health outcomes, including a stronger focus
Liver disease on nutrition and the development of more specific
Endocrine pancreatic insufficiency
and potent antibiotics. However, a key intervention
(diabetes mellitus)
has been the development of specialized CF centres
Reproductive Male infertility characterized by a multidisciplinary team of health
professionals including respiratory physicians, gastro-
General Growth delay enterologists, physiotherapists, nutritionists, nurses,
surgeons, social workers and mental health therapists.
Metabolic Salt depletion The goal of treatment is to maintain as high a qual-
ity of life as possible for as long as possible in order
Other Osteoporosis
to slow the relentless progression of lung disease that
Urinary incontinence 513
occurs in CF.
 14.6 RESPIRATORY DISORDERS

The key elements of respiratory management con- and liver disease respectively. Gene therapy is still
sist of: in the experimental phase.
• prompt use of antibiotics to reduce bacterial
colonization and biofilm formation
• aggressive treatment of recurrent respiratory
infections
• promotion of mucociliary clearance by daily
Summary
physiotherapy Cough is the commonest manifestation of respiratory
• minimization of other causes of lung damage (e.g. problems in children. Although it can be a distressing
smoking, aspiration) symptom, its presence is vital for respiratory health.
• additional vaccinations: pneumococcal vaccine and Chest radiography and spirometry are the minimal inves-
yearly influenza vaccine tigations in a child with a chronic cough (for more than
• promotion of normal growth through high-energy 4 weeks). When cough is associated with other symp-
diet and pancreatic supplementation toms (‘specific cough’), investigations and/or r­eferral
• identification and treatment of complications
as they arise (asthma-like disease, allergic
bronchopulmonary aspergillosis (ABPA),
haemoptysis, pneumothorax, etc.).
Respiratory infections should be treated aggressively, Practical points
because recurrent infection and the accompanying
inflammation promotes loss of lung function. The 1. Children with chronic cough should:
most common respiratory bacteria are Staphylococcus • be evaluated carefully for symptoms and signs of an
underlying respiratory or systemic disease (termed
aureus and Haemophilus influenzae in the early years, ‘specific cough pointers’; see Box 14.6.2)
followed by Pseudomonas aeruginosa and Burkholderia • have a chest X-ray performed and (if age appropriate)
cepacia. With increasing use of antibiotics, a pleth- spirometry
ora of other microorganisms is increasingly isolated, • be followed up, because minimal airway secretions
including fungi (Aspergillus species, Scedosporium pro- may be present in dry cough and hence wet cough
lificans) and other bacteria (Stenotrophomonas malto- may initially present as dry cough
philia, non-tuberculous mycobacteria, etc.). Most • be assessed for a history of environmental exposures,
particularly tobacco smoke exposure, and intervention
clinic structures currently segregate children to prevent initiated if appropriate
cross-colonization. • be reviewed to ensure there is resolution of the cough.
Gastroenterological and nutritional management 2. Chronic cough can be classified based on the likelihood
consists of: of an underlying disease or process, specific cough and
• pancreatic enzyme replacement (lipase, protease, non-specific cough (an overlap is present).
amylase) at each meal 3. Over-the-counter (OTC) or prescription medications are
ineffective for chronic non-specific cough and should not
• high-energy diet be used for the symptomatic relief of cough.
• vitamin supplementation with vitamins A, D, E and 4. Treatment for chronic cough should be aetiology based.
K, and salt tablets Medications are largely unhelpful for non-specific cough.
• early identification of liver disease If medication trials are undertaken, a follow-up review to
• early identification of distal intestinal obstruction assess response should be undertaken. Asthma should
syndrome. not be diagnosed based on a single episode in the
absence of other symptoms of asthma.
CF is a life-long chronic condition. As children
5. Chronic suppurative lung disease or bronchiectasis should
grow and mature into adolescents and young be suspected in children with chronic wet cough that does
adults, the psychosocial aspects of the disease not resolve on oral antibiotics or that recurs frequently.
take on different dimensions for individuals, sib- These children should be investigated for an underlying
lings and ­ parents. In adolescence, attention to cause such as cystic fibrosis, primary ciliary dyskinesia,
body image issues and feelings of difference due to immune deficiency and aspirated foreign body.
chronic disease can help maintain young people's 6. Children with chronic suppurative lung diseases should
be managed by a multidisciplinary team. The medical
adherence with the health-care regimen. Declining
elements include airway clearance techniques, attention
health despite good a­ dherence can be especially to nutrition, and early intervention for pulmonary
demoralizing. Lung and liver ­transplantation are exacerbations and other complications.
increasingly undertaken to treat end-stage lung

514
 An approach to chronic cough and cystic fibrosis 14.6
are required to identify the cause. Non-specific cough
is largely managed expectantly, trying to explore par- Acknowledgements
ent anxieties, minimize investigations and identify envi- The authors thank Professor Susan Sawyer for her
ronmental triggers such as tobacco smoke. There is little contribution to the previous version of this chapter
evidence that the common causes of persistent, isolated from which this new version has been adapted.
cough in adults (asthma, GOR, sinusitis and nasal dis-
ease) are common causes of chronic cough in children.

515
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 15
PART

CARDIAC DISORDERS

517
 15.1 Suspected heart disease:
assessment
Michael Cheung

Oesophageal and gastric pain may be indicated by the

Scale of the problem history. Brief episodes of chest discomfort may be
Cardiac abnormalities or disease affect approximately associated with viral illnesses and myopericarditis.
1% of children in the developed world and 2–3% in Palpitations associated with collapse are clearly con-
developing countries. This difference is largely due to cerning but the majority of children presenting with
the higher incidence of rheumatic heart disease in the palpitations do not lose consciousness with episodes
latter. of tachycardia. It is useful to determine the rate, dura-
The prevalence of congenital heart disease is approx- tion, nature of onset and offset of these episodes, in
imately 8 in 1000 newborn infants. In Australia, heart addition to the circumstances surrounding them. Most
disease remains one of the major causes of infant children may be able to tap out with their hand how
mortality. fast their heart rate is, or parents can be taught to
­measure the pulse and keep a diary of events.

Pulses
Presentation Examination of pulses should include both left and
Significant heart disease in children presents with symp- right arms and femoral pulses. The upper and lower
toms and signs of heart failure or cyanosis. These will, limb pulses are best compared when palpated simul-
of course, vary depending on the age of the patient and taneously. Relatively reduced lower-limb pulses sug-
severity of disease. Milder forms of heart disease may gest coarctation, but femoral pulses may be difficult
present by the detection of an a­ symptomatic murmur. to feel in the first few days of life. Bounding pulses
due to a wide pulse pressure may be associated with
patent ductus arteriosus, significant aortic regurgita-
tion, and high cardiac output states. The physiologi-
cal increase in heart rate in children varies markedly
Assessment with activity and so it is the resting rate that should be
History noted (Table 15.1.1).
It is important to determine the onset and type of
Blood pressure
symptoms. In babies, breathlessness, feeding difficul-
ties, inability to complete feeds and poor weight gain Measurement of blood pressure should be a routine
are important to elucidate and may be indicative of part of examination in children. Use of an appropriate
a significant heart problem. Cyanosis due to heart cuff is vital. The balloon/bladder of the cuff should be
disease is usually persistent but may intermittently wide enough to cover two-thirds of the upper arm. In
increase in severity. Intermittent peripheral and cir- practice, the largest cuff that can be fitted to the upper
cumoral cyanosis are common in normal children, arm without covering the antecubital fossa is used.
typically occurring when cold (e.g. swimming) or con- Blood pressure should normally be recorded by aus-
versely when febrile. Cyanosis may also be associated cultation of Korotkoff sounds, as in adults, although
with breath-holding in children with normal hearts, palpation (of the brachial or radial pulse) may be
and in these situations clearly defining the sequence of employed to assess systolic pressure in young chil-
events leading up to the cyanotic episode is important. dren and infants if auscultation proves to be difficult.
Chest pain in children is rarely due to heart disease. Significant errors in blood pressure are more likely to
The history of the chest pain is useful in distinguish- result from the use of a cuff that is too small than one
ing cardiac from non-cardiac chest pain; however, that is overlarge. Newer automated devices are able
this may be difficult to elicit in young children. Pain to detect the arterial pulsation and limit the upper
consistently associated with exertion is more likely ­pressure of inflation; however, these devices are still
to be cardiac in nature, although its location may relatively slow and may overestimate blood ­pressure in
518
­indicate a ­musculoskeletal rather than cardiac origin. restless or uncooperative children.
 Suspected heart disease: assessment 15.1
Table 15.1.1 Approximate normal upper limit for pulse, respiratory rate and systolic blood pressure at rest; resting
measurements consistently above these values should arouse suspicion

Age group Pulse rate (beats/min) Respiratory rate (breaths/min) Systolic BP (mmHg)

0–8 weeks 160 50 70

Older infant (2–12 months) 145 40 85

Toddler (1–3 years) 130 30 100

Older child (4–7 years) 115 20 115

For measurement of leg blood pressure, a cuff may and e­xpiration (Fig. 15.1.2) and is also typically
be placed on the thigh. An adult arm cuff may be large widely split.
enough for young children, but larger children or ado- Accentuation of the pulmonary component of the
lescents will require a ‘thigh cuff’, which is larger than second sound tends to be associated with a loud sec-
an adult arm cuff. ond sound, which may be palpable, often with no
Normal blood pressure varies at different ages (see definite splitting, and implies the presence of pul-
Table 15.1.1). monary hypertension. However, it should be noted
that the normal aortic closure sound may be loud
in children with a thin chest wall and is sometimes
Palpation of the cardiac impulse
palpable at the upper left sternal border. The pres-
Location of the apex beat and documentation of any ence of an ejection click (see Fig. 15.1.1) is a use-
abnormal/forceful impulses/thrill of the precordium is ful ancillary auscultatory finding. Such sounds are
important. heard shortly after the first heart sound and tend to
be high-frequency and discrete in character. If heard
at the apex, it usually implies a bicuspid aortic valve
Auscultatory findings
or aortic valve stenosis. When originating from the
Splitting of the second heart sound should be noted pulmonary valve, it is heard at the left sternal edge
(Fig. 15.1.1). Splitting is widened during inspira- and varies with respiration, being louder on expi-
tion. Fixed splitting, a feature of atrial septal defect, ration. This finding is characteristic of pulmonary
implies absence of variation between inspiration valve stenosis.

Variation in splitting of the second sound

Normal heart sounds Inspiration

A2 M1 A2
M1
T1 T1
P2 P2

S1 S2 S1 S2

Ejection click Expiration

M1 EC A2 M1 A2
T1 T1
P2 P2

S1 S2 S1 S2
519
Fig. 15.1.1 Illustration of normal heart sounds, normal splitting of the second sound and ejection click (EC).
 15.1 CARDIAC DISORDERS

Inspiration

A2
M1
T1
P2

S1 S2

Expiration Fixed splitting

A2
M1
T1
P2

Tricuspid 'flow'
S1 S2 murmur

A2 A2
M1 M1
T1 T1
P2 P2

S1 S2 S1 S2

Fig. 15.1.2 Auscultatory signs associated with an atrial septal defect showing ejection systolic murmur, fixed splitting of S2 and
tricuspid flow murmur (see Chapter 15.2).

Murmurs volume and velocity of blood flow relative to the

stethoscope position.
The following features of the murmur should be
determined:
• timing Characterization
• location Ejection murmurs (Fig. 15.1.3) are systolic and
• amplitude (grading) ­crescendo–decrescendo in character, starting shortly
• characterization after the first sound. Good examples are the murmurs
• radiation. of pulmonary or aortic valve stenosis.
Pansystolic murmurs (Fig. 15.1.3) are murmurs
Timing that commence at the first sound and continue to the
Murmurs may be systolic (limited to systole), diastolic ­second sound. They may be due to atrioventricular
(limited to diastole) or continuous (extending from valve incompetence (e.g. mitral incompetence) or a
systole into diastole). Note that continuous murmurs ventricular septal defect (VSD).
are not necessarily present throughout the cardiac Diastolic murmurs may be early diastolic (see
cycle. Murmurs may be timed by simultaneously pal- Fig. 15.1.4) (commencing at the second sound) or mid-
pating a peripheral pulse. diastolic (see Fig. 15.1.2). The former reflect either aor-
tic or pulmonary incompetence, whereas mid-diastolic
Location
murmurs occur during ventricular filling and reflect
The point of maximum intensity of the murmur
either stenosis of or increased blood flow through an
should be identified.
atrioventricular valve (e.g. mitral stenosis or second-
Amplitude ary to a large left–right shunt due to a VSD).
Murmurs may be graded according to the scale in Other characteristic murmurs include early (see
Table 15.1.2. The amplitude of the murmur is affected Fig. 15.1.4) and late systolic murmurs (reflecting a tiny
520
by the thickness of the chest wall, and the direction, muscular VSD or mitral valve prolapse, respectively),
 Suspected heart disease: assessment 15.1
Table 15.1.2 Grading of murmurs

Grade Amplitude Thrill Comments

1 Very soft Absent Scarcely audible

2 Soft Absent Easily audible

3 Loud Absent Very easily audible

4 Loud Faint/localized Very easily audible

5 Very loud Easily felt/widespread Very easily audible

6 Very loud Easily felt/widespread Heard with stethoscope off chest wall

Ejection systolic Pansystolic Innocent murmurs

There are four characteristic types of innocent mur-
mur that are, by definition, not associated with cardiac
symptoms:
S1 S2 S1 S2 • Still's murmur
• pulmonary flow murmur
Continuous
• carotid bruit
• venous hum.
Still's murmur
This is a short mid-systolic murmur best heard at the
left sternal border or between the apex and left sternal
S1 S2 edge. This murmur is sometimes referred to as ‘Still's’
murmur (see Fig. 15.1.4) or a ‘vibratory’ murmur. The
Fig. 15.1.3 Common murmurs and their relationship to the
murmur is of medium frequency and has a vibratory
heart sounds S1 and S2.
or slightly musical quality. It tends to become softer
Early systolic Early diastolic if the patient stands and is louder when the patient is
squatting or lying supine.
Pulmonary flow murmur
This is a soft, blowing ejection murmur, maximal in
S1 S2 S1 S2 the pulmonary area. Murmurs of this kind are fre-
quently heard in early infancy and may radiate softly
Mid systolic 'Still's' to the axillae, when they may be labelled as innocent
with a high degree of confidence, and are less common
later in childhood. In older children, distinction from
an atrial septal defect or mild pulmonary stenosis can
S1 S2 be difficult, and may warrant further investigation.

Fig. 15.1.4 Other murmurs: early systolic, early diastolic and Carotid bruit
Still's murmur. This medium-frequency, rough ejection systolic mur-
mur heard over the carotid artery (right or left or
and the late diastolic murmur associated with atrial bilateral) at the root of the neck is very common in
contraction in patients with mitral stenosis. children, being usually softer or inaudible below the
Characterization of murmurs also includes assess- clavicle.
ment of the pitch of the murmur and its quality, for
Venous hum
example ‘harsh’, ‘musical’ or ‘vibratory’.
A high-pitched, blowing, rather variable, continuous
Radiation murmur, heard over the sternoclavicular junctions or
A murmur that is easily audible/loud away from the over the neck and changing with the position of the
precordial area (e.g. the neck or axilla) is said to ‘radi- head, is frequently heard in children. This murmur
521
ate’ towards the area in question. almost always disappears completely when the patient
 15.1 CARDIAC DISORDERS

lies flat and may be eliminated by gentle compression ratio exceeds 0.5 in an adult or 0.55 in a child. In
of the neck veins. infancy, the cardiothoracic ratio may be as large as
It should be appreciated that innocent murmurs may 0.6 (Fig. 15.1.6). If vascular shadows in the hilum
be heard in around 50% of normal school-aged chil- are increased, this implies high pulmonary flow (pul-
dren and adolescents. In early infancy, the frequency monary plethora; Fig. 15.1.6) or pulmonary venous
of soft murmurs is probably around 80%. Because of congestion. Diminished vascular marking, with abnor-
the very high frequency of soft heart murmurs, it is mally dark lung fields (pulmonary oligaemia), is asso-
essential that all doctors involved in caring for infants ciated with the decreased pulmonary flow occurring in
and children become familiar with the common inno- some forms of cyanotic heart disease (e.g. tetralogy of
cent murmurs; they should be able to recognize them Fallot). Individual cardiac chamber size is often dif-
with confidence and be able to exclude organic heart ficult to assess on plain chest X-rays, although varia-
disease (Fig. 15.1.5). Where doubt exists, patients tions in cardiac contour may provide useful clues.
should be referred for formal cardiological assessment.
Electrocardiography
Cyanosis
The ECG can provide information about heart rate
The distinction between peripheral and central cya- and rhythm, and about atrial or ventricular hypertro-
nosis is important. Central cyanosis is generalized. phy or hypoplasia.
Examination of the tongue and mucous membranes In the newborn infant, right ventricular forces tend
will usually exclude central cyanosis. Where doubt to dominate, whereas by the end of the first year of
exists about the presence of cyanosis the use of pulse life left ventricular forces predominate. This evolution
oximetry is helpful. reflects changes in ventricular wall thickness, and eval-
uation of ventricular hypertrophy needs to take into
account the normal values for children of each age
group. Additionally, normal values for heart rate, PR
Manifestations of heart failure interval, QRS duration, QT interval and T-wave axis
Cardiac failure in infancy tends to be dominated by vary at different ages.
pulmonary congestion, which leads to dyspnoea/
tachypnoea. Echocardiography
Dyspnoea contributes to feeding difficulties, reduced
intake and increased metabolic rate. These may com- This is the main modality for cardiac imaging and
bine to cause failure to thrive. Chronic dyspnoea may assessment of cardiac physiology in children. Current
lead to the appearance of Harrison's sulci, which are echocardiographic systems allow the sectional anat-
deformations of the rib cage at the site of the diaphrag- omy of the heart, as it beats in ‘real time’, to be
matic attachments. Crepitations at the lung bases are displayed. This is referred to as two-dimensional echo-
more often a manifestation of superimposed infection cardiography (Fig. 15.1.7).
rather than heart failure in infants. Doppler echocardiography allows quantification of
Systemic venous congestion is manifest by liver the direction and velocity of blood flow at individual
enlargement and/or oedema. Liver enlargement results sites. Colour Doppler imaging gives semiquantitative
in a firm liver with its edge palpable below the costal information about flow volume, direction and veloc-
margin. In infants, oedema is often diffuse and diffi- ity. Pulse-wave and continuous Doppler techniques
cult to detect. It is often best seen around the face and may be utilized to measure the speed of blood flow
eyes (periorbital oedema). Raised jugular venous pres- with more accuracy. This can provide useful quanti-
sure cannot be assessed easily in infancy. tative information about the presence and severity of
Other evidence of cardiac failure may include per- valvar stenoses, regurgitation and septal defects. Use
sistent tachycardia, a chronic dry cough and profuse of the Bernoulli principle allows the assessment of
sweating, especially of the forehead and scalp. relative pressure differences within the heart and blood
vessels. Newer systems also allow the same Doppler
technique to be applied to the myocardium to assess
heart function.
Investigations
Chest X-ray Cardiac catheterization
The chest X-ray provides information about heart size, Cardiac catheterization allows measurement of
shape and lung vascularity. The heart is enlarged when, intracardiac pressures and shunts. It also allows for
522
on a posteroanterior chest film, the c­ardiothoracic angiographic demonstration of abnormal anatomy.
­
 Suspected heart disease: assessment 15.1
Symptoms present? (Cyanosis/ Yes
Symptoms breathlessness/failure to thrive) Refer

No

Timing Systolic Continuous Diastolic Refer

Varies with posture? No variation with

Refer (?PDA)
posture (present
when supine)

Innocent venous hum

Grade Grade 3
Amplitude Refer
1–2/6 or louder

Location Murmur loudest Murmur loudest Murmur softer/

at mid-left over pulmonary absent below
sternal edge area clavicle?

Heart sounds Murmur Murmur

separate mainly over easily heard Refer (?AS)
from murmur carotid artery in aortic area?

Yes No
Innocent carotid bruit

2nd sound 2nd sound Ejection click

'normal'? widely split? present? Refer (?PS)

Refer (?ASD)

Innocent pulmonary flow murmur

(but get X-ray and ECG if any doubt)
1st sound
and/or 2nd
cannot be Refer (?VSD)
heard clearly

Murmur 'musical'/vibratory? Murmur 'harsh/

varies with posture: high pitched'? Refer (?VSD)
louder when supine/squatting,
softer when standing

Innocent vibratory murmur

(Still's murmur)

Location, Timing, Character Different from any Refer

described above
523
Fig. 15.1.5 An approach to the child with a murmur. AS, aortic stenosis; ASD, atrial septal defect; ECG, electrocardiography; PDA,
patent ductus arteriosus; PS, pulmonary stenosis; VSD, ventricular septal defect.
 15.1 CARDIAC DISORDERS

The number of catheters performed for therapeutic

purposes, however, has increased as new devices have
been developed. These procedures include balloon
dilatation of valves (valvuloplasty) for pulmonary
or aortic valve stenosis, or placement of an occlu-
sion ‘device’ to close a persistent ductus arteriosus,
atrial septal defect or VSD. Stenotic vessels can also
be ­balloon-dilated (angioplasty) or may require to be
helped open with stents. More recently, transcatheter
techniques have evolved to implant pulmonary and
aortic valves in suitable patients.

Treatment
Cardiac failure
The development of heart failure in a newborn should
be regarded as an emergency requiring urgent hospital-
ization, usually at a major cardiac centre. The transpor-
tation of such patients can present a major challenge
and may be best achieved by arranging for the patient to
Fig. 15.1.6 Chest X-ray showing cardiomegaly and pulmonary
be accompanied by well trained medical and/or nursing
plethora in a child with a large ventricular septal defect (see
Chapter 15.2).
personnel with appropriate resuscitation equipment.

ABC
The basics of resuscitation should be followed (see
Chapter 5.2).

Respiratory support
In the presence of severe cardiac and/or respiratory
failure, positive pressure ventilation may be helpful in
allowing stabilization of the child's condition.

A B Circulatory support
Fig. 15.1.7 Echocardiogram: ‘four chambers view’. (A) Four Intravenous inotropic support may be required but
chambers with the mitral valve (curved arrow) and tricuspid should be started in consultation with experienced
valve (straight arrow) closed during ventricular systole. (B) Same
anatomy during diastole with the mitral (large arrows) and
medical staff.
tricuspid (small arrows) valves open. The atrial and ventricular
septa can be seen separating the left heart chambers (LA and Correction of acidosis
LV) from the right-sided chambers (RA and RV).
Where respiratory or metabolic acidosis are present,
these should be corrected by ventilatory support and/
As much of this can be obtained using echocardiogra- or circulatory support.
phy, the requirement for catheterization has diminished
Prostaglandin
substantially. The number of d ­iagnostic procedures
performed has fallen further with the advent of In infants developing symptoms in the newborn period,
the additional non-invasive imaging modalities of due to congenital heart disease, a ‘ductus-dependent
­computed tomography (CT) and magnetic resonance congenital defect’ is often responsible. Infants with
imaging (MRI). In the vast majority of cases, a diag- such defects (e.g. left heart obstruction, obstructed
nosis can be made and treatment instituted on the pulmonary blood flow) may benefit from infusion of
basis of non-invasive investigations without ­cardiac prostaglandin E1 to reopen/maintain patency of the
catheterization. However, catheterization may be ductus. Care should be used when starting prostaglan-
­necessary for planning surgical treatment, especially in din because it has the side-effect of causing hypoten-
524
more complicated heart defects. sion due to vasodilatation and can also induce apnoea.
 Suspected heart disease: assessment 15.1
Diuretics
labelled as innocent. The persistent ductus was an incidental
Frusemide is usually the diuretic of choice. This may finding and the normal heart size on X-ray, normal ECG and
be given parenterally initially. A potassium-sparing absence of chamber enlargement demonstrated by the
diuretic (e.g. spironolactone) is typically used in combi­ echocardiogram all indicated that the shunt was small and
nation in order to prevent significant hypokalaemia. hence not likely to be contributing to her current symptoms.
Her pneumonia was treated with appropriate antibiotics
and the PDA was reassessed and treated (probably with a
Angiotensin converting enzyme inhibitors catheter procedure to implant a coil or occlusion device) after
Inhibition of the angiotensin converting enzyme (ACE) she had recovered from her current illness.
results in a reduction in systemic vascular resistance
and the amount of work that the heart has to perform
with each contraction. These effects may be useful Clinical example
in the management of large left-to-right shunts (e.g.
VSD) or in patients with heart failure due to reduced Ryan was a 2-month-old infant with recent
ventricular function (e.g. dilated cardiomyopathy). onset of episodic cyanosis when distressed.
He had been noted to have a heart murmur a
few days ago but had been feeding well and
Oxygen gaining weight normally. His mother thought that his colour
Oxygen should be administered if significant hypoxia was normal most of the time, but when he cried his lips and
is detectable, although in the presence of significant fingers became purple. His chest X-ray was normal but the
electrocardiogram indicated right ventricular hypertrophy.
cyanotic congenital heart disease the administration Pulse oximetry showed a saturation of 92% while he was
of oxygen will seldom produce much improvement asleep, but when upset the saturation was 65%.
in oxygenation. Furthermore, even moderate central This baby was likely to have a cyanotic heart defect, as
­cyanosis when due to cyanotic heart disease is often evidenced by his low saturations on pulse oximetry – both
well tolerated in the neonatal period. at rest and more so when crying. Minor desaturation (with
saturations above 85%) may be difficult to detect clinically
and Ryan might appear to be pink when he was comfortable.
Feeding
However, when distressed, his oxygen demands would
Gavage feeding via nasogastric tube may be help- increase and he would become more obviously hypoxic,
ful if the infant is too breathless to feed adequately. with reduced saturations and clinically apparent cyanosis.
An echocardiogram was organized to establish the nature of
Introduction of high-calorie/more concentrated feeds
his heart defect – the commonest problem to present like this
may be helpful. Infants with heart failure tend to being Fallot's tetralogy (see Chapter 15.2).
­tolerate small, frequent feeds better than larger feeds.
In the presence of more severe congestive failure, feed
volume should be reduced to 120 mL per kg per 24 h Surgery
(or less) to avoid fluid overload. In many cases, surgical treatment offers the best means
of alleviating the problem that has produced heart fail-
ure, and medical treatment should be pursued only
Clinical example in an effort to achieve stabilization of the infant's
­condition and allow a diagnosis to be reached so that
Stacey, aged 6 years, presented with fever, planning of surgical management may proceed.
cough and breathing difficulty. She had been
known to have a heart murmur since infancy,
which was labelled as being ‘innocent’ by her
paediatrician. Examination showed her to be febrile with a
Practical points
temperature of 39.6 °C, a red throat and crepitations over the
lungs, with widespread rhonchi. A grade 2/6 murmur was • In developed countries, most heart disease in childhood is
audible at the upper sternal edge that extended from systole congenital, but various acquired disorders are important.
into early diastole. Her chest X-ray showed a normal cardiac • Clinical assessment, including auscultation, remains vital
contour with patchy opacity in the right lower zone. The ECG and should not be omitted – even though investigations
was normal. An echocardiogram showed a small patent such as echocardiography may be necessary.
ductus arteriosus (PDA) with no chamber enlargement. • Cardiac catheterization is seldom required to establish
Stacey had pneumonia following a viral respiratory the diagnosis but is frequently used for therapeutic
infection. Her murmur was ‘continuous’, although audible (interventional) procedures.
only during systole and early diastole. It could easily be • Many serious heart defects, which lead to symptoms
mistaken for a purely systolic murmur unless careful attention in the early days/weeks of life, are ‘ductus dependent’.
was paid to assessing the timing. For this reason (being Use of prostaglandin E1 infusion to reopen the ductus may
judged to be a soft systolic murmur) it had been incorrectly be life-saving. 525
 15.2 Heart disease Michael Cheung

Congenital malformations affecting the heart and/or Presentation and clinical findings
great vessels occur in a little under 1% of newborn
With a small VSD, there is usually a loud, harsh,
infants. Eight defects are relatively frequent and
high-pitched systolic murmur audible at the left ster-
together make up approximately 80% of all con-
nal border, frequently associated with a thrill. The
genital heart disease (Table 15.2.1). The remaining
heart sounds otherwise may be normal and there are
20% of defects comprise a large number of abnor-
often no other abnormal findings. The murmur is usu-
malities, some being quite rare and/or complex
ally ‘pansystolic’ in timing, indicating flow across the
malformations.
defect throughout systole. Alternatively there may be a
short early systolic murmur, which is often well local-
ized at the mid left sternal border and reflects a small
muscular defect that becomes smaller during ventricu-
Presenting features lar contraction.
The major presenting features are: With a larger VSD, left heart dilatation occurs,
• presence of an abnormal murmur signs of cardiac failure may be present and the physi-
• development of symptoms or signs of congestive cal signs are different. These may include a parasternal
heart failure heave, a displaced apex, and the systolic murmur may
• central cyanosis be softer and less harsh. Large shunts are associated
• any combination of the above. with an apical diastolic murmur, owing to increased
flow through the mitral valve. Infants with a large
VSD have difficulty feeding due to tachypnoea and fail
to thrive, owing to a combination of poor intake and
increased metabolic demands. Tachypnoea, increased
Acyanotic defects work of breathing and hepatomegaly are frequent
These comprise approximately 75% of all congenital clinical findings.
heart defects and can be subdivided into: (1) those that
are associated with an isolated left-to-right shunt, and Investigation
(2) obstructive heart defects.
Common defects with a left-to-right shunt are: With small defects, the chest X-ray and electrocardio-
• ventricular septal defect (VSD) gram (ECG) are frequently normal. With larger defects,
• patent ductus arteriosus (PDA) the chest X-ray shows cardiomegaly and increased pul-
• atrial septal defect (ASD) monary plethora (see Fig. 15.1.6). The ECG often
• atrioventricular septal defect (AVSD). shows biventricular hypertrophy. The site and size
of the defect can be documented well with echocar-
diography. Cardiac catheters to document degree of
­shunting are rarely done but may be ­performed to
Ventricular septal defect
measure ­pulmonary vascular resistance and response
These comprise around 30% of all cardiac defects. to pulmonary vasodilators in patients thought to have
They vary from tiny defects, of pinhole size, to huge ­pulmonary hypertension secondary to a left-to-right
defects. Small defects are more common than large shunt.
ones and are usually asymptomatic. Defects are
­frequently situated in the region of the membranous
Management
septum (perimembranous defects), but VSDs involving
the muscular septum are also common (Fig. 15.2.1). The natural history of a VSD varies. Small defects
Very tiny muscular defects may be demonstrated by frequently undergo spontaneous closure, which may
echocardiography in infants with no clinical signs to occur in 50% or more. Some moderate defects may
526 suggest a septal defect. also diminish in size and the shunt becomes minor.
 HEART DISEASE 15.2
defects may not cause symptoms or significant signs
Table 15.2.1 Relative frequency of common congenital
heart defects
in the first few days of life. As pulmonary vascular
resistance naturally declines in the first few months of
Approximate life there will be an increasing volume of pulmonary
Defect frequency (%) blood flow. Children with isolated large VSDs who are
Ventricular septal defect (VSD) 30
asymptomatic aged more than a few months of age
are concerning, because this indicates that the natural
Persistent arterial duct (ductus arteriosus; PDA) 12 fall in pulmonary vascular resistance has not occurred.

Atrial septal defect (ASD) 8

Indications for closure of VSD
Pulmonary stenosis 8
• Heart failure/failure to thrive unresponsive to
Aortic stenosis 5
medical therapy
• Pulmonary hypertension, which is still responsive
Coarctation of the aorta 5 with medical therapy
• Aortic valve prolapse
Tetralogy of Fallot 5 • Infective endocarditis.
VSDs may be closed by open heart surgery or by
Transposition of the great arteries 5
transcatheter techniques if suitable for the latter.
Perimembranous VSDs are currently closed mainly
by open heart surgery due to concerns regarding heart
block following transcatheter closure.
Perimembranous VSD Muscular VSD
SVC
Patent ductus arteriosus
Failure of the ductus arteriosus (which connects the
pulmonary artery to the descending aorta) to close
LA LA in the newborn period may be due to severe prematu-
RA RA rity or to a congenital abnormality. The duct typically
closes in the first few days of life. The clinical find-
LV LV ings depend on the size of the duct and the amount of
RV RV blood flow across the vessel. Patients with a small PDA
are usually asymptomatic, with the only abnormality
IVC
being a continuous murmur audible at the upper left
Fig. 15.2.1 Sites of ventricular septal defect (VSD). In the sternal border or left infraclavicular area.
left panel, the defect is close to the membranous part of the Such murmurs may be present throughout the car-
ventricular septum (perimembranous VSD). In the right panel, the diac cycle (‘machinery murmur’), but may disappear
defect is in the muscular septum. IVC, inferior vena cava; LA, left
during diastole and be mistaken for a systolic murmur,
atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; SVC,
superior vena cava.
especially if the duct is large and there is associated
pulmonary hypertension.
With a large duct, the large left-to-right shunt causes
Important complications include progressive aortic left heart dilatation. Symptoms such as failure to thrive,
regurgitation, when the adjacent leaflet of the aortic dyspnoea and recurrent chest infections are similar to
valve is sucked (prolapses) into the defect, due to the those of a large VSD. Bounding pulses may be palpa-
Venturi effect of high-velocity left-to-right flow across ble. The apex may be displaced and forceful, and an api-
the VSD. Aortic valve prolapse due to this mechanism cal mid-diastolic murmur may be heard; as with a VSD,
does not occur with defects that are far away from this is due to increased flow through the mitral valve.
the aortic valve. In some cases of VSD, infundibular The presence of cardiomegaly and pulmonary pleth-
pulmonary stenosis or right ventricular cavity muscle ora on the chest X-ray indicates a large shunt, and left
bundles may develop. Small isolated defects are gener- ventricular hypertrophy may be seen on the ECG. The
ally left alone if the investigation shows no significant diagnosis can be confirmed by echocardiography.
haemodynamic disturbance and the patient remains In symptomatic premature infants, medical treat-
symptom-free. ment with indomethacin or other non-steroidal anti-
Large VSDs are associated with a variable degree inflammatory drugs, which inhibit prostaglandin
of increased pulmonary pressure. The natural fall in synthesis, may be effective in promoting ductal con-
527
pulmonary artery pressure from birth means that large striction. Unfortunately, drug treatment is typically not
 15.2 CARDIAC DISORDERS

effective in mature infants and in such patients inter- may be palpable. An ejection systolic murmur, due to
vention to close the ductus is indicated. This should be increased pulmonary blood flow, is present in the pul-
carried out at an early stage in symptomatic patients monary area but not usually louder than grade 2/6 and
(including premature infants if indomethacin is inef- not harsh in character. A soft mid-diastolic murmur
fective) but may be delayed in asymptomatic patients. may be heard at the lower sternal border, secondary
With small PDAs, intervention is indicated to elimi- to increased flow across the tricuspid valve. The aor-
nate the risk of infective endocarditis, rather than to tic and pulmonary components of the second heart
treat cardiac failure or pulmonary hypertension. The sound are fixed and widely split (i.e. loss of the normal
risk of endocarditis occurring, however, is very small. variation in separation during inspiration and expira-
The preferred method of duct occlusion is by a trans- tion; see Fig. 15.1.2).
catheter approach. The type of device used depends on The chest X-ray characteristically shows cardiomeg-
the size and shape of the PDA. Large ducts, especially aly with pulmonary plethora. The ECG often shows
those in small infants, may, however, require surgical features of partial right bundle branch block. The
ligation, typically from a left lateral thoractomy. diagnosis may be confirmed by echocardiography.
Closure of the defect is recommended in patients
where there is evidence of a significant shunt as indi-
Atrial septal defect
cated by right heart enlargement. In many cases a trans-
Defects of the atrial septum are usually in the central catheter procedure can be performed with placement
part of the septum and are termed ‘secundum’ ASD of an ‘occluder’ device. This is a non-surgical option
(Fig. 15.2.2). Unlike small VSDs and PDAs (which for patients with central defects of small to moder-
tend to be associated with loud murmurs), small ate size with good margins that are able to support
ASDs may go completely undetected because the vol- the device without interfering with surrounding struc-
ume of blood flow across the defect is small and also tures such as the mitral valve, right-sided pulmonary
the ­pressure gradient across the defect, and hence veins or the vena cavae. Surgical repair either by direct
the velocity of blood flow, are both low. With larger suture or patch closure may be required for defects
defects, a ­significant shunt is present, and this is rarely that are unsuitable for a transcatheter approach.
associated with pulmonary hypertension. Even large
ASDs seldom cause symptoms in early childhood.
Atrioventricular septal defect
If patients with large defects reach adult life without
surgery, they may develop atrial arrhythmias in mid- This category of defect accounts for approximately 3%
dle adult life and often have reduced exercise capacity, of all congenital cardiac defects and includes a group
even if arrhythmias are not a problem. Isolated ASDs of septal defects low in the atrial septum (primum
hardly ever lead to Eisenmenger syndrome. ASD) that abut on the atrioventricular valves and may
The characteristic findings in children with an ASD involve the upper part of the ventricular septum.
are related to the increased blood flow through the When the ventricular septum is intact (partial AVSD
right side of the heart and right heart enlargement. or primum ASD), only an atrial communication is
A parasternal heave related to a dilated right ventricle present. In addition to the septal defect, the atrio-
ventricular junction and valves are abnormal in all
forms of AVSD. The left-sided atrioventricular valve
ASD secundum ASD primum in this condition typically has three leaflets rather
(partial AV septal defect) than the usual two-leaflet mitral valve. This is some-
times described incorrectly as a cleft in the mitral valve
and is associated with varying degrees of regurgita-
tion. Children with a primum ASD or partial AVSD
behave physiologically and symptomatically like those
LA LA
with an ASD. Those with significant regurgitation of
RA RA the left-sided atrioventricular valve, however, develop
­symptoms much earlier in infancy and early childhood.
When a significant VSD coexists (complete AVSD;
Fig. 15.2.3), the presentation resembles that of a VSD
with difficulty feeding and failure to thrive. This defect
is commonly associated with Down syndrome.
Fig. 15.2.2 Common types of atrial septal defect (ASD).
The chest X-ray usually shows quite marked cardio-
Secundum defects are in the fossa ovale (mid-atrial septum).
Primum defects are low in the atrial septum and abut on the megaly and pulmonary plethora, especially in the com-
atrioventricular (AV) valves, which are abnormal and often plete form of the defect. The ECG c­ haracteristically
528
incompetent. LA, left atrium; RA, right atrium. shows left-axis deviation accompanied by partial right
 HEART DISEASE 15.2
ASD primum AV canal tract (­ infundibular stenosis) and supravalvular or
(partial AV septal defect) (complete AV septal defect) branch pulmonary stenosis.
Most patients are asymptomatic in infancy and
childhood because very severe (‘critical’) obstruction is
uncommon and even moderate obstruction is generally
well tolerated. An ejection systolic murmur is heard at
LA LA
RA RA the left upper sternal edge and radiates through to the
back. An early ejection sound (ejection click) is usu-
ally audible at the left sternal border (Fig. 15.2.4) with
valvar stenosis.
The size of the heart is usually normal on chest
X-ray, but the main pulmonary artery is often prom-
Fig. 15.2.3 Atrioventricular (AV) septal defect. The complete inent due to post-stenotic dilatation. The ECG is
form is associated with a common AV valve and the septal ­normal with mild obstruction but shows right ventric-
defect allows communication between all four cardiac ular hypertrophy in more severe cases.
chambers. ASD, atrial septal defect. Mild pulmonary stenosis is generally a benign con-
dition and is often non-progressive. More severe pul-
monary stenosis leads eventually to effort intolerance
bundle branch block. The presence of left-axis devi- and cardiac failure. ‘Critical’ (very severe) pulmonary
ation distinguishes ‘primum’ ASDs from ‘secundum’ stenosis may present in early infancy with cyanosis due
defects. Echocardiography confirms the diagnosis and to right-to-left shunting through the foramen ovale or
will differentiate partial from complete atrioventricu- an associated ASD.
lar defects. The diagnosis may be confirmed by echocardiogra-
Surgical repair is almost always required. When pul- phy. Treatment involves a catheter technique known
monary hypertension is present, this is generally rec- as balloon valvuloplasty. This involves manipulating
ommended in the early months of life (3–4 months) a catheter-mounted balloon to lie across the pulmo-
in order to obviate the risk of pulmonary vascular nary valve, typically using the femoral vein for access,
­disease, particularly in children with Down syndrome. and then inflating the balloon to open the valve more
In patients with an isolated primum ASD, when fully. This procedure is simple and effective in most
pulmonary hypertension is absent, surgery may be
­ cases, requires only a very short hospital stay and
delayed until the age of 2–4 years. Operation involves saves the patient an open heart operation. If this is not
placement of a patch to close the ASD and repair of
the left atrioventricular valve. Although there is an
Mild pulmonary stenosis
association with both types of AVSD, left ventricular
outflow tract obstruction is more likely to occur with EC
A2
partial than complete AVSDs. M1 T1

P2

Obstructive heart defects

The following defects have no shunt when they occur
S1 S2
in isolation, and are obstructive lesions:
• pulmonary stenosis
Mild aortic stenosis
• aortic stenosis
EC
• coarctation of the aorta.
M1 T1 A2

Pulmonary stenosis P2

Pulmonary stenosis usually occurs at valve level and

is the commonest of the pure obstructive malforma-
tions. The pulmonary valve often has thickened leaf-
S1 S2
lets and partially fused commissures. In some cases
the valve may be bicuspid. Other sites of pulmonary Fig. 15.2.4 Auscultatory findings in pulmonary and aortic
stenosis, occurring as isolated abnormalities, are less stenosis. The ejection click (EC) is earlier in pulmonary stenosis
frequent. These include muscular subpulmonary and the second sound is widely split. In aortic stenosis the click is 529
obstruction involving the right ventricular o
­ ­utflow best heard at the apex.
 15.2 CARDIAC DISORDERS

e­ ffective, as is often the case when the valve leaflets are

very thickened or the valve annulus is small, surgical
­valvotomy may need to be performed. Balloon valvu- Ao
loplasty is not used for subpulmonary obstruction and Normal with
is rarely effective in supravalve stenosis. PA 'ligamentum'

Aortic stenosis
Valve stenosis with thickened, often bicuspid, leaf-
lets and fused commissures is the most common form
of aortic stenosis. Subaortic stenosis due to either a
fibrous stricture or muscular obstruction in the left Ao
ventricular outflow tract, or supra-aortic stenosis
Isolated
(i.e. above the aortic valve) are less common causes of PA small PDA
left heart obstruction.
Except in very severe cases, affected children are
symptom-free in infancy and early childhood, and
present with the chance finding of an ejection sys-
tolic murmur over the precordium and in the aortic
area. Characteristically, with valvar stenosis the mur-
mur is best heard to the right of the sternum and radi- Ao
ates to the carotids. A thrill is commonly present over Coarctation of
the carotids and may also be felt in the aortic area. PA the aorta
An ejection click is usually heard with valvar stenosis (+small PDA)
(see Fig. 15.2.4) and is often most easily audible at the
apex or lower left sternal border. In more severe cases a
forceful apical impulse due to left ventricular hypertro-
phy may be apparent. In subaortic stenosis the mur- Fig. 15.2.5 Aorta (Ao) and pulmonary artery (PA) showing
mur is best heard at the left sternal edge and a click is persistent ductus and site of coarctation (often associated with
not heard. Conversely, the murmur of supravalvar ste- patent ductus arteriosus, PDA).
nosis is often best heard over the carotid artery.
The natural history of aortic stenosis is generally one
of gradual progression. With more severe obstruction, ­arteriosus (Fig. 15.2.5). Coarctation of the aorta is
symptoms include dizziness and syncope on exertion, often ­associated with other cardiac defects, includ-
chest pain, effort intolerance and sudden death. In a ing aortic stenosis, ventricular septal defect and
small minority of cases, with ‘critical’ stenosis, severe mitral valve abnormalities. A bicuspid aortic valve is
congestive heart failure may appear in early infancy. present in 40% of cases even in the absence of other
In mild and even moderate aortic stenosis, the chest malformations.
X-ray and ECG may show little abnormality. In more Coarctation usually leads to the development of
severe cases the ECG shows left ventricular hypertro- severe cardiac failure in the newborn period, with oli-
phy. Echocardiography allows assessment of the site guria and acidosis, often in the first 2 weeks of life
and severity of the obstruction. when the ductus closes. In around 30% of cases, pre-
Treatment should be recommended if severe ste- sentation may be delayed until late in childhood or
nosis is present, even in the absence of symptoms. In even adolescence or adult life. These older patients
cases of moderate stenosis the presence of symptoms may present with asymptomatic hypertension, poor
as described above or ECG changes on exercise are an exercise capacity or lower limb claudication.
indication for treatment. Balloon aortic valvuloplasty The characteristic physical findings are of dimin-
is an alternative to surgery, but is more likely to induce ished or absent femoral pulses. Simultaneous palpa-
aortic regurgitation. Surgical repair involves aortic tion of the right brachial pulse and a femoral pulse
valvotomy using cardiopulmonary bypass. shows quite obvious delay in the pulses in older chil-
dren and adults, but this is difficult to detect in young
children. Upper limb hypertension may be present
Coarctation of the aorta
and there may be a significant difference in upper and
In this condition a stricture is present in the distal part lower limb blood pressure. Continuous murmurs may
of the aortic arch with the maximal site of obstruc- be audible over the back due to the development of
530
tion usually close to the aortic end of the ductus collateral vessels.
 HEART DISEASE 15.2
The chest X-ray and ECG findings vary according
to the age of presentation. In symptomatic infants
cardiomegaly and pulmonary congestion are usually Patent 'ductus' (PDA)
seen on the chest X-ray, and the ECG shows right ven- Ao
tricular hypertrophy. In older children the X-ray may
show an abnormal appearance of the aortic knuckle
and rib notching due to the presence of enlarged inter-
costal arteries, which act as collateral vessels to bypass PA LA
the obstructed segment of aorta. This is seldom seen
before the age of 8 years. The ECG may show left
­ventricular hypertrophy.
LV
In infancy the onset of congestive heart failure
occurs after closure of the ductus arteriosus. In the RA
presence of ductal patency, the lower body is sup- RV
plied by deoxygenated blood due to right-to-left flow
through the duct from the pulmonary artery and into
the descending aorta. Reopening the duct by the intra-
venous infusion of prostaglandin E1 may be helpful in
Fig. 15.2.6 Hypoplastic left heart syndrome showing
resuscitation. Basic principles of resuscitation should hypoplasia of left ventricle, mitral valve, aortic valve and
be followed in addition to this therapy. Surgery to ascending aorta. The ductus provides the only effective route
relieve the obstruction is indicated when the neonate is through which the systemic circulation can be maintained from
in the best possible condition. the right ventricle with right-to-left shunting across the duct. Ao,
In other patients intervention may be deferred until aorta; LA, left atrium; LV, left ventricle; PA, pulmonary artery; PDA,
later in childhood. In selected cases, with a localized patent ductus arteriosus; RA, right atrium; RV, right ventricle.
coarctation shelf, balloon angioplasty (or placement
of a stent) may be employed as an alternative to sur-
gical repair. Patients who have required surgical relief Fontan circulation) is possible and can produce long-
of coarctation (especially those operated on in early term survival. Heart transplantation for this condi-
infancy) and those who have had balloon angioplasty tion, in the newborn period, is offered to some families
as a primary procedure may develop restenosis at the in North America.
coarctation site. These areas of recurrent stenosis may
be amenable to further balloon angioplasty or stent
implantation.
Patients with coarctation who undergo repair in
Cyanotic defects
later childhood and as adults (i.e. those who escape The presence of cyanosis in a child with congenital
detection during childhood) are at increased high risk heart disease indicates that deoxygenated blood from
of persisting systemic hypertension, left ­ventricular the systemic venous circulation is being directed back
­failure, aortic dissection and cerebrovascular ­accidents. into the systemic arterial circulation without going
Children successfully repaired in early childhood are through the lungs (i.e. right-to-left shunt). Cyanotic
less prone to these complications in later life. defects account for approximately 25% of all con-
genital heart malformations. Such defects are almost
always associated with the presence of a septal defect,
Hypoplastic left heart syndrome
coupled with additional abnormalities such that right-
A small subgroup of infants with both severe aortic to-left shunting within the heart occurs.
stenosis and coarctation may present with associated Three major subgroups exist. In the first group
hypoplasia of the left ventricle. In some cases the aor- (exemplified by tetralogy of Fallot) pulmonary blood
tic valve and/or mitral valve are atretic (Fig. 15.2.6). flow is reduced as a result of a combination of obstruc-
Presentation is similar to that for other forms of tion to the right ventricular outflow tract and a septal
severe left heart obstruction, and these infants pres- defect below the obstruction through which blood
ent with severe cardiac failure or shock in the first few may flow from the right ventricle to left. In tetral-
days of life. All peripheral pulses are diminished or ogy of Fallot the shunt is almost completely right to
absent and manifestations of cardiac failure are severe. left, whereas in some other defects associated with
The condition is invariably fatal without surgery. low pulmonary flow the physiology is more c­ omplex,
Medical treatment, including infusion of prostaglandin with right-to-left shunting at one level and left-to-
and other measures, may lead to improvement. Palliative right shunting at another (e.g. tricuspid atresia or
531
surgery (the initial Norwood procedure and subsequent ­pulmonary atresia).
 15.2 CARDIAC DISORDERS

In the second group of cyanotic defects bidirec- Clinical features

tional shunting is associated with very large commu-
Cyanosis is not usually obvious in the newborn period
nications between the left and right sides of the heart
but appears later in infancy in most affected children.
with free mixing of blood (e.g. ‘single ventricle’) and
Oxygen saturations (with pulse oximetry) may be n ­ ormal
truncus arteriosus. In such defects pulmonary blood
or mildly depressed in the early weeks of life. A harsh
flow is usually high and pulmonary hypertension is
ejection systolic murmur is audible at the left sternal
a feature. Cyanosis is generally mild and may pass
edge and/or in the pulmonary area (infundibular steno-
unnoticed.
sis) and radiates through to the back. The second heart
A third group of cyanotic defects, best exemplified
sound is often quite loud but may be s­ ingle because the
by transposition of the great arteries, may be con-
pulmonary closure sound is quieter (Fig. 15.2.8).
sidered as a ‘plumbing problem’. In transposition,
Cyanosis appears gradually during the first 6–12
the aorta and pulmonary artery are connected to the
months of life or rarely later, and is characteristically
wrong side of the heart and as a result systemic venous
more obvious on crying or exertion. The development
blood is directed straight through into the systemic
of intermittent episodes of severe cyanosis (‘hypoxic
­circulation again (see below).
spells’), which may appear spontaneously but are quite
commonly precipitated by stress or exercise, is concern-
Tetralogy of Fallot ing. Such spells are characterized by marked pallor
or cyanosis with some infants going floppy or los-
Of the four components that comprise Fallot's tetral-
ing consciousness. Hypoxic spells are associated with
ogy (VSD, pulmonary stenosis, right ventricular
increased right-to-left shunting and a sharp reduction
hypertrophy, overriding aorta), the important ones
in pulmonary flow. In the past these have been attrib-
are pulmonary stenosis and the VSD (Fig. 15.2.7).
uted to infundibular ‘spasm’, but the physiology is
The presence of severe pulmonary stenosis, which is
more complex and spasm may not in fact occur. Initial
typically infundibular muscular obstruction ­coupled
treatment of spells, which are potentially dangerous,
frequently with valvar hypoplasia and commissural
involves soothing and pacifying the distressed infant.
fusion, leads to right-to-left shunting into the aorta.
In severe cases intramuscular morphine may be help-
The degree of outflow tract obstruction determines the
ful. Older children often adopt a squatting posture
degree of right-to-left shunt and, hence, the amount
at intervals or during these episodes. This manoeu-
of pulmonary blood flow and the degree of cyanosis.
vre increases systemic vascular resistance, reducing
Tetralogy may be associated with microdeletion of the
right-to-left shunting and leading to a transient rise
long arm of chromosome 22.
in pulmonary blood flow with improved oxygenation.
Placing an infant into the knee–chest position will
achieve the same effect. Oxygen, intravenous fluid,
correction of acidosis, beta-blockade and mechanical
ventilation may be required in severe spells.
Pulmonary valve
Ao and infundibular
stenosis Course and prognosis
Cyanosis generally progresses gradually, with dimin-
PA ishing exercise tolerance, finger clubbing and in severe
LA cases growth retardation. Following surgery, children
Override
of aorta
A2 (loud)
VSD
LV
RV
P2 (inaudible)

RV hypertrophy
S1 S2
Fig. 15.2.7 Fallot's tetralogy, showing infundibular and valvar
pulmonary stenosis and hypoplasia of the branch pulmonary Fig. 15.2.8 Auscultatory signs in Fallot's tetralogy. The systolic
arteries, all of which are frequent. Ao, aorta; LA, left atrium; murmur is ‘ejection’, owing to the pulmonary stenosis. The aortic
532 LV, left ventricle; PA, pulmonary artery; RV, right ventricle; VSD, closure sound is accentuated and pulmonary closure is so soft
ventricular septal defect. as to be inaudible. The second sound appears to be ‘single’.
 HEART DISEASE 15.2
typically show catch-up growth. Development of open heart surgery to replace the valve. Selected
­cardiac failure is unusual but the severe cyanosis leads patients may be suitable for transcatheter pulmonary
to compensatory polycythaemia, and cerebral throm- valve replacement.
boembolic complications (e.g. stroke) may occur.
Infective endocarditis and cerebral abscess also are
Transposition of the great arteries
important complications.
In this condition the aorta and pulmonary arteries
arise from the incorrect ventricles (Fig. 15.2.9). There
Investigations
are therefore two parallel circulations with: (1) systemic
The chest X-ray shows the heart size to be normal venous blood flowing through the right side of the heart
with an uptilted apex and concave pulmonary seg- back into the aorta, and (2) pulmonary venous blood
ment associated with reduced lung vascularity (oligae- through the left side of the heart back into the pulmo-
mia). In severe cases the cardiac contour may resemble nary circulation. Survival is dependent on mixing of
the shape of a wooden clog – coeur en sabot – often blood between these two parallel circuits via the fora-
referred to as ‘boot-shaped’. The ECG usually shows men ovale, ductus arteriosus or a septal defect. Affected
right ventricular hypertrophy. Echocardiography is infants generally survive for several days or even weeks
diagnostic. Cardiac catheterization is rarely performed because of shunting through the foramen ovale and/
but may be indicated if coronary anatomy is unclear or ductus arteriosus, but few live longer than a month
on ultrasound imaging. without help, unless they have a coexisting septal defect,
such as a VSD. Chromosomal defects are rarely present
in patients with transposition of the great arteries.
Differential diagnosis
In infancy, before the onset of cyanosis, the murmur
Clinical features
is often mistaken for that of a small VSD. Other cya-
notic defects, such as tricuspid atresia, may be differ- Cyanosis is present from the early hours of life and
entiated by ancillary investigations, such as ECG and usually progresses gradually over the next few days.
echocardiography. Metabolic acidosis may develop, because of tissue
hypoxia, if the situation persists untreated. Apart from
cyanosis the infant may appear completely normal.
Treatment
Palpation reveals a forceful right ventricular impulse
Total correction involving repair of the VSD and relief at the left sternal edge, but on auscultation there is
of the infundibular and pulmonary valve stenosis can ­frequently no murmur audible.
be carried out even in early infancy if the anatomy is
suitable. In those children who have small branch pul-
monary arteries, it may be useful to delay repair by car-
rying out a palliative systemic–pulmonary artery shunt
operation first to increase pulmonary blood flow. Most
Ao
surgeons use a prosthetic tube graft to create an anas-
tomosis between a subclavian artery and the ipsilateral
pulmonary artery (modified Blalock–Taussig shunt). PA
Infants who are having significant hypoxic spells
can be treated medically in the short term with beta-
adrenergic blocking drugs, for example ­propranolol,
to ­prevent spells while the child is awaiting surgery. Pulmonary
venous
LV blood
Follow-up
RV
The long-term problems following repair of t­etralogy
of Fallot are related to chronic pulmonary regurgi-
tation, recurrence of right ventricular outflow tract Systemic
obstruction, and the development of arrhythmias. venous
Most patients with repaired tetralogy will require blood
­further procedures to replace the pulmonary valve. Fig. 15.2.9 Transposition of the great arteries. Systemic venous
The approach to this depends on the age and size of blood is ejected from the right ventricle (RV) to the aorta (Ao),
the patient and the morphology of the outflow tract. while pulmonary venous blood passes from the left ventricle (LV) 533
The majority of patients currently undergo f­urther to the pulmonary artery (PA).
 15.2 CARDIAC DISORDERS

Investigations Clinical features

The chest X-ray shows a normal-sized or mildly Cyanosis develops early. A systolic murmur is audible
enlarged heart with a contour that sometimes resem- along the left sternal border.
bles ‘an egg on its side’. Pulmonary vascular markings
are usually increased. The ECG shows normal ven-
Diagnosis
tricular complexes, but may manifest T-wave abnor-
malities. The diagnosis may be established rapidly by The diagnosis may be suspected on the character-
echocardiography. istic ECG pattern of left axis deviation, right atrial
hypertrophy, left ventricular hypertrophy and right
ventricular hypoplasia. Echocardiography confirms
­
Treatment the diagnosis.
Balloon atrial septostomy
Cardiac catheterization may be required as an emer- Treatment
gency procedure to improve systemic arterial oxy-
gen saturation. Venous access is typically through A palliative arterial shunt may be needed in infancy
the umbilical vein or femoral vein. An inflatable (see above under Tetralogy of Fallot). Later in child-
­balloon-tipped catheter is passed into the left atrium hood, cardiac surgery is usually feasible and involves
via the foramen ovale under ultrasound guidance. the creation of a bidirectional cavopulmonary con-
The balloon is then inflated and forcefully withdrawn nection (bidirectional Glenn) by anastomosing the
into the right atrium, in order to tear the atrial sep- superior vena cava to the right pulmonary artery.
tum and create an ASD. This results in an increase Subsequently the inferior vena cava is also connected
in highly saturated pulmonary venous blood flow- to the pulmonary arteries, to allow the majority of
ing into the right atrium and then into the ­systemic systemic venous blood to pass directly into the pul-
circulation. monary circulation (Fontan operation). The Fontan
procedure is used in several forms of congenital heart
Surgery disease where there is either only one functional ventri-
After successful balloon septostomy most infants will cle (e.g. hypoplastic left heart syndrome or pulmonary
manage comfortably for many days or weeks. Surgical atresia with intact ventricular septum) or the cardiac
correction involves transecting the great arteries above anatomy is too complex to allow biventricular repair.
the level of the sinuses and re-anastomosing them to
the appropriate ventricle. It is also necessary to trans-
Pulmonary atresia
fer the coronary arteries across from the aortic root
(initially above the right ventricle) to the new aor- In this condition the origin of the pulmonary artery
tic origin from the left ventricle. The arterial switch from the right ventricle is completely obstructed or
procedure is preferably performed in the first few
­ absent. Blood in the right side of the heart passes via
weeks of life. After this time, the normal decline in an ASD, foramen ovale or VSD into the left ventricle
pulmonary vascular resistance leads to atrophy of and aorta. Pulmonary blood flow depends on collat-
the left ventricle such that it becomes less accustomed eral flow from the aorta via a PDA or other collateral
to working at higher workload, which is problematic channels.
when restored to the systemic circulation postopera-
tively. If the operation is delayed and there is concern Clinical features
regarding the ability of the left ventricle to support the
systemic circulation then strategies such as prepara- Cyanosis develops early and many infants have an eas-
tory banding of the pulmonary artery or postopera- ily audible continuous murmur due to the associated
tive mechanical support may be employed. PDA or other collaterals feeding the pulmonary circu-
lation from the aorta.
Tricuspid atresia
Diagnosis
In this malformation the tricuspid valve is blocked
completely and there is no communication between The diagnosis is usually confirmed by echocardiogra-
the right atrium and ventricle. Systemic venous blood phy, although it may be suspected strongly on clinical
passes via the foramen ovale or an ASD into the left grounds coupled with ECG and X-ray findings. Other
side of the heart, and at ventricular or arterial level forms of cardiac imaging may be needed to clarify
a left-to-right shunt exists (via a VSD or PDA). This the pulmonary blood flow especially if multiple aor-
allows blood to perfuse the pulmonary circulation, topulmonary collaterals (MAPCAs) are detected on
534
usually in reduced amounts. echocardiography.
 HEART DISEASE 15.2
Treatment
over the precordium and in the pulmonary area. A soft
Initial medical therapy may involve prostaglandin diastolic murmur was also heard at the apex.
infusion to maintain patency of the ductus. Early A chest X-ray showed a large heart and plethoric lungs.
An ECG showed left ventricular hypertrophy.
surgical treatment usually involves a systemic-to-
­
The fact that the murmur had not been heard before
pulmonary shunt procedure. At a later stage, which suggested that it might have been soft or dismissed
depends on the associated defects, surgical correction as being innocent. The signs suggested a significant
may be ­performed by opening up a way through from ventricular septal defect or patent ductus arteriosus with
the right ventricle into the pulmonary arteries, often by pulmonary hypertension. It was not possible to make
insertion of a valved conduit and closure of the VSD. a definite diagnosis without echocardiography, which
needed to be organized as soon as possible. The X-ray
and ECG abnormalities indicated a major haemodynamic
Truncus arteriosus disturbance and the defect was likely to be large. Aaron's
failure to thrive was likely to be the consequence of the
This defect is associated with the presence of a s­ ingle cardiac abnormality.
artery, which branches shortly after arising from the The diagnosis, confirmed by echocardiography, was a
heart to give rise to the pulmonary artery and aorta. large patent ductus arteriosus. The absence of a continuous
murmur was due to the presence of severe pulmonary
The truncal valve usually sits astride a large VSD and
hypertension.
receives blood from both right and left ventricles.

Clinical features
Acquired heart disease
Cyanosis is usually mild or absent and congestive
heart failure often appears in the newborn period. in children
Most infants will have a systolic murmur and in some There are several forms of acquired heart disease in
cases a diastolic murmur may be heard that is due to children.
regurgitation of the abnormal truncal valve.

Kawasaki disease
Diagnosis
This condition is described elsewhere (see Chapter 13.3.).
The diagnosis can be made by echocardiography. Chest It may lead to the development of c­ oronary artery aneu-
X-ray and ECG findings are usually non-specific. rysms, with risk of myocardial ischaemia or infarction.

Treatment Myocarditis
The only effective treatment is surgical correction, This condition follows a viral infection, and the patho-
which needs to be carried out in early infancy. The pul- genesis is immunologically mediated. A wide variety
monary artery is separated from the truncus and, after of common viruses have been implicated in this dis-
closure of the VSD leaving the aorta arising from the ease. The auscultatory signs are non-specific, with soft
left ventricle, a valved conduit is placed to connect the heart sounds, a gallop rhythm but no murmur in most
right ventricle to the pulmonary arteries. cases. Congestive heart failure may develop rapidly
or insidiously, and the condition is accompanied by
ECG, X-ray and echocardiographic evidence of myo-
cardial damage, ventricular dilatation and depressed
myocardial function. In the past, the condition was
Clinical example frequently fatal, although some patients recovered.
Aaron was 6 months old and had gained
The use of immunoglobulin or immunosuppressive
weight poorly since birth. Birth weight was drug therapy (e.g. steroids, azathioprine, ciclosporin)
2.8 kg and his present weight was 4.1 kg. may be of help, although the mainstay of therapy is
Several doctors had examined him but had supportive treatment.
failed to find a cause for his poor weight gain.
Examination showed a thin infant who was tachypnoeic
with a respiratory rate of 60 per minute. All pulses were Cardiomyopathy
easily palpable and of large volume (bounding). The cardiac
impulse was forceful, with the apex displaced towards the
This term encompasses a group of conditions with
anterior axillary line. Auscultation revealed a grade 2/6 heart muscle disease and myocardial dysfunction,
ejection systolic murmur of non-specific character audible often associated with progressive effort intolerance,
535
­arrhythmias and/or heart failure. The condition may
 15.2 CARDIAC DISORDERS

result from an earlier episode of myocarditis, but in positive antibody titres). If such evidence is found,
most cases the aetiology is unknown and no specific however, the presence of two minor criteria and one
treatment is available. Some forms of cardiomyopathy major criterion as listed above, or the presence of two
may be inherited. In those patients where the condition or more major criteria, may be regarded as indicative
progresses to end-stage heart failure, cardiac transplan- of the presence of rheumatic fever.
tation offers the only prospect of survival currently.
Treatment
Rheumatic heart disease
Treatment involves bed rest and administration of
Rheumatic heart disease is now very uncommon in the aspirin in full anti-inflammatory doses. Steroids may
developed world. The condition follows acute rheu- also be administered in the presence of more severe
matic fever, although a clear history of rheumatic carditis and will usually reduce the duration of the
fever may be absent in some cases. The host's abnor- acute episode, although they probably do not affect
mal immune response to certain streptococcal anti- the development of chronic valve disease. Supportive
gens results in an autoimmune disorder affecting the treatment for heart failure and rhythm disturbance
heart, synovial membranes and other tissues. may also be needed.
The main cardiac sequelae of rheumatic fever are
the development of damage to heart valves, resulting
Infective endocarditis
in the development of mitral stenosis and/or incompe-
tence and aortic stenosis/incompetence. Other valves Turbulent blood flow predisposes the adherence of
are occasionally affected. In the acute phase, inflam- bacteria and establishment of infection. In addition
mation of the heart muscle (myocarditis) and pericar- to the generalized effects of infection, collections of
dium (pericarditis) can also occur. Myocarditis may infection have the potential to damage local structures,
cause reduced ventricular function and also arrhyth- and vegetations may also embolize. The development
mias, typically causing heart block. of a transient bacteraemia is usually the precursor of
such infection, although the source of the bacteraemia
is often not clear.
Clinical manifestations
Systemic symptoms include fever, rigors, anorexia
Rheumatic fever follows a streptococcal infection, and weight loss, which can typically occur over sev-
usually tonsillitis. eral weeks. Physical signs may include evidence of
Major criteria for diagnosis include: anaemia, sometimes with petechial haemorrhages,
• migratory polyarthritis affecting mainly large joints splinter haemorrhages in the nail beds, splenomegaly
• evidence of carditis with tachycardia, cardiac and finger clubbing. In many cases the manifestations
enlargement, the development of new murmurs are relatively subtle and a high index of suspicion is
and, in severe cases, cardiac failure required if the diagnosis is to be reached. Any child
• choreiform limb movements – Sydenham chorea with known structural heart disease, whether oper-
• a transient demarcated skin rash on the ated on or not, is at risk (though very unlikely with
trunk – erythema marginatum a PDA or a secundum ASD that has been closed
• the development of nodules over bony prominences. surgically or with a device more than 6 months
­
Minor criteria are: ­previously). Should such a patient become chronically
• fever unwell or have prolonged unexplained fever, infective
• arthralgia endocarditis should be considered. Investigations
• previous history of rheumatic fever should include a full blood count and ESR, multi-
• raised erythrocyte sedimentation rate (ESR) or ple blood cultures and careful echocardiography. In
C-reactive protein level the majority of children transthoracic echocardiog-
• prolonged PR interval on ECG. raphy is sufficient to exclude or establish a diagno-
All patients with suspected rheumatic fever should sis, which is in contrast to adult ­recommendations.
have throat cultures and be tested for evidence of Transoesophageal echocardiography may be neces-
streptococcal antibodies (antistreptolysin O (ASO) sary in some children where assessment is suboptimal
titre, anti-DNAase titre). on transthoracic imaging.
Occasionally, infective endocarditis may develop in
a patient with no previously known cardiac defect. The
Diagnosis
responsible organism is most commonly Streptococcus
The diagnosis cannot usually be regarded as estab- viridans or Staphylococcus (both aureus and albus).
lished unless evidence of a recent streptococcal infec- Other organisms include enterococci, Escherichia coli
536
tion is demonstrable (i.e. a positive throat culture or and fungi, especially Candida albicans.
 HEART DISEASE 15.2
Treatment involves intravenous antibiotic therapy adenosine will usually terminate the episode, or
initially, usually for a total duration of antibiotic ther- ­alternatively a DC cardioversion may be needed if the
apy of 6 weeks. Drug choice is guided by identifica- patient is haemodynamically compromised.
tion of the organism and sensitivity of the organism Some patients have recurring and troublesome
to antibiotics. Surgical removal of vegetations may be attacks over many years. If the episodes are infre-
necessary if response to therapy is poor, significant quent, brief or can be easily terminated by Valsalva
damage to valve function occurs, or systemic compli- manoeuvres, some families may opt for conserva-
cations occur. tive management. For the longer, frequent and hae-
Prophylaxis against endocarditis should be advised modynamically significant episodes of tachycardia,
in all patients who are considered to be at risk, and chronic antiarrhythmic drug treatment or invasive
should be administered on occasions when a bacter- transcatheter electrophysiological treatment may be
aemia is likely to result from surgical or dental pro- needed.
cedures. Such procedures include dental extractions
and other dental procedures involving significant
gingival trauma, other oropharyngeal instrumen-
tation and surgery on the bowel and genitourinary Ventricular tachyarrhythmias
tract. Effective cover can usually be achieved with Sustained ventricular tachyarrhythmias are uncom-
amoxicillin (in combination with an aminoglycoside mon during childhood; however, the presence of
to cover ­procedures on the genitourinary or gastro- ventricular premature beats may be detected as
intestinal tract). A single dose of antibiotic, admin- irregularities in the pulse on routine examination
istered an hour prior to the procedure (oral dose) or on a chance ECG. The presence of such pre-
or at induction of anaesthesia (intravenous dose), is mature beats in an otherwise normal child with no
­usually adequate. other evidence of structural defects or heart mus-
cle disease may be benign, and even when prema-
ture beats occur frequently they very rarely lead to
any symptoms or require treatment. It is important,
however, to exclude family history of arrhythmia or
Cardiac arrhythmias cardiomyopathy. In older children, the suppression
Phasic variation in heart rate (sinus arrhythmia) is of ventricular ectopy on exercise stress testing is a
normal in children. It is related mainly to respiration, reassuring sign.
although not exclusively.

Long QT syndrome
Supraventricular tachycardia There are families or individual children who have
This condition is characterized by the sudden onset of prolonged repolarization with increase in the cor-
very rapid tachycardia, usually with a rate of 200–300 rected QT interval on the ECG. These patients are
beats per minute. Affected infants may become pale at risk of ventricular tachyarrhythmias (ventricular
and appear mildly distressed with tachypnoea and poor tachycardia or ventricular fibrillation), typically in
feeding. Heart failure may develop and the appearance association with sudden surges in adrenergic drive
of supraventricular tachycardia in an infant requires (e.g. exercise, morning alarm clock). Any patient
urgent treatment. Older children are often aware of developing dizziness or syncope on exertion should,
their rapid heart rate and observers may notice rapid therefore, be assessed with a view to excluding this
pulsations in the neck. condition, which often is familial and may lead to
The ECG between episodes will show evidence of sudden death.
pre-excitation in Wolff–Parkinson–White syndrome. Treatment may involve antiarrhythmic medication
In other forms of supraventricular tachycardia, the and implantation of an automatic defibrillator.
resting ECG may be normal. The ECG during the epi-
sodes will usually show a tachycardia with a narrow
QRS complex. It is particularly useful for a 12-lead
Heart block
ECG to be recorded during attempts to terminate the
tachycardia. Congenital complete heart block is an uncommon
The acute episode may sometimes be terminated by problem in the newborn period. It may be detected
vagal manoeuvres, such as the application of ice packs on antenatal assessment with fetal bradycardia. As
537
to the face or the Valsalva manoeuvre. Intravenous ECG is difficult to perform, echocardiography can
 15.2 CARDIAC DISORDERS

be used to distinguish complete heart block from

sinus bradycardia. Among affected infants, 50% have Practical points
no structural cardiac abnormality but a range of con-
genital anomalies may be associated with heart block. • Ventricular septal defect (VSD) is the commonest congenital
Those with otherwise normal hearts may have devel- heart defect.
oped heart block due to the presence of maternal auto- • Minor heart defects (small VSD/patent ductus arteriosus
immune antibodies causing damage to the conduction (PDA); mild pulmonary or aortic stenosis) may be well
system, for example in association with maternal sys- tolerated with no symptoms.
temic lupus erythematosus or Sjögren syndrome. • Necessity for treatment depends on careful assessment of
the severity of disturbance to cardiac function and risk of
Some fetuses may develop hydrops and its associated complications (including endocarditis). Some defects (e.g.
complications in utero. small VSD; mild pulmonary stenosis) pose little threat and
The heart rate is usually in the range of 40–70 do not need intervention.
beats per minute and the response of the newborn to • Treatment for congenital heart defects was, in the past,
­bradycardia is variable. Children with symptomatic usually surgical. In the current era, many of the simpler
­bradycardia may require administration of a positive heart defects can be managed with catheter interventions –
but choice of surgery versus catheter procedures still
chronotropic agent (e.g. isoprenaline) or positive ino-
requires careful assessment of the risks and benefits of
tropes whilst waiting for implantation of a temporary the different options.
or permanent pacemaker.

538
 16
PART

HAEMATOLOGICAL
DISORDERS AND
MALIGNANCIES

539
 16.1 Anaemia Paul Monagle

with cardiac disease may tolerate less reduction in

Definition haemoglobin before developing tissue hypoxia, and
Anaemia is a common medical condition throughout all hence often have considerable urgency in treating
ages of childhood. However, the common causes vary their anaemia. No single haemoglobin (Hb) level
with age. Anaemia refers to a reduction in ­haemoglobin can be used as an indication for transfusion therapy
(and hence red cell mass) below that which is consid- as these other factors need to be considered.
ered normal for the patient in question. Normative • in the presence of anaemia, cardiac output must
haemo­globin data differs with age and, in teenage years, be increased to maintain tissue oxygen delivery
sex. Clinicians need to ensure that, when considering a (Hb saturation cannot be increased above 100%).
diagnosis of anaemia, correct age-specific and, where Failure of this compensatory mechanism or
applicable, sex-specific r­ eference ranges are used. These limitation of cardiac output by another disease
reference ranges may vary according to the laboratory will result in tissue hypoxia. Cardiac output is
analyser in use. Thus each laboratory should report determined by cardiac stroke volume and heart rate.
their own specific age-related reference ranges. An Therefore, heart rate is an important measure of the
example of the age-related variation is shown by the ref- stress the anaemia is placing on the patient's cardiac
erence ranges in Table 16.1.1. The majority of reference reserve. All anaemic patients should have their vital
ranges in clinical use reflect 95% confidence intervals, so signs, especially heart rate and respiratory rate,
that 2.5% of individuals who are in fact ‘normal’ would assessed as part of their initial medical evaluation,
be expected to consistently have haemoglobin levels just and these parameters should be used to monitor
below the lower limit of the reported reference range. progress and response to therapy.
• Hb saturation is normally close to 100% in children
without cyanotic congenital heart disease or
significant lung pathology. Thus, in otherwise well
Physiology children with severe anaemia, or children in whom
the Hb saturation is measured as 99–100%, inspired
The prime function of haemoglobin is tissue oxygen oxygen therapy makes little if any contribution to
delivery. Hence anaemia threatens this critical bodily improving tissue oxygenation. Recovery of red cell
function. Acutely, severe anaemia can lead to hypoxic mass (and hence Hb) is the most effective therapy.
tissue injury, and chronic anaemia can lead to growth • in children with cyanotic congenital heart disease
failure and organ dysfunction as a result of chronic or pulmonary pathology, the natural compensation
hypoxia or failure of compensatory mechanisms. for reduced Hb saturation is to increase Hb
The physiology of tissue oxygen delivery is critical to concentration. Hence, if a child with cyanotic
understand, as it enables the clinician to understand congential heart disease who usually has a relatively
the concepts of relative anaemia and to determine increased Hb was to develop a ‘relative anaemia’, they
appropriate treatment of the anaemic patient. might develop symptoms of anaemia at Hb levels
Tissue oxygen delivery (mL/min) that would be considered normal in most children.
= cardiac output ( L/min ) × haemoglobin (g/L) Treatment of ‘relative anaemia’, if required, is based
× haemoglobin saturation (%) × 1.34 (mL/g) on the same principles as treatment of ‘true anaemia’.

where 1.34 is a constant and represents the amount of

oxygen carried by 1g normal haemoglobin.
The key issues in this basic physiological equation
Clinical presentations
are that: Children with anaemia most often present with pallor
• the parameters are multiplied, such that small (reflecting the reduced Hb) or signs of reduced exercise
decreases in cardiac output and haemoglobin and tolerance (reflecting inability to increase tissue oxygen
haemoglobin saturation lead to an overall large delivery to meet the demands of exercise). Reduced exer-
540 decrease in tissue oxygen delivery. Thus patients cise tolerance manifests differently according to age.
 Anaemia 16.1
In infants, poor feeding is often described. In older lethargy are more common. Alternatively, inciden-
children, shortness of breath on exertion or g­ eneralized tal finding of anaemia when full blood examination
has been p­erformed for another indication is also very
Table 16.1.1 Normal haemoglobin values for age common.
Once the presence of anaemia has been confirmed,
Age Haemoglobin (g/L) thorough history-taking and examination of the
Birth 135–200 patient is required. Patient age and the duration of
symptoms is important as a first step in determining
1 month 100–180 the likely aetiology of the anaemia.
In addition, during the history and examination,
2 months 90–140 other key considerations are:
• Is there evidence of cardiac decompensation or
6 months 95–135
other adverse events as a result of the anaemia?
1 year 105–135 This clearly makes appropriate therapy a matter
of urgency.
2–6 years 110–145 • Are there clues to the aetiology of the anaemia?
• Is there evidence of multilineage cytopenias
6–12 years 115–155 (neutropenia and thrombocytopenia)?
> 12 years (female) 120–160
• Is there evidence of an associated, perhaps causative,
disease?
> 12 years (male) 130–180 Information that assists in answering these questions is
shown in Table 16.1.2.

Table 16.1.2 Relevant information required on history and examination for patients with anaemia

Critical question Information obtained on history and examination

Cardiac decompensation Exercise tolerance

Heart rate and respiratory rate
Signs of congestive heart failure
Altered conscious state, irritability, restlessness

Aetiology Duration of symptoms (bone marrow failure and haematinic deficiency usually have a longer duration
of symptoms)
Family history (hereditary spherocytosis, G6PD deficiency, haemoglobinopathies and others are inherited
causes of anaemia. Maternal history (e.g. veganism may be associated with B12 deficiency in infants)
Birth and neonatal history (blood loss at birth, birth asphyxia and maternal blood group compatibility
are all important in assessing neonatal anaemia. Jaundice at birth may give a clue to an episodic
haemolytic disorder in older children)
Presence or absence of jaundice (haemolysis)
Drug exposure: as a cause of haemolysis, or bone marrow suppression
Blood loss: trauma, recent surgery, iatrogenic in neonates, epistaxis, menstrual loss
Dietary history: iron deficiency can be predicted in infants less than 12 months of age fed cow's milk, or
in toddlers who have failed to transfer to solid foods adequately

Multilineage cytopenias Bruising or bleeding, especially petechiae (thrombocytopenia)

Infection, mouth ulceration (neutropenia)

Associated disease Gastrointestinal symptoms (e.g. coeliac disease, inflammatory bowel disease)
Joint or bone pain (e.g. leukaemia, sickle cell disease, arthritis)
Renal disease
Malignancy
Infection: as a primary cause (e.g. malaria), a precipitant of acute deterioration in a more chronic
anaemia, or a trigger to acute haemolysis
Neurological disorders, developmental delay/regression, failure to thrive may reflect functional B12
deficiency in infants. Pica may be associated with iron deficiency
Eating disorders in older children
Bleeding disorders
541
 16.1 HAEMATOLOGICAL DISORDERS AND MALIGNANCIES

and evidence of regeneration will usually suggest the

Initial investigations cause of the anaemia and direct the next stage of
Progressive selective investigation, guided by the his- investigation. The presence of abnormal leukocytes
tory, the clinical findings and the result of the blood or abnormal platelet numbers may suggest a specific
count, is recommended. The first investigation will be diagnosis such as leukaemia. Examples of a normal
a blood count, which automatically includes red cell blood film and blood films in some conditions associ-
indices (full blood examination (FBE) or complete ated with anaemia are shown in Figure 16.1.1. Further
blood count (CBC)), reticulocyte count and exami- investigations are suggested by the algorithms in
nation of the blood film. These initial investigations Figures 16.1.2 and 16.1.3.
will usually allow classification of the anaemia. The
presence or absence of polychromasia on the blood
film, and the reticulocyte count, enable the anaemia
to be classified as regenerative or aregenerative. This Practical points
is a most important initial decision to be made. The
red cell indices, in particular the mean corpuscular vol- Determining the urgency of investigation of anaemia
ume (MCV), and the blood film, enable the anaemia • Mild anaemia (Hb >  8 g/L) may still require urgent
investigation and management, depending on the cause.
to be classified by red cell size into microcytic, normo- Hence, until the cause of anaemia has been determined
cytic and macrocytic. Finally, the blood film enables in a broad sense, discharge from emergency department/
any specific red cell morphology to be determined, and hospital should not be considered.
confirms the platelet and leukocyte parameters. At this • Acute regenerative anaemia (blood loss or haemolysis)
stage, a probable aetiology is likely and thus the direc- has the capacity rapidly to develop severe anaemia.
tion of further investigations can be determined. Blood loss is usually obvious, so haemolysis must be
excluded or the rate of haemolysis (multiple Hb levels
In the interpretation of these initial tests, there are over a number of hours) understood before a patient can
a number of important considerations. First, sample safely leave hospital. Thus, a FBE, reticulocyte count, blood
integrity is vital, and preanalytical variables such as a film examination and serum bilirubin are almost always
clotted or inadequately mixed specimen can cause sig- indicated in initial investigations.
nificant erroneous results. If the results do not match • Megaloblastic anaemia in infancy, irrespective of the level
the clinical findings, repeat testing should always be of anaemia, requires urgent investigation because of the
potential for rapid neurological deterioration. Hence the
considered. Second, MCV also varies with age. MCV
MCV is a crucial piece of information in the initial FBE, as
is highest in the neonate (98–118 fL), falls to its low- is the blood film examination. A history of failure to thrive
est value between 6 and 24 months of age (79–86 fL, and neurological impairment in infancy should lead to
then increases progressively throughout childhood consideration of megaloblastosis, as anaemia is often not
(75–92 fL). A low MCV indicates microcytosis and the presenting symptom. A FBE with careful consideration
a high MCV indicates macrocytosis. Reticulocyte of the red cell parameters is always warranted in this
counts may be expressed as a percentage of the total circumstance.
red cell count (3–7% in the neonate, thereafter 0–1%), • Anaemia as part of a multilineage failure may have a
degree of urgency because of the potential for febrile
or more usually as an absolute count (normally 20–100 neutropenia or thrombocytopenic haemorrhage.
× 109/L). If expressed as a percentage, the reticulocyte
count can be misleading, so an absolute count is pref-
erable. An increased reticulocyte count indicates active
regeneration of red cells, seen after blood loss, haemol-
ysis or in response to correct haematinic therapy. Blood Specific disease entities
loss and previous haematinic therapy can usually be Disorders of stem cell proliferation
excluded on history, so that an increased reticulocyte
count is often suggestive of haemolysis. A low reticu-
Pluripotential stem cell failure (aplastic anaemia)
locyte response in the presence of anaemia indicates a Normal marrow function is dependent on stem cell
lack of marrow response, because of a deficiency of renewal and maturation of all cell lines. Failure of
the necessary iron or vitamins or inappropriate ther- stem cell proliferation and differentiation results in
apy for the anaemia, or inability to respond, such as aplastic anaemia. Both genetically determined and
marrow ­aplasia or infiltration. acquired forms occur (Table 16.1.3).
Fanconi anaemia
Examination of the blood film
Fanconi anaemia, the commonest of the genetic
This is as important as the evaluation of the red cell forms of aplastic anaemia, is recessively inherited and
indices, leukocyte count and platelets. The p
­ resence of is characterized by a variable phenotype, progressive
542
abnormal red cell size, shape, inclusions, Hb c­ ontent, marrow failure and an increased risk of m ­ alignancy.
 Anaemia 16.1

A B

C D

E F

Fig. 16.1.1 Blood films. (A) Normal. (B) Macrocytosis – note hypersegmented polymorph. (C) Spherocytes in hereditary spherocytosis.
(D) Autoimmune haemolytic anaemia showing red cell agglutination. (E) Sickle cell disease. (F) Thalassaemia major showing
hypochromic microcytes and macrocytes, with nucleated red cells.

There appear to be multiple gene defects in this stenosis of auditory canals, micro-ophthalmia, hypogen-
condition, which explains the diversity of clinical italism and a variety of anomalies of the gastrointestinal
manifestations. tract may also occur. The child shown in Figure 16.1.4
Approximately 75% of children have congenital abnor- has many features of this disorder.
malities, with a wide range of defects. The commonest The diagnosis may be suspected at birth if there are
are café-au-lait spots, short stature, microcephaly and congenital abnormalities. Haematological abnormalities
skeletal anomalies, with thumb and radial hypoplasia are rare at birth. Pancytopenia develops gradually, usu-
543
or aplasia being most characteristic. Renal anomalies, ally by the age of 10 years. Onset is earlier in boys than
 Polychromasia/increased reticulocytes:
regenerative anaemia

Consider blood loss,

Biochemical markers No
recently treated
of haemolysis* haematinic deficiency,
or recovering aplasia
Yes

Consider problems intrinsic or

extrinsic to the red cells#

Intrinsic problems: Extrinsic problems:+

1. Membrane: hereditary spherocytosis 1. Antibody mediated
or pyropoikilocytosis (in newborns) 2. Mechanical
2. Enzyme: G6PD deficiency, pyruvate 3. TTP/HUS
kinase deficiency, rare defects 4. Infection (severe sepsis, malaria)
3. Haemoglobin: thalassaemia, sickle cell, 5. Drugs
other haemoglobinopathies, unstable
haemoglobin

Relevant investigations:##
1. Direct antiglobulin (Coombs’) test, viral
serology, mycoplasma serology
Relevant investigations:** (if cold antibody)
1. E5M 2. Imaging of cardiac lesion or to search
2. G6PD assay for vascular anomaly
3. Hb electrophoresis/HPLC, sickle 3. Renal function
solubility, DNA analysis, isopranolol 4. Blood cultures, thick and thin films
or heat stability test if relevant

Reasonable first line investigation screen in haemolytic patients includes FBE, reticulocyte count, serum bilirubin, E5M,
G6PD assay, Hb HPLC, DAT, renal function, and in neonates urine and blood culture.

BEWARE: Severe intravascular haemolysis (G6PD, some antibodies, microangiopathic (TTP/HUS, mechanical, sepsis))
may release free Hb which falsely elevates the measured haemoglobin. Always check that the red cell count is proportional
to the measured Hb. Methaemoglobinaemia in severe G6PD haemolysis may increase tissue hypoxia for any given measured
haemoglobin. All acute haemolytic anaemias have the potential for life-threatening haemolysis to develop within hours and as
such should be treated with extreme caution. In general, admission to hospital, close monitoring of vital signs and FBE until
the tempo of the haemolysis is established is recommended. Folate deficiency in haemolysis may reduce the ability of the
bone marrow to respond and worsen the anaemia as well as causing diagnostic confusion.

* Biochemical markers of haemolysis: in most cases the presence of an elevated unconjugated serum bilirubin is sufficient. Haptoglobins and
LDH are frequently non contributory in small children.
# Blood film may be diagnostic. E.g. G6PD-blister and bite cells, spherocytosis (in neonates reflects either HS, ABO incompatability or
severe sepsis), sickle cells.
** E5M requires less than 0.5 mL and is offered by many laboratories. G6PD assay may be elevated in the presence of a reticulocytosis so
borderline results should be repeated after the acute event and at least 3 months post transfusion if the clinical and blood film findings are
suggestive. Most laboratories perform HPLC to detect abnormal haemoglobins and use electrophoresis to identify abnormal bands.
DNA testing should not be ordered acutely, but as a confirmatory test electively. HPLC and sickle solubility are most useful initial tests.
+ Antibody mediated haemolysis may be warm (usually IgG, spherocytes on film) or cold (usually IgM, +/– complement fixation, agglutination
on film). Haemolysis due to mechanical, TTP/HUS or severe sepsis (DIC) are usually characteristically microangiopathic in blood film
morphology.
## The Direct Antiglobulin (Coombs’) Test (DAT) is crucial to perform in all haemolysing children as IgG mediated haemolysis can be life
threatening, and so the diagnosis should not be missed.

Fig. 16.1.2 Further investigation and initial management of regenerative anaemia. DAT, direct antiglobulin test; DIC, disseminated
intravascular coagulopathy; E5M, eosin-5-maleimide; FBE, full blood examination; G6PD, glucose-6-phosphate dehydrogenase;
544 Hb, haemoglobin; HPLC, high-performance liquid chromatography; HUS, haemolytic–uraemic syndrome; Ig, immunoglobulin;
TTP, thrombotic thrombocytopenic purpura.
 Anaemia 16.1
Aregenerative anaemia

Microcytic Normocytic Macrocytic

Likely causes: Likely causes: Likely causes:

1. Iron deficiency 1. Acute blood loss 1. Megaloblastosis
2. Beta Thalassaemia minor 2. Red cell aplasia* a.Vitamin B12
or alpha thalassaemia a.DBS b.Folate
3. Chronic disease/ b.TEC 2. Fanconi’s anaemia
inflammation 3. Bone marrow failure 3. Dyserythropoietic anaemias
Rare causes: 4. Bone marrow 4. Hypothyroidism
4. Lead poisoning replacement/infiltration 5. Liver disease
5. Sideroblastic anaemia/ 5. Renal disease
Pearson syndrome 6. Anorexiaprotein
malnutrition

Relevant Investigations: Relevant investigations: Relevant investigations:

1. Ferritin # 1. Bone marrow aspirate 1. Bone marrow aspirate**
2. HPLC, DNA analysis, 2. Renal function If clinically indicated:
family studies 3. Search for clinical 2. Serum B12, folate, urine
If rare causes suspected: bleeding site if indicated MMA, serum homocysteine,
1. Serum lead TCII levels
2. Bone marrow aspirate 3. DEB chromosomal fragility
4. Liver function
5. Thyroid function

BEWARE: Megaloblastic anaemia in infancy (<2 years) is often accompanied by severe failure to thrive and
neurodevelopmental regression. Often these patients deteriorate very rapidly once they have finally reached medical attention,
and investigation is a matter of urgency so that replacement therapy can be commenced ASAP and long term neurological
sequelae minimized. The bone marrow aspirate confirms megaloblastic tissue quickly, such that treatment can be commenced
pending further investigations of the child and if a breastfed infant, investigation of the mother for Vitamin B12 or folate deficiency.

*Red cell aplasia may be isolated or part of a broader marrow dysfunction. The differential between transient erythroblastopenia of childhood (TEC)
and Diamond-Blackfan Syndrome (DBS) is often difficult, even with thorough investigations.
# Investigation of iron deficiency in children needs to be appropriate. In children with a classic history of cow’s milk intake before 12 months, or
inadequate transition to solids, no investigations may be required after the blood film diagnosis, and treatment should be commenced. In otherwise
normal children, ferritin is the most useful investigation and other iron studies are rarely contributory. Ferritin is an acute phase protein, so testing
may need to be delayed if an acute febrile illness is coexistent. Full iron studies may be of value in children with complex medical problems.
** In the absence of clear renal, liver or thyroid disease, bone marrow aspirate is indicated for most significant normocytic or macrocytic anaemias.
Bone marrow aspirates must always be examined in conjunction with the peripheral blood smear, and ancillary investigations. Hence consultation
with a haematologist early in the investigation of such patients is often worthwhile. With the exception of megaloblastic anaemia, where bone
marrow examination is often an emergency procedure to allow commencement of replacement therapy immediately, BMA can often be performed
electively, and should never delay transfusion of a borderline or decompensating patient. In cases of suspected aplasia, bone marrow trephine
may assist in assessing marrow cellularity.

Fig. 16.1.3 Further investigation of aregenerative anaemia. DBS, Diamond–Blackfan syndrome; DEB, diepoxybutane; HPLC,
high-performance liquid chromatography; MMA, methylmalonic acid; TCII, transcobalamin II; TEC, transient erythroblastopenia of
childhood.

girls. Macrocytosis is followed by t­hrombocytopenia, cytopenic at birth and have radial anomalies without
neutropenia, then anaemia. Bone marrow aspirate and thumb abnormalities.
trephine show hypoplasia or aplasia. The diagnosis of Fanconi anaemia is established
In contrast, infants with the ­thrombocytopenia– by special chromosome studies of lymphocytes.
545
absent radius (TAR) syndrome are severely thrombo- Chromosomes from patients with Fanconi anaemia
 16.1 HAEMATOLOGICAL DISORDERS AND MALIGNANCIES

Table 16.1.3 Causes of anaemia due to defective stem cell proliferation

Pathological process Aetiology Disease entity Usual age of presentation

Pluripotential stem cell failure Congenital Fanconi anaemia Variable, majority < 10 years
Acquired Aplastic anaemia Any age
Drugs
Infection
Idiopathic

Erythroid stem cell failure Congenital Blackfan–Diamond syndrome Neonate to 1 year

Acquired < 5 years
Idiopathic Transient erythroblastopenia
of childhood
Erythropoietin deficiency Chronic renal failure
Hypothyroidism
Unknown Chronic infection
Chronic inflammatory disease

Bone marrow replacement Malignant transformation Leukaemia Infant–adult

of progenitors
Marrow infiltration Disseminated malignancy
Abnormal accumulation of Lipid ‘storage’ disease
metabolic substrates

show markedly increased spontaneous and alkylating

agent (cells incubated with mitomycin C or diepoxybu- level of 80 g/L and a white cell count of 1.4 × 109/L with
tane) induced chromosomal breaks, gaps, rearrange- neutrophils 0.7 × 109/L. The platelet count was 25 × 109/L.
A bone marrow aspirate showed hypocellular fragments,
ments, exchanges and endoreduplication. Antenatal
and trephine biopsy confirmed marrow aplasia. Cytogenetic
diagnosis is possible. studies on peripheral blood lymphocytes confirmed that
Androgen therapy may produce long remissions of John had Fanconi anaemia by showing an increased rate
the anaemia but has little effect on thrombocytope- of spontaneous and mitomycin C-induced chromosome
nia and neutropenia. Its use is associated with mas- breaks. His sister was found to be HLA-identical with normal
culinization and is therefore undesirable in young cytogenetic studies, and plans were made for elective bone
children, particularly girls. Granulocyte–macrophage marrow transplantation within the next few months.
colony-stimulating factor has been used with some
success. Bone marrow transplantation offers the only Acquired aplastic anaemia
­possibility of cure of the aplasia. Supportive care with A number of agents may cause marrow failure, either
­transfusions and antibiotics is required for patients in a dose-dependent fashion (irradiation and cyto-
without a marrow donor, but death from infection, toxic drugs) or in an idiosyncratic fashion. Some viral
bleeding or the development of leukaemia usually infections are associated with marrow suppression.
occurs within a decade of diagnosis. No cause is identified in about 50% of children with
marrow failure. Fanconi anaemia must be excluded by
cytogenetic studies, as not all affected individuals have
congenital abnormalities.
Clinical example
Common causes are:
John, aged 5 years, presented with pallor • drugs: chloramphenicol, anticonvulsants, non-steroidal
and bruising of several months duration. He anti-inflammatory agents and cytotoxic drugs
had a past history of tracheo-oesophageal • chemicals: benzene, organic solvents, insecticides
fistula and had always been small, with • viral hepatitis: usually non-A, non-B, non-C
his height and weight on the third centile for age. His hepatitis, less commonly Epstein–Barr virus,
teacher had expressed concern about his hearing. On
cytomegalovirus, parvovirus or human
examination he was pale and had multiple bruises and
several café-au-lait spots. He had a convergent squint
immunodeficiency virus (HIV)
and his external auditory canals were narrow. There • preleukaemic: acute lymphoblastic leukaemia
was no hepatosplenomegaly or lymphadenopathy. occasionally has a transient period of aplasia before
A blood test showed a macrocytic anaemia with a Hb the onset of the disease
546
• paroxysmal nocturnal haemoglobinuria.
 Anaemia 16.1
donor exposure through the appropriate selection
of blood products. Early referral to a tertiary cen-
tre is vital. Although a small number of children will
recover within a few weeks, bone marrow transplan-
tation from an HLA-compatible sibling is generally
regarded as the treatment of choice for severe aplastic
anaemia, particularly in those aged under 5 years. Only
30% of children will have a matched sibling donor. For
the remainder, antithymocyte globulin, together with
granulocyte colony-stimulating ­factor and cyclospo-
rine, produces improvement or complete recovery in
about two-thirds of children. Onset of response may
not occur for 2–3 months after initiation of therapy,
and supportive care during this time is vital. For those
failing to respond, unrelated donor transplantation is
an option and a donor search should be initiated early.

Red cell aplasia (erythroid stem cell failure)

Isolated aplasia of red cells results in a normocytic
normochromic anaemia without reticulocytosis. The
platelets and white blood cells are normal. Congenital
and acquired forms occur.
Congenital red cell aplasia (Diamond–Blackfan
­syndrome). This disorder is almost certainly hetero-
geneous, with sporadic, dominant and recessive forms
occurring. Faulty ribosome biogenesis, resulting in
pro-apoptotic erythropoiesis leading to erythroid fail-
ure, is hypothesized to be the underlying defect.
Normocytic anaemia may be present at birth and
usually is evident by 2–3 months of age. However,
diagnosis beyond 1 year of age is reported. Early treat-
ment with steroids results in a reticulocytosis and an
increase in Hb levels in about two-thirds of patients.
Fig. 16.1.4 Child with Fanconi anaemia. Note short stature,
In steroid responders, long-term low-dose steroids are
absent right radius and thumb, micro-ophthalmia and the
presence of a hearing aid. recommended before total weaning is attempted. Some
steroid-responsive patients are successfully weaned off
steroids, but many remain steroid-dependent. Those
Presentation is with the gradual onset of pallor, leth- failing to respond to steroids or requiring large doses
argy and bruising. There may be a history of recent will need regular blood transfusion and chelation ther-
infection. Physical examination reveals little other than apy. Bone marrow transplantation has corrected the
pallor, bruising, petechiae and oral mucosal bleeding. condition in steroid-resistant patients.
Importantly there is no enlargement of liver, spleen or Acquired red cell aplasia. Pure red cell aplasia (PRCA)
lymph nodes, but there may be fever and focal infec- is primarily a disease of adults but cases have been doc-
tion associated with the neutropenia. umented in teenagers. A large number of d ­ isorders,
The blood shows a pancytopenia with a normocytic including thymoma, malignancy, a­utoimmune dis-
anaemia without regeneration. Bone marrow aspi- ease, viral infection and drug administration, have
rate and trephine biopsies reveal absent or decreased been implicated. Therapy is directed primarily toward
haemopoiesis. the cause but may include immunosuppression, plas-
Initial management depends on the severity and clin- maphaeresis, thymectomy and splenectomy.
ical manifestations of the aplasia. Potentially causative Transient erythroblastopenia of childhood (TEC).
agents must be removed. Infections are treated vigor- This self-limiting aregenerative anaemia occurs typi-
ously. Supportive red cell and platelet transfusions are cally in children between 1 and 3 years of age. The aeti-
given as required. The general principles of transfusion ology remains unclear but antibodies directed against
therapy in aplastic anaemia are to avoid HLA sensiti- early red cell precursors have been documented in
zation by using leukocyte-depleted ­cellular products, some children. Parvovirus B19 has not been isolated 547
and to minimize alloimmunization by m ­ inimizing consistently.
 16.1 HAEMATOLOGICAL DISORDERS AND MALIGNANCIES

The typical presentation is with pallor of gradual and immature granulocytes (left shift) may be seen in
onset in an otherwise well child. The only abnormal the peripheral blood (leukoerythroblastic blood pic-
clinical finding is pallor. The anaemia may be marked, ture). Replacement of marrow with storage cells (e.g.
without evidence of regeneration. A bone marrow Gaucher disease), fibrous tissue (myelofibrosis) or
aspirate will generally show absent or diminished bone (osteopetrosis) will have a similar result. Careful
erythropoiesis, but if spontaneous recovery is already examination of the blood film looking for leukae-
occurring at the time of presentation there may be mic blasts, and a bone marrow examination that will
many early erythroid progenitors present. identify abnormal cells, are required in any child with
As the onset of the anaemia is gradual, most chil- pancytopenia.
dren will have compensated well and tolerate quite
marked degrees of anaemia. If, however, there is no
Dyserythropoietic/ineffective erythropoiesis
evidence of recovery occurring by the time the Hb
level falls to below 50 g/L, transfusion is likely to be Congenital dyserythropoietic anaemias
required. Folic acid supplements should be given dur-
This group of rare hereditary disorders of erythro-
ing the recovery phase. Spontaneous recovery usually
poiesis is characterized by ineffective erythropoiesis
occurs within 1–2 months and it is unusual for more
resulting in shortened red cell survival with associ-
than one transfusion to be required. Steroids have no
ated jaundice, a variable degree of anaemia, with
role in the management of this disorder.
normocytic to macrocytic red cell morphology, and
In some cases the distinction between Diamond–
anisopoikilocytosis and fragmentation in some types
Blackfan syndrome (DBS) and TEC is extremely diffi-
(Table 16.1.4). Bone marrow findings are character-
cult. Neither the clinical scenario nor the bone marrow
ized by erythroid hyperplasia, multinuclearity and
findings are absolutely diagnostic. In such cases, trans-
internuclear bridging. The aetiology is unknown.
fusion therapy without steroids may be useful initially
Some patients in whom haemolysis is severe require
to enable the patient every opportunity to recover. If
regular transfusions.
steroids are introduced early, on the presumption of
DBS, and recovery occurs, one is reluctant to cease ste-
roid therapy quickly for fear of relapse, and a spon- Megaloblastic anaemia
taneously recovering TEC could potentially receive
Megaloblastic anaemias in childhood are rare but
unnecessary steroids for a prolonged period.
prompt diagnosis of the cause, especially in infants,
Transient erythroid aplasia in chronic haemolytic
is important to prevent potentially irreversible neuro-
anaemias. An aplastic crisis may occur in patients with
logical damage, which may result from deficiencies of
one of the chronic haemolytic anaemias, such as sickle
vitamin B12 or its transport protein transcobalamin II.
cell disease, hereditary spherocytosis and autoimmune
haemolytic anaemia. Infection with human parvovi- Vitamin B12 deficiency
rus B19 has been documented as the usual cause. Folic Because the daily requirement for vitamin B12 is low
acid deficiency may be a further precipitating factor. and body stores are generally high, dietary deficiency
Because of the shortened red cell survival, there is of vitamin B12 is rare, occurring only after prolonged
a precipitous fall in Hb concentration when erythroid inadequate intake, as may occur in vegans. Breastfed
proliferation ceases. Pallor and lethargy develop rela- infants of vitamin B12-deficient mothers are at risk
tively quickly. The absence of jaundice, lack of increase and may present with anaemia in the first year of life.
in the degree of splenomegaly and absence of a reticu- The commonest causes of maternal deficiency are
locyte response enables an aplastic crisis to be distin- undiagnosed pernicious anaemia and veganism. In
guished from increased haemolysis. Blood transfusion infants with megaloblastosis it is important to deter-
is likely to be required. Spontaneous recovery usually mine whether maternal deficiency, transcobalamin
begins within 10–14 days. II deficiency or a cobalamin pathway defect is the
cause. Maternal deficiency requires short-term paren-
teral therapy of the infant; however, transcobalamin
Marrow replacement
II deficiency requires long-term high-dose parenteral
Infiltration with neoplasia, particularly leukaemia, B12 injections. The majority of older children with
is the commonest cause of marrow failure in child- vitamin B12 deficiency have a malabsorptive problem,
hood. Several other childhood malignancies (neuro- either specific to vitamin B12, as in pernicious anaemia,
blastoma, non-Hodgkin lymphoma, Ewing sarcoma or secondary to inflammation or loss of the ileum,
and rhabdomyosarcoma) metastasize to the bone the portion of the small bowel in which vitamin B12
marrow. Progressive pancytopenia with a normocytic absorption occurs.
anaemia and an associated shift to the left in the ery- Vitamin B12 deficiency results in an anaemia with
548
throid and myeloid series develops. Nucleated red cells oval macrocytosis, hypersegmentation of ­neutrophils
 Anaemia 16.1
Table 16.1.4 Anaemias that are due to ineffective erythropoiesis and dyserythropoiesis

Pathological process Aetiology Disease entity Usual age of presentation

Impaired DNA synthesis Unknown Congenital dyserythropoietic Infancy to adulthood

(megaloblastosis) anaemia
Vitamin B12 deficiency
Congenital Transcobalamin II deficiency Neonate to 12 months
Cobalamin pathway defect Neonate to 12 months
Congenital pernicious anaemia < 3 years
Acquired Maternal B12 deficiency 3–12 months
Juvenile pernicious anaemia < 10 years
Ileal resection Any age
Regional ileitis Any age
Blind loop syndrome Any age
Folate deficiency
Congenital Rare metabolic abnormalities Infancy
Acquired Dietary deficiency Any age
Malabsorption (coeliac disease) > 6 months
Increased utilization (haemolysis) Any age

Defective haem synthesis Iron deficiency Dietary deficiency Infancy, adolescence

(microcytosis) Malabsorption Any age
Blood loss
Occult
Overt

Reduced/absent Gene deletion/ β-thalassaemia major 6 months to 5 years

globin-chain synthesis mutation HbH disease (α-thalassaemia) Any age
Thalassaemia traits > 6 months

Abnormal globin-chain Gene mutation/amino Haemoglobinopathies Any age

production acid substitution Sickle cell disease 1–4 years

and thrombocytopenia. Bone marrow examina- Extra folate is required at times of rapid growth,
tion shows erythroid hyperplasia with megaloblas- during pregnancy and in patients with haemolytic
tosis characterized by abnormally large erythroid anaemia. Deficiency is most likely to occur under these
and myeloid progenitors, in which nuclear maturation circumstances. Dietary deficiency most commonly
is delayed compared with cytoplasmic maturation. occurs in infants fed exclusively on goat's milk, which
Intramedullary destruction of erythroid precursors is deficient in the vitamin. Malabsorption occurs in
leads to a mild unconjugated hyperbilirubinaemia. generalized malabsorptive syndromes such as coeliac
Raised serum homocysteine and urinary methyl disease and Crohn's disease.
­malonic acid are useful to confirm the presence of Some anticonvulsant drugs (e.g. phenytoin) may inter-
intracellular vitamin B12 deficiency. fere with folate absorption, and megaloblastic changes
Therapy depends on the cause of the vitamin B12 are common among patients taking these drugs.
deficiency. Dietary deficiency is treated by an initial Inherited disorders of folate metabolism are rare
dose of parenteral vitamin B12, followed by dietary and may present diagnostic difficulty.
correction. Abnormalities of absorption, whether Folate deficiency presents with a macrocytic anae-
due to pernicious anaemia, ileal malabsorption or mia without neurological abnormality. Oral adminis-
resection, require long-term intramuscular injec- tration of folic acid is effective in reversing deficiencies.
tion of the vitamin (hydroxycobalamin) at 1–3- Doses required are small, as 0.1 mg daily produces an
month intervals according to the severity of the optimal haematological response. In patients with
malabsorption. increased requirements or malabsorption, higher doses
of 0.5–5 mg daily are given. It is essential to exclude
Folate deficiency coexistent vitamin B12 deficiency before treatment as
Daily folate requirements are low, but body stores are the haematological picture may improve initially with
small. Folate is heat-labile and, although ubiquitous in folate therapy, but progression of the neurological
549
food, is often destroyed by cooking. effects of vitamin B12 deficiency will still occur.
 16.1 HAEMATOLOGICAL DISORDERS AND MALIGNANCIES

Defective haem synthesis tion and transferrin binding falls and there is reduced
intracellular iron availability for haem synthesis, with
Iron deficiency
a consequent reduction in Hb production, leading to
Iron deficiency is the commonest cause of anaemia microcytosis and the development of anaemia.
in childhood, being particularly common in the first Symptoms of early iron deficiency with no or
2 years of life when iron requirements are increased minimal anaemia may include poor attention span
­
because of rapid growth and dietary intake is often and ­irritability. As anaemia develops, cognitive deficits
inadequate. Early adolescence is another risk period may increase and lethargy and pallor become appar-
for development of iron deficiency because of rapid ent. Some chronically iron-deficient children exhibit
growth. pica (the ingestion of non-food items such as dirt and
Low-birth-weight infants and infants having clay, and chewing of ice).
exchange transfusions or frequent blood sampling Examination reveals pallor, most easily detected in
have low total body iron stores and are at high risk the palmar creases and conjunctivae. Signs of cardiac
of early development of iron deficiency anaemia, as decompensation will occasionally be present if the
iron stores and dietary intake are inadequate to keep anaemia is severe. Mild splenomegaly is found occa-
up with rapid postnatal growth. Breast milk and cow's sionally but is more common in thalassaemia minor,
milk have a similar iron content but iron bioavailabil- from which iron deficiency must be distinguished.
ity from breast milk is approximately 50%, compared Therapy of iron deficiency involves correction of
with 10% from cow's milk. Breastfed term babies the underlying cause and replenishment of iron stores.
therefore are rarely iron-deficient in the first 6 months Improvement in the dietary intake of iron-containing
of life, but iron concentrations in breast milk decline foods is the most important strategy in the major-
postnatally and the iron content of breast milk is ity of iron-deficient children. Reduction in the total
insufficient to meet the needs of the infant over the milk content of the diet may be necessary to allow the
age of 6 months. child to develop an appropriate appetite. If a source
Oral iron supplementation (2 mg/kg daily) is given of blood loss is identified, appropriate therapy is
to low-birth-weight infants, generally from approxi- ­undertaken and iron supplements are given until the
mately 3 months of age. Iron-containing foods should deficiency is corrected.
be introduced by 6 months of age to all term babies. Therapeutic iron is optimally given orally in two to
Most infant formulae are iron-fortified. Infants three divided doses daily in a dose of 6 mg per kg per
weaned early on to cow's milk (before 12 months of day of elemental iron. Absorption is enhanced when
age), particularly those in whom milk continues to be iron is taken with vitamin C and between meals, but
the major component of the diet without the appropri- the side-effects of abdominal discomfort are reduced
ate introduction of mixed solid feeding, are the group when iron is taken with food. Ferrous sulphate is
presenting most commonly with gross iron deficiency. cheaper and better absorbed than ferrous gluconate,
In some, iron deficiency is exacerbated by the devel- although the gluconate is better tolerated. A reticulo-
opment of cow's milk protein enteropathy, leading to cyte response to iron should be seen within 7–10 days,
peripheral oedema secondary to hypoalbuminaemia in but iron therapy should continue for 3 months to
addition to anaemia. replenish iron stores. The stools are grey–black in
Older children with diets poor in iron-containing ­individuals on iron.
foods (red meat, white meats, legumes, green vegeta-
bles, egg yolk) are also at risk. Blood loss must always
be considered in an iron-deficient child or adolescent
without an appropriate dietary history. Menorrhagia Clinical example
is an important cause of iron deficiency in adolescent
girls. Occult blood loss is usually gastrointestinal in Tan, a 15-month-old boy, had been breastfed for
10 months and then was given cow's milk. He
origin, from such diverse causes as cow's milk enter-
had occasional solid foods only, and rarely had
opathy, polyps, haemangiomas, Meckel's diverticulum any foods with a significant iron content. He had
and hereditary telangiectasia, but repeated epistaxes become irritable, seemed to be low in energy and slept more
and chronic blood loss from the renal tract must be than his parents thought was usual. When he was seen by
excluded. his doctor because of an upper respiratory tract infection,
Iron malabsorption is uncommon and is usually he was noted to have pale conjunctivae and pale palmar
associated with malabsorption syndromes such as coe- creases.
Tan's Hb level was 51 g/L, his MCV was 51 fL, and his mean
liac disease or chronic inflammatory bowel disease.
corpuscular haemoglobin concentration (MCHC) was 15 pg.
Iron deficiency initially leads to depletion of marrow The total WBC was normal and his platelet count was
iron stores without any haematological ­abnormality. 432 × 109/L. The blood film showed microcytic and
550
When iron stores are exhausted, serum iron concentra-
 Anaemia 16.1
b-Thalassaemia
hypochromic red cells; there was no reticulocytosis and no
basophilic stippling. The serum ferritin concentration was
β-Thalassaemia occurs as a result of point mutations
4 μg/L (normal range 16–300). or deletions within one or both of the two β-globin
Tan's anaemia had all the features of an iron-deficiency genes, resulting in reduced or absent production of
anaemia due to a deficient iron intake in his diet. A dietitian β-globin chains. The heterozygous state is termed thal-
assisted in instructing his mother in ways to improve his assaemia minor and the homozygous state thalassae-
diet by including foods such as red and white meats, green mia major.
vegetables, legumes and egg yolks. Tan was given ferrous
b-Thalassaemia minor. Affected individuals are usu-
gluconate mixture at a dose of 6 mg/kg of expected weight
per day, to be taken as two doses daily. His parents were
ally asymptomatic, with mild anaemia detected either
asked to give this with orange juice to improve absorption. during investigation of another illness or as a result of
They were warned that the mixture could make Tan's stools family screening. Mild pallor and splenomegaly may
a grey–black colour, but that this was not of concern. They be noted, but the examination is often unremarkable.
were asked to brush his teeth after each dose to prevent any There is a mild microcytic hypochromic anaemia with
minor staining. They were warned of the toxic effects of iron occasional target cells. The differential diagnosis is
if taken in overdose accidentally by an inquisitive toddler;
iron deficiency, although both may coexist. The HbA2
the mixture was provided in limited amounts only in a bottle
with a safety top, and they were asked to keep it in a secure level is raised. If present, iron deficiency may mask
place, preferably a locked cupboard. the thalassaemia minor, preventing diagnosis until the
The iron mixture was continued for 3 months. Tan's iron deficiency is corrected.
reticulocyte count rose in a few days, and his Hb level began b-Thalassaemia major (Cooley anaemia). This is
to rise in 10 days. By 6 weeks of therapy, the Hb concentration caused by the inheritance of two abnormal β genes. At
was normal; the iron mixture was continued for another birth, the haemoglobin is normal but, as the γ–β switch
6 weeks to ensure that his iron stores were replenished.
occurs, there are no (β0) or insufficient (β+) β chains to
balance α chains. Excess α chains precipitate, causing
It is rarely necessary to use the parenteral route for shortened red cell survival with destruction within the
iron administration but, in occasional children with bone marrow (ineffective erythropoiesis) and spleen.
poor absorption or poor compliance, intravenous HbA production is inadequate to compensate for the
infusions of iron may be required. gradual fall in HbF as γ-chain production switches to
inadequate β-chain production.
Children with thalassaemia major usually pres-
Haemoglobinopathies ent between 3 months and 1 year of life with pallor
Haemoglobin is a compound protein made up of two and hepatosplenomegaly. There may be mild jaun-
pairs of globin chains with a haem molecule inserted dice. Occasionally presentation is delayed to 4–5 years,
into each. One of these globin chains is designated as with these children having increased skin pigmenta-
the alpha (α) chain, the other variably being termed tion, frontal bossing and malar prominence due to
beta (β), delta (δ), epsilon (ε), gamma (γ) and zeta (ζ). chronic marrow expansion. The Hb level may be very
ζ and ε chains are expressed only in early embryonic low, with blood examination revealing hypochromia,
life, with ζ-chain production switching to α-chain pro- red cell stippling, microcytosis, macrocytes, target cells
duction, and γ-chain production replacing ε-chain and nucleated red cells (see Fig. 16.1.1F). An increased
synthesis in the early weeks of gestation. In the perina- HbF level (usually 50–100%) confirms the diagno-
tal period there is a further switch from γ- to β-chain sis. Globin chain synthesis studies can differentiate
production. The predominant fetal haemoglobin is between β+ and β0 thalassaemia.
HbF (α2γ2). In children beyond 6 months of age and Without treatment, the severe chronic anaemia leads
adults, the major haemoglobins are HbA (α2β2) and to growth retardation, poor musculoskeletal develop-
HbA2 (α2δ2). A number of abnormalities of globin ment and increased iron absorption, resulting in skin
chain production or point mutations within globin pigmentation. Extramedullary haemopoiesis in liver
genes may result in significant disease. and spleen together with hypersplenism result in organ
enlargement and abdominal distension. Marrow
expansion produces the characteristic facial appear-
Thalassaemias
ance with frontal bossing, maxillary hypertrophy with
These are genetic disorders characterized by reduced exposure of the upper teeth, prominence of the malar
or absent production of one or more of the globin eminences and a flattened nasal bridge. Skull X-rays
chains of haemoglobin. show expansion of the diploic space, and the subperi-
The thalassaemias are found commonly in people osteal bone has a typical ‘hair on end’ appearance.
originating from the Mediterranean region, the Middle There is cortical thinning of long bones, and fractures
East, the Indian subcontinent, south Asia and Africa. may occur. Death usually occurs within 10 years from
551
The inheritance is in a Mendelian recessive manner. cardiac failure, cardiac arrhythmias or infection.
 16.1 HAEMATOLOGICAL DISORDERS AND MALIGNANCIES

Current treatment is with regular transfusion at Haemoglobin Barts (hydrops fetalis syndrome). All
3–4-weekly intervals, aiming to suppress endogenous four α genes are deleted and no α chains are pro-
haemopoiesis (preventing marrow expansion) and to duced. The haemoglobins present are HbBarts (γ4)
keep the Hb level above 100 g/L. Regular transfusion 70%, HbH (β4) 0–20% and HbPortland (ζ2γ2). Severe
results in iron loading, and chelation therapy must fetal anaemia develops, resulting in cardiac failure,
accompany transfusion support to prevent the toxic hepatosplenomegaly and generalized oedema. The
effects of iron on the myocardium, liver, pancreas and infants are generally stillborn or die shortly after birth.
gonads (cardiac arrhythmias, cardiac ­failure, ­diabetes In utero transfusions may result in a liveborn infant, and
mellitus, hepatic fibrosis, infertility). The recent exchange transfusion followed by ongoing transfusion
availability of effective oral iron chelation therapy
­ support has led to the survival of a few patients. Bone
has dramatically improved the quality of life for these marrow transplantation should cure these patients.
patients. Many centres now transfuse by erythrocy-
Sickle cell disease
taphaeresis to reduce iron loading. All patients receive
Haemoglobin S (HbS) results from a single amino
folic acid supplements and hepatitis B v­ accination, and
acid substitution in the β-globin chain (β6Glu–Val). Under
are encouraged to participate in all normal activities.
hypoxic conditions, deoxyhaemoglobin S polymer-
Splenectomy, preceded by appropriate ­vaccinations, is
izes into fibre bundles, which distort the cell into a
occasionally required.
sickle shape. Sickling may be reversible on reoxygen-
Bone marrow transplantation from matched s­ iblings
ation or may become irreversible. The sickle cell gene
is producing high cure rates provided it is carried out
occurs in people from Africa, the Middle East and
before hepatic dysfunction develops, but long-term
the Mediterranean region, as well as in the African
results are still to be evaluated.
American population.
With improvements in therapy, some patients are
The heterozygous carrier (sickle trait) is asymp-
now surviving into the fifth decade. A proportion of
tomatic, with normal Hb and red cell morphology.
adults have preservation of gonadal function and have
Haemoglobin electrophoresis reveals a HbA of approx-
had children.
imately 60% and a HbS level of 30–40%.
Haemoglobin E/β-thalassaemia. Haemoglobin E
In the homozygous state (sickle cell anaemia) there
(β26Glu–Ly) occurs extensively throughout South-East
is a normochromic normocytic haemolytic anaemia
Asia. Neither the heterozygous nor the homozygous
with target cells, sickle cells, nucleated red cells, frag-
state produces clinical abnormalities. The doubly hetero-
ments and spherocytes (see Fig. 16.1.1E). The diagno-
zygous state of HbE with β-thalassaemia results in a clini-
sis is confirmed by finding a raised HbS level (60–90%)
cal condition similar to thalassaemia major. Diagnosis is
on electrophoresis with approximately 2% HbA2, the
confirmed by blood examination and Hb electrophoresis.
remainder being HbF. The higher the level of HbF the
Clinical presentation and management are similar to that
less severe the symptoms of the disease.
of a moderately severe β-thalassaemia.
The doubly heterozygous sickle trait–β-thalassaemia
a-Thalassaemia is expressed with clinical features very similar to those
There are four α-globin genes, and α-thalassaemia of homozygous sickle cell disease. In contrast to sickle
results from the loss of one or more of these. The cell anaemia, the red cells are microcytic and hypo-
loss of one gene produces neither haematological chromic, and target cells are present. Sickling can
nor clinical abnormality (silent carrier). Loss of two be demonstrated and both HbS and HbA2 levels are
genes results in hypochromia and microcytosis, but raised. Examination of the parents' blood confirms
no anaemia, and is known as α-thalassaemia trait. sickle cell trait in one and thalassaemia minor in the
α-Thalassaemia occurs with a very high incidence in other. The management of this condition is similar to
Asian populations and is assuming increasing impor- that for sickle cell anaemia.
tance in our community. The clinical course of the patient with sickle cell dis-
Haemoglobin H disease. The loss of three α genes ease, or doubly heterozygous sickle/thalassaemia, is
results in the formation of excess β chains, which form characterized by ‘crises’ as a result of sickling of red
an unstable tetramer (β4), accounting for 30–40% of cells that obstruct the lumen of capillaries and small
the total haemoglobin. The clinical picture is similar to venules, causing infarction of surrounding tissues.
that of β-thalassaemia intermedia, with pallor, jaundice Haemolytic ‘crises’ may also occur during infective
and moderate hepatosplenomegaly. There is a moder- illness.
ate anaemia (Hb level 80–100 g/L) and persistent retic- Presentation is usually between the ages of 6 months
ulocytosis. The anaemia is aggravated by infections, and 4 years with pallor, jaundice, abdominal or limb
pregnancy and oxidant drugs (e.g. p ­ henacetin or prima- pain and/or swelling of the hands and feet. Haemolytic
quine), which should be avoided. No specific treatment crises are characterized by increased pallor and
552 is necessary other than folic acid supplements. ­jaundice, infarctive ‘crises’ with acute pain, generally
 Anaemia 16.1
of limbs or back, and aplastic crises with an aregen- Patients with splenic sequestration require prompt
erative anaemia. Splenic sequestration crises occur restoration of intravascular volume and correction of
in young children predominantly under the age of acidosis.
5 years. In this potentially life-threatening complica- Patients with frequent crises may be managed with
tion, red cells are trapped in splenic sinusoids, result- hydroxycarbamide (hydroxyurea), which increases the
ing in hypovolaemia, a rapid increase in splenic size proportion of HbF and reduces the number of sickle
and profound anaemia. Stroke is also common before crises. Hydroxycarbamide is not usually commenced
5 years of age. Patients with sickle cell disease have an until at least 3 years of age, but usually 5 years. In
increased risk of infection, particularly pneumococcal more severe cases, regular blood transfusions to sup-
infection. Functional asplenia secondary to repeated press endogenous HbS production are required. These
splenic infarction occurs in most patients. patients also require iron chelation. Successful bone
The emphasis in management is on avoidance of marrow transplantation has been reported.
environmental factors known to precipitate a crisis.
The following protective measures are recommended:
Genetic counselling
• good nutrition with regular folic acid supplements
• penicillin prophylaxis from infancy, with prompt Current DNA techniques allow prenatal diagno-
treatment of infections sis of the thalassaemias and sickle cell disease. With
• appropriate immunization schedule increased community awareness and education, many
• maintenance of adequate hydration, particularly couples who carry either a thalassaemia or sickle trait
during hot weather are now seeking antenatal counselling and prenatal
• prevention of vascular stasis. This may occur with diagnosis. This will have significant effects on the inci-
tight clothing, the use of tourniquets applied during dence of newly diagnosed homozygotes in the future.
an operative procedure, and exposure to cold.
Vaso-occlusive crises require prompt control of pain,
Anaemia due to increased red cell destruction
the maintenance of hydration and treatment of under-
(haemolysis)
lying infection. Severe crises (pulmonary ­ syndrome
or cerebral infarction) require blood transfusion to Anaemia secondary to haemolysis (Table 16.1.5)
reduce the HbS concentration. Occasionally exchange occurs when bone marrow replacement does not keep
transfusion may be required. pace with the rate of destruction.

Table 16.1.5 Anaemias due to increased red cell destruction

Pathological process Aetiology Disease entity Usual age of presentation

Oxidative cell damage Enzyme defects of the glycolytic G6PD deficiency Neonate to 10 years
pathway Pyruvate kinase deficiency Neonate to adult

Membrane abnormality Congenital – splenic destruction Hereditary spherocytosis Neonate to adult

(decreased red cell Hereditary pyropoikilocytosis Neonate
deformability)

Antibody-mediated Fetomaternal Rh and ABO Haemolytic disease of In utero to 24 hours

membrane damage incompatibility newborn
Autoantibodies ± complement Autoimmune haemolytic Any age
reacting with red cell membrane anaemia
Infection
Drugs
Autoimmune disease

Toxic membrane damage Infection Clostridium perfringens Any age

Heavy metals Wilson disease Late childhood to adult

Mechanical membrane Membrane damage Disseminated intravascular Any age

damage coagulopathy
Haemolytic–uraemic syndrome Childhood
Cardiac prosthesis

G6PD, glucose-6-phosphate dehydrogenase.

553
 16.1 HAEMATOLOGICAL DISORDERS AND MALIGNANCIES

Haemolysis may be intravascular or may occur by variants; favism (acute haemolysis after ingestion of
phagocytosis within the spleen or liver. Intravascular broad beans or inhalation of pollen) is a feature of
haemolysis occurs in some autoimmune haemolytic the Mediterranean variant, whereas oxidative-stress-
anaemias, acute haemolysis in glucose-6-phosphate induced haemolysis (drugs, infection), although com-
dehydrogenase (G6PD) deficiency, and acute transfu- mon to all variants, is the predominant feature in
sion reactions. Free haemoglobin is released and com- affected individuals of African descent. Individuals
bines with haptoglobin. The complex is cleared by the of northern European descent have chronic moder-
reticuloendothelial system of the liver and spleen. If ate haemolysis, whereas other variants experience
the free plasma haemoglobin concentration exceeds haemolysis only with appropriate stress. Patients
the haptoglobin binding capacity, haemoglobinuria ­typically present severely anaemic with dark urine,
occurs. The colour of the urine may vary from pink having been well until 1–2 days prior to presentation.
through brown to almost black, depending on the The precipitating factor is usually identifiable on his-
amount of free haemoglobin excreted. tory. Because of the rapidity of the fall in haemoglo-
If haemolysis occurs predominantly in the reticulo- bin, there often is profound lethargy and restlessness
endothelial system (autoimmune haemolytic anaemia, at presentation.
membrane abnormalities), there is little free haemo- Examination of the blood film shows polychroma-
globin in plasma. Haemoglobin is converted to biliru- sia and anisocytosis, and typically ‘blister’ cells. The
bin within phagocytes, transported to the liver bound diagnosis is established by enzyme assay in mature red
to albumin, then conjugated and excreted into the bile. cells. Enzyme levels are higher in reticulocytes in some
Jaundice is variable, depending on the rate of haemol- variants and a normal enzyme level at the time of an
ysis and hepatic conjugation. To compensate for the acute haemolytic episode does not exclude the diag-
reduced red cell survival, the bone marrow increases nosis. Management is to avoid precipitating factors.
its output of red cells, releasing immature reticulocytes Patients having acute crises may require blood transfu-
and, in acute severe haemolysis, nucleated red cells sion, although a brisk reticulocyte response may result
into the peripheral blood. in rapid spontaneous recovery.

Intracellular enzyme defects

Mature red cells lack a nucleus and intracellular Clinical example
organelles necessary for synthesis of proteins and gen-
eration of adenosine triphosphate (ATP) via oxidative Thomas was an 8-year-old boy from Hong
pathways. Energy production for maintenance of the Kong. He presented with the onset of pallor
integrity of the red cell is via one of the two glycolytic over 24 hours and was passing very dark urine.
metabolic pathways within it. About 95% of glucose He had recently been treated for tonsillitis. He
had no past history of serious illness. On examination, apart
metabolism is via the anaerobic Embden–Myerhof
from marked pallor, splenomegaly was present. His urine
pathway and 5% through the hexose monophosphate contained haemoglobin. Blood tests revealed a haemoglobin
shunt (pentose phosphate pathway). Enzyme defects concentration of 40 g/L with a raised reticulocyte response.
in either pathway result in oxidative damage and hae- Blister cells were evident on the blood film. The G6PD assay
molysis. Deficiencies or abnormalities of G6PD, the was borderline normal and assays on the parents showed
first enzyme in the hexose monophosphate shunt, are that Thomas's mother was heterozygous for G6PD deficiency.
extremely common worldwide. All the documented One month after this episode, Thomas was shown to have
a severe deficiency of G6PD activity. The earlier borderline
enzyme deficiencies of the Embden–Myerhof pathway result was caused by the presence of many young red cells
resulting in haemolytic anaemias are rare. Examples with high G6PD activity.
are pyruvate kinase deficiency and glucose phosphate
isomerase deficiency.
G6PD deficiency Intrinsic membrane defects
This X-linked enzyme deficiency is the commonest
inherited disorder of the red cell. It is expressed fully Abnormalities of the red cell membrane result in
in hemizygous males and in homozygous females. alterations of cell shape, usually due to changes in
Heterozygous females show a variable level of enzyme transmembrane electrolyte flux. Changes in cell
activity due to variation in X-chromosome inactiva- shape cause decreased deformability, splenic ­trapping
tion. There are more than 200 variant enzymes and and ­ destruction within the spleen, resulting in
the clinical expression of the disorder is variable, chronic haemolytic anaemia. The commonest mem-
with four major clinical syndromes. Neonatal jaun- brane ­abnormality is hereditary spherocytosis, most
554 dice is common in the Chinese and Mediterranean ­commonly a ­dominantly inherited condition.
 Anaemia 16.1
Hereditary spherocytosis Extrinsic membrane damage
There is a marked variability in the severity of hae- Acquired membrane damage leading to haemolysis
molysis in this condition. Neonatal jaundice is com- can result from antibody–antigen reactions, mechan-
mon. Some children present with anaemia in infancy, ical insults (e.g. intravascular prosthetic patches),
whereas others remain asymptomatic until a haemo- burns, toxins (e.g. copper) and infective agents (e.g.
lytic or aplastic crisis occurs in association with a viral Clostridium perfringens).
infection. Hypersplenism or gallstones may result in
the presentation of a previously asymptomatic patient
with well-compensated haemolysis. A positive family Antibody-mediated haemolysis
history is often obtained. Examination reveals pallor,
The binding of immunoglobulin or complement, or a
often mild jaundice and a variable degree of spleno-
combination of the two, to the red cell membrane may
megaly. The diagnosis is suggested by the presence of
result in premature cell destruction or immune hae-
spherocytes in the peripheral blood (see Fig. 16.1.1C).
molysis. The antibody involved may be immunoglob-
The best test currently to confirm the diagnosis is
ulin (Ig) G (warm antibody) or IgM (cold antibody).
the E5M test. In this test, the dye eosin-5-maleimide
Immune haemolytic anaemias may be classified as
reacts covalently with Lys-430 on the extracellular
follows.
loop of band 3 protein. Reduced E5M staining is seen
in patients with hereditary spherocytosis, congenital
dyserythropoietic anaemia type II and South-East Isoimmune haemolysis in the newborn
Asian ovalocytosis and cryohydrocytosis. • Rhesus incompatibility (mother Rh negative, baby
Folic acid supplements should be given. Blood trans- Rh positive)
fusion may be required for anaemia resulting from • ABO incompatibility (mother group O, baby group
inadequately compensated haemolysis and for aplas- A or B).
tic crises, during which the haemoglobin level may fall
precipitously. Aplastic crises usually are associated Autoimmune haemolysis in children
with parvovirus B19 infection. Haemolysis is abol- • Idiopathic. In many instances of IgG warm-antibody-
ished by splenectomy. Overwhelming postsplenectomy mediated haemolysis, no definite aetiological agent is
infection may occur, particularly in children less than identified.
5 years of age. Pneumococcal, meningococcal and • Postinfectious. Many common infectious diseases,
Haemophilus influenzae b immunizations should be such as measles (IgG), infectious mononucleosis
given before splenectomy, and penicillin prophylaxis (IgM) and mycoplasmal infection (IgM) may be
should be continued indefinitely after splenectomy. associated with acute haemolysis.
Decisions about splenectomy should be based on • Drug related. This is very uncommon in children.
the following: Some drugs (e.g. α-methyldopa) stimulate the
• degree of haemolysis and anaemia production of antibodies that are directed against
• age red cell antigens but not against the drug. A second
• size of spleen mechanism involves a drug, such as penicillin,
• presence of gallstones. binding to the red cell membrane, with antibody
to the drug being formed and attaching to the
drug. The antibody-coated red cells then undergo
Clinical example destruction in the spleen. The third mechanism of
drug-related haemolysis involves the deposition
Angela was 9 years of age. In the neonatal of antibody–antigen complexes on the red cell
period she required exchange transfusion for surface with activation of complement and brisk
severe jaundice. She had always been pale and
intravascular haemolysis.
had a small appetite. With upper respiratory tract
infections, her pallor increased and jaundice had appeared. • Associated with connective tissue disease or
At 2 years of age hereditary spherocytosis was diagnosed malignancy. This is rare in childhood but may be
and folic acid supplements were commenced. Angela's associated with systemic lupus erythematosus in
father also had this condition. She presented with abdominal adolescence.
pain, pallor, icterus and splenomegaly of 6 cm. Ultrasound Presentation of a child with immune-mediated
examination confirmed the presence of gallstones. Following
haemolysis is usually acute with rapid onset of
pneumococcal and Haemophilus influenzae b vaccination,
splenectomy and cholecystectomy with removal of gallstones
­pallor, severe anaemia and dark urine. Jaundice may
was undertaken. Prophylactic penicillin was commenced after be p­resent. Life-threatening anaemia may develop
the surgery and would continue indefinitely. rapidly, with vasoconstriction, cardiac failure and
hypoxia. Modest splenomegaly is often present. 555
 16.1 HAEMATOLOGICAL DISORDERS AND MALIGNANCIES

The peripheral blood shows a predominantly Major acute blood loss due to trauma, acute haemo-
normocytic anaemia with spherocytes (IgG), or lytic anaemias and chemotherapy-induced anaemia
­rouleaux f­ormation/red cell agglutination (IgM) (see are the most likely causes of acute anaemia to require
Fig. 16.1.1D). As a compensating reticulocytosis transfusion. The exact transfusion trigger will be a
develops, polychromasia and macrocytosis are seen. function of the physiological considerations discussed
A positive direct antiglobulin test (DAT) confirms the previously in this chapter. Major ­haemoglobinopathy
diagnosis. The specificity of the positive DAT classi- and bone marrow failure syndromes may require
fies the type of antibody involved. The commonest chronic transfusion programmes. Nutritional anaemia
are warm IgG antibodies, but cold IgM antibodies are rarely requires transfusion therapy in the absence of
found in association with mycoplasmal infection and cardiovascular instability.
infectious mononucleosis. There are specific indications for exchange transfu-
Urgent blood transfusion may be required. In some sion in neonates and, for example, older children with
cases the presence of strong autoantibody in recipient sickle cell disease.
plasma makes the provision of compatible blood and
the exclusion of underlying alloantibodies difficult.
Transfused cells may be haemolysed rapidly and care- Risks of blood transfusion therapy
ful observation is required. Repeated transfusions may
Parents worry about viral infections from blood trans-
be necessary. Adequate hydration must be maintained
fusion, although this remains an extremely low risk. If
to avoid renal tubular damage from haemoglobinuria.
the clinician has used the principles above to deter-
Where a warm antibody is identified, steroid therapy
mine the need for transfusion, then the risks of not
is instituted and maintained until the Hb concentra-
transfusing usually far outweigh the risks of transfu-
tion stabilizes, then tapered gradually. Haemolysis is
sion. In terms of viral safety, Australia has one of the
usually self-limiting over the course of days to weeks.
safest blood supplies in the world. Factors contrib-
Occasional patients may have severe ongoing haemol-
uting to this are that every blood donor is a volun-
ysis, or frequent relapses. Plasma exchange, exchange
teer (unpaid) and must meet strict selection criteria,
transfusion or high-dose immunoglobulin may be use-
including answering a comprehensive questionnaire
ful but, if these measures fail, splenectomy may be
about their health and lifestyle, and undergoing a
life-saving.
personal interview by trained staff at which they sign
a declaration. Every blood donation is screened for
syphilis, hepatitis B and C, HIV and human T-cell
Blood loss
leukaemia/lymphoma virus (HTLV). Two types of
Blood loss, if acute, results in vasoconstriction, then test for hepatitis C and HIV are now performed –
tachycardia and finally hypotension. The haemoglo- antibody testing and nucleic acid testing (detects viral
bin, if measured very early in the course of a ­bleeding materials directly and therefore infection at an earlier
episode, will be normal or only slightly reduced. When stage). Only blood that is negative for all these tests is
there has been time for haemodilution to occur, the released for use.
haemoglobin level falls. A compensatory reticulocyto-
sis occurs after approximately 48 hours. Chronic blood
Current risks of transfusion transmitted
loss results in iron-deficiency anaemia.
infection
Australian Red Cross Blood Service (ARCBS) uses
sophisticated mathematical models to calculate the cur-
rent infection risks for blood transfusions in Australia,
Blood transfusion therapy as shown in Table 16.1.6. These risks are very small
The majority of children with anaemia do not compared to the risks of everyday living. The chance
require transfusion therapy. The critical questions of being killed in a road accident in Australia is about
that must be addressed in deciding whether to trans- 1 in 10 000.
fuse are:
• Has the patient evidence of cardiovascular
Non-viral risks associated with blood and blood
decompensation?
products
• Is the anaemia likely to be progressive and at what rate?
• What is the likely timing of spontaneous recovery? ABO incompatibility remains one of the most com-
• Are there alternative therapies that are likely to mon fatal complications of blood transfusion and
succeed? most cases are due to avoidable errors (most c­ ommonly
556
 Anaemia 16.1
Table 16.1.6 Risks based on Australian Red Cross Blood
Service (ARCBS) data, 1 July 2000 to 30 June 2003 Practical points

Infection Residual risk with tested blood per unit Deciding if a patient needs a red cell transfusion
transfused • The actual haemoglobin level, although important, does
not alone determine the need for a transfusion.
HIV 1 in 7 299 000
• Consider the cause and time course of the anaemia.
Haematinic deficiencies rarely need transfusion. Acute
Hepatitis C 1 in 3 636 000
blood loss (especially if ongoing) and acute haemolysis
frequently need transfusion.
Hepatitis B 1 in 1 339 000
• Coexistent disease is important in determining the likely
ability of the patient to cope with a degree of anaemia.
HTLV Considerably less than 1 in 1 000 000
Cardiac and lung function, as well as haemoglobin level,
are important determinants of oxygen delivery. The ability
Syphilis Considerably less than 1 in 1 000 000
to maintain oxygen delivery is the key question when
considering most acute red cell transfusion questions.
Variant CJD Unknown: possible and cannot be excluded
• Reduced oxygen saturation measured by pulse oximetry
CJD, Creutzfeldt–Jakob disease; HIV, human immunodeficiency may reflect lung disease, cyanotic heart disease or abnormal
virus; HTLV, human T-cell leukaemia/lymphoma virus. Hb with reduced oxygen affinity (e.g. methaemoglobin), and
may reduce the transfusion threshold. In the absence of
adequate cardiac output or Hb, normal pulse oximetry does
not equate to adequate tissue oxygen delivery.
• Clinical signs of cardiac stress (increased heart rate) or
hypoxia (restlessness, altered conscious state/behaviour)
a­ssociated with patient/sample identification). are critical indicators of the need for urgent transfusion.
Table 16.1.7 gives estimates of risk based on reports In children, hypotension is a late sign in acute blood loss.
from a number of countries, which are subject to the These factors should be monitored closely in anaemic
problem of underestimation due to lack of reporting patients. In a child with cardiovascular decompensation
from anaemia, do not delay urgent transfusion therapy in
and recognition of transfusion reactions (hence the
favour of thorough investigation. A live child who remains
broad ranges). The transfusion of autologous blood is a diagnostic dilemma is better than a dead child in whom
not without risk and the same indications apply as for you know the diagnosis.
the use of homologous blood.

Table 16.1.7 Non-viral serious risks of blood transfusion (per unit transfused unless specified)

Morbidity Mortality

Bacterial sepsis
Red cells 1 in 40 000–500 000 1 in 4 000 000–8 000 000
Platelets 1 in 10 000–100 000 1 in 50 000–500 000

Haemolytic reactions
Acute 1 in 12 000–38 000 1 in 600 000–1 500 000
Delayed 1 in 1000–12 000 1 in 2 500 000

Anaphylaxis – IgA deficiency 1 in 20 000–50 000

Fluid overload/cardiac failure 1 in 100–700 per patient

TRALI* 1 in 5000–100 000 1 in 5 million

TA-GVHD† Rare 90% cases fatal

* Transfusion-related acute lung injury (TRALI) is characterized by acute respiratory distress (within hours of transfusion) with
non-cardiogenic pulmonary oedema. Full recovery in 48 hours is usual if the patient is well resuscitated/supported. TRALI is likely to
be significantly under-reported.
†
Transfusion-associated graft versus host disease (TA-GVHD) is due to viable engraftment of T lymphocytes and usually affects
severely immunocompromised patients or recipients who share an HLA haplotype with a specific donor. Gamma-irradiation of
blood products for specific at-risk groups of patients (refer to hospital guidelines) prevents this rare but usually fatal event.

557
 16.2 Abnormal bleeding
and clotting
Ben Saxon, Chris Barnes

Bleeding disorders range from those that are severe and When did the bleeding start?
potentially life-threatening through to mild d­ isorders
Prenatal and neonatal
that may be difficult to distinguish from normal.
Abnormal bleeding is the result of a disorder of one
• Congenital infection may result in a bleeding
disorder.
of the following:
• Mucosal bleeding occurs with haemorrhagic disease
• the platelets
of the newborn.
• the coagulation mechanism
• Umbilical stump bleeding is associated with factor
• the blood vessel or its supporting tissue.
XIII deficiency and dysfibrinogenaemias.
• Intracranial haemorrhage may occur with factor
deficiencies and with neonatal alloimmune
thrombocytopenia.
Clinical approach to diagnosis • Prolonged bleeding following circumcision
As a general rule, history-taking, physical examination is suggestive of haemophilia and may be the
and a small number of relatively simple laboratory tests presenting feature of haemorrhagic disease of the
will find most causes of abnormal bleeding. The history, newborn.
with particular reference to the past and family history,
will usually provide the most valuable information. Early childhood
• Bleeding often implies a congenital defect.
• Bruising, muscle and joint bleeding is strongly
suggestive of haemophilia.
Practical points • Petechiae and mucosal bleeding suggests a platelet
problem or von Willebrand disorder.
Bleeding disorder assessment
Sudden onset
• History to determine normal from abnormal is the most
valuable tool. • Usually indicates an acute problem such as immune
• Simple coagulation tests such as platelet count, activated thrombocytopenic purpura.
partial thromboplastin time (aPTT), prothrombin time (PT/ • Non-accidental injury may have a haemorrhagic
international normalized ratio (INR)) and fibrinogen will presentation with inadequate explanations for
confirm the majority of diagnoses. each specific bruise, which may have an unusual
• Mucosal bleeding needs assessment for von Willebrand distribution (see Chapter 3.9). Skeletal trauma and
disorder.
other stigmata of non-accidental injury may be
• Assessment of other family members is often required.
present.

History
What is abnormal? Where is the bleeding?
The main question to answer in the history is whether Specific bleeding sites have characteristic associations:
the bleeding symptoms are within or outside normal • Joint bleeding: haemophilia A and B
limits. Isolated bruises over the shins are common, • Nasal mucosa: local irritation; von Willebrand
whereas spontaneous petechiae are abnormal. Finger- disorder and platelet dysfunction
induced epistaxis is common and not indicative of • Gums, periosteum, skin: scurvy
a bleeding disorder; however, recurrent nose bleeds • Gastrointestinal: haemorrhagic disease of the
­lasting for more than 10 minutes or leading to anaemia newborn in babies; liver disease in older children
are often related to a bleeding disorder. Table 16.2.1 • Retro-orbital: haematological malignancy or
gives some clinical guidance. disseminated solid tumour.
558
 ABNORMAL BLEEDING AND CLOTTING 16.2
Table 16.2.1 What symptoms and signs may be related to a bleeding disorder?

Site Within normal May be abnormal and due to a Often due to a bleeding disorder
limits number of causes

Nose Finger-induced Unilateral Recurrent, requiring medical

intervention or causing anaemia

Oral Blood on brush Gum ooze < 30 min Gum ooze > 30 min

Gut Rectal fissure, blood in Haematemesis, melaena

nappy

Menstrual loss 4–7 days ‘Same as Mum’ Loss leading to anaemia or

transfusion

Skin Shins do not count Bony prominences Spontaneous bruising over soft
areas, laceration bleeding > 30 min

Joints and muscles Trauma induced Spontaneous

Intracranial Neonatal, trauma-induced Spontaneous

What is the context of bleeding? Physical examination

Family history The following should be noted on physical examination.
Haemophilia A and B are X-linked; most von Willebrand
disorder subtypes and haemorrhagic hereditary telan­
The type of skin bleeding
giectasia are recessive and several platelet function
­disorders are dominantly inherited. Clinical penetrance Petechiae alone strongly suggest a platelet or vessel
in haemophilia carriers and von Willebrand disorder problem, whereas ecchymoses alone suggest a f­actor
may be variable. It is important to review whether the deficiency. Combined petechiae and ecchymoses
family has a history of bleeding complicating surgical ­suggest a severe disorder, often of platelet origin.
challenges and it may be helpful to explore any history
of menorrhagia in family members.
The site of the bleeding
Other aspects of history Confirmation of history, defining the number of all
Easy bruising, bruising at abnormal sites, p ­ rolonged different bleeding sites, and assessment of severity of
bleeding following trivial trauma or ­bleeding follow- bleed and functional implications are all important
ing surgery and dental extractions are all indications aspects for both diagnosis and management.
for investigation. Bleeding may also occur in the pres-
ence of disorders such as systemic lupus e­ rythematosus,
Splenomegaly
liver disease, extrahepatic portal hypertension, gross
splenomegaly, giant h­ aemangiomas, reticuloend­othelial Hypersplenism occurs when a large spleen removes ­platelets
malignancies and leukaemia. from the circulation, leading to bleeding. The problem is
the underlying cause of the splenomegaly. Hepatomegaly,
Drug ingestion splenomegaly, lymphadenopathy and/or anaemia, in
Drugs may produce abnormal bleeding through: association with bleeding, strongly suggest leukaemia.
• depression of clotting factors: anticoagulants, liver
toxins
Miscellaneous
• bone marrow depression: chloramphenicol, cytotoxic
agents, radiation Bleeding in association with eczema is a feature of
• antigen–antibody reactions with platelet membranes: Wiskott–Aldrich syndrome; telangiectasia and mucosal
quinine group of drugs bleeding are typical of hereditary haemorrhagic telan-
• direct inhibition of enzymes in platelets: aspirin giectasia. Hyperelastic skin, hyperextensible joints and
effects on platelet cyclo-oxygenase. bruising are associated with Ehlers–Danlos syndrome.
559
 16.2 HAEMATOLOGICAL DISORDERS AND MALIGNANCIES

Investigation of bleeding in childhood Immune thrombocytopenic purpura

The tests in Table 16.2.2 are the most important. Immune thrombocytopenic purpura is the most com-
mon acquired bleeding disorder in children. It may
Other tests be acute or chronic (defined as lasting longer than
12 months), episodic or continuous. Common to all
Measurement of von Willebrand factor level (antigen),
clinical variations is the marked reduction in platelet life
activity (ristocetin co-factor and/or collagen binding
span due to immune-mediated splenic sequestration.
assay) and factor VIII level are required to diagnose von
Features of typical acute immune thrombocyto­
Willebrand disorder. The bleeding time has lost favour
penic purpura:
because of its scarring potential but is characteristically
prolonged in thrombocytopenia (normal 2–7 min), von
• 80–90% of paediatric immune thrombocytopenic
purpura cases
Willebrand disorder and platelet function disorders,
• preceding viral illness is common
and is normal in other coagulation disorders.
• peak age 2–5 years
• abrupt onset of bleeding
• mucosal and skin bleeding
Bleeding due to platelet • petechiae common
• otherwise normal examination – no
disorders lymphadenopathy or hepatosplenomegaly
Bleeding disorders resulting from platelet abnormalities • platelet count usually < 20 × 109/L
are usually due to thrombocytopenia but may be due to • normal red cell and white cell parameters.
qualitative platelet defects. The various types of inherited There is no need for other investigations if these ‘typi-
and acquired thrombocytopenia are listed in Table 16.2.3. cal’ features are present.

Table 16.2.2 Interpretation of initial blood tests in children with abnormal bleeding

Test Result More common causes Less common causes

Blood count Isolated thrombocytopenia ITP Congenital anomaly

NAIT Early SAA
Pancytopenia Leukaemia Myelodysplasia
SAA Osteopetrosis
High white cell count and Leukaemia Myeloproliferative
thrombocytopenia Infections disorders

Blood film Thrombocytopenia and red cell Microangiopathic anaemia

fragmentation (e.g. HUS, DIC)
Small platelets Wiscott–Aldrich syndrome
Giant platelets Bernard–Soulier syndrome

Prothrombin time Isolated prolongation Vitamin K deficiency Congenital factor VII deficiency
(PT/INR) Warfarin therapy
Prolonged PT and aPTT DIC Factor X, factor V, prothrombin or
Septicaemia fibrinogen deficiency
Liver disease

aPTT Isolated prolongation Unfractionated heparin Factor XI deficiency

therapy
Haemophilia A or B Contact system* deficiency
‘Lupus anticoagulant’

Fibrinogen Low DIC Congenital fibrinogen disorders

All tests Normal Non-accidental injury

Henoch–Schönlein purpura

*Contact system refers to factor XII, prekallikrein and high-molecular-weight kininogen.

aPTT, activated partial thromboplastin time; DIC, disseminated intravascular coagulation; HUS, haemolytic–uraemic syndrome;
INR, international normalized ratio; ITP, immune thrombocytopenic purpura; NAIT, neonatal alloimmune thrombocytopenia; PT,
560 prothrombin time; SAA, severe aplastic anaemia.
 ABNORMAL BLEEDING AND CLOTTING 16.2
Table 16.2.3 Inherited and acquired thrombocytopenias

Disorder Key Information

Acquired
Neonatal Immune thrombocytopenia Neonatal alloimmune or maternal autoimmune
Intrauterine infection TORCH
Pre-eclampsia
Birth asphyxia
Giant haemangioma ‘Kasabach–Merritt syndrome’ features platelet
consumption
Any age Immune thrombocytopenia (ITP) The most common acquired thrombocytopenia

Inherited
With platelet dysfunction Examples include Bernard–Soulier syndrome and Rare
Wiskott–Aldrich syndrome
Without platelet Examples include Fanconi anaemia and Alport Rare
dysfunction syndrome
Mediterranean macrothrombocytopenia Large platelets, autosomal dominant

TORCH, toxoplasmosis, other (e.g. HIV and parvovirus B19), rubella, cytomegalovirus, herpes simplex.

Differential diagnosis is predominantly that of ­ latelets in response to several stimuli. The more
p
evolving aplastic anaemia. common ­disorders in this group are the ‘aspirin-like’
Chronic immune thrombocytopenic purpura occurs syndrome and platelet storage pool disorders. The
in 10–20% of cases and often has an insidious onset most severe ­disorder is Glanzmann disease. Before
in children aged over 7 years; it affects girls more undertaking platelet function studies, it must be
commonly than boys. Recurrent immune thrombo-
­ ensured that there has been no ingestion of aspirin
cytopenic purpura is rare and is characterized by for at least 7 days.
­thrombocytopenia at more than 3-month intervals.
Treatment approaches to immune thrombocytopenic
purpura are shown in Table 16.2.4.
Practical points
Bleeding due to qualitative platelet defects
Acute bleeding history
The child with a functional platelet defect will have
• Splenomegaly, lymphadenopathy or hepatomegaly
a normal platelet count but abnormal platelet func- indicate a systemic illness (e.g. Epstein–Barr virus infection,
tion test results. These tests analyse aggregation of leukaemia).
• Always examine the fundi for bleeding changes.
• Careful review of the blood film is important to exclude
other causes of thrombocytopenia.
• Anaemia and reticulocyte response aid determination of
severity and duration of bleeding.
Clinical example
• Assess for the presence of ‘wet’ purpura (mucosal
bleeding) as some authorities claim that this may be
Chloe presented at the age of 4 years,
associated with an increased likelihood of intracranial
2 weeks after a viral upper respiratory infection,
bleeding.
with a 3-day history of a petechial rash on her
face and gum bleeding with toothbrushing.
Examination revealed several fresh skin bruises along with
the petechiae. There was no hepatosplenomegaly and the
only palpable lymph nodes were slightly tender tonsillar
nodes, 2 cm in diameter. The only abnormality on full blood Bleeding due to coagulation
examination was a platelet count of 9 × 109/L. Chloe was
treated with prednisolone 4 mg/kg daily in three divided disorders
doses for 4 days as an outpatient, with alternate daily
The coagulation system, as monitored by the available
platelet counts. On the second day of treatment her platelet
count was 65 × 109/L and the count became normal within 5 investigations, is shown in Figure 16.2.1. Initiation
days. She had no further episodes of thrombocytopenia. of coagulation and the production of a fibrin clot is
561
shown in Figure 16.2.2.
 16.2 HAEMATOLOGICAL DISORDERS AND MALIGNANCIES

Table 16.2.4 Treatment options for acute immune thrombocytopenic purpura with either bleeding problems or if the platelet
count is less than 10 × 109/L

Treatment option Advantages Disadvantages Time course to resolution

First-line therapies
Conservative No drug side-effects Longest time to platelet count 75% remission in 4–6 weeks
> 20 × 109/L 15% take 4–6 months
< 1% risk of ICH while awaiting
platelet recovery
Corticosteroids (standard No blood product exposure Steroid side-effects‡ common 1 week
dose*)
Corticosteroids (high No blood product exposure Steroid side-effects‡ less common Platelets > 20 × 109/L: 2 days
dose†) Rapid rise in platelets Platelets > 50 × 109/L: 3–4 days
Intravenous Rapid rise in platelets Pooled blood product with at least Platelets > 20 × 109/L: 1–2 days
gammaglobulin (IVIG)§ two viral inactivation steps Platelets > 50 × 109/L: 3 days

Second-line therapies
Anti-Rh(D) antibody Only useful in Rhesus-positive children
Similar efficacy to IVIG and steroids
Splenectomy Most useful in children Immunizations for meningococcus, Rapid in the majority
> 5 years old with Haemophilus influenzae and
chronic ITP pneumococcus are mandatory
Lifelong antibiotic prophylaxis

Evolving therapies
Thrombopoietins Patients with refractory Few short-term and long-term Variable
chronic ITP may respond clinical data in paediatrics
Rituximab Patients with refractory Profound B-cell immune Variable
chronic ITP may respond suppression

*Standard dose: prednisolone 2 mg/kg body weight daily for 21 days.

†
High dose: prednisolone 4 mg/kg body weight daily for 4 days.
‡
Steroid side-effects include gastric irritation, transient diabetes and other metabolic derangements, immune suppression,
cushingoid body fat distribution, growth delay, osteopenia and rarely avascular necrosis of the femoral head.
§
IVIG 0.8 g/kg body weight, repeat within 1–7 days if platelet count remains < 10 × 109/L or any platelet count with problematic
bleeding. Lower doses may be equally effective. IVIG side-effects include flu-like symptoms and rarely transient aseptic meningitis.
Blood products may theoretically transmit viral and prion particles.
ICH, intracranial haemorrhage; ITP, immune thrombocytopenic purpura.

Practical points Clinical example

Albert was born at term, received

Understanding coagulation
intramuscular vitamin K, and developed a
• The aPTT and PT/INR are screening tests that represent large bruise in his thigh. No circumcision
how various ‘factors’ interact in the test tube; they are
was performed. He always seemed to have
useful tests to determine which factor may be low.
fingerprint bruises under his arms from being picked up.
• In vivo coagulation does not occur as a ‘cascade’, rather When he began sitting unaided he developed buttock
a series of positive feedback reactions starting with
bruising, and when he began walking he presented to
tissue factor and factor VII and culminating in a thrombin
the accident and emergency department with a swollen,
burst.
hot right ankle. The joint had virtually no movement and
• Clotting occurs at the site of injury by thrombin cleaving ultrasonography confirmed a fluid-filled joint. The history
fibrinogen to fibrin.
was highly suggestive of haemophilia. The INR was normal,
• Thrombin inhibits coagulation by binding with the aPTT was 90 seconds and the factor VIII level was less
thrombomodulin on normal blood vessels.
562 than 1%. Haemophilia A was diagnosed and prophylaxis
 ABNORMAL BLEEDING AND CLOTTING 16.2
X II
with 25 U/kg recombinant factor VIII three times per week
was commenced. VIII
TF Va
At the age of 4 years Albert fell from a chair on VIIa Xa IIa
to his occiput after missing a dose of prophylaxis.
Within 2 hours he had a falling level of consciousness TF- bearing cell
VIIIa
and respiratory depression. Computed tomography
diagnosed a subdural haematoma. Treatment with TF
VIIa V Va Platelet
high-dose factor VIII and neurosurgical intervention IX
led to an uneventful recovery.

IXa X II
Fibrinogen
Xa IIa
Haemophilia
IXa VIIIa Va Fibrin
Prevalence
• Haemophilia A (factor VIII deficiency): 5–10 males Activated platelet
per 100 000 population
• Haemophilia B (Christmas disease, factor IX Fig. 16.2.2 Initiation of coagulation and the production of a
deficiency): 0.5–1 per 100 000 fibrin clot. TF, tissue factor.
• Factor XI deficiency (haemophilia C): rare
• Other factor deficiencies: exceedingly rare.
Severity
Genetics
Severity is defined by plasma factor level and ­correlates
Haemophilia A and B are both X-linked. Up to one- with clinical severity:
third of all new cases of haemophilia are due to • severe: < 2%, frequent spontaneous deep tissue bleeding
new mutations. Female carriers sometimes have low • moderate: 2–5%, infrequent spontaneous bleeding
­levels of factor VIII or IX and may have a bleeding • mild: 6–30%, bleeding with trauma and surgery, not
disorder. spontaneously.

Prothrombin Time (PT) INR Activated Partial Thromboplastin Time (aPTT)

Prekallikrein Kallikrein
VII XI
Extrinsic HMWK
pathway XII XIIa
Tissue
factor XIa
Contact
system
VIIa Intrinsic
pathway
IX IXa

VIIIa
X Xa X Xa

Va Common Va
pathway II IIa
II IIa

Fibrinogen Fibrin Fibrinogen Fibrin

Fig. 16.2.1 The coagulation system as measured by initial blood tests: prothrombin time (PT) and activated partial thromboplastin time
(aPTT). HMWK, high-molecular-weight kininogen; ‘a’ indicates activated factor. This figure does not represent in vivo coagulation, rather 563
the coagulation factors (in test tubes) that influence the PT and aPTT. INR, international normalized ratio, is a function of the PT.
 16.2 HAEMATOLOGICAL DISORDERS AND MALIGNANCIES

Clinical manifestations occurred in more than 50% of patients receiving blood

products in the years 1980–1985. Hepatitis C infection
Neonatal
is also common prior to viral identification, screen-
A positive family history or known carrier status allows
ing and viral inactivation of plasma products. Variant
for definitive diagnosis in the newborn period. Cord
Creutzfeldt–Jakob disease (vCJD) is a prion d ­ isease. It
blood genetics are most reliable. Some laboratories
has been shown to be transmissible in blood ­products
perform factor VIII or factor IX assays on cord blood,
and is not removed by current viral inactivation
but technical difficulties may arise and results should
­processes. Fortunately there have been no cases of vCJD
be interpreted with caution. There is prolonged bleed-
described in patients with haemophilia.
ing following circumcision. Intracranial haemorrhage
is suspicious of a bleeding disorder in the term neonate.

Early childhood Complications

Skin and soft tissue bleeds are common in the first year Inhibitors are anti-factor VIII or anti-factor IX
and beyond. Haemarthroses usually only occur once antibodies, which prevent regular doses of factor
the child is walking. The ankles are common b ­ leeding concentrate from working. Central lines may be
sites in young children; elbow and knee bleeding required to ensure venous access in young children.
(Fig. 16.2.3) occur more commonly in older children. These may be complicated by infection or large vein
thrombosis.
Specific bleeds
Bleeding into the forearm may occlude the neurovascu-
lar bundle and cause a Volkmann ischaemic contracture. Management
Bleeding into the posterior pharyngeal wall may inter- Correct or prevent the bleeding tendency
fere with respiration and cause dysphagia. Iliopsoas • Mild and moderate haemophilia A often responds
bleeding may be complicated by femoral nerve com- to desmopressin acetate infusions to increase
pression. Intracranial vascular accident is the cause of plasma factor VIII levels.
death in 7% of patients with haemophilia. Haematuria • One unit of factor VIII per kilogram body weight
is common in adolescents and is seldom serious. given intravenously increases the factor VIII level
by approximately 2%.
Chronic illness • Life-threatening bleeds require plasma factor levels
There is synovial hypertrophy and arthritis. Psychosocial greater than 80%.
problems arise as a result of chronic ­illness, lifestyle • Most other bleeds require plasma factor levels of
restrictions and the need for injections. HIV/AIDS 30–60%.
• Prophylactic infusions of 25–40 U/kg three times a
week ‘convert’ severe disease into moderate disease,
thereby decreasing the risk of spontaneous bleeding.

Choice of product
• Most developed countries, including Australia,
now offer recombinant product to all patients with
haemophilia.
• Plasma-derived factor products are still available.
These are screened for HIV and hepatitis B and C,
and then undergo two viral inactivation steps in the
processing.

Orthopaedic
• Rest, immobilization, ice, compression and elevation
(RICE) are usually sufficient to control pain.
• Splinting followed by physiotherapy and exercises
when pain has settled preserves function.

Haemophilia centres
• Provide a focus of education and training for
564 patient and family.
Fig. 16.2.3 Haemarthrosis of the right knee in a boy with • Multidisciplinary group with expertise in
haemophilia. haemophilia management.
 ABNORMAL BLEEDING AND CLOTTING 16.2
Inhibitors • factor X
• Inhibitors are found in up to 30% of patients. • protein C and S
• At least half of these are low-titre inhibitors, which These fall in neonates as a result of nutritional
can be treated by high-dose factor VIII. deficiency.
• High-titre inhibitors require ‘immune tolerance’ • Bleeding is usually from the gastrointestinal tract or
therapy for eradication of inhibitor, and following circumcision
infusions of the factor VIII and IX bypass agent, • Occurs early, often on day 2–3
recombinant factor VIIa, to treat bleeds. • Prophylactic vitamin K eliminates this disease
• Vitamin K 1 mg, given by the intramuscular route,
stops bleeding rapidly.
Clinical example

Vanessa was a 13-year-old girl with

menorrhagia since menarche. She had always Disorders of bleeding due to
had ‘easy bruising’ and required a transfusion vascular defects
after tonsillectomy due to excessive bleeding.
She often bled from her gums after brushing her teeth. Her The commonest vascular defects seen in childhood are:
older sister and her mother both had heavy periods but • anaphylactoid purpura
neither had had severe postsurgical bleeding. Platelet count, • infective states
INR and aPTT were all normal. Von Willebrand antigen was
30%, activity (ristocetin co-factor) 25% and factor VIII 35%.
• nutritional deficiency.
Vanessa was diagnosed with mild von Willebrand disorder.
Anaphylactoid purpura (Henoch–Schönlein purpura)
Von Willebrand disorder The aetiology of this relatively common disorder is
still not clear. It is readily recognized by the charac-
This disorder has the following features:
teristic distribution of the rash over the b
­ uttocks, legs
• Quantitative (types 1 and 3) or qualitative (type 2) and backs of the elbows (Fig. 16.2.4). Frequently, it
defect in von Willebrand factor (vWF), a molecule
is accompanied by abdominal pain, melaena, joint
that assists platelet adhesion to the subendothelium
• Common: 125 per million population
• Type 1 is inherited as autosomal dominant with
variable penetrance, is mild and is the most common
• Types 2 and 3 are rare
• Mucosal bleeding, excessive bruising and
postoperative or post-traumatic bleeding
• Prolonged bleeding time but normal INR and
aPTT, unless severe disease is present
• Abnormal vWF antigen and activity (ristocetin
co-factor)
• Treatment for type 1 vWF is desmopressin
(DDAVP), which releases stored vWF/factor VIII
• DDAVP may be repeated once stores have
reaccumulated, usually after 12–24 hours
• Plasma-derived factor VIII products often contain vWF
and may be used in those unresponsive to DDAVP
• Cryoprecipitate should be avoided due to lack of
virus inactivation.

Haemorrhagic disease of the newborn

Haemorrhagic disease of the newborn fortunately is
now rare, since the introduction of routine vitamin K
administration for all babies at the time of delivery.
Features of haemorrhagic disease of the newborn:
• Coagulation factors requiring vitamin K for post-
transcriptional modification:
• factor II (prothrombin) 565
• factor VII Fig. 16.2.4 Anaphylactoid purpura. The rash is typically
• factor IX distributed over the buttocks and backs of the legs.
 16.2 HAEMATOLOGICAL DISORDERS AND MALIGNANCIES

swellings and occasionally glomerulonephritis. In ana- extremities. Congenital deficiencies of either p

­ rotein
phylactoid purpura, investigations for assessment of C or p­rotein S are the cause of neonatal purpura
coagulation are normal. Thus, diagnosis must be made fulminans.
on the clinical picture alone.
The outlook for patients with a­ naphylactic purpura is
Miscellaneous
excellent, except for an occasional child who develops a
progressive renal lesion (see Chapter 18.1). It is impor- Bleeding from vascular wall defects is a feature of a
tant to document the child's blood pressure at presenta- group of rare disorders. These include hereditary haem-
tion. There is a reasonable amount of scientific evidence orrhagic telangiectasia, polyarteritis nodosa, other vas-
to suggest that the use of corticosteroids may prevent culitides and uraemia. Anoxia, and thus damage to the
­long-term renal impairment but also reduce the ­duration capillary wall, may cause purpura in the asphyxiated
of the acute symptoms of abdominal and joint pain. newborn. The bleeding that accompanies Cushing syn-
drome, Ehlers–Danlos syndrome and cutis laxa is the
result of defects in vascular supporting tissue.
Infective states
The purpura associated with such disorders as menin-
gococcaemia and dengue haemorrhagic fever result in
activation of the coagulation mechanism producing Clotting due to coagulation
disseminated intravascular coagulation. Management disorders
involves that of the infection and of the associated
Physiology of anticoagulation
vascular collapse.
The formation of a fibrin clot is tightly regulated in its
local environment by anticoagulants. Local thrombin
Nutritional deficiency
binds thrombomodulin located on normal e­ ndothelium
Scurvy is uncommon and occurs in the artificially fed which activates protein C. Activated protein C (APC)
infant with inadequate vitamin C supplementation. with the co-factor, protein S, inhibits factors Va and
The child is often pale, with skin bruises, is immobile VIIIa by cleaving the molecules. A mutation of factor V
in the frog position because of painful subperiosteal at one cleavage point prevents the APC inhibitory effect
haemorrhages, and has gingival bleeding. and is termed APC resistance. The mutation is called
factor V Leiden. The other key coagulation inhibitor is
antithrombin, a direct inhibitor of thrombin and also
Purpura fulminans (e.g. post-varicella infection)
of factors Xa, IXa, XIa and XIIa. Heparins potentiate
This is a life-threatening and rare form of non-throm- the effect of antithrombin greatly. The largest risk fac-
bocytopenic purpura that may follow such infections tor for paediatric thrombosis is not a protein deficiency
as scarlet fever, varicella, measles and some other but the presence of a ­central venous catheter.
viral infections. Typically there are rapidly spreading Table 16.2.5 lists the causes and features of throm-
skin haemorrhages involving the buttocks and lower bosis in childhood.

Table 16.2.5 Major causes of thrombosis in childhood

Cause Clinical features Diagnostic tests Treatment

Venous access device Blocked access/emboli, limb Echocardiography and Heparin. Removal of device
swelling contrast radiography

Phospholipid antibodies Superficial/deep vein Prolonged INR/aPTT, not Often no therapy; may
thrombosis corrected by normal require corticosteroids or
plasma heparin

Protein C and S homozygous Purpura fulminans Very low protein C or S Protein C replacement +
heparin

Protein C and S heterozygous Superficial/deep vein Low protein C or S Heparin followed by long-term
thrombosis; rare cerebral, warfarin
mesenteric and renal vein
thrombosis
566
 ABNORMAL BLEEDING AND CLOTTING 16.2
Table 16.2.5 Major causes of thrombosis in childhood—cont'd

Cause Clinical features Diagnostic tests Treatment

Factor V mutation (Arg506 to Early-onset vascular disease Activated protein C Heparin and long-term
Gln), ‘Factor V Leiden’ in family resistance test warfarin

Antithrombin deficiency Venous thrombosis in Decreased level of Antithrombin replacement,

adolescence antithrombin heparin and warfarin

Dysfibrinogenaemia Rare thrombosis in childhood Prolonged thrombin Replacement therapy

time and snake venom
times

Homocysteinaemia Arterial and venous Biochemical tests Diet and short-term

thrombosis anticoagulants

aPTT, activated partial thromboplastin time; INR, international normalized ratio.

567
 16.3 Cancers Antoinette Anazodo, Tracey O'Brien

Over the past 30 years we have seen dramatic improve- I have done or passed on to my child?’ With the excep-
ments in the treatment and survival of childhood tion of several known predisposing genetic syndromes
­cancer. Survival rates have climbed from below 30% to (Table 16.3.2), the proportion of paediatric cancers
more than 80%. This improvement is largely due to the that have a clearly hereditary component is very small.
use of clinical cancer trials conducted through collabor- Similarly, despite extensive e­pidemiological studies,
ative national and international childhood cancer study few environmental agents have been linked ­consistently
groups and underpins the need for a continued cohe- with childhood malignancy.
sive approach to the treatment of rare diseases. Despite It is hypothesized that cancer initiation results from
these remarkable improvements, 20–25% of children a series of genetic mutations resulting in the inabil-
diagnosed with cancer are not cured with current thera- ity of a cell to respond normally to intracellular and/
pies and many cured patients will be left with long-term or extracellular signals that control cell proliferation,
complications of therapy. This clearly ­dictates the need ­differentiation or death (apoptosis). Examples include
for ongoing research to improve s­ urvival outcomes. mutations involving tumour suppressor genes (e.g. RB1,
p53 or WT1) or activation of cellular ­proto-oncogenes
(e.g. myc or abl). The number of required genetic alter-
ations may differ depending on the type of malignancy
Incidence and distribution of from as few as one to a complex cascade arising directly
childhood cancers or indirectly from inherited gene mutations, environ-
mental, chemical or radiation-induced DNA damage
Approximately 1 in 600 children will be diagnosed with or random errors in DNA synthesis.
cancer before the age of 15 years, and the incidence
has slowly increased since the 1970s. The distribution
of cancer types in children aged 0–14 years is shown
in Table 16.3.1. The incidence varies by sex and ethnic Approach to management
origin, and the types of tumour also vary by age.
Acute leukaemia – acute lymphoblastic (ALL) or
of a patient with suspected
acute myeloblastic leukaemia (AML) – accounts for just malignancy
over one-third of all childhood cancers. Primary brain Treatment types and duration vary for individual
or central nervous system (CNS) tumours account for children and adolescents depending on the age at
another third and are the most common solid cancer diagnosis, type of cancer, stage and specific biologi-
tumours. Lymphomas (non-Hodgkin lymphoma and cal differences of the tumour. Prompt referral to a
Hodgkin disease) make up 10% of all childhood malig- ­paediatric oncology centre for diagnostic work-up and
nancies. The most common ­abdominal tumours are management is critical for all children and adolescents
neuroblastoma and Wilms' tumours, accounting for with a suspected malignancy. A centralized multidis-
6–8% of childhood cancers respectively. Bone tumours ciplinary team approach, utilizing skills of ­specialist
(e.g. Ewing sarcoma and osteosarcoma) and soft tis- medical, nursing and allied health practitioners is the
sue sarcomas (e.g. rhabdomyosarcoma) account for a ‘gold standard’ in delivery of excellence in care to
small proportion of childhood cancers. In adolescent ­children with cancer. A number of steps are involved
patients, melanoma, bone sarcomas, thyroid cancers before a child can start treatment:
and germ cell tumours are more common.
• Diagnosis will be made by a combination of diagnostic
tests, radiological imaging and biopsies that varies
dependent on the cancer type. Examples of these will
be shown later as we discuss specific tumour groups.
Aetiology of childhood cancer • Staging investigations are then needed to document
When confronted with a diagnosis of childhood whether the cancer has spread. These tests give
­cancer, parents often ask: ‘Why did this happen to important information about survival and allow
568
my child?’ or ‘Did this happen because of something clinicians to decide on the most suitable clinical trial.
 CANCERS 16.3
Table 16.3.1 Frequency of malignancy in childhood
• Treatment usually involves combinations of four
common treatment options, although scientists are
Malignant disease Frequency (%) researching new novel treatments that may improve
survival:
Leukaemia 35
• Chemotherapy with drugs that kill rapidly
Primary central nervous system tumours 20 dividing cancer cells. Unfortunately, these drugs
cause side-effects by affecting normal cells such
Lymphoma: non-Hodgkin and Hodgkin 10 as bone marrow or hair follicles. Depending
on the chemotherapy agent, the drug may be
Wilms' tumour 6–8 given intravenously, orally, intramuscularly or
intrathecally (into the cerebrospinal fluid, CSF).
Neuroblastoma 6–8
• Surgery – some tumours can be removed by
Rhabdomyosarcoma, soft tissue sarcoma 5 a surgical procedure at diagnosis; others are
removed after chemotherapy to make the tumour
Sarcoma of bone: Ewing and osteosarcoma 4 smaller or easier to remove.
• Radiotherapy is the medical use of ionizing
Histiocytosis 5 radiation as a cancer treatment or part of
treatment to control cancer cells. Some tumours
Teratoma 2
are very radiosensitive (e.g. lymphomas),
Retinoblastoma 1 whereas others, such as osteosarcomas, are not
radiosensitive.
Hepatic 1 • Bone marrow transplant treats diseased
bone marrow by ablating the marrow with
Other 5 a combination of chemotherapy and/or
radiotherapy, coupled by replacement with a stem
cell infusion (of bone marrow, peripheral stem
Table 16.3.2 Inherited/genetic syndromes associated cells or cord blood).
with increased risk of childhood malignancy

Cancer Associated syndrome

Leukaemia Trisomy 21, Bloom syndrome,

Fanconi anaemia, ataxia
Acute leukaemia
telangiectasia, neurofibromatosis, Leukaemia is the abnormal proliferation of lym-
Kostmann syndrome, Klinefelter
phoblasts (ALL) or myeloblasts (AML) in the bone
syndrome, Li–Fraumeni syndrome,
Diamond–Blackfan anaemia, marrow. ALL accounts for 80% of all childhood leu-
Noonan syndrome kaemia, with AML accounting for the majority of
the remainder. In ALL, presentation peaks at age 2–5
Central nervous Neurofibromatosis, tuberous years, whereas there is no peak in AML. Chronic leu-
system tumours sclerosis, Li–Fraumeni syndrome, kaemia, including chronic myeloid leukaemia (CML)
von Hippel–Lindau syndrome and juvenile myelomonocytic leukaemia (JMML), is
rare, accounting for fewer than 5% of cases.
Lymphoma Immunodeficiency disorders
The cause of leukaemia is unknown, but the the-
Wilms' tumour Denys–Drash syndrome, Beckwith– ory is that a abnormal stem cell develops capable
Weidermann syndrome, WAGR of indefinite renewal. These cells occupy the mar-
syndrome row space, leading to reduced numbers of normal
haematopoietic cells, resulting ultimately in pancy-
Rhabdomyosarcoma Li–Fraumeni syndrome
topenia. Secondary involvement of the reticuloen-
WAGR, Wilms' tumour, aniridia, genitourinary anomalies and dothelial s­ystem (leading to lymphadenopathy and
mental retardation. ­hepatosplenomegaly), bone, joints and, rarely, CNS,
testes and skin can occur.
A two-step pathogenesis for ALL (Greaves' hypothe-
• Toxicity assessment such as echocardiography, sis) has been suggested, with the initial event, occurring
glomerular filtration rate and audiology are during fetal life, driving clonal expansion and a second
regularly carried out to ensure that treatment does trigger occurring during childhood, possibly resulting
not affect normal structures such as the heart, from viral stimuli of cellular proliferation. This theory
569
kidneys and hearing. stems from evidence that a significant proportion of
 16.3 HAEMATOLOGICAL DISORDERS AND MALIGNANCIES

children presenting with ALL have molecular evidence

of leukaemic clones identified ­retrospectively at birth
on newborn screening cards.
Leukaemia can be further classified into distinct
categories:
• precursor B-cell ALL (early pre-B, pre-B,
transitional pre-B): 80–85%
• mature B-cell ALL: 2–3%
• T-cell ALL: 10–15%.
Classification is on the basis of:
• Morphological characteristics – appearance of the
blood film, bone marrow aspirate and bone marrow
trephine under the microscope Fig. 16.3.1 Bone marrow aspirate in acute lymphoblastic
• Cytogenetics – the study of tumour chromosomal leukaemia.
material using techniques such as florescence in situ
hybridization (FISH) and comparative genomic
A lumbar puncture is also done during the ­staging
hybridization (CGH)
work-up; approximately 5–10% of patients show
• Immunophenotyping – a technique used to ­leukaemic spread to the CSF.
identify surface markers and antigens on
leukaemia and lymphoma cells to aid diagnosis Classification and prognostic factors
and classification.
Specific chromosomal translocations can also be iden-
tified, for example t(8;14) in B-cell ALL and the unfa-
Acute lymphoblastic leukaemia vourable t(9;22) or the BCR-abl gene (Philadelphia
chromosome) identified in CML and 5% of paediatric
Presentation patients with ALL.
The clinical presentation of ALL can be quite vari- Table 16.3.3 shows prognostic risk factors for ALL.
able, but most children will present with a 3–4-week Clinical features such as age and WCC at ­diagnosis are
prodrome that may include pallor, increased bruising becoming less significant as protocols s­ tratify treatment
or bleeding, lethargy, anorexia, recurrent infection or based on the response to treatment; for e­ xample, reduc-
fevers, anorexia, bone pain or reluctance to walk. tion of initial blast count following steroid t­ herapy is an
Common physical examination findings include pal- important prognostic factor, as is d­ etection of m ­ inimal
lor (80%), petechiae (50%), lymphadenopathy (35%), residual disease (MRD) by molecular m ­ ethods after
hepatomegaly or splenomegaly (50–60%). Rarely, skin chemotherapy.
infiltration (chloroma) and testicular infiltration (usu-
Treatment
ally presenting as a painless swelling) are seen.
T-cell leukaemia, more common in older boys, pres- Current combination chemotherapy protocols for ALL
ents with a mediastinal mass in 50% of cases. This result in cure of 80% of patients. Much of the required
can result in life-threatening airway compromise and therapy can be given on an outpatient basis. Treatment
obstruction of the superior vena cava. Some 30% of consists of phases of therapy including induction,
patients with T-cell ALL present with a leukocyte consolidation, CNS-directed therapy, ­
­ re-induction,
count greater than 100 × 109/L, and there is a higher and continuation or maintenance therapy.
incidence of CNS disease. By the end of the first month of therapy (induction)
with 3–4-drug combination chemotherapy (vincristine,
asparaginase, prednisone, daunorubicin), ­ remission
Investigations
will be achieved in more than 95% of patients. Further
The peripheral blood film can be normal but will usu- combination therapy is required to prevent relapse.
ally demonstrate the presence of leukaemic blasts with The optimal total duration of therapy varies in clinical
or without anaemia and thrombocytopenia. The white trials between 2 and 3 years.
blood cell count (WCC) is frequently raised at diag- CNS-targeted therapy using high-dose intravenous
nosis (leukocytosis), with a presenting WCC below and intrathecal methotrexate has allowed cranial irra-
10 × 109/L in 25%, 10–50 x 109/L in 50% and above diation to be avoided except in patients with overt CNS
50 x 109/L in 25% of patients. A bone marrow aspi- disease or high-risk disease requiring a bone ­marrow
rate and biopsy (trephine) are the ‘gold standard’ transplant. This has reduced, but not e­liminated,
diagnostic tests and will show replacement of normal potential long-term cognitive, endocrine and growth
570
­haematopoiesis by ­leukaemic cells (Fig. 16.3.1). complications.
 CANCERS 16.3
Table 16.3.3 Risk group classification for acute lymphoblastic leukaemia

Risk group Clinical features Molecular/genetic features

Low risk Age 2–10 years, WCC < 50 × 109/L DNA index > 1.16
Not T-cell phenotype Absence of:
No central nervous system or testicular disease t (9;22) BCR–abl
Rapid response to induction therapy t(4;11) MLL/AF4
t (1;19)
MLL rearrangement
t (12;21) TEL/AML1

High risk and very high risk Induction failure t (9;22), t (4;11)
Age < 12  months MLL rearrangements
Poor prednisone response
High MRD levels

MRD, minimal residual disease; WCC, white blood cell count.

Presentation
Clinical example
Presenting symptoms and signs are similar to those of
Sally was a 3-year-old girl who presented ALL, and can include pallor, bleeding, fever, anorexia,
with a 2–3-week history of intermittent fever, malaise and bone pain. Certain subtypes of AML
lethargy and poor appetite. Reluctance to have more distinctive presenting clinical features.
walk and increased bruising were also noted Acute promyelocytic leukaemia (APML) can present
for 1–2 days prior to presentation. Examination confirmed with serious haemorrhage or disseminated intravascu-
a pale child with truncal petechiae, limb bruising, cervical
lar coagulation (DIC), whereas acute ­monoblastic or
lymphadenopathy, splenomegaly and hepatomegaly. What
was the differential diagnosis?
myelomonoblastic leukaemia may present with skin
The presence of fever suggested infection, pallor infiltration (chloroma) or gum hypertrophy. CNS
suggested anaemia, and petechiae and bruising ­leukaemia is diagnosed in 5–15% of patients.
suggested thrombocytopenia. A blood count would
confirm this. Lymphadenopathy and hepatosplenomegaly
were consistent with infection (e.g. infectious Classification and prognostic factors
mononucleosis, cytomegalovirus) or leukaemic infiltration.
As well as bone marrow aspirate and trephines, it is
Reluctance to walk, fever and mild anaemia may be
consistent with a primary joint problem such as juvenile
important to exclude testicular disease in boys and CNS
rheumatoid arthritis or osteomyelitis. A blood count and disease, as these are both sanctuary sites of disease.
film were warranted and a bone marrow aspirate was In AML, characteristic morphological features
needed to confirm the diagnosis of acute leukaemia. include the presence of Auer rods as well as positive
Other paediatric malignancies that may present with bone staining for myeloperoxidase and monocyte-associated
marrow involvement should be considered, including esterases (Fig. 16.3.2). Classification into one of
lymphoma, neuroblastoma, rhabdomyosarcoma and
Ewing sarcoma.

Acute myeloid leukaemia

AML is a cancer of the myeloid white blood cells,
which are produced in the bone marrow. AML
accounts for 20% of acute leukaemia.

Differential diagnosis
Like ALL, the differential diagnosis can include infec-
tion, juvenile rheumatoid arthritis, ­idiopathic throm- Fig. 16.3.2 Bone marrow aspirate in acute myeloid leukaemia, 571
bocytic purpura, aplastic anaemia and osteomyelitis. showing the presence of Auer rods.
 16.3 HAEMATOLOGICAL DISORDERS AND MALIGNANCIES

eight morphological subclasses using the French–

American–British (FAB) system is possible.
In addition to morphology and immunopheno-
type, genetic features of leukaemic cells can provide
diagnostic and prognostic information. In AML,
characteristic translocations are seen within FAB
­
­morphological ­subgroups; for example, M3 or APML
is identified by the translocation t(15;17), and t(8;21)
is a favourable cytogenetic abnormality seen in FAB
M1 and M2. Fig. 16.3.4 Dual-colour fluorescence in situ hybridization
with probes PML (15q22) and RARA (17q12), demonstrating
the presence of a PML–RARA fusion resulting from the 15:17
Treatment translocation arrows in acute promyelocytic leukaemia.

In contrast to ALL, therapy for AML is of shorter

duration but more intensive, often requiring frequent APML is a subtype of AML which is caused by an
hospital admissions with aggressive supportive care, accumulation of immature granulocytes called promy-
including blood products and antimicrobials during elocytes. This is due to the formation of a transloca-
lengthy periods of marrow suppression. tion t(15;17) fusion gene, which causes an arrest in the
Overall, the outlook for patients with AML is less maturation of myeloid cells at the promyelocyte stage.
optimistic, with survival rates reported of 50–75%. Patients often present with a coagulopathy, which
requires urgent careful management. In addition to
standard AML therapy, these patients also need treat-
ment with ATRA, which allows the maturation of
Clinical example promyelocytes.

Monica is an 8-year-old girl who presented

with a 1-week history of lethargy, poor appetite, Haematopoietic stem cell transplant
recurrent epistaxis and gum bleeding when
brushing her teeth. Examination revealed
For most patients with high-risk, relapsed or refractory
anaemia, gum hypertrophy, bruising on the lower limbs and leukaemia, haematopoietic stem cell transplantation
trunk, hepatosplenomegaly and inguinal lymphadenopathy. is the treatment of choice. Stem cells can be sourced
A full blood count confirmed anaemia and from the bone marrow, from peripheral blood or from
thrombocytopenia with a haemoglobin level of 8.2 g/L the umbilical cord of a newborn infant. Siblings have
and platelets 12 × 109/L, and a white cell count of 1.6 × 109/L a 25% chance of being an identical match. Patients
with circulating blast cells. Her coagulation profile was
lacking a sibling donor are reliant on volunteer bone
prolonged, consistent with mild disseminated intravascular
coagulation. marrow and cord blood donors sourced through
Bone marrow aspirate confirmed the diagnosis of international donor registries. Umbilical cord blood
acute promyelocytic leukaemia (Fig. 16.3.3), and this was ­transplants are used with increased frequency because
confirmed by immunophenotyping and cytogenetics of the advantages of speed of availability and greater
(Fig. 16.3.4). Lumbar puncture was performed to exclude likelihood of matching.
CNS spread.

Brain and central nervous

system tumours
Brain tumours or tumours of the CNS are the most
common primary solid cancer, representing approx-
imately 20% of all childhood malignancies. Brain
tumours as a group are heterogeneous with regard to
clinical ­presentation, location, histological type and
­natural history.
95% of CNS tumours occur within the brain, often
in specific sites for different age groups. Posterior fossa
tumours are more common in childhood, except dur-
Fig. 16.3.3 Bone marrow aspirate in acute promyelocytic ing the first year of life, and in adolescence, when
572
leukaemia. supratentorial sites predominate. Box 16.3.1 shows
 CANCERS 16.3
Treatment
Box 16.3.1 Classification of central nervous system
tumours Treatment of brain tumours depends on the tumour
type and location, and can include surgery, chemother-
1. Supratentorial
apy and radiation therapy. A number of factors affect
a. Hemisphere: astrocytoma; glioblastoma; primitive
neuroectodermal tumour
outcome and survival, including age, tumour location
b. Midline: craniopharyngioma; optic nerve glioma; and operability, histological subtype and presence or
pineal absence of metastatic dissemination.
2. Infratentorial Survival has improved considerably over time for
a. Cerebellar and fourth ventricle: astrocytoma; some types of tumour, notably medulloblastoma. For
medulloblastoma; ependymoma other tumour subtypes, however, such as brainstem
b. Brainstem: brainstem glioma
gliomas, outcome remains poor. Additionally, increas-
3. Spinal cord
Astrocytoma; ependymoma ing attention is being paid to the longer-term toxic-
ity of treatment. This is particularly true of radiation
therapy, which, where possible, is spared in younger
children because of the potential impact on cognition
a working classification of CNS tumours. The most and growth.
common histological subtypes are:
• astrocytomas (50%)
• primitive neuroectodermal tumours (21%)
• gliomas (15–20%) Clinical example
• ependymomas (9%).
Ben is an 18-month-old boy who developed
a squint of his right eye, and his mother
Presentation noted that his right eye had begun to bulge.
Early symptoms and signs of CNS tumours may In retrospect, he was also falling more
frequently and bumping into things. He had a number
be few and difficult to elicit (Box 16.3.2). Evidence
of café-au-lait spots on his trunk and abdomen, but no
of raised intracranial pressure is the most common subcutaneous nodules. He had proptosis and his right
­presentation because posterior fossa and deep midline optic disc was pale.
tumours usually obstruct CSF pathways. An ophthalmology review showed he had no vision in
his right eye and reduced vision in his left eye. Magnetic
resonance imaging of his brain and orbit (Fig. 16.3.5)
confirmed the presence of a bilateral optic tumour but
Box 16.3.2 Signs and symptoms of brain and central no signs of raised intracranial pressure. Chromosomal
nervous system tumours analysis and family tree confirmed that Ben had
neurofibromatosis type 1 (NF1), which is associated with
Raised intracranial pressure optic gliomas.
• Headache, often on waking
• Vomiting
• Papilloedema
• Tense fontanelle and increased head circumference in
infants indicating hydrocephalus
• Drowsiness, bradycardia and hypertension (late signs)

Posterior fossa signs

• Truncal ataxia due to central cerebellar tumours
• Coordination difficulties and tremor due to lateral lesions
• Cranial nerve palsies, suggesting a brainstem lesion
• Defective upward gaze with tumours of the pineal region
• Deep midline tumours around the third ventricle
• Impaired visual acuity and visual field defects due to
craniopharyngioma or optic nerve glioma
• Diabetes insipidus and growth failure
• Severe wasting and anorexia due to the diencephalic
syndrome of a hypothalamic tumour

Seizures
• Uncommon as sole presenting symptom
• Consider tumour with focal seizures or progressively more Fig. 16.3.5 Brain magnetic resonance image confirming the
difficult to control seizures presence of a bilateral optic tumour with no evidence of raised 573
intracranial pressure.
 16.3 HAEMATOLOGICAL DISORDERS AND MALIGNANCIES

Neurofibromatosis type 1 (NF1) is an autosomal superior vena caval and/or airway obstruction (a medi-
dominant disorder associated with benign and malig- cal emergency) producing stridor and cough, usually
nant tumours. The severity in individuals shows with an associated pleural effusion and ­characteristically
variable expression. There are two types; type 1 is asso- occurring in pre-teen or early teenage males.
ciated with tumours of the optic nerve known as optic Abdominal lymphoma accounts for 35–40% of
gliomas, neurofibromas, freckling of the groin and NHL, is of B-cell immunophenotype, and charac-
axilla, café-au-lait spots, skeletal abnormalities and teristically presents either as a local tumour caus-
Lisch nodules in the iris. ing intussusception or as massive, diffuse abdominal
Optic gliomas are the most common tumours of ­disease, often with ascites. An acute abdomen is not
the optic nerve. Biopsy is not required if radiology ­infrequently misdiagnosed as appendicitis.
shows a classical appearance. Treatment with sur-
gery and chemotherapy is highly variable. Optic Investigations
gliomas are usually low-grade and slow-growing in
children, and affected patients with NF1 have a more Diagnosis and staging involves ultrasonography of
­favourable prognosis. palpable lymph nodes and computed tomography
(CT) of the chest, abdomen and pelvis. Positron emis-
sion tomography (PET) has been useful in diagno-
sis and reassessment, but is not currently used in risk
Lymphoma stratification in NHL.
Lymphoma is a tumour of the lymph tissues (lymph Discussion about the appropriate biopsy site
nodes, lymph vessels, spleen, bone marrow, thymus between oncologist and surgeons and interventional
and tonsils), which are part of the immune system. radiologist is important to minimize risk. Lymph
The lymphatic system runs throughout the body, node biopsy or resection, bone marrow aspirates and
which means you can get a lymphoma almost any- ­trephine samples are analysed for morphology, immu-
where in the body. nophenotyping and cytogenetics. CSF examination is
Lymphomas account for approximately 10% of also required.
childhood cancers and are the third most common When more than 25% of bone marrow is involved,
form of malignancy in childhood. There are two basic disease is classified as T- or B-cell ALL. NHL in child-
types: non-Hodgkin lymphoma (NHL) and Hodgkin hood can be classified as:
disease. Both are more common in boys than in girls. • lymphoblastic NHL – diffuse, poorly differentiated,
Although lymphadenopathy attributable to an infec- primarily T-cell lineage
tious aetiology is common in childhood, any child • small non-cleaved (undifferentiated) Burkitt or
with persistent adenopathy (> 2–3 weeks) should be non-Burkitt subtypes, primarily of B-cell origin.
considered for a biopsy. The site of adenopathy (e.g. A t(8;14) translocation is characteristic of Burkitt
supraclavicular) or character (firm, large > 2 cm) may lymphoma
indicate the need for earlier biopsy. • large cell lymphoma – can be cleaved or non-
cleaved and of B- or T-cell origin.
Non-Hodgkin lymphoma
Childhood NHL has quite different features from its Treatment
adult counterpart. Childhood NHL is more often dis- Multiagent chemotherapy is the treatment of choice,
seminated, diffuse, not nodular, high-grade, immature although surgical resection may be part of the treat-
T- or B-cell lineage with frequent spread to extrano- ment. The intensity and duration depends upon the
dal sites, marrow and CNS. In contrast, adult NHL histological type and stage. Stages I and II have a more
is usually a low-grade malignancy with predominantly than 90% cure rate, and stages III and IV a 70–80%
nodal involvement. cure rate.

Presentation
Clinical example
NHL usually presents acutely or subacutely with
very short symptom intervals. Nodal disease may Luke is a 12-year-old boy who presented
be present, but is rare. Systemic symptoms such as with acute cough, wheeze and sudden
fever, weight loss, and night sweats referred to as B onset of faint stridor. Examination revealed
­symptoms are not as common as in Hodgkin disease. supraclavicular adenopathy, a mass palpable in
Specific symptoms depend on the site of involvement. the suprasternal notch, decreased air entry and dullness to
percussion note at the right base. Luke's face was suffused
A mediastinal primary of T-cell immunophenotype
574 with venous distension.
accounts for 25% of NHL and often presents with acute
 CANCERS 16.3
rates of secondary cancers (associated with the use
Symptoms and signs suggested superior vena caval
syndrome with airway obstruction. This constituted an
of radiation and etoposide) and reducing long-term
oncological emergency. Chest X-ray confirmed a large organ morbidity (e.g. lung toxicity from bleomycin,
mediastinal mass and a right pleural effusion. Urgent cardiomyopathy from anthracyclines) without com-
­
diagnosis and commencement of therapy (steroids) promising cure rates.
was required to prevent complete airway obstruction.
Thoracocentesis and cytological analysis confirmed a
diagnosis of T-cell lymphoblastic lymphoma. Precautionary
admission to the intensive care unit was recommended. Full
staging work-up required chest/abdomen/pelvis CT, nuclear Clinical example
medicine PET, bone marrow biopsies and lumbar puncture.
Although uncommon, the diagnosis of an obstructive Amy is a 15-year-old girl who had just started
mediastinal mass should be entertained in children or treatment for stage 4 Hodgkin's disease. The
adolescents with onset of wheezing, particularly when there day after starting treatment with steroids and
is no prior history of asthma. chemotherapy, her blood electrolytes were
markedly deranged, with increased potassium, urate and
phosphate, low calcium and poor urine output. Her blood
pressure was in the normal range, but was higher than her
Hodgkin disease pre-treatment blood pressure.
Amy's fluid input was increased, she was started
Hodgkin disease is commonly seen in adolescent and on rasburicase (recombinant urate oxidase) and her
young adult patients, more commonly in boys than electrocardiogram (ECG) was monitored continuously for
girls, and is rare before age 5 years. Epstein–Barr virus arrhythmias. Blood electrolytes and venous gases were
(EBV) can be identified in some Hodgkin cells, but the measured frequently to ensure Amy did not develop renal
failure.
significance is not clear. There are five types of Hodgkin
disease: classical Hodgkin disease is either mixed cellu-
larity, nodular sclerosis, lymphocyte-depleted or lym-
phocyte-rich on histology, whereas n ­ odular lymphocyte
Tumour lysis syndrome is the rapid development
predominant is a s­ eparate entity.
of metabolic abnormalities, from the release of intra-
cellular contents into the bloodstream due to cell
Presentation death, which can result in renal failure. Tumour lysis
syndrome can result in significant renal impairment
A painless, progressive swelling of lymph nodes (above and life threatening electrolyte disturbances (hyper-
the diaphragm in two-thirds of patients) is the most kalaemia, hyperphosphatemia and hypocalcaemia).
common clinical presentation. Dissemination to This can happen spontaneously or at the start of
spleen, liver, lungs, bones and bone marrow can occur. treatment, and is commonest with leukaemias and
Patients with mediastinal disease may present with lymphomas, although it can occur with large solid
shortness of breath, cough, orthopnoea or chest pain. tumours.
Constitutional symptoms (B symptoms) occur in one- Recognition of patients at risk and prevention by
third of patients. Adolescent or young adult patients assessment of electrolytes, fluid balance, weight and
who drink alcohol may complain of pain at the sites of blood pressure is important in the first 3–5 days after
nodal disease (10%). the start of treatment. Vigorous hydration with intra-
venous fluid, forced diuresis and allopurinol are stan-
Diagnosis dard. Dialysis is occasionally required. Allopurinol is
a xanthine oxidase inhibitor that is given to reduce the
The diagnosis and staging investigation are the same conversion of nucleic acid by-products to uric acid and
as for suspected NHL. PET has been useful in diag- therefore prevent urate nephropathy. In patients with
nosis and reassessment, and in reducing late effects a high WCC or very bulky disease or renal impair-
by enabling risk stratification; patients with a good ment, recombinant urate oxidase converts poorly solu-
response to treatment continue on chemotherapy but ble uric acid to soluble allantoin, lowering plasma uric
no longer require radiotherapy. acid levels.

Treatment Neuroblastoma
Multiagent chemotherapy and radiotherapy clini- Neuroblastoma accounts for about 8–10% of child-
cal trials have achieved excellent cure rates, with sur- hood cancers. It is the most common extracranial
vival greater than 90%. The emphasis has now turned solid tumour in childhood. Most cases occur in
575
to reducing late effects, preserving fertility, reducing ­children under the age of 5 years, with a median age
 16.3 HAEMATOLOGICAL DISORDERS AND MALIGNANCIES

at ­presentation of 23 months. Neuroblastomas origi- • Staging investigations include CT/magnetic

nate from primordial neural crest cells that normally resonance imaging (MRI) of the primary tumour,
give rise to adrenal medulla and sympathetic ganglia; bilateral bone marrow aspirate and trephine (core)
they can develop at any site of the sympathetic ner- biopsies, bone scan and meta-iodobenzylguanidine
vous system. Some 70% arise in the abdomen, either (MIBG) scan. MIBG is a radiolabelled compound
in the adrenal gland or in retroperitoneal sympathetic taken up by cells of the sympathetic nervous
ganglia, and 30% arise in cervical thoracic or pelvic system that demonstrates catecholamine synthesis.
ganglia. Approximately 90–95% of neuroblastomas show
uptake of MIBG.
Presentation
The clinical manifestations of neuroblastoma vary Stage 4S disease
depending on the primary site of disease, m ­ etastatic
burden and metabolically active by-products.
­ Stage 4S disease is seen in infants less than 18 months
Variations in the location, degree of differentiation, who have a localized tumour with metastatic disease
clinical and biological behaviour of these tumours to skin, liver or bone marrow, but not bone cortex
are diverse. Spontaneous regression and differentia- ­disease. These infants generally have excellent s­ urvival,
tion into benign neoplasms is seen at one end of the with tumours spontaneously regressing without the
spectrum and highly aggressive tumours resistant to need for treatment.
intensive chemotherapy at the other. Metastatic neuro-
blastoma in children older than 18 months has a poor
prognosis. Unfortunately, more than 75% of patients Prognostic factors
present with metastatic disease at the time of diagnosis. • Biochemical – NSE < 100 ng/mL, normal ferritin,
Common presentations include: high vanillylmandelic acid/homovanillic acid
• Non-specific symptoms, such as pallor, irritability, (VMA/HVA) ratio and low LDH are good
bone pain and gait changes prognostic factors.
• Abdominal disease – abdominal mass or abdominal • Biological – The N-myc oncogene is present in
pain increased numbers of copies in about 30% of
• Cervical or thoracic disease – cervical mass, cough, neuroblastomas and correlates with poor survival.
dyspnoea, dysphagia, Horner syndrome 17q gain and loss of heterozygosity are also poor
• Paraspinal disease – presents with back pain, prognostic factors, whereas hyperdiploidy is a good
tenderness, limp, bladder and sphincter dysfunction prognostic factor.
• Skin disease – subcutaneous nodules
• Paraneoplastic syndromes:
• opsomyoclonus–myoclonus Treatment
• excessive catecholamine secretion, causing
Low risk:
sweating, flushing, pallor, headaches, palpitations
and hypertension
• usually surgery is enough
• usually infants
• vasoactive peptide secretion, causing intractable
diarrhoea resulting in failure to thrive and
• > 95% cure rate.
Intermediate risk:
hypokalaemia
• 90% cure rate
• Common sites for metastatic disease are bone,
lymph nodes and bone marrow.
• treated with surgery and low-dose chemotherapy.
High risk:
Investigations • metastatic, N-myc amplified
• need surgery, intensive chemotherapy, transplant,
• Haematological – full blood count (FBC) and radiation, maintenance therapy.
coagulation Novel cytotoxic agents, targeted ­radionucleotide ther-
• Biochemistry – urea, electrolytes and creatinine apy and immune-mediated therapy are all ­currently
(UEC), comprehensive metabolic panel (CMP), being investigated in clinical trials.
liver function tests (LFTs)
• Tumour markers – raised lactate dehydrogenase
Wilms' tumour (nephroblastoma)
(LDH), ferritin, non-specific enolase (NSE)
• Urine catecholamines positive in 90% of patients Wilms' tumours account for 6% of childhood malignan-
• Biopsy is required for histological diagnosis and cies and are the fifth most common childhood malig-
biological samples that are required to stratify nancy. They represent the vast majority of ­primary
576
patients to risk groups. renal cancers in childhood. Over 90% of children
 CANCERS 16.3
­ iagnosed with Wilms' tumour are under 5 years of
d
age. Thanks to collaborative multicentre clinical trials, Clinical example
the overall survival of these patients exceeds 90%.
Brigitte, aged 4 years, was brought to the
emergency department with a short history of
Presentation abdominal pain, fever, general malaise and
weight loss. On examination, she appeared to
Children usually present with a painless abdomi- be an irritable child with tachycardia and mild hypertension.
nal swelling or an asymptomatic abdominal mass She had a distended abdomen with a large, poorly defined,
picked up by one of their parents. Occasionally the palpable, hard mass in the periumbilical area. A plain
tumour may bleed or rupture, causing pain in 20% X-ray showed calcification within the mass. A large primary
of patients. Malaise, gross or microscopic haematu- adrenal mass was confirmed on CT. Open biopsy confirmed
neuroblastoma, and the remaining staging examination
ria, fever, anorexia or hypertension occur in approxi-
(bone marrow biopsy, nuclear medicine bone scan and MIBG
mately 25% of patients. Some 8–10% of patients with scan) demonstrated metastatic disease to the bone marrow
Wilms' tumour have an acquired von Willebrand fac- and bone cortex of three vertebrae consistent with stage
tor abnormality with prolonged coagulation studies at 4 disease. Tumour biology from lymph node biopsy and
diagnosis. bone marrow aspirate confirmed the presence of increased
Most Wilms' tumours are not associated with a copies of the N-myc oncogene, a bad prognostic indicator.
genetic syndrome, but it is very important to take a Differential diagnosis of an abdominal mass in childhood
includes neuroblastoma, Wilms' tumour, lymphoma,
three-generation family tree history and examine the
rhabdomyosarcoma and germ cell tumours.
child for genital abnormalities (hypospadias, crytor-
chidism), hemihypertrophy (asymmetry of the left
and right side of the body) and aniridia (iris hypo-
plasia). Some examples of predisposing syndromes
associated with Wilms' tumours include Beckwith–
Sarcomas
Wiedemann syndrome, Denys–Drash syndrome, Sarcomas are tumours arising from connective t­issue.
congenital aniridia, hemihypertrophy and trisomy These cells originate from bone, cartilage and fat
18. These children are screened every 6 months by ­tissues, and are given a number of different names
abdominal ultrasonography. depending on the type of tissue from which they arise.

Investigations Bone cancers (osteosarcoma and Ewing sarcoma)

The common sites of blood-borne metastases are liver Primary bone tumours in childhood occur less
and lung. Extension to regional lymph nodes, hepatic ­frequently than bony metastases to the skeleton. Bone
adhesion, and tumour invasion of the renal vein and tumours are the sixth most common tumour type in
inferior vena cava, which can extend up to the right childhood, but the third most frequent tumour type in
atrium, occur rarely. adolescents and young adults. Osteosarcoma (OS) is
Baseline investigations usually include a FBC, renal more common than Ewing sarcoma.
and liver function, coagulation screen and urinalysis.
If tumour extension or involvement of the inferior
Osteosarcoma
vena cava is suspected, contrast-enhanced CT of chest,
abdomen and pelvis is carried out for staging. Osteosarcomas are commonly located at the metaph-
Biological studies on the tumour have identified yseal region of the distal femur, proximal tibia and
heterozyygosity at 16q or 1p as an adverse prog- proximal humerus, although they can be found in the
nostic factor increasing the chance of relapse and pelvis, skull and jaw. They are more common in ado-
death. lescents and young adults, with a peak in the second
decade of life, but they also affect younger children.
There is a slightly higher incidence in males and in
Treatment
patients of African descent.
Surgery can be performed at diagnosis or after The aetiology of osteosarcoma is not clear, but
response to some initial chemotherapy. The frequency there is a known association with exposure to ioniz-
and intensity of chemotherapy following surgery then ing radiation, bone dysplasias such as Paget disease,
depends on stage and histological subtype (favour- and syndromes such as retinoblastoma, Rothumund–
able versus unfavourable or anaplastic). Radiotherapy Thomson syndrome and Li–Fraumeni syndrome.
is used in patients with stage III and IV disease. Cure Mutations in recessive oncogenes (the retinoblastoma
rates exceed 90% for stage I–III and 85–90% for stage susceptibility locus and p53) have been postulated to
577
IV disease. play a role in the tumorigenesis in osteosarcoma.
 16.3 HAEMATOLOGICAL DISORDERS AND MALIGNANCIES

Presentation in the middle of the bone (diaphysis), and the primary

Common presentation includes joint swelling, bone site of disease is either in the extremities (53%) or in
pain especially with activity that becomes constant, the axial skeleton (47%).
pain worse at night, and not relieved by painkillers
Presentation
(non mechanical pain). It is common to have associ-
Like osteosarcoma, these patients usually present
ated history of trauma. Systemic symptoms and path-
with a long history of pain (96%) and a palpable mass
ological fractures are rare.
(61%). About 15% of patients have a pathological
The sentence should be unfortunately these patients
fracture at time of diagnosis. Approximately 25% of
can present with long symptom intervals. This may be
patients have evidence of metastatic disease at diagno-
because the failure to report symptoms, clinicians do
sis. Common sites of spread are lung, bone and bone
not think about malignancies in this age group or they
marrow (not seen in osteosarcoma).
have a confounding history of trauma or musculoskel-
etal problems. Investigations
Diagnostic tests include plain X-ray of the lesion in two
Investigations planes. The typical X-ray appearance of Ewing sarcoma
Common sites of blood-borne metastases are lung shows a poorly defined, destructive or ‘moth-eaten’ pat-
and, less commonly, bones. Diagnostic workup should tern, often accompanied by a multilaminated ‘onion skin’
include a plain X-ray and MRI or CT of the primary periosteal reaction with elevation (Codman's triangle).
lesions. Lung CT and bone scan are needed to identify MRI of the lesion is the ‘gold standard’ for local
potential disease spread, followed by a surgical biopsy staging, but CT of the primary lesion may also
for a definitive histological diagnosis. PET is still being be required, particularly to demonstrate cortical
evaluated in diagnosis and staging. ­fractures. A bone scan, bilateral bone marrow aspi-
Treatment rates and biopsies, and CT of the chest are performed
Treatment consists of chemotherapy followed by at diagnosis to define the metastatic spread of disease.
surgical resection of tumour and then further che- A tumour biopsy is required in all patients to confirm
motherapy. Most patients can have limb salvage the histological diagnosis. Molecular testing will iden-
surgery (surgery to spare the limb) rather than ampu- tify a translocation involving t(11;22) or EWS (Ewing
tation surgery. Osteosarcomas are rarely sensitive to sarcoma gene) in more than 90% of Ewing tumours.
radiotherapy. Treatment
Cure rates for patients with non-metastatic disease Treatment consists of a combination of multiagent che-
at diagnosis are over 70%. The histological response motherapy, surgery and radiotherapy. The majority
of tumour following chemotherapy is a predictor of of patients are able to have limb salvage surgery (sur-
outcome; patients with a good response (defined as gery to spare the limb). Recent research has shown that
> 90% necrosis) have a long-term survival rate greater intensifying chemotherapy by compressing chemother-
than 80%, compared with poor or standard responders, apy cycles (from 28 to 21 days) with ­granulocyte colony-
whose survival rate is 40–60%. The survival of patients stimulating factor (G-CSF) s­ upport increases survival.
with metastatic disease at diagnosis remains poor Several prognostic factors have been identified,
(< 50%). The addition of the immune-enhancing drug including tumour site, tumour size, histological grade,
muramyl tripeptide (MEPACT) has increased survival response to therapy, and the presence or absence
from 70% to 78% in localized disease. Clinical trials are of overt metastatic disease at diagnosis. Currently,
looking at the addition of immune enhancing drugs 60–70% of patients with localized disease will be
such a muramyl tripeptide (MEPACT) and Interferon. cured. The survival rate for patients with metastatic
disease remains less than 50%, underpinning the need
Ewing sarcoma for ongoing investigation into novel agents.
This is the second most common bone cancer, account-
Rhabdomyosarcoma and soft tissue sarcoma
ing for 10–15% of primary malignant bone tumours. In
contrast to OS, the peak incidence of Ewing sarcoma Soft tissue sarcomas make up 5% of paediatric can-
tumours occurs between 15 and 19 years of age after cer; about 50% of these are rhabdomyosarcomas.
which rates show a decline, but they are also seen in Rhabdomyosarcomas occur in early childhood with a
younger children and young adults. Ewing sarcoma is median age at diagnosis of 5 years, although a small
more common in males than in females and, unlike OS, number are seen in adolescent and young adult patients,
it is very uncommon in patients of African descent. who tend to present with more metastatic tumours.
Most of these tumours originate in the bone, There is a recognized association between rhabdo-
although they can occasionally arise in soft tissue myosarcoma and familial syndromes, including neuro-
578
(extraosseous Ewing). These tumours usually appear fibromatosis and Li–Fraumeni syndrome. L ­ i–Fraumeni
 CANCERS 16.3
syndrome includes clusters of soft tissue sarcomas,
was a bone or soft tissue sarcoma. Plain X-ray of the tibia
­adrenocortical carcinoma and early-onset breast cancer, confirmed a soft tissue mass and destructive bony lesion
and results from germline mutations in the p53 tumour with a ‘sunburst’ appearance, reflecting periosteal elevation
suppressor gene. Rhabdomyosarcomas are included in in the metaphyseal region. CT and MRI were used to
the small, round, blue cell tumours of childhood and delineate anatomy, followed by biopsy, which confirmed
are thought to arise from mesenchymal cells committed osteosarcoma. A history of trivial injury is often associated
to muscle differentiation. There are two major histologi- with bone tumours, but there is scant evidence to suggest
a causal relationship; more probably the injury serves as a
cal subtypes of rhabdomyosarcoma: embryonal (80%)
trigger to seek medical attention.
and the more aggressive alveolar (20%).
Presentation
Differences in presentation are seen depending on the
clinical site. The common clinical sites and presenta- Rare tumours
tion include:
A detailed review of all childhood malignancy is beyond
• orbit, head and neck including parameningeal the scope of this chapter. The reader is referred to more
(40%) – proptosis, loss of or change in vision,
extensive paediatric oncology material for a review on
rhinorrhoea and nasal obstruction
retinoblastoma, hepatoblastoma, germ cell tumours,
• extremities (20%) – painless mass, regional or histiocytic disorders, nasopharyngeal carcinomas and
distant lymphadenopathy
other malignant diseases occurring in childhood.
• genitourinary (20–25%) – bladder or bowel
dysfunction, paratesticular mass or mass arising
from cervix or vagina, change in menstruation
pattern or menorrhagia Late effects of cancer therapy
• trunk (10–15%). Survival for most childhood malignancies has
Investigations improved, so that, in 2011, 1 in every 250 adults was
Approximately half of all patients will have irresect- a survivor of childhood or adolescent cancer. In addi-
able tumours at diagnosis. Less than 25% of patients tional to improving survival, clinical trials are now
will have metastatic disease at diagnosis involving lung, focusing on ways in which the potential late effects of
bone marrow, bone or lymph nodes, but this increases cancer treatments can be reduced. The late effects of
in adolescent patients. MRI of primary tumour is the cancer treatment can affect every organ, and unfor-
investigation of choice for children with rhabdomyo- tunately 50% of survivors have at least one long-term
sarcomas. Technetium-99m bone scan, CT of the lung problem following treatment. Systematic surveillance
and bone marrow biopsy are required to assess for and management of late effects of therapy is now the
metastatic disease. focus of many childhood cancer units and cooperative
study groups. Examples of potential late effects are:
Treatment • Psychosocial – effect of treatment on education and
Therapy for rhabdomyosarcomas depends on the employment attainment, entry into certain jobs,
location and stage of disease, and is often multi- relationships with peers, and health insurance
modal, involving surgery, adjuvant chemotherapy and • Neurocognitive effects – secondary to surgery,
radiotherapy. Prognostic variables include metastatic chemotherapy or radiotherapy
­disease at diagnosis, site of disease, surgical resectabil- • Endocrine effects – poor growth, pituitary dysfunction
ity, histological subtype and age. Early-stage d ­ isease due to surgery, chemotherapy or radiotherapy,
is curable in more than 85% of patients. Patients with infertility, obesity
more aggressive disease have a poorer prognosis, • Cardiac – cardiomyopathy secondary to
­ranging from 30% to 50% depending on risk factors. anthracycline chemotherapy or heart damage due
to radiotherapy
• Respiratory – pulmonary fibrosis secondary to
Clinical example chemotherapy (e.g. busulphan or bleomycin) or
Peter, aged 13 years, had a 4-month history
radiotherapy
of pain around the knee. In the last 2 weeks • Effects on eyes, hearing or teeth – cataracts,
this had become severe and he was able to keratoconjunctivitis, decreased tear production,
walk only short distances. Peter recalled a failure of primary or secondary teeth to develop,
minor injury playing sport at the onset of his symptoms discoloration or increased dental caries, hearing
4 months ago. Examination demonstrated swelling on loss due to chemotherapy
the medial aspect of the proximal tibia with a diffuse,
firm, non-tender mass present. The most likely diagnosis
• Second malignancy – due to chemotherapy, 579
radiotherapy or an increased genetic susceptibility.
 16.3 HAEMATOLOGICAL DISORDERS AND MALIGNANCIES

including pain, dyspnoea, nausea/vomiting and bowel

Clinical example abnormalities, is important, as is optimization of psy-
chological, social and spiritual needs. Open discussion
Emily is a 12-year-old girl who was treated regarding the desired place of death (e.g. home, hospi-
at age 13 months for stage 4 neuroblastoma
tal or hospice) should take place in advance. A child's
with chemotherapy, surgery and total body
irradiation. Eleven years after treatment she
understanding of death will vary depending on age and
is a survivor of childhood malignancy but has a number of the individual, but many studies suggest that children
complications of treatment that require regular follow-up. as young as 6 years have an understanding of death
Emily has short stature due to radiotherapy and chronic and should be given the opportunity to talk openly
illness, and started growth hormone 1 year ago, which about their illness. Following the death of a child, one
has increased her growth velocity. She has high-frequency of the essential roles of the treating team is to provide
hearing loss requiring bilateral hearing aids, and poor
bereavement support for parents and siblings.
renal function secondary to cisplatin chemotherapy. She
has bilateral cataracts and problems with her teeth due to
radiotherapy. She enjoys school and will be starting in high
school next term, but has delayed numeracy and literacy
skills requiring extra educational support. The continual Practical points
medical needs require a coordinated multidisciplinary team
and have long-term financial and psychosocial effects on Childhood cancer
Emily and her family. • Childhood cancer is rare, with excellent survival rates for
most cancer types.
• A multidisciplinary team approach delivers best therapy to
children with cancer.
• Acute leukaemia and brain tumours account for a
Palliative care significant proportion of all childhood cancers.
• Treatment depends on cancer type and stage and
Cancer is the most common cause of non-accidental can include surgery, radiation, chemotherapy and
death in childhood. Approximately 20–25% of children immunotherapies.
diagnosed with a malignancy die from their disease. • The long-term consequences of therapy must be
considered, including the impact on growth, fertility,
Optimal palliation requires open and ongoing com- learning and development, as well as late organ toxicity
munication between all members of the h ­ ealth-care and second cancers.
team, the child and family. Management of symptoms,

580
 17
PART

SEIZURE DISORDERS
AND DISORDERS
OF THE NERVOUS
SYSTEM

581
 17.1 Seizures and epilepsies
Jeremy Freeman, Simon Harvey

Few events are more alarming to parents than their sible, by the cause of the particular condition and
child having a first febrile convulsion or epileptic by the epileptic syndrome. An epileptic syndrome is
­seizure. Seizures occur in up to 5% of children, but an electroclinically distinctive condition identifiable
fortunately most are single episodes of a non-serious on the basis of a typical age of onset, specific EEG
nature. This chapter is concerned with the diagnosis findings, seizure types, and often other features that,
of seizures and related disorders, less so with the treat- when taken together, permit a specific diagnosis. The
ment of epilepsy and co-morbid conditions. syndrome diagnosis often has implications for treat-
ment, management and prognosis. One practical way
of o ­ rganizing the list of recognized syndromes is by
age of onset (Box 17.1.2). Some of the recognized
­syndromes are known to be due to single-gene muta-
Terminology and classification tions, primarily of genes coding for neuronal ion
An epileptic seizure is a transient occurrence of signs channels. Some epilepsies are due to cerebral or cor-
and/or symptoms due to abnormal excessive or syn- tical malformation, and others are associated with
chronous neuronal activity in the brain. Epilepsy is rare metabolic disorders. Some are due to prenatally
characterized by an enduring predisposition of the or postnatally acquired brain injuries. Unfortunately,
brain to generate epileptic seizures and by the neuro- the causes of the most common syndromes remain
biological, cognitive, psychological and social conse- unknown, although a polygenetic basis is most likely.
quences of this condition. For practical purposes, this Prospective studies of new-onset epileptic s­ eizures in
definition has generally excluded individuals with single childhood reveal that approximately 50% of patients
seizures, neonatal seizures, febrile seizures and seizures with a first seizure have a recurrence. Epilepsy, with
considered provoked by acute neurological insults or recurrent unprovoked seizures, has an incidence of
systemic illness. Children with conditions that do not about 60–80 in 100 000 and a prevalence of about 5 in
meet the criteria for diagnosis of epilepsy make up the 1000 in childhood, the incidence and prevalence being
vast majority of those presenting with seizures. highest in infancy. Studies of new-onset epilepsy in
The International League Against Epilepsy recog- childhood indicate a greater proportion with focal sei-
nizes two major categories of epileptic seizures, based zures than generalized and undetermined seizures.
on clinical and electroencephalographic (EEG) f­ eatures: Prospective studies of treated and untreated n ­ ew-onset
focal seizures and generalized seizures. Focal seizures epilepsy reveal that about 80% of children go into
originate within neural networks ­involving one hemi- remission, some with subsequent seizure relapses, and
sphere of the brain and are more or less localized at about 20% of children have treatment-resistant epilepsy.
onset, whereas generalized seizures start in and rapidly
involve networks in both cerebral hemispheres. Several,
pathophysiologically distinct generalized s­eizure types
are recognized by their different clinical and EEG pat- Common epilepsies of infancy,
terns, the most common being tonic–clonic, absence and childhood and adolescence
myoclonic seizures. Focal seizures have common patho-
Febrile seizures
physiological features and are not f­ urther classified, but
can be distinguished by the region of brain involved and Fever and seizures may occur together with infections
the resultant clinical manifestations; the terms ‘simple’ of the central nervous system (CNS) and with febrile
and ‘complex partial’ are no longer applied to focal sei- illnesses in children with epilepsy. However, fever and
zures according to degrees of impaired consciousness, seizures most often coexist as a manifestation of the
although this is still an important clinical distinction. syndrome of febrile seizures, a condition in which some
Epileptic spasms are not definitively focal or general- infants and young children have a presumed genetic pre-
ized in nature, hence are given a separate category in the disposition to seize in the presence of fever. Although
­current s­ eizure classification (Box 17.1.1). not included within the classical definition of epilepsy,
582 The conditions that predispose to epileptic seizures the syndrome of febrile seizures shares features in com-
(the epilepsies), are best characterized, when pos- mon with certain epilepsies, including an age-limited
 Seizures and epilepsies 17.1
Box 17.1.1 Classification of epileptic seizure type, based Box 17.1.2 Epileptic syndromes by age of onset*
on clinical and EEG features
Neonatal period and infancy
Generalized • Early myoclonic encephalopathy
• Tonic–clonic • Early infantile epileptic encephalopathy with suppression
• Absence burst (Ohtahara syndrome)
• Myoclonic • Epilepsy of infancy with migrating focal seizures
• Clonic • Benign familial neonatal and infantile epilepsy
• Tonic • Generalized epilepsy with febrile seizures plus (GEFS+)
• Atonic • Infantile epileptic encephalopathy with epileptic spasms
(West syndrome)
Focal • Benign myoclonic epilepsy of infancy
• Severe myoclonic epilepsy of infancy (Dravet syndrome)
Uncertain
• Epileptic spasms Childhood
• Childhood absence epilepsy
• Benign childhood epilepsy with centrotemporal spikes
(rolandic epilepsy)
predisposition to seizures and a family history of sei- • Early-onset benign occipital epilepsy (Panayiotopoulos
zures in more than 30% of children. Some families are syndrome)
described in which the same neuronal ion channel gene • Late-onset benign occipital epilepsy (Gastaut type)
mutation is found in individuals with ­epilepsy and those • Epilepsy with myoclonic–atonic seizures (Doose syndrome)
• Epilepsy with myoclonic absences
with febrile seizures alone. Febrile seizures are not just a • Childhood epileptic encephalopathy with tonic seizures
non-specific seizure susceptibility in infants. (Lennox–Gastaut syndrome)
Simple febrile seizures are defined as brief, general- • Autosomal-dominant nocturnal frontal lobe epilepsy
ized tonic and/or clonic seizures in which there is nei- • Epileptic encephalopathy with continuous spike-and-wave
ther clinical nor laboratory evidence of CNS infection, during sleep
the temperature is 38 °C or higher, and the child has no • Landau–Kleffner syndrome
history of previous afebrile seizures, neurological defi-
Adolescence
cits or developmental delay to suggest an underlying • Juvenile absence epilepsy
neurological problem. Most febrile seizures are associ- • Juvenile myoclonic epilepsy
ated with upper respiratory or urinary tract infections • Epilepsy with generalized tonic–clonic seizures alone
or viral exanthemas and occur once at the beginning • Progressive myoclonus epilepsies
of the illness. Complex febrile seizures are those that
are prolonged, focal or multiple. Less specific age relationship
• Epilepsies with focal seizures due to structural brain
Febrile seizures occur in approximately 3% of the pop-
abnormalities (e.g. temporal lobe and frontal lobe epilepsy)
ulation, commencing between the ages of 5 months and • Reflex epilepsies (e.g. photosensitive epilepsy)
5 years, with most manifesting in the first 2 years of life.
In approximately one-third of ­children febrile ­seizures *This table excludes consideration of common conditions
are recurrent, the risk increasing to 50% if onset is in presenting with seizures in childhood, but not fulfilling criteria for
infancy or there is a family history of febrile seizures. epilepsy. These include: benign neonatal seizures, febrile seizures,
single seizures and acute symptomatic (provoked) seizures.
Only 3% of children with febrile seizures develop epi-
lepsy. The risk is increased when there is abnormal
development or neurological impairment, when there
is a family history of epilepsy or if the febrile seizures about the role of antipyretics and gentle cooling.
are complex. When epilepsy follows febrile seizures it is Seizures have usually ceased before medical help is
invariably a later manifestation of the same underlying obtained; however, if a febrile seizure continues after
seizure predisposition. Very rarely, later epileptic sei- 3–5 ­minutes, it should be terminated urgently, u ­ sually
zures may be the result of brain injury from ­prolonged with buccal, intramuscular or intravenous midazolam.
and focal febrile ­seizures (febrile status epilepticus). Meningitis or encephalitis should be strongly consid-
Febrile seizures are not associated with increased mor- ered if the child has a history of vomiting, is younger than
tality or later ­intellectual impairment. 6 months, has repeated seizures following ­presentation,
has been treated with antibiotics, has not ­recovered
promptly from the seizure or seems more ill than
would be expected following a simple febrile seizure.
Treatment
Antiepileptic medication does not diminish the like-
The cause of the febrile illness is investigated and lihood of later epilepsy and is rarely prescribed for the
treated on its own merits. There is no role for EEG syndrome of febrile seizures. Parents and carers need 583
or brain imaging in febrile seizures. There is debate explanation and reassurance about the benign nature of
 17.1   SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

the condition, the likelihood of further febrile seizures, including prenatal, perinatal or postnatal brain injury
and the management of subsequent febrile illnesses and (stroke or infection), focal or diffuse brain malforma-
seizures. Children with a history of prolonged febrile sei- tions, tuberous sclerosis and metabolic conditions. In
zures may be prescribed emergency buccal midazolam. these cases, the outcome for seizures and development
is usually poor. In children where no cause is identi-
fied, outcome is more variable; if there is a prior his-
West syndrome
tory of developmental delay and spasms are not
West syndrome, also known as infantile spasms, is quickly controlled with treatment, outcome is again
the most common and important to recognize severe poor. Overall, 70–80% of children with West syndrome
epileptic syndrome in infancy. The principal seizure develop some degree of intellectual disability and
type is epileptic spasms, which are essentially brief 30–50% develop intractable seizures. In many children
tonic seizures that typically occur in series over a with chronic epilepsy following West syndrome, the
minute or more, usually many times a day. Onset of electroclinical ­picture evolves to that of the Lennox–
spasms is usually between 3 and 8 months of age, and Gastaut syndrome with refractory tonic and other sei-
males are affected more often than females. Flexor or zures, g­eneralized slow spike–wave and paroxysmal
salaam spasms are the most common and consist of fast ­activity on EEG, and severe ­intellectual ­disability.
sudden drawing up of the legs, hunching forward of The neurological sequelae of West syndrome are the
the neck and shoulders, and flinging out of the arms; result of both the underlying cause and the deleterious
opisthotonic or extensor spasms are less common. effects of the ­epileptic encephalopathy on the develop-
The EEG usually shows a diffusely disorganized pat- ing brain.
tern with high-voltage, multifocal epileptic activity,
called hypsarrhythmia (Fig. 17.1.1). Development
Treatment
may be delayed prior to the onset of spasms, or there
may be loss of visual attention and arrest or regres- West syndrome needs urgent diagnosis, investigation
sion of development at seizure onset. The develop- and treatment. Treatable metabolic conditions need
mental regression that occurs in West syndrome is exclusion, and pyridoxine-dependent seizures should
attributable to the epileptic disorder and the condi- be considered in children with prior epileptic seizures.
tion is therefore considered to be an epileptic enceph- Corticosteroid therapy (oral ­prednisolone or intramus-
alopathy. Differential diagnosis includes a variety of cular adrenocorticotrophic hormone, ACTH) is more
normal or benign infant behaviours, such as sleep efficacious than vigabatrin and other a­ ntiepileptic drugs
jerks, colic, shuddering attacks, benign myoclonus for achieving rapid cessation of spasms. For children with
of infancy and gastro-oesophageal reflux, as well as no identified predisposing c­ondition, ­ corticosteroid
other less sinister myoclonic epilepsies of infancy. therapy also leads to better d ­ evelopmental outcome.
West syndrome is an age-dependent manifestation Vigabatrin is a second-line agent, except in children with
of a severe disturbance in the immature CNS. An tuberous sclerosis where it is often used first. Other anti-
underlying cause is identified in about 80% of infants, epileptic medications are of lower efficacy or unproven

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Fig. 17.1.1 The EEG pattern of hypsarrhythmia, showing diffuse, continuous, high-amplitude, irregular sharp waves, spikes, and slow
waves on a disorganized background, typical of that seen in West syndrome.
 Seizures and epilepsies 17.1
benefit. In infants with unilateral strokes or malforma- Absence epilepsy
tions and drug-resistant seizures, epilepsy surgery may
Absence seizures are manifest by sudden cessation of
be considered. The aims of all treatments are to stop
activity with staring, usually lasting only 5–15 seconds.
seizures, suppress the epileptic EEG disturbances and
Blinking, upward deviation of the eyes, slight mouth-
maximize neurological development.
ing movements and some fidgeting hand movements
(automatisms) may occur. The child is unresponsive,
does not fall, is rarely incontinent and returns promptly
Clinical example to normal activity at the offset of the absence, with no
memory of the seizure. The EEG shows generalized
Baby Jonathan presented at the age of spike–wave activity during the seizure (Fig. 17.1.2).
5 months with episodes of stiffening and Usually, many attacks occur in a day. Absence s­ eizures
drawing up of his legs, thought to be colic. can generally be precipitated in the clinic room and dur-
The attacks lasted only seconds but occurred
ing EEG recordings with hyperventilation. Differential
in clusters up to 10 times each day, often after waking.
During the attacks, his eyes rolled up, he appeared
diagnosis of absence ­seizures includes day-dreaming
unaware and he would cry briefly. Jonathan's parents and focal seizures of temporal lobe origin.
were also concerned that he seemed irritable, was not Epilepsies with absence seizures usually present
fixing on their faces and was no longer smiling. The after 4 years of age and in otherwise normal children.
pregnancy, birth and early developmental milestones had There are two main syndromes described. In child-
been unremarkable. hood absence epilepsy (formerly ‘petit mal’ epilepsy),
On examination, Jonathan made little eye contact and
absences begin before 10 years of age, tonic–clonic
had poor head control. A cluster of typical symmetrical
epileptic spasms occurred during the assessment. seizures are rare, the EEG shows runs of regular
An EEG that day showed a modified hypsarrhythmic 3-Hz spike–wave activity, and prognosis for seizure
pattern, confirming West syndrome, and high-dose oral remission is good. In juvenile absence epilepsy, onset
prednisolone was started promptly. MRI examination, of absences is later, sometimes in the teen years, the
metabolic testing and molecular karyotype were normal. EEG may show faster and more irregular spike–wave
Spasms ceased after the third day of prednisolone and ­activity, there may be associated tonic–clonic sei-
there was improvement in visual attention in the following
zures, and prognosis for seizure remission is poorer.
week. EEG after 2 weeks of treatment showed a marked
reduction in epileptic activity with normal background
activity. Prednisolone was tapered over the next 3 weeks
and there was no recurrence of seizures after 1 month.
Treatment
Close observation for recurrent seizures, monitoring EEG is needed to confirm absence seizures and charac-
of developmental progression and repeat EEG were
terize the epileptic syndrome; brain imaging is unneces-
planned. The prognosis given to his parents was hopeful
but not overly optimistic concerning developmental
sary. Sodium valproate, ethosuximide and lamotrigine
outcome. are the medications used commonly to treat absence
seizures. Treatment is usually for 2 years in typical

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Fig. 17.1.2 The EEG of childhood absence epilepsy during an absence seizure, showing a paroxysm of generalized 3-Hz spike–wave
activity.
 17.1   SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

childhood absence epilepsy, with an expectation of zure and EEG focus is low in the central sulcus (rolan-
­seizure remission, and through puberty into the teen dic) region on one or both sides, and benign occipital
years in juvenile absence epilepsy. Rare refractory cases epilepsy, in which the seizure and EEG focus is in the
may respond to treatment with a ketogenic diet. occipital lobe on one or both sides. The cause of the
benign focal epilepsies is unknown; they are not due
to underlying structural brain lesions, and current evi-
dence of a genetic association is lacking. An age-lim-
Clinical example
ited, maturational disturbance in these brain regions is
Nadine, a 6-year-old girl, was noted by her postulated. The EEG abnormalities of the benign focal
parents to frequently ‘blank out’ while sitting epilepsies can be found in children with no history of
at the dinner table and, most recently, to stop seizures, sometimes leading to ­diagnostic errors.
walking and talking while shopping with her In benign rolandic epilepsy, seizure onset is usually
mother. These episodes were occurring several times a day between 5 and 10 years of age and there is a male pre-
and seemed to last only a few seconds. Her schoolteacher
dominance. Focal seizures feature tingling or twitch-
had not noticed any problems. Hyperventilation in the
clinic room provoked a typical episode lasting 12 seconds, ing of the mouth and preserved consciousness, often
during which Nadine was seen to stop hyperventilating, be with associated drooling, choking noises and inability
unresponsive, fidget with her shirt and have slight bobbing to speak. Seizures may progress to jerking of one side
of her eyes. Childhood absence epilepsy was confirmed with of the body, with or without impairment of conscious-
an EEG, which showed 3-Hz generalized spike–wave activity ness. Some children have convulsions in which the focal
during spontaneous and hyperventilation-induced absence onset is not recalled or witnessed. Attacks typically
seizures. Sodium valproate was introduced slowly over
3 weeks, with no absences noted after the second week of
occur from sleep. EEG recordings that include sleep
treatment and none precipitated with hyperventilation when reveal frequent focal epileptiform activity over the cen-
reviewed. Slight irritability and moodiness were reported by trotemporal regions on one or both sides (Fig. 17.1.3).
Nadine's parents as potential side-effects of treatment. In benign occipital epilepsy, the presentation is usu-
ally before 6 years of age and there is a female predom-
inance. The focal seizures are characteristically from
sleep, beginning with staring, vomiting, head rotation,
Benign focal epilepsies of childhood
eye deviation, and may lead to hemiclonic or bilateral
The benign focal epilepsies of childhood are some of jerking. Again, the focal onset may be unwitnessed.
the most common epileptic syndromes in children. Seizures can sometimes be prolonged and raise con-
They occur in otherwise normal preschool and primary cern about encephalitis. Daytime attacks may occur
school-aged children, and typically manifest with infre- with episodic visual distortions or hallucinations and
quent, sleep-related focal seizures and prominent focal migraine-like headaches. EEG recordings that include
epileptiform patterns on EEG. The two most common sleep reveal focal epileptiform activity over the occipi-
varieties are benign rolandic epilepsy (benign childhood tal regions. In typical cases of benign focal epilepsy,
epilepsy with centrotemporal spikes), in which the sei- brain imaging is unnecessary.

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Fig. 17.1.3 The EEG of benign childhood epilepsy with centrotemporal spikes (rolandic epilepsy) showing independent bilateral focal
epileptiform activity in the central regions.
 Seizures and epilepsies 17.1
Treatment of the actual seizure. Generalized tonic–clonic seizures
often occur during febrile illnesses in young children
Seizures tend to be infrequent in the benign focal epi-
and either during sleep or following periods of sleep
lepsies and many children have only one or two s­ eizures
deprivation or stress in older children and adolescents.
in total. Because of this, and the tendency for noctur-
The epilepsies with generalized tonic–clonic seizures
nal occurrence, treatment with antiepileptic medications
are a heterogeneous group of disorders that typically
is not always necessary. If warranted, treatment with
begin in childhood or adolescence and sometimes
sodium valproate or c­arbamazepine for 1–2 years is
feature additional absence and myoclonic seizures.
usually adequate. Prognosis is excellent, with absence of
Although the majority of the epilepsies with gener-
cognitive and behavioural ­problems, and remission of
alized tonic–clonic seizures are of unknown cause,
seizures by the teenage years – hence the term ‘benign’.
genetic factors are strongly implicated and some
In rare instances, these epilepsies may manifest in an
examples of single-gene defects are known. In general,
atypical way with more problematic seizures, continu-
there is no structural brain or metabolic abnormal-
ous bilateral EEG disturbances, and deleterious effects
ity, usually normal intellect and often a family his-
on language and motor d ­ evelopment; this tends to occur
tory of seizures. Sometimes there is a history of prior
in children with p
­ re-existing ­neurological problems.
febrile seizures or absence seizures; in these cases,
the later occurrence of tonic–clonic seizures repre-
sents an age-dependent expression of the same geneti-
Clinical example cally determined seizure tendency. The routine EEG
shows generalized spike–wave and polyspike–wave dis-
Michael, a developmentally normal charges. Juvenile ­myoclonic epilepsy typically begins in
8-year-old boy, presented to the emergency teenage years with generalized tonic–clonic seizures,
department of a regional hospital after being early morning myoclonic jerks, and sometimes brief
found seizing in his motel bed at 5 a.m. while
holidaying with his family. The seizure was brief, had bilateral
or subtle absence seizures. Photosensitive epilepsy is
tonic–clonic movements, was associated with prominent another syndrome with generalized tonic–clonic sei-
gurgling noises, and was followed by a 10–15-minute period zures, where the seizures and EEG abnormalities are
during which his speech was slurred and his face drooped almost exclusively related to flashing light stimulation.
on one side. The parents recalled hearing similar noises from The differential diagnosis of generalized tonic–
Michael's bedroom once or twice previously and occasionally clonic seizures includes: focal seizures that spread to
finding his pillow wet with saliva in the morning. Michael
become bilateral and convulsive; syncope, which typ-
described waking from his sleep in this seizure, having a
fuzzy feeling in his mouth and being unable to call out to his
ically involves clonic movements; and psychogenic
parents, who were sleeping in the same room. seizures. A preceding aura, focal or asymmetrical
An EEG arranged subsequently showed very frequent features to the seizure, transient postictal unilateral
left central–temporal epileptiform discharges that became weakness (Todd's paresis), focal neurological defi-
almost continuous in sleep. A diagnosis of benign rolandic cits on examination, or a history of a prior cere-
epilepsy was made. Following much parental counselling bral trauma or infection should suggest a focal basis
and reassurance about the benign nature of this type of
for an apparently generalized tonic–clonic seizure.
epilepsy, it was decided to not perform magnetic resonance
imaging (MRI) and to defer treatment with antiepileptic Seizures of brief duration with rapid recovery and
medication. General safety and lifestyle advice was given seizures occurring in typical vasovagal settings (see
about seizures, although it was appreciated that seizure below) should suggest syncope rather than epilepsy.
occurrence in the day was unlikely. Psychogenic seizures are highly variable in their man-
ifestations and can occur in patients with epilepsy,
making their diagnosis sometimes difficult; signs that
Epilepsies with generalized tonic–clonic suggest psychogenic seizures include eye closure dur-
seizures ing the event, resistance to ­passive eye-opening, and
intermittent or waxing and waning motor activity.
Generalized tonic–clonic seizures begin with loss of
consciousness, stiffening (tonic), temporary cessa-
Treatment
tion of breathing and falling if standing, then gradu-
ally progress to a phase with generalized, rhythmic Sodium valproate is the drug of choice for ­generalized
jerking (clonic), which is initially rapid but gradually tonic–clonic seizures, especially when there is
slows. Generalized tonic–clonic seizures invariably ­gener­alized spike–wave on EEG or a history to suggest
cease spontaneously, usually within a few minutes, and absence or myoclonic seizures. Carbamazepine is some-
are followed by a postictal period with depressed con- times used for generalized tonic–clonic seizures, but
sciousness and headache, during which the person usu- there is a risk of exacerbating absence and myoclonic
ally sleeps. There are no warning symptoms (auras), no 587
­seizures in predisposed patients. Several other anti-
significant focal features to the seizure, and no memory epileptic m
­ edications are also effective (Table 17.1.1).
 17.1   SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

Table 17.1.1 Antiepileptic medications most effective in different seizure types

Seizure type Antiepileptic medication

Focal Carbamazepine, oxcarbazepine, levetiracetam, lamotrigine, sodium valproate,

topiramate, gabapentin, pregabalin, lacosamide, zonisamide, benzodiazepines,
phenytoin, phenobarbital

Generalized tonic–clonic Sodium valproate, lamotrigine, topiramate, levetiracetam, carbamazepine,

phenytoin, oxcarbazepine, benzodiazepines, phenobarbital

Absence Sodium valproate, ethosuximide, lamotrigine

Myoclonic, atonic, tonic Sodium valproate, lamotrigine, benzodiazepines, topiramate, levetiracetam

Epileptic spasms Prednisolone/ACTH, vigabatrin

Seizure control is usually possible with medication and Epilepsies with focal seizures due to structural
­lifestyle adjustments (e.g. avoiding sleep deprivation). brain abnormalities
Many children with tonic–clonic seizures alone out-
Focal seizures can arise in any part of the brain and
grow their need for medication, but adolescents with
the manifestations of the seizure depend on the loca-
juvenile ­myoclonic epilepsy usually require treatment
tion and extent or spread of the seizure. An aura is the
into adult life.
phase of a focal seizure without loss of consciousness
that manifests as a feeling or experience rather than
as a movement or behaviour. Epilepsies with focal sei-
zures can be described in terms of the location of the
Clinical example seizure onset and the underlying pathology. Seizures
begin at any age but onset in late childhood and ado-
Stephanie, a 13-year-old girl with a history of lescence is common, even when due to congenital mal-
a single febrile seizure in infancy, presented formations. In infants and young children, lesions
to a regional hospital emergency department
may be multilobar or hemispheric. Where no lesion is
after having a generalized tonic–clonic seizure
at school camp. The seizure occurred in the shower at identified on MRI there may be clinical, EEG or func-
7 a.m., the morning after girls in Stephanie's cabin had tional imaging features that suggest an occult lesion.
stayed awake until 4 a.m. Stephanie was heard to fall in Seizures in temporal lobe epilepsy (TLE) charac-
the shower and was found by a friend convulsing on the teristically manifest by motionless staring, fearful
shower floor. She sustained a forehead bruise and hot or bewildered facial expression, unresponsiveness,
water scalding on her back. There was no history of staring
hand and mouth movements that resemble voluntary
episodes or isolated jerking of the limbs. Stephanie recalled
that on one occasion she had had to walk away from a
actions (automatisms), and postictal amnesia and con-
computer game that her brother was playing because she fusion. In some patients there may be head-turning or
felt sick and her head started jerking. There was no family stiffening or jerking of the limbs on one side during
history of epilepsy. the seizure. Autonomic disturbances, such as facial
Subsequent EEG recording showed frequent bursts of flushing or pallor, salivation and sometimes vomiting,
generalized fast spike–wave activity at rest and during may occur; apnoea may be the predominant manifes-
photic stimulation. A diagnosis of epilepsy with generalized
tation in infancy. An aura is often present but may
tonic–clonic seizures and associated photosensitivity was
made. Long discussions were held with Stephanie and not be described at the time or recalled in a young
her parents over the initial and subsequent consultations, or developmentally delayed child; fear, unusual smells
highlighting safety and lifestyle factors. Sodium valproate or tastes, abdominal discomfort and dizzy or dreamy
was commenced after discussion of the high likelihood of states are the usual descriptions. Seizures may spread
further seizures. The potential for weight gain and mild hair to become bilaterally convulsive. Seizures in TLE last
loss as side-effects of treatment was also discussed, these longer than absence seizures, generally 30–60 seconds,
concerning Stephanie more than the risk of further seizures.
and are followed by postictal confusion and sleepi-
The family was given a guarded prognosis for seizure
remission in the later teen years and regular review was ness. They are usually infrequent and commonly
arranged. occur in clusters over several days, alternating with
588 seizure-free periods.
 Seizures and epilepsies 17.1
Seizures in frontal lobe epilepsy (FLE) often occur
stiffening of the right hand and rocking movements. Twice
from sleep, are brief in duration, and typically ­manifest during illnesses, seizures became bilaterally convulsive. None
with prominent motor features such as unilateral or of the three antiepileptic medications used over the years had
bilateral stiffening or jerking, asymmetrical tonic pos- controlled Steven's seizures.
turing with head deviation to one side, loud vocaliza- MRI showed a lesion of benign appearance in the uncus
tion, and hyperkinetic automatisms such as tapping, of the left temporal lobe, thought to be a developmental
cycling and running. Seizures may occur on a mul- tumour. Video-EEG recording of seizures showed electrical
onset in the left temporal lobe region. Cognitive testing
tiple nightly basis. Consciousness may be ­preserved
showed normal intellect but decreased verbal abilities.
even when there are bilateral motor f­ eatures, or be lost Left temporal lesionectomy was performed and the
when the seizure discharge spreads bilaterally. histopathology revealed a ganglioglioma. After a year free of
The EEG in epilepsies with focal seizures may be seizures, Steven was gradually weaned off his medication.
normal, show non-specific abnormalities, or show Learning and behavioural difficulties persisted but were
localized epileptic patterns over the affected brain better managed with understanding of their cause, abolition
region. Video-EEG monitoring with recording of sei- of seizures, and institution of specific behavioural and
educational strategies.
zures is sometimes necessary to confirm the diagnosis
and localize the seizures. The differential diagnosis of
TLE, with episodes of staring and confused behaviour,
includes day-dreaming, absence seizures, behavioural Non-epileptic episodic disorders
outbursts, migraine and psychogenic seizures. The dif-
ferential diagnosis of FLE, with nocturnal convulsive Not all episodes of neurological dysfunction in infancy
or thrashing seizures, includes parasomnias and epi- and childhood are epileptic. Sleep disorders, move-
lepsy with generalized tonic–clonic seizures. Benign ment disorders, circulatory disturbances, migraine and
focal epilepsies can usually be distinguished from TLE some normal behaviour may mimic epileptic s­ eizures
and FLE by their characteristic clinical and EEG fea- (Box 17.1.3). Disorders frequently misdiagnosed as
tures. If typical features of benign focal epilepsy are seizures are breath-holding attacks in infancy and
not present, the diagnosis cannot be made confidently, syncope in older children and adolescents, because
and brain imaging with MRI is needed to search for an of their paroxysmal nature with loss of conscious-
underlying lesion. ness and associated convulsive movements. In such
attacks, the neurological manifestations are secondary
to ­transient cerebral ischaemia and not to any intrinsic
Treatment cerebral dysfunction.
Carbamazepine is the drug of first choice for epilepsies
with focal seizures, including TLE and FLE. Seizures Breath-holding attacks
may be resistant to treatment and over time the patient
may be tried on other medications (see Table 17.1.1). Attacks usually start in the first or second year
Cognitive, physical and behavioural problems may be of life and are reported in up to 4% of children.
present in some children and are usually manifestations Crucial to the diagnosis is recognition that attacks
of the underlying cerebral disturbance or lesion. These are ­precipitated by either physical trauma, such as a
co-morbid problems may require specific assessment knock or a fall, or emotional trauma such as fright,
and intervention in their own right. Spontaneous seizure
remission occurs in some patients, mainly when a lesion is
not identified on MRI. In children with uncontrolled sei-
Box 17.1.3 Differential diagnosis of epileptic seizures
zures that impact significantly on the life of the child and
family, or are exerting detrimental effects on neurologi- • Normal behaviours (e.g. sleep jerks, day-dreaming,
cal development, epilepsy surgery should be considered. masturbation)
• Parasomnias (e.g. night terrors, sleepwalking)
• Breath-holding spells
• Syncope (e.g. vasovagal, cardiac arrhythmia/outflow
Clinical example obstruction)
• Migraine and migraine variants (e.g. benign paroxysmal
Steven, a 9-year-old boy with a history of learning
vertigo/torticollis)
problems, was referred for management of
• Movement disorders (e.g. tics, tremor, clonus, shuddering
refractory seizures. Seizures began at age
attacks)
5 years, occurred in clusters each week, and
• Non-neurological (e.g. gastro-oesophageal reflux,
were characterized by a scared feeling in the abdomen
hypoglycaemia)
followed by cessation of activity, loss of responsiveness,
• Psychiatric (e.g. rage attacks, psychogenic seizures)
589
 17.1   SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

anger or f­rustration, but precipitants are not always

severe or noticed. Attacks usually commence with cry- Assessment of children with
ing, but this may be brief or absent. Apnoea and bra-
dycardia then occur, either suddenly or gradually, with
seizures
cyanosis or pallor following. The attack may termi- Three important and successive steps in the assess-
nate without loss of consciousness or progress, with ment of a child with suspected seizures are to:
the child becoming unconscious, limp, and sometimes • distinguish epileptic seizures from non-epileptic
briefly stiffening or jerking in response to the cerebral attacks
­ischaemia. Recovery is usually rapid, although some • determine the type(s) of seizure the child is having,
children are drowsy and lethargic after an attack with most importantly whether they are generalized or
convulsive features. Attacks usually cease by the third focal, and determine whether unrecognized minor
or fourth year of life. seizures are occurring
The pathophysiology of breath-holding attacks is • determine the type of epilepsy and underlying
not well understood, but affected children probably aetiology in the child having recurrent seizures.
have an age-related dysfunction in cardiorespiratory The diagnosis of epileptic seizures is made on
reflexes. Iron-deficiency anaemia is an exacerbating ­clinical grounds with investigations used to confirm
factor in some children with frequent attacks or prom- the diagnosis, help characterize the seizure disorder
inent convulsive features. Breath-holding attacks are and determine the underlying cause. Detailed history
not a cause of death, epilepsy, intellectual disability from the patient and observers, sometimes combined
or cerebral damage and families should be reassured with home video-recordings of attacks, are the basis
about their benign nature. EEG is unnecessary, but of making a correct diagnosis. Children with epilepsy
ECG may be considered if there are ­atypical features. should be examined for dysmorphic features, neurocu-
taneous stigmata, focal neurological deficits, signs of
raised intracranial pressure and markers of systemic
Syncope
disease.
Syncope, or fainting, is common in childhood. As Metabolic disturbance, especially hypoglycaemia
in adults, it is the result of decreased cardiac output and hypocalcaemia, should be considered in infants
and cerebral perfusion leading to loss of conscious- with seizures and children with no identifiable cause
ness and falling. Brief tonic stiffening, clonic jerk- for their epilepsy. Pyridoxine dependency, although
ing or incontinence often accompanies the loss of very rare, should be considered in refractory infant-
­consciousness and may lead to misdiagnosis as an onset epilepsy.
epileptic s­eizure. Recovery is usually prompt follow- EEG is invaluable in the characterization of seizures
ing syncope. Light-headedness, dizziness, visual loss, and epilepsies, and should generally be requested in
and auditory or sensory changes may be recalled prior all children with definite afebrile seizures. EEG is of
to loss of c­ onsciousness; these are manifestations of no value in the investigation of febrile seizures. In epi-
focal cortical ischaemia. Sweating and tachycardia lepsy, the EEG helps to distinguish focal from gener-
during recovery are common, as a result of reflex alized seizures and aids diagnosis of specific epileptic
sympathetic drive. However, a more important clue syndromes, especially the epilepsies with generalized
to the diagnosis than the recalled or observed clinical seizures and benign focal epilepsies of childhood.
features is the situation in which the episode occurred. In this way, the EEG may assist in making the cor-
Syncope should be suspected as the basis of loss of rect choice of antiepileptic medication and determin-
consciousness or convulsing when attacks occur con- ing the need for brain imaging. It is important to note
temporaneously with vomiting illnesses, prolonged that the interictal EEG is normal in many patients
standing (e.g. classroom, church), hair-brushing, with epilepsy, particularly those with focal epilepsies
injury, venepuncture or other medical procedures, and due to known or suspected structural brain abnor-
witnessing medical or veterinary procedures. Syncope malities. Conversely, epileptiform abnormalities, par-
without a precipitant, or syncope during exercise or ticularly centrotemporal spikes and brief generalized
while in water, should prompt concern about a pri- spike–wave bursts in drowsiness, are seen in up to 5%
mary cardiac cause, such as prolonged QT syndrome of normal children without seizures, and more fre-
or left ventricular outflow obstruction. No investi- quently in children with underlying neurological and
gations, other than perhaps an ECG, are needed in developmental problems. EEG should therefore never
syncope, and most patients and families need only be used to ‘rule out’ epilepsy in a child with undiag-
explanation and reassurance. Recognition of precipi- nosed attacks. In children with undiagnosed recurrent
tating situations and presyncopal symptoms is helpful attacks, or children with epileptic seizures of ­uncertain
in taking evasive action. type, video-EEG monitoring may be needed.
590
 Seizures and epilepsies 17.1
Brain imaging is indicated when one suspects an
underlying cerebral abnormality. MRI should be General principles of treatment
requested in children with focal seizures or signifi-
cant focal EEG abnormalities, except when they are
of seizures in children
characteristic of a benign focal (rolandic or occipital) Explanation and reassurance, provision of informa-
­epilepsy. MRI should also be performed in c­hildren tion about the child's specific seizure disorder, first-aid
with focal or generalized seizures who have significant advice about how to manage future seizures, discussion
developmental delay, abnormal neurological find- of potential seizure precipitants, consideration of life-
ings on examination, a history of a prior neurological style modification, and safety advice regarding bath-
insult, or poorly controlled seizures. Brain imaging is ing, swimming, heights and driving are all important
unnecessary in typical cases of benign focal e­ pilepsy, aspects of seizure management. The decision to treat a
epilepsies with absence seizures and e­pilepsies with child with antiepileptic medication, and the choice and
generalized tonic–clonic seizures in otherwise n ­ ormal duration of treatment, depend on the type of epilepsy
children. Computed tomography (CT) is indicated only and several patient and family factors. Antiepileptic
in children suspected of conditions that may require medications reduce the likelihood of seizures but do
immediate intensive care or neurosurgical interven- not alter the course of epilepsy; that is, seizures do not
tion, such as stroke, traumatic brain injury or raised remit any sooner on treatment. The appropriate anti-
intracranial pressure. To limit unnecessary i­ rradiation, epileptic drug is usually indicated by the predominant
CT should never be requested in an ­otherwise well seizure type (see Box 17.1.1).
child. Seizures can usually be controlled with one medica-
tion at an optimal dose. Children vary greatly in their
dosage requirements and tolerance of antiepileptic
drugs; patient age and associated disabilities are the
main determinants. Except in status epilepticus and
Practical points other situations with frequent or severe seizures, anti-
epileptic medications are usually started singly and in
Diagnosis low dosage, then increased gradually to a dose where
• A detailed description of the attacks and the situations seizure control is obtained or side-effects appear. The
in which they occurred, sometimes supplemented duration of therapy depends on the type of epilepsy
with a home video-recording, are the keys to correct and its natural history, the degree of seizure control
diagnosis of epileptic seizures and non-epileptic and the patient's lifestyle. Several years of freedom
events.
from seizures are desirable before antiepileptic drugs
• The differential diagnosis of episodic staring includes
day-dreaming or inattention, absence seizures, and focal are ceased, and this is best done slowly over a period
seizures with impaired consciousness. of months. Antiepileptic drug interactions are com-
• The differential diagnosis of collapse and convulsing mon, both pharmacokinetic and pharmacodynamic,
includes syncope, generalized tonic–clonic seizures, focal some being advantageous (e.g. sodium valproate and
seizures and psychogenic attacks. lamotrigine) and others leading to side-effects (e.g.
• EEG is helpful in characterizing seizures and epilepsies but barbiturates and benzodiazepines).
should not be done to clarify the nature of undiagnosed
events. Further history, home video-recording or video-
Almost all antiepileptic drugs produce side-effects
EEG monitoring may be needed for undiagnosed episodic such as drowsiness and unsteadiness if given in excess.
phenomena. These effects are common when medications are com-
• Benign focal epilepsies and epilepsies with absences menced and the dose is increased but they often wear
or generalized tonic–clonic seizures usually have off after the maintenance dose is reached. Some anti-
characteristic epileptic patterns on routine EEG; if these epileptic medications have side-effects of an idiosyn-
are not present, consideration of non-epileptic episodes
cratic type, such as rash or behaviour disturbance
or epilepsy with focal seizures due to structural brain
abnormality is required. (Table 17.1.2).
• MRI is performed when the seizures, EEG, history or Use of serum levels for monitoring some antiepi-
examination suggest an underlying cerebral abnormality leptic medications is particularly useful if seizure con-
or cannot exclude one. MRI is not performed in benign trol is inadequate, side-effects attributable to toxicity
focal epilepsies and in epilepsies with absences or are suspected or compliance is uncertain. Blood level
generalized tonic–clonic seizures. monitoring is of particular value in young infants,
• Learning and behavioural problems in a child with in children with intellectual disability and in patients
epilepsy are often the result of the underlying neurological
problem rather than being secondary to seizures or with impaired consciousness (i.e. patients who are not
medications. able to describe side-effects). Barbiturate and pheny­
toin levels correlate well with both seizure control and
591
 17.1   SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

Table 17.1.2 Side-effects of antiepileptic medications

Medication Side-effects

Toxicity
Able to be produced by most antiepileptic Drowsiness, ataxia, tremor, nystagmus, dysarthria, confusion, nausea, vomiting,
medications, especially in combination sleepiness or insomnia, mood disturbance

Idiosyncratic
Carbamazepine Rash, leukopenia, hyponatraemia, irritability, weight gain
Clonazepam Behaviour disturbance, increased bronchial and salivary secretions
Lamotrigine Rash, severe hypersensitivity syndrome
Levetiracetam Behaviour disturbance
Oxcarbazepine Rash, hyponatraemia
Phenytoin Rash, serum-sickness-type illness, extravasation injury
Phenobarbital Rash, behaviour disturbance
Sodium valproate Weight gain, alopecia, pancreatitis, behaviour disturbance, fulminant hepatitis (rare)
Topiramate Kidney stones, weight loss, speech disturbance, oligohydrosis/hyperthermia
Vigabatrin Peripheral vision impairment, behaviour disturbance, weight gain
Pregabalin Weight gain, constipation, ankle oedema
Zonisamide Rash, oligohydrosis/hyperthermia

side-effects, less so for carbamazepine. However, there and vocation, problems related to adjustment to the
is little role for blood level monitoring with the other diagnosis, and associated psychological and behav-
­
antiepileptic medications, including sodium valproate ioural problems may be more difficult to manage than
and the benzodiazepines. the seizures. Disentangling the effects of s­eizures,
In addition to regular prescription of antiepileptic medications, underlying lesions and conditions, pre-
medication to prevent seizures, some parents and car- existing states, family dynamics and psychosocial
ers are instructed in the use of rectal diazepam or buc- factors can often be difficult, and requires specialist
cally administered midazolam to treat prolonged or ­involvement. It is beyond the scope of this chapter to
recurring seizures, in children with a tendency to pro- cover these important areas.
longed or clustering seizures.
For children with uncontrolled epilepsy, in whom
seizures continue despite correct diagnosis and cor-
rect prescription of antiepileptic medications, special-
ized treatments such as epilepsy surgery, a ketogenic Practical points
diet and vagus nerve stimulation may be considered.
Surgical treatment is reserved for children with well Treatment
characterized and drug-resistant focal epilepsy in • Explanation, reassurance, lifestyle modification and
first-aid advice are important aspects of epilepsy
whom seizures are impacting greatly on quality of life management.
or development. Surgery is most effective when the • For febrile seizures, reinforce that febrile seizure
seizure focus is discrete, away from critical functional recurrence is common, epilepsy development is
cortex and associated with a lesion on MRI. Epilepsy uncommon and neurodevelopmental sequelae are rare.
surgery is carried out only after detailed evaluation in • In a child with epilepsy, the decision to treat, the choice of
a centre with special experience in paediatric epilep- medication and the duration of therapy are determined by
the type of seizure and epilepsy.
tology. A ketogenic diet, with high fat and low car-
• As a general rule in antiepileptic drug therapy, ‘start low
bohydrate and protein intake, is sometimes effective and go slow’ and withdraw medications slowly.
in refractory epilepsy, especially in younger ­children, • Antiepileptic drug level monitoring is important with
and in epilepsies with absence and ­myoclonic ­seizures. phenobarbital and phenytoin, often helpful with
Vagus nerve stimulation, a form of chronic brain carbamazepine, but of limited value with sodium
­stimulation for the treatment of refractory ­epilepsy, valproate and other drugs.
is being utilized increasingly in children with uncon- • If seizures continue despite treatment with antiepileptic
medication, consider whether the diagnosis of epilepsy
trolled seizures where drugs and surgery are ineffective.
and the seizure/syndrome type are correct, whether
When treating epilepsy it is necessary to consider the the choice of medication is appropriate, and whether
whole child and family in their environment, and not medication is being given and taken in appropriate doses.
592
only the seizures. Problems pertaining to ­education
 Cerebral palsy and 17.2
neurodegenerative
disorders
Dinah Reddihough, Kevin Collins

there appears to have been no single event but rather

Cerebral palsy a sequence of events or ‘causal pathways’ that have
Cerebral palsy (CP) describes a group of permanent ­culminated in the motor damage.
disorders of the development of movement and
posture, causing activity limitation, that are attributed Historical aspects
to non-progressive disturbances that occurred in
the developing fetal or infant brain. The motor There has been a fundamental change in our under-
disorders of cerebral palsy are often accompanied standing of aetiological factors during the past
by disturbances of sensation, perception, cognition, 20 years. Before this, most cases of cerebral palsy were
communication, and behaviour, by epilepsy, and by thought to be caused by lack of oxygen during labour
secondary musculoskeletal problems. or at birth, and it was expected that improvement in
(Rosenbaum P et al 2007 Dev Med Child obstetrics and neonatal care would lower c­erebral
Neurol Suppl 109:8–14) palsy rates. However, despite an increased use of
­interventions such as caesarean section and electronic
The term is generally applied to children with perma- fetal monitoring, cerebral palsy rates have remained
nent motor impairment due to non-progressive brain constant.
disorders occurring before the age of 5 years. There Current research suggests that about 8–10% of cases
are many different causes, a wide range of manifesta- are associated with perinatal asphyxia, a condition in
tions of the motor disorder, and various associated which there have been perinatal events likely to reduce
problems. oxygen supply, evidenced by significant acidosis, and
Cerebral palsy is not a single disorder, but a group failure of function in at least two organs (­ usually
of disorders with diverse implications for children and the brain and kidney). Perinatal asphyxia may not
their families. For some young people with mild cere- ­necessarily be the primary cause of the cerebral palsy
bral palsy, the only motor deficit may be a minimal and is generally not preventable. Because it is often
hemiplegia, causing clumsiness with certain move- impossible to ascribe clinical signs and symptoms to
ments. In other children with severe cerebral palsy, the an event during birth, the term ‘birth asphyxia’ should
motor deficit may be spastic quadriplegia with little be avoided.
or no independent movement. Because each child with
cerebral palsy is different, individual assessment and
treatment are essential. Current knowledge about aetiology
When does the brain insult occur?
• Prenatal events are responsible for approximately
Prevalence 75% of all cases of cerebral palsy.
Cerebral palsy is the most common physical disability in • Perinatal events contribute 10–15%.
childhood. The prevalence of cerebral palsy is between • Postneonatal causes (occurring after 28 days of life)
2.0 and 2.5 per 1000 live births and has remained fairly account for about 10% of all cases.
stable since 1970 (Fig. 17.2.1). A prenatal cause is assumed in the absence of clear evi-
dence for a perinatal or postnatal cause.

Aetiology
What are the prenatal causes?
The cause of cerebral palsy is unknown in many chil-
dren. Known risk factors include low birth weight, Malformations. Disturbances of brain development,
prematurity and multiple pregnancy. In a signifi- usually between 12 and 20 weeks’ gestation, resulting
593
cant proportion of children who have cerebral palsy, in a variety of abnormalities. They may be identified
 17.2 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

14

Stillbirths
12 Neonatal deaths
Cerebral palsy

Rate per 1000 live births

10

0
19 3
19 4
19 5
19 6
19 7
19 8
19 9
19 0
19 1
19 2
19 3
19 4
19 5
19 6
19 7
19 8
19 9
19 0
19 1
19 2
19 3
19 4
19 5
19 6
19 7
19 8
99
7
7
7
7
7
7
7
8
8
8
8
8
8
8
8
8
8
9
9
9
9
9
9
9
9
9
19

Year of birth

Fig. 17.2.1 Cerebral palsy, stillbirth and neonatal death rates per 1000 births in Victoria using published and unpublished data from
the Victorian Cerebral Palsy Register and the Victorian Perinatal Data Collection Unit. (Source: Reid S, Lanigan A, Reddihough DS 2005
Report of the Victorian Cerebral Palsy Register.)

by brain i­maging, magnetic resonance ­imaging (MRI) Infective. Maternal infections during the first and
being the preferred investigation. Some malformations second trimesters of pregnancy, including the TORCH
have a genetic basis. group of organisms (toxoplasmosis, rubella, cyto-
Vascular. Vascular events such as middle cerebral megalovirus and herpes simplex virus). There is also
artery occlusion (Fig. 17.2.2). evidence that maternal infections in the perinatal
­
period may form part of the causal pathway to cere-
bral palsy.
Genetic. Uncommon genetic syndromes.
Metabolic. Iodine deficiency in early pregnancy, an
important cause in many parts of the world.
Toxic. Lead, methylmercury ingestion and other
toxins are rare associations.

What are the perinatal causes?

Problems during labour and delivery. Obstetric emer-
gencies such as obstructed labour, antepartum haem-
orrhage or cord prolapse compromising the fetus.
Neonatal problems. Conditions such as severe hypo-
glycaemia or untreated jaundice may be involved.

Why are premature and low-birth-weight infants

at risk of cerebral palsy?
Premature and low-birth-weight children have a higher
risk of cerebral palsy. For those born at less than
33 weeks’ gestation, the risk is up to 30 times higher
than for those born at term. Some premature infants
develop brain damage from complications of their
Fig. 17.2.2 Magnetic resonance image of the brain of a
immaturity, such as intraventricular haemorrhage,
2-year-old boy with left spastic hemiparesis, showing loss of whereas others are damaged earlier in pregnancy.
brain tissue in right temporal and frontal lobes, consistent with Intrauterine growth retardation is associated with
594
an old (prenatal) right middle cerebral artery territory infarct. cerebral palsy in both term and pre-term infants.
 Cerebral palsy and neurodegenerative disorders 17.2
Periventricular white matter injury and the more
localized pattern of periventricular leukomalacia is a Practical points
common radiological finding in premature children
with cerebral palsy. It is caused by an ischaemic process, • Cerebral palsy is a diverse disorder with multiple risk
usually occurring between 28 and 34 weeks’ gestation, factors and aetiologies.
in the watershed zone that exists in the periventricu- • When determining aetiology, distinguish risk factors from
lar white matter of the immature brain. Periventricular causes.
white matter injury is also found in infants born at • Most cases of cerebral palsy relate to events long before birth.
term, suggesting that the insult occurred early in the • Perinatal asphyxia is responsible for only a small
proportion of cases (approximately 8–10%).
third t­rimester even though the pregnancy progressed
• It is important to establish the cause of cerebral palsy if
to term. at all possible. It is helpful for families and essential for
genetic counselling.
• Magnetic resonance imaging (MRI) should be undertaken
Why is multiple pregnancy a risk factor? if the cause is not apparent.
Multiple pregnancy is associated with pre-term deliv-
ery, poor intrauterine growth, birth defects and intra-
Classification
partum complications and with an increased risk of
both mortality and cerebral palsy. Intrauterine death Cerebral palsy is classified by motor type, topo-
of a co-twin is associated with a substantially increased graphical distribution and the severity of the motor
rate of cerebral palsy. disorder.

What are the postneonatal causes of cerebral palsy? Type of motor disorder
• Infections, for example, meningitis, encephalitis and Cerebral palsy is a disorder of movement (difficulties
septicaemia. with voluntary movement and/or abnormal move-
• Injuries may be accidental (such as motor vehicle ments), posture and muscle tone. Children with cerebral
accidents and near drowning episodes), or palsy have various types of movement disorder.
non-accidental. Improved road safety and Spastic cerebral palsy (70%). This is the most com-
mandatory fencing around home swimming pools mon type. Spasticity involves increased muscle tone
are important preventative measures. with characteristic clasp-knife quality. Children with
• Apparent life-threatening events and cerebrovascular spasticity often have underlying weakness. In spas-
accidents. tic cerebral palsy, there is damage to the motor cor-
• Meningitis, septicaemia and infections such as tex or corticospinal tracts, in contrast to dyskinetic
malaria are important causes of cerebral palsy in and ataxic cerebral palsy, which are associated with
developing countries. abnormalities of the basal ganglia and cerebellum,
respectively.
Dyskinetic cerebral palsy (10–15%). This refers to a
group of cerebral palsies with involuntary movements
Clinical example and is characterized by abnormalities of tone involv-
ing the whole body. Several terms are used within this
Caitlin is aged 2 years and 6 months. Her
mother went into labour at 33 weeks’ gestation group:
after an uneventful pregnancy. The delivery was • Dystonia is the term used for sustained muscle
rapid. Apgar scores were 6 at 1 minute and 8 at contractions that frequently cause twisting or
5 minutes. Her parents remember some panic in the labour repetitive movements, or abnormal postures.
ward and felt that more could have been done to slow the • Athetosis refers to slow writhing movements
labour. Caitlin developed hyaline membrane disease and mild
involving the distal parts of the limbs.
jaundice. In the early neonatal period she had difficulty sucking,
which was attributed to her prematurity. She was slow in her • Chorea is the term for rapid jerky involuntary
motor development and did not sit until the age of 15 months. movements.
A diagnosis of cerebral palsy was made at that time. Ataxic cerebral palsy (less than 5%). Children
When Caitlin was 2 years old, her parents requested have a fine tremor, more noticeable when move-
an opinion as to whether subsequent children were likely ments are initiated, and often have poor balance and
to have cerebral palsy, believing that her prematurity and hypotonia. Ataxia is associated with other neuro-
problems at birth were responsible for her condition. MRI of
logical conditions that must be excluded before this
the brain demonstrated a brain malformation with bilateral
clefts in the cerebral cortex, dating the problems to early ­diagnosis is made.
pregnancy rather than the perinatal period. Some children have more than one type of motor
595
disorder.
 17.2 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

Topographical distribution Presentation

The terms diplegia, hemiplegia and quadriplegia gen- The diagnosis of cerebral palsy is not always easy,
erally apply to children with spastic cerebral palsy parti­cularly in children born prematurely. Signs evolve
as the extrapyramidal types (dyskinesia and ataxia) during the first year of life. For example, spasticity is
­usually involve four limbs: not usually present in the early weeks of life and invol-
• The term diplegia is used where the predominant untary movements are generally not seen in the first
problem is in the lower limbs but signs are usually year of life. Conversely, abnormal neurological signs
also present in the upper limb. Most of these may disappear. Cerebral palsy may present as follows:
children have normal intelligence. Spastic diplegia • Follow-up of ‘at risk’ infants, such as those born
is the pattern most commonly seen in premature prematurely or those with a history of neonatal
infants who have the radiological finding of encephalopathy.
periventricular white matter injury. • Delayed motor milestones, particularly delay in
• Children with spastic hemiplegia usually have normal learning to sit, stand and walk.
intelligence, frequently have epilepsy (50–70%) and • Development of asymmetrical movement patterns,
visual deficits (homonymous hemianopsia), and may for example a strong hand preference in the early
have sensory impairments in the upper limb. months of life.
• Children with spastic quadriplegia often have intellectual • Abnormalities of muscle tone, particularly
disability, epilepsy and visual impairment. Poor trunk spasticity or hypotonia. Hypotonia in isolation
control and oromotor difficulties may also be present. may be an early sign of global developmental delay
rather than cerebral palsy.
Severity of the motor disorder • Management problems, for example severe feeding
The Gross Motor Function Classification System difficulties or behavioural abnormalities such as
(GMFCS) provides information about the severity of unexplained irritability. These problems should
the movement problems based on children's motor abil- be investigated carefully as many other conditions
ities and their need for walking frames, wheelchairs and present with these symptoms.
other mobility devices. There are five levels: children in
levels I and II walk independently; children in level III Examination and investigation
need walking frames or elbow crutches; and children in
levels IV and V use wheelchairs. This classification sys- • Look for abnormalities in muscle tone, posture
tem does not consider cognitive and other deficits. and deep tendon reflexes, along with persistence of
Growth Motor Development Curves for each of the primitive reflexes.
GMFCS levels are available and provide some guid- • Exclude other conditions that may present
ance regarding prognosis for motor development. with motor delay including neuromuscular,
The Manual Abilities Classification System (MACS) neurodegenerative and metabolic disorders.
describes how children with cerebral palsy use their • Undertake an MRI brain scan where the cause or
hands to handle objects in daily activities. It also has causes are uncertain or unknown.
five levels, from level I, where children handle objects
easily and successfully, to level V, where children are
unable to handle objects and have severely limited Practical points
­ability to perform even simple actions.
• Observation of the child often provides more information
than ‘hands on’ examination. It will provide information
about the presence or absence of age-appropriate motor
skills and their quality.

Practical points
Associated disabilities
• Cerebral palsy can be classified according to motor type,
distribution and severity. The following associated disabilities may be present.
• GMFCS provides information about severity of gross motor • Visual problems including strabismus, refractive errors,
function; MACS provides information about how children visual field defects and cortical visual impairment in
use their hands. about 40% of children with cerebral palsy.
• Classifying motor severity using the GMFCS provides • Hearing deficits in 3–10% of children with cerebral
information about motor prognosis.
palsy. High-frequency hearing loss may be found in
• Co-morbidities such as epilepsy are more common in
certain types of cerebral palsy. children with congenital rubella or other congenital
596
infections.
 Cerebral palsy and neurodegenerative disorders 17.2
• Communication disorders including receptive and • Constipation is common and results from
expressive language delays and articulation problems. immobility, low-fibre diet and poor fluid intake.
• Epilepsy in up to 50% of children with cerebral Dietary and laxative advice is important.
palsy, most commonly in those with spastic • Chronic lung disease develops in some children
hemiplegia and quadriplegia. with severe cerebral palsy due to aspiration from
• Cognitive impairments – intellectual disabilities, oromotor dysfunction or severe gastro-oesophageal
learning problems and perceptual deficits are reflux. Coughing or choking during mealtimes,
common. There is a wide range of intellectual or wheeze during or after meals, may signal the
ability and some children with severe physical possibility of aspiration, but it may also occur
disabilities may have normal intelligence. without clinical symptoms or signs. There is no
Some children with cerebral palsy have only a motor ‘gold standard’ test for aspiration, but barium
disorder. videofluoroscopy may be helpful. Alternative
feeding regimens, such as the use of a gastrostomy,
should be considered if aspiration is present.
Management • Hydrocephalus requiring ventriculoperitoneal
A team approach is essential, involving a range of shunts is present in many children, particularly
health professionals and teachers, with input from the those born prematurely.
family of paramount importance. Caring for a child • Dental problems – children should have regular
with cerebral palsy involves: dental surveillance.
• management of the associated disabilities, health • Osteopenia causing pathological fractures may
problems, and the consequences of the motor occur in children with severe cerebral palsy.
disorder • Emotional problems may be responsible for
suboptimal performance, with either academic or
• developmental assessment and referral to
appropriate services for the child and family. self-care tasks.

Consequences of the motor disorder

Management of the associated disabilities, • Drooling (dribbling or poor saliva control). Speech
health problems and consequences of pathologists can assist with behavioural approaches
the motor disorder and methods to improve oromotor control.
Medication (anticholinergics) and surgery are
Associated disabilities
helpful for some children.
• All children require a hearing and visual assessment.
• Assessment and advice about epilepsy and • Incontinence. Children may be late in achieving
bowel and bladder control due to cognitive deficits
prescription of antiepileptic medication when
or lack of opportunity to access toileting facilities
appropriate.
because of physical disability and/or inability to
• Children benefit from a formal cognitive assessment
communicate. Sometimes children have detrusor
and may need help with their educational
overactivity causing urgency, frequency and
programme. Assessment of cognitive abilities can
incontinence. If continence cannot be achieved,
be difficult when children have severe physical
provide advice about incontinence aids.
disabilities.
• Undescended testes require the same treatment as
Health problems in other boys with this problem (usually scrotal
• Growth should be monitored and dietary advice orchidopexy). The testes may be in the normal
provided to ensure adequate nutrient and calorie position at birth but ascend with time (secondary to
intake. Failure to thrive and undernutrition chronic spasm of cremaster muscle).
frequently occur due to eating difficulties resulting • Orthopaedic problems. Children may develop
from oromotor dysfunction. Nasogastric or contractures that require orthopaedic intervention.
gastrostomy feeds should be considered if there Surgery is undertaken mainly on the lower limb,
is difficulty in achieving satisfactory weight gains, but is occasionally helpful in the upper limb.
or if the length of time taken to feed the child is Physiotherapists are essential in the postoperative
excessive. Conversely, obesity may interfere with rehabilitation phase.
progress in motor skills and increase difficulties for • The hip. Non-walkers and those partially
caregivers as the child gets older. ambulant (GMFCS levels III–V) are at risk of
• Gastro-oesophageal reflux occurs commonly in hip subluxation and dislocation. Early detection
cerebral palsy. It can result in oesophagitis or is vital and hip X-rays should be performed at
gastritis, causing pain and poor appetite, and, if regular intervals according to hip surveillance
597
severe, aspiration can result. guidelines. If there is evidence of subluxation or
 17.2 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

dislocation, children should be referred for an

orthopaedic opinion. Dislocation causes pain Clinical example
and difficulty with perineal hygiene. Ambulant
children rarely develop hip problems. Tom was born at 26 weeks’ gestation. He had
many neonatal problems, including a severe
• The knee. Flexion contractures at the knee may
(grade IV) intraventricular haemorrhage. The
require hamstring surgery. parents were informed that some degree of
• The ankle. Equinus deformity at the ankle is the cerebral palsy was likely. At 4 months of corrected age, his
commonest orthopaedic problem in children mother noted that his right hand was fisted. The diagnosis
with cerebral palsy. Toe-walking is treated of cerebral palsy was confirmed and a physiotherapy
conservatively in young children, with orthoses, programme was commenced.
inhibitory casts and botulinum toxin A therapy. When Tom began to walk independently at 24 months
of corrected age, his gait was noted to be asymmetrical
Older children benefit from surgery for a
with a tendency to walk on his toes on the right side. This
definitive correction of the deformity. problem was more apparent by 30 months and Tom fell
• Multilevel surgery. Sometimes children require more than would be expected for his age. He was fitted
surgery at several different levels (for example, with an ankle–foot orthosis (AFO) and his walking pattern
hip, knee and ankle). This involves a single was much improved. After a further 10 months the problem
hospitalization and is called ‘single-event had recurred. This time Tom appeared not only to walk in
multilevel surgery’. It is of most benefit to equinus, but he also was flexed at the knee. Hamstrings as
well as calf muscles were tight. Botulinum toxin A injections
children who walk independently or with the
were given to both muscle groups, with an excellent result.
assistance of crutches. The usual age is between A new AFO was made as Tom had grown considerably over
8 and 12 years. An accurate assessment of this time. When Tom was 5 years old, he required further
the walking problems is undertaken in a gait botulinum toxin A injections. At 7 years of age, surgery was
laboratory. The aims of surgery are to correct undertaken by the same orthopaedic surgeon who had been
deformities and to improve both the appearance monitoring him since the age of 24 months. Now Tom is
10 years old and no treatment is currently planned, although
and the efficiency of walking. A carefully planned
the family has been advised that further surgery may be
intensive rehabilitation physiotherapy programme required following his adolescent growth spurt.
lasting for up to 1 year is required to maximize
the benefits.
• The upper limb. Procedures can be offered
following careful assessment.
Developmental assessment and referral to
• Scoliosis. Correction is sometimes necessary. appropriate services for the child and family
• Spasticity management is aimed at improving
function, comfort and care and requires a team The role of the team. Careful multidisciplinary assess-
approach. Options include: ment is essential to enable children to achieve their opti-
• Oral medications, for example diazepam, mal physical potential and independence:
dantrolene sodium and baclofen. These • Physiotherapists give practical advice to parents
medications are not always effective or may cause on positioning, handling and play, to minimize the
unwanted effects. effects of abnormal muscle tone and encourage
• Inhibitory casts aim to increase joint range. the development of movement skills. They also
The main application is below-knee casts for give advice regarding the use of orthoses, special
equinus, but occasionally casts are used in the seating, wheelchairs and other mobility aids.
upper limb. • Occupational therapists help parents to develop
• Botulinum toxin A is injected into muscles and their child's upper limb and self-care skills, and also
reduces localized spasticity. recommend suitable toys, equipment and home
• Intrathecal baclofen is administered by a pump adaptations.
implanted under the skin. This treatment is • Speech pathologists assist in the development of
suitable for a small number of children with communication skills, including advising about
severe generalized spasticity and/or dystonia, and augmentative communication systems for children
may enhance quality of life. with limited verbal skills. They provide guidance
• Selective dorsal rhizotomy is a neurosurgical about feeding difficulties and saliva control
procedure whereby specific posterior spinal roots problems.
are sectioned to reduce spasticity. It has been • Orthotists, medical social workers, psychologists,
used mostly in young children aged between special education teachers and nurses are helpful.
3 and 7 years with spastic diplegia. An intensive Therapy approaches. Therapy to address ­movement
rehabilitation period is required. problems and to optimize children's progress in all
598
 Cerebral palsy and neurodegenerative disorders 17.2
areas of development is incorporated into early child- Life expectancy
hood intervention and school programmes. The two
Children with mild and moderate cerebral palsy have a
most commonly used approaches by therapists in
normal lifespan. Those with severe motor impairment,
Australia are:
particularly those who are wheelchair-dependent and
1. Neurodevelopmental therapy (NDT or ‘Bobath’
require tube-feeding, have a reduced life expectancy.
therapy). This is a therapeutic approach to the
Chronic lung disease is the most common cause of
assessment and management of movement
morbidity and mortality in this group.
problems with the goal of maximizing the child's
functional ability. Family members receive
education in NDT principles so that they can
implement the programme at home, preschool and Practical points
school.
2. Programmes based on the principles of Conductive
• In the child with cerebral palsy, the associated disorders
Education. Conductive Education is a Hungarian and health problems may require more attention than the
system for educating children and adults with motor disorder itself.
movement disorders. It provides an integrated • A family-centred multidisciplinary approach provides
group programme whereby children and parents optimal management of the child with cerebral palsy.
learn to develop daily living, physical, social,
cognitive and communication skills.
Assistive technology. Appropriate equipment tai-
lored for the individual child can enhance communi-
cation, mobility, learning and socialization. Examples Neurodegenerative disorders
include powered wheelchairs, electronic communica- This section addresses the problem of the child who
tion devices, and computers for educational and rec- presents because of concern about regression in devel-
reational purposes. opment that has been normal previously, or with
Trends in service provision. Services are best pro- apparent worsening of a pre-existing neurological dis-
vided within local communities. Therapists and special order or developmental delay. In infants and young
education teachers work with children at home and children, concern may arise because of loss of gross
later in childcare centres, kindergartens and schools. and fine motor, personal social and language skills, as
Most children attend mainstream preschools and introduced in Chapter 2.2. Declining school perfor-
schools, but others benefit from attendance at centre- mance may lead to referral of the older child.
based early childhood intervention programmes and An approach to this problem will be outlined, with
special schools. Parents should be made aware of all examples of the many disorders that may present in
available options. this way. Some of these disorders are mentioned in
Alternative therapies. There are many non-main- Chapter 10.5. Broader management issues are covered
stream (or ‘alternative’) treatments available. Sometimes in Chapter 3.8.
great claims, usually not justified, are made for alterna- The diagnostic process is presented here as a series
tive approaches. Families can be reassured that any new of questions.
treatment that is of value will be assessed and incorpo-
rated into mainstream practice. There is no evidence to
Is there evidence of regression or lack of
suggest that alternative methods are superior to conven-
progress in any area of development?
tional treatments, and some may do harm. It is impor-
tant to be aware of alternative approaches and to be This is sought in a sequential history of progress in
prepared critically to examine their claims. each area of development, supplemented by questions
Working with families. Care of the child with cere- such as: ‘How is your child's speech now, compared
bral palsy involves developing a trusting and coop- with this time last year? Is there any area where your
erative relationship with the parents. The child is child has gone backwards or shown no progress at all?’
part of a family, and concerns in parents or siblings An ongoing loss of former skills, as shown in the lat-
must be addressed. As with all children, a supportive ter part of curve C in Figure 17.2.3, clearly raises con-
home environment builds self-esteem and confidence. cern about a progressive disorder, but this may be less
Parents may need practical support, such as provision certain during the earlier ‘plateau’ phase before actual
of respite care, and may be helped by meeting other regression appears. This is to be distinguished from
families in similar circumstances, or by attending par- the pattern of abnormally slow but consistent prog-
ent support groups. Provision of information about ress shown in curve A. This pattern is often found in
financial allowances is an important aspect of care. children with an intellectual disability or cerebral palsy
599
 17.2 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

A dyskinetic cerebral palsy, and the tendency for some

n t children with autism to show arrest or regression in
p me
lo social and language skills during the second year of life.
ldeve
r ma
No

Practical point
Early onset, non-progressive

B • When evaluating a child whose development is delayed

Development

in any area, it is important to enquire specifically about

regression or loss of skills, as parents do not always
volunteer such information.

Acute onset, non-progressive

If this is a progressive disorder, what is its
C distribution in terms of brain anatomy?
Important anatomical patterns to consider are as
follows.

Progressive disorder One lesion

Age Progressive hemiparesis, perhaps associated with
focal seizures, suggests a cerebral hemisphere tumour,
Fig. 17.2.3 Curves demonstrating the course of development
whereas spinal cord tumours may produce progressive
over time in a child with static (A and B) and progressive
neurological disease (C) compared with expected normal weakness and spasticity affecting the lower limbs, either
development. The actual age scale will vary, and a different alone or with variable upper limb involvement, thus
curve may apply to each aspect of development in each child or imitating diplegic cerebral palsy. This clinical pat-
disease process. tern, sometimes with associated ataxia, is also seen in
slowly progressive hydrocephalus, even in the absence
of a cerebral neoplasm. The triad of cranial nerve
(due to a static brain disorder), who may fall behind palsies, corticospinal tract signs and ataxia suggests a
other children in abilities, while continuing to acquire brainstem glioma. Most other childhood tumours
new skills, but at a slower pace. of the nervous system raise clear concern because of
A variation on this pattern, demonstrated in curve symptoms of raised intracranial pressure, but the
B, occurs in the child whose initially normal progress is insidious visual loss associated with optic nerve glioma
interrupted by an acute injury or illness (for example, and craniopharyngioma often is not recognized as a
meningitis or encephalitis) causing brain damage with progressive problem until late in its course.
later slow development.
One functional system or group of systems
Could the apparently progressive symptoms
The prototype of ‘system degenerations’ is Friedreich
be due to a static disorder complicated by
ataxia. In this disorder, abnormalities of spinocer-
other factors?
ebellar, corticospinal and sensory tracts arise in the
Such factors may be amenable to treatment, and second decade of life. In other cerebellar ataxia syn-
include the following: dromes there is involvement not only of neural path-
• frequent seizures, especially subtle myoclonic and ways but also of other body organs, as with ataxia
atonic episodes, which may severely impair alertness telangiectasia, in which chromosomal breaks, immu-
and coordination nological defects and skin lesions occur. A system dis-
• drug toxicity, particularly from antiepileptic drugs order involving basal ganglia or extrapyramidal motor
• psychological or emotional factors, including function may be inferred from the signs of dystonia,
depression, withdrawal and psychosis rigidity and choreoathetosis. An important example in
• joint deformities due to soft tissue contractures this category is Wilson disease, which is treatable by
in spastic cerebral palsy, leading to worsening of removal of copper from the body.
postural stability and gait. Peripheral neuromuscular diseases, which also may be
Finally, the natural history of some conditions should regarded as system disorders, are discussed ­separately in
600
be considered, including the evolution of s­pastic and Chapter 17.3.
 Cerebral palsy and neurodegenerative disorders 17.2
A multifocal process, with several discrete lesions the remaining steps in diagnosis require knowledge of
in the brain a growing number of recognized but rare diseases. In
practice, this will involve specialist consultation.
This is exemplified by recurrent cerebral infarctions
associated with cyanotic congenital heart disease. In
the absence of cardiac disease, repeated cerebral vas- Which disorders are known to occur in children
cular occlusions are suggestive of moya-moya disease, of this age, and to produce the other clinical
a well-recognized but poorly understood syndrome. features present in this child?
Angiography shows progressive occlusion of the major
Individual neurodegenerative diseases tend to have a char-
cerebral arteries, with a network of fine collateral ves-
acteristic age of onset. It is useful to consider broad age
sels in the basal ganglia.
ranges (early infancy, late infancy and later childhood) in
Among a group of disorders, known collectively
narrowing the diagnostic field. Next, by matching possi-
as mitochondrial encephalomyelopathies, one form
ble diagnoses against associated ­clinical findings, such as
(MELAS) may present with repeated stroke-like epi-
enlargement of liver and spleen, o ­ cular abnormalities or
sodes and multifocal brain lesions, associated with
unusual facial features, the physician may further refine
abnormal mitochondria in muscle, increased lactate
the search and select the most ­relevant diagnostic tests.
levels in blood and cerebrospinal fluid, and deletions
of the nuclear or mitochondrial DNA controlling
mitochondrial enzyme activity.
Homocystinuria, an inborn error of amino acid
Clinical example
metabolism, may present with recurrent cerebral
venous or arterial thromboses. Although multiple scle- Vincent, aged 6 years, was referred to a
rosis is a major cause of multifocal lesions in young paediatric neurologist because the teachers
adults, it seldom begins in childhood. at his special school were concerned about
his deterioration over several months,
with loss of speech and comprehension of language,
A diffuse degenerative disorder of the impaired coordination and increasingly hyperactive,
aggressive behaviour. He had been diagnosed as having
nervous system
developmental delay at age 3 years because of limited
Diseases causing widespread loss of neurological func- speech and overactive behaviour. On examination, in
tion are generally separated into those that begin by addition to the developmental and behavioural findings,
he had slightly coarse facial features with thickened
affecting predominantly cortical grey matter, or nerve
eyebrows, an enlarged liver and a mild thoracic kyphosis.
cell bodies, and those in which white matter, or nerve These features raised the clinical suspicion that he had
sheath myelin, is primarily involved. Although this Sanfilippo disease, one of a group of disorders in which a
distinction is of clinical value, many disorders are not deficiency of lysosomal enzymes leads to an accumulation
easily classified in this way. of mucopolysaccharides in the tissues and excretion in
Diffuse disorders of grey matter. These tend to cause the urine. The diagnosis was confirmed on specific blood
seizures (often myoclonic) and early loss of intellectual and urine tests. Much professional support was needed
by Vincent's parents, confronted with the prospect of their
function, with progressive impairment of language, son's progressive dementia and immobility as well as the
comprehension and memory. In addition, involvement autosomal recessive inheritance of his condition.
of nerve cells in the retina leads to a variable pattern of
visual loss. This clinical syndrome is seen in several of
the lipid storage disorders, of which Tay–Sachs disease
is the best known. Subacute sclerosing panencephalitis A diagnosis is often reached merely by answering
is an infrequent complication of measles, and evolves these questions. If not, it is useful next to turn from
as a sequence of behavioural change, intellectual clinical features to pathophysiology.
decline, myoclonic jerks and later rigidity.
Diffuse disorders of white matter. By involving corti-
Are any other, less evident, diagnoses
cospinal tracts, these tend to present with early motor
suggested by a systematic review of known
impairment and spasticity, and may masquerade ini-
mechanisms of disease?
tially as cerebral palsy. Impaired vision, when present,
reflects optic pathway disease. Peripheral nerve myelin The previous selective clinical correlations can be
also may be involved, with clinical effects, as in Krabbe investigated further by considering in turn the major
disease and metachromatic leukodystrophy, both of categories of:
which are lipid storage disorders. • disease process, including metabolic errors,
The above three questions can generally be answered neurocutaneous disorders, slow virus infections and
601
after a careful clinical history and examination, but chronic intoxications
 17.2 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

• biochemical substrates, such as lipids, vitamins and • Intoxications: lead poisoning, glue sniffing,
minerals prescribed medications and, occasionally, chronic
• cellular organelles, including lysosomes, peroxisomes drug administration by a disturbed parent.
and mitochondria, with their respective disorders. • Inborn errors of metabolism. The use of a
This search may yield a further short list of possible modified diet in phenylketonuria is well known,
diagnoses, known to the clinician but not considered, but may also be of value in other rare disorders.
usually because of limited experience with them. Removal of toxic agents, for example copper in
Wilson disease, may be possible. In seizures due
to pyridoxine dependency and in other vitamin-
Are there any treatable disorders among the
dependency syndromes, large doses of vitamins
diagnoses being considered in this child?
may effectively compensate for the metabolic
This important question may alter the priority of defect.
investigation, as a potentially treatable disorder, how- • Deficiency states, especially of vitamins required for
ever unlikely, must be rigorously excluded at an early normal growth and function of the nervous system
stage. The major groups to recognize are the following: or the musculoskeletal system, including vitamin
• Neoplasms and other space-occupying lesions B12 and vitamin D.
involving the brain, and especially the spinal cord Effective treatment is not yet available for most degen-
or optic nerves, where they are often not suspected erative neurological disorders of childhood, but accu-
until late, after irreversible damage. rate diagnosis remains the basis for genetic counselling,
• Subacute and chronic infections of the nervous and for offering a realistic prognosis. A specific diag-
system, such as tuberculous or cryptococcal nosis or ‘answer’ is of great value to parents in coping
meningitis and HIV infection. with the distress of having a child with a disability.

602
 Neuromuscular disorders
Monique Ryan, Andrew Kornberg
17.3
Neuromuscular disorders of childhood have become a • frequent falls
focus of increasing attention in recent years. Although • tires easily.
many of these conditions are difficult to diagnose Another trap in the recognition of neuromuscular dis-
without sophisticated investigations, and they are gen- ease in childhood is that classical neurological signs,
erally incurable, this group of disorders cannot be readily demonstrated at the end of a disease process in
ignored because of the significant morbidity and mor- adult patients, are often absent in children at the begin-
tality associated with them, their genetic implications ning of the disease process. For example, adults with
and the arrival of potential therapies. Early diagno- Charcot–Marie–Tooth disease very often have pes
sis is important in the rational management of these cavus, distal muscle wasting and generalized areflexia.
disorders as it allows provision of accurate prognos- In children, Charcot–Marie–Tooth disease presents
tic and genetic information. Accurate diagnosis in this with an abnormal walk or run, clumsiness and fre-
wide array of disorders is dependent on a careful clini- quent falls. Foot deformity is a presenting symptom in
cal assessment followed by confirmatory and appro- a minority. In addition, although areflexia is the rule
priate investigations. Recent advances have unravelled in adult patients, about 10% of children with Charcot–
the molecular biology of many neuromuscular condi- Marie–Tooth disease have normal reflexes at presenta-
tions, but the clinical assessment of patients remains tion. Not understanding the age-dependent symptoms
the cornerstone of diagnosis and management. and signs of neuromuscular disorders will lead to fail-
The management of neuromuscular disorders requires ure to recognize them in childhood.
recognition, diagnosis, therapy and counselling. Other modes of presentation include a family his-
tory of neuromuscular disease; weakness, hypotonia,
respiratory or feeding difficulty in the neonatal period;
Recognition that a child's presenting
delayed motor milestones; abnormal gait (particularly
symptoms or signs may be due to peripheral
toe-walking); and orthopaedic abnormalities such as
neuromuscular disease
foot deformity or scoliosis. Some patients present with
Please listen to the patient; he's trying to tell you non-neuromuscular problems, such as intellectual dis-
what disease he has. ability or delayed language development, for example
(Michael H. Brooke 1977 A Clinician's View of in Duchenne muscular dystrophy.
Neuromuscular Disease. Williams and Wilkins:
Baltimore)
Although the hallmark of neuromuscular disorders
Diagnosis of neuromuscular disease based on
is weakness, parents do not come into the consulting
anatomical, electrophysiological, biochemical,
room saying, ‘I'm worried because my child is weak’.
histopathological or DNA identification
The physician needs to recognize that the presenting After recognizing that the symptoms are due to neu-
symptoms or signs relate to the neuromuscular sys- romuscular disease, the differential diagnosis is based
tem before the diagnostic process begins. Failure of on a logical anatomical approach. Although this may
this recognition results in diagnostic delay. Although appear overly simplistic, as some disorders may affect
this failure may not affect the ultimate prognosis, it more than one anatomical area or be multisystemic,
adds considerably to patient and parental frustration. this approach will provide a broad differential diagno-
A tragedy occurs when opportunities for prevention sis that leads on to definitive diagnosis.
are missed and a second affected child is born to the The anatomical localization is based on the clinical
immediate or extended family. findings listed in Table 17.3.1 and includes disorders
Common presenting complaints of neuromuscular affecting the:
disorders include: • anterior horn cell
• difficulty walking and running • anterior and posterior nerve roots
• poor at sports • peripheral nerve (motor, sensory, autonomic)
• clumsy or poorly coordinated • neuromuscular junction 603
• not able to keep up with peers • muscle.
 17.3 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

Table 17.3.1 Clinical clues helpful in establishing the site of the lesion in neuromuscular disease

Clinical feature Anterior horn cell Peripheral nerve Neuromuscular junction Muscle

Weakness Proximal Distal Cranial/proximal Proximal

Hypotonia ++ + +/− ++

Hyporeflexia +/− Early +/− Late

Fasciculations +++ + − −

Sensory abnormalities − +/− − −

Myotonia − − − +/−

Autonomic dysfunction − +/− − −

Muscle enlargement − − − +/−

The use of a timeframe of symptoms, such as acute, Chronic

subacute or chronic, will also provide an important
In childhood the chronic disorders characterized
frame for the differential diagnosis.
pathologically by degeneration of anterior horn cells
The definitive diagnosis rests on a combination of:
and associated clinically with progressive ­ muscle
• clinical history and examination
weakness are called the spinal muscular atrophies
• family history
(SMAs). The important SMA syndromes and their
• serum muscle enzymes, particularly creatine kinase
­classification are listed in Table 17.3.2.
(CK)
• electrophysiology (e.g. nerve conduction studies,
electromyography, repetitive nerve stimulation)
Spinal muscular atrophy type I
• histology of muscle and/or nerve (Werdnig–Hoffmann disease)
• metabolic studies (e.g. muscle glycogen, carnitine
assay, mitochondrial studies) This autosomal recessive disorder occurs in approxi-
• DNA studies. mately 1 in 6000 live births, making it the most com-
mon fatal autosomal recessive disorder of early
childhood. The earliest symptom may be decreased
fetal movements in late pregnancy. Presentation is
Anterior horn cell disorders invariably before 6 months of age and is either at
Acute birth with hypotonia, weakness, joint deformity and
respiratory difficulty, or more commonly later with
Poliomyelitis
marked hypotonia and limb weakness, poor feeding,
This disorder is rare in developed countries, but poor cough and cry. The onset is sometimes ­relatively
should still be considered where there is acute onset rapid and when first seen the child is ­usually severely
of weakness of a single limb, or with patchy asym- weak (Fig. 17.3.1). Weakness, although ­generalized, is
metrical ­distribution, particularly if this is associated ­maximal proximally in the shoulder and hip ­girdle mus-
with fever, vomiting, neck or back stiffness, and mus- cles. Intercostal muscle weakness leads to chest defor-
cle pain or spasms. Sensory abnormalities are absent. mity, a poor cough and a weak cry. The ­respiratory

Table 17.3.2 Clinical classification of childhood-onset proximal spinal muscle atrophy

Designation Symptom onset (months) Course Age at death (years)

I (severe) 0–6 Never sits without support <2

II (intermediate) < 18 Never stands without aid >2

III (mild) > 18 Stands alone Adult

604
 Neuromuscular disorders 17.3
Spinal muscular atrophy type 2
The genetic abnormality in SMA types 2 and 3 is
allelic to that of SMA type 1, but these are milder
forms of the disease. The clinical onset of SMA type
2 is almost invariably before 3 years of age, with hypo-
tonia, weakness and delayed motor milestones. The
clinical picture is one of severe generalized weakness
and wasting, with proximal predominance. Deep ten-
don reflexes are decreased or absent and often there
are fasciculations of the tongue. The facial muscles
may be mildly weak but eye movements remain nor-
mal and the patient is usually normal intellectually.
Many patients have a fine, rapid tremor of the hands.
Children with SMA type 2 never walk unsupported.
Survival varies from 18 months through to adult life.
Major management problems include the prevention
of orthopaedic deformity, especially scoliosis, and the
management of the respiratory complications of mus-
cle weakness. Prompt treatment of chest infections
prolongs survival, and many children and adults with
SMA type 2 benefit from nocturnal non-invasive ven-
tilatory support. Patients with a later onset and a mod-
Fig. 17.3.1 Child with spinal muscular atrophy type 1, showing erately benign clinical course are classified as SMA
profound hypotonia and weakness. type 3 (Kugelberg–Welander syndrome). Most have
onset in the first two decades, with only a few in the
­ attern becomes diaphragmatic. Deep tendon reflexes
p third decade, and survival is usually for many decades.
are absent. Fasciculations of the tongue are an impor- Persons with SMA type 3 are able to walk at some
tant clinical clue, but this can be a difficult sign to be point, and many remain ambulant into adulthood.
certain about and one can only be confident if the baby
is relaxed and there are no ‘voluntary’ movements of
the tongue. Facial weakness in SMA is very mild and
the extraocular movements remain full, giving the Peripheral nerve disorders
baby an alert appearance. Death, usually from pneu- A number of peripheral neuropathies with various
monia and respiratory failure, occurs by 18 months of time courses (acute, subacute or chronic) occur in
age in 95% of patients, with those with onset in the childhood. They may be inherited or acquired; they
first 2 months of life having the shortest survival. may involve motor, sensory or autonomic fibres, or
commonly a mixture of all three. Pathologically, they
may be associated with combinations of demyelin-
Practical points ation and axonal degeneration. Some central nervous
system degenerative disorders, such as Krabbe dis-
• Tongue fasciculations can be seen with certainty only ease and metachromatic leukodystrophy, also affect
when the tongue has no voluntary movement, i.e. is at the peripheral nerves. The most common nerve disor-
rest in the floor of the mouth and the child is not crying or ders of childhood are Guillain–Barré syndrome (GBS)
actively moving the tongue. and Charcot–Marie–Tooth disease (CMT). Chronic
• The presence of deep tendon reflexes makes it extremely inflammatory demyelinating polyneuropathy (CIDP),
unlikely that the child has type 1 SMA and an alternative
while uncommon, is important because it is responsive
diagnosis should be considered.
to immunotherapies.

SMA is caused by homozygous deletions of the SMN1 Acute neuropathies

gene, causing loss of SMN protein production in motor
neurons of the anterior horn of the spinal cord. Prenatal
Guillain–Barré syndrome
diagnosis and carrier testing of relatives are available. GBS is the most common acute neuropathy in clin-
Various therapeutic strategies are being trialled. ical practice and can occur at any age, although it
Most are designed to upregulate SMN protein expres- is rare in infancy. An infection, commonly of the 605
sion via a variety of mechanisms. upper respiratory tract or gastrointestinal tract
 17.3 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

(Campylobacter jejuni), precedes the neurological Charcot–Marie–Tooth disease (hereditary motor

syndrome in at least 50% of cases. Typical GBS is and sensory neuropathy)
a monophasic illness with symmetrical, ascending
CMT is the most common form of genetic neuropathy,
weakness involving proximal and distal muscles.
affecting about 1 in 3000 people. The numerous forms
Paraesthesia and muscle pain may be presenting
of CMT are classified on the basis of their clinical
complaints but sensory impairment is usually mini-
presentation, neurophysiological findings and genetic
mal. Severe back pain and stiffness may occur, espe-
cause. Autosomal dominant, X-linked and recessive
cially in young children. The deep tendon reflexes
forms of CMT are recognized. Approximately 60% of
are lost early in the course of the illness. Cranial
affected persons have onset of symptoms in the first
nerve involvement, particularly of the facial nerve,
decade of life.
is relatively common. Autonomic involvement can
Pes cavus, loss of foot dorsiflexion and eversion,
cause wide fluctuations of the blood pressure as well
hyporeflexia and sensory loss are typical findings
as cardiac arrhythmias and bladder dysfunction.
in childhood CMT. However, relatively asymptom-
Respiratory failure occurs in about 30% of patients.
atic children may present because of a family history,
GBS typically progresses over less than 4 weeks, with
whereas others present with gait disturbance, particu-
most patients reaching their maximal deficit within
larly toe-walking, frequent falling or poor coordina-
2 weeks of onset. Artificial ventilation is occasionally
tion. Weakness and wasting in the legs may progress
required. Recovery continues over weeks to months,
slowly, and distal weakness in the arms is sometimes
with most children returning to normal function.
seen. Enlarged peripheral nerves can occasionally be
Some more severely affected children have residual
palpated. Parents of children with suspected CMT
weakness, most commonly of ankle dorsiflexion.
should also be examined as they may have mild clini-
Fatigue is common during the recovery period.
cal changes suggestive of the diagnosis.
Diagnosis is based on the clinical features, with
The diagnosis can be confirmed by nerve conduc-
increased cerebrospinal fluid (CSF) protein with
tion studies, although DNA studies (targeted, or a
only a few, if any, cells in the CSF. Spinal magnetic
chromosomal microarray) are generally the usual first
resonance imaging (MRI) and/or nerve conduc-
step in diagnosis. In CMT1A, the most common form
tion studies are useful in difficult diagnostic situ-
of CMT, DNA studies show a duplicated region on
ations. All children with suspected GBS should be
chromosome 17p involving the PMP22 gene.
admitted to hospital for monitoring of their respi-
There is as yet no cure for CMT, but physiotherapy,
ratory status, blood pressure and cardiac rhythm.
occupational therapy, orthotics and orthopaedic sur-
Management of GBS requires special expertise
gery are often helpful in minimizing weakness and
in medical and nursing care, and affected children
functional problems.
should be referred to centres used to dealing with
this condition. Supportive therapy is very impor-
tant. Intravenous gammaglobulin or plasmapher-
esis, if used early, may hasten recovery, but is not Clinical example
always required for milder cases.
Claudine, a 5-year-old girl, was seen by her
paediatrician because of frequent falls and an
Chronic neuropathies unusual gait. He found areflexia and bilateral
foot drop without proximal weakness. There
Chronic inflammatory demyelinating peripheral was an extensive family history (with an autosomal dominant
neuropathy (CIDP) inheritance pattern) of a chronic neuropathy, presumed to be a
form of CMT, although Claudine's mother was asymptomatic.
This rare but treatable autoimmune neuropathy pres- Examination of Claudine's mother revealed minor sensory
ents subacutely or as a chronic neuropathy. The course loss in the feet and hyporeflexia. Both mother and child
can be monophasic but is more commonly relapsing/ underwent chromosomal microarrays (molecular karyotypes),
remitting. Acute presentations can occur and may which showed a duplication at 17p11 including the PMP22
gene, confirming the diagnosis of CMT1A.
cause confusion with GBS. Symptoms and signs of
weakness, often most prominent proximally, bring the
child to medical attention. The diagnosis is confirmed
by nerve conduction studies, increased CSF protein Children with neuromuscular disease often do not
and, if there is diagnostic doubt, pathological abnor- have all the clinical features seen in adults, and some-
malities on nerve biopsy. CIDP is treated with intra- times it is the family history that gives the vital clue.
venous immunoglobulin, corticosteroids and other The severity of CMT varies considerably and some
immunosuppressive agents. adults are asymptomatic and undiagnosed. Careful
606
 Neuromuscular disorders 17.3
clinical examination of a parent and further diagnostic ­ roximal limb muscle weakness of recent onset should
p
studies sometimes unmask the apparent missing link. raise the suspicion of myasthenia gravis. Fatigability,
The absence of foot deformity or sensory disturbance the hallmark of myasthenia, is usually prominent, but
in a child does not exclude CMT. this is not invariable. In some children muscle weakness
may be confined to the extraocular muscles. Suspicion
of myasthenia gravis should trigger an urgent diagnos-
tic assessment.
Neuromuscular junction disorders Diagnosis is based on clinical observation of fatiga-
Acute bility, often best seen in the upper eyelid, response to
intravenous or intramuscular anticholinesterase agents
Infant botulism
such as edrophonium or neostigmine, repetitive nerve
Infant botulism results from production of Clostridium stimulation testing and assay of acetylcholine recep-
botulinum toxin in the gastrointestinal tract. It dif- tor antibodies. Symptomatic relief may be obtained
fers from botulism associated with food poisoning, in by oral administration of an anticholinesterase, com-
which there is ingestion of preformed toxin from con- monly pyridostigmine. Corticosteroids, thymectomy,
taminated food. In infant botulism, botulinum spores intravenous immunoglobulin and plasmaphaeresis
are ingested. The disease usually occurs in infants have a role in selected circumstances. Although myas-
under 9 months of age because of immaturity of the thenia gravis is a serious long-term and potentially
immune system within the infant gut. fatal disorder, the disease remits in some children.
Constipation for days or weeks typically precedes
the onset of floppiness, weakness and ptosis, which Transient neonatal myasthenia gravis
develop over hours or 1–2 days at most. Feeding and
swallowing difficulty, a poor cough, weak cry, hypo- Transient neonatal myasthenia gravis occurs in about
reflexia and respiratory insufficiency are typical. 10% of offspring of mothers with myasthenia gravis. It
Extraocular movements may be impaired and dilated; is due to placental transfer of anti-acetylcholine recep-
sluggishly reacting pupils are often seen and can be tor antibodies from a myasthenic mother to her fetus
helpful diagnostically. Deterioration may be rapid, during pregnancy. Affected children present in the first
with many patients requiring artificial ventilation for few days of life with feeding difficulties, respiratory
up to 2 months while the neuromuscular junctions difficulty, weakness or hypotonia. Myasthenic symp-
regrow. toms in the mother may be minimal. Appropriate sup-
Diagnosis is clinical, supported by isolation of the portive measures and anticholinesterase medication
organism and its toxin from faeces. Treatment is sup- are used until the syndrome resolves over the ensuing
portive. Botulinum antitoxin has been used but has not weeks.
been shown to be helpful. Human intravenous botu-
lism immune globulin (BabyBIG) may have a place in Congenital myasthenic syndromes
therapy if the child is treated early. The prognosis is
Congenital myasthenic syndromes are genetic dis-
excellent, with full recovery unless complications from
orders of the neuromuscular junction. They are not
cerebral hypoxia intervene. Prompt recognition and
autoimmune disorders. Detailed electrophysiologi-
transfer to a facility capable of long-term ventilatory
cal and morphological testing, available in only a few
support is essential.
laboratories, is usually required to diagnose and char-
acterize these disorders definitively. Hypotonia, limb
Chronic weakness, facial weakness, ptosis, ophthalmoplegia
and apnoeic episodes, particularly with infections,
Autoimmune myasthenia gravis
may be seen, but the emphasis varies with the par-
Myasthenia gravis is an autoimmune disorder caused ticular syndrome. Some show improvement with time
by antibodies directed against post-synaptic acetyl- despite life-threatening episodic apnoea in infancy,
choline receptors of the neuromuscular junction. whereas others cause persisting weakness and oph-
Onset occurs at any time from the second year of thalmoplegia. Some affected children respond to anti-
life. Symptoms develop quickly in most patients, and anticholinesterase preparations, and others respond to
there can be rapid progression to respiratory failure if fluoxetine, ephedrine or 3,4-diaminopyridine. As these
myasthenia gravis remains untreated. Symptoms and are not autoimmune disorders, the immunomodula-
signs are similar to those in adults. Ptosis, ophthal- tory therapies normally used in myasthenia gravis are
moplegia, diplopia, difficulty chewing and swallow- not indicated for children with congenital myasthenic
ing, and slurred speech with or without predominantly syndromes.
607
 17.3 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

Muscle disorders
Acute myopathies
Acute muscle disorders are uncommon in childhood.
Probably the most common is benign acute myositis,
a disorder of mid-childhood, typically affecting boys.
Symptoms include calf pain and difficulty walking
after a viral illness. Affected children often toe-walk or
adopt a wide-based, stiff-legged gait. Muscle tender-
ness is generally isolated to the gastrocnemius–soleus
muscles. Creatine kinase levels are raised but no other
significant biochemical changes are seen, and most
children recover completely within 1 week.
Fig. 17.3.2 Muscle biopsy in central core disease.
Rhabdomyolysis with myoglobinuria appears occa-
sionally after an upper respiratory tract infection or
after exercise, and is probably related to an underly- Muscular dystrophies
ing metabolic disorder of muscle. Rhabdomyolysis can The muscular dystrophies are a group of inherited dis-
also follow snake bite or be triggered by medications. orders of muscle characterized by weakness presenting
The dominantly inherited, sometimes fatal, syndrome from birth to late adulthood, with the common feature
of malignant hyperthermia during anaesthesia also being the pathological appearance of dystrophic muscle
causes muscle necrosis and myoglobinuria. This disor- (Fig. 17.3.3). These disorders primarily affect skeletal
der is associated with central core disease (see below) muscle but other tissues may be involved; for example,
and a number of other inherited myopathies. congenital muscular dystrophies may be associated with
developmental abnormalities in the brain.
Chronic myopathies The various forms of muscular dystrophy share a
common pathogenesis of muscle plasma membrane
Congenital myopathies instability secondary to the lack, or abnormality, of
The congenital myopathies are a group of inher- proteins and glycoproteins linking the subsarcolemmal
ited disorders that are clinically non-specific but that cytoskeleton to the extracellular matrix (Fig. 17.3.4).
have distinctive findings on morphological analysis of Absence or dysfunction of these structural proteins
the muscle biopsy. Common congenital myopathies makes the muscle fibre more prone to damage. Muscle
include central core disease (Fig. 17.3.2) and nemaline fibre death is followed by fibre regeneration with grad-
myopathy. ual accumulation of connective tissue and fat, result-
These myopathies, usually inherited, are character- ing in the eventual development of muscle weakness.
ized by onset of weakness and hypotonia at or shortly Many of the muscular dystrophies share common
after birth, or occasionally later in childhood or adult- clinical features, although their severity varies. The age
hood. Weakness may be mild or severe and is usually only of onset, pattern of weakness, family history and rela-
slowly progressive. Pathologically there are ­structural tively specific findings on examination are important
changes in the contractile apparatus within muscle fibres in diagnosing specific forms of muscular ­dystrophy.
caused by changes in muscle-specific genes. The iden-
tification of these disorders allows important genetic
and prognostic information to be given to the family,
and enables appropriate monitoring for disease-specific
complications such as cardiac involvement, s­coliosis,
hip dysplasia and development of contractures.

Practical points

• In a family exhibiting autosomal dominant inheritance of

a muscle disorder consistent with a congenital myopathy,
central core disease should be considered a possibility
and precautions taken against malignant hyperthermia if
608 an anaesthetic is given (e.g. for muscle biopsy).
Fig. 17.3.3 Dystrophic muscle biopsy.
 Neuromuscular disorders 17.3
delayed language development. The mean IQ of boys
with DMD is approximately 85.
Proximal muscle weakness accounts for the motor
Basement membrane difficulties. This can be demonstrated on formal mus-
Laminin-2
cle strength testing or by functional tests looking at
Sarcoglycan α ability to arise from the floor, climb stairs and run. On
complex
arising from the floor, boys with DMD usually use a
δ β γ
α-dystroglycan Gowers’ manoeuvre (Fig. 17.3.5). A Gowers’ sign is
25 not specific for DMD and is seen in other disorders
with proximal muscle weakness. Enlargement (pseudo-
hypertrophy) and firmness of the calf, quadriceps and
β-dystroglycan triceps muscles is also common in DMD (Fig. 17.3.6).
There is some variability in the course, but the follow-
C
ing generalizations apply to most children with DMD.
Between the ages of 4 and 6 years there is an appar-
N F-actin Syntrophins
Dystrophin ent improvement in mobility, with children acquiring
new motor skills. This is because normal muscle devel-
Fig. 17.3.4 Subsarcolemmal cytoskeleton. opment (and regeneration) outstrips the degenerative
process. After this period of improvement a decline in
function occurs, with increasing proximal limb weak-
Some of the muscular dystrophies are named because
ness. The trunk muscles are also weakened. This leads to
of their pattern of weakness, but these labels will
a waddling gait, increasing lumbar lordosis and increas-
probably change with the identification of specific
­
ing equinovarus foot deformities. Independent mobility
protein defects.
is lost, usually between 8 and 13 years of age, with the
The clinical features of the more common muscular
child becoming wheelchair-bound, after which scolio-
dystrophies are described below.
sis generally develops. During the second decade of life
Duchenne muscular dystrophy there is a gradual decline in pulmonary function, related
Duchenne muscular dystrophy (DMD) is the most to scoliosis and progressive muscle weakness. Death is
common muscular dystrophy, occurring in 1 in 3500 usually due to respiratory complications, although
boys. It is an X-linked disorder and occurs nearly ­cardiac failure secondary to cardiomyopathy can occur.
exclusively in males. It is a disease of devastating pro- Cardiac arrhythmias may be a terminal event.
portions because it is progressive, it has significant The diagnosis of DMD should be based on the family
genetic implications, there are no curative treatments history (if any), clinical features, serum CK, DNA test-
available and it has serious medical complications, ing and muscle biopsy. Pathological confirmation of the
causing death from respiratory or cardiac failure in or diagnosis is essential except where the diagnosis has been
after the second decade of life. confirmed in another family member or by a genetic test-
DMD is caused by a mutation on chromosome ing, which shows a deletion in more than 70% of cases.
Xp21, causing loss of dystrophin, a muscle protein Less common mutations, such as nonsense mutations
important for stabilizing the contractile apparatus or duplications, may be seen only on advanced forms of
within muscle fibres. Two-thirds of patients have a genetic testing. Measurement of the CK level is a reli-
family history of muscular dystrophy or are isolated able screening test and is invariably grossly increased
cases with an unsuspecting female carrier mother. In in a child with DMD, even from the neonatal period.
one-third of cases boys are affected as a result of a Conversely, a normal CK test result after the neonatal
spontaneous mutation. period excludes the later development of DMD.
Development in the first year of life is usually nor- Effective genetic counselling can be offered only if
mal. The first symptoms are usually recognized from the first case in the family is diagnosed before other
18 months to 4 years of age, with delayed walk- affected males are born. The early diagnosis of DMD
ing being the most common presenting complaint. can be facilitated by using the following criteria for
Approximately 50% of children with DMD walk later ordering serum CK estimations in males:
than 18 months of age. Abnormal walking or run- • known or suspected family history of muscular
ning, toe-walking, difficulty in climbing, difficulty in dystrophy
getting up from the floor or chair, and frequent falls • male not walking before 18 months of age without
are other prominent early features. Although many are obvious cause
intellectually normal, a significant proportion of boys • unexplained gait disturbance (particularly toe-walking)
with DMD have developmental problems other than • unexplained mental retardation 609
motor delay, such as static intellectual impairment or • unexplained language delay.
 17.3 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

Fig. 17.3.5 Gowers’ sign in a patient with Duchenne muscular dystrophy, illustrating the sequence of manoeuvres required to rise
from the supine position. (Reproduced with permission from Williams 1982.)

Detection and counselling of female carriers is a

most important aspect of family management. The
male offspring of a known carrier have a 50% risk of
having DMD, and 50% of female offspring will be car-
riers. Females may still be carriers even though there is
no other family history. Only 60% of known carriers
have a raised CK level and hence a normal level does
not exclude the carrier state. Antenatal diagnosis by
deletion testing or linkage analysis is available.
Currently there is no cure for DMD. Management
involves a very positive approach to meeting the emo-
tional, social and educational needs of the affected
boy and his family, together with judicious use of
physiotherapy, occupational therapy, orthotic devices,
and surgery for scoliosis and joint contractures.
Corticosteroid therapy improves muscle strength in
this condition, prolonging independent ambulation
and helping preserve respiratory and cardiac muscle
function. Daily oral steroid therapy is generally initi-
ated at age 4–6 years, or when boys show evidence of
decreasing muscle strength and increasing fatigability
and falls. Early treatment with angiotensin-converting
enzyme (ACE) inhibitors prevents and slows develop-
610
Fig. 17.3.6 Pseudohypertrophy of muscles. ment of cardiomyopathy in DMD. Adolescents and
 Neuromuscular disorders 17.3
young adults with DMD often benefit from treatment or stimulation. Myotonia can be detected during
with non-invasive ventilatory support for nocturnal attempted relaxation of a voluntary contraction, such
hypoventilation caused by respiratory muscle weak- as after shaking hands or eyelid closure, by percussion
ness. These treatments, and improved physiotherapy, of a muscle or by electromyography. Older children
occupational therapy and orthopaedic management, may describe myotonia as stiffness or cramping.
have had a significant impact on life expectancy in Many of these disorders are due to defects of m
­ uscle
DMD, which is now into the third or fourth decade of ion channels. In some instances different m ­ utations
life for boys diagnosed in the last decade. within the one gene can cause myotonia and/or
­periodic paralysis.

Practical point
Myotonia congenita (Thomsen disease)
• The most common reason for the late diagnosis of There are autosomal dominant and autosomal reces-
Duchenne muscular dystrophy is not thinking of the sive forms of this disorder. Onset is in infancy or early
diagnosis in a young male with delayed motor, mental or childhood with symptoms due to myotonia, such as
language development. stiffness, difficulty initiating rapid movements and
sometimes feeding difficulties. Muscle hypertrophy
is common. The myotonia decreases with continued
Becker muscular dystrophy activity and may be aggravated by cold. Symptoms
Becker muscular dystrophy is allelic to DMD but improvement occurs with increasing age. Symptomatic
much less common. It is less severe than DMD and treatment of myotonia with quinine or mexiletine is
has a variable age of presentation. sometimes required.
Facioscapulohumeral syndrome
Facioscapulohumeral (FSH) muscular dystrophy is Myotonic dystrophy (Steinert disease)
a relatively common autosomal dominant myopathy
that predominantly affects the shoulder girdle, in par- Myotonic dystrophy is an autosomal dominant disor-
ticular the periscapular, humeral and facial muscles. der, but the affected parent may be relatively asymp-
It is a relatively mild disorder with very slow progres- tomatic and may not be diagnosed prior to the birth of
sion. Onset is most commonly in adolescence or early their more significantly affected children. The disease
adult life, although FSH occasionally presents in early is due to an excessive number of repeats of the CTG
childhood. sequence on chromosome 19. The spectrum of clini-
Facial muscle weakness is generally one of the first cal severity in myotonic dystrophy is extremely broad.
symptoms. Patients have difficulty closing the eyes, This is a severe multisystemic disease that is diagnosed
blowing out the cheeks, whistling or sucking through on genetic testing. Antenatal diagnosis is available
a straw. Shoulder girdle weakness usually begins at and cascade testing of other family members is often
the same time as the facial weakness and can be quite required when an affected infant is born to a family.
asymmetrical. Symptoms include difficulty lifting the Juvenile type
arms above the head. There is obvious winging of the The clinical features are similar to those seen in adults,
scapulae in adult patients, but this may not be obvious with ptosis, facial and distal muscle weakness and
in children. On abduction of the shoulders, the scap- wasting, and myotonia. Cataracts, frontal alopecia,
ulae move upwards and give the shoulders a charac- testicular atrophy, cardiac arrhythmias and cardiomy-
teristic appearance. Foot drop is not uncommon. The opathy may occur in adult life.
infantile form of FSH dystrophy is associated with
more severe weakness. Congenital type
The locus for autosomal dominant FSH has been Congenital myotonic dystrophy is invariably inherited
mapped to the distal arm of chromosome 4. from the mother, and is more severe than in the mother
Treatment is symptomatic. Sensorineural hearing because of expansion of the CTG repeat sequence dur-
loss and Coats’ disease, a proliferative retinopathy, are ing meiosis. Congenital myotonic dystrophy presents
associated with early-onset FSH dystrophy. Aggressive at birth with hypotonia, marked weakness, arthrogry-
treatment of these associated disorders is important. posis, feeding and respiratory difficulties. Intellectual
disability is virtually invariable if the child survives
the neonatal period. Affected children have persisting
Myotonic disorders weakness and are at risk of ongoing respiratory insuf-
Myotonia is the common feature of this clinically ficiency, endocrine problems and cardiac involvement
heterogeneous group of myopathies. Myotonia is the in later life. Myotonia is not present at birth in this
611
inability of muscles to relax after voluntary c­ ontraction ­disorder, but can generally be elicited by late childhood.
 17.3 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

The underlying metabolic defects are usually of

Clinical example glycogen metabolism (e.g. Pompe disease), lipid
metabolism (e.g. carnitine deficiency, carnitine pal-
Mrs McGill, aged 25 years, had myotonic mitoyltransferase deficiency), potassium metabolism
dystrophy, as did her father, sister and brother.
(e.g. the periodic paralyses associated with hyper-,
She had a son and twin daughters who were
normal at birth and who remained asymptomatic.
hypo- or normo-kalaemia) or mitochondrial function
Her next child, Tessa, was 4 weeks premature and at birth (e.g. myopathies due to abnormalities of respiratory
was very hypotonic, had respiratory difficulty and required chain enzymes).
gavage feeding. There was marked bilateral facial weakness, Knowledge of the underlying metabolic causes of
talipes equinovarus and mild flexion deformity at the knees. many of these disorders is increasing and the hope is
The respiratory and feeding difficulties gradually resolved, but that, once the underlying pathophysiological processes
the facial muscle weakness remained and Tessa later showed
have been elucidated, more specific and effective thera-
delay in motor and language milestones. There was no clinical
myotonia when she was seen at 3 years of age. pies will become available.
Tessa had typical features of the congenital form of
myotonic dystrophy, which typically occurs when it is the
mother who is the affected parent. Some babies are stillborn,
whereas others do not survive the neonatal period. Tessa The ‘floppy’ infant syndrome
was affected only moderately and will survive into adult
life, but will almost certainly require special schooling. The Hypotonia, or floppiness, is a common observation in
dominant inheritance is clear from the family history. Mrs infancy and has many different causes. Muscle tone is
McGill and her husband wanted to know whether the other assessed by observation of posture, and assessment of
children might develop the disease. Although they were
the resistance of joints to passive movements and of
asymptomatic at the time, there was still a chance that
they had inherited the abnormal gene. DNA testing for the range of movement. Normal muscle tone depends not
triplet expansion on chromosome 19 could be used to allow only on the peripheral neuromuscular system but also
antenatal diagnosis. on spinal cord and higher centres. Neonatal hypotonia
is more often due to disorders of the ­central nervous
system than to peripheral neuromuscular disorders.
When an infant or young child is found to be
Practical point signi­ficantly hypotonic, an important question is
whether the hypotonia is ‘central’ or ‘peripheral’ in
• Facial diplegia with respiratory difficulty or pharyngeal origin. Hypotonia of neuromuscular origin usually
­
incoordination in a neonate should raise the suspicion of
is ­associated with significant weakness (e.g. Werdnig–
congenital myotonic dystrophy.
Hoffmann disease), with decreased or absent reflexes,
whereas central hypotonia is usually not associated
Inflammatory myopathy with significant weakness (e.g. Down syndrome or
Prader–Willi syndrome). In practice, the differentia-
Dermatomyositis, the only common chronic inflam- tion in early childhood can sometimes be quite ­difficult.
matory myopathy of childhood, presents with proxi- Apart from the absence of significant w ­ eakness, clues
mal weakness that is often very insidious in onset, a to a central cause of hypotonia may be:
pinkish (heliotrope) facial rash, irritability and exercise • a history of adverse perinatal events
intolerance. Diagnosis is often delayed. The serum CK • abnormal behaviour in the neonatal period
level is moderately increased. Muscle ultrasonography • delayed mental development
or MRI can be useful, but a muscle biopsy is generally • seizures
required for diagnosis. Long-term immunosuppressive • abnormality of head size or shape
therapy is often required. Complications of childhood • the presence of normal or brisk deep tendon reflexes.
dermatomyositis (which unlike its adult counterpart is Hypotonia of peripheral neuromuscular o ­rigin
not associated with malignancy) include gastrointesti- is usually, but not invariably, accompanied by
nal involvement, calcinosis and joint contractures. hyporeflexia in an alert baby with normal mental
development.
Metabolic myopathies
A large number of individually uncommon meta-
bolic disorders may produce episodic, acute or chronic
muscle weakness, hypotonia, stiffness or cramping,
Acknowledgements
­exercise intolerance or myoglobinuria. Symptoms are We would like to thank Dr Lloyd K. Shield, who has
sometimes accentuated or precipitated by exercise, rest been our mentor and the person who kindled our
612
after exercise, fasting or excessive carbohydrate intake. interest in neuromuscular disorders.
Neural tube defects, large 17.4
heads and hydrocephalus
Peter Flett, Ray Russo

of myelomeningocele was 0.97 per 1000 births, with

Neural tube defects no upward or downward trend. Despite the total
The neural tube is the embryological structure from incidence remaining stable, prenatal diagnosis and
which the brain and spinal cord develop. The term ­termination of pregnancy resulted in an 84% fall in the
neural tube defect (NTD) refers to a group of mal- birth prevalence of all NTDs during the years stud-
formations involving the brain and/or spinal cord ied. Screening by serum α-fetoprotein (AFP) mea-
in association with varying degrees of absence or surements or mid-trimester ultrasonography, or both,
malformation of the overlying tissues: meninges, detected more than four-fifths of cases in 1986–1991
bone, muscle and skin. Anencephaly occurs when in South Australia.
the neural tube fails to close at the head, and the Recurrence risks in families such as close relatives
brain and skull bones do not develop normally. have been documented extensively. Recurrence risk
Myelomeningocele (myelo meaning ‘cord’; meninges, statistics suggest a polygenic or environmental aeti-
coverings of the spinal cord; cele, ‘sac’) involves all ology. The risk of recurrence following the birth of
the tissue layers including the skin and bone, and the first child with a NTD is approximately 4–8%, or
is an outpouching of the spinal cord through the 1 in 25. A woman is at equal risk of either spina bifida
posterior bony vertebral column that has failed to or anencephaly in future pregnancies, regardless of
form. Meningocele is an outpouching of the menin- whichever of these NTDs occurred in the previous
ges or coverings of the ­spinal cord only, and not the pregnancy. The risk increases to at least 10% after the
cord itself. The term spina bifida refers to the nor- birth of two affected children.
mal bony projection over the spine being divided NTDs are found commonly in spontaneous first-
or ‘bifid’. Spina bifida occulta is the failure of the trimester miscarriages. They are also more common in
­formation of the posterior elements of the vertebrae females than in males, in lower socioeconomic groups,
but without any outpouching of the meninges or spi- different ethnic groups, and in women taking certain
nal cord. It occurs in 5–10% of the population and is anticonvulsant drugs.
most often asymptomatic. X-rays of the spine docu-
menting the incomplete vertebral arch confirm the
Embryology and pathogenesis
diagnosis. Accompanying associated features may
include dermal hyperpigmentation, a fatty swell- The human neural tube closes just before the 30th
ing, a tuft of hair or a dermal sinus on the back. day following fertilization and thus any influence
Spina bifida cystica refers to myelomeningocele and affecting the closure of the neural tube must be pres-
meningocele. Myelomeningocele is the more s­ erious ent before this early stage of pregnancy. The typical
and commoner type of spina bifida c­ ystica. Spinal motor, sensory and sphincter dysfunctions of spina
­dysraphism, which includes spina bifida occulta, bifida and myelodysplasia are the most evident clini-
meningocele and myelomeningocele, is part of the cal manifestations but represent only one aspect of
family of NTDs that encompasses abnormalities of this complex teratological anomaly. There is a high
the cranium and its contents (anencephaly, encepha- incidence of gross and microscopic brainstem, cer-
locele and cranial meningocele) as well as abnormal- ebellar and cerebral malformation. The aetiology
ities of the spine. of NTDs is still debated. Polygenic inheritance and
environmental and teratogenic factors have been
implicated. It has been demonstrated unequivo-
Incidence
cally that vitamin supplementation with folic acid
The incidence has varied in different countries, the reduces the incidence of recurrence in high-risk pop-
highest rates being recorded in the past in Northern ulations. Dietary factors may therefore play a major
Ireland, the west of Scotland and south Wales. In part in low-risk populations. Many other potential
South Australia, the total incidence of NTDs ­during ­aetiological causes have been examined also during
1966–1991 was 2.01 per 1000 births and the incidence the last 20 years. 613
 17.4 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

Antenatal diagnosis, antenatal counselling and the facets of raising a child with this diagnosis. The
fetal surgery antenatal scan can offer some guidance, but it must
be remembered that ultrasound scan findings cannot
The presence of abnormally high levels of AFP in the
predict all aspects of functioning (physical and cog-
amniotic fluid has a high correlation with myelomenin-
nitive) accurately. In addition, families can be offered
gocele. AFP is a component of fetal cerebrospinal fluid
further counselling through community-based organi­
(CSF) and it probably leaks into the amniotic fluid
zations (e.g. the Spina Bifida and Hydrocephalus
from the open NTD. Closed lesions often do not cause
Association). All families should be made aware of
increased AFP levels. The false-positive rate for the
preventative measures (periconceptional folate) and
determination of myelomeningocele is less than 0.5%
offered genetic counselling if they wish to have other
and the false-negative rate is 2%. AFP is synthesized by
children in the future.
the yolk sac, hepatic cells and gastrointestinal tract of
Fetal surgery (for closure of the myelomeningocele
the fetus and is normally excreted in the amniotic fluid
lesion) at 20–30 weeks' gestation, after which the fetus
in fetal urine. The detection rate for open NTDs using
is returned to the uterus, has been developed with the
maternal serum screening is approximately 80%, with a
hope of preventing significant complications in the
low false-positive rate. Ultrasonography can detect or
affected child. Early studies have demonstrated good
confirm the extent of the NTD.
cosmetic closure of the lesion but the complication
Offering counselling for the family with an ante-
rate (primarily due to the fetus being delivered prema-
natal diagnosis of a NTD is important, especially as
turely) was found to be high. The primary o ­ utcome
the family will probably consider their options about
is a significant reduction of the development of
whether to continue with the pregnancy or elect for
­hydrocephalus in the treatment group.
termination. Great care should be taken about the
information conveyed. Preferably, it should be given
by a specialist experienced in caring for children with
Clinical features
a NTD, in an appropriate environment and with time
available to answer the family's questions about all NTDs may be classified as in Box 17.4.1.

Box 17.4.1 Classification of neural tube defects

Anencephaly Spina bifida cystica

• At birth, presents as an opened, malformed skull and brain • Meningocele (Fig. 17.4.2), where the spinal cord is not
• Most babies are stillborn involved:
• No effective treatment is possible • Herniation consists of meningeal cyst filled with
• Death usually occurs within hours or days cerebrospinal fluid, in absence of other malformations,
neurological signs are normal
Cranium bifidum • Not associated with hydrocephalus
Cranial meningocele • Constitute less than 10% of all cases of spina bifida cystica
• The underlying brain is normal • Myelomeningocele (Figs 17.4.3 & 17.4.4), in which vertebral
• A meningeal sac protrudes through a skull defect column skin, meninges and spinal cord are involved:
• Almost always obvious at birth
Encephalocele • May occur anywhere along the length of the spinal column,
• A midline sac protrudes that may contain brain with lumbar and lumbosacral regions being the most
• Hydrocephalus is common frequent anatomical levels
• Abnormal spinal cord tissue and nerve roots may be readily
Spina bifida occulta (Fig.17.4.1) apparent macroscopically
• One or more vertebral arches are incomplete posteriorly but • There may be spinal abnormalities such as kyphosis at the
the overlying skin is intact site of the lesion
• Diagnosed incidentally, for example as the result of X-ray of • Functional deficits almost always include:
the spine • Arnold–Chiari type 2 malformation and hydrocephalus
• Spinal cord usually normal; however, abnormalities of the • paraplegia, with motor and sensory impairment;
spinal cord can occur intellectual impairment and neuropathic sphincter
• Ectodermal abnormalities may be associated with disturbance (bowel and bladder)
pigmented naevus, angioma, hirsute patch, dimple or
dermal sinus on overlying skin Sacral agenesis
• The ectodermal component may communicate with • Genetic disorder, marked by total absence of coccyx and
the dura; may pose some risk of intraspinal infection lower two or three sacral vertebrae
(if associated with a dural sinus) • Functional deficits include flaccid neurogenic bladder, motor
614 • The fatty swelling may be a lipomeningocele and, to lesser extent, sensory deficits of lower extremities
 Neural tube defects, large heads and hydrocephalus   17.4
Dermal pit Management of myelomeningocele
A
A team approach that includes the parents is essential
for the proper management of myelomeningocele. An
important factor, which compounds the d ­ isability, is
that the defect is apparent at birth. Information given
to the parents and the manner in which it is conveyed
will influence their reaction at this most ­vulnerable
time and will affect the future of the child and the
­family. Medical specialists in this team include the
neurosurgeon, orthopaedic surgeon and urologist.
The medical team leader is most appropriately a pae-
Hairy patch diatrician or paediatric rehabilitation specialist with
B on skin
special skills in the field of child development and
rehabilitation. The medical team leader will coor-
Dermoid cyst dinate care but, importantly, will also manage and
advise on the multiple problems experienced by the
children and their f­amilies. These include disability
issues, school i­ntegration, interventions to improve
functional o­ utcome, and ­various activities to support
the parents and child through the many problems,
both physical and psychological, that invariably arise.
The physiotherapist, occupational therapist, speech
Fatty lump
pathologist, dietitian, orthotist, psychologist and
– skin
C medical social worker, together with trained hospital
discoloration
and community-based nursing staff and teachers, are
important members of this team. The team has three
major goals:
• to promote good health in the short and long term
• to promote maximum function in the child so
that, as nearly as possible, normal developmental
sequences and timing can be followed to enable
maximal independence for the child and family
• to support good family functioning to assist the
Fig. 17.4.1 Schematic representation of spina bifida occulta. child to reach their maximum potential within the
(A) Dermal sinus. (B) Intraspinal cyst pressing on the cord. family and community.
(C) Lipomatous mass infiltrating the cord elements.

Cerebrospinal Skin and

fluid dura

Pia and
arachnoid

Spinal
cord

Central
canal

Nerve Bone
root

Transverse section Longitudinal section

615
Fig. 17.4.2 Meningocele: diagrammatic representation.
 17.4 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

in discussion with the family, supportive care only

may be recommended. If the infant survives the
perinatal period, elective surgical care may be
indicated. In the absence of such adverse factors,
in discussion with the family, early surgical repair/
removal of the lesion usually is recommended.
2. Careful serial evaluation of head circumference
and ventricular size by ultrasonography or
computed tomography (CT) will indicate whether
hydrocephalus is developing. Once it is established
that progressive hydrocephalus is present, a shunt
procedure is recommended.
3. Baseline orthopaedic, urological and neurosurgical
assessments provide the basis for ongoing
discussions with the family and management of
Fig. 17.4.3 A lumbosacral myelomeningocele. the condition. Occasionally, active urological
intervention is required for urinary retention.
Specific problems in the management of the 4. It is critical to begin to establish an empathetic,
newborn with spina bifida therapeutic relationship with the parents in the
newborn period that forms the foundation for
It is possible to predict with considerable accuracy the
ongoing support throughout childhood.
potential for future impairment in a number of areas.
These include ambulation and subsequent mobility,
probable bowel and bladder function, and hydroceph- Ongoing management
alus, with its probable sequelae. It is much more dif-
Management of physical disability and mobility
ficult to predict the effects that these impairments will
have on the lifestyle of the individual and family. Also, Physiotherapists play an essential role in reducing
it is possible to recognize early those lesions that are deformities and encouraging mobility. Foot deformi-
inoperable because of massive bony deformity and ties are common at birth as a result of unopposed mus-
extensive skin loss, which would prevent closure of the cular activity in utero. Splinting and passive stretching
defect. The specific problems are as follows: are the mainstays of treatment in early life. Persistent
1. Children with high lesions (thoracic and foot deformities may require corrective orthopaedic
thoracolumbar), significant hydrocephalus at surgery. Surgery also may be needed for dislocated
birth, major kyphosis or other significant problems hips, particularly if the child is likely to walk. At times,
(either congenital or acquired) have a significantly three-dimensional gait analysis (3DGA) is beneficial
increased mortality rate in early life and substantial for surgical decision-making and can assist in planning
morbidity if they survive. In these circumstances, for this intervention.

Neural
Neural plaque plaque

Nerve
roots
Skin

Spinal
cord

Central
canal

Bone

Transverse section Longitudinal section

616 Fig. 17.4.4 Myelomeningocele: diagrammatic representation.

 Neural tube defects, large heads and hydrocephalus   17.4
The outlook for walking depends on the level of the Neuropathic bowel
spinal cord lesion, intelligence and motivation. Most
Most children have limited or absent rectal sensation,
children with a lesion at L4 or lower will walk, with
and have little or no bowel control. Constipation with
or without splints and crutches. Children with higher
megacolon, faecal impaction and overflow inconti-
lesions may walk with orthotics in early childhood, but
nence is the major risk in spina bifida. Faecal soft-
most will choose wheelchair mobility by mid to late
eners may be needed in infancy. Some children can
childhood.
attain continence simply by regular toileting, whereas
others may need high-fibre diets, faecal softeners,
Spinal deformities suppositories or microenemas. Aperients are avoided
A significant proportion of children will develop scolio- whenever possible. Refractory cases may require reg-
sis and many of these will require spinal instrumenta- ular bowel washouts. Another technique that may
tion. Spinal jackets are not well tolerated and have a very increase independence is the anterograde colonic
limited role in the management of paralytic scoliosis. enema (ACE). This surgical procedure creates a
stoma on the anterior abdominal wall through which
a catheter can be passed to allow for easier access
Neuropathic fracture for the provision of an enema. The advantage is that
Fractures of the lower limbs, due to o­ steopenia, are the enema is completed independent of others and
common in children with myelomeningocele. Fractures can assist greatly in the management of refractory
­neuropathic bowel.
may occur with minimal trauma. Encouraging
­children to walk, or stand in a standing frame on
a regular basis may improve the mineralization of Sexual function
long bones and lessen the likelihood of further frac-
Many people with spina bifida achieve satisfactory sexual
tures. However, nutrition, calcium and vitamin D
relationships. In females, pregnancy has been achieved
from ­ sunlight may also be important factors in
in many individuals and is generally a positive experi-
management.
ence. Predictably, there are a number of potential diffi-
culties with pregnancy and confinement. Urinary tract
Sensory deficit and skin care infections, worsening pressure sores, worsening mobil-
ity and spinal problems are particularly common. In
Pressure ulcers or burns in anaesthetic areas are com-
males, the situation is more complex. Difficulties range
mon. Parents are encouraged to check anaesthetic
from impotence to retrograde ejaculation and infertility.
areas daily for the presence of pressure sores. Early
Sexual counselling is important in adolescence.
recognition and treatment is essential to prevent long
periods of morbidity and hospitalization.
Tethered spinal cord

Neuropathic bladder Following repair of a myelomeningocele, the lower

end of the spinal cord may become tethered to the site
Almost all children with myelomeningocele have a of repair. As the child grows, this may cause progres-
neuropathic bladder. Failure to empty the bladder sive neurological deterioration in motor or sensory
may lead to recurrent urinary tract infections, vesi- function, or in bladder control. Regular monitoring
coureteric reflux, renal calculi and hydronephro- of the neurological state is essential particularly dur-
sis. Hypertension and renal failure may be seen in a ing the rapidly growing phase. MRI is performed to
small number of cases. Management of the neuro- demonstrate the tethering process. If the neurologi-
pathic bladder is by clean intermittent catheteriza- cal deterioration is significant, or the child experi-
tion performed four or five times daily by the parents, ences significant pain, consideration should be given
and later by the child. This is usually commenced at to ­neurosurgical release of the tethered cord.
around 3–4 years of age, or earlier if repeated uri-
nary infections occur. Prophylactic antibiotics may
Arnold–Chiari malformation
be required for recurrent urinary infections. Bladder
augmentation and/or artificial sphincter operations This has been described (Fig. 17.4.5). It is present in
may be indicated if the clinical situation dictates. The a significant number of children with myelomeningo-
use of anticholinergic medications and of oxybutynin cele and is elegantly demonstrated by MRI. Symptoms
to increase bladder capacity may be tried. Regular are variable: they may be quite minor (e.g. strabismus
assessment of renal function is essential throughout or mild difficulties with chewing and swallowing) or
the person's life. they may be severe, with laryngeal stridor and apnoeic 617
 17.4 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

Social and emotional adjustment and transition

to adulthood
A child with a chronic disability places severe strains
on the emotional and financial resources of a family.
Members of the team must be alert to signs of distress
and be ready to provide the necessary support. During
the teenage years, the usual problems of adolescence
are superimposed on the difficulties associated with
the disability, and these young people need sensitive
counselling. For the families, parent groups provide
valuable practical and emotional support.

Adults with spina bifida

There are now increasing numbers of young adults with
spina bifida. A coordinated approach to management
is still desirable but more difficult to attain, because of
Fig. 17.4.5 Magnetic resonance image of a child with a the wish of the young people to be independent and to
spina bifida showing the Arnold–Chiari malformation. Note the break away from what they perceive as overprotection
herniation of the cerebellum into the upper cervical canal. by the medical fraternity. Ongoing health-care issues in
adult life include urological, g­ astroenterological, mus-
culoskeletal, sexual health, skin, neurological, cogni-
spells. Life-threatening episodes may necessitate neuro- tive impairment, other chronic health issues, and also
surgical intervention to decompress the posterior fossa. vision and hearing. There is recent evidence to sup-
Related feeding difficulties can often be managed by port continuing high mortality throughout adult life
full evaluation of feeding and swallowing function, in persons with open spina bifida, and many deaths
adjustment of the diet (e.g. giving foods of a pureed are unexpected.
consistency) and, at times to prevent life-threatening
aspiration events, discontinuing oral feeding and using Prevention of neural tube defects
alternative means of feeding (e.g. gastrostomy).
NTDs (spina bifida, anencephaly and encephalocele)
result from defective closure of the neural tube in early
Education
pregnancy. The human neural tube closes just before the
Children with myelomeningocele often have intel- 30th day post-fertilization and thus any influence affect-
lectual disability and/or specific learning problems, ing the closure of the neural tube must be present before
requiring assistance at school. This is often evalu- this early stage of pregnancy. Primary prevention of this
ated by a clinical psychologist to determine the child's group of conditions may now be feasible. Research has
strengths and weaknesses to assist the school in maxi- suggested a relationship between maternal diet and the
mizing the learning progress of the child. Overall intel- birth of an affected infant. Medical evidence has con-
ligence is generally in the low average range, with a wide firmed that folic acid (a water-soluble vitamin found in
range of abilities. Verbal IQ is usually considerably many fruits, leafy green vegetables, wholegrain breads,
higher than performance IQ, and many children have cereals and legumes) may prevent the majority of NTDs.
apparently very good expressive language but with A randomized controlled clinical trial carried out
a paucity of meaning and content of speech (often by the UK Medical Research Council demonstrated
referred to as ‘cocktail party syndrome’). Difficulties a 72% reduction in risk of recurrence by periconcep-
with mathematical concepts are very common, as are tional (i.e. at least 1 month before and for 3 months
problems with abstract reasoning. Many children have after conception) folic acid supplementation of 4 mg
a poor attention span and distractibility, but also poor daily. Other epidemiological research, including work
memory. Problems with fine motor control and visual done in Australia, suggests that primary occurrences
perceptual difficulties are frequently present. Most of NTD births may also be prevented by folic acid,
children with spina bifida attend normal schools, with either as a supplement or in the diet, and this has
varying levels of assistance for physical and cognitive/ been confirmed in a randomized controlled trial from
learning difficulties from support teachers. Schools Hungary, which found that a daily multivitamin sup-
may require modification to provide access and suit- plement containing 0.8 mg folic acid was effective in
618
able toilet arrangements. reducing the occurrence of NTDs in first births.
 Neural tube defects, large heads and hydrocephalus   17.4
The National Health and Medical Research Council • There should be continued research into the
of Australia has recommended the following: mechanisms of action of folic acid and the
• All women planning a pregnancy or likely to become minimum dose of folic acid required for prevention.
pregnant should be offered advice about folate • Close monitoring of both the prevalence of NTDs
and encouraged to increase their dietary intake of (including terminations of pregnancy) and the increase
folate-rich foods, particularly in the month before in folate intake should be undertaken to evaluate
and in the first 3 months of pregnancy. the effectiveness of any health promotion campaigns.
In addition: • Further research should be monitored, and these
• Low-risk women (no family history of NTDs, not on recommendations reviewed in the light of any
anticonvulsants) should be offered periconceptional developments.
folic acid supplementation (0.5 mg daily). Generally, In Australia, health promotion campaigns have been
periconceptional supplementation with other undertaken to inform health professionals and women
vitamins is not necessary. When supplements are about folate and the prevention of NTDs. For example,
used, the potential risks of vitamin overdose should folic acid (folate) in fruit and vegetables is easily destroyed
be considered. In particular, large therapeutic doses by cooking and prolonged storage. It is wise to eat fruit and
of vitamin A may predispose to birth defects. vegetables that are fresh, and either raw or lightly cooked.
• Women with a close family history of NTDs (e.g. For good health and enough folate per day, one would need
they or their partner has spina bifida, they have to aim for at least two servings of fruit, five servings of veg-
already had an affected child, they have a sibling or etables, and seven servings of bread and cereals every day.
other close relative with a NTD) should: The safety of increased folate ingestion before and during
• be referred for genetic counselling early pregnancy appears to be confirmed. Furthermore, an
• be advised to take periconceptional folic intake of folate from fortified food is unlikely to be high
acid supplementation 5 mg daily (the 4-mg enough to constitute a hazard for those people in the com-
formulation is not available in Australia) munity with unknown and untreated vitamin B12 defi-
• continue to be offered prenatal diagnosis with AFP ciency, which can worsen their symptoms if folate is given
estimation and tertiary-level ultrasonography, by an to these individuals without also ­giving vitamin B12.
operator experienced in anatomical scans, at 16–18
weeks' gestation. Although the risk of recurrence is
reduced significantly if folic acid supplementation
is used appropriately, there is a residual risk of
Large heads (macrocephaly)
about 1% in women taking supplements who have Macrocephaly can be defined as head circumference
previously had an affected infant. more than two standard deviations above the mean on
• Women on anticonvulsant drugs should take folic growth charts.
acid supplementation only under the supervision of The more common causes include:
and with close monitoring by their physician. • normal variant (often familial)
• Because of the increased risk of NTDs in the • an oversized, overweight brain (as in megalencephaly)
offspring of women taking some anticonvulsants • hydrocephalus (progressive or ‘arrested’)
(notably sodium valproate), these women also • a tiny cerebrum (as with large chronic subdural
should be counselled and offered prenatal diagnosis. effusions or hygromas in infancy)
• no cerebrum (as in hydranencephaly).
Normal variants tend to be diagnosed by exclusion, based
Fortification of staple foods with folic acid/folate
upon careful history (including family history), measure-
Fortification of bread-making flour with folic acid was ment of head circumferences including those of the par-
introduced in Australia in September 2009. Mandatory ents and siblings, and of neuroradiological investigations.
addition of folic acid to flour in the USA and Canada Head enlargement in megalencephaly can be a late
has been in place now for more than 10 years. After manifestation of many cerebral degenerative disorders
mandatory wheat flour fortifications in the USA, there such as lysosomal storage diseases or leukodystrophies.
was a 30% reduction in NTDs. Folic acid fortification Megalencephaly also occurs in a wide variety of other
of flour is inexpensive. clinical disorders and syndromes, such as n
­ eurocutaneous
syndromes and cerebral gigantism (Sotos syndrome).
It can be unilateral ­ (hemimegalencephaly) or bilat-
Education, research and monitoring
eral, and may also be familial and associated with a
• There should be educational programmes, for wide spectrum of developmental symptoms and signs
health professionals and the public, on how to ­including normal development.
achieve adequate folate intake with diet and Hydranencephaly is a condition of uncertain aetiology. 619
supplementation to prevent NTDs. The cerebral cortex is represented by a thin membrane
 17.4 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

composed of glial cells, with islands of cerebral cortex • an increase in CSF volume
sometimes scattered in this tissue. The third ventricle, • ventricular dilatation
basal ganglia, brainstem and cerebellum are present but • increased intraventricular pressure.
may reveal morphological abnormalities. The head size Hydrocephalus occurs when there is an imbal-
is usually normal at birth but increases rapidly within a ance between the formation and absorption of CSF.
few weeks of life. Neurological function may initially be Impaired absorption is almost always due to some
normal, shortly after gross ­neurological abnormality is degree of obstruction along the CSF pathways. If the
evident (rigid muscle tone, tremors, and persistent and passage of CSF is obstructed within the ventricular
exaggerated p ­ rimitive reflexes). Optic atrophy is common system, the resultant hydrocephalus is labelled non-
and the head transilluminates readily. The child sleeps communicating, whereas if obstruction exists in the
excessively, is ­irritable, feeds poorly and has unstable ther- surface pathways, the hydrocephalus is described as
moregulation. Electroencephalography reveals a flat trac- being communicating. The rate of this volume change
ing or few low voltages over islands of cerebral cortex. varies from patient to patient and depends in large part
on the degree of obstruction. The lesions that com-
Hydrocephalus
monly produce hydrocephalus are listed in Box 17.4.2.
Hydrocephalus (Greek: hydro meaning ‘water’, and In supratentorial lesions, CSF obstruction is a
cephale, ‘head’) refers to a group of conditions char- late event, so that neurological or endocrinologi-
acterized by: cal abnormalities often precede symptoms of raised

Box 17.4.2 Lesions producing hydrocephalus

Non-communicating • Differential diagnosis includes craniopharyngioma,

Aqueduct stenosis or atresia gliomas, pinealomas and arachnoid cysts
• Commonest site of intraventricular obstruction in infants with • Haematoma
congenital hydrocephalus • Galenic vein aneurysm
• May occur as an isolated anomaly or be associated with
myelomeningocele and the Arnold–Chiari malformation Communicating
• Histologically, subependymal gliosis around the aqueduct is Arnold–Chiari malformation
demonstrable With myelomeningocele (type 2) (see Fig. 17.4.3)
• May be slowly progressive in some, not being clinically apparent Without myelomeningocele (type 1)
for several years before obstructive symptoms appear • Consists of:
• Sporadic • downward displacement and elongation of the hind brain
• Familial • herniation of the medulla, cerebellar vermis and inferior
• Inherited as a sex-linked trait; features include a short flexed part of the fourth ventricle into the upper cervical canal
thumb, mental retardation and other cerebral abnormalities • CSF flow is impaired, usually within the subarachnoid space
• Hydrocephalus usually develops in early infancy
Obstruction at the fourth ventricle • Frequently associated with cranium bifidum,
• Dandy–Walker syndrome myelomeningocele and hydromyelia
• Cystic dilatation of the fourth ventricle, with cerebellar
hypoplasia; other structural brain anomalies may also occur Encephalocele
• Associated with atresia of the exit foramina of the fourth Meningeal adhesions
ventricle • Postinflammatory
• Hydrocephalus may be present at birth or may develop • Posthaemorrhagic
subsequently • May be secondary to neonatal meningitis (post
• Diagnosis is suggested in typical cases by the shape of inflammatory adhesions), or intraventricular or subarachnoid
the skull and the presence of cerebellar signs haemorrhage
• Arachnoiditis • Hydrocephalus is common, and is usually communicating
(but may be non-communicating)
Obstruction due to intracranial mass lesions • Neurological deficit, developmental delay and seizures
• Should always be considered in any child where head are usually the result of the infective process, but the
enlargement develops in late infancy or childhood hydrocephalus, if not relieved, will aggravate the brain injury
• Neoplasm, cysts
• Childhood tumours usually arise in the posterior cranial Choroid plexus papilloma
fossa and include medulloblastoma, astrocytoma and • A rare cause of hydrocephalus
ependymoma • Hydrocephalus is produced by excessive fluid secreted by
• Intracranial pressure develops early, because of their the tumour, sometimes with obstruction to CSF flow
close proximity to the fourth ventricle • Recurrent haemorrhage from the tumour may play a role
• Ataxia, incoordination, nystagmus and papilloedema are • Total excision of the tumour usually leads to a resolution of
620 suggestive of the diagnosis the hydrocephalic process
 Neural tube defects, large heads and hydrocephalus   17.4
i­ ntracranial pressure. Less commonly, cerebral tuber- symptoms of raised i­ntracranial pressure are often
culoma, ­torular meningitis or an aneurysm of the associated with changes in ­behaviour, a clumsy gait,
vein of Galen may simulate intracranial neoplasms. abnormal articulation, ­ tremors and ­incoordination.
The latter should be suspected if, in addition to If an increase in ventricular pressure occurs abruptly,
hydrocephalus, a loud intracranial bruit, high out- attacks of nausea, vomiting, head retraction and
put failure and v­ ascular naevi are also present in extensor spasms are prominent. In very ill children,
the patient. symptoms of a primary illness, such as cranial infec-
tion and haemorrhage, may obscure symptoms of
intracranial hypertension. It is important in all cases
to ascertain any neurological symptoms, determine
Clinical example the time of onset of head enlargement and assess the
Ivan, a 5-year-old boy, presented with a
developmental progress of the child.
2-month history of early morning headache and An acute increase in intracranial pressure should
vomiting. This was associated with a decline in prompt consideration of the possibility of drug intox-
his school performance and he was noted to ication (tetracycline, vitamin A, nalidixic acid), lead
be increasingly unsteady on his feet. The significant findings encephalopathy, subdural haematoma and Reye
on examination included a wide-based, unsteady gait, syndrome.
horizontal nystagmus and severe bilateral papilloedema.
In children with myelomeningocele and shunted
Computed tomography (CT) revealed the presence of a
large mass in the cerebellar vermis, which was distorting the hydrocephalus, raised intracranial pressure is usually
fourth ventricle. secondary to a blocked shunt. Children may present
Ivan underwent a craniotomy and the tumour arising in with features typical of a blocked shunt (irritability,
the cerebellar vermis was excised. Following the operation headache, somnolence, vomiting, loss of conscious-
the symptoms of raised intracranial pressure subsided and ness), but may also present with atypical features
serial CT scans showed a resolution of the dilated lateral and such as seizures or unusual behaviours. Diagnosis
third ventricles.
requires exclusion of other underlying causes, and
With this patient, excision of the obstructing mass was an
effective form of treatment for a significant degree of non- a high index of suspicion prompting the clinician to
communicating hydrocephalus. The presenting symptoms question shunt dysfunction.
were in part due to raised intracranial pressure and in part
due to interference with cerebellar function.

Approach to clinical diagnosis Clinical example

The clinical appraisal of the hydrocephalic child involves: William was an 11-year-old boy with spina bifida
• establishment of the diagnosis and aetiology and shunted hydrocephalus. During the course
• neurological and developmental examination of the clinical consultation as part of long-term
• a search for other associated malformations. follow-up of his condition, he complained that
It is essential to determine the age and rapidity of he had been experiencing some facial pain on the right side
onset of hydrocephalus and its rate of progression. of his face for the past 3 days. He had a decreased appetite
and his mother noted that he had been confused about his
In most clinical situations, in infants with hydroceph- daily routine, which surprised her.
alus, the child presents with a large head, which may On examination, William had a flaccid lower limb
already be apparent at birth or at a few months of paralysis and was wheelchair-mobile. He had mild
age. Despite the obviously large head, many babies hyperreflexia in his upper limbs and nystagmus of gaze,
thrive and may develop normally, apart from poor both longstanding problems associated with his condition.
head control. Other infants with hydrocephalus, His shunt appeared to empty, but was slow to refill. His
fundi did not show evidence of papilloedema. There was
however, feed poorly, are irritable, vomit excessively
no history of recent trauma or infection to explain his facial
and fail to gain weight. In infants with congenital pain, and it was decided that he should have a CT scan to
hydrocephalus, the birth weight, nature of delivery exclude hydrocephalus as a cause. This revealed enlarged
and neonatal course should be noted. In addition, ventricles and William was taken to theatre that day by the
enquiry as to whether there has been a similar illness neurosurgical team to revise his shunt.
in an older sibling or possible intrauterine infection In this situation, the classical signs of raised intracranial
is relevant. pressure were not present and the diagnosis of shunt
dysfunction required a high index of suspicion. This boy
Hydrocephalus that develops in an older and
might well have progressed to developing further signs later,
­previously normal child suggests the possibility of a pos- but by then the risk of an adverse outcome would probably
terior fossa neoplasm. Because ventricular d ­ ilatation is have increased. 621
generally subacute in children with ­cerebellar tumours,
 17.4 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

Physical examination and metabolic disorders such as precocious puberty,

diabetes insipidus and abnormal thermoregulation.
Classically, in the infant, hydrocephalus is ­recognized by
NTDs, skeletal defects and cutaneous naevi are
a progressive increase in occipitofrontal head circum-
known to coexist with ­obstructive hydrocephalus.
ference out of proportion to other bodily ­dimensions.
A single head circumference measurement that greatly
exceeds the 97th percentile strongly suggests the exis- Investigations
tence of hydrocephalus. Where head enlargement is
The child's assessment, based on the history and exam-
equivocal, and neurological abnormality is absent,
ination, will often enable a diagnosis of hydrocephalus
serial head measurements will often indicate the need
to be made with some degree of certainty. However,
for further diagnostic studies. It must be emphasized
in all cases, investigations are required to confirm the
that, once enlargement of the skull is clinically obvious,
diagnosis, determine the extent of the disorder and, if
the ventricles are already grossly dilated and the cere-
possible, define the aetiology. Investigations are also
bral cortex is thinned.
of assistance in deciding the need or otherwise for
Clinical signs that frequently precede obvious
active treatment and also as a means of assessing the
enlargement of the head include:
success or otherwise of treatment.
• a large and bulging fontanelle The widespread use of ultrasonography (Fig. 17.4.6)
• thinning of the bones of the calvarium has in recent times greatly facilitated the assessment of
• widening of the coronal, sagittal and lambdoidal infants with suspected hydrocephalus. Real-time ultra-
sutures.
sound imaging through the open fontanelle provides a
With advancing hydrocephalus:
clear demonstration of the ventricles and may define
• the scalp thins and becomes shiny and pale other structural anomalies well. This non-invasive risk-
• there is upward retraction of the eyelids free investigation can be undertaken with little or no
• the eyes are fixed in a downward gaze (the ‘setting sedation and can be repeated as often as required. When
sun’ sign)
the fontanelle closes, satisfactory imaging can no lon-
• hair appears sparse ger be obtained. Ultrasound examination during preg-
• superficial scalp veins become distended nancy can indicate whether the fetus has hydrocephalus.
• the brow overhangs the small, triangular face. In the older child, and occasionally in infants where
Despite the enormous head size, papilloedema is
more detail is required, computed tomography (CT)
uncommon in congenital hydrocephalus. The shape of
(Fig. 17.4.7) is typically the initial investigation. This
the skull should be noted. A large protruding occiput
is typical of a Dandy–Walker cyst, whereas an asym-
metrical head may be due to unilateral obstruction at
the foramen of Monro. In addition, auscultation for
cranial bruit should be performed over the eyeballs
and over the calvarium.
Many mildly affected hydrocephalic children have
remarkably normal development and minimal neu-
rological deficit. Gross abnormalities in a child
with mild hydrocephalus are usually related to the
underlying disorder that caused the hydrocephalus.
However, prolonged stretching and compression of
neural structures will lead ultimately to profound
neurological injury. Where the increase in intracra-
nial pressure is rapid and there has been no compen-
satory increase in head size, the highly irritable child
frequently gives a short, high-pitched ‘cerebral cry’.
During these screaming episodes, decerebrate postur-
ing may be evident. In the older child with ‘arrested’
hydrocephalus, it is important to evaluate the men-
tal and psychological status. These children are fre-
quently talkative, jovial and euphoric (‘cocktail
party syndrome’), but their capacity for concentra-
Fig. 17.4.6 Frontal view of a real-time ultrasound study
tion, language comprehension and abstract think- showing markedly dilated lateral ventricles on either side of
ing is often lacking. Manifestations of longstanding a large posterior fossa cyst in a patient with Dandy–Walker
622 hydrocephalus include a variety of endocrinological malformation.
 Neural tube defects, large heads and hydrocephalus   17.4
of head growth and, less commonly, by the finding of
neurological abnormality and developmental delay.
Serial imaging will confirm progression of ventricular
dilatation. In this group treatment is essential if brain
injury is to be avoided or minimized.
In a lesser number of patients limited enlargement
of the ventricles will occur and then cease. The term
‘arrested hydrocephalus’ has been applied to this
group. The ventricles remain somewhat larger than
normal but there are no clear signs of raised intracra-
nial pressure and brain function appears normal. The
head may be large but the rate of growth will either be
normal or only slightly excessive, and serial images will
show no significant alteration in ventricle size. With
this pattern, decisions regarding treatment are less well
defined. If the degree of dilatation is mild to moderate
there is no good evidence that treatment will influence
the outcome favourably. Under these circumstances,
frequent assessment is required to ensure that stability
is maintained.
With the widespread use of head imaging tech-
Fig. 17.4.7 Computed tomogram demonstrating gross
niques, it has become apparent that hydrocephalus
ventricular dilatation in hydrocephalus.
may be a temporary state in certain circumstances.
Posthaemorrhagic hydrocephalus in the low-birth-
technique provides excellent detail of the intracra- weight infant is often of this type, as is the disorder
nial anatomy, and the images may be enhanced by the complicating certain forms of meningitis. In these
injection of contrast material. Many children can have patients it appears likely that the CSF pathways have
CT without sedation, whereas others require sedation regained their patency. These patients are usually
or occasionally a general anaesthetic. The radiation defined by repeating imaging. Such studies would show
involved in a single scan is of an acceptable degree. reduction in size of ventricles to normal and this satis-
Magnetic resonance imaging (MRI) (see Fig. 17.4.5) factory state would be associated with the disappear-
is rarely undertaken as a primary investigation but ance of all physical signs of progressive hydrocephalus.
may be of value in defining the cause of the condition. Obviously, no long-term treatment is required in this
Small tumours in the region of the aqueduct causing group but intermittent removal of CSF by either a
obstruction to CSF flow may not be visualized by CT lumbar puncture or a ventricular puncture may help
but are clearly defined on MRI. to resolve the process and prevent any excess ventricu-
lar dilatation during the period before effective CSF
Treatment flow is established via normal pathways. On occasions,
a reservoir may be inserted into a lateral ventricle to
The indications for treatment are based on a clear
facilitate such intermittent removal. In addition, drugs
understanding of the natural history of the disorder.
that reduce CSF production, such as acetazolamide
Three patterns may be described:
and isosorbide, have been used with the same intent.
• the process continues, followed by neurological
deterioration Operative treatment
• the process progresses to a point, and then stabilizes The definitive treatment of hydrocephalus is a surgical
(‘compensated hydrocephalus’) procedure. The usual method of treatment is by a shunt
• the process is temporary. that diverts the CSF to some other site in the body.
In the majority of patients, the ventricles will con- In some cases of non-communicating h ­ ydrocephalus,
tinue to enlarge and the overlying brain will become ventriculostomy may successfully re-establish normal
stretched, compressed and thinned. If the process CSF pathways.
starts in infancy before the skull bones have devel- Ventriculoperitoneal shunt. This is the operation
oped significant attachment to each other, massive performed most frequently in paediatric patients with
head enlargement will result, and under these circum- hydrocephalus. A Silastic catheter is placed in a lat-
stances significant brain injury will result. This type of eral ventricle through a burr-hole and the other end
progression will be detected by the presence and per- of the tube is passed subcutaneously to the abdomen
sistence of signs of raised pressure, an excessive rate and then placed in the peritoneal cavity. A valve is 623
 17.4 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

interposed and an adequate length of tube is placed in of patients suffer from repeated episodes of obstruc-
the peritoneal cavity to allow for growth. The perito- tion, and management can be difficult and may involve
neum absorbs CSF effectively. many variations of shunt equipment and surgical
Ventriculoatrial shunt. In this procedure the lower technique.
end of the shunt is passed via a neck vein to the right
atrium. The catheter is designed so that CSF can pass
from the catheter tip but blood cannot flow back into
the lumen. The turbulent blood flow in the atrium pre- Clinical example
vents thrombus formation around the catheter. This
operation is not undertaken often in childhood as Sara, a 6-year-old child with a past history
maintenance may involve the lengthening of the atrial of having had a ventriculoperitoneal
catheter on several occasions. shunt inserted in infancy for congenital
hydrocephalus, presented at the outpatient
Complications of ventricular shunts clinic for review having missed a previous planned
The operation is generally well tolerated with infre- attendance. Her mother stated that Sara was generally well
but was concerned by her visual function. Sara insisted on
quent early difficulties. Common complications include
sitting immediately adjacent to the television set and had
meningitis, ventriculitis and shunt obstruction. been moved to the front of her class to enable her to see the
The most common presentation of a child with a blackboard.
blocked shunt is that of a vague illness. Irritability and When examined, Sara appeared to be generally well, but
vomiting are frequent and headache may be p ­ resent. head measurement indicated an excessive rate of growth.
The symptoms are very similar to those of many Her visual acuity was markedly diminished in each eye
­childhood illnesses, and difficulties are often experi- and funduscopy revealed severe secondary optic atrophy.
On palpation the shunt tubing was disconnected and an
enced in trying to decide whether the symptoms are
immediate CT scan showed very large ventricles. The shunt
a consequence of shunt malfunction or an unrelated was revised immediately, but unfortunately there was no
illness. Definite signs of raised intracranial pressure, improvement in Sara's poor vision.
if present, are of great assistance but are often not The shunt had obviously been malfunctioning for a
ascertained readily. Palpation of the shunt mecha-
­ prolonged period of time and had resulted in chronic
nism may also frequently be inconclusive. Thus, when raised intracranial pressure. Sara had not complained of
assessing a child with potential shunt dysfunction, a any symptoms but the presence of intracranial pressure
produced marked optic atrophy over this interval of time. If
neurosurgeon should always be consulted. Sara had attended for the planned reviews, the abnormality
The treatment of shunt obstruction is usually a might well have been recognized and corrected before visual
simple procedure and involves the replacement of deterioration resulted.
the defective component. However, a small number

624
 Headaches
Ian Wilkinson, Gopinath Musuwadi Subramanian
17.5
Headache occurs in most children at some time. In a Migraine
number of these, frequent headaches are a disabling
Epidemiological features
problem. In one study in primary schools in Australia,
23% of parents believed that their children suffered Migraine is:
from ‘frequent headaches’. A population study of • the commonest cause of recurrent headaches
4–18-year-olds in the USA, published in 2009, found • showing increasing prevalence. In a 1974 Finnish
that 17% had suffered from frequent or severe head- study using rigid criteria, 1.9% of 7-year-old
aches in the previous 12 months. children suffered from migraine headaches. In 1992
Many processes result in headache. These will be the study was repeated with the same criteria and
considered in two major classes: ‘cranial’ headaches, the prevalence had increased to 5.7%.
where the cause of pain is a process directly involving • more common with increasing age of the child
the brain and associated structures, including menin- • more common in males before puberty but in
ges, cerebral blood vessels and scalp; and ‘extracra- females after puberty
nial’ headaches, where the primary cause is remote • a leading cause of referrals to paediatricians and
from the brain. child neurologists.
The mechanisms of headache are multiple, but it
should be recognized that the brain itself is insensitive
Clinical manifestations
to pain. Some neurosurgical operations for intractable
epilepsy are actually performed on the brain with the Childhood migraines result from the same biological
patient awake. process as those in adults but clinical manifestations
This chapter deals particularly with recurrent or may be quite different. Some of these differences relate
chronic headaches and not with those that accompany to the difficulty a child has in describing or explaining
acute events such as trauma, intracranial bleeds or the features; for example, young children may not be
infections of the nervous system. able to describe throbbing, or lateralization, or sensory
associations. Nevertheless, there are some features,
such as dizziness and vomiting, that are clearly more
common in children.
‘Classical’ migraine (which is a relatively uncommon
Cranial causes type of migraine even in adults) includes aura, or tran-
Migraine and stress or tension types are the most sitory neurological dysfunction, especially of the visual
common of chronic or recurrent headaches with system, and may involve sophisticated hallucinations
origins in and around the brain. The migraine sub- such as fortification spectra, which often precede the
set is numerically the biggest in Australian children. onset of headache and then disappear as the head-
Stress and tension components often interact with ache commences. This classical sequence may occur in
a predisposition to migraine. Pure stress and ten- older children and adolescents but often instead there
sion headaches are less common than in adults. is a description of sensory hallucination that occurs
Often headaches in children that are classified as with, or during, the headache. This may be a visual
‘stress’ or ‘tension’ start out as migraine headaches disturbance described in unsophisticated terms, such
but, as a consequence of recurrent pain, disability as ‘flashing lights’, ‘seeing things double’ or ‘blurry,
and fear of the next headache, develop strong fea- like looking through a curtain’, or something more
tures suggesting that stress or tension is the primary complex and bizarre-sounding, and often very fright-
cause. Of the different headache types in children, ening. Such hallucinations include the appearance that
migraine, because of its great prevalence and asso- objects are too big or too small, or that things moving
ciated morbidity, will receive most attention in this in the environment appear to be going too fast or too
discussion. slow, or that body images are distorted. It is suggested
625
 17.5 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

that Lewis Carroll drew on personal migraine expe- Formulating rigid diagnostic criteria for childhood
riences in writing Alice in Wonderland when describ- migraine has proven very controversial and strict
ing Alice's distorted body perception after she ate the requirements for certain features to be present in com-
magic substance. bination before a diagnosis can be made may be coun-
Such hallucinations can involve the auditory pro- terproductive in clinical practice. In practice, children
cess, for example things sounding too loud or some- with headaches with some of the previously mentioned
one speaking too fast. At times, the aura for a child features, occurring intermittently and with symptom-
defies description but may involve a sense of unreality free periods, who are normal to neurological examina-
or depersonalization. tion, may be considered to suffer from migraine.
What can make the migraine process more difficult The single feature that has caused most disagree-
to unravel in a child is the not uncommon situation ment between those studying children with head-
where the actual sensory hallucination is not accompa- aches and those studying adults is a requirement for
nied (during that event) by a headache. This is referred the headache to be of a certain duration. A diagnosis
to as migraine dissociée, and there may be more alarm of migraine had originally required, by International
and distress for a child or parent than when there is an Headache Society criteria, a duration of at least
accompanying headache. 4 hours. Eventually it was conceded that childhood
Other variations from adult migraine involve the migraine attacks may last as little as 1 hour.
location of the pain. Whereas in adult migraine Classical teaching about headaches due to tumours
attacks the pain can often be lateralized (a true ‘hemi- and other situations of raised intracranial pressure has
crania’ – one origin of the word migraine), this is fre- been that they are present upon awakening, or actively
quently not the case in young children, who will sim- cause the patient to waken. Although in reality this is
ply point to their forehead (without lateralization) as not always the case, a contrast remains with childhood
being the location. As the child grows older a descrip- migraine, where the onset is more commonly later in
tion of pain that is unilateral and sometimes located in the day, perhaps approaching midday or during the
one or other temple becomes more common. The pain afternoon or evening.
is more often in the frontal half of the head, and pain Childhood migraine is a very cyclical condition.
that is located only posteriorly raises the possibility of Patients may have a bout of recurrent headaches that
more sinister causes of headache. lasts for weeks or months, followed by a period of remis-
A description of the quality of the pain in migraine sion that may last for a year or more, to be followed by
in children is often difficult for them. The pain tends another bout. Hot weather may be a factor in relapses.
to be more of an aching type ‘like a tummy ache’
rather than sharp ‘like a needle’. A combination of
Types of migraine
the two may be described. Further, in adults with
pure migraine attacks it is frequent for the pain to In the International Classification of Headache
be described as throbbing, implying involvement of Disorders (ICHD, second edition, 2004) there are six
vascular structures. Children with migraine may well categories and 17 subcategories of migraine. Precise
experience throbbing pain but may not be able to classification is necessary in migraine research but is
describe it as such, although, as the child becomes not always so important in clinical diagnosis and man-
older, he or she may describe it as ‘beating like a drum’ agement, and there is often overlap between different
or ‘like a hammer’. types in children. To categorize according to the pres-
Although many adults do not acknowledge head- ence or absence of ‘aura’ in children can be very diffi-
aches as being migraine unless they are severe and cult. The ‘aura’, in children who can describe it, may
resulting in cessation of usual activities, in children often occur during the headache and not precede it,
there can be a great range in the severity of migraine and frequently involves some sense of disequilibrium,
events, from the situation where the child is able to con- perhaps true vertigo. Visual auras are often basic, such
tinue in school or at play, to the level where all activity as blurring or double vision, and unsophisticated.
must cease and the child retreats to bed in misery. There are some conditions that are considered to be
Adults with migraine attacks may not change part of the migraine phenomenon, although appearing
greatly in external appearance, but children are often to have little relationship with adult migraine types:
extremely pale. • Unexplained attacks of vomiting, without associated
Nausea and vomiting may occur in association with headache, may also be precursors of migraine. These
adult migraine and not uncommonly continue through- attacks can be very puzzling diagnostically and often
out and exacerbate the headache, resulting in treatment very debilitating, possibly recurring after a predictable
with an antiemetic. During the attack, abdominal pain, interval and sometimes requiring intravenous fluids
nausea and vomiting are extremely common in chil- and hospitalization. With the passage of time,
626
dren, but the sequence may be that a single vomit, often headaches may become more of a feature of these
followed by a sleep, terminates the attack. attacks, which are labelled ‘cyclical vomiting’.
 Headaches 17.5
• Recurring episodes of unexplained abdominal pain Aetiology
defying diagnosis despite multiple investigations can
also be very debilitating. There may be a family history The causative mechanisms for migraine are very com-
of migraine and as time goes by the child's pain, known plex and much researched, and it is beyond the scope
as ‘abdominal migraine’ may become associated with of this textbook to go into great detail.
and eventually replaced by migraine headaches. At a chemical level, both noradrenergic and seroto-
• In early childhood, usually before the age of 5 years, nergic transmitter pathways are implicated, and this
patients may experience recurrent episodes of sudden has relevance to drug therapy.
onset of true vertigo. These are extremely distressing Certainly genetics plays a major role and as many
and cause the child to seek a cuddle, or lie on the ground as 90% of children with migraine will have parents or
to relieve the feeling of spinning. These events last a few siblings with the same condition.
minutes, sometimes hours, and may be associated with Many different mechanisms of inheritance have
pallor, nausea and vomiting, and possibly nystagmus. been postulated. In recent years there has been clear
In some studies up to 80% of these children, who evidence that familial hemiplegic migraine is associated
are described as having ‘benign paroxysmal vertigo’, with mutations on three different chromosome sites
subsequently develop migraine headaches. (chromosomes 19, 1 and 2), although they all pres-
The most recent ICHD (2004) now includes a section ent with similar clinical features. The sites on chromo-
entitled ‘Childhood periodic syndromes that are com- somes 19 and 2 disrupt calcium and sodium channel
mon precursors of migraine’, incorporating (1) c­ yclical function respectively.
vomiting, (2) abdominal migraine and (3) benign In 1944 Leao described ‘spreading depression of
paroxysmal vertigo. activity in cerebral cortex’. The slow spread of this
In infancy, ‘paroxysmal torticollis’, where the head electrical change across the visual cortex was synchro-
becomes tilted strongly to one or either side for peri- nous with the spread of the visual aura accompanying
ods of hours or days, may be a precursor of migraine, the migraine attack. It was thought that this spreading
although simultaneous headache may not be appar- depression was produced by ischaemic changes result-
ent. A similar process involving the trunk has been ing from vasoconstriction, and that the subsequent
described. These infants have been demonstrated to be vasodilatation of innervated blood vessels produced
at greater risk of later developing migraine headaches. the pain response.
Hemiplegic migraine may present with unilateral This vascular theory of migraine held sway for 50 years,
weakness, and possibly unilateral sensory disturbance, but in the last decade a new theory has arisen, which pro-
and this often precedes the actual headache. poses that the cortical depression results from an abnor-
Expressive or receptive language difficulties also mal excessive depolarization of neurons, which spreads
may be a presenting feature of some attacks, with the across the cortex producing neurological dysfunction.
headache not occurring till an hour or so later. This has been well demonstrated during the march of
In acute confusional migraine the patient is quite depolarization across the motor cortex that accompanies
disoriented and distressed, with short-term memory the spreading weakness of hemiplegic migraine, but can
loss. This condition raises concerns about more sinis- also occur in sensory and cerebellar cortex.
ter neurological processes, or drug intoxication, often This neurogenic theory postulates that the depo-
leading to invasive investigations. Again, the headache larization producing the motor or sensory dys-
may not become apparent until later in the event. function sends afferent (or inward) messages into
brainstem centres that interact, reach a critical
threshold, and then send efferent (or outward) mes-
Clinical example sages via the trigeminovascular system to blood
vessels in pain-sensitive structures, which undergo
Jarrod, aged 13 years, was sitting in class when dilatation as well as sterile inflammatory change,
he developed tingling in his right arm. He tried resulting in headache.
to put his arm up to tell the teacher but it was
Given that some children are at risk genetically of
too weak. When he tried to call his teacher, he
could not find the words to say. He became very distressed
developing migraine, it is clear that there may be pro-
and confused. An ambulance took him to hospital where he voking factors for individual attacks. These include
was found to have a right hemiparesis. He had developed head injuries, not necessarily severe ones. The head
a headache on the left side and underwent computed injury may be the commencing point for recurrent
tomography of his head, and lumbar puncture. Both were bouts of migraine headache, and this may have legal
normal. The weakness, numbness and confusion resolved ramifications. Other provoking factors are:
over the 3 hours from onset, but the headache lasted for
6 hours. It was discovered that his father had suffered similar
• intercurrent systemic infections, particularly with fever
attacks of hemiparesis and headache when he was a • strenuous physical exercise 627
teenager. This is an example of familial hemiplegic migraine. • hot weather
• dehydration
 17.5 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

• worry and stress, either domestic, social or Ergotamine has long been a useful antimigraine
educational in origin. While these factors remain, drug in adults, particularly at the beginning of the
they may greatly complicate treatment. The attack. Although some studies have shown efficacy of
distinction from ‘stress’ or ‘tension’ headaches oral dihydroergotamine in children, ergotamines have
without an underlying migraine basis may be very had limited use because children often delay seeking
difficult treatment and also because they may produce side-
• foodstuffs. This is a very controversial area, with effects such as vomiting and abdominal discomfort.
evidence for and against. Citrus fruit, cheese, Triptans are serotonin agonists with multiple meth-
chocolate and processed meat have been implicated ods of action against migraine attacks, and may be use-
• food additives, such as monosodium glutamate, ful in children and adolescents. Sumatriptan has been
sodium nitrite, benzoic acid, tartrazine. the most employed in this age group, and the nasal
spray, either 10 or 20 mg has been shown to be effec-
tive in patients aged 12–17 years. It should be admin-
Treatment
istered as early as possible in the course of the attack.
Treatment can be divided into the following tiers: Sumatriptan and other triptans have little proof of
• avoidance of triggers efficacy when given orally or subcutaneously to chil-
• non-specific analgesia for attacks dren and adolescents.
• specific anti-migraine medication for attacks Antiemetics such as promethazine, prochlorpera-
• prophylactic medication zine and metoclopramide may be useful in situations
• non-medication treatments. where the migraine attack is associated with pernicious
Avoiding specific triggers in childhood migraine can vomiting, but this is unusual in children, and often a
be difficult. In many, they do not exist. In Australia, vomit followed by a sleep brings about the end of the
hot weather and exercise are common precipi- particular attack. Antiemetics may produce significant
tants that are part of a normal childhood lifestyle. drowsiness, and metoclopramide in particular may be
Ensuring adequate hydration in the above situations associated with acute dystonic reactions.
may be helpful. Prophylactic treatment to prevent migraine attacks
The role of restrictive diets is controversial. If it may be indicated when there is significant suffering and
is evident that certain foodstuffs or drinks regularly disruption of the patient's lifestyle. It is difficult to define
provoke attacks then they should be avoided. Placing what frequency of attacks should dictate a decision to
children on very limited diets is not only unpleasant implement prophylaxis; opinions vary between two and
and difficult to enforce, but may even have nutritional four events per month. The decision process should
consequences. combine the frequency of the attacks with the negative
The use of non-specific analgesics in attacks is the impact on the young person's lifestyle. Many commonly
simplest means of treatment. The most commonly used medications may have significant side-effects.
used is paracetamol, best given in an initial dose of One of the problems in managing migraines in this
20 mg/kg. Unfortunately, children may not seek medi- age group is the difficulty in obtaining proof that indi-
cation, or as a result of being at school may not be able vidual medications are effective. Controlled trials are
to access medication, until the attack is advanced. The complicated by the cyclical nature of migraine in the
paracetamol may not be effective at this time, or may young, with bad bouts being followed shortly after-
be vomited. There may be a role for rectal paracetamol wards by periods of temporary or permanent remis-
in this latter situation. sion, and by the very high placebo response rates.
A recent study has indicated that ibuprofen in a dose A 2008 revision of a Cochrane database study again
of 10 mg/kg may be more effective than paracetamol. concluded a lack of evidence for the benefit of pro-
Other non-steroidal anti-inflammatory drugs (NSAIDs) phylaxis in childhood migraine. The only proven treat-
may be helpful. ments were for propranolol (in a study, subsequently
In recent years aspirin has been avoided in child- contradicted) and flunarizine in repeated studies.
hood because of concerns about its relationship with Unfortunately flunarizine is not readily available in
Reye syndrome, a rare but severe acute encephalopa- Australia, although it is used widely in Europe.
thy with potentially fatal outcome. Nevertheless, aspi- Nevertheless, the following medications are com-
rin in doses of 15 mg/kg may be employed in older monly used in clinical practice:
children with recurrent headaches. • Cyproheptadine, an antihistamine with serotonin-
The use of codeine and powerful narcotics in blocking and calcium channel-blocking properties.
childhood headache is not usually necessary and Side-effects include drowsiness (which may be
is potentially hazardous, although restricted infre- minimized with a single night-time dose regimen)
quent use of combinations of paracetamol and and increased appetite. Effective doses range from
628
codeine in older children may be necessary and 0.1–0.3 mg per kg per day, given either once or
effective. twice daily.
 Headaches 17.5
• Propranolol, a β-adrenergic blocking drug, also have indicated an overall 30–40% 10-year remission rate.
blocks release of serotonin from platelets. It is It is not uncommon when taking a family history to find
contraindicated in asthma. Doses range from 0.5 to that parents, when pressed, remember having childhood
2.0 mg per kg per day in two or three equal doses. migraines long since in remission. Similarly, in apparent
The value of propranolol and similar drugs has adult-onset migraine, a long forgotten history of severe
been proven in adults, but trials in children have childhood headaches may eventually be recalled. Other
produced conflicting results. children, like adults, will have a history of infrequent
• Pizotifen, with antiserotonin and antihistamine migraines throughout their developing years.
properties, has side-effects of increased appetite,
weight gain and drowsiness. The last may be
avoided by a single night-time dose. Doses are
limited by the single-size pill format (0.5 mg) but Clinical example
range from one to three at night.
Jason, aged 8 years, presented in March with
• Clonidine, a vasoactive drug, has been trialled in a range headaches that had occurred about twice a
of conditions in children but lacks good evidence for week for the previous 3 months, although he
use in migraine and has significant potential side-effects. had had some after playing soccer the previous
• Amitriptyline, originally marketed as an winter. The headaches commenced after lunch at school,
antidepressant, has been used for migraine were frontal and throbbing, and Jason looked very pale.
prophylaxis in children. It may be particularly useful Paracetamol sometimes helped him but often he would
vomit, go to sleep, and then awake without headache and
where there are stress and depressive features, but care
eat his evening meal. His mother had a history of migraine.
must be taken to avoid provoking cardiac arrhythmias. Neurological examination in Jason was normal. After
In recent years there has been increasing evidence that daily treatment with cyproheptadine for 2 weeks, Jason's
drugs introduced as anticonvulsants may have a role in headaches ceased. The history is consistent with childhood
psychiatric treatment, and also in prevention of migraine migraine.
headaches. Sodium valproate has been shown to be effec-
tive in some studies but may be associated with unaccept-
able weight gain. Topiramate is approved in Australia Tension-type headache
for migraine prophylaxis but can affect alertness and
­cognition, and may be associated with weight loss. In adults, tension-type headache (TTH) represents the
Many of the preventative medications, early and recent, most common type of primary headache. This is not
have channel-blocking effects and this may explain their true in children, where TTH affects 15–20% of ado-
benefit, as increasingly there is evidence for channelopa- lescents and an even smaller proportion of younger
thies as underlying the pathogenesis of migraine. children. The term TTH replaces the previous terms
Because of the high remission rates in children, pro- ‘muscle contraction headache’ and ‘tension headache’,
phylactic medications should not be used continuously etc. The International Headache Society classification
for more than 6 months without attempting to wean describes the typical features of TTH as ­non-throbbing
patients from them. but as an oppressing or tightening pain that is usually
Non-medication treatments may at times be suc- bilateral and is present anywhere in the cranium or
cessful, but again there is a paucity of controlled suboccipital regions. The headache is usually of mild
trials in children. Biofeedback and relaxation tech- to moderate intensity and lasts for 30 minutes to sev-
niques have been used, particularly in Europe and eral days. The absence of vomiting and nausea, and
North America. Acupuncture has proved to be suc- the absence of photophobia and phonophobia, are
cessful in adults but is a potentially painful procedure. distinguishing features from migraine. On a pain scale,
Homeopathic formulations are enjoying increased TTH is placed on the lower end of continuum whereas
popularity in many conditions but lack evidence in migraine with aura is placed on the severe end.
childhood migraine. Chiropractic treatments are con- A TTH may occur periodically (episodic), or fewer
troversial, lack controlled trials and may be danger- than 15 days a month, the most common being once
ous in young children. or twice a month, to be distinguished from a headache
Although discussion in this section has focused on that occurs daily or for more than 15 days a month,
migraine, the non-specific medications and treatments also known as chronic TTH. The latter is described
cited may be useful in all headache types. under the chronic headaches.
There is no single cause for TTH. As the name sug-
gests, the most common cause for such a phenomenon
Prognosis
is stress, and this is present usually in the environment
Childhood migraine is often cyclical, with bad bouts fol- of the child which includes the school, family, friends,
629
lowed by prolonged remissions, sometimes followed by peers, etc. A small proportion is passed on as an inher-
relapses in later childhood or adult life. Various s­ tudies ited trait that runs in families.
 17.5 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

The rule of targeted history-taking and focused the past, and over a few days these children present
examination is very important to exclude organic with unrelenting headache. There are studies high-
causes as clinical features of a TTH can be n
­ on-specific. lighting that specific trigger factors are remembered
A quick run through into the psychosocial environ- as the initiating factor to the headache. The last cat-
ment and the daily functioning of a child is useful as egory, hemicrania continuum with autonomic fea-
this will provide the most common triggering for such tures accompanying the unilateral headache, is the
headaches. least common form.
The treatment of TTH is usually a combination To qualify for a label of CDH, the subject over a
of non-drug and drug strategies. Among the non- period of time presents with a baseline headache with
drug strategies the initial focus should be on lifestyle fluctuating severe headache, which is never accom-
changes (sleep, dietary changes), physiotherapy, stress panied by symptoms related to increased intracra-
management and relaxation techniques, and, most nial pressure; clinical examination is normal; imaging
importantly, counselling. The drug strategies for TTH is negative; overall secondary or organic pathology
are no different to those for symptomatic treatment should be ruled out, so the diagnosis is arrived at by
of headache, and are usually successful with over-the- exclusion.
counter pain medications. Various theories exist regarding pathogenesis
The overall prognosis for TTH is better than that for of CDH, but none offers a complete explanation.
migraine headaches, with at least one-third becoming Nevertheless, the scenarios listed are common. The
completely symptom-free on longer follow-up studies, aetiology in selective cases may be amply clear in that
and the majority much improved. the symptom of headache may be used in a conscious
and malingering fashion to avoid a specific situa-
tion, or in a manner as seeking desperately for help.
Chronic daily headache
A more common situation is where the child has suf-
Patients with daily, or near-daily, recurring head- fered headaches infrequently in the past but extra-
aches form a very challenging subgroup among chil- neous factors bring a crescendo effect, resulting in a
dren and adolescents presenting with headache. A chronic headache. Further along is a situation where
proportion of these would have been labelled as hav- the child or adolescent is a part of a high-function-
ing ‘stress and tension headaches’ before the current ing family unit. The subject balances a delicate and
classification became accepted. There has always demanding combination of school, additional tutor-
been a need for precise categorization of chronic ing, sport and performing arts, etc. really well until
headaches. a major event such as a protracted viral infection or
Chronic daily headache (CDH) is formally defined a surgical illness or a minor head injury occurs. Very
as occurring when headaches are present for more commonly, the child experiences headache among
than 3 months, during which the patient has more other symptoms during the acute phase. A slow con-
than 15 headaches per month that last for more than valescence leads to a protracted or a delayed catch-up
4 hours per day. of premorbid functioning. Failure to catch up or fear
According to the ICHD (2004), the chronic forms of permanently losing the skills achieved earlier may
of primary headache are subgrouped into four types lead to recurrence of headache and other generalized
based on the existing and past clinical features.: fatigue symptoms following the acute illness. This sce-
1. Transformed/chronic migraine nario fits new-onset chronic headache. In others, a
2. Chronic tension-type headache psychiatric disposition or related diagnosis increases
3. New-onset daily persistent headache the risk of suffering anxiety, stress or somatic com-
4. Hemicrania continua. plaints leading to chronic headache. On the same
The most common is transformed or chronic note, family dynamics, past or present, and lifestyle
migraine. This group of children or adolescents has issues including sleep and diet have been implicated.
a history of infrequent migraine headache in the In some cases, there are no antecedents and headache
past and may not even have a label until the new presentation may be frustratingly difficult for the cli-
daily pattern occurs. The severe and daily occur- nician attempting to come to grips with the nature of
rence of headache may obscure the diagnosis, but these headaches. Although subgroups are useful to
the past history and migraine features suggest the classify, a mixed bag of two different headaches is not
diagnosis. The second group is of patients with an uncommon and may coexist.
occasional TTH who transform to a daily headache Evaluation includes thorough history-taking to
pattern without any history of migraine headache include antecedent events, evolution of symptoms and
features in the past. The third group is of those with the impact of illness on the child at home in the family,
new daily persistent headaches. As the name sug- and at school. Headache is rarely the only symptom
630
gests, there is no history of remembered headache in in CDH. The clinician should ask for other ­symptoms
 Headaches 17.5
including dizziness, abdominal pain, fatigue, ­syncope, ­ anagement of other chronic headache on simi-
m
concentration and attention issues, personality and lar lines is often practised, with little evidence. In the
mood changes, and sleep hygiene. School grades, latter situation, treatment should also be tailored to
school absences and peer interaction should be treat co-morbidity – as a priority, rather than placing
documented. Medication use and overuse should emphasis just on headache treatment. Where the head-
be assessed. Headache diaries help maintain and ache appears secondary to, or aggravated by, a psychi-
document events, triggers and treatment response. atric disorder, consultation with a child psychiatrist is
Family history should focus on parent relationships, strongly advised.
interactions and separation, etc. Often, there is Acute pain management for intense CDH is often
nothing abnormal to note on clinical examination. less effective in the longer period. Most patients will
A wide list of differentials ranges from c­ ommon to have tried various forms and combinations of over-
rare diagnoses, but detailed history-taking and nor- the-counter analgesics. A significant proportion in
mal clinical examination eliminates several of them. the long term does not report benefit, which leaves
Most often, a key feature to note during consultation two categories of medication users. One group
is the scenario of encountering a child or adolescent avoids using any form of pain medication because
who appears completely indifferent to his or her pre- of lack of therapeutic effect. The other group is
senting symptoms, ranging through to an individ- at risk of overuse following an attempt to control
ual manifesting intense anxiety. At times, parental pain, resulting in escalation of doses and medica-
anxiety dominates the consultation. Investigations tion frequency. This group is also at risk of rebound
have often already been performed and results are headache when medications are discontinued. In a
available, the patient having been tested for infec- rare situation, emergency or acute-care presentation
tion, nutritional markers and immunological prob- may require a cocktail of management – opioids,
lems, etc. ­antiemetics and sedatives. At times, selective agents
Children with CDH complain of two types of head- such as ketorolac, dihydroergotamine or triptans
ache. One is a continuous baseline headache that may be useful.
waxes and wanes and is present 24/7. The other is a Prophylactic medications should be given consid-
severe intermittent headache occurring with a period eration in patients where chronic headache symp-
of exacerbation lasting for hours to days on top of the toms impair social/school functioning or personal
baseline headache. well-being, and in those patients at risk of medication
Investigations for chronic headache are almost overuse.
always negative. More often than not, brain imaging is Evidence-based medicine on current medications
performed on the grounds of excluding a host of rare of chronic daily headache is limited by the impres-
conditions, from malignant tumours to brain infec- sive response rate from placebo arm of trials. This
tion. Radiological investigations rarely contribute to a leaves clinicians to consider the better known and
positive diagnosis, but a normal result may be the only used choices. The key to successful treatment should
way to alleviate anxiety. In the situation of a conver- focus on considering a medication option as one of
sion reaction, it may reinforce to the patient that there the treatment arms and not as a cornerstone of man-
really may be an organic problem. A counter effect agement. A slow titration to an effective dose may be
may result and this needs to be thought through and ­time-consuming and the therapeutic effect may take
discussed with the family, in order to avoid unneces- weeks to manifest.
sary screening tests. The authors’ line of practice is to use cyprohepta-
A lumbar puncture may also be required if the his- dine, pizotifen, amitriptyline and propranolol as
tory and clinical features suggest a longstanding head- options. The choice is based on considering c­o-
ache and the investigation of headache has given morbidities (weight gain is an undesirable effect with
normal imaging results. The presence of high cerebro- the first three agents mentioned above), and the suit-
spinal fluid (CSF) opening pressure can be diagnostic ability or unsuitability of the side-effect profile (avoid
of idiopathic intracranial hypertension, which may be the last agent in children with asthma) from medication.
disguised. Once an effective dose has been achieved, maintenance
Treatment is often difficult. It should be emphasized treatment can be tailored to the next 3–6 months, with
to the family that any medication intervention, current an attempt to wean subsequently.
or future, may not yield dramatic relief but that the Several non-pharmacological therapies may have a
goal in such a situation is to reduce the frequency of role. These include: muscle relaxation, stress avoidance,
the severe headaches and make the baseline headache biofeedback, hypnosis and acupuncture. These thera-
less intense. Acute headache management should go pies are resource-intensive and are n ­ on-conventional
along with daily preventive medication management
­
management options. These are most often self-
631
if an underlying migraine basis is identified. Pain referred and belief-centred.
 17.5 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

Abscesses can develop by spread from infections

Clinical example of the paranasal sinuses. Headaches resulting
from abscesses are often associated with systemic
Chloe is an 8-year-old girl presenting with manifestations such as fever, and tend to build up in
recurring headaches. For the last year she has
severity over days or weeks.
been complaining of a headache several times
a week. Her headaches occur mostly on school
• Arachnoid cysts occur in a number of different
days but have not been severe enough to cause her to locations, often adjacent to the surface of the
miss school. She rarely mentions having a headache during brain. They result from fluid collecting within
weekends or vacations. She has never had a headache that a split arachnoid membrane and usually are
awakened her from sleep. When asked, she does not recall asymptomatic, but can produce headaches.
where her head usually hurts. • Fluid, including blood, can collect in the subdural
There is no history of nausea, vomiting, visual or auditory
or extradural spaces, often as a result of trauma.
symptoms. The patient's general health has been good.
There is no family history of headache. Her parents mention Accompanying headaches are often crescendo in
that she is average at schoolwork, required speech therapy frequency and severity, and may be associated with
at school entry, and has trouble learning mathematics and focal signs.
English. She enjoys outdoor activities with her siblings. • Headaches due to tumours are most often due to
Chloe's neurological examination reveals no focal deficits. mass effect, or obstruction of CSF pathways, and
She is well spoken and appeared to interact well during are less likely to be due to direct local involvement
the consultation. A school counsellor has assessed her
of pain-sensitive structures. Intracranial tumours
and identified that Chloe has difficulty interpreting complex
sentences, solving simple word problems, and subtracting in children are usually primary and are most
two-digit numbers. frequently found in the posterior fossa, where they
The history is consistent with chronic daily headache. readily obstruct fluid pathways. It is not uncommon
that there is a substantial delay in detection of the
tumour in such headaches.
• Aneurysms are uncommon in children, but
arteriovenous malformations or cavernous
Headaches due to raised intracranial pressure
angiomas are found in this age group. These
The possibility of childhood headaches being caused may produce headache owing to their size, or
by raised intracranial pressure, especially due to obstruction of fluid pathways.
tumours, is often a cause for great concern in the treat- The signs associated with raised pressure often involve
ing physician as well as the child and family. In reality, the eyes.
only a very small number of childhood headaches are Papilloedema may take days to develop, even in the
due to raised pressure. Even when there is increased presence of grossly increased pressure. Abnormalities
pressure, the ability of the child's skull to expand may of ocular movements, particularly failure of abduction
mitigate some of the effects. with resultant paralytic convergent strabismus, or fail-
Although headaches due to raised intracranial pres- ure of upward gaze, can occur. Sluggish pupillary light
sure have classically been described as worse in the morn- reflexes may be found. Deep tendon reflexes are often
ing upon awakening, or causing the patient to awaken, brisk. There may be neck stiffness. Bradycardia and
and associated with vomiting, this is not always the case. systemic hypertension are later effects.
Raised intracranial pressure can be a result of Treatment of such headaches usually involves surgi-
abnormal fluid collections, solid masses or vascular cal approaches, either directly to the mass or to drain
malformations. fluid from the ventricles or brain surface via a shunt.
Fluid can collect abnormally either within ventricles, Oedema surrounding a mass may be treated with cor-
within the substance of the brain or over the surfaces: ticosteroids or osmotic diuretics, but these are tempo-
• Build-up of fluid within the ventricles is referred rary measures only.
to as hydrocephalus (see Chapter 17.4). This often
presents in infancy, and the ability of the skull to
Idiopathic intracranial hypertension (previously
expand, coupled with the inability of the child to
known as benign intracranial hypertension)
report the pain, may be the reason that headache is
not always a presenting feature. In older children, This condition, sometimes also referred to as ‘pseudo-
the onset of hydrocephalus is often associated with tumour cerebri’ because the clinical features can mimic
a mass lesion obstructing the intracerebral CSF a tumour, occurs in children and adults. It results
pathways, and this may result in major headaches. from a build-up in intracranial pressure, without a
• Intracranial abscesses are uncommon in children ­space-occupying lesion, probably due to an imbalance
in Western society. Children with cystic fibrosis between production and reabsorption of CSF. It is
632
or cyanotic heart disease are at increased risk. ­potentially serious as it can eventually result in visual
 Headaches 17.5
loss. There is often an association with adolescent Patients must be seen by an ophthalmologist, to moni-
females, who may be overweight but otherwise appar- tor visual function, as prolonged papilloedema can
ently healthy. This may have a hormonal basis. lead to optic nerve damage.
Specific causes of intracranial hypertension in indi- The prognosis for idiopathic intracranial hyperten-
vidual cases include: sion is generally good. The process, particularly where
• recurrent middle ear infections, sometimes associated no underlying cause is demonstrated, often remits
with mastoiditis, where the draining cerebral venous spontaneously.
sinuses near the ear become obstructed
• head trauma
• oral contraceptives
• the use or withdrawal of corticosteroids Clinical example
• excessive amounts of vitamin A
• tetracyclines Lisa, 14 years old, developed daily headaches.
• growth hormone treatment. These were often present by the time she had
breakfast, and were distressing, but she could
In some cases a specific cause is not found and the old
get to school most days. The pain continued
entity of ‘benign intracranial hypertension’ should throughout the day and was all over her head. She had
probably be divided into idiopathic and symptomatic noticed some visual difficulty. The problem started after she
categories. was placed on an oral contraceptive for dysmenorrhoea.
The clinical features include: On examination, Lisa was obese. There was papilloedema
• headache, which tends to be daily, often worse in but no other neurological abnormality. Her blood pressure
the morning but not necessarily severe was normal. Cranial tomography was normal and a lumbar
puncture resulted in the fluid pressure rising out of the top of
• abnormalities of the eyes, most commonly the tube. The fluid was normal in the laboratory.
papilloedema (which may be asymptomatic), Lisa responded to cessation of the contraceptive and
possibly lateral rectus palsies due to pressure on the treatment with 250 mg acetazolamide each morning.
abducens nerves, and enlarged blind spot The history is consistent with idiopathic intracranial
• nausea and vomiting hypertension.
• raised pressure at lumbar puncture, to values of
20–40 cmH2O or more
• normal CSF laboratory findings.
In the presence of papilloedema or other eye signs it is Seizure-related headaches
prudent to perform a structural study, preferably magnetic In adults, severe headaches are common following a
resonance imaging (MRI), before performing the lumbar major seizure. In young children, postictal headaches
puncture. Magnetic resonance venography (MRV) may tend to be less debilitating. Children may describe a
be helpful in demonstrating obstructed venous sinuses. headache during an actual epileptic event, while con-
Cerebral images are usually otherwise quite nor- scious. This can be associated with focal discharges,
mal, without a space-occupying lesion or dilatation possibly from the temporal lobe, and may be only a
of the ventricles. Even in the presence of a normal brief event, not always associated with other clinical
scan result, it is reasonable to examine the CSF for features. Electrical discharges in the occipital region
malignant cells, as in rare cases undifferentiated may give visual hallucinations, vomiting and head-
tumours can present with raised intracranial pressure aches not always associated with motor convulsions.
in the presence of apparently normal scan findings. This condition may be familial and often difficult to
Treatment is varied but includes: diagnose.
• repeated lumbar punctures to remove fluid;
this is quite traumatic and not always effective.
Occasionally a single puncture may bring resolution
• acetazolamide, which potentially reduces Extracranial causes
production of CSF by interfering with the carbonic
anhydrase enzymes, or more powerful diuretics, Headache is a frequent associate of systemic illness,
such as furosemide, if acetazolamide fails without there being a primary pathological process in
• steroids the nervous system:
• shunting procedures to remove fluid from the • The most frequent association is with systemic
cranial cavity. These should be reserved for drug- febrile illnesses not directly involving the nervous
resistant cases system.
• decompression procedures on the optic nerves • Connective tissue disease, especially ‘mixed
• anticoagulation if there are thrombosed draining connective tissue disease’, may lead to vascular-type
633
venous sinuses. headaches.
 17.5 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

• Systemic hypertension is much less common in children, Acute sinusitis is a potential cause of headache in
and hypertensive encephalopathy is not seen frequently. children, often associated with other features such as
Nevertheless, in persistent severe hypertension in fever, purulent nasal or postnasal discharge, local ten-
children a major encephalopathy may develop, with derness and puffiness around the eyes. The pain can
headache, seizures and altered consciousness. Acute be widespread in the skull, and the location can be
glomerulonephritis may present in this way. confusing. This is a potentially dangerous condition,
• Metabolic pathway disturbances such as urea cycle occasionally leading to intracranial abscesses.
defects can produce headaches, especially during More frequently seen is the situation where recurrent
biochemical decompensation. frontal migraine headaches are attributed to chronic
• Hypoglycaemia is a potent trigger for migraine but sinusitis and referral for a plain radiographic series is
can also result in non-specific headaches and may the first investigation. These are frequently negative.
be a result of poor diabetic control. With the increasing availability of computed tomog-
• Hunger without demonstrable hypoglycaemia raphy (CT) and MRI performed for other reasons, it
sometimes provokes headaches. is not uncommon that asymptomatic fluid collections
• Although controversial, allergic disorders can be are detected in paranasal sinuses, usually with no clini-
associated with migraines and other headaches. cal consequences.
• Obstructive sleep apnoea and other sleep disorders The frontal and other sinuses are not formed in
not uncommonly produce a clinical picture of early childhood and may not be capable of harbouring
daytime headaches and somnolence. infections until the end of the first decade.
In these situations treatment of the underlying cause is
preferable to symptomatic relief.

Headaches found in adults that

Overrated causes of childhood are unusual in children
headaches • Giant cell or temporal arteritis is a potentially
Children with recurrent headaches are frequently ini- serious cause of headaches in the elderly and
tially referred to optometrists or ophthalmologists. can lead to visual impairment or cerebrovascular
The basis for these headaches is often migraine. accidents if not treated. Fortunately, it is not a
Glaucoma (rarely seen in children) and iritis may condition of childhood.
produce aching in and around the orbit. Convergence • Acute angle-closure glaucoma is another cause of
insufficiency and other ocular muscle imbalances are pain in the ocular region. It is uncommon for this
common findings in children. Headaches may be attrib- to occur in isolation in childhood.
uted to these problems but the evidence is not convincing. • Cluster headaches are a condition of adult life and
Minor refractive errors detected on examination, but can result in some of the most severe headaches
with doubtful clinical relevance, may be blamed incor- known. They can be very resistant to treatment, but
rectly as a cause of childhood headache. Spectacles or are not usually seen in children.
ocular movement exercises may result in apparent tem- • Headaches due to arthritic changes in the neck,
porary relief of the headaches, but not infrequently often chronic disabling headaches, generally relate
they return. to long-standing degenerative processes and are not
common in children.

Clinical example

Reuben is 9 years old. He had recurring, but not Investigations

daily, frontal headaches. His mother took him
to an optometrist near their home who found Childhood headaches are frequently over-investigated.
he had mild hypermetropia and dispensed In general, blood investigations have little yield. Plain
spectacles. The headaches settled for a few months then radiography of the skull may demonstrate signs of
recurred. An ophthalmologist thought that the refractive error chronically raised pressure, or sinusitis, but is of little
was minor and could find no other abnormality. use in most situations.
Reuben's father revealed a history of similar headaches CT can demonstrate hydrocephalus, other fluid
until he went to high school. Reuben started cyproheptadine
at night. The headaches resolved after a month and had
collections and tumours, although it is not ideal for
not recurred after 8 months of treatment. The story was visualization of the middle or posterior fossae, and
consistent with migraine. is associated with significant radiation exposure
634 and risk of subsequent malignancy. MRI is more
 Headaches 17.5
likely to detect tumours and masses, particularly Electroencephalography (EEG) is sometimes use-
in the middle and posterior fossae. Magnetic reso- ful in situations where headaches coexist with clin-
nance arteriography (MRA) or venography (MRV) ical ­seizures, or in the situation described above
is quite sensitive for detecting vascular abnormal- where there is an association with significant visual
ities and is relatively non-invasive. Lumbar punc- aura and vomiting, but is otherwise not often useful.
ture is the diagnostic test for idiopathic intracranial Specialist consultation is frequently more rewarding
hypertension. and less expensive then laboratory investigation.

635
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 18
PART

URINARY TRACT
DISORDERS AND
HYPERTENSION

637
 18.1 Urinary tract infections
and malformations
Colin Jones, Joshua Kausman

Urinalysis and microscopy

Urinary tract infections
Microscopy for bacteria with Gram stain has the high-
Urinary tract infection (UTI) is the second most est accuracy for rapid detection of UTI (sensitivity
­common bacterial infection affecting children. UTI 91%, specificity 96%) but requires laboratory facili-
can cause septicaemia or chronic ill-health with failure ties. The finding of a positive urinary dipstick test
to thrive, and is often an indication of an underlying for leukocyte esterase is sensitive for urinary infec-
urinary tract malformation. tion (approximately 80% of urine infections detected)
and urinary nitrite testing is specific (97% of positive
tests indicate infection). Taking the prevalence rates
Epidemiology for urine infection at different ages (see Epidemiology)
into account, positive tests for both nitrites and leuko-
Epidemiological studies have shown that 2% of boys
cyte esterase in a child under 3 months of age predicts
and 8% of girls have had a UTI by the age of 7 years;
a 90% chance of a urine infection. Negative rapid test
75% of UTIs occur under the age of 1 year in males
results are found in 10% of infants with infection. This
and 50% under the age of 1 year in females. The
is not good enough to use negative tests to exclude uri-
prevalence of UTI in febrile infants under the age
nary infection for clinical purposes, because the diag-
of 3 months presenting to emergency departments is
nosis would be missed in a significant number of ill
20–30%, and boys outnumber girls. After the age of
infants. In a child aged 3 years or more or in a circum-
3 months, the prevalence of UTI in febrile children
cised male, the prevalence of urine infection is much
falls to around 8% in female and 2% in male children.
lower and the finding of negative tests (leukocyte ester-
The incidence of UTI in uncircumcised boys is 4–10
ase and nitrites) is reassuring as there is then only a 1%
times that in c­ ircumcised boys in the first 3 months of
chance of urine infection. Thus, negative test results are
life. Common clinical patterns of UTI are described
quite useful in this older age group in excluding urinary
in Table 18.1.1.
infection and at least justifying withholding antibiotic
treatment until the results of urine culture are available.
Microscopy will usually reveal leukocytes and non-
Diagnosis
glomerular red cells (red cells that appear normally
The frequency of symptoms of UTI in a recent series haemoglobinized and of uniform size and shape under
of 304 children less than 5 years of age presenting phase-contrast microscopy) in freshly examined urine.
to a Sydney hospital emergency department is listed The presence or absence of bacteria on microscopy can
in Table 18.1.2. The presentation varies with age be unreliable: the presence of bacteria on microscopy
because of the developmental status of the child. of a fresh, well collected specimen (e.g. by suprapubic
Although a wide range of symptoms can occur, aspiration of urine) can be sensitive and specific for
an infant will probably have an acute illness with UTI, particularly if the white cell count is high (more
fever and ­vomiting or a chronic illness with failure than 10 white cells/μl). The finding of epithelial squa-
to thrive, reflecting the systemic response to infec- mous cells indicates a poorly collected sample, and
tion at this age. The preschool child, who has usu- the absence of leukocyturia in a sample with mixed
ally achieved continence, will often show wetting or growth or low colony count on culture may indicate a
frequency, complain of generalized abdominal pain contaminated sample.
and sometimes indicate dysuria. The teenage girl will Urinary nitrite tests are frequently used to moni-
usually present with symptoms of cystitis (fever, fre- tor the urine of children prone to recurrent UTI (e.g.
quency, dysuria, strangury and accurately localized continent children with vesicoureteric reflux). Nitrite
pain) or pyelonephritis (fever, often with rigor, and testing of early morning urine on a weekly basis has
loin pain and tenderness). At any age, symptoms of been reported to detect UTI in asymptomatic children,
fever, vomiting and systemic unwellness occur with enabling treatment to be initiated earlier than would
638 pyelonephritis. otherwise occur.
 Urinary tract infections and malformations 18.1
Table 18.1.1 Common clinical patterns of urinary tract infection

Infant Toddler and young child Adolescent

Presentation Males more common than for females, Common for females, Common for females, rare
especially under 3 months uncommon for males for males
High fever Mild fever, wetting, dysuria and Pyelonephritis or cystitis
Systemically unwell smelly urine
Commonly recurs Frequent recurrences

Precipitating Males: High-grade VUR (often associated Low-grade VUR – ?associated Often history of VUR
factors with significant congenital renal with development of Sexual activity
malformation), physiological phimosis acquired renal injury Vulvovaginitis
Females: Low-grade VUR, usually Dysfunctional elimination
associated with no or minor renal symptoms
malformation Detrusor dyssynergia
Both: Immature voiding pattern with Infrequent voiding
high voiding pressure and detrusor Constipation
hyperactivity Vulvovaginitis

Prevention of Prophylactic antibiotic Treatment of precipitating Counselling

recurrence factors identified Adjustment of sexual habit
(void post-intercourse,
antibiotic at time of sexual
activity)

VUR, vesicoureteric reflux.

with more complicated anatomical malformations and

Practical points in those who have had surgical procedures, especially
where foreign materials (e.g. urinary stents) have been
Dipstick testing left in situ. Enterococci cause around 5% of UTIs and
• Positive leukocyte esterase is a reasonably sensitive test are the most common organism found that is resistant
but is not at all specific for urinary tract infection (UTI). to gentamicin. Approximately 5% of children have two
• Positive nitrites are less sensitive but quite specific for UTI. organisms isolated. Viral causes of infection have been
• Negative testing for leukocyte esterase and nitrites does thought to be rare in children who were not immu-
not exclude UTI, especially in babies. Some 10% of babies nosuppressed, but recent urinary polymerase chain
with UTI will have negative dipstick testing.
reaction (PCR) testing for adenovirus has shown a
• Always send urine for culture if UTI is suspected.
• Negative dipstick testing may reasonably be used in number of children with classical symptoms and often
making the decision to withhold antibiotics from children ­macroscopic haematuria have this cause.
over 3 years of age while awaiting urine culture results.

Initial treatment
Once the urine culture has been obtained, a decision
Urine culture on acute treatment must be made. Intravenous therapy
Urine culture is the ‘gold standard’ for diagnosis, but is required if: the child is systemically unwell (dehy-
management decisions often have to be made before drated, signs of septic shock such as hypotension,
the results are available. tachycardia and decreased conscious state); vomit-
The five common forms of urine collection are com- ing and unable to retain oral medications; and in
pared in Table 18.1.3. infants under the age of 6 months generally, because
oral absorption is unreliable. In the child in whom an
Microbiology infection is likely on the basis of urinalysis and pre-
Escherichia coli accounts for 80–90% of pathogens sentation, and the child is reasonably well (gener-
isolated. Proteus species are the cause of infection in ally older and not vomiting), oral antibiotics may be
30% of boys over 1 year of age. Coagulase-negative commenced, with review once the culture is through
Staphylococcus species are common in teenagers in 24–48 hours. In the child in whom urinary infec-
and Klebsiella is frequent in the neonatal period. tion is a possibility and the child is not unwell, culture
Pseudomonas species are frequently isolated in children results should be awaited before starting treatment. 639
 18.1 URINARY TRACT DISORDERS AND HYPERTENSION

to the emergence of resistant organisms or candidia-

Table 18.1.2 Frequency of symptoms in children under
5 years with symptomatic urinary tract infections
sis). They are usually given until the results of imaging
tests are available. Long-term antibiotic prophylaxis to
Symptom % reduce the risk of further UTI is an area of medical
controversy: systematic review of higher quality stud-
History of fever 79.6
ies has shown that about 16 children need to be treated
Axillary temperature > 37.5 °C 59.5 with prophylactic antibiotics to prevent one UTI.

Irritability 52.3
Investigations
Anorexia 48.7 The investigation necessary after a first UTI is an area
of medical controversy. After several decades where
Malaise/lethargy 44.4
the trend was to perform several detailed investiga-
Vomiting 41.8 tions, many centres are now more conservative and
reserve more invasive investigations, and those involv-
Diarrhoea 20.7 ing irradiation, for special situations.
Investigations are aimed at excluding obstructive
Dysuria 14.8 urinary tract lesions and determining whether there
are significant underlying urinary tract malformations.
Offensive urine 13.2
Nearly all centres perform renal ultrasonography. This
Abdominal pain 13.2 enables the presence, site, size and shape of the kid-
neys to be determined. In the age group under 5 years,
Family member with past history of UTI* 11.2 only 15% of abnormalities found on dimercaptosuc-
cinic acid (DMSA) scan (‘scars/dysplasia’) will be seen
Previous unexplained febrile episodes 10.5 on ultrasound examination. The ureters are not visu-
alized unless enlarged. The finding of hydronephrosis
Frequency 9.5
or hydroureter leads to further nuclear medical imag-
Urinary incontinence† 6.6 ing (discussed below) to diagnose obstructive lesions
of the urinary tract. An idea of bladder function can
Macroscopic haematuria 6.6 be determined by measuring the post-void residual
volume (normally less than 20 mL in children under
Febrile convulsion 4.6
7 years).
* First-degree relative. Radiological examination of the urethra and blad-
†
 Defined as a noticeable increase in the frequency of der by means of micturating cystourethrography
daytime wetting. (MCU) is performed in some centres as a routine on
UTI, urinary tract infection. infants (less than 1 year of age) and selectively at older
Source: Craig JC, Irwig LM, Knight JF et al 1998 J Paediatr ages where visualization of the bladder surface and
Child Health 34:154–159. urethra is required. This investigation is performed
less frequently than in the past because the demon-
stration of vesicoureteric reflux (VUR; see below)
The i­ntravenous antibiotics and oral antibiotics used does not alter management at many centres. The
acutely are listed in Table 18.1.4. Intravenous antibi- patient and parental acceptability of the test is poor
otics are usually ceased within 2–3 days once culture and against the ethos of ‘pain- and anxiety-free’ pae-
results have been obtained and the child has improved diatric procedures. The authors generally have MCU
clinically. Acute treatment is completed with oral anti- performed under general anaesthesia in children older
biotics, usually of 5 days’ duration. than 6 months.
Nuclear medicine investigations with technetium-
­99 m-labelled radioisotopes are useful for a number of
Prophylactic antibiotics
purposes. These investigations carry radiation toxicity
After acute treatment the child may be placed on of less than one-tenth of a routine chest X-ray.
prophylactic antibiotics given once each night. The The diethylenetriamine penta-acetic acid (DTPA)
antibiotics usually used for prophylaxis are listed radionuclide is injected intravenously, is filtered by the
in Table 18.1.4. These antibiotics are excreted in the glomerulus and then is neither secreted nor absorbed
urine, achieve high urinary concentrations and are well by the tubule of the kidney. Like creatinine or insulin,
tolerated over long periods of time without inducing it can be used to obtain an accurate measure of the
640
excessive microbiological changes in the gut (leading glomerular filtration rate.
Table 18.1.3 Comparison of methods of urine collection

Urine collection method Advantages Disadvantages Recommended use

Paediatric bag Widespread use in primary care Contamination with skin flora common so that Collection of urine from infant or toddler at low risk for UTI
paediatrics only results of < 108 cfu/L (excluding infection) (not febrile and no known urological abnormality) for
Considered convenient are useful urinalysis: if positive for leukocytes or nitrites, another
Avoids invasive procedure urine collection method should be used for culture
Should not be used where immediate antibiotic
treatment is required

Clean catch Non-invasive Perceived to be difficult to collect (majority can Method of choice in infants and toddlers
Good correlation with SPA/MSU/CSU be collected within 1 h) > 108 cfu/L indicates infection, although presence of
results squamous epithelia and lack of pyuria indicates
contamination

Midstream urine collection Non-invasive Poor technique (failure to withdraw foreskin or Method of choice in toilet-trained child
> 108 cfu/L indicates infection, although presence of

Urinary tract infections and malformations

(MSU) Widespread patient acceptance wash labia) results in contamination
Difficult with phimosis or for obese females squamous epithelia and lack of pyuria indicates
contamination

Catheter sample (CSU) Usually results in collection of sample of Invasive – poor acceptance by parents and Second choice to SPA in infants and toddlers with high
urine; reasonable for diagnosis especially can establish fear in child of future clinic risk of UTI (febrile and proven urological abnormalities)
if first drops of urine visits where treatment is required before culture available
discarded Difficult with phimosis > 103 cfu/L may indicate infection, although presence
of squamous epithelia and lack of pyuria indicates
contamination

Suprapubic aspirate of urine ‘Gold standard’ as avoids contamination ‘Dry tap’ relatively common (ultrasound Method of choice in infants and toddlers at high risk of UTI
(SPA) Less invasive than CSU collection confirmation of full bladder can minimize Useful in obese females with recurrent contaminated
this) MSUs
Any growth significant

cfu, colony-forming unit on bacterial culture; UTI, urinary tract infection.

18.1
641
 18.1 URINARY TRACT DISORDERS AND HYPERTENSION

Table 18.1.4 Antibiotic treatment of urinary tract infection

Antibiotic Dose Organisms sensitive* (%)

Acute
Intravenous
(sick, < 6 months old, pyelonephritis)
1. Benzyl penicillin 50 mg/kg (max. dose 2 g) 6 hourly Covers Enterococcus
and
2. Gentamicin 7.5 mg/kg daily for age < 10 years, 6 mg/kg daily for age ≥ 95
> 10 years (max. dose 360 mg)
Monitoring: trough level < 1 mg/L taken on 3rd day and
serum creatinine 3rd day
Oral
Trimethoprim 4 mg/kg (max. dose 150 mg) 12 hourly ≥ 85
or
Co-trimoxazole (40 mg/200 mg per 5 mL) ≥ 85
0.5 mL/kg (max. dose 20 mL) 12 hourly
or
Cefalexin 15 mg/kg (max. dose 500 mg) 8 hourly 95
or
Augmentin† 10–25 mg/kg 8 hourly 95

Prophylactic
Co-trimoxazole (40 mg/200 mg per 5 mL) ≥ 85
0.25 mL/kg nightly
Nitrofurantoin 1–2 mg/kg nightly ≥ 85
Cefalexin‡ 5 mg/kg nightly ≥ 95

* Percentage of bacteria causing urinary tract infection diagnosed in the emergency department of major Australian hospitals that
are sensitive to antibiotics.
†
Amoxicillin alone only covers 60% of organisms encountered, so Augmentin is preferred.
‡
The suspension forms of the cephalosporins and penicillins lose activity after a few weeks.

The mercapto-acetyl-triglycine (MAG3) scan has Delayed uptake of any of these three radionuclides
largely replaced the DTPA scan because, in addition may occur in conditions where perfusion to the kidney
to some glomerular filtration, the isotope is secreted is abnormal (e.g. renal artery stenosis in a unilateral
mainly by the proximal tubular cells into the urine so case or dehydration in a bilateral case).
that the signal to background ratio is higher than in The ongoing management depends on the results of
the DTPA scan. This is particularly useful in children investigations. A flow diagram of possibilities is shown
with renal impairment or infants in the first 3 months in Figure 18.1.1.
of life when the glomerular filtration rate is low. Both
of these investigations are useful for diagnosing the
Urinary tract infection and normal renal
presence of obstruction to urinary flow from the kid-
ultrasound findings
neys to the bladder, for determining the ‘split’ of kid-
ney function (between the right and left kidneys), and If the child responds to antibiotics, there is no need
for estimating overall renal function. to perform another urine culture at the end of treat-
The DMSA radionuclide is filtered by the glom- ment. In the case of an infant, some would con-
erulus and taken up by the proximal tubular cells. tinue prophylactic antibiotics for 6–12 months. In
Scanning takes place when it has been taken up by the case of an older child with recurrent infections
these cells, which are in the renal cortex. Lack of and ­normal baseline investigations, ultrasonography
uptake gives a defect on the scan and this can be due would be repeated and an examination for precipitat-
to either transient impairment of the tubular cell func- ing f­actors (see Table 18.1.1) such as constipation or
tion (e.g. following acute inflammation with pyelone- a ­functional ­voiding disorder (daytime wetting) would
phritis for a period of up to 3–4 months) or absence of be undertaken. Sexual activity should be considered in
642
kidney tissue (renal ‘scarring/dysplasia’). teenagers.
 Urinary tract infections and malformations 18.1
UTI

Ultrasound

Dilation of urinary tract Normal

Hydronephrosis Small kidney (s)
Hydroureter or
Renal Injury

+/- MCU *
MAG 3 scan
Assess renal function – blood pressure,
protein excretion, estimate GFR

Long term medical/renal follow up

Obstruction No obstruction

Urology referral for possible MCU Manage urinary infections

cystoscopy, retrograde or +/- prophylactic antibiotics
pyelogram and corrective Repeat US * +/- treat precipitating causes
surgery

DMSA scan 1- 2 years after last UTI

Renal Injury Normal

Follow up for Discharge

hypertension

* Some centers will perform an MCU to diagnose vesicoureteric reflux but in other centers the test is not routinely performed.
Until the last decade MCU was routine in children with UTI under the age of 1-2 years.

Bladder studies (urodynamic assessment of bladder volume and pressure, uroflow studies of micturition and post voiding
residual volume) should be considered in all children with recurrent infection

Fig. 18.1.1 Flow diagram of ongoing management following a proven urinary tract infection (UTI). A normal ultrasound result does not
exclude scarring. This age is chosen for convenience. Boys uncommonly have recurrent infections after 1 year; girls commonly have
recurrent infection until about 3 years. Follow up includes a yearly blood pressure check. A normal dimercaptosuccinic acid (DMSA)
scan result normalizes the risk of developing hypertension. MCU, micturating cystourethrography; MSU, midstream urine collection; US,
ultrasonography; VUR, vesicoureteric reflux.

Clinical example

Johnnie had a birth weight of 3.3 kg. He was to complete 3 days of oral co-trimoxazole therapy and then to
breastfed and weighed 5.1 kg at 2 months of commence night-time co-trimoxazole prophylactic antibiotic
age. For the next month he put on no weight treatment. MCU and renal ultrasonography were performed in
and his mother noted that he was irritable, fed the next few days.
poorly and had the occasional vomit. The family doctor took The ultrasound scan showed bilateral hydronephrosis and
a bag sample of urine and found more than 108/L colony- hydroureter. MCU showed a mildly trabeculated bladder with
forming units of an organism growing on culture the next day. bilateral vesicoureteric reflux; the urethra was abnormal in
The doctor arranged for a suprapubic aspirate of urine to be appearance with dilatation of the posterior urethra, suggesting
performed at the emergency department. This was done after a diagnosis of posterior urethral valves (Fig. 18.1.2). Prophylactic
a bladder scan showed a moderately full bladder. Johnnie was antibiotic treatment was continued and Johnnie was referred
admitted to hospital and received treatment with gentamicin to both a paediatric urologist (for cystoscopy and evaluation of
and penicillin given intravenously for 48 hours before an E. coli the urethra and bladder) and a nephrologist (for renal function
sensitive to co-trimoxazole was identified. He was discharged assessment). 643
 18.1 URINARY TRACT DISORDERS AND HYPERTENSION

Clinical example Abnormalities of the urinary tract

Amy, a 14-year-old girl, presented to her local Vesicoureteric reflux
doctor on three occasions over 6 months with
culture-proven UTIs. There was no family history This is a disorder in which urine passes in a retrograde
of urinary infections, Amy had never had a UTI direction from the bladder through the vesicoure-
before, and there was no evidence of a wetting disorder. teric junction into the ureter. It is a common disorder,
Further history revealed the onset of sexual activity at about affecting 40% of children under 1 year of age who are
the same time as the UTIs started. investigated for a first UTI. The diagnosis is made by
Amy was counselled regarding contraception and
MCU or by an indirect MCU done without urinary
sexually transmitted diseases, and she and her parents
were offered counselling regarding her sexual activity.
catheterization.
She was advised to have a 300-mL glass of water with a VUR is a familial trait affecting between 30%
citravescent sachet immediately before or just after sexual and 50% of first-degree relatives of index cases.
intercourse. However, 1 month later Amy re-presented with This developmental abnormality is character-
another UTI. She was then advised to take nitrofurantoin ized by the distal end of the ureter running less
(100-mg capsule) immediately after sexual intercourse. She obliquely through the wall of the bladder and hav-
was seen for review 3 and 6 months after this treatment,
ing less muscle around it. In some cases, it is asso-
reported no further symptoms and remained compliant with
the treatment. Because she was frequently changing sexual ciated with renal malformation (variously referred
partners, Amy was advised to continue on the treatment. to as renal scarring, ­ dysplasia, reflux-associated
nephropathy), excessive dilatation and tortuosity of
the ureter, occurrence on the ­contralateral side, and
Asymptomatic infection abnormalities of bladder ­function including prema-
ture detrusor contractions (causing urgency symp-
Up to 4% of adolescent girls have asymptomatic toms and wetting) and poor bladder emptying.
bacteriuria. A number of these children will have Higher grades of VUR are associated with higher
vesicoureteric reflux or reflux-associated nephropathy recurrence rates of UTI.
(see below). There is no evidence that treatment of The treatment of VUR has been controversial.
asymptomatic bacteriuria is beneficial, and coloni- Controlled trials (Box 18.1.1) have shown no advantage
zation frequently recurs after treatment, sometimes of either anti-reflux surgery or antibiotic prophylaxis
­precipitating symptomatic infection caused by a more in preventing urinary infections, hypertension, renal
pathogenic organism. injury or renal failure. In fact, it is not clear whether
these treatments are better than no treatment or epi-
sodic treatment of urinary infection alone. Much of
the renal injury leading to renal failure in a small num-
Practical points
ber of patients with VUR is congenital and the signifi-
cance of acquired injury is debated. Thus, the aim of
Management of urinary tract infection in infancy
treatment of VUR is prevention of s­ ymptomatic UTI,
• Suspect in a febrile infant with vomiting or failure to thrive
• Urine sample:
• Acutely unwell: suprapubic aspiration (SPA), or catheter-
specimen urine (CSU)
• Not unwell: clean catch Box 18.1.1 Management of vesicoureteric reflux (VUR):
• Unwell: commence treatment with intravenous gentamicin evidence and controversies
and intravenous penicillin initially, changing to oral
antibiotic to finish course when improved Evidence-based analysis of surgical versus antibiotic
• Prophylactic antibiotic until renal ultrasound findings treatment of VUR shows:
evaluated • No difference in overall rate of urinary tract infection (but
• Long-term follow-up essential unless DMSA scan results reduced rate of pyelonephritis with surgery)
normal • No difference in occurrence of ‘new scarring’ or extension
of ‘old scarring’
Management of recurrent urinary tract infection • No difference in incidence of renal failure
in childhood • No difference in incidence of hypertension
• Characterize symptoms as pyelonephritis or cystitis Continuing controversies:
• Identify precipitating factors: wetting, vulvovaginitis, • Whether VUR surgery or antibiotics make any difference to
phimosis or balanitis, constipation development of acquired renal injury
• Bladder abnormality • The frequency of acquired or congenital renal injury as a
• Individualize therapy to minimize development of cause of reflux nephropathy
symptomatic urinary infection • The effectiveness of prophylactic antibiotic therapy
644 • Longer-term follow-up essential unless DMSA result normal • The significance of smaller renal scars
 Urinary tract infections and malformations 18.1
not prevention of renal injury. Attention to reduc-
ing and treating precipitating factors for UTI, the use
of antibiotic treatment in a prophylactic or ­episodic
manner, and the selective use of anti-reflux surgery for
patients with intractable symptoms form the basis of
treatment.
VUR often resolves spontaneously (of a cohort of
children with reflux, 20% will have resolution occur-
ring spontaneously each 3-year period, with less severe
degrees of reflux resolving earlier than more severe
degrees). Resolution of reflux is often not a­ ssociated
with resolution of urinary infection, which can be
expected to occur periodically throughout life in
affected females, particularly with sexual activity and
pregnancy.

Reflux-associated nephropathy
Once thought to be due to the combination of A
VUR and infection, this abnormality of the kid-
ney is most often congenital in origin. It is found
in approximately 10% of children with VUR. The
importance of this lesion lies in the possibility of
development of hypertension, which is rare in early
childhood but occurs in up to 15% of cases by the
age of 20 years. Bilateral extensive reflux-associated
nephropathy is a cause of renal failure occurring
from mid childhood.

Posterior urethral valves

This abnormality is also referred to as congenital
obstructive posterior urethral membranes (COPUMs).
It affects males and causes obstruction to urine flow at
the level of the posterior urethra. The bladder is often
thick-walled and trabeculated; there may be associ-
ated VUR with tortuous and dilated ureters draining
grossly hydronephrotic kidneys. Antenatal ultrasonog- B
raphy demonstrating hydronephrosis and megacys-
tis is a common presentation, as is urinary infection Fig. 18.1.2 (A) Micturating cystourethrogram (from the Clinical
in early infancy, but some children present later with example) showing a dilated posterior urethra, mildly irregular
dribbling and wetting. appearance of the edge of the bladder (‘trabeculation’) and
bilateral vesicoureteric reflux into dilated tortuous ureters.
Diagnosis is made on the urethrogram phase of the
(B) Hydronephrosis with ‘clubbing’ of the calyces.
MCU (see Fig. 18.1.2), and confirmation is obtained
by cystoscopy. Treatment involves complex surgi-
cal procedures performed in the setting of a team
Duplication
approach to the patient, involving medical staff and
continence physiotherapists. Preparation for end-stage A kidney is said to be duplex if two separate collecting
renal failure treatment is often necessary. systems are identified. The ureters may join before entry
into the bladder, or they may have separate openings
into the bladder. The upper pole ureter enters the uri-
Bladder abnormalities
nary tract more distal to the lower pole ureter and may
Bladder malfunction is strongly associated with enter the urethra, giving rise to incontinence, or may
UTIs and often overlooked in clinical management. be obstructed at its lower end (ureterocele), in which
Table 18.1.5 describes common bladder abnormalities case the upper pole of the kidney will be abnormal. The
645
and their management. lower pole ureter often has vesicoureteric reflux.
 18.1 URINARY TRACT DISORDERS AND HYPERTENSION

Table 18.1.5 Common bladder abnormalities

Bladder abnormality causes Urodynamic assessment Symptoms Treatment

Small bladder Low volume Day and night wetting Frequent voiding
Primary High pressure UTI Bladder augmentation
Posterior urethral valves Hydroureter
Bladder exstrophy
 Neurogenic

Large bladder Large volume Infrequent voiding Frequent voiding

Primary Low pressure UTI Drainage by vesicostomy, CIC
 Neurogenic High residual volume Wetting or catheterizable conduits
Vesicoureteric reflux
Detrusor dyssynergia Premature detrusor Urge symptoms Anticholinergic drugs
syndrome contractions Wetting Frequent voiding
Primary UTI Usually resolves
Vesicoureteric reflux

Neurogenic All of the above found Wetting with ‘overflow’ Bladder drainage by
Cord injury* UTI vesicostomy, CIC or
‘Non-neurogenic’† Obstructive nephropathy catheterizable conduit
Bladder augmentation

* Cord injury may be clinically apparent (spina bifida) or determined by ultrasonography in a neonate when the cord can be
imaged, or by MRI at later ages.
†
 Non-neurogenic neurogenic bladder is a term used for the clinical and investigational features of a neurogenic bladder in a child
who does not have demonstrable spinal pathology.
CIC, clean intermittent catheterization; UTI, urinary tract infection.

Other causes of urinary obstruction i­nfecting organisms often urea-splitting (such as

Proteus ­mirabilis), or renal colic. Other stones
Pelviureteric junction (PUJ) obstruction
­occasionally encountered are composed of cystine
This is now most commonly diagnosed following the (autosomal recessive cystinuria), calcium oxalate
­
evaluation of hydronephrosis detected on antenatal and, ­uncommonly, uric acid.
scanning of the fetus. At least 9 out of 10 such cases
Antenatal renal abnormalities
will resolve spontaneously over the first year of life.
The advent of almost routine antenatal scanning at
Periodic renal ultrasound observation, sometimes
18 weeks’ gestation has led to the detection of approxi-
supplemented by diuretic renography using DPTA or
mately 1 in 200 infants having an increased renal pelvis
MAG3 radioisotopes, is used to follow these infants.
diameter (> 4 mm at 18 weeks). The postnatal diagno-
Pelviureteric junction obstruction may present in later
ses are shown in Table 18.1.6.
childhood with renal colic and these patients usually
require surgery.
Vesicoureteric junction (VUJ) obstruction Management
This often presents following investigation of UTI,
Antenatal ultrasound imaging should be repeated
with the ultrasonography showing a dilated ureter and
in the third trimester of pregnancy. The presence of
MAG3 scan showing delayed passage of urine from
bilateral severe hydronephrosis with an enlarged blad-
the ureter to the bladder with a widened ureteric image.
der in the male infant suggests the diagnosis of poste-
Treatment is stenting of the VUJ or reimplantation of
rior urethral valves. The presence of oligohydramnios
the ureter.
suggests reduced urine output, and this is associated
Renal calculi with the development of pulmonary hypoplasia and a
These may present following UTI, in which case higher risk of renal failure.
the calculus is usually a triple phosphate (mag- After birth, the infant should be placed on prophy-
nesium, ­calcium and ammonium) stone and the lactic trimethoprim until the diagnosis is determined. If
646
 Urinary tract infections and malformations 18.1
the child is unwell or if significant severe a­ bnormalities
Table 18.1.6 Antenatal renal abnormalities: postnatal
diagnoses
are suspected, imaging of the kidneys and urinary tract
should be performed immediately. In contrast, if the
Diagnosis % baby is well and without severe urinary tract dilatation,
postnatal ultrasound imaging is undertaken towards
Non-refluxing non-obstructive hydronephrosis 55
the end of the first week of life when the baby is well
Vesicoureteric reflux 15 hydrated. Further investigations, usually looking for
reflux or obstruction, are p ­ erformed, depending upon
Pelviureteric junction obstruction 5 the results of this ultrasound examination.

Multicystic kidney 5 Cystic renal disease

Vesicoureteric junction abnormalities 5 Common forms of cystic renal disease and the modes
of presentation are listed in Table 18.1.7. Solitary cysts
Duplex 5 are uncommon in childhood and may be an indication
of evolving polycystic kidney disease.
Agenesis 5

Posterior urethral valves 2

Table 18.1.7 Forms and presentation of cystic renal disease

Cystic renal disease Incidence Genetics Clinical features

Autosomal dominant 1–2 in 1000 Three gene defects Usually discovered because of family history
polycystic kidney M = F cause it; 50% risk in Uncommon cause of hypertension or loin/abdominal
disease subsequent children discomfort in childhood
Progresses to renal failure later in life

Autosomal recessive 1–2 in 10 000 births One gene defect Often present in infancy with enlarged
kidney disease M = F identified; 25% hyperechogenic kidneys, oliguria, respiratory
risk in subsequent distress associated with pulmonary hypoplasia
pregnancies Later may develop hypertension, renal impairment
Associated with hepatic fibrosis causing portal
hypertension in mid-childhood

Cystic renal dysplasia Common Polygenic; low Often asymptomatic

recurrence risk Associated with vesicoureteric reflux
May be bilateral

Multicystic dysplastic Relatively Unknown; low Enlarged, completely cystic non-functioning kidney
kidney uncommon recurrence risk without blood flow
Contralateral kidney usually normal but may be
associated with vesicoureteric reflux or pelviureteric
junction obstruction

647
 18.2 Glomerulonephritis, renal
failure and hypertension
Steven McTaggart

hypothesized that streptococcal antigens deposit in

Haematuria glomeruli with activation of the complement system.
Isolated microscopic haematuria The pathological appearance consists of proliferation
of mesangial and endothelial cells with neutrophil
Asymptomatic isolated microscopic haematuria is infiltration (Fig. 18.2.1). Crescents may be present.
common and can be detected on a single occasion in Immunofluorescence shows IgG and C3, and electron-
0.5–2% of school-aged children. The majority of these dense deposits (humps) are demonstrated by electron
children will not have significant kidney disease and, microscopy.
in the absence of symptoms or other abnormalities on Clinically this disorder usually presents with mac-
urinalysis, further investigation is required only if hae- roscopic haematuria, acute fluid overload and hyper-
maturia is documented in at least three different speci- tension in a school-aged child. Lassitude, fever and
mens taken over a period of 2–3 weeks. loin pain also may be present. Physical examination
Persistent microscopic haematuria is usually benign, may reveal hypertension, papilloedema, facial and leg
provided there is no infection or proteinuria, renal oedema. Serum urea, creatinine and potassium con-
function is normal and no structural abnormality is centrations are often raised, and urinalysis shows red
present on ultrasonography. Possible diagnoses include blood cell casts and dysmorphic red cells. Mild nor-
idiopathic hypercalciuria, thin membrane disease or a mocytic normochromic anaemia is common and is
mild proliferative glomerulonephritis such as immu- due to haemodilution from fluid overload. The anti-
noglobulin A (IgA) nephropathy (see below). A fam- streptolysin O titre (ASOT) and anti-streptococcal
ily history of microscopic haematuria is suggestive of DNase B are raised in 90% of cases. Activation of
thin basement membrane disease, which is often inher- the classical complement pathway leads to low serum
ited in an autosomal dominant fashion. levels of C3, which generally returns to normal within
6–12 weeks.
Glomerulonephritis The major complications of acute post-streptococcal
glomerulonephritis are secondary to acute kidney
The clinical features of glomerulonephritis are: injury resulting in salt and water retention. Fluid over-
• haematuria load is responsible for hypertension and in severe cases
• acute fluid overload – oedema, pulmonary oedema, can result in hypertensive encephalopathy or left ven-
congestive cardiac failure tricular failure. Fluid overload is best managed ini-
• hypertension tially with furosemide 2–4 mg/kg daily, fluid restriction
• renal impairment – oliguria, raised plasma and a low-salt diet. More severe hypertension may be
creatinine level. treated with oral nifedipine or prazosin. Bed rest is
Acute presentation with these clinical features is seen necessary only when the blood pressure is increased.
most commonly in post-streptococcal glomerulone- A course of oral penicillin for 10 days eradicates any
phritis. Other forms of glomerulonephritis in child- existing streptococcal infection, but does not alter the
hood may have a less severe onset (Box 18.2.1). Most natural history of this condition.
forms of glomerulonephritis result from an immuno- The period of oliguria lasts for up to 10 days and
logically mediated injury involving either deposition dialysis is indicated in cases where the blood urea
of circulating immune complexes in the glomerulus rises above 50–60 mmol/L, or when hyperkalaemia
or a specific antibody to the glomerular basement or p­ ulmonary oedema is not controlled by diuret-
membrane. ics and fluid restriction. The long-term prognosis is
excellent, with only 1% developing chronic kidney dis-
ease. Microscopic haematuria may continue for up to
Post-streptococcal glomerulonephritis
2 years, but proteinuria should clear within 6 months.
This disorder follows 7–14 days after group Renal biopsy is not indicated unless there is uncer-
A β-haemolytic streptococcal throat infection and tainty of diagnosis with the initial investigations or the
648
3–6 weeks after streptococcal skin infection. It is period of oliguria lasts for longer than 3 weeks.
 GLOMERULONEPHRITIS, RENAL FAILURE AND HYPERTENSION 18.2
Box 18.2.1 Causes of acute nephritis

• Post-infectious glomerulonephritis
• Henoch–Schönlein purpura
• IgA nephropathy
• Lupus erythematosus
• Membranoproliferative glomerulonephritis
• Vasculitis

Fig. 18.2.1 Mesangial proliferation and neutrophil infiltration in

post-streptococcal glomerulonephritis (periodic acid–Schiff stain,
original magnification ×800).

Fig. 18.2.2 Immunofluorescence shows mesangial IgA

Other infectious agents including viral and bac-
deposits (original magnification ×600).
terial organisms rarely can produce an illness simi-
lar to post-streptococcal nephritis. These organisms
include staphylococci and Pneumococcus, and Echo, is preceded by upper respiratory tract infection in
Coxsackie and Epstein–Barr viruses. 30–50% of patients. These children present with a
­petechial or purpuric rash that is localized over lower
limbs and buttocks, abdominal pain and arthritis. A
IgA nephropathy
mild nephritis with microscopic haematuria and pro-
This glomerulopathy is present in 50% of children who teinuria is seen in 50–70% of cases. Rarely, blood
have recurrent episodes of macroscopic haematuria. pressure and serum creatinine levels are raised. Renal
The episodes of haematuria often occur simultaneously histology shows a proliferative glomerulonephritis
with intercurrent viral infections and may be associated with IgA in the mesangium. The prognosis is good,
with flank pain. Other presentations include abnormal with less than 5% developing chronic kidney disease.
urinalysis on medical examination and, rarely, an acute
glomerulonephritis with renal failure. Renal biopsy
Lupus erythematosus
shows a focal proliferative glomerulonephritis with IgA
in the mesangium (Fig. 18.2.2). Although the prognosis Systemic lupus erythematosus (SLE) presents in child-
for most children with IgA nephropathy is good, long- hood in 20% of cases and is more common in children
term studies show that about 10% progress to chronic from Asian countries. Facial rash, arthritis and fever
renal failure by 15 years after onset of disease. Bad are common presenting symptoms. Serum C3 comple-
prognostic features include impaired renal function at ment is usually low and anti-nuclear antibodies can
presentation, heavy proteinuria and hypertension. often be detected, especially to double-stranded DNA.
Renal biopsy is indicated if haematuria and protein-
uria are present. The type of glomerular disease in
Henoch–Schönlein purpura
SLE can vary from a mild focal proliferative glomeru-
This disease is a vasculitic illness involving predomi- lonephritis to a diffuse crescentic glomerulonephritis.
nantly small vessels in the skin, large joints and gas- The treatment is complex but generally involves vari-
649
trointestinal tract (see Chapter 16.2). The illness ous combinations of immunosuppressant medications
 18.2 URINARY TRACT DISORDERS AND HYPERTENSION

such as prednisolone, azathioprine, cyclophosphamide Minimal change nephrotic syndrome

or mycophenolate. The amount of immunosuppres-
The majority of children present between the ages of
sion is dependent on clinical severity of kidney disease
1 and 4 years with generalized oedema (Fig. 18.2.3).
and renal histology. This disorder is discussed further
Renal biopsy is not initially indicated if clinical fea-
in Chapter 13.3.
tures suggest minimal change disease (Box 18.2.3).
Unless large pleural effusions, gross ascites or
Alport syndrome
severe genital oedema are present, strict bed-rest is
This is a familial disorder in production of type IV col- not necessary and the child should be allowed nor-
lagen and is inherited as an X-linked dominant (85% mal ward activity. A low-salt diet is encouraged.
of cases), autosomal dominant or autosomal reces- Fluid intake is generally not restricted because of
sive condition. In males, this disorder presents in the the risk of hypovolaemia, but mild fluid restriction
first 10 years of life with microscopic or macroscopic may be beneficial in some children with significant
haematuria and proteinuria, and is followed by onset oedema. Prednisolone 2 mg/kg or 60 mg/m2, daily,
of renal failure in the teenage years. High-tone nerve induces remission in 90% of cases. The prednisolone
deafness and eye abnormalities are the other features dose is then reduced over 6 months, with later doses
of the syndrome. being given on alternate days to reduce side-effects. If

Proteinuria
Isolated proteinuria
Transient proteinuria can be seen in many conditions
including fever, exercise and seizures, and disap-
pears when the condition resolves. Proteinuria that
is detected in the standing position but not when
recumbent is known as orthostatic or postural pro-
teinuria; this occurs in 10% of children and is more
common in adolescence. Testing with urinary dip-
sticks or urine protein : creatinine ratio shows neg-
ligible amounts of protein in first daytime void and
increased protein excretion during the day. This phe-
nomenon is benign but proteinuria in an overnight
urine specimen will usually require biopsy to deter-
mine the cause.

Nephrotic syndrome
Nephrotic syndrome is defined as:
• proteinuria (> 40 mg per m2 per h or protein/
creatinine ratio > 250 mg/mmol)
• hypoalbuminaemia (< 25 mg/dL)
• oedema, and
• hyperlipidaemia.
The annual incidence in children is approximately 2–4
per 100 000. The major conditions associated with a
primary nephrotic syndrome are listed in Box 18.2.2. Fig. 18.2.3 Child with facial oedema due to the nephrotic
syndrome.

Box 18.2.3 Clinical features of minimal change nephrotic

Box 18.2.2 Classification of primary nephrotic syndrome syndrome

• Minimal change disease • Age 1–10 years

• Focal segmental glomerulosclerosis • Blood pressure normal
• Membranoproliferative glomerulonephritis • Renal function normal
• Membranous glomerulopathy • Microscopic haematuria 30%
650 • Congenital nephrotic syndrome • Complement levels normal
 GLOMERULONEPHRITIS, RENAL FAILURE AND HYPERTENSION 18.2
remission, as defined by ­complete loss of proteinuria, ­ ccurrences that require prompt treatment with anti-
o
has not occurred by 4 weeks, the nephrotic syndrome coagulants. The avoidance of bed-rest and the treat-
is steroid-resistant and a renal biopsy is then indi- ment of hypovolaemia may account for the decreasing
cated to exclude other pathology, particularly focal incidence of these complications.
segmental glomerulosclerosis. Approximately 90% of children with relapsing ne­phrotic
Approximately 70% of children have relapses, which are syndrome cease relapsing by 16 years of age. Even those
more likely to occur in association with viral upper respira- children who continue to relapse into adult life usually
tory tract infections. Frequent relapsers (four or more epi- remain steroid-sensitive. It is very rare for a child with
sodes per year) may be treated with regular prednisolone a steroid-sensitive minimal-change lesion nephrotic syn-
5–15 mg, given on alternate days. Children with significant drome to progress to chronic kidney disease.
steroid side-effects require specialist assessment for consid-
eration of alternative immunosuppressive regimens.
Focal segmental glomerulosclerosis
The major complications of the nephrotic syndrome
are infections, hypovolaemia and thromboembolism. This glomerulopathy comprises 5–10% of children
Infections such as peritonitis and septicaemia can be with nephrotic syndrome. The presentation is often
caused by both Gram-positive and Gram-negative similar to a minimal-change lesion but with steroid
organisms. The susceptibility to infections is related to resistance. Renal biopsy (Fig. 18.2.4) shows segmental
loss of opsonins and immunoglobulins in the urine. If sclerosis or hyalinosis, whereas other glomeruli may be
the patient develops a serious infection, the initial anti- completely sclerosed. Immunofluorescence shows IgM
biotic treatment should cover both Gram-positive and and IgG in the affected segmental lesions. Mutations
Gram-negative organisms until cultures and sensitiv- in podocin, a podocyte structural protein, are found
ity results are available. Hypovolaemia is due to loss of in 10–30% of sporadic cases of steroid-resistant focal
plasma water into the tissues with a consequent fall in segmental glomerulosclerosis.
the circulating blood volume. It occurs in 5% of cases The majority of children with this lesion are resistant
and should be suspected if a child develops oliguria to immunosuppressive medications. Those children
(< 100 mL/day), poor peripheral perfusion, abdominal who remain nephrotic require treatment with diuretics
pain, tachycardia or postural hypotension. This com- (furosemide, spironolactone), mild fluid restriction and
plication is confirmed by a high haematocrit and a low a low-salt diet. Approximately 60% progress to end-
urine sodium (< 10 mmol/L). The preferred treatment is stage kidney disease over 10 years. This glomerulopa-
intravenous 20% albumin (1 g/kg over 3–6 h), which may thy has a 30% recurrence risk in a transplanted kidney,
need to be repeated, according to response. Intravenous and in some cases plasmaphaeresis is beneficial.
furosemide (2 mg/kg) is given in the middle and at the
end of the infusion to promote a diuresis.
Congenital nephrotic syndrome
A hypercoagulable state exists for a number of rea-
sons. These include haemoconcentration and loss Congenital nephrotic syndrome (CNS) is defined as
of antithrombin III in the urine. Renal vein throm- nephrotic syndrome occurring in the first 3 months of
bosis and pulmonary embolism are relatively rare life. Nephrotic syndrome in this age group is often due
to genetic causes, most commonly due to a mutation in
the podocyte slit-diaphragm protein nephrin. This form
Clinical example

Sasha, a girl aged 5 years, presented with

nephrotic syndrome at 2 years. At presentation
serum albumin was less than 15 g/L, 24-hour
urine protein 2.5 g/day and urine microscopy
30 red blood cells per mm3. Blood pressure and complement
were normal. Prednisolone 60 mg/m2 per day induced
remission in 10 days. In the next 2 years Sasha had six
relapses with upper respiratory tract infections and was
then managed with prophylactic prednisolone. In the last
6 months she had had two further relapses while still on
maintenance prednisolone. She was now cushingoid and
her height percentile had fallen from the 25th to below
the 10th percentile. She commenced a 10-week course of
cyclophosphamide (2.5 mg/kg daily).
Sasha had steroid-dependent nephrotic syndrome with
significant steroid side-effects requiring a change in therapy. Fig. 18.2.4 Segmental and global sclerosis (periodic acid–Schiff 651
stain, original magnification ×500).
 18.2 URINARY TRACT DISORDERS AND HYPERTENSION

of nephrotic syndrome is most common in Finland and • microangiopathic haemolytic anaemia

is often referred to as congenital nephrotic syndrome of • thrombocytopenia
the Finnish type (CNF). Oedema is noted in the first • acute renal insufficiency.
weeks of life, with placentomegaly and p ­rematurity It has been broadly classified into two groups: the typi-
being common precursors. There is no specific treat- cal or epidemic form, also known as diarrhoea-asso-
ment and the natural history involves progression to ciated (D+) HUS, and the atypical or sporadic form,
end-stage kidney disease and transplantation. CNS diarrhoea-negative (D−) HUS.
with other histological patterns includes focal segmen- Diarrhoea-associated disease most commonly presents
tal glomerulosclerosis (often due to podocin mutations) in children under the age of 3 years with bloody diarrhoea.
and diffuse mesangial sclerosis, which may be part of a Over the next few days, the child becomes pale, oliguric
multisystem syndrome such as Denys–Drash syndrome. and unwell. Examination of the blood film shows frag-
Nephrotic syndrome can also result from congenital mented red blood cells and thrombocytopenia. Urinalysis
infections such as syphilis and cytomegalovirus. reveals haematuria and proteinuria. The serum creatinine
level is usually raised and hypertension may be severe.
Pathogenesis is related to verocytotoxin production
Practical points by Escherichia coli, usually serotype O157 : H7, although
other serotypes are also involved. The toxin crosses the
Glomerular disease damaged gut mucosa and adheres to endothelial cells in
• Microscopic haematuria without proteinuria is rarely arterioles, with consequent swelling and widening of the
associated with significant renal disease. subendothelial space with fibrin deposition. Management
• Control of hypertension and fluid overload is the key to is supportive and dialysis is often necessary. Most chil-
management of acute post-streptococcal glomerular
nephritis. dren (90%) make a complete recovery. Bad prognostic
• Non-postural proteinuria is an important diagnostic and signs are oliguria lasting for more than 2 weeks, cerebral
prognostic finding and requires specialist assessment. involvement and age of onset over 5 years.
• Children with typical features of nephrotic syndrome that Non-diarrhoeal HUS (D−) is associated with a vari-
respond to prednisolone treatment do not require a renal ety of systemic disorders and may follow pneumococ-
biopsy.
cal pneumonia. Recurrent HUS is often a recessively
• Children with frequently relapsing (2 relapses within
6 months of initial episode or ≥ 4 per year) or steroid-
inherited disorder in regulation of the alternative
dependent (relapse on prednisolone) nephrotic syndrome pathway of complement activation.
require specialist referral.

Chronic kidney disease

Acute kidney injury The incidence of chronic kidney disease in children is
The causes of acute kidney injury are listed in 2–4 per million total population per year. The com-
Table 18.2.1. monest causes include:
• structural abnormalities of kidneys and renal tract
(reflux nephropathy, obstructive uropathy)
Haemolytic–uraemic syndrome
• renal dysplasia/hypoplasia
Haemolytic–uraemic syndrome (HUS) is the most • chronic glomerulonephritis.
common cause of acute intrinsic kidney failure in The principles of management are as follows:
childhood and is characterized by the triad of: • Control of hypertension.

Table 18.2.1 Causes of acute kidney injury

Pre-renal Renal Post-renal

Hypovolaemia Kidney disease Posterior urethral valves

Gastroenteritis Glomerulonephritis Neurogenic bladder
Haemorrhage Haemolytic–uraemic syndrome Ureterocele
Hypoalbuminaemia Interstitial nephritis Calculi

Peripheral vasodilatation Myoglobinuria, haemoglobinuria Tumours

Sepsis Nephrotoxic drugs Uric acid (tumour lysis syndrome)

Decreased cardiac output

652 Congestive cardiac failure
 GLOMERULONEPHRITIS, RENAL FAILURE AND HYPERTENSION 18.2
• Adequate nutrition. Salt and fluid intake will vary
with the type of renal disease but children with Hypertension
obstructive uropathy or renal dysplasia may require Hypertension is defined as average systolic and/or dia-
supplemental salt and water for adequate growth. stolic blood pressure that is equal to, or greater than
• Growth retardation may also be improved by growth the 95th percentile for sex, age and height on three or
hormone. Resistance to endogenous growth hormone more occasions. Blood pressure of 120/80 mmHg or
is caused by low free insulin-like growth factor-1 levels. above in adolescents, or between the 90th and 95th
• Prevention of renal osteodystrophy. percentile in children at any age, is labelled as prehy-
Hyperphosphataemia should be treated vigorously pertension. When measuring blood pressure, the cuff
with a low-phosphate diet and dietary phosphate bladder length should cover 80–100% of the circum-
binders in an attempt to prevent secondary ference of the upper arm, as a smaller cuff may lead
hyperparathyroidism. Vitamin D supplementation to a falsely high reading. In borderline hypertension,
with calcitriol (1,25-dihydroxycholecalciferol) is 24-hour ambulatory blood pressure recordings are
given in early renal failure to prevent rickets. useful to distinguish persistent blood pressure increase
• Administration of alkali may be required to control from ‘white coat hypertension’. Normal blood pres-
acidosis (2–4 mmol/kg daily). sure for children varies with sex, age and height, and
• Anaemia is corrected by erythropoietin. This is raised levels on screening (Table 18.2.2) should be con-
administered subcutaneously at intervals from firmed by reference to standard tables.
weekly to monthly. Iron supplementation is The major causes of hypertension are given in
necessary. Box 18.2.4. Renal disease accounts for approximately
80% of cases prior to adolescence.

Clinical example

Edward, aged 30 months, had chronic Table 18.2.2 Screening values for hypertension in
renal failure from birth from urethral valves children: look up standard tables if…
and dysplastic kidneys. He had a poor
Age (years) Systolic BP (mmHg) Diastolic BP (mmHg)
appetite and required nasogastric feeding
from 3 months. X-ray of the wrist at 18 months showed 3–5 ≥ 100 > 60
rickets requiring treatment with calcitriol. At 24 months
he developed anaemia (haemoglobin 9.5 g/L) and 6–8 ≥ 105 > 70
commenced weekly subcutaneous darbepoietin-α.
Edward had grown 2 cm in the last 12 months. 9–11 ≥ 110 > 75
Investigations showed a haemoglobin concentration
of 11.3 g/L, serum sodium 136 mmol/L, potassium 12–14 ≥ 115 > 75
4.5 mmol/L, urea 42 mmol/L, creatinine 650 μmol/L,
calcium 2.4 mmol/L, phosphate 2.4 mmol/L, alkaline ≥ 15 ≥ 120 ≥ 80
phosphatase 850 U/L. The parathyroid hormone level was
increased. Source: Mitchell CK, Theriot JA, Sayat JG et al 2011 J Paediatr
Edward had now reached end-stage kidney disease Child Health 47:22–26.
and needed to commence peritoneal dialysis. Growth
hormone was indicated for growth failure. He continued
to take calcium carbonate at mealtimes in addition to
calcitriol for renal osteodystrophy and erythropoietin for
anaemia. Box 18.2.4 Causes of hypertension – REDCAT

R Renal parenchymal disease

• Acute glomerulonephritis
Dialysis and transplantation are now standard • Chronic glomerulonephritis
for young children with end-stage renal failure. • Reflux nephropathy
Young children tolerate peritoneal dialysis bet- • Obstructive uropathy
• Haemolytic–uraemic syndrome
ter than haemodialysis, and the use of automated • Polycystic kidneys
machines for overnight dialysis facilitates normal Renovascular (renal artery stenosis, renal vein thrombosis)
daytime activities and is preferred for school-aged E Essential hypertension
children. Both deceased donor and living-related D Drugs (corticosteroids, ciclosporin)
transplants are performed in children, with good C Coarctation of aorta
results. Approximately 80% of children survive for A Adrenogenital syndrome, hyperaldosteronism
T Tumours (Wilms’ tumour, phaeochromocytoma,
at least 10–15 years after entering dialysis/transplant
neuroblastoma) 653
programmes.
 18.2 URINARY TRACT DISORDERS AND HYPERTENSION

The investigation of hypertension should commence Head

with a good history and examination. The history Cushing facies
Eyes
William Syndrome
should specifically include enquiries about urinary tract Retinal changes
Flushing
infections, neonatal umbilical artery catheterization, (catecholeamine
­medication use, and hypertension or early stroke in any Chest excess)
relatives. Examination of hypertensive children focuses on Murmur (William
identification of secondary causes and assessment of end- syndrome, Turner Neck
suyndrome) Hyperthyroidism
organ damage (Fig. 18.2.5). Initial investigations include Left ventricular
serum biochemistry, urinalysis and renal ultrasonography. hypertrophy
Treatment of hypertension depends on the sever-
ity, presence of symptoms and underlying cause Abdomen
(Table 18.2.3). Children with a hypertensive emergency Mass (tumours)
Bruits (renal artery
usually present with signs and symptoms involving the: stenosis) Pulse
• nervous system – encephalopathy, facial palsy, Palpable kidneys Tachychardia
retinopathy (polycystic kidney (catecholeamine
disease) excess)
• heart – left ventricular hypertrophy or congestive
cardiac failure
Extremities Skin
• kidneys – raised serum creatinine level, proteinuria. Oedema Cafe-au-lait
An acute hypertensive emergency requires immediate (glomerulonephritis) (neurofibromatosis
intervention with intravenous drugs (sodium nitro- Arthritis (SLE)
prusside, labetalol, hydralazine, diazoxide), which Fig. 18.2.5 Examination of the hypertensive child. SLE, systemic
can produce a controlled reduction in blood pressure. lupus erythematosus.
The aim is to decrease blood pressure by 25% over
the first 8 hours, with gradual normalization over the
subsequent 24–48 hours. Severe hypertension with- Medications used for treatment of chronic hyper-
out imminent serious clinical sequelae is managed as tension in children are similar to those used in adult
a hypertensive urgency, and blood pressure may be patients. Angiotensin-converting enzyme (ACE) inhib-
reduced gradually over 24–48 hours with oral drugs itors are commonly used as initial therapy, except in
(e.g. nifedipine or minoxidil). patients with renal artery stenosis.

Table 18.2.3 Management of hypertension

Frequency of BP measurement Therapeutic lifestyle changes Pharmacological therapy

Prehypertension Recheck in 6 months Weight management None unless compelling

counselling if overweight; indications such as chronic
introduce physical activity kidney disease, diabetes
and diet management mellitus, evidence of end-
organ damage

Stage 1 hypertension Recheck in 1–2 weeks As above Initiate therapy if symptomatic,

(between 95th and 99th or sooner if patient is presence of above indications,
percentile plus 5 mmHg) symptomatic; evaluate if or persistent hypertension
persistently raised on despite non-pharmacological
2 additional occasions measures

Stage 2 hypertension Evaluate or refer for As above Initiate therapy

(> 5 mmHg above 99th investigation within 1 week
percentile) or immediately if patient is
symptomatic

654
 GLOMERULONEPHRITIS, RENAL FAILURE AND HYPERTENSION 18.2

Clinical example Practical points

Sally, aged 6 years, had a blood pressure
Hypertension
recording of 140/100 mmHg at the time of
tonsillectomy. Urine analysis, renal function • Hypertension is defined as repeated systolic blood
pressure and/or diastolic blood pressure measurements
and renal ultrasound findings were normal;
≥ 95th percentile for sex, age and height. Some
echocardiography showed left ventricular hypertrophy; a
hypertensive children may have a normal blood pressure
mercapto-acetyl-triglycine (MAG3) scan showed that the left
at presentation if they are in cardiac failure.
kidney contributed 44% and the right kidney 56% of total
function; renal angiography showed a mid-aortic syndrome • ‘White coat’ hypertension is common in children and
can be excluded by 24-hour ambulatory blood pressure
with bilateral renal artery stenosis from fibromuscular
monitoring.
hyperplasia.
Sally's blood pressure was controlled with metoprolol • All hypertensive children should be evaluated for target
organ damage and have investigations to identify
7.5 mg daily and amlodipine 5 mg daily. Left balloon
secondary causes of hypertension.
angioplasty to 3–4 mm was performed, and Sally is awaiting
a similar procedure on the right renal artery. • Intravenous treatment to achieve a slow, controlled
reduction of blood pressure is indicated for hypertensive
emergencies.
• The goal for antihypertensive treatment is reduction of
blood pressure to ≤ 95th percentile.

655
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 19
PART

ENDOCRINE
DISORDERS

657
 19.1 Growth and variations
of growth
Sarah McMahon

Growth is a multifactorial process influenced by growth. In developed countries, both undernutrition

genetic, nutritional, hormonal, psychosocial and and overnutrition may have long-lasting effects on
other factors, including the general health of a child. growth patterns. Undernutrition, particularly intra-
As such, growth mirrors the psychosocial and physical uterine or at significant postnatal periods, may affect
wellbeing of a child and adolescent. both the weight and height growth patterns and also
Physiological and pathological processes exert the development of body organs. For example, chil-
effects on growth and development at different stages dren who are born small for gestational age and who
of life. The three major determinants of growth are: experience significant catch-up growth in the first few
• genetic factors months of life have been shown to have an increased
• nutritional factors risk of cardiovascular morbidity and mortality as well
• hormonal factors. as type 2 diabetes later in life.
Many situations throughout childhood can cause
poor nutrition and affect the growth of the child.
Undernutrition due to poor quality and low quantity
Genetic factors of food may lead to poor growth, particularly if pro-
longed. In addition, chronic disease may also lead to
The genetic background of individuals is the major
poor nutrition. Finally, emotional deprivation also has
determinant of growth potential: tall parents generally
a profound influence on growth. On the other hand,
have tall children, whereas short parents have short chil-
overnutrition may lead to o ­ besity with advanced lin-
dren. Although children's heights at maturity resemble
ear growth and early pubertal maturation.
those of their parents, little is known about the exact
location of the individual height controlling genes, how
many genes are involved or how they direct cellular
growth. Major genetic disturbances such as chromo- Hormonal factors
somal abnormalities are often reflected in poor growth
patterns. For example, with loss of a sex chromosome Those of significance in growth are:
in 45,XO Turner syndrome, as shown in Figure 19.1.1 • growth hormone (GH)
(see also Chapter 10.3), adult stature is severely com- • thyroid hormone
promised. Other less severe chromosomal abnormali- • testosterone and adrenal androgens
ties also may result in abnormalities in stature. • oestrogens.
Many inherited genetic conditions can also result in
growth disturbance. The most striking of these are the Growth hormone–insulin-like growth
skeletal dysplasias, which often follow an autosomal factor I axis
dominant mode of inheritance. The classical example
The major hormonal influence involved in growth
of a skeletal dysplasia is achondroplasia, described in
regulation at all ages is the growth hormone–insulin-
Chapter 10.3. Chromosomes may also influence tall
like growth factor I axis (GH–IGF-I). GH is secreted
stature, as seen in the case of an individual with an
by the anterior pituitary gland in a pulsatile pattern.
extra sex chromosome, for example Klinefelter syn-
Major peaks of secretion occur particularly at night.
drome XXY, which frequently leads to an adult height
GH is bound to a specific growth hormone-binding
above that anticipated from the family pattern.
protein and subsequently acts on a broad range of tis-
sues via cell surface receptors, resulting in a range of
metabolic and growth-related effects. Many of these
effects are mediated via IGF-I, which is produced by
Nutritional factors the liver and many other tissues. The secreted IGF-I
Nutrition is the second most important factor deter- then acts either locally on adjacent tissues (paracrine
mining normal growth in childhood and adolescence. action) or via endocrine mechanisms (i.e. via the
658
Malnutrition is the world's primary cause of poor circulation). IGF-I levels are age-dependent, being
 Growth and variations of growth 19.1
to oestrogens and will rapidly cause bone age advance-
ment and may limit the potential for final height.

Oestrogens
Oestrogens in small doses may synergize with GH to
cause growth promotion. In higher doses, oestrogens
will inhibit growth and promote early fusion of the
bony epiphyses.

Phases of growth
There are three main phases of growth: fetal growth,
childhood growth and the pubertal growth spurt.

Fetal growth
Fetal growth is the most rapid phase of growth. Initial
embryonal/fetal growth is characterized by rapid dif-
ferentiation of body organs, whereas late fetal growth
involves continued rapid enlargement in tissues and
organs, and growth in length. The most rapid linear
growth velocity of all ages occurs in the weeks before
birth. Factors controlling fetal growth include pla-
cental supply of nutrients and oxygen, and a range of
Fig. 19.1.1 Turner syndrome. Note webbing of the neck and local growth factors including insulin-like growth fac-
widely spaced nipples. tors (IGFs). Pituitary GH probably plays a relatively
small part in this phase of growth, whereas thyroxine is
involved in brain and bone growth in the fetus. Pituitary
low in the fetus, rising through infancy and child- gonadotrophins (luteinizing hormone (LH) and follicle-
hood, peaking during puberty and then falling to stimulating hormone (FSH)) regulate testicular testos-
adult levels. IGF-I is very sensitive to nutritional terone synthesis in the male fetus, which is essential for
status and its measurement is of limited diagnos- normal growth of the male phallus. Thus a male infant
tic value in the assessment of short stature. It cir- with hypopituitarism may have a micropenis at birth.
culates bound to one of its major binding ­proteins
(IGFBPs). Childhood growth
During the first years of life, linear growth velocity is
Thyroid hormone still very rapid (on average 8–12  cm/year) but plateaus
through childhood to an average of approximately
Thyroxine is very important for postnatal growth.
5–6  cm/year. The growth velocity immediately before
Children with untreated hypothyroidism may show
the pubertal growth spurt may be lower than this and
both intellectual impairment and profound growth
represents a transient phase of poor growth. If the onset
retardation, with delayed bony maturation (see
of the pubertal growth spurt is delayed, this phase of
Chapter 19.2).
poor growth may be prolonged. During the childhood
growth phase the limbs grow faster than the trunk, so
the ratio of upper to lower body segments (divided at the
Testosterone and adrenal androgens
pubic symphysis) diminishes from approximately 1.7 : 1
These hormones are anabolic and growth promoting. In during infancy to 1 : 1 by age 10. It may fall to around
males, testosterone and GH act synergistically to pro- 0.8 by mid-puberty. The arm span : height ratio increases
mote the adolescent growth spurt. Excess androgens in ­during childhood and reaches 1 : 1 during puberty.
childhood may be produced as a consequence of adre- Factors controlling this phase of growth include
nal enzyme disorders (congenital adrenal hyperplasia), genetic determinants, nutrition, absence of chronic
precocious puberty and tumours, or may come from disease and normal secretion of hormones, the most
659
exogenous treatment. Some androgens are aromatized important of which are GH and thyroxine.
 19.1 ENDOCRINE DISORDERS

Pubertal growth spurt charts, including linear height and weight charts
(Fig. 19.1.2) as well as height velocity charts, indicat-
Puberty is associated with the onset of sex hormone
ing annual rate of growth (Fig. 19.1.3).
production in boys and girls under the influence of
These charts demonstrate the range of normal growth,
pulsatile release of gonadotrophins (FSH/LH) from
expressed either as percentiles or as standard deviations
the pituitary gland. In girls, ovarian oestrogen secre-
(sd) from the mean for age. The percentile curves are
tion leads to the earliest pubertal sign of breast devel-
derived from the normal distribution (bell-shaped curve)
opment at an average age of 10–11 years, followed by
of the data. The median is the 50th percentile and indi-
pubic and axillary hair growth in response to adrenal
cates that 50% of the measurements of a normal group
and ovarian androgens. The earliest sign of puberty in
of children are above and 50% are below that point. The
boys, at an average age of 11 years, is testicular enlarge-
50th centile ‘final’ height value for males is 176 cm and
ment (volume ≥ 4 mL measured with an orchidometer).
for females is 163 cm. Children whose height or weight
Penile and scrotal growth follow, with development of
are 2 sd above or below the mean fall approximately
pubic and axillary hair in response to testosterone syn-
between the 3 rd and 97th percentiles (Fig. 19.1.2). There
thesis. In boys testosterone also leads to muscle growth,
will be three normal children in every 100 who will be at
whereas in girls oestrogens cause pelvic broadening and
or below the 3 rd centile and three in every 100 who will
fat redistribution, leading to a female body shape. In
be at or above the 97th centile.
both sexes, the onset of puberty is followed by a peak
Assessment of growth velocity (Fig. 19.1.3) is of far
linear growth velocity, at an a­ verage age of 11.5 years
greater clinical significance than single measurements
in girls and 13.5 years in boys.
of height, and should be based on sequential measure-
The hormonal changes of puberty include an
ments taken at 3-monthly intervals during a period of
increase in the amplitude of GH pulses, probably due
6–12 months. When measured over this time period, a
to sex hormone effects. IGF-I levels rise during puberty
normal child will tend to follow the same height percen-
in association with the high GH levels. Oestrogens
tile (Fig. 19.1.2). A child with an organic or endocrine
have direct effects at the skeletal growth plate, ulti-
disease will tend to deviate from the percentile and may
mately leading to fusion of the bony epiphyses and
move across percentile lines. Thus serial measurement of
cessation of growth at an average age of 15 years in
­children is the key to the assessment of their growth status.
girls and 17 years in boys. The pubertal growth spurt
may be influenced by genetic factors and may also be
affected adversely by poor nutrition or chronic disease, Practical points
both of which can cause pubertal delay.
Growth
• There is a wide variation of normal growth.
Practical points • Some 3% of normal children will be above the 97th
percentile and 3% will be below the 3rd percentile.
Puberty • Assessment of growth velocity (growth over time) is
• The earliest sign of puberty in females is breast budding, of more value than a single growth measurement.
at an average age of 10–11 years. • The average growth rate during childhood is 5–6 cm/year.
• The earliest sign of puberty in males is testicular
enlargement, at an average age of 11 years.
• Pubic and axillary hair development usually follow the
onset of breast development in girls and of testicular Bone age
enlargement and genital development in boys.
Bone age is an index of physiological maturity, indicat-
• The pubertal growth spurt occurs at an average age of
11.5 years in females and 13.5 years in males. ing the state of bony epiphyseal maturation. A bone
• The growth spurt in puberty is the most rapid phase of age is obtained by performing an X-ray of the left wrist
postnatal growth. and hand, and is interpreted according to an atlas of
age- and sex-specific standards. The bone age indicates
the average age of children at a similar stage of bony
maturation and is a guide to the remaining growth
Assessment of growth potential of the child. In normal children, the bone age
will be within 1.5–2 years of the chronological age.
Percentile charts
Any health professional who deals with children must
Mid-parental height
have a working knowledge of normal variations in
growth and development, and must be able to use a The mid-parental height (MPH), also known as the
percentile chart. Childhood and pubertal growth target height, allows the height of any individual
660
patterns can be appreciated by examining growth
­ child to be considered in relation to the heights of
 Growth and variations of growth 19.1
Supine length (recommended up to the age of 3 so that there is overlap with standing
height at 2 to 3) is taken on a flat surface, with the child lying on his back. One observer 97 190
holds the child’s head in contact with a board at the top of the table and another
straightens the legs and turns the feet upward to be at right angles to the legs and
brings a sliding board in contact with the child’s heels.
90 185

Standing height (recommended from age two onwards) should be taken without shoes, 75 180
the child standing with his heels and back in contact with an upright wall. His head is
held so that he looks straight forward with the lower borders of the eye sockets in the
same horizontal plane as the external auditory meati (i.e. head not with the nose tipped 50
175
upward). A right-angled block (preferable counterweighted) is then slid down the wall
until its bottom surface touches the child’s head and a scale fixed to the wall is read.
25
During the measurement the child should be told to stretch his neck to be as tall as 170
possible, though care must be taken to prevent heels coming off the ground.
Gentle but firm pressure upward should be applied by the measurer under the mastoid 10
processes to help the child stretch. In this way the variation in height from the morning to 165
evening is minimised. Standing height should be recorded to the last completed 0.1 cm. 3
160 1
160

155 C = M[1 = L.S.Z] 1/L 155

Where C is the centile required, LMS are those parameters
published by CDC and Z is the standard deviation equivalent
150 to the centile required. 150
1st Centile calculated by Associate Professor Peter Davies,
Cjildren’s Nutrition R`esearch Centre, Brisbane.
145 145

140 140

135 135

130 130

125 125

120 120
Simplified calculation of Body Surface Area (BSA)
115 HT (cm) × Wt (Kg)
115
BSA (m2) √
3600
110 110

105 105

100 100
Height

95 95
cm
90

85
5+
Penis 4+
80 stage 3+
2+
97 90 75 50 25 10 3
75
5+
Pubic 4+
hair 3+
70 stage 2+
97 90 75 50 25 10 3

65 Testes 12 mL
vol. 4 mL
97 90 75 50 25 10 3
60

cm

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Age (years)

Fig. 19.1.2 Male height centile chart. A similar chart is available for females. CDC, Centers for Disease Control. (Reproduced with
permission from Pfizer.)
661
 19.1 ENDOCRINE DISORDERS

High velocity
The standards are appropriate for velocity calculated over a whole year period, not less, since a smaller period requires wider limits (the
3rd and 97th centiles for a whole year being roughly appropriate for the 10th and 90th centiles over six months). The yearly velocity
should be plotted at the mid=point of a year. The centiles given in black are appropriate to children of average maturational tempo,
who have their peak velocity at the average age for this event. The blue line is the 50th centile line for the child who is two years early in
maturity and age at peak height velocity, and the grey line refers to a child who is 50th centile in velocity but two years late. The arrows
mark the 3rd and 97th centiles at peak velocity for early and late maturers.
14 14

Centiles of a whole year

13 velocity for maturers
13
at average time
12 12

97 and 3 centile at peak

11 height velocity for
11
Early (+ 2SD) maturers
10 Late (–2SD) maturers 10

9 9

8 8
cm/year

7 7

6 6

5 5

4 4

3 3

2 2
97
90
1 75 1
3 10 25 50

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

Age (years)

Fig. 19.1.3 Male height velocity chart. A similar chart is available for females. (Reproduced with permission from Pfizer.)

his/her b­ iological parents. The mid-parental height pathology but will either be following a familial pattern
(in centimetres) can be calculated using the ­following or have a variant of normal growth. The main causes
formulae: of short stature in order of frequency of diagnosis are
summarized in Box 19.1.1. As can be seen, endocrine
For boys : MPH = (father ′s height + (mother ′s causes of short stature are the least common.
height + 13)) / 2, ± 7.5cm
For girls : MPH = (mother ′s height + (father ′s
height − 13)) / 2, ± 6 cm Practical points

Short stature
• The majority of short children are normal and healthy.
Short stature • The most common causes of short stature are familial
short stature and constitutional delay of growth.
The management of a child with short stature requires • Chronic disease is a major cause of short stature and is
consideration of a number of issues. It is important to characterized by a decrease in both height and weight velocity.
662
realize that the majority of short children will have no
 Growth and variations of growth 19.1
fail to demonstrate catch-up growth in the first 2 years
Box 19.1.1 Causes of short stature
of life and remain small.
• Genetic/familial short stature
• Constitutional delay Chronic disease
• Small for gestational age
• Chronic illness – inflammation and malnutrition Chronic disease is a major cause of growth failure:
• Skeletal dysplasia • Usually the growth failure is associated with a
• Chromosomal abnormality/syndrome similar fall off in weight velocity.
• Psychosocial
• Endocrine
• An endocrine problem is unlikely to be the cause
of poor growth if both the weight and height are
affected.
• Nutritional insufficiency may contribute to the
Variations from normal growth failure of chronic disease as a result
Familial (genetic) short stature of inadequate or inappropriate intake, poor
absorption or impaired or excessive tissue
Important features of familial short stature are as follows: utilization.
• Height will track parallel to and below the 3rd centile.
• The growth rate (growth velocity) is usually normal.
• The adult height percentiles of both parents should be Skeletal disorders
plotted on the child's growth chart to assess whether Skeletal disorders are usually familial, involving
the child's height is appropriate for the heights of the intrinsic cartilage or bone defects. Examples include
parents. achondroplasia, hypochondroplasia and the muco-
• Pubertal development usually occurs at the polysaccharidoses. The major distinctive feature of
appropriate time. these disorders is body segment disproportion, with
• Markers of physical maturation such as bone age increased upper to lower body segment ratios. The limbs
tend to be consistent with chronological age. are usually short, leading to a reduced arm span : height
ratio. Weight gain is usually n
­ ormal. These disorders in
Constitutional delay in growth and puberty their mild form are relatively c­ ommon and often over-
looked. More information is given in Chapter 10.3.
Constitutional delay in growth and puberty is a very
common variation of growth and leads to short stat-
ure during childhood with an adult height prognosis Iatrogenic
consistent with the mid-parental height expectation. High-dose corticosteroid treatment may cause poor
Important features are: growth in children with conditions such as severe
• affects boys more commonly than girls, and boys asthma, cystic fibrosis, arthritis, inflammatory bowel
are more likely to present to medical attention disease, nephrotic syndrome and malignancies such
• often there is a family history of a parent being as leukaemia. Marked growth failure is associated
short as a child, with delayed puberty and eventual with weight gain. Irradiation to the head and spine
catch-up with peers may result in hypothalamic–pituitary dysfunction and
• these children are the so-called ‘slow growers and poor spinal growth. Poor growth of the trunk is char-
late bloomers’ acterized by an increased arm span : height ratio and a
• markers of physical maturation such as bone age reduced upper to lower body segment ratio.
are delayed
• the delay in puberty and associated delay in fusion
of bony epiphyses means that both the pubertal Chromosomal abnormalities and syndromes
growth spurt and the completion of growth will be
Turner syndrome and its variants are the most
delayed
­common chromosomal cause of short stature. This
• these children (most often boys) tend to grow into condition must be excluded in any girl with short stat-
their late teenage years or early twenties.
ure, because the typical phenotypic features may not
be seen, particularly in the mosaic forms of Turner
Pathological causes syndrome. The most common associated abnormal-
ity is ovarian dysgenesis resulting in failed puber-
Small for gestational age
tal ­development in 95% of cases. Other commonly
Babies may be born small for gestational age (SGA) seen features include a webbed neck (see Fig. 19.1.1),
as a result of a number of fetal, maternal and environ- small ears, increased carrying angle, bicuspid aortic
663
mental factors (see Chapter 11.2). Some SGA children valve, coarctation of the aorta, horseshoe kidney,
 19.1 ENDOCRINE DISORDERS

Box 19.1.2 Features of Turner syndrome

General • Madelung deformity

• Short stature • Kyphoscoliosis
• Delayed puberty • Broad chest
• Primary amenorrhoea
Metabolic
Lymphatic abnormalities • Autoimmune thyroid disease
• Neck webbing • Impaired glucose tolerance/type 2 diabetes
• Low posterior hairline • Abnormal liver function test results
• Lymphoedema
• Nail convexity/dysplasia Miscellaneous
• Recurrent middle ear infections
Skeletal abnormalities • Sensorineural hearing loss
• Micrognathia • Bicuspid aortic valve
• High arched palate • Coarctation of the aorta
• Short 4th/5th metacarpals • Renal abnormalities (e.g. horseshoe kidney)
• Increased carrying angle • Naevi

dysplastic nails and recurrent otitis media. All or Natalie was referred to a paediatric endocrinologist who
none of these dysmorphic and clinical features may advised them that Natalie's growth could be improved with
be present. The full range of features is summarized GH injections. It was very likely that she would eventually
in Box 19.1.2. need hormonal induction of puberty and would have
infertility owing to the gonadal dysgenesis associated with
Common dysmorphic syndromes presenting with
Turner syndrome. Natalie's parents were also informed that
short stature include Noonan syndrome and Russell– she would need ongoing care into adulthood to monitor for
Silver syndrome. other health issues such as hypertension, hyperlipidaemia,
type 2 diabetes, and aortic dilatation and dissection, all
of which occur more commonly in women with Turner
Psychosocial syndrome.
Psychosocial causes of short stature cover the spec- Natalie was referred to other specialists regarding other
problems associated with Turner syndrome. Renal ultrasound
trum from severe deprivation to overt abuse, and
imaging was normal and her heart was structurally normal.
may be associated with nutritional deficiencies. Fall- She continued to have middle ear infections and required
off in weight gain is usually as striking as failure of insertion of grommets. She was commenced on GH
­linear growth. Short stature due solely to psychosocial injections 6 days per week and responded well. By the age
­deprivation is uncommon. of 7 years her height was on the 5th percentile.

Endocrine
Clinical example Endocrine causes of short stature are the least com-
mon pathological cause and include hypothyroid-
Natalie's parents were concerned about her ism, GH deficiency (possibly associated with other
growth and saw a paediatrician when she was
pituitary hormone deficiencies), Cushing syndrome
4 years old. Her birth weight and length were
around the 25th centile. At 2 years her length (hypercortisolism) and adrenal insufficiency. These
was on the 10th percentile, but then her growth had seemed conditions are more likely to be associated with weight
to slow, particularly after the age of 3 years. gain than a fall-off in weight centiles.
On assessment by the paediatrician at 4 years of age,
her height was 6 cm below the 1st percentile. She had had
a few middle ear infections in the last 2 years but had Assessment
otherwise been well. Her early development was normal.
Her cardiovascular examination was normal. She had
Issues to determine
widely spaced nipples but no other dysmorphic features. Assessment of short stature involves determination of
Initial investigations including full blood count, electrolytes the following issues:
and liver function tests, thyroid function tests and a coeliac
screen were normal. Her bone age was the same as her
• Is she or he short?
chronological age. Her karyotype was consistent with Turner • Is she or he growing slowly (could this be
syndrome. pathological)?
664
• What is the underlying cause?
 Growth and variations of growth 19.1
• What is the adult height prognosis? Examination
• How is s/he coping with the short stature?
On examination ensure/look for:
• Is any specific therapy warranted?
• accurate height (using a stadiometer) and weight,
• Is any supportive therapy indicated?
and body proportions (arm span, upper and lower
The approach to the assessment of short stature
segments)
should include history, examination, investigations if
• assessment of pubertal status – the characteristic
necessary, therapy and follow-up.
pubertal changes in males and females are
illustrated in Figures 19.1.4 and 19.1.5 (further
History issues regarding puberty are considered later in this
section)
When taking the history, the following should be
• general physical examination including evidence of
sought:
chronic disease, nutritional state and dysmorphic
• What is the height compared to peers? features suggesting a syndrome
• How long has the child been short?
• any sign of goitre or clinical signs of
• Who is concerned about the short stature and is hypothyroidism, including dry hair and skin,
there teasing at school?
bradycardia and delayed reflexes
• What is the school performance?
• evidence of ‘midline brain development syndromes’,
• What are the birth details and past medical which may result in hypopituitarism. This includes
history?
cleft palate, single central incisor and small male
• Was there unexplained neonatal hypoglycaemia genitalia (associated with gonadotrophin deficiency
(suggesting pituitary hormone deficiency) or early
in utero). The combination of neonatal hypoglycaemia
illnesses?
and small genitalia suggests hypopituitarism
• Determine milestone development, specific disease
• visual fields and optic fundi to exclude the
symptoms and nutritional status.
possibility of a pituitary lesion, in particular
• Has puberty commenced? craniopharyngioma.
• Are previous growth measurements available (child
health record or measurements from local doctor or
school)? Management
• What are the current heights and ages of pubertal The single most important aspect of the assessment
onset of the parents and siblings? and management of short stature is to plot the current
• Is there a family history of specific diseases? and previous heights and weights and parental heights

A B
Pubic hair stage 2 Pubic hair stage 3 Genital 2/Pubic hair 2 Genital 3/Pubic hair 3

Pubic hair stage 4 Pubic hair stage 5 Genital 4/Pubic hair 4 Genital 5/Pubic hair 5

665
Fig. 19.1.4 (A) Pubertal pubic hair changes in the female. (B) Pubertal genital and pubic hair changes in the male.
 19.1 ENDOCRINE DISORDERS

at 3–4-monthly intervals over that time. Examination

of the growth data plus the points obtained in history
and examination should allow d ­ istinction between a
variation of normal and a p
­ athological cause of short
stature.

Stage 1–prepubertal
Investigations
Investigations should be performed if there is any evi-
dence of specific chronic disease, if there is a sugges-
tion of chromosomal abnormality or if the growth
velocity is subnormal. The following investigations
may be performed:
Stage 2–elevation of breasts and papilla
• bone age X-ray
• full blood count
• urea, creatinine and electrolytes
• calcium and phosphate
• thyroid function tests
• C-reactive protein (CRP) and iron studies
• chromosomes (girls only)
• screening test for coeliac disease (total
Stage 3–further enlargement and elevation of immunoglobulin (Ig) A and tissue transglutaminase
breast and areola but no separation of contour antibodies)
• urinalysis ± microscopy and culture.
It is important to note that all girls with unexplained
short stature should have a karyotype to exclude the
possibility of Turner syndrome.
If puberty is markedly delayed it may be worthwhile
measuring gonadotrophins (FSH/LH) and testoster-
one or oestradiol.
Stage 4–areola and papilla form a secondary
mound above level of the breast
The listed investigations provide a screen for under-
lying chronic disease, infection or nutritional d
­ eficiency
as well as hypothyroidism and Turner s­yndrome.
Other investigations may be indicated by specific phys-
ical findings. In a child with unexplained ­combined
weight and height fall-off, a m ­ alabsorptive ­disorder
should be excluded and consideration should be given
to ­measuring tissue transglutaminase ­antibodies as a
Stage 5–areola recedes to the general contour possible indicator of the presence of coeliac ­disease.
of the breast If these are raised, a small-bowel biopsy may be
Fig. 19.1.5 Pubertal breast changes in the female. ­necessary (see Chapter 20.3).

on a percentile chart in order to answer the following

questions:
Clinical example
• Is the child short and below the 3 rd height
centile? Is this appropriate for mid-parental Ben was a 14-year-old boy whose mother
height? complained that he did not seem to be growing
• Is the child growing slowly and is there evidence at all. She said to her general practitioner
that the height is falling across the percentile lines? that she had not needed to buy Ben any new
This can be further plotted on a height velocity clothes for the past 3 years. She remembered that her older
son was always growing out of his clothes at this age. She
chart (see Fig. 19.1.3). was also concerned because Ben did not seem to have as
A height velocity below the 25th centile for bone age is much energy as other boys his age, and he ate much less
potentially abnormal in a short child. A reliable height than she would have expected at this age, based on her
666 velocity requires at least 6 months of growth data, and experience with her older son.
preferably 12 months with ­consistent ­measurements
 Growth and variations of growth 19.1
clinical information, results of MRI brain scans
Further history revealed that Ben had always been a very and GH tests
healthy boy in the past, with no significant medical problems. • overnight sleep studies of GH secretion
He had become a fussy eater during the past couple of
• exercise GH tests – performed in the fasting state
years. He said that many foods he had previously eaten now
made him feel sick in the stomach and gave him stomach
on a bicycle ergometer with blood for GH levels
cramps. When asked if he had diarrhoea, Ben said ‘no’, taken before and 30 minutes after exercise. This
but when asked how many times he went to the toilet he is a screening test with 20% of normal children
admitted that he needed to go at least six times a day, and failing to reach cut-off levels
that this pattern had developed only in the last year. Ben said • Pharmacological tests of GH sufficiency, including:
he thought this was normal. • glucagon stimulation test
Physical examination confirmed that Ben's height and
weight were almost the same as when he was 11 years
• arginine stimulation test
old. Apart from being a little pale, there were no other • clonidine stimulation test.
abnormal physical findings on general examination. Ben Although no one test is superior to another, the glu-
was pre-pubertal. cagon stimulation test is at present the preferred
Baseline investigations included a full blood count pharmacological test of GH secretion. The glucagon
and CRP estimation. These showed that Ben had a low stimulation test also provides information about the
haemoglobin level and his CRP was 30 mg/L. All the other hypothalamic–pituitary–adrenal axis.
baseline tests including electrolytes, liver function tests, renal
For the purposes of defining GH deficiency and assess-
function, screening tests for coeliac disease and thyroid
function tests were normal. Ben's bone age was significantly ing eligibility for human GH as a pharmaceutical benefit
delayed. At 14 years of age his bone age was only that of 10 in Australia, biochemical GH deficiency is defined as fail-
years. ure to achieve a peak serum GH concentration of more
The history of poor growth and the abdominal symptoms than 10 mU/L in response to two stimulation tests, at least
together with the low haemoglobin and raised CRP level one of which is a pharmacological test, or in response to
suggested the possibility of a chronic gastrointestinal one test in the presence of other evidence suggestive of
problem such as inflammatory bowel disease. Ben was
referred to a paediatric gastroenterologist and had an
GH deficiency, such as structural CNS abnormalities or
endoscopy and colonoscopy, which demonstrated that he low plasma IGF-I and IGFBP-3 levels.
had Crohn's disease. After appropriate management his
symptoms improved. He started to gain weight and over the
next 12 months his growth also improved.
Treatment
Short stature is considered by some children and their
families to be a physical and psychosocial disability.
The major growth-promoting agent used in the treat-
Investigation for growth hormone deficiency
ment of short stature is biosynthetic GH. This has
GH deficiency may be suggested by association with been available commercially in Australia since 1985.
midline defects or by the presence of other pituitary GH can be administered only by subcutaneous
hormone deficiencies, including secondary hypothy- injections, usually given 6–7 days per week. Despite
roidism or gonadotrophin deficiency. Biochemical the availability of biosynthetic GH, the annual cost of
GH deficiency is an indication for magnetic resonance GH therapy remains very high.
imaging (MRI) of the central nervous system (CNS) The Commonwealth Department of Health and
and biochemical testing for other pituitary deficits. Ageing has provided guidelines for the use of GH in
Specific underlying causes of GH deficiency include Australia. Current indications include:
idiopathic (most common), pituitary or hypothalamic • short stature (less than 1st percentile) and slow growth
tumours or structural abnormalities, cranial irradia- (growth velocity below 25th percentile for bone age)
tion and genetic GH deficiency (e.g. gene defects of • biochemical GH deficiency associated with short
pituitary transcription factors). stature and slow growth
Specific tests to determine the presence of GH defi- • growth retardation secondary to an intracranial
ciency include: lesion or cranial irradiation
• Physiological tests of GH sufficiency, such as: • Turner syndrome
• measurement of IGF-I and IGFBP-3 levels. • chronic renal insufficiency
These tests are used for screening for GH • Prader–Willi syndrome.
deficiency prior to proceeding to more involved
pharmacological tests. As yet the data are not
Psychological support and counselling
sufficiently reliable to recommend that these tests
be performed as a single diagnostic entity in a Psychological support and counselling are undoubt-
clinical setting. They may, however, be useful edly the most important part of the management of
667
when considered in combination with other short stature and can be provided by either health
 19.1 ENDOCRINE DISORDERS

­ rofessionals or lay support groups. Often, reassur-

p It is also important to ascertain whether the appear-
ance regarding the normality of the child and the reas- ance of precocious puberty may be due to an aberrant
surance of a ­reasonable height prognosis is all that is source of androgen or oestrogen production, such as
required. an adrenal or ovarian tumour.

Syndromes causing tall stature

Tall stature Marfan syndrome may present with the classical pic-
Tall stature is a relatively infrequent presenting prob- ture of arachnodactyly, ligamentous laxity, chest
lem compared with the number of children who pres- deformity, cardiac abnormalities, high arched palate
ent because of short stature. In general, very few tall and subluxation of the lenses. Often, however, one sees
children have an organic disease process as a basis tall, thin children with some marfanoid features but
for their condition. The most common reason for tall who are difficult to classify. Children with homocystin-
stature is genetic tall stature. Compared with 20 years uria have a marfanoid phenotype but have intellectual
ago, relatively few teenagers and their parents are con- impairment. Homocystinuria may be diagnosed by a
cerned about tall stature, as it is now more socially study of urinary and serum amino acids. Tall girls with
acceptable for girls to be tall. As with short stature, intellectual impairment should also be screened for
there is no clear demarcation between normal and tall the triple X syndrome, and tall boys with disorders of
stature. A child whose height is above the 97th percen- pubertal maturation, with small testes, gynaecomastia
tile for age should be considered tall. and sometimes behavioural disturbance, should have
chromosomal analysis. They may have either XYY
syndrome or Klinefelter syndrome (XXY).
Causes
The following may be causes of tall stature:
Endocrine causes of tall stature
• familial or normal variant
• precocious puberty Hyperthyroidism is relatively uncommon in childhood
• syndromes – Marfan, Klinefelter, triple X, and is an infrequent cause of tall stature. The clinical fea-
homocystinuria, Sotos tures of hyperthyroidism are discussed in Chapter 19.2.
• endocrine causes: hyperthyroidism and pituitary Pituitary gigantism is extremely rare but should be sus-
gigantism. pected if the history and examination suggest pituitary
involvement in association with tall stature. Children
with pituitary gigantism will have an abnormally rapid
Familial/normal variant tall stature
growth rate as well as tall stature, in contrast to geneti-
Most tall children are normal in all respects and their cally tall children who grow above but parallel to the
height is genetically determined. Some children with 97th percentile but have a normal growth velocity.
early but otherwise normal pubertal development will
appear tall in relation to their peers and family dur-
Approach to diagnosis and treatment
ing adolescence, but will have a predicted final height
within the accepted normal range. These early devel- The approach to diagnosis in a tall child consists of a
opers have an advanced bone age and are at the oppo- full history, including a history of family heights and
site end of the spectrum to the short children with pubertal maturation patterns. In addition, it is important
constitutional delay, who have delayed puberty but to ascertain whether there are associated ­abnormalities
who will also reach a normal adult height consistent or developmental delay that may ­ suggest one of the
with their mid-parental height. ­chromosomal or syndromal ­disorders ­causing tall stature.
A full physical examination is essential, with empha-
sis on accurate height measurement, body shape, limb
Precocious puberty
proportions and pubertal status. Neurological assess-
Precocious puberty is defined as pubertal development ment should include fundoscopy, assessment of visual
at less than 8 years of age in girls and less than 9 years fields and intellectual function, and should determine
in boys. Because of rapid acceleration of bone matura- any evidence of hyperthyroidism.
tion and early epiphyseal fusion, many children with In most instances, a tall child will have a normal
precocious puberty are excessively tall in early to mid growth velocity with height tracking above but paral-
childhood but finish up as relatively short adults. It is lel to the 97th centile. An accurate height measurement
important to recognize precocious puberty, as treat- and bone age assessment by an experienced radiolo-
ment can be provided to switch off the premature acti- gist or paediatric endocrinologist will enable an adult
668
vation of the hypothalamic–pituitary–gonadal axis. height prediction to be made.
 Growth and variations of growth 19.1
In the past, sex steroids were used to reduce the final
Table 19.1.1 Causes of delayed puberty
height in both males and females where the estimate
of final height was thought to be excessive. High-dose Cause Clinical examples
oestrogen treatment was used in tall girls. However,
recent studies have suggested an increased risk of Associated with
normal or low serum
­psychological problems and impaired fertility in women gonadotrophin levels
treated with high-dose oestrogen for tall stature in ado- Constitutional delay Usually familial: associated with a
lescence. Currently this treatment is not advocated. delayed bone age
Chronic illness Cystic fibrosis, inflammatory bowel
disease, juvenile idiopathic arthritis
Endocrine causes Hypopituitarism (congenital and
Variations of pubertal acquired), isolated gonadotrophin
deficiency, Kallman
development syndrome, hypothyroidism,
Early normal puberty hyperprolactinaemia
Inadequate nutrition Anorexia nervosa, excessive
In many countries, including Australia, children appear exercise
to be starting puberty younger than previous genera-
tions. This is called the secular trend in growth and Associated with
raised serum
development. The earlier age of puberty is probably
gonadotrophin levels*
due to effects of improved nutrition and living circum- Gonadal dysgenesis Turner syndrome, Klinefelter
stances, and absence of chronic disease. Many girls syndrome
present just before 8 years of age with breast develop- Anorchia
ment. After assessment by a specialist, no specific treat- Gonadal damage Vascular damage, irradiation,
ment is usually required. Interestingly, although there chemotherapy, mumps (boys),
has been a trend towards earlier onset of breast devel- torsion, autoimmune disease,
galactosaemia (girls)
opment, the average age of menarche (onset of p ­ eriods)
remains approximately 12.8 years for white girls. *This usually signifies primary gonadal dysfunction.

Delayed puberty
Delayed puberty is very common and occurs in approx- possibility of occult chronic disease, such as inflamma-
imately 2% of the adolescent population. Delayed tory bowel disease, which may become apparent ­initially
puberty is defined as the absence of pubertal changes as a delay in the onset of puberty. If the h ­ istory is sug-
over the age of 13 years for girls and over the age of gestive of familial or ­constitutional delayed puberty,
14 years for boys. In general, adolescents have a height- and this is confirmed by physical ­ examination, no
ened awareness of body image and are often preoccu- ­further investigation may be ­necessary. If the ­diagnosis
pied with the normality or otherwise of their pubertal is not clear, the following investigations may need to be
development. Boys in particular may suffer major psy- performed:
chological effects resulting from delayed puberty as • full blood count
they may experience bullying, may be left out of sport- • urea/creatinine and electrolytes
ing teams and may be less generally able to compete • liver function tests
with their peers due to poor muscular development. • CRP, iron studies
The most common causes of delayed puberty are famil- • screening test for coeliac disease (total IgA and
ial or constitutional delay in puberty for which there is tissue transglutaminase antibodies)
often a family history, particularly in the parents, uncles • thyroid function tests
or aunts of a teenage boy. Puberty may also be delayed • chromosomes
in the presence of any chronic illness of childhood or • bone age X-ray
adolescence. The causes of delayed puberty are usually • serum FSH and LH, testosterone or oestradiol
considered on the basis of the serum gonadotrophins • serum prolactin.
(LH/FSH) and are outlined in Table 19.1.1.
Treatment
Diagnosis and management
Indications for treatment of delayed puberty are
Assessment of delayed puberty requires a complete primarily psychological. Induction of pubertal
­history, including a family history of pubertal matura- development in boys through the judicious use of
669
tion patterns. It is important to look carefully for the intramuscular or oral testosterone preparations may
 19.1 ENDOCRINE DISORDERS

be useful in alleviating the psychological stress caused raised gonadotrophin levels. True precocious puberty
by delayed puberty. Pubertal development at a normal is much more common in girls than boys, and girls are
time is also important for peak bone mass accumu- less likely to have an identifiable underlying patho-
lation. Treatment of delayed puberty should be car- logical cause than boys. Girls with this disorder will
ried out only by paediatricians and endocrinologists have accelerated growth and accelerated development
experienced in this area, as excessive administration of breasts and pubic hair. Boys with true precocious
of sex steroids can adversely accelerate bony epiphy- puberty have evidence of enlargement of both testes as
seal m
­ aturation and affect long-term height outcome. well as accelerated linear and genital growth and pubic
hair development. Various intracranial pathologies
(including hypothalamic or pituitary tumours) can
Psychological support and counselling
cause precocious puberty by triggering early ­activation
Psychological support and counselling are an extremely of the hypothalamic–pituitary–gonadal axis.
important part of the management of pubertal delay Gonadotrophin-independent precocious puberty
and in some instances may be all that is required while may be seen with congenital adrenal hyperplasia, adre-
waiting for the onset of spontaneous pubertal devel- nal, testicular or ovarian neoplasms, and tumours that
opment. It is very important to reassure the adolescent secrete non-pituitary gonadotrophin such as human
and their family that they are normal and that appro- ­chorionic gonadotrophin (hCG). The M ­ cCune–Albright
priate pubertal and sexual development will occur or ­syndrome is also a cause of gonadotrophin-independent
can be relatively easily assisted with hormonal inter- precocious puberty.
vention. Such reassurance and support can profoundly If precocious puberty is suspected, referral should
improve an adolescent's self-esteem. be made to a paediatric endocrinologist, who will
organize appropriate investigations. These may include
measurement of serum FSH and LH, testosterone
Clinical example or oestradiol levels, dynamic tests of g­ onadotrophin
secretion such as gonadotrophin-releasing hormone
Andrew was a 15½-year-old boy. His father (GnRH) testing, bone age assessment, and MRI of
was concerned he was growing poorly and
was underdeveloped for his age. Andrew's
the brain and pituitary gland. Treatment of precocious
father had also been a late developer, puberty should be managed by a paediatric endocri-
and was bullied at school and left out of the rugby nologist experienced in this area. Treatment options
team because of his size. He reported that he was still include GnRH agonists, medroxyprogesterone acetate
growing when he left school and became an apprentice or anti-androgens. Consideration for treatment for
mechanic. precocious puberty will include factors such as the age
Further history revealed that Andrew was a healthy
of the child and the rate of progression of the pubertal
young man who had always grown along the 3 rd
percentile, but from 14 years of age his height had fallen
development.
away from the 3 rd percentile line. He was a very keen
sportsman and had always been a very fast runner
but could no longer compete successfully with boys Practical points
his age. Because of this he had recently taken up golf,
which he and his father played together every Saturday. Delayed puberty
Andrew's physical examination confirmed that he was
• Delayed puberty is a common pubertal problem.
completely pre-pubertal, with an otherwise normal physical
• Delayed puberty is defined as absence of pubertal
examination. development in girls older than 13 years and boys older
The most likely diagnosis was constitutional delay in than 14 years.
puberty. Andrew was not distressed at all by his delayed
• Constitutional delay in puberty is the most common
puberty, and his father was reassured when the diagnosis cause, particularly in boys, often with a positive family
was explained. During the next 3 years, Andrew's growth history.
rate increased and he went through a delayed but otherwise
• Chronic disease may cause delayed puberty.
normal puberty, eventually being the same height as his
father.

Conditions resembling precocious puberty

Precocious puberty Premature thelarche
Precocious puberty is an uncommon problem and Isolated breast development, either unilateral or bilat-
occurs much less frequently than delayed puberty. eral, is relatively common in girls under 2 years of age
Precocious puberty is defined as pubertal develop- but may occur at any time throughout childhood. By
ment before age 8 years in girls and 9 years in boys. definition, premature thelarche has no other features
670
True or central precocious puberty is associated with of precocious puberty. All cases should be referred
 Growth and variations of growth 19.1
for assessment by a paediatrician or endocrinologist. and regresses. Rare causes of marked pubertal gyn-
In most cases, observation and follow-up is all that is aecomastia include Klinefelter syndrome, adrenal
required. and gonadal tumours, and drugs such as cimeti-
dine, nifedipine, spironolactone and marijuana use.
Hormonal therapy does not influence the natural
Premature adrenarche
history of pubertal gynaecomastia. If significant
The appearance of isolated pubic hair development breast enlargement is causing psychosocial difficul-
under the age of 8 years in a girl may occur as a variant of ties, it may be ­necessary to refer a teenage boy to
normal but may also be associated with an adrenal dis- a plastic surgeon for consideration for subareolar
order such as a non-classical form of congenital adrenal mastectomy.
hyperplasia. Careful assessment for any associated signs
of virilization, such as clitoral enlargement, hirsutism
or acne, should be performed. The appearance of pubic
Asymmetrical breast development
hair in a boy before the age of 9 years rarely occurs as
a normal variant and should always be investigated. In Asymmetrical breast development can occur in both
all cases of premature pubic hair ­development, referral males and females. In males, it is clearly a variant of
should be made to a p ­ aediatrician or paediatric endo- pubertal gynaecomastia. In females, asymmetry may
crinologist so that appropriate i­nvestigation of adrenal be apparent at the beginning of breast budding or may
androgens can be performed. evolve subsequently through breast development.
It is important to consider an underlying chest
wall or pectoral muscle abnormality. In rare cases, an
Isolated premature menarche
underlying vascular abnormality or lipoma may cause
Girls with this rare condition of unclear aetiology by one breast to appear larger than the other. This can
definition have no other features of pubertal develop- usually be readily determined by a physical examina-
ment. Most girls will have fewer than three episodes tion and confirmed by ultrasonography.
of bleeding and then puberty will eventually occur at In most cases, however, asymmetrical breast devel-
a normal time. Before making the diagnosis of prema- opment is a physiological variant of puberty, and
ture menarche, the specialist must eliminate all other reassurance and monitoring are usually all that is
­
causes of premature oestrogen secretion and/or any required. For self-esteem and cosmetic reasons,
local causes of vaginal bleeding. advice should be given to teenage girls about tem-
porary use of breast prostheses or padded bras to
equalize the breast form. In most situations, the asym-
Pubertal gynaecomastia
metry resolves with full pubertal development. On
Gynaecomastia is very common in adolescent rare o­ ccasions, however, referral to a reconstructive
boys, occurring in 40–70% of 14-year-olds. In most surgeon for breast reduction or augmentation may
instances the breast development is minor, transient need to be considered.

671
 19.2 Thyroid disorders Fergus Cameron, Justin Brown

Normal thyroid function throughout infancy, child- de-iodination of T4 in peripheral tissues. Thyroid
hood and adolescence is essential for a normal hormones bind to a nuclear receptor. T3 binds to
developmental and physiological outcome. Thyroid this receptor with 10 times the affinity of T4. Once
disease is one of the most common groups of endo- bound, thyroid hormones regulate gene tran-
crine disorders in childhood and adolescence, with scription, increasing cytoplasmic proteins, which
approximately 1–2% of all children having a thyroid stimulate mitochondrial activity, thus increasing
disorder at some time. Therefore, knowledge of thy- metabolic rate.
roid disease and its ­management is fundamental to Disorders of thyroid function in childhood can be
paediatric medicine. divided into the following categories:
• hypothyroidism
• hyperthyroidism
• thyroid masses.
Thyroid physiology
The thyroid gland removes iodide from the blood-
stream, combines it with tyrosine and releases
iodinated tyrosine to the peripheral tissues. The
Hypothyroidism
thyroid gland is able to trap iodide and synthe- Congenital
size iodothyronine from 70 days' gestation. Release
Screening for congenital hypothyroidism has been
of ­thyroxine, however, does not occur until 18–20
performed in most developed countries for the
­
weeks' ­gestation. Thyroid gland growth is regulated
past 15–20 years. In Australia, screening for con-
by ­thyroid-stimulating hormone (TSH) released from
genital hypothyroidism, phenylketonuria and cystic
the anterior pituitary gland, which is in turn regu-
fibrosis occurs on day 3–5 of life. Because of such
lated by ­ thyrotropin-regulating hormone (TRH)
screening the clinical picture of ‘cretinism’ (the
released from the hypothalamus. These regulating
later effects of ­congenital hypothyroidism, includ-
hormones are in turn controlled by negative feedback
ing severe i­ntellectual disability) thankfully is now
from tri-iodothyronine (T3), the active metabolite of
rarely seen.
the major thyroid hormone t­ hyroxine (or tetra-iodo-
thyronine, T4).
The thyroid gland is extremely effective at ­trapping Incidence
serum iodide, with a concentration gradient from thyroid
to serum of 30–40-fold. This ­gradient increases in times The incidence of congenital hypothyroidism is 1 in
of iodide deficiency. Once trapped, iodide is oxidized 3000–5000, with some geographical variation.
to iodine and organification occurs. Organification
is the iodination of ­thyroglobulin-bound tyrosyl resi-
Aetiology and genetics
dues to form mono-iodotyrosine (MIT) and di-iodo-
tyrosine (DIT). Some 75% of cases are due to dysgenesis (agenesis,
Organification and iodide oxidation (to iodine) ectopia), 10% to dyshormonogenesis, 5% to hypo-
are catalysed by thyroid peroxidase. Thyroid perox- thalamic–pituitary deficiency (central hypothyroid-
idase couples the iodotyrosines to form iodothyro- ism) and 10% to transient hypothyroidism (iodine
nines within the thyroglobulin molecule, resulting exposure, maternal antithyroid antibodies, etc.).
in T4 and T3. In the absence of iodine deficiency, Although thyroid disease appears to be sporadic
the T4 : T3 synthesis ratio is 10–20 : 1. In adults, in the majority of children born with hypothyroid-
the release rate of T4 to T3 is 3 : 1. Once released, ism, evidence for a genetic component is increas-
both hormones bind to thyroxine-binding globu- ing. Hypothyroidism is familial in up to 2% of cases,
lin (TBG). Some 80% of circulating T3 results from and children with c­ ongenital hypothyroidism have a
672
 THYROID DISORDERS 19.2
higher incidence of associated ­abnormalities (cardiac, Investigation results
renal, hip ­dysplasia) than the general population.
An unconjugated hyperbilirubinaemia (due to gluc-
Studies in mouse models with congenital defects
uronyl transferase deficiency) is common. A raised
of thyroid development have provided the basis for
level of TSH detected on testing of a heel-prick drop
molecular genetic studies in humans with congenital
of blood collected on filter paper on day 3–5 of life is
hypothyroidism. Mutations have been described in
seen in primary hypothyroidism.
a number of genes, resulting in absent, misplaced,
­hypoplastic or unresponsive glands (Table 19.2.1).
In some instances, a specific phenotype can be rec- Management
ognized, and prognosis is affected. For example, Confirmatory investigations are needed if the screen-
in individuals with the NKX2.1 mutation, neuro- ing tests suggest an abnormality: repeat T4 and TSH;
logical outcome is poor despite early thyroxine thyroid scan (showing absent, lingual or increased
treatment. uptake of radioisotope), X-ray distal ­femoral epiph-
Hypothyroid patients with normally located and ysis (absence implying prolonged/prenatal hypo-
normally sized glands have defects in thyroid hor- thyroidism), and assessment and imaging of the
mone biosynthesis. Recessive mutations in thy- pituitary gland if indicated. Treatment involves
roglobulin, thyroid peroxidase, pendrin (causing commencement of therapy (thyroxine replacement
­
Pendred syndrome – sensorineural deafness and at 8–10 μg/kg daily). Thyroid imaging results for
hypothyroidism) and sodium/iodide symporter congenital hypothyroidism of varying causes are
­
(NIS) genes have been described. Mutations in the shown in Figure 19.2.1.
TRH receptor gene, TSH β subunit and transcrip-
tion factors regulating pituitary development have Prognosis
also been described in some individuals with central
hypothyroidism. Normal intellectual and physical development is likely
if treatment is commenced promptly and monitored
Clinical picture closely. Overtreatment may result in craniosynostosis.
Often the condition is subclinical and is detected on
Acquired
routine screening. Clinical features that should be
looked for are jaundice, dry skin, a hoarse cry, puffy Acquired hypothyroidism in the child or adolescent
face, prominent tongue, listlessness, umbilical hernia, is relatively uncommon. In iodine-sufficient regions
hypothermia, bradycardia and failure to thrive. of the world the most common cause is autoimmune

Table 19.2.1 Mutations in genes involved in thyroid development resulting in congenital hypothyroidism

Gene Thyroid gland imaging Clinical features Genetics Comments

PAX-8 Hypoplastic and Mild to moderate CH Autosomal dominant

cystic

TTF-2 Thyroid agenesis Developmental delay, cleft Familial Rare ‘Bamforth syndrome’
palate, choanal atresia,
spiky hair

NKX2.1/TTF-1 Normal, hypoplastic, CH, lung disease, Sporadic; heterozygous Poor neurological outcome
agenesis hypotonia, loss-of-function despite thyroid
developmental delay and mutations replacement
choreoathetosis

TSH-R Normal to severely Compensated Recessive, inactivating Heterozygous carriers may

hypoplastic; normally hypothyroidism to mutations in compound be relatively common;
located severe CH heterozygotes activating mutations
cause congenital
hyperthyroidism

CH, congenital hypothyroidism; TSH-R, TSH receptor; TTF, thyroid transcription factor.
673
 19.2 ENDOCRINE DISORDERS

A B

Fig. 19.2.1 Thyroid uptake scan appearances in congenital hypothyroidism. (A) Thyroid agenesis. No functioning thyroid tissue present
in the neck or in the usual ectopic sites. (B) Dyshormonogenesis. The radioangiogram reveals relatively increased thyroid perfusion.
The uptake of pertechnetate in 20 min is 14% (normal = 2–5%). The thyroid scan reveals a diffuse goitre normally located in the neck.
(C) Lingual thyroid. There is no evidence of perfused thyroid tissue in the neck. The thyroid scan reveals a prominent midline lingual thyroid.
The uptake of pertechnetate in 20 min is 1% (normal = 2–5%). (D) Normal thyroid. The radioangiogram of the head, neck and upper torso
is unremarkable. The uptake of pertechnetate in 20 min is 5% (normal = 2–5%). The thyroid scan reveals a normally located bilobed gland.

thyroiditis. Accordingly, acquired hypothyroidism is Aetiology

seen twice as commonly in females as in males, usually
The causes in order of frequency are as follows: primary
manifesting in early puberty.
hypothyroidism – chronic lymphocytic, autoimmune
(Hashimoto) thyroiditis, late-appearing congenital
Prevalence
dyshormonogenesis, exogenous factors (e.g. high-dose
Between the ages of 1 and 18 years, the prevalence is iodine exposure (Wolff–Chaikoff effect), radiation) and
1.2%. Acquired hypothyroidism is rare prior to 4 years severe iodine deficiency; and central h
­ ypothyroidism –
of age. congenital and acquired hypopituitarism.
674
 THYROID DISORDERS 19.2
Clinical picture
Hyperthyroidism
The most common presentation is growth retardation
and goitre. In addition, the triad of short stature, obe- Congenital
sity and mental dullness indicates hypothyroidism until This is always due to maternal thyrotoxicosis and is
proven otherwise. Growth impairment usually affects a rare clinical event. However, if unrecognized and
mainly the limbs so that body proportions predomi- untreated, neonatal hyperthyroidism may be fatal.
nantly remain infantile. Other features include hypother-
mia, bradycardia, slow reflex relaxation, constipation, Incidence
dry hair and skin, pallor, facial puffiness (‘myxoedema’)
and dental delay. The onset is often insidious, with delays Maternal thyrotoxicosis is uncommon (1–2 cases per
of up to 4–5 years being reported between the onset of 1000 pregnancies). Neonatal disease occurs in 1 per 70
growth retardation and the diagnosis of hypothyroid- cases of pregnancies affected by thyrotoxicosis.
ism. Although delayed puberty usually occurs, some
cases of precocious puberty have been reported. Aetiology
Autoimmune thyroiditis may be associated with Neonatal hyperthyroidism is the result of the transpla-
other autoimmune diseases (autoimmune polyglan- cental passage of TSH receptor-stimulating antibod-
dular ­syndromes) such as type 1 diabetes, autoim- ies from a mother with either active or inactive Graves
mune ­ adrenalitis (Addison disease), vitiligo and disease. Measurement of maternal antibody status,
pernicious anaemia. Occasionally, autoimmune rather than thyroxine levels, is predictive of the likeli-
­hypothyroidism can be preceded by a period of tran- hood of neonatal hyperthyroidism.
sient hyperthyroidism.

Investigation results
Goitre (detected either clinically or sonographically) Clinical example
is common in acquired hypothyroidism. Blood tests
show a low circulating T4 and (usually) a high circulat- Sarah had been struggling at school ever since
ing TSH level. Bone age is delayed and there may be she started year 7. At the age of 13 years, her
positive thyroid autoantibodies (in autoimmune thy- parents had become concerned that she was
having difficulty settling into her new school
roiditis). There is patchy uptake of isotope on thyroid
as she was always complaining of feeling tired and having
scan (in autoimmune thyroiditis). Hypothalamic or ‘tummy pains’. Sarah's parents were at a loss to explain
pituitary anomalies may be seen on computed tomog- why she was behaving this way as she was a good student
raphy (CT) or magnetic resonance imaging (MRI) at primary school and had lots of friends. More recently
(in tertiary or secondary disease). Sarah's parents had noted that her weight had increased
dramatically (they attributed this to her lack of activity, as
she didn't seem to eat all that much), so much so that she
Management now had a very ‘fat’ neck. She was also complaining of
Replacement thyroxine (usually 50–100 μg/day in a feeling cold all the time and was constantly wearing extra
clothes even when the weather was warm. Her parents
single dose) is required. An appropriate individual
were concerned that she had a body image problem
dose is determined by measuring serum TSH at 6 or as a consequence of her recent weight gain. The school
more weeks after commencing therapy. counsellor felt that Sarah might be depressed and her
parents were most concerned.
On examination Sarah was moderately overweight with
Prognosis cool hands and she had a resting pulse rate of 50 bpm. She
Severely hypothyroid children often show dramatic had dry hair and skin. She had a smooth, uniformly enlarged
thyroid gland. Her reflexes showed a markedly delayed
clinical changes with treatment. These include: weight
relaxation phase.
loss, rapid growth, loss of primary teeth, some tran- Investigations revealed that Sarah had a serum TSH
sient hair loss and increased energy/alertness. The level of 35 IU/mL (high) associated with a T4 of 5 nmol/L
long-term neurodevelopmental outcome is good, (low). Her bone age was equivalent to that of 10 years and
given that the rapid growth phase of the brain in a plain X-ray of her abdomen showed faecal loading. Her
the first 2 years of life has usually been protected. antithyroid microsomal antibody titre was positive.
Despite short-term rapid catch-up growth, restora- Sarah was commenced on 100 μg thyroxine per day.
Within 2 weeks she was reporting much improved energy
tion of full growth potential often does not occur,
levels and affect. At 1-month review she had lost 5 kg in
because of rapid advancement of bone age in the weight, her school performance had improved and her goitre
first 18 months of treatment. Long-term treatment is was showing some signs of shrinkage. 675
­usually required.
 19.2 ENDOCRINE DISORDERS

Clinical picture toxic thyroid nodule (rare). There is often a family his-
tory of autoimmune thyroid disease (either Graves or
Neonates may present with any of the following: irritabil-
Hashimoto disease). The primary defect is the presence
ity, poor weight gain, tachycardia, cardiac arrhythmias,
of stimulating autoantibodies (thyroid receptor anti-
flushing, hypertension, goitre, exomphalos, jaundice and
bodies) that mimic the action of TSH. Overstimulation
hepatosplenomegaly. Although presentation soon after
of the TSH receptor leads to thyroid growth and excess
birth is more common, if the mother has been taking
thyroxine production. There is often an associated oph-
antithyroid drugs, presentation may be delayed until day
thalmopathy due to the deposition of proteoglycans in
8–9 after birth, when the antithyroid medication has
the extraocular muscles and retro-orbital spaces.
been eliminated from the neonate's circulation.

Clinical picture
Investigation results
The clinical features of hyperthyroidism result from
High circulating T4 or T3 levels and low TSH levels are sympathetic drive causing a hypermetabolic state.
detected in the neonatal blood sample. Many of the florid signs of thyrotoxicosis that are seen
in adults are less pronounced in children. Symptoms
Management include deteriorating school performance, weakness/
fatigue, restlessness/sleeplessness, polyuria, hunger,
Immediately after diagnosis, sedation and treatment heat intolerance, excessive sweating, anxiety and diar-
with either beta-blockade or digoxin may be required. rhoea and weight loss. Clinical signs include: goitre or
Subsequent treatment with antithyroid medication localized thyroid mass, tremor, tachycardia and brisk
(carbimazole, methimazole) is usually required. A ther- reflexes. Approximately 30% of children will have asso-
apeutic response should be seen within 24–36 hours ciated proptosis and other signs of thyroidal ophthal-
after commencing treatment. Owing to concerns mopathy (lid lag, lid retraction and ophthalmoplegia).
regarding hepatotoxicity, first-line treatment with pro-
pylthiouracil in childhood is no longer recommended.
Investigation results
Suppressed serum TSH levels are seen and are associated
Prognosis
with increased T4 or T3 levels. There will also be raised
Mortality rates of up to 25% have been reported. The levels of thyroid autoantibodies (TSH receptor antibody-
half-life of thyroid-stimulating antibodies in the fetal positive in Graves disease). The bone age is advanced
circulation is approximately 12 days; however, the clin- and there is sonographic evidence of thyromegaly.
ical course may extend for a period of up to 12 weeks. Generalized and localized increased uptake of isotope is
seen in Graves disease and toxic adenoma respectively.

Acquired
Management
Hyperthyroidism in childhood and adolescence is less
common than either euthyroid goitre or hypothyroid- In the setting of autoimmune hyperthyroidism there
ism. As with acquired hypothyroidism, it is most com- are three treatment options. The first of these, anti-
monly due to autoimmune disease and is usually seen thyroid medication, is the most commonly used.
in young adolescent females. Carbimazole and methimazole have traditionally
been used most commonly in Australia and Europe,
whereas propylthiouracil has been more commonly
Incidence used in North America. Propylthiouracil is no longer
Females are affected 6–8 times more commonly than recommended as first-line treatment because of the
males. Some ethnic groups (such as Asian females) risk of severe hepatotoxicity. Both types of medication
have a greater reported incidence of autoimmune block organification and are similarly efficacious, with
hyperthyroidism. comparable side-effect profiles. Beta-blockade (with
propranolol) may also be used in the first 2–4 weeks
of therapy to gain symptom control. This is contrain-
Aetiology
dicated in children who suffer from asthma. Treatment
Autoimmune hyperthyroidism (Graves disease) is with organification blocking drugs is continued for
the most common form of acquired hyperthyroidism 2 years in the first instance. Other treatment options
in childhood and adolescence. Less frequent causes include thyroidectomy (subtotal or total) and radioac-
include the acute toxic phase of autoimmune hypo- tive iodine. In the setting of toxic adenoma, surgery is
676
thyroidism (Hashimoto disease; hashitoxicosis) and a usually the preferred treatment option.
 THYROID DISORDERS 19.2
Prognosis
Thyroid masses
After 2 years of medical therapy, approximately
20–50% of patients can be expected to enter sponta- Goitre
neous remission, with resolution of thyroid autoanti- The commonest cause of goitre on a worldwide basis
body status. Among those patients who do not remit remains iodine deficiency. In developed countries this
spontaneously, long-term drug therapy is both safe had become rare until recent times, with the iodization
and effective. In the advent of poor compliance with of table salt and some infant milks. Recently, iodine
medical therapy, lack of control or increasing thyro- deficiency has been reported again in Australian pop-
megaly, a second treatment option – surgical subto- ulations, presumably due to low-salt diets encouraged
tal or complete thyroidectomy – is considered. This for cardiovascular health reasons.
results in 20% of patients becoming euthyroid, 50% of
patients becoming hypothyroid and 30% of patients
Incidence
becoming thyrotoxic in the long term. Other paedi-
atric and adult centres use a third treatment option, Goitres or diffuse enlargement of the thyroid gland
that of radioactive iodine. This treatment results in occur in 4–5% of all children. They are more common
total thyroid ablation and requires subsequent lifelong in girls during puberty and are often not detected.
­thyroxine replacement therapy.
Aetiology
In Australia the main causes in order of frequency
are: Hashimoto thyroiditis (majority are euthyroid),
Graves disease, mild dyshormonogenesis, tumour
Clinical example
(benign/malignant), acute/subacute thyroiditis and
Tina, aged 15, had noticed increasing iodine deficiency. Foods that inhibit thyroxine synthe-
anxiety levels recently. She was quite bright sis and can lead to goitre (goitrogens) include cabbage,
academically and had set high standards for soybeans and cassava.
herself at school. Her parents were concerned
that her anxiety was associated with some recent difficulties
Clinical picture
in concentrating during classes. Her teachers complained
that she ‘fidgeted’ all the time and was quite restless. Despite Most often the goitre is asymptomatic and is f­ requently
a healthy appetite (‘she eats more than anyone else in the detected on routine examination undertaken for other
family’) Tina had been losing weight and had frequent loose
reasons. Thyroid hypofunction or hyperfunction will
bowel actions. Her mother also reported that, despite it
being winter, Tina refused to wear appropriate cold weather
present with the signs and symptoms described above.
clothing, preferring a T-shirt most of the time. Occasionally, pressure symptoms related to the enlarged
On examination, Tina appeared quite anxious and had thyroid (dysphagia, stridor or neck discomfort) may be
very prominent eyes (proptosis). She had difficulty in sitting the presenting feature. Thyroidal tenderness is seen in
still on the examination couch and squirmed around quite a acute/subacute thyroiditis. Regional lymphadenopathy
lot. Her resting pulse was 110 bpm and she had a fine tremor associated with a ­goitre or thyroid nodule is suggestive
when her hands were held out. Her palms were very sweaty.
of malignancy and is an ominous sign.
She had a firm, smooth goitre with an audible bruit. Her
reflexes were very brisk and she had difficulty standing from a
squatting position. Investigation results
A provisional diagnosis of Graves disease was made. This
was confirmed by finding that Tina's serum TSH levels were Sonography, serum thyroid function tests and serum
unrecordably low in the face of a T4 level of 52 nmol/L (high). thyroid antibody levels will distinguish most causes
Her anti-TSH receptor antibody titre was raised. Thyroid of goitre. Fasting urinary iodine levels will also help
ultrasonography demonstrated a uniformly enlarged thyroid
to define iodine status. Thyroid scanning will show
with no focal changes.
Tina was commenced initially on both carbimazole increased uptake with mild dyshormonogenesis and
and propranolol. Her symptoms had largely abated patchy distribution in Hashimoto thyroiditis.
within 3 weeks and her propranolol was ceased at this
time. Ophthalmological review confirmed the presence of
proptosis, with no other thyroidal eye signs being present. Management
Over the following year Tina's goitre diminished in size; Smoothly enlarged goitres with normal thyroid func-
however, her proptosis remained unchanged. She was
tion can be managed simply by observation and iodine
initially treated with carbimazole for 2 years. At this time she
was still TSH receptor antibody-positive and it was decided to supplementation if required. Goitres with functional
continue treatment for a further 2 years. consequences will require either thyroxine supplemen-
677
tation or suppressive medication.
 19.2 ENDOCRINE DISORDERS

Prognosis Investigations
This depends on the cause of the goitre. As most cases Nodules may be detected both sonographically and by
of asymptomatic goitre result in no disturbance of thyroid scanning. The finding of multiple hot nodules
thyroid function, the prognosis is usually good. associated with positive thyroid antibody titres and/
or disturbed thyroid function is against a diagnosis of
malignancy. Alternatively, a single cold nodule with or
Thyroid nodules without serum calcitonin levels (associated with med-
Nodules within the thyroid gland are palpable, local- ullary carcinomas) is suggestive of malignancy. Fine-
ized swellings. They may be single or multiple. The needle aspiration is not widely used in the diagnosis of
Chernobyl nuclear reactor disaster in 1986 led to a thyroid nodules in children.
markedly increased incidence of benign and malig-
nant thyroid nodules in children from the surrounding
iodine-deficient areas. Management
If there is any doubt as to the nature of any thyroid
Incidence nodule it is appropriate to proceed to open biopsy.
Solitary benign nodules are usually excised. Papillary
Fewer than 2% of children have thyroid nodules. Of thyroid cancers are treated with total thyroid exci-
these, approximately 2% are malignant. If the nodule sion, with subsequent radioactive iodine therapy if
is single the risk of malignancy increases to 30–40%, metastases are thought to be present. Medullary thy-
higher than in adults. roid cancers are unresponsive to radioactive iodine
and early total thyroidectomy remains the treatment
of choice. In individuals with RET proto-oncogene
Aetiology
mutations from families with a strong history of
Benign nodules include cysts, cystic adenomas and medullary carcinomas, prophylactic thyroidectomy is
variations of Hashimoto thyroiditis. Malignant nod- considered.
ules are carcinomas and occur in the following order:
papillary/mixed, follicular, medullary and anaplastic.
In one series of children with thyroid cancers reported Prognosis
in the 1950s, 80% had a history of having received
head/neck radiotherapy. However, head/neck irradi- Most thyroid nodules are benign and have an excellent
ation is now used less commonly and the aetiology prognosis. In the case of papillary carcinomas, serial
of most thyroid cancers remains obscure. Radiation- thyroid scans for the first 3 years after surgery will
exposed children need close follow-up, and regular detect any residual thyroid tissue or tumour r­ ecurrence.
ultrasound surveillance substantially increases the In patients suffering from medullary c­ arcinomas, serial
detection of thyroid malignancy. Medullary carcino- measures of serum calcitonin levels are the monitoring
mas may be sporadic, familial (autosomal dominant strategy of choice.
mode of inheritance) or part of a multiple endocrine
neoplasia (MEN2) complex. Patients with MEN2
have been found to have mutations in the RET
proto-oncogene. Practical points

• Normal thyroid function is essential for normal growth and

Clinical picture development.
The most common presentation is the lobular, irregular • Thyroid disorders are common and affect up to 2% of
children and adolescents.
thyroid gland seen in Hashimoto thyroiditis. Nodules
• Neonatal screening for congenital hypothyroidism
are usually asymptomatic and are often detected coin- allows early detection and treatment, resulting in normal
cidentally upon routine examination. Rarely, nodules development in the majority of affected infants.
may be hyperfunctional (‘toxic adenoma’). Medullary • Symptoms of acquired hypothyroidism may be subtle in
carcinomas may be associated with phaeochromo- childhood and adolescence. Short stature may be the only
cytoma (in later life) and parathyroid hyperplasia presenting feature of hypothyroidism.
(MEN2A), or multiple mucosal n ­ euromas, ­Marfan-like • Hyperthyroidism is much less common than
hypothyroidism and non-specific associated symptoms
habitus and phaeochromocytoma (MEN2B). It is very
may result in delay in diagnosis.
rare for children with MEN2 to present with c­ linical • Thyroid malignancy in isolated thyroid nodules is much
disease. They are usually detected as part of a kindred more common in children than in adults.
678
subjected to genetic screening.
 THYROID DISORDERS 19.2
physical development, and the potential for malig-
Summary nancy in thyroid nodules, a ­ clinical awareness of
Disorders of the thyroid gland can have many manifes- potential thyroid problems in paediatrics is essential.
tations: hypofunction, hyperfunction, p­ ressure symp- Once detected, most thyroid problems can be success-
toms and incidental tumours. Given the importance fully managed, with excellent clinical outcomes.
of normal thyroid function for both ­neurological and

679
 19.3 The child of uncertain sex
Jan Fairchild

Disorders of sexual development are congenital In males, the presence of the sex-determining region
­conditions in which the development of chromosomal, on the Y chromosome (SRY gene) directs the bipoten-
gonadal or phenotypic sex is atypical. This includes tial gonad to become a testis. At least four other genes
infants with a genital appearance that does not permit are also required for normal testicular development. By
gender assignment: 7–8 weeks the testis has recognizable tubules and starts
• bilateral non-palpable testes producing androgens, including testosterone from the
• perineal hypospadias with a bifid scrotum Leydig cells and müllerian-inhibiting substance (MIS)
• hypospadias and unilateral non-palpable gonad from the Sertoli cells. Circulating hormone levels are
• clitoromegaly low and masculinization of the internal genital ducts
• posterior labial fusion occurs by locally acting (exocrine) secretion of these
• a phenotypical female with a palpable gonad hormones down the wolffian duct.
• and those with discordant genitalia and sex High levels of testosterone promote the ipsilat-
chromosomes. eral development of the wolffian duct to become the
The birth of a child with a disorder of sexual develop- ­epididymis, vas deferens and seminal vesicle. High ­levels
ment presents a psychosocial crisis for the family and of MIS lead to ipsilateral müllerian duct regression.
may indicate an underlying medical condition such as This process occurs during a critical period between
congenital adrenal hyperplasia, which could be life- 8 and 12 weeks. The Leydig cells also produce a relaxin-
threatening if undiagnosed and untreated. like factor that, together with MIS and androgens,
Disorders of sexual development (DSDs) are masculinizes the gubernaculum. The gubernaculum
rare (1 in 4500), often complex, and always require holds the testis near the inguinal ligament during early
urgent expert consultation. Optimal care requires an development and from 25 weeks it begins to e­ longate,
­experienced multidisciplinary team. steering the testis towards the scrotum.

Normal sexual differentiation Clinical example

An understanding of normal sexual differentiation is
essential in the evaluation of the child with a disor- A healthy, full-term infant was born with
ambiguous genitalia. On examination there was
der of sexual development. Normal sexual develop-
an enlarged clitoris (2 cm in length), posterior
ment in the embryo consists of three related sequential fusion of the labia, with a single opening visible,
processes: and no gonads were palpable. The genitalia were noted to
1. Establishment of chromosomal sex at fertilization, be hyperpigmented. There was no history of consanguinity
with XY as male and XX as female but a previous male sibling had died at 2 weeks of age after
2. Determination of gonadal sex, when the a vomiting illness.
Initial investigations confirmed that the baby's
bipotential gonad develops into a testis or an
chromosomes were 46,XX and pelvic ultrasonography
ovary showed the presence of a normal uterus and ovaries.
3. Development of phenotypic sex, as a result of The 17-hydroxyprogesterone level at 48 hours of age was
gonadal differentiation and gonadal hormone markedly increased, confirming the diagnosis of congenital
production. adrenal hyperplasia due to 21-hydroxylase deficiency.
Treatment with hydrocortisone was commenced. Daily
electrolytes were normal until the 6th day of life, when
Internal genitalia hyperkalaemia developed, confirming the salt-wasting
form of the condition. Fludrocortisone therapy was then
Up until about 7 weeks, male and female embryos added. The child was referred to a paediatric surgeon for
develop in an identical fashion, with bipotential gonads consideration of corrective genital surgery. She will require
and both wolffian and müllerian internal ­genital ducts lifelong replacement therapy and monitoring.
680 present (Fig. 19.3.1).
 THE CHILD OF UNCERTAIN SEX 19.3
External genitalia
The hyperpigmentation was due to the adrenocorticotrophic
hormone (ACTH) excess and resolved with adequate Up until about 8 weeks, the external genitalia of male
replacement therapy. It was likely that the previous male sibling and female embryos also have an identical appearance.
had also had the condition, as it is inherited as an autosomal Both sexes have a genital tubercle, two genital swell-
recessive trait. The genitalia of affected males are usually normal ings and two genital folds (Fig. 19.3.2).
at birth apart from some hyperpigmentation, and affected male In males, between 8 and 12 weeks, androgen
infants typically present with a salt-wasting crisis in the first few
action on the external genitalia results in the devel-
weeks of life. It is often confused with pyloric stenosis, which also
presents at this age with vomiting and dehydration. opment of normal male genitalia. Circulating lev-
els of testosterone are insufficient for this action but
testosterone is converted in the periphery to dihy-
drotestosterone (DHT) by the enzyme 5α-reductase.
In females, the absence of testosterone and MIS Dihydrotestosterone binds to the androgen recep-
leads to wolffian duct regression and müllerian duct tors much more strongly than testosterone, thereby
preservation. The müllerian ducts develop into the amplifying its effect. The genital tubercle devel-
uterus, fallopian tubes and upper vagina. ops into the glans penis, the genital swellings fuse

Internal genitalia

Indifferent gonad
Müllerian ducts
Wolffian ducts

SRY gene present 6th week SRY gene absent

(male) (female)
Indifferent gonads
and internal genitalia

Gubernaculum

12th–15th week

Development of
female internal genitalia

25th week to term

Transinguinal testicular descent

Fig. 19.3.1 Normal prenatal development: internal genitalia. 681

 19.3 ENDOCRINE DISORDERS

External genitalia

Indifferent stage

Genital tubercle

Labioscrotal folds

Cloacal membrane

8th week

Male Female
Genital tubercle
forms phallus
Glans clitoris
Urethral plate
canalizes to Labia minora
form urethra
Labia majora
Labioscrotal folds
fuse to form scrotum

11th week 11th week

Clitoris
Urethral orifice

Hymen

12th week 12th week

Fig. 19.3.2 Normal prenatal development: external genitalia.

to form the s­ crotum, and the genital folds elongate

and fuse to become the shaft of the penis and the Evaluation of the child with a
penile urethra. The prostate forms in the wall of the disorder of sexual development
urogenital sinus. With the exception of the phallus,
circulating androgens masculinize the external gen- The initial evaluation of the child with a disorder of
italia only during a critical period between 8 and sexual development should include a history, physical
12 weeks. examination, urgent karyotype, ultrasound imaging of
In females, in the absence of androgen, the genital the internal anatomy, and assessment of adrenal and
tubercle forms the glans clitoris and the short female gonadal function.
urethra. The genital swellings remain unfused and
History
become the labia majora. The genital folds become
the labia minora and the vaginal plate, a thickening of A careful history should include:
682
the posterior wall of the urogenital sinus, canalizes to • prenatal exposure to androgens
form the lower vagina. • maternal virilization during pregnancy
 THE CHILD OF UNCERTAIN SEX 19.3
• family history of females who are childless Initial investigations
or have amenorrhoea (complete androgen
The initial investigations that should be undertaken are:
insensitivity)
• urgent karyotype, including fluorescence in situ
• family history of unexplained infant deaths hybridization (FISH) with SRY probe – this permits
(congenital adrenal hyperplasia)
classification of the infant into one of three diagnostic
• consanguinity. categories and determines further evaluation
• ultrasonography to determine the presence of
gonads, uterus and vagina
Physical examination
• investigations to exclude congenital adrenal
The physical examination should include: hyperplasia:
• careful inspection of the external genitalia and • serum electrolytes and blood glucose series
palpation to determine the presence, location and • serum 17-hydroxyprogesterone and other adrenal
symmetry of the gonads steroids.
• if both gonads are palpable and symmetrical they
are almost always testes Further evaluation
• gonadal asymmetry implies one testis present, This will be guided by the initial investigations and
suggesting a mixed chromosomal pattern may include:
• if both gonads are impalpable, the gonadal and • evaluation of adrenal function with an ACTH stimul­
duct status is unknown. ation test and assessment of urinary steroid profile
• standardized measurement of the phallus • evaluation of gonadal function with MIS,
• a normal term male infant has a stretched penile gonadotrophins, sex steroids and a human chorionic
length of ≥ 2.5 cm gonadotrophin (hCG) stimulation test to confirm a
• a normal term female infant has a clitoral length normal rise in gonadal hormones with stimulation,
≤ 9 mm with the testosterone/DHT ratio reflecting
• general examination looking for: 5α-reductase activity
• dysmorphic features or non-genital abnormalities • surgical procedures: genital skin biopsies for androgen
that may point to a specific disorder receptor assay, panendoscopy and/or laparotomy to
• hyperpigmentation and/or systemic illness delineate internal genitalia ± gonadal biopsy.
which may suggest congenital adrenal
hyperplasia.
Practical points

Initial evaluation of the child with a disorder of sexual

Clinical example development
• History: androgen exposure, family history of DSD or infant
A full-term infant with normal birth weight (3.1 kg) deaths, consanguinity.
was noted to have a small penis (stretched • Examination: determine the presence of palpable gonads,
penile length 1.5 cm, normal > 2.5 cm) and hyperpigmentation, systemic illness, non-genital abnormalities.
undescended testes. Karyotype was 46,XY. • Investigations: include an urgent karyotype, assessment
The infant had had two episodes of hypoglycaemia treated of adrenal secretion, ultrasonography to assess internal
with intravenous dextrose and on general examination was anatomy.
noted to have a small cleft in the palate. Hypoglycaemia • Assignment to one of the three diagnostic categories will
is unusual in a full-term infant of normal birth weight, and determine further evaluation: virilized XX, undervirilized XY
in the presence of a midline defect raises the possibility of or mixed chromosome pattern.
hypopituitarism. A diagnostic blood sample taken at the time
of the hypoglycaemia revealed low levels of cortisol, growth
hormone and free thyroxine, confirming the diagnosis. The
baby was commenced on hydrocortisone and thyroxine Diagnostic categories for
with resolution of the hypoglycaemia. He was given a short
course of testosterone at 6 months of age, which resulted in
disorders of sexual development
an increase in his penile length to 2.5 cm. Growth hormone The results of the karyotype, in particular the sex chro-
therapy was commenced when his growth rate slowed at 12 mosomes, will allow the infant to be classified into one
months of age. of three diagnostic categories which will determine
Micropenis and cryptorchidism can occur with either
gonadotrophin deficiency or growth hormone deficiency and
further evaluation:
is a useful clinical sign of congenital hypopituitarism in male • virilized XX
infants. • undervirilized XY 683
• mixed chromosome pattern.
 19.3 ENDOCRINE DISORDERS

Virilized XX
In the virilized XX child, the gonads are ovaries
and the internal genitalia are female; therefore no
gonads are palpable (Fig. 19.3.3). The external gen-
italia are virilized to a variable degree, from mild
clitoromegaly to complete labial fusion with ure-
thral tubularization to the tip of the enlarged phal-
lus (Fig. 19.3.4). If the exposure occurred after
12 weeks there will be isolated clitoromegaly with-
out labial fusion.
Causes of the virilized XX state may be:
• androgen excess from the fetal adrenals:
• congenital adrenal hyperplasia (most common
cause)
• androgen excess from the mother:
• maternal ingestion of androgens
• androgen-producing tumour
• placental aromatase deficiency.
Fig. 19.3.4 Ambiguous genitalia of a female infant with
congenital adrenal hyperplasia associated with salt-wasting.

A Urinary bladder Undervirilized XY

The undervirilized XY child usually presents with a
small phallus, posterior hypospadias, poorly d
­ eveloped,
bifid scrotum and testicular maldescent.
The causes of the undervirilized XY state may be:
• inadequate androgen production:
Normal Rectum • hypoplastic testes (luteinizing hormone (LH)
clitoris deficiency)
Vagina • dysplastic testes
• testosterone synthesis defects
• inability to convert testosterone to DHT
Urethra (5α-reductase deficiency)
• impaired response to androgen:
B Normal uterus Normal • androgen insensitivity syndrome.
and tube ovary

Clinical example

A 16-year-old girl presented for investigation

of primary amenorrhea. On examination she
Enlarged was found to be a tall girl for her family. She
clitoris had breast development at stage 5 but sparse
Persistent pubic hair (stage 2–3) and no axillary hair. She also had
urogenital an inguinal mass, which was occasionally painful when
sinus knocked during sport. Investigations revealed a 46,XY
Urogenital karyotype, no uterus on pelvic ultrasonography and
opening serum levels of testosterone characteristic of normal men.
A diagnosis of complete androgen insensitivity was made.
Fig. 19.3.3 Schematic illustration of normal and ambiguous Gonadectomy was performed as there is a high incidence of
female genitalia as in congenital adrenal hyperplasia. Note the germ cell cancer and oestrogen replacement therapy was
urogenital sinus leading to a single opening and the enlarged commenced. Psychological support was important in helping
684 clitoris induced by androgens. (Adapted from Moore and her come to terms with the diagnosis.
Persaud, 1993.)
 THE CHILD OF UNCERTAIN SEX 19.3
Mixed chromosomal pattern be handled sensitively. Every effort should be made to
encourage the parents to bond with their baby. Gender
Ovotesticular disorder of sexual development
assignment must be avoided before expert evaluation.
In ovotesticular DSD, both testicular and ovarian tissues The parents should be honestly informed that the sex
coexist. The gonads are usually ovary and t­ estis, or ovary their baby is meant to be is not yet known, but reas-
and ovotestis. The chromosomes are usually 46,XX, sured that this will be determined as soon as possible.
although 46,XY mosaicism can occur. Asymmetry of Instruct all staff to refer to the infant as ‘your baby’, not
the gonads, internal and external genitalia is the hall- he, she or it. The parents will require guidance as to how
mark of this condition. to deal with family and friends, and the support of an
experienced social worker or psychologist is invaluable.
Mixed gonadal dysgenesis The parents should be advised not to name the baby or
register the birth until sex assignment has been decided.
In mixed gonadal dysgenesis there is also gonadal
asymmetry with a testis on one side and a streak
gonad on the other. The testis may be dysgenetic and
Congenital adrenal hyperplasia
the streak gonad usually contains ovarian stroma The urgent medical issue is the exclusion of congenital
without oocytes. The chromosomes are commonly adrenal hyperplasia and the attendant risk of adrenal
45,XO/46,XY, and these infants may have the pheno- crisis. Congenital adrenal hyperplasia is the most com-
typic features of Turner syndrome, but other mosaic mon cause of XX virilization and one of the causes
patterns can occur. The risk of gonadoblastoma is of XY undervirilization. Serum electrolytes and blood
high in dysgenetic testes and gonadectomy in the first glucose should be monitored closely and serum sent
decade of life is recommended. for urgent measurement of 17-hydroxyprogesterone
and other adrenal steroids.
DSD with unambiguous genitalia Congenital adrenal hyperplasia refers to a group
of autosomal recessive disorders resulting from the
It is important to note that some patients with DSD
deficiency of one of the five enzymes required for the
have unambiguous genitalia. These patients have com-
synthesis of cortisol in the adrenal cortex. The most
plete sex reversal with a phenotype the reverse of what
common enzyme deficiency is 21-hydroxylase defi-
would be expected from their genotype. Examples of
ciency, accounting for more than 90% of cases. The
this would be an XY child with complete gonadal dys-
deficiency of cortisol results in ACTH-mediated adre-
genesis or complete androgen insensitivity syndrome.
nal hypertrophy and excessive production of corti-
DSD may be missed if the diagnosis of hypospadias
sol precursors, which are diverted to the synthesis of
is made without due care. This diagnosis should never
androgens. Concomitant aldosterone deficiency leads
be made without full investigations, unless both testes
to salt-wasting in 75% of cases.
are descended in a fused scrotum.
Symptoms and signs of a salt-wasting adrenal crisis
include vomiting, diarrhoea, hypovolaemia, hypona-
traemia with hyperkalaemia, hypoglycaemia and car-
Management diovascular collapse, and can occur within the first few
The birth of a child with a disorder of sexual develop- days to weeks of life. If symptoms or signs of adrenal
ment presents a unique set of challenging and often crisis are present, stress doses of hydrocortisone and
difficult management issues. A multidisciplinary team intravenous fluid therapy with normal saline and 5%
approach involving the paediatrician, paediatric endo- dextrose should be started immediately.
crinologist, surgeon, geneticist, psychologist, social
worker and adolescent gynaecologist is required for
optimal management. Practical points

Initial management Management goals for the child with a disorder of sexual
development
The initial management of the child with a disorder • Gender assignment must be avoided before expert
of sexual development requires attention to medical evaluation.
and psychosocial issues. Evaluation of the child must • An accurate and expeditious diagnosis is essential – and
be carried out urgently, so that a decision about the requires urgent expert consultation.
sex of rearing can be made as quickly as possible and • Rational sex assignment is important.
life-threatening medical conditions can be identified. • Therapy is directed towards achieving successful sex
assignment.
Urgent expert consultation should always be sought.
• Psychological support for the family is required.
The birth of a child with a disorder of sexual devel- • Genetic counselling is an integral part of management. 685
opment is a psychosocial crisis for the family and must
 19.3 ENDOCRINE DISORDERS

Gender issues Long-term management

The issue of timing and approach to genital recon- Once gender has been assigned, every effort should be
struction is controversial and evolving. An evidence- made to encourage the child's sex of rearing. Both the
based approach is hampered by the lack of long-term child and parents will benefit from long-term psycho-
outcome studies involving large numbers of patients. social support, and many individuals and their fami-
Gender assignment and sex of rearing should be lies derive benefit from support groups.
based on the most probable adult gender identity and Specific management of the gonadal tissue in
potential for adult function. It involves consideration infants of uncertain sex may be required to reduce the
of the diagnosis, degree of virilization, capacity to risk of gonadal malignancy, torsion and infertility.
respond to androgen, potential for adult sexual func- Abdominal gonads bearing Y-chromosome material
tion and fertility as well as the parent's social and cul- should be brought into the scrotum or removed sur-
tural background. There are no data demonstrating a gically. The age of surgery will vary according to the
link between early genital surgery and psychosexual underlying condition.
orientation and, although early surgery may make Sex steroid replacement should be provided consis-
life easier for the parents and the child, these irrevo- tent with the sex of rearing and age of the child to
cable decisions may complicate the lives of adults. ensure adequate growth and pubertal development,
Decisions about sex of rearing and genital reconstruc- and to prevent osteoporosis.
tion should be made only by an informed family after
careful ­evaluation and counselling by an experienced
­multidisciplinary team.

686
 Diabetes
Jennifer Couper, Timothy W. Jones
19.4
associated insulin resistance, vitamin D insufficiency,
Diabetes mellitus and enteroviruses. Congenital rubella is a proven, very
Diabetes mellitus is caused by a deficiency in the secre- rare, environmental trigger.
tion or action of insulin. It is one of the most common
chronic diseases of childhood and adolescence, and
causes considerable morbidity due to acute metabolic
derangements and chronic, long-term microvascular
Metabolic effects of insulin
and macrovascular complications. In childhood and Insulin is the hormone of energy storage and anabo-
adolescence the most common form of diabetes is type lism. It allows glucose to enter cells and be stored as
1 diabetes (previously known as insulin-dependent dia- glycogen in the liver and muscle, and as triglyceride in
betes). The incidence of type 1 diabetes has doubled fat. Insulin deficiency prevents glycogen and triglycer-
over the last 20 years in Australia, now at 22 cases per ide storage and causes their breakdown, as well as that
100 000 population. This trend is also seen in Europe of protein. In addition, insulin deficiency promotes
and North America. The sex ratio is equal. Diabetes is hepatic gluconeogenesis. The combined effect of gly-
uncommon in infancy. In parallel with the overweight cogen breakdown, enhanced gluconeogenesis and fail-
and obesity epidemic, there has been increased rec- ure of glucose entry into cells results in a rise in blood
ognition of type 2 diabetes in youth in Australia and glucose levels. When the renal threshold is exceeded,
New Zealand, especially in Aboriginal and Polynesian glycosuria occurs. The osmotic effect of the glycos-
populations. Other less common forms of diabetes uria causes polyuria and eventually dehydration.
result from pancreatic disease (such as cystic fibrosis- Breakdown of triglyceride (lipolysis) releases free fatty
related diabetes) and a rare group of specific genetic acids into the circulation. In the liver these are con-
causes of deranged insulin secretion. verted to ketoacids (ketogenesis), with eventual devel-
opment of ketoacidosis.

Pathogenesis of type 1 diabetes

There are two major factors in the pathogenesis:
Clinical presentation
• genetic predisposition When the autoimmune process has destroyed approx-
• environmental triggers or protectors. imately 90% of the beta-cell mass, persistent hyper-
glycaemia causes the initial symptoms of polyuria,
polydipsia, weight loss and fatigue. In routine practice,
Autoimmune destruction of beta cells
symptoms are usually present for 1–3 weeks before the
Type 1 diabetes is caused by autoimmune destruction diagnosis is made; however, a child with a suspected
of the beta cells (insulin-producing cells) of the islets diagnosis of diabetes should be investigated immedi-
of Langerhans. T-cell infiltration of the islets and cir- ately. A raised postprandial blood glucose to above
culating autoantibodies precede the development of 9 mmol/L may be detected months before symptoms
diabetes by months to years. This preclinical phase, develop and before the fasting blood glucose concen-
when blood glucose is normal and circulating anti- tration rises.
bodies to target antigens are present, provides clues As insulin deficiency progresses, diabetic ketoaci-
for prevention or postponement of the onset of clini- dosis develops and, if not treated, results in death.
cal diabetes. There is an increased frequency of certain Ketoacidosis initially causes vomiting and later, rapid,
HLA types (HLA DR3/DQ2 and DR4/DQ8) in type deep breathing (Kussmaul respiration). The hyper-
1 diabetes. ventilation is a compensatory mechanism to c­orrect
Environmental factors that are potential candi- metabolic acidosis by removing carbon dioxide.
dates in the initiation or progression of autoimmu- Chemical breakdown of acetoacetic acid in the body
nity include the heavier childhood population with yields acetone, which can be detected on the patient's 687
 19.4 ENDOCRINE DISORDERS

Box 19.4.1 Type 1 diabetes: clinical features at

presentation and useful investigations at diagnosis
Differential diagnoses
The diagnosis of type 1 diabetes in childhood is not
Clinical presentation usually difficult, provided the clinician is aware that
• Polyuria and polydipsia this condition can occur even in the very young. The
• Enuresis and nocturia
• Weight loss and fatigue
most common misdiagnoses are to mistake:
• Thrush • polyuria for urinary frequency due to urinary tract
• Vomiting (with increasing ketosis) infection
• Kussmaul breathing and coma (with increasing acidosis) • the respiratory pattern of metabolic acidosis for a
respiratory tract infection or asthma
Investigations • vomiting and abdominal pain for gastroenteritis or
• Urinalysis for glucose and ketones
an acute abdomen.
• Random blood glucose (postprandial)
• Blood electrolytes and acid–base
Children with intercurrent infections, acute asthma
• Blood or other cultures and blood count (if infection or hypernatraemic dehydration may have transient
suspected) hyperglycaemia and glycosuria that resolves with the
• Islet antibodies (if type 2 diabetes suspected) intercurrent illness. Only very rarely do these children
develop type 1 diabetes. Islet cell autoantibodies can
be tested to determine whether the child is at risk of
developing type 1 diabetes.

breath. Abdominal pain may mimic an acute surgi-

cal abdomen. Dehydration due to continuing urinary
losses caused by the osmotic diuresis may progress
Treatment of diabetic
to shock. The acidosis, dehydration and changes in ketoacidosis
plasma osmolality cause initial irritability, then con- The aims of therapy are:
fusion, drowsiness and eventually coma. A summary • emergency isotonic fluid replacement (10–20 mL
of the clinical features and useful investigations at the per kg per h), if shock is present
time of presentation of type 1 diabetes is presented in • correction of dehydration slowly over 48 hours,
Box 19.4.1. using normal (isotonic or 0.9%) saline
• replacement of electrolyte losses and slow
correction of acidosis: supplemental potassium
of 40–60 mmol/L in intravenous fluids is required
to maintain normal serum potassium levels after
commencing insulin therapy
Clinical example
• correction of insulin deficiency with an infusion of
For 2  weeks, a mother noticed that her 4-year- soluble insulin.
old son, Harry, was irritable, thirsty and wetting Treatment should be undertaken in a centre equipped
the bed at night, having previously been dry. with paediatric intensive care facilities; the child may
After being generally less well for 24 hours he need to be transported there by an expert retrieval
became lethargic and began vomiting. On presentation at team. Frequent biochemical monitoring of the blood
the emergency department, he was noted to be drowsy,
glucose, electrolytes and blood gases is required. The
dehydrated and had deep sighing respirations (Kussmaul
breathing). The diagnosis of diabetic ketoacidosis was
initial rate of insulin infusion is 0.1 unit per kg per h,
confirmed when he was found to have a blood glucose and should be adjusted to produce a slow fall in the
level of 22 mmol/L, blood ketones were 5.2 mmol/L, serum blood glucose level. Rapid reductions in the blood glu-
sodium 126 mmol/L, potassium 5.2 mmol/L, bicarbonate cose or serum sodium concentration alter the plasma
10 mmol/L, pH 7.15 and the base deficit 26. He was treated osmolality quickly and may increase the risks of the
with intravenous isotonic fluids, intravenous potassium and rare but life-threatening complication of cerebral
intravenous insulin.
oedema. Cerebral oedema is the commonest cause of
Harry was discharged 4  days later, on two injections
of insulin per day, a diabetes food plan and home blood death in children with diabetic ketoacidosis.
glucose testing. During the hospital admission, his family
received education from the diabetes educator and Stabilization of newly diagnosed
dietitian, and the education programme was continued type 1 diabetes
on an outpatient basis. A community diabetes educator
visited Harry's kindergarten to educate the staff about When ketones clear, subcutaneous insulin is begun
688 hypoglycaemia. with regular food intake. Most children are stabilized
on two to four daily injections of ultra-short- and
 DIABETES   19.4
intermediate- or long-acting insulins. Within days to
weeks of the introduction of insulin, some recovery
of the remaining viable beta cells may occur. During
this period of partial remission (also known as the
‘honeymoon’ phase), insulin requirements fall. This
phase may last for weeks or months but, as the under-
lying autoimmune destruction of beta cells is still in
progress, insulin requirements eventually rise perma-
nently. The process of islet destruction may continue
for years, providing a potential window of opportu-
nity to increase viable beta cells by immune modula-
tion during the pre-clinical phase and the first years
after diagnosis.

Management
Aims of management
Type 1 diabetes is a permanent disorder. The long-
term aims are for the child to achieve normal
physical and psychological development, to lead
a fulfilling life with as little restriction on lifestyle
and occupation as possible, and to minimize the Fig. 19.4.1 Child with insulin pump.
risk of long-term microvascular and macrovascular
complications.

a ­continuous subcutaneous insulin infusion (insu-

Management principles
lin pump) (Fig. 19.4.1). This requirement increases
Because of the complexity of diabetes management, with more variability during puberty. Preschool
an interdisciplinary team is essential for adequate children may be sensitive to short-acting insulin
treatment of a child with diabetes. The team mem- and, therefore, receive predominantly intermediate-
bers should have expertise in both paediatric care and acting insulin. Regimens using bolus doses of ultra-
diabetes, and would normally include a paediatrician, short-acting insulin analogue before meals and longer-
diabetes nurse educator, dietitian, social worker and acting insulin analogue before bed, or insulin pump
psychologist. regimens (basal insulin infusion subcutaneously and
The adequacy of diabetes care to maintain good bolus doses of insulin with meals and snacks), are
metabolic control during childhood is a crucial deter- especially suitable for the adolescent needing more
minant of long-term outcomes. Good metabolic con- flexibility in the treatment schedule. These regimens
trol is often difficult to achieve, especially in the age and newer delivery systems improve metabolic con-
group under 5 years and in adolescents. The aim is to trol and reduce hypoglycaemia, provided compliance
keep preprandial and postprandial blood glucose lev- is excellent and there is accompanying blood glucose
els as close to normal as possible. Children are asked monitoring.
to measure their capillary blood glucose four or more The dose of insulin is adjusted according to blood
times per day. The key influences on the blood glucose glucose measurements, anticipated carbohydrate
levels are: intake, and exercise. Glycosylated haemoglobin
• insulin (HbA1c) levels indicate the level of control dur-
• diet ing the preceding 6–8 weeks and provide the most
• exercise. meaningful guide when blood glucose levels are
erratic. The target range for HbA1c is a value less
than 7.5%, and has fallen considerably during the
Insulin
last 10 years. Target blood glucose levels are gener-
Insulin therapy is individualized. Generally pre- ally 4–8 mmol/L. Target HbA1c and blood glucose
pubertal children require around 0.8 units/kg levels may need to be higher in preschool children
body weight per day. Insulin is usually given as or in children with a history of recurrent severe 689
two to four subcutaneous injections daily or via hypoglycaemia.
 19.4 ENDOCRINE DISORDERS

The early education programme can be provided by

Practical points the diabetes educator and dietitian as an outpatient.
Follow-up visits are usually every 3 months once the
Poor metabolic control with high HbA1c child is stabilized, to assess:
• Is the prescribed insulin dose adequate? • general wellbeing
• Is insulin omission a potential problem? • history of hypoglycaemia
• Is food intake excessive or inappropriate? • home blood glucose monitoring
• Consider education/dietary/psychological review. • insulin schedule
• Consider an eating disorder, especially in girls. • food plan
• Consider increasing doses, changing insulin types and
intensifying the insulin schedule if insulin omission is not a • school progress
problem. • height and weight
• injection sites
• size of the thyroid gland
Diet • presence of skin infections
• signs of accompanying insulin resistance (increasing
Carbohydrate raises the blood glucose level, which
waist circumference, acanthosis nigricans).
must be balanced by the glucose-lowering effect of
The blood glucose profile is examined in the logbook
insulin and exercise. This balance is usually achieved
kept by the patient, or downloaded from the patient's
by having the diet supply carbohydrate throughout the
blood glucose monitor, and the adequacy of the dietary
day in meals and snacks. However, toddlers usually
and insulin regimen is assessed. Continuous intersti-
have a grazing pattern of food intake and older ado-
tial glucose monitoring (Fig. 19.4.2) may be useful for
lescents may not need three snacks per day. Children
fine-tuning of the insulin schedule after a change to a
and adolescents receiving insulin pump therapy have
new insulin schedule or insulin pump, or when there
more flexibility with timing of meals and the amount
are concerns about undetectable nocturnal hypogly-
of carbohydrate intake.
caemia. The glycosylated haemoglobin (HbA1c) mea-
The usual diabetes diet is relatively high in complex
sures glycaemic control during the lifespan of the
carbohydrates, low in simple carbohydrates (sugar)
red cells (120 days). HbA1c can be measured in capil-
and low in saturated fats. The glycaemic index is a clas-
lary blood within minutes in the outpatient clinic setting.
sification of foods based on their postprandial blood
With the combined efforts of the family, the child
glucose response and is a more predictable guide than
and the diabetes management team, most children
merely measuring the carbohydrate content of foods.
grow and develop normally, achieve their educa-
Individual and flexible food plans are essential to
tional potential, and have a satisfying childhood and
encourage adherence to the diet. It is also necessary to
adolescence. However, fewer than 50% of children in
account for pre-existing family and cultural customs.
Australia achieve target HbA1c levels below 7.5%.
Regular review by an experienced dietitian is necessary
to cope with changing requirements as the child grows.
Co-morbidities
Exercise Several autoimmune disorders develop more frequently
Exercise increases glucose uptake by the exercis- in type 1 diabetes. These are coeliac disease, autoimmune
ing muscles and lowers the blood glucose level. This thyroid disease (which may result in hypothyroidism or
effect is seen only if the diabetes is well controlled and hyperthyroidism) and rarely Addison's disease. Screening
serum levels of insulin are adequate (exercise under- for these conditions is part of routine management.
taken during poor control and with low insulin levels
may paradoxically raise blood glucose levels). To off- Long-term microvascular and macrovascular
set the hypoglycaemic effect of exercise, the child may complications
need extra carbohydrate food or a small reduction in
the preceding insulin dose. Regular exercise does not Long-term vascular complications are:
per se improve metabolic control, but may do so indi- • nephropathy
rectly in some individuals by modifying appetite and • retinopathy
by improving wellbeing and self-esteem. • neuropathy
• cardiovascular disease
• peripheral vascular disease.
Outpatient management
It is extremely rare for children and adolescents to show
For most children with diabetes, the initial hospital- clinical signs of vascular complications, but subclini-
ization or day stay admission at diagnosis for stabili- cal signs may be detected from adolescence onwards.
690
zation and education is their only hospital admission. These form the basis of complication s­creening
 DIABETES   19.4
programmes and early intervention. It is recommen­ • assessment of urinary albumin/creatinine ratio on
ded that from 5 years’ duration of type 1 diabetes, the an early morning sample
patient has an annual review including: • fundoscopy on dilated pupils by an
• measurement of resting blood pressure ophthalmologist, or retinal photography.

08/03/2005 (Tue)
22.2

16.7
Glucose - mmol/L

11.1
10.0

5.6

3.9
0.0

03:00 06:00 09:00 12:00 15:00 18:00 21:00

Time of Day
Legend

Paired Meter Value Meal Other

Unpaired Meter Value Insulin Time Change (From)
Sensor Value Exercise Time Change (To)
A

02/03/2005 (Wed)
22.2

16.7
Glucose - mmol/L

11.1
10.0

5.6

3.9
0.0

03:00 06:00 09:00 12:00 15:00 18:00 21:00

Time of Day
Legend

Paired Meter Value Meal Other

Unpaired Meter Value Insulin Time Change (From)
Sensor Value Exercise Time Change (To)
B

Fig. 19.4.2 Continuous interstitial glucose monitoring obtained from an indwelling subcutaneous sensor in three patients with type 1
diabetes. In (A), the pattern of results shows that the patient is in the remission phase. In (B), excellent control is seen, but the a.m. rise
in glucose concentration requires an increase in a.m. ultra-short-acting insulin. 691
Continued
 19.4 ENDOCRINE DISORDERS

17/11/2004 (Wed)
22.2

16.7
Glucose - mmol/L

11.1
10.0

5.6
3.9

0.0

03:00 06:00 09:00 12:00 15:00 18:00 21:00

Time of Day
Legend

Paired Meter Value Meal Other

Unpaired Meter Value Insulin Time Change (From)
Sensor Value Exercise Time Change (To)
C

Fig. 19.4.2, cont'd In (C), the results show asymptomatic nocturnal hypoglycaemia and daytime hyperglycaemia. This requires
adjustment of night-time long-acting insulin and daytime ultra-short-acting insulin.

Serum lipids can be measured every few years, par- drugs such as alcohol, and hypoglycaemic unaware-
ticularly if there is a family history of a lipid disorder ness may develop with recurrent episodes of severe
or of premature cardiovascular disease. hypoglycaemia.
The major risk factors for the development of long-
term vascular complications are:
• level of metabolic control Practical points
• duration of type 1 diabetes
• smoking Recurrent hypoglycaemia
• hypertension • Is it severe, moderate or mild; is it daytime or nocturnal?
• dyslipidaemia • Is there hypoglycaemic unawareness and at what blood
glucose level does the patient detect symptoms of low
• family history.
blood glucose?
It should be reinforced for the patient and their family
• What is the HbA1c level?
that any improvement in their metabolic control, even • Consider a change of insulin dose, insulin type or insulin
if still not ideal, will reduce their risk of developing timing schedule.
complications. There are current international guide- • Exclude coeliac disease, Addison's disease and
lines to introduce angiotensin-converting enzyme autoimmune thyroid disease.
(ACE) inhibitors for hypertension (above 95th c­ entile • Consider continuous interstitial glucose monitoring,
particularly if nocturnal hypoglycaemia is suspected.
for age and sex) and persistent microalbuminuria,
• Consider continuous subcutaneous insulin infusions
and statin therapy for raised low-density lipoprotein (insulin pump therapy).
(LDL) cholesterol.

Special problems in management Hypoglycaemia may occur if the insulin dose is exces-
sive, if insufficient food is eaten or if extra exercise is
Hypoglycaemia
undertaken. Severe hypoglycaemia is most common
For parents, the occurrence of severe hypoglycaemia during the night, when the glucose threshold for coun-
in their child (loss of consciousness or a convulsion) ter-regulatory hormone responses is lower. Minor hypo-
is one of the most distressing aspects of diabetes. glycaemic episodes are relatively frequent and reflect
No long-term harmful effects generally result from the difficulties in achieving stable control with current
a severe hypoglycaemic episode. However, the risk insulin delivery to the systemic rather than enteropor-
692
remains, particularly if the adolescent uses other tal circulation. Insulin analogues (ultra-short-acting
 DIABETES   19.4
and basal) and insulin pump therapy have reduced the Hashimoto thyroiditis, coeliac disease or, less commonly,
risk of hypoglycaemia. All patients with type 1 diabe- adrenal insufficiency can also cause pubertal and
tes should carry some rapidly absorbable carbohydrate growth delay.
(e.g. glucose tablets or glucose-containing sweets) for
immediate treatment of hypoglycaemic symptoms.
The clinical features of hypoglycaemia can be Psychological stresses
divided into: The relevance of psychological wellbeing to good dia-
• stimulation of the sympathetic nervous system – betes control is of such importance that the social
anxiety, palpitations, tachycardia, pallor, worker and psychologist are integral members of
perspiration, headaches and abdominal pain the management team. Stress is common to all fami-
• effects on the central nervous system – lethargy, lies with diabetes, and psychosocial support is essen-
dizziness, ataxia, weakness, confusion, personality tial. Patient and parent support groups and diabetes
changes, visual disturbance, unconsciousness, camps also nurture self-esteem and confidence. Family
localized and generalized convulsions. dysfunction, teenage rebellion and other emotional
These clinical features appear rapidly in a previously well problems may cause a more profound instability, and
child and there is no difficulty in differentiating hypo- psychological counselling may be required for the
glycaemic coma from the coma of diabetic ketoacidosis. child and family. Clinicians must be alert to the higher
The emergency treatment for the unconscious hypo- incidence of mood disorders and eating disorders in
glycaemic child is: adolescents with type 1 diabetes than in the normal
• lay them on their side and check the airway adolescent population.
• do not give oral fluids
• give intramuscular or subcutaneous glucagon Adherence
(0.5 mg for children < 5 years of age; 1 mg for older
children and adults) or intravenous glucose (2.5 mL Excellent diabetes control in childhood and ado-
20% dextrose per kilogram of body weight). lescence is difficult in the best of circumstances. It
All families with a diabetic child should have glucagon becomes impossible when the child or the family
at home and should be able to give it subcutaneously. cannot adhere to diet, monitoring or injections of
The response to therapy is seen within minutes. For the insulin. Problems in adherence are not unusual peri-
less severely affected child, mild hypoglycaemia can be odically and represent a natural rebellion against the
treated with oral glucose. never-ending discipline that characterizes diabetes
management. The usual cause of recurrent diabetic
ketoacidosis and chronic poor metabolic control in
Management of sick days adolescence is i­nsulin omission. Patience and counsel-
Children with well controlled diabetes are no more ling are necessary, especially in adolescence, when nor-
prone to infections than the non-diabetic child. mal risk-taking behaviour and growing independence
However, the infection, especially if associated with may not combine well with diabetes.
fever, may cause a temporary insulin resistance and
increased insulin requirements, or, in the case of enteric
infections with vomiting/diarrhoea, reduced insulin
Clinical example
requirements.
Advice to parents when child is sick at home: Michelle, a 14-year-old girl with a 5-year history
• measure blood glucose levels frequently of diabetes, had three episodes of diabetic
• measure blood ketone levels regularly ketoacidosis in 3  months. Her blood glucose
• give frequent small doses (10–20% of daily logbook showed the values to be 4–10 mmol/L,
requirements) of short-acting insulin every 3–4 hours although a glycosylated haemoglobin level (HbA1c) was 10.8%
(normal range 4–6%). Her insulin dose was 0.9 units per kg per
if blood glucose and/or ketone levels are rising
day and the recorded blood glucose levels appeared spurious.
• low doses of glucagon can help prevent Admission to hospital for stabilization confirmed increased
hypoglycaemia in the child with vomiting blood glucose levels. Management required appropriate
• regular phone contact with the diabetes doctor or increases in insulin dose, education and counselling. The
educator. dietitian suspected that Michelle might also have had an
eating disorder complicating her insulin omission, and
psychological review was arranged.
Growth and delayed puberty Sometimes it is necessary for someone else (e.g. the
parents or a community nurse) temporarily to take over
Because insulin is the principal hormone of energy responsibility for the insulin injections when there is a serious
storage and anabolism, poor diabetic control can problem with insulin omission. 693
cause growth disturbances and pubertal delay.
 19.4 ENDOCRINE DISORDERS

Factors limiting management

Box 19.4.2 Characteristics of type 2 diabetes at diagnosis
Factors to consider when diabetes is proving difficult
to manage are: • Obesity
• Acanthosis nigricans
• difficulties in family functioning
• Family history of type 2 diabetes
• psychological stresses • Absent or mild ketosis (although ketosis and ketoacidosis
• adherence problems can occur)
• eating disorders (particularly in adolescent girls) • Absence of islet antibodies
• exaggerated fear of hypoglycaemia held by the • Raised C-peptide/insulin levels
family or patient. • Microvascular complications, hypertension and lipid
abnormalities may be present
• Hyperandrogenism may be present
• More common in Aboriginal and Polynesian
Future directions populations

Families frequently ask about research and manage-

ment advances, and it is important that they have
access to up-to-date information through regular sem-
inars and reliable websites.
Oral and transdermal insulins are under investiga-
tion. Technical advances in interstitial glucose moni-
toring (continuous glucose monitoring systems) and
insulin pump delivery are advancing the availability of
a closed loop system that can monitor glucose levels
and adjust insulin delivery.
Specific immunomodulation of the autoimmune
process is being trialled in subjects with preclinical and
newly diagnosed diabetes, in an attempt to prolong the
life of beta cells.
Transplantation of isolated islets of Langerhans in
adults using less beta-cell toxic immunosuppressive
drugs has shown promise and is available for some adult
patients with hypoglycaemic unawareness. Whole-
pancreas transplants have been performed successfully
in conjunction with renal transplantation. However,
prevention of rejection of both types of transplant
requires lifelong immunosuppression and the supply of
human pancreas tissue is not plentiful. Stem cells and
islet regeneration are other major research directions.

Type 2 diabetes
The true incidence of type 2 diabetes in youth is not
known, as patients are frequently asymptomatic.
Characteristics of type 2 diabetes at diagnosis are
shown in Box 19.4.2.
The distinction between type 1 and type 2 diabe-
tes in childhood may be difficult to make on clinical
grounds alone (for example, many children with type
1 diabetes are overweight and have a family history of
type 2 diabetes), although children with type 2 diabe-
tes often have acanthosis nigricans of the axilla and/or
neck (Fig. 19.4.3A,B). Measurement of islet antibodies Fig. 19.4.3 Acanthosis nigricans of axilla (A) and neck (B).

694
 DIABETES   19.4
to show their absence is usually necessary to confirm Screening for microvascular and macrovascular com-
the diagnosis. The distinction is important, as patients plications should begin from the time of diagnosis in
with type 2 diabetes are treated with a weight-reduc- type 2 diabetes. Insulin resistance is always present and
ing diabetes diet and metformin as first-line measures. there may be other features of the metabolic syndrome
Insulin may still be required, especially during inter- such as dyslipidaemia, hypertension, non-­ alcoholic
current acute infections when ketoacidosis can occur. hepatosteatosis and hyperandrogenism in girls.

695
 19.5 Bone mineral disorders
Colin Jones, Joshua Kausman

Hypocalcaemia, rickets and hypercalcaemia are the

most common manifestations of disorders of calcium, Clinical example
phosphate and vitamin D metabolism. Disorders of
magnesium metabolism are rare but share many fea- Kylie, a 6-year-old girl, has nephritis with
tures of calcium disorders. a metabolic acidosis (pH 7.32, [HCO3−] =
15 mmol/L, Pco2 30 mmHg). She has an
albumin of 20 g/L, serum total [Ca2+] =
1.0 mmol/L and serum [phosphate] = 3.6 mmol/L. Is it
safe to correct the acidosis with intravenous NaHCO3?
Calcium, magnesium and From Table 19.5.1, if the serum albumin was normal, 46%
phosphorus (Table 19.5.1) of the total serum Ca2+ would be ionized. However, the
serum albumin concentration is reduced by 50%, thus the
Calcium and phosphate form the major structural com- amount of calcium bound to albumin will be reduced by
ponents of bone, in the form of hydroxyapatite. The 50% (the proportion of total calcium bound to albumin will
be reduced to approximately 20%), leaving the ionized
majority of magnesium is also found in bones. A large
proportion of total serum calcium increased from the normal
proportion of each mineral in bone is freely exchange- 46% to approximately 66% = 0.66 mmol/L. Increasing the
able with the extracellular fluid (ECF). Calcium and pH to 7.4 could reduce the ionized portion and precipitate
phosphate ions, under normal circumstances, are pres- overt symptoms of hypocalcaemia. Thus, the calcium
ent in supersaturated solution. A rise in phosphate will concentration should be corrected before giving NaHCO3.
lead to the deposition of more calcium phosphate into
bone as hydroxyapatite and cause hypocalcaemia. The
distribution of calcium and phosphate between bone serum calcium below 2 mmol/L (ionized calcium
and the ECF is determined by hormonal regulation of 0.75 mmol/L), although some patients can tolerate
the concentrations of these minerals. The most impor- much lower levels and remain asymptomatic. The signs
tant hormones are 1,25-dihydroxyvitamin D3 (acti- of hypocalcaemia are due to neuromuscular excit-
vated vitamin D) and parathyroid hormone (PTH). ability. Jitteriness, apnoea, laryngeal spasm causing
The actions of these hormones are summarized in stridor and convulsions are frequent in infants.
Figure 19.5.1. Tetany, carpopedal spasm and the Chovstek (facial
The ionized ECF forms of calcium and magnesium twitch on percussion of the facial nerve near the
are responsible for physiological effect. The ionized temporomandibular joint) and Trousseau (tetany
form of calcium should be measured to confirm that produced by inflating the sphygmomanometer with
abnormalities in concentration are present, because above systolic blood pressure for up to 2 min) signs
the equilibrium between the ionized and protein-bound are seen mainly in older children. Intracerebral
forms can change. For instance, an increase of 0.1 pH calcification and cataracts are complications. The
unit decreases the ionized calcium by 10%, and hypo- electrocardiogram (ECG) may show a prolonged QT
albuminaemia reduces total serum calcium but not the interval.
ionized calcium concentration, because 90% of bound Some causes of hypocalcaemia are listed in
calcium is bound to albumin. Box 19.5.1.
Early neonatal hypocalcaemia is common in pre-
mature infants and infants of diabetic mothers. In
premature infants, it is possibly an exaggerated
Hypocalcaemia response to the normal interruption of the mater-
In the neonatal period, hypocalcaemia is conven- nofetal calcium transfer; the serum calcium falls fol-
tionally a total serum calcium concentration below lowing delivery to a nadir, reached at a few days of
1.8 mmol/L (ionized calcium 1.0 mmol/L). Beyond age, and then increases to normal levels at 1–2 weeks
this age, a total plasma calcium below 2.1 mmol/L of age. Signs are seen within hours of birth, become
(ionized calcium 1.2 mmol/L) constitutes hypocal-
­ most severe about 48 hours after birth and then
696
caemia. Clinical signs usually occur only with total improve spontaneously. Hypocalcaemia can be
 BONE MINERAL DISORDERS 19.5
Table 19.5.1 Distribution, serum concentrations, dietary requirements and sources of calcium, magnesium and phosphate

Calcium Magnesium Phosphorus

Body distribution (%)

Bone* 99 60 80
Intracellular — 40 20
Serum status (%)
Ionized† 46 55 85
Complexed 14 25 5
Protein bound 40 20 10
Serum levels (mmol/L)
Cord blood‡ 2.4 0.7 1.6
Neonatal 2.1–2.7 0.75–1.1 2.0–3.3
Adult 2.2–2.6 0.75–1.1 1.0–1.3§

Dietary intake, RDI (mg/day)

0_6 months 210 30 100
7–12 months 270 75 275
1–3 years 500 80 460
4–8 years 700 130 500
9–18 years 1300 240–410 1250

Milk content (mg/L)

Human 300–500 40 100–300
Cow 1500 130 1000
Other food sources Tinned fish, dairy products Green vegetables, seeds, nuts Meats, dairy products

RDI, recommended dietary intake.

* Ionic exchange occurs readily between extracellular fluid (ECF) and bone, enabling ECF concentrations to be kept fairly constant.
†
The ionized form of phosphorus at pH 7.4 is HPO 4 2− (70%) and H2PO 4 − (20%).
‡
Cord blood concentrations are higher than maternal blood concentrations, indicating that active transport mechanisms are
involved in transplacental transfer. Parathyroid hormone-related peptide (PTHRP) is probably involved in these processes.
§
Levels of phosphate decline slowly during childhood and reach adult levels on completion of bone growth.

aggravated by early phosphate-rich formula ­feeding hypomagnesaemia or idiopathic congenital hypo-

or hypoxic–ischaemic injury. Treatment of symptom- parathyroidism. An abnormality of the calcium-
atic infants involves intravenous (IV) calcium admin- sensing receptor on the parathyroid cells (an activat-
istration and commencement of diet, following the ing mutation decreasing PTH release) is also a cause.
guidelines in Box 19.5.2. Treatment is based on the use of calcitriol, often in
Late neonatal hypocalcaemia usually presents as combination with phosphate restriction.
tetany after the first few days of life. The main cause Late-onset hypoparathyroidism may occur
is transient hypoparathyroidism, as demonstrated with destructive injury of the parathyroids (cop-
by high plasma phosphate and low serum PTH con- per deposition in Wilson disease, iron deposition
centrations in the face of hypocalcaemia. A similar in haemosiderosis, or autoimmune type I poly-
clinical picture is seen in infants of mothers with glandular syndrome). In this latter condition,
hyperparathyroidism and in infants with congeni- children, usually girls, present with tetany or con-
tal heart disease. Treatment may involve calcium vulsions, and may have candidiasis and adrenal
infusion, calcitriol, oral calcium supplementation insufficiency or other autoimmune disorders such
and a low-phosphate formula. The infant can often as alopecia, malabsorption, thyroiditis and dia-
be weaned from this treatment after a few weeks. betes. Pseudohypoparathyroidism is due to end-
Persistence of the hypocalcaemia beyond this time organ resistance to PTH, and blood levels of PTH
should prompt a search for other causes of hypo- are high. Mental deficiency and skeletal abnor-
parathyroidism, such as DiGeorge syndrome (aplasia malities (particularly a short fourth metacarpal)
of the parathyroids, thymic aplasia with T-cell immu- may be associated. Treatment is the same as for
nodeficiency and cardiovascular abnormalities), hypoparathyroidism. 697
 19.5 ENDOCRINE DISORDERS

[ Ca ]i Parathyroid
[ PTH ]
gland1
[ PO4 ]

Ca release Bone
PO4 release

Calcitonin2 Kidney

Renal tubular PO4 loss

phosphate
reabsorption

Renal calcium
excretion

[ Ca ]i
1α−hydroxylase activity
[ PO4 ]

Ca PO4 Mg Small 1,25-(OH)2-vitamin D3

intestine
absorption

Remodelling Bone 2

1. Calcium-sensitive receptors on the parathyroid cells lead to PTH production

increasing with a rise and decreasing with a fall in ionized calcium concentrations.

2. Calcitonin is a hormone produced in the medullary (parafollicular)

cells of the thyroid gland in response to an increase in calcium concentrations.
It inhibits resorption of bone.

Fig. 19.5.1 Hormonal control of calcium, magnesium and phosphate. PTH, parathyroid hormone.

dialysis. Rickets due to vitamin D deficiency or disor-

Practical points ders of vitamin D metabolism can cause hypocalcaemia
(see below).
Hypocalcaemia
• Suspect symptomatic hypocalcaemia with tetany,
unexplained stridor, irritability or convulsions. Clinical example
• Confirm diagnosis with total and ionized calcium
concentrations and draw blood for estimation of Kylie has induction treatment for T-cell lymphoma.
magnesium, phosphate and parathyroid hormone She develops hypocalcaemia associated with a
concentrations. raised serum phosphate level in the days after
• Treat symptomatic hypocalcaemia with IV 10% calcium this treatment. How should the hypocalcaemia be managed?
chloride 0.2 mL per kg per dose given slowly into a The administration of intravenous calcium, combined with the
well-placed IV line, and monitor the ECG. elevated serum phosphate, would exceed the solubility product
of calcium phosphate and lead to its metastatic deposition.
The calcification would occur in blood vessels and soft tissues.
Hyperphosphataemia can cause hypocalcaemia Such an approach might, in fact, be necessary if Kylie had
acutely (as seen in tumour lysis syndrome, where cell symptomatic hypocalcaemia (convulsions), but it would be
death following the initiation of chemotherapy for bulky preferable to lower the serum phosphate concentration first.
tumours results in the release of phosphate). Acute renal This can be achieved by implementing a low-phosphate diet
failure with retention of phosphate is associated with and administering oral phosphate binders (such as calcium
carbonate) which bind the phosphate in the gut (calcium
hypocalcaemia. The primary treatment in these con-
complexes phosphate and is not absorbed by the intestine). It
ditions is to reduce serum phosphate concentrations would be uncommon to use dialysis or haemofiltration, but these
through dietary restriction of phosphate, the use of treatments would also lower serum phosphate concentrations.
698 phosphate binders (such as calcium carbonate) and
 BONE MINERAL DISORDERS 19.5
and development of deformity, particularly in the
Box 19.5.1 Causes of hypocalcaemia
weight-bearing bones. In established bones there is con-
Neonatal tinued bone resorption but failure of mineralization
• Early neonatal – prematurity, IDM, IUGR, birth asphyxia results in soft, rarefied bones (this is osteomalacia,
• Late neonatal – DiGeorge syndrome, phosphate load, low which is the same disease as rickets, in the adult).
magnesium, IDM Causes of rickets are deficiency of the effect of vitamin D
Pseudohypocalcaemia and phosphate depletion. Figure 19.5.2 outlines the
• Hypoalbuminaemia
causes of vitamin D deficiency and abnormal ­metabolism
Vitamin D deficiency
• Nutritional deficiency of vitamin D in relation to the physiological production
• Disorders of vitamin D metabolism of the active product, 1,25-dihydroxy­vitamin D3.
• 1α-hydroxylase deficiency The recommended dietary intake of vitamin D is
• vitamin D-dependent rickets 400 international units (IU) per day. With exposure
Parathyroid hormone-associated to a small amount of afternoon sunlight, vitamin D
• Hypoparathyroidism supplementation is unnecessary. Breast milk contains
• idiopathic 20–50 IU/L, yet rickets is uncommon in breastfed
• autoimmune polyglandular disease (with
mucocutaneous candidiasis, or Addison disease) infants in the first year of life, provided the mother
• calcium-sensing receptor activating mutations or does not have osteomalacia. Most commercial milk
antibodies formulas have 400 IU/L vitamin D.
• hypomagnesaemia
• destructive lesions of the glands
• hypoplasia Vitamin D
• PTH receptor defect – pseudohypoparathyroidism Skin
• Hyperphosphataemia Food (fat) 7-dehydrocholesterol
• tumour lysis
Nutritional deficiency UV light
• renal failure
Pancreatitis
Vitamin D2 Lack of sunlight
Medical treatment
• Large blood transfusion/exchange transfusion
Malabsorption
IDM, infant of diabetic mother; IUGR, intrauterine growth
retardation; PTH, parathyroid hormone.

Small bowel Liver Vitamin D3

Box 19.5.2 Treatment of hypocalcaemia

Vitamin D Severe liver
Emergency disease
• Patients with hypocalcaemia and symptoms should be Anticonvulsant
therapy
treated with intravenous calcium* 25-(OH)-vitamin D
• ECG monitor (bradycardia)
• IV calcium chloride 10% 0.2 mL per kg per dose (max
1 g) repeated 4–6-hourly or followed by infusion 1 mmol
(= 1.5 mL 10% CaCl2) per kg per day Kidney
• Correct concurrent hypomagnesaemia (magnesium
chloride 0.2 mmol/kg over 1 h)

Maintenance 25-(OH)-vitamin D
• Treat underlying condition (see text) Chronic renal failure
1α-Hydroxylase
*Note: Extravasation of IV calcium causes skin and deficiency
subcutaneous tissue necrosis. 1,25-(OH)2-vitamin D

Rickets 1,25-(OH)2-vitamin D3 actions Peripheral resistance

Rickets is impaired mineralization of osteoid tissue in to 1,25-(OH)2

vitamin D3
the growing child. The mineralization defect affects
the epiphyseal growth plates where cartilage cells
Gut Bone Other
­proliferate and unmineralized osteoid tissue accumu-
699
lates, resulting in widening metaphyses, weak bones Fig. 19.5.2 Vitamin D metabolism and rickets.
 19.5 ENDOCRINE DISORDERS

In the past 30 years, the incidence of vitamin D defi- s­uspected, ‘stoss therapy’ using 50 000–150 000 IU
ciency has increased in Australia. This increase has vitamin D every 6 weeks may be used. Radiological
been seen in the children of migrants from the Middle improvement is usually apparent within 4 weeks.
East, southern Europe and Asia, especially where the Some cases are refractory and require longer treat-
mother wears a hejab. Reduced sunlight and darkly ment periods. If there is no response, tests for
pigmented skin combined with a range of social fac- 1α-hydroxylase deficiency, peripheral resistance to
tors, including poor housing, lack of adequate infant 1,25-dihydroxyvitamin D3 or hypophosphataemic
welfare services for non-English-speaking migrants rickets should be undertaken.
and unusual feeding patterns, have combined to make
rickets more prevalent.
Malabsorption associated with gastrointestinal, he- Practical points
patic or pancreatic disease can cause vitamin D defi-
ciency. In approximately 50% of cases, hypocalcaemia is Rickets
present at the time of diagnosis. Severe liver disease and • Suspect with bowing of the long bones, exaggerated
prolonged use of anticonvulsant therapy with diphe- lumbar lordosis, splayed wrists and other rachitic changes
nylhydantoin or phenobarbital (through an increased in an irritable child.
hepatic turnover of vitamin D) can cause rickets. • Examine for signs of hypocalcaemia and treat
symptomatic hypocalcaemia.
1α-Hydroxylase deficiency (type I vitamin
• Suspect nutritional vitamin D deficiency in breastfed infants
D-dependent rickets, characterized by normal or high of mothers where covering clothing is worn at all times,
25-dihydroxyvitamin D3 and low 1,25-dihydroxyvitamin children of dark skin colour, children with malabsorption or
D3 levels) and peripheral resistance to 1,25-dihydroxyvi- liver disease.
tamin D3 (type II vitamin D-dependent rickets, charac- • Suspect another cause with failure to respond to vitamin
terized by high concentrations of 1,25-dihydroxyvitamin D, low PTH concentrations and very low phosphate
D3) present as severe hypocalcaemic vitamin D defi- concentrations.
ciency that fails to respond to treatment with vitamin D.
The clinical features of these forms of rickets are quite
variable: young children may present with ­tetany and con- Hypophosphataemic rickets
vulsions, older children incidentally when a chest X-ray is X-linked dominant hypophosphataemic (vitamin D
performed for an intercurrent chest infection. Early signs resistant) rickets is caused by failure of phosphate
in nutritional rickets include weakness of the outer table resorption in the renal tubule and lack of an appropri-
of the skull (craniotabes), thickening of the costochon- ate increase in 1α-hydroxylase activity (low phos-
dral junctions (the ‘rachitic rosary’), and widening of phate concentrations normally increase the activity of
the wrists and ankles. Later, asymmetry of the head with this enzyme, which produces 1,25-dihydroxyvitamin
delayed closure of the anterior fontanelle, frontal and D3). In 50% of cases it is familial; the rest of the cases are
occipital bossing of the skull, development of a Harrison due to new mutations. Clinically, the rickets affects the
groove, scoliosis and lumbar lordosis, delayed dentition, lower limbs predominantly, and investigations show the
and bowing and bending of the legs develop. Muscular calcium and PTH concentrations are normal, whereas
weakness, ligament laxity and fractures are common. the phosphate concentration is quite low. Males are usu-
The radiology of the ends of long bones is character- ally no more severely affected than females. Treatment
istic, showing widening of the space between metaphy- consists of large amounts of dietary phosphate supple-
sis and epiphysis (Fig. 19.5.3). The metaphyseal ends mentation and large doses of calcitriol.
of the long bones are widened, and appear cupped and Chronic phosphate deficiency (e.g. renal Fanconi
frayed. The biochemical changes are a normal or low syndrome, dietary phosphate deficiency) from any
serum calcium, a low serum phosphate, a high serum cause will result in rickets.
alkaline phosphatase and a high PTH level.
Treatment of nutritional vitamin D deficiency is
with oral vitamin D at a dose of 3000–5000 units
per day for 6 weeks. In some cases treatment precipi-
Renal osteodystrophy
tates uptake of calcium into bones (‘hungry bones’) This condition predictably occurs when the glomerular
to such an extent that hypocalcaemia is accentu- filtration rate in chronic renal failure decreases to less than
ated and large doses of calcium supplement may be 25% of normal. It occurs as a result of a combination of
required to maintain normocalcaemia for the first events, including an increase in plasma phosphate and
week(s). In the longer term, adequate calcium intake decreased 1α-hydroxylation of 25-hydroxyvitamin D3
(600–1500 mg/day) needs to be maintained, as does in the kidney, leading to a fall in 1,25-dihydroxyvitamin
an adequate intake of vitamin D, 400 IU/day to age D3 production. This leads to hypocalcaemia and an
700
4 years. In cases where poor compliance may be increase in PTH concentration. The combination of
 BONE MINERAL DISORDERS 19.5

A B

C D

Fig. 19.5.3 X-rays of the wrist (A) and knee (C) of a child with nutritional rickets at 18 months of age when the diagnosis was made,
and 8 months later (B, D) after treatment was finished.

rickets and secondary hyperparathyroidism can result hypertension and failure to thrive. Ensuing hypercalciuria
in gross skeletal deformation. Treatment consists of a may cause nephrocalcinosis and urinary calculi. The ECG
graded range of measures beginning with dietary phos- may show a shortened QT interval.
phate restriction, use of phosphate binders (calcium A list of causes of hypercalcaemia is given in Box 19.5.3.
carbonate) and addition of calcitriol. Most of these are rare. Primary hyperparathyroidism
occurs with some frequency in the second decade of life
and is due to hyperplasia or adenoma of the parathyroid
Hypercalcaemia glands. It may occur as part of the multiple endocrine
Hypercalcaemia is a total serum calcium above 2.7 mmol/L neoplasia syndromes (type I hyperparathyroidism asso-
(ionized calcium > 1.3 mmol/L). Symptoms of hypercalcae- ciated with prolactinoma or gastrinoma; type II with
701
mia include nausea and vomiting, polyuria and polydipsia, hyperfunction of the adrenal, parathyroid and medullary
 19.5 ENDOCRINE DISORDERS

Box 19.5.3 Causes of hypercalcaemia

Neonatal
• Hyperparathyroidism
• primary
• maternal hypoparathyroidism
• maternal pseudohypoparathyroidism
• Idiopathic infantile hypercalcaemia
• Williams syndrome
• Familial hypocalciuric hypercalcaemia
• Subcutaneous fat necrosis
Vitamin D excess
• Iatrogenic
• Ectopic production — sarcoidosis, tuberculosis, lymphoma
Parathyroid hormone excess
• Primary hyperparathyroidism Fig. 19.5.4 Renal ultrasound image showing nephrocalcinosis
• multiple endocrine neoplasia (MEN) syndromes of the medullary pyramids in a 4-year-old child with idiopathic
• Familial hypocalciuric hypercalcaemia nephrocalcinosis.
• Abnormalities related to PTH receptor or PTH-related
peptide (PTHRP)
Other (see Box 19.5.3), with the notable exception of famil-
• Bone disease, trauma and immobilization ial hypocalciuric hypercalcaemia. Normocalcaemic
• Thyrotoxicosis and hypothyroidism hypercalciuria is caused by furosemide or corticoste-
roid therapy, immobilization of limb fractures, distal
cells of the thyroid). Investigations reveal high PTH con- renal tubular acidosis and some rare syndromes.
centrations, and X-ray appearances include subperiosteal Idiopathic hypercalciuria is common and appears to
resorption of bone (particularly the phalanges), ‘salt and be an autosomal dominant condition with incomplete
pepper’ appearance of the cranium and cyst formation penetrance. On a calcium-rich or calcium-sufficient
in long bones. Treatment of symptomatic disease usually diet there is intestinal hyperabsorption of calcium
involves subtotal parathyroidectomy. and the PTH and 1,25-dihydroxyvitamin D concen-
Familial hypocalciuric hypercalcaemia is an auto- trations are normal. On a lower calcium diet, ‘renal’
somal dominant, usually asymptomatic, condition loss of calcium occurs and higher levels of PTH and
caused by an inactivating mutation of the parathyroid 1,25-dihydroxyvitamin D are found. Excessive bone
calcium-sensing receptor. resorption occurs in some patients and can cause osteo-
Idiopathic hypercalcaemia of infancy is a condi- porosis. Thus, the therapeutic safety of a low calcium
tion in which there is increased absorption of dietary diet is limited because of the risks of development of
calcium. The condition usually resolves by the end of osteoporosis. Hypercalciuria can cause nephrocalcino-
the first year of life. Occasionally it is associated with sis (Fig. 19.5.4) and urinary calculi. Where treatment
cardiovascular abnormalities (supravalvular aortic ste- is necessary, thiazide diuretics have proven useful.
nosis) and dysmorphic facial ‘elfin’ features (Williams
syndrome). The genetic defect for Williams syndrome
involves the elastin gene, and cases may be diagnosed Osteoporosis
using fluorescence in situ hybridization (FISH) studies.
Osteoporosis is decreased mineral content of the skele-
Treatment is directed at the cause of the hypercal-
ton. Measurement of bone mineral density has improved
caemia. Severe symptoms may necessitate initiation
over the last decade with the use of dual-energy X-ray
of a diuresis using sodium chloride infusion, dietary
absorptiometry (DEXA). DEXA must be interpreted
phosphate supplements to bind calcium, glucocorti-
carefully, in consideration of the size of the bone where
coids to reduce intestinal calcium absorption in vita-
measurements are taken and the age of the patient,
min D excess and bisphosphonates to prevent calcium
especially with regard to pubertal development of the
release from bone. A low-calcium milk formula is used
child. Osteoporosis is apparent radiologically only when
to treat idiopathic hypercalcaemia of infancy.
approximately half of the bone mineral content has been
lost. Causes of osteoporosis are given in Box 19.5.4.
Idiopathic juvenile osteoporosis is a rare condi-
Hypercalciuria tion that occurs in mid-childhood with gross demin-
The normal upper limit of urinary calcium excretion is eralization of the skeleton that can result in extensive
0.15 mmol per kg per day or < 0.7 mmol per mmol cre- fractures (particularly vertebral crush fractures). The
702
atinine. Hypercalcaemia usually causes hypercalciuria disease remits spontaneously with the onset of puberty.
 BONE MINERAL DISORDERS 19.5
Box 19.5.4 Causes of osteoporosis
Magnesium disorders
Calcium deficiency Causes of hypomagnesaemia are given in Box 19.5.5.
• Nutritional The symptoms of hypomagnesaemia resemble those
• Malabsorption
of hypocalcaemia, with increased neuromuscular irri-
Malignancy
• Leukaemia
tability. Severe hypomagnesaemia interferes with the
Glucocorticoid excess release of PTH, and consequently hypomagnesaemia
• Iatrogenic and hypocalcaemia often coexist.
• Cushing disease Hypermagnesaemia occurs rarely in the absence of
Homocystinuria renal failure. The exception is the neonate born pre-
Osteogenesis imperfecta maturely to a mother given magnesium sulphate for
Immobilization
pre-eclampsia.
Idiopathic juvenile osteoporosis

Box 19.5.5 Causes of hypomagnesaemia and

Osteopetrosis hypermagnesaemia

Osteopetrosis is a rare familial disorder of the skeleton Hypomagnesaemia

in which there is a defect in bone and cartilage resorp- • Malabsorption, prolonged intravenous therapy
tion, and hence of bone remodelling. This leads to a • Diuretic therapy
dense but brittle type of bone, which fractures easily. • Renal tubular acidosis
• Hereditary disorders of renal tubular resorption
Infants usually present early in life with a severe leu-
koerythroblastic anaemia, symptoms of compression Hypermagnesaemia
of cranial nerves (particularly optic atrophy leading • Neonate of mother given magnesium sulphate for
to blindness) and marked hepatosplenomegaly. The pre-eclampsia
bones show a characteristic dense and poorly mod- • Medications containing magnesium given to patients with
elled X-ray appearance. renal failure

703
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 20
PART

GASTROINTESTINAL
TRACT AND HEPATIC
DISORDERS

705
 20.1 Abdominal pain and
vomiting
Spencer Beasley, Andrew Day

Acute abdominal pain and vomiting are common

symptoms in children and a frequent reason for Abdominal pain later in the
­children to be taken to the doctor. Their causes are first year
many and diverse; those that require surgery must
be distinguished from those with a medical origin. The main surgical cause of abdominal pain between
Although there is considerable overlap of age in many 3 and 12 months of age is intussusception. Vomiting
disorders, other conditions occur only within a s­ pecific is a frequent accompanying feature, such that, when
age range; for example, pyloric stenosis is not seen the colicky abdominal pain is not pronounced, intus-
after the age of 3 months. susception must be distinguished from other causes of
vomiting in this age group (see below).

Intussusception
Abdominal pain in the first
In intussusception, the distal ileum (the intussuscep-
3 months of life tum) telescopes into adjoining distal bowel (the intus-
Abdominal pain without other symptoms is unusual suscipiens), resulting in intestinal obstruction. It can
in early infancy. Severe pain may be accompanied by occur at any age but is most likely in the infant between
other symptoms such as vomiting, abdominal disten- 3 and 18 months who suddenly develops screaming
sion or constipation. When pain is associated with attacks of pain with vomiting. During each episode of
other symptoms, it is more likely to have a surgical pain the infant becomes pale and may draw up the legs.
cause (e.g. malrotation with volvulus). The spasms of pain tend to last for 2–3 min-
Infantile colic is a very common condition that usu- utes and occur at intervals of about 10–20 minutes,
ally commences in the first few weeks of life. The cause although after a while the pain becomes more persis-
is poorly understood. The term ‘colic’ is sometimes tent. Vomiting is an early symptom. The passage of
used because of the common assumption that this pat- a few loose stools early on represents evacuation of
tern of behaviour is due to colicky abdominal pain but the bowel distal to the obstruction. The small volume
this explanation is controversial, and there are other and limited duration of loose stools in intussuscep-
more likely hypotheses including an irritable tempera- tion helps differentiate it from acute gastroenteritis.
ment (see Chapter 4.1). The term ‘infant irritability’ is Congestion of the intussusceptum may lead to the
now more commonly used. passage of blood-stained or ‘redcurrant jelly’ stools.
The infant with irritability/colic: Many infants with intussusception present with little
• has attacks of screaming more than pallor, lethargy and vomiting, and may have
• draws up the legs little evidence of abdominal pain. Should these symp-
• is unable to be comforted. toms be ignored, the infant may progress to develop
Significant vomiting is absent, bowel actions are signs of septicaemia or shock.
passed normally and the infant is otherwise thriving. The infant with intussusception looks pale, lethar-
There are no specific abnormal findings on examina- gic, anxious and unwell. A vague mass may be felt in
tion, or evidence of acute surgical problems such as the right or left upper quadrants of the abdomen but,
a strangulated inguinal hernia. The symptoms usually once abdominal distension has developed, the mass
disappear by the fourth month of age; until then, treat- becomes obscure and difficult to palpate (Fig. 20.1.1).
ment is supportive. The apex of the intussusceptum may be palpable on
In a vulnerable or unstable family situation, rectal examination in a few, and the examining glove
repeated irritability may place the infant at risk of may be blood-stained. A plain X-ray of the abdo-
abuse. men will often be normal but may show an unusual

706
 Abdominal pain and vomiting 20.1
Differential diagnosis
Gastroenteritis is often confused with intussuscep-
tion but becomes obvious on clinical grounds by the
volume and persistence of the fluid stools. The plain
radiological appearance of the abdomen may be simi-
lar in both conditions. Where doubt persists, ultraso-
nography or a gas or barium enema is indicated. Other
causes of intestinal obstruction include volvulus sec-
ondary to malrotation, a band from a Meckel diver-
ticulum, a duplication cyst or a strangulated inguinal
hernia. Examination of the groin will detect the irre-
ducible tender lump of a strangulated hernia.
Fig. 20.1.1 Abdominal mass evident on left side of the
abdomen in this toddler presenting with characteristic features
of intussusception.
Acute abdominal pain in
bowel gas distribution or features of bowel obstruc- older children
tion. Ultrasound examination may be helpful in mak-
ing the diagnosis. Where intussusception is suspected Children often present with abdominal pain and in
clinically or confirmed on ultrasonography, a gas or most no specific cause is found. Constipation and mes-
barium enema must be performed (unless the child has enteric adenitis are probably the most common non-
peritonitis). The enema will demonstrate the position surgical identifiable causes.
of the apex of the intussusception (Fig. 20.1.2).
Acute appendicitis
Treatment
Appendicitis may occur at any age, although it is rare
Intussusception can be reduced non-operatively by under 5 years of age. Early diagnosis is difficult in the
gas enema or by hydrostatic reduction under ultra- young child (under 5 years) and in developmentally
sonographic control: these techniques are success- delayed children; many of these children have estab-
ful in 80–90% of patients. If gas enema facilities are lished peritonitis or an appendix abscess at presenta-
not available, a barium enema under continuous flu- tion. Delays in the diagnosis of acute appendicitis in
oroscopic control is a less effective but satisfactory childhood is related in part to its variable symptomatol-
alternative. Peritonitis and septicaemia, which suggest ogy. For example, there may be relatively l­ittle abdomi-
the presence of dead bowel, are the only contraindi- nal pain, vomiting may be absent and ­diarrhoea may be
cations to attempted enema reduction. A dehydrated a misleading feature.
child should have intravenous fluid resuscitation and Nevertheless, the most important and consistent
be wrapped in warm blankets before commencing an feature is localized abdominal pain. The pain may be
enema reduction. The success of enema reduction intermittent and colicky initially, or situated in the epi-
is recognized when there is sudden or rapid flow of gastrium or periumbilical region, but soon shifts to
gas or barium into the ileum. If partial reduction is the right iliac fossa. Constant pain that is worse with
achieved, and the child remains in good clinical condi- movement is the result of peritoneal irritation (‘peri-
tion, a further enema should be attempted after several tonism’). Vomiting occurs in the majority of children,
hours (so called ‘delayed repeat enema’), and in about and some may pass a loose stool. The temperature is
half of these patients it will be successful. Recurrence usually normal or slightly raised, but occasionally may
of intussusception occurs in about 9% of children be in excess of 38 °C.
after enema reduction, usually within days. Surgery is Physical examination of the abdomen should be
reserved for: directed at showing that movement of adjacent peri-
• those in whom enema reduction has failed toneal surfaces exacerbates the pain. The child's
• those who have clinical evidence of necrotic bowel, cooperation makes assessment easier, and repeated
such as peritonitis and septicaemia examination of the abdomen may be required to make
• those in whom there is evidence of pathological the diagnosis. A child with appendicitis usually will
lesions at the lead point. exhibit tenderness and guarding localized to the right

707
 20.1 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

Fig. 20.1.2 Abdominal X-ray demonstrating air enema with apex of intussusception in the right lower quadrant.

iliac fossa. Gentle palpation and percussion tender- ­ iagnosis of acute appendicitis to be made. Bowel
d
ness, performed while observing the child's face, will sounds may be normal or reduced and contribute little
provide the most reliable evidence of abdominal ten- to the diagnosis.
derness and involuntary guarding. Rebound tender- Peritonitis should be suspected when the child is
ness is an unreliable sign in children, and attempts to acutely ill with abdominal pain and fever and is reluc-
elicit the sign may cause unnecessary pain and destroy tant to move. On examination, there will be general-
the child's confidence in the doctor. Rectal examina- ized abdominal tenderness and guarding.
tion is required rarely and is primarily indicated if a Laboratory studies are rarely helpful in making the
pelvic appendix or pelvic collection is s­uspected. It diagnosis but the urine should be checked routinely.
should not be performed when examination of the ven- Ultrasonography has a role when the diagnosis is
708 tral abdominal wall has already enabled a c­ onfident uncertain.
 Abdominal pain and vomiting 20.1

Clinical example

Mark, a 10-year-old boy, had 36 hours of

constant lower abdominal pain, which steadily
became more severe. He vomited once initially,
and was ‘off his food’. Movement made the
pain worse. On examination, he was afebrile but appeared
flushed. He was tender to gentle palpation in the right
iliac fossa and had percussion tenderness in the same
region. The urine contained a few white and red cells but
no bacteria. No other investigation was performed. At
laparoscopy an acutely inflamed appendix was removed.

Differential diagnosis
Mesenteric adenitis is the most difficult disorder to
distinguish from acute appendicitis. In g­ eneral, local-
ization of pain and tenderness is variable and less spe-
cific, and the temperature may be higher. Guarding is
rarely present in mesenteric lymphadenitis.
Other conditions that may mimic acute appendici-
tis are relatively uncommon. Meckel diverticulitis has
symptoms identical to those of appendicitis, such that
differentiation is possible only at laparoscopy or lap- Fig. 20.1.3 Plain X-ray of the abdomen demonstrating gross
arotomy. Pain in the right iliac fossa may represent faecal overload in a child with severe constipation causing
radiation from torsion of the right testis or a strangu- abdominal pain. The child also had regular soiling.
lated inguinal hernia, and highlights the importance
of examination of the genitalia in all boys with lower
abdominal symptoms (see Chapter 9.1). Acute abdom- Less common causes of abdominal pain include uri-
inal pain may occur with renal colic, pyelonephritis nary tract infection, haemolytic–uraemic syndrome
and, at times, acute glomerulonephritis. Pain and ten- and diabetes. Ovarian torsion may present with pain
derness is usually referred to the loin. Urine analysis and vomiting in girls. Acute hepatitis, cholecystitis and
and radiology will confirm the diagnosis. In Henoch– pancreatitis, although all rare in childhood, may also
Schönlein purpura, the abdominal pain is often severe cause abdominal pain.
and colicky, and may be accompanied by vomiting. In pancreatitis, vomiting is prominent and epigastric
The characteristic skin lesions over the buttock and tenderness with guarding may be marked. These chil-
legs may be inconspicuous or absent when the child is dren often look ill and obtunded. Pancreatitis is most
first examined. commonly due to viral illnesses or may follow a blunt
In the appropriate ethnic group, sickle cell anae- injury to the abdomen, (e.g. a handlebar injury), and
mia is a prominent cause of acute abdominal pain and several weeks later may produce a pancreatic pseu-
should be considered in a pale child with splenomegaly. docyst. The diagnosis is suggested by increased levels
Children with cystic fibrosis frequently experience of plasma or urinary amylase or plasma lipase, and
episodes of abdominal pain from faecal impaction is confirmed by ultrasonography initially, followed by
(called ‘meconium ileus equivalent’), a well-known magnetic resonance imaging (MRI) if indicated clini-
manifestation of this disease. The symptoms resolve cally. The management of acute pancreatitis involves
following a bowel washout. correction of shock, intravenous fluid administration,
It is unusual for constipation in an otherwise nor- bowel rest, nasogastric suction to keep the stomach
mal child to produce sufficient abdominal pain to sug- empty, and analgesia.
gest a surgical emergency. A plain X-ray of the abdomen Right lower-lobe pneumonia may masquerade
will demonstrate the extent of faecal accumulation as appendicitis. The child is usually febrile, with an
(Fig. 20.1.3). It should be remembered, however, that the increased respiratory rate, and has a cough. Signs of
diagnosis of constipation can almost exclusively be made pneumonia may be difficult to elicit clinically, so that a
on clinical grounds. Abdominal X-ray is not a standard chest X-ray will be required.
tool in assessing for constipation and should be reserved A general summary of disorders associated with
solely for other indications or more complex cases. abdominal pain is listed in Box 20.1.1. 709
 20.1 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

rarely requires investigation or specific therapy. Gastro-

Box 20.1.1 Causes of abdominal pain in childhood
oesophageal reflux disease (GORD), defined as reflux
Common associated with symptoms or complications, can also
• Appendicitis begin in infancy. It may also resolve over time, but may
• Mesenteric adenitis persist into later childhood, with symptoms of belch-
• Constipation ing, acid rise and intermittent vomiting. Substernal
• Intussusception and epigastric pain (‘heartburn’) may suggest reflux
• Urinary tract infection
oesophagitis. Oesophageal pH monitoring measures
• Torsion of the testis
lower oesophageal pH over a period of 24 hours and
Uncommon can be used to quantify the reflux episodes and to
• Volvulus secondary to malrotation establish the relationship of reflux to symptoms (see
• Meckel diverticulitis Chapter 20.4). Oesophagoscopy and biopsy may con-
• Renal colic firm oesophagitis and also exclude other causes (such
• Pyelonephritis as eosinophilic oesophagitis) of symptoms.
• Acute glomerulonephritis
Initial management of GORD involves the admin-
• Glandular fever
• Peptic ulceration istration of acid suppressors (e.g. H2-receptor antag-
• Reflux oesophagitis onists or proton pump inhibitors). However, when
• Inflammatory bowel disease (e.g. Crohn's disease) medical therapy is unsuccessful or when significant
• Drug ingestion (e.g. salicylates, non-steroidal anti- complications of GORD are present (e.g. episodes of
inflammatory drugs, corticosteroids, some antibiotics, reflux aspiration), surgical management of the GORD
imipramine, phenytoin, iron) by laparoscopic fundoplication may be indicated.
• Abdominal migraine
• Lower-lobe pneumonia

Rare
• Sickle cell anaemia Recurrent abdominal pain
• Henoch–Schönlein purpura
• Pancreatitis in children
• Cholecystitis Recurrent bouts of abdominal pain is a fairly common
• Acute hepatitis
• Diabetes mellitus
paediatric presentation and one that may cause great
• Haemolytic–uraemic syndrome anxiety to parents. The following clinical example is
• Torsion of the ovary illustrative of this syndrome.

Peptic ulceration Clinical example

The abdominal pain of peptic ulceration is epigastric
Thomas, aged 7 years, was brought in by his
and may be worse prior to meals. Nausea and vom-
mother, who stated that for the last 4 months
iting may occur. Haematemesis and melaena suggest he had had severe bouts of abdominal pain.
the diagnosis; alternatively it may be made following The attacks occurred at any time, but were
investigation of iron deficiency anaemia. more frequent at breakfast time. He was never awakened at
Acute gastritis and acute duodenitis produce abdom- night by them. Vomiting was not a feature, and his bowels
inal pain with epigastric tenderness. A positive urea had been regular. The pain usually was localized to the
periumbilical region and usually lasted less than 1 hour. His
breath test is suggestive of Helicobacter pylori infection.
parents felt that Thomas was pale and had a poor appetite.
Culture of biopsy specimens taken during e­ ndoscopic He was of normal height and weight. Physical examination
examination of the upper ­ gastrointestinal tract will was unremarkable. The urine was clear. Further questioning
confirm H. pylori (see Chapter 20.4). Treatment with elicited the fact that the bouts of abdominal pain had
a combination of antibiotics (e.g. ampicillin and clar- occurred periodically since the age of 3 years.
ithromycin) and acid suppressors (e.g. omeprazole) is
usually successful, but relapse may occur if the treat-
ment course is incomplete.
Doctors will be impressed by the concern exhibited
by parents of these children, who vividly describe the
Gastro-oesophageal reflux disease and
severe pain the child experiences; but there is a dispar-
reflux oesophagitis
ity between the parents’ description and the physical
Physiological gastro-oesophageal reflux is very com- findings on examination of the abdomen. Investigation
mon in infancy and resolves with growth. This requires almost invariably produces negative results. Enquiry
710
an expectant approach with reassurance and only into the personality of the child and into the home
 Abdominal pain and vomiting 20.1
s­ituation may reveal that the child is anxious or
stressed, but often the pain occurs for no apparent Vomiting in the neonatal period
reason. Sometimes the episodes of pain appear to be In the first 24 hours of life, neonates frequently vomit
related to stress within the family, or occur on school small amounts of mucus and blood swallowed during
days only. labour. If this vomiting does not clear spontaneously,
A diagnosis of non-organic recurrent abdominal gastric lavage with normal saline will usually relieve it.
pain (RAP) can be made only after careful appraisal In the early weeks of life, many normal newborn babies
of the child in relation to the environment, and regurgitate after feeds. Also known as ‘spitting up’ or
when the physical examination is normal. Most chil- ‘possetting’, this is a benign feature of physiological
dren need no investigations apart from urine culture. immaturity in the upper gut and resolves with time.
Further investigation is required if the abdominal pain
is associated with abdominal tenderness or distension,
symptoms that wake the child from sleep, bile-stained Systemic infection
vomiting, persistent diarrhoea, fever, weight loss or
Vomiting is one of the many non-specific signs of
urinary symptoms. Differentials to consider when such
infection in the neonate. Thus, unexplained vomiting
symptoms are present include inflammatory bowel
should be an indication to culture the blood, urine and
disease, coeliac disease, malrotation with intermit-
cerebrospinal fluid. Urine will usually be obtained by
tent volvulus, and abdominal migraine. Appropriate
suprapubic aspiration in this age group.
investigations would depend on the pattern of symp-
toms, but may include full blood count, erythrocyte
sedimentation ratio (ESR), C-reactive protein (CRP), Bowel obstruction
liver chemistry and albumin, screening for coeliac dis-
ease, markers of malabsorption (such as iron, folate, In duodenal obstruction, vomiting appears early and
and vitamins D and B12), stool testing, and endoscopic is bile-stained because the site of the obstruction is
studies of the upper and lower gastrointestinal tract. almost always at the second part of the duodenum,
The urine should also be examined. If the vomitus just distal to the ampulla of Vater. In duodenal atre-
is bile-stained, malrotation with volvulus should be sia, there may be other abnormalities such as Down
excluded by an urgent barium meal. syndrome and imperforate anus. The bile-stained vom-
The general status of the patient must be assessed. iting commences from birth. The diagnosis is made on
Retardation of height and growth may occur in plain X-ray of the abdomen (see Chapter 11.5). Where
chronic inflammatory bowel disease and malabsorp- there is bowel obstruction beyond the duodenum (e.g.
tion syndromes. Pallor may be associated with anae- small bowel atresia, Hirschsprung disease and meco-
mia or conditions such as lead poisoning, sickle cell nium ileus), vomiting commences slightly later and
anaemia and other haemolytic diseases. Abdominal is associated with increasing abdominal distension
migraine may be seen in children with a family his- (see Chapter 11.5). A strangulated inguinal hernia
tory of classical migraine; as time goes by the may cause a bowel obstruction when a loop of ileum
child's abdominal pain may become associated with becomes trapped within the hernial sac at the external
and eventually be replaced by classical migraine inguinal ring. The diagnosis becomes evident when a
headaches. tender irreducible lump is observed in the groin (see
Chapter 9.1).

Management of recurrent abdominal pain

Malrotation with volvulus
Parents will find it helpful to realize that the prob-
lem has been taken seriously by the doctor, and the Volvulus in a neonate or infant with malrota-
doctor must understand the parents’ perception of the tion causes a high bowel obstruction and produces
abdominal pain. With this knowledge and the nega- ­bile-stained vomiting. The volvulus may cut off the
tive physical findings, reassurance can be given more blood supply to the midgut and lead to small bowel
positively. Once parents are convinced that there is infarction, septicaemia and death if not identified
no significant organic basis to the RAP, they are usu- and managed promptly. Any infant with bile-stained
ally much relieved. The child should be encouraged vomiting, otherwise unexplained, should be assumed
in all activities and self-esteem improved. Recurrent to have malrotation with volvulus until proven other-
pain tends to disappear by the age of 12 years but in wise. A barium meal will confirm the diagnosis. An
females may recur at the time of menarche. However, urgent laparotomy is required to untwist the bowel
some children with recurrent pain in childhood pres- (Fig. 20.1.4) and to perform a Ladd procedure to
ent in adult life with symptoms of irritable bowel broaden the m ­ esentery of the small bowel; this will
711
syndrome. prevent s­ ubsequent volvulus.
 20.1 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

r­ ecessively, and a number can now be treated. Frequently,

the presentation is with unexplained vomiting, lethargy,
collapse, seizures and coma (see Chapter 10.5).

Vomiting in infancy
Vomiting is a common non-specific symptom in
infancy, and disease of almost every system may pres-
ent with vomiting.

Infection
Fig. 20.1.4 Malrotation with volvulus. The small bowel is Vomiting is frequently associated with acute infections
twisted upon its mesentery. such as tonsillitis, otitis media, pneumonia, meningi-
tis and urinary tract infection. Physical examination
will exclude many of these but early signs may be
Hypoglycaemia minimal in meningitis and pneumonia, such that a
Vomiting may be the only symptom of hypoglycaemia ­lumbar puncture and chest X-ray will be required if
in the neonatal period. It is more common in ‘small for these are suspected. In infants with urinary tract infec-
dates’ babies and in infants of diabetic mothers, but tion, ­dysuria, frequency of passing urine and loin pain
may be seen in any stressful situation in the neonatal ­cannot be relied upon for diagnosis, and the urine
period, including low birth weight, neonatal meningi- must always be examined (see Chapter 18).
tis, septicaemia and severe Rhesus isoimmunization.
Symptomatic hypoglycaemia does not usually occur
Lesions of the gastrointestinal tract
with a blood glucose in excess of 2 mmol/L.
Conditions that produce vomiting in infancy are dif-
Renal disease ferent from those seen in the neonatal period, except
for duodenal obstruction from volvulus complicating
In the neonatal period, urinary infection and renal malrotation, and GORD. Failure to recognize mal-
insufficiency may present with vomiting and poor rotation with volvulus may result in infarction of the
weight gain, reflecting an underlying urinary tract entire midgut (see Chapter 11.5). Bowel trapped in a
abnormality. Initial urological investigation will strangulated inguinal hernia in an infant will also pro-
include urine culture, renal ultrasonography, micturat- duce vomiting. The diagnosis can be made easily if the
ing cystourethrography, and estimation of electrolytes, inguinal orifices are examined (see Chapter 9.1).
urea and creatinine. Renal tubular lesions occasionally
present in the neonatal period with vomiting.
Gastro-oesophageal reflux disease
Adrenal insufficiency See Chapter 20.4.
Congenital adrenal hyperplasia, in which there
is deficiency of the enzyme 21-hydroxylase (see Pyloric stenosis
Chapter 19.3), presents with ambiguous genitalia in
the female. If this is not recognized (as in the male), This is one of the most dramatic causes of vomiting
it may lead to unexplained vomiting, dehydration and in infancy. Typically, the onset is sudden, commencing
collapse early in the second week of life. If the adre- between the second and sixth week of life. Males are
nal insufficiency is of the salt-losing type, the diagno- affected five times more often than females and there is a
sis is further suspected by finding low levels of sodium definite familial incidence. Before the onset of vomiting,
and increased levels of potassium in the serum, and is these infants feed well and are thriving. The ­vomiting
­confirmed by appropriate hormonal studies. is forceful and rapidly becomes projectile. The infant
loses weight and becomes dehydrated. Despite vomiting,
these infants remain hungry and are keen to feed even
Inborn metabolic errors
immediately after vomiting. The v­ omitus is not bile-
Although individually rare, there are a number of stained but may contain altered blood. The ­diagnosis is
inborn errors involving, separately, amino acid, carbohy- made clinically by feeling the thickened pylorus (‘pyloric
712
drate and organic acid metabolism. Most are ­inherited tumour’) in the midline in the epigastrium between
 Abdominal pain and vomiting 20.1
the rectus abdominis muscles or in the angle between
the right rectus and the liver edge. The pyloric tumour
is palpable as a hard mobile mass about the size of a
small pebble or olive. Peristaltic waves passing from the
left costal margin to the right hypochondrium (‘golfball
waves’) may be visible long after the last feed. Palpation
of the tumour is sufficient to establish the diagnosis.
Pyloric stenosis can also be shown on ultrasonography
(which reveals a thickened pylorus) and barium meal
(which shows delayed gastric emptying and a narrow
pyloric canal). These infants develop a hypokalaemic,
hypochloraemic metabolic alkalosis which, together
with dehydration, must be corrected before surgery.
Pyloromyotomy is curative (Fig. 20.1.5).
Fig. 20.1.5 Thickened pylorus in pyloric stenosis as seen during
pyloromyotomy.
Gastroenteritis
Vomiting in association with fluid stools is suggestive
of gastroenteritis, particularly if the stools c­ontain
mucus or blood. However, these features may be
Strangulated inguinal hernia
seen in a variety of other medical and surgical disor- Strangulation of an inguinal hernia is common in
ders, which include intussusception and appendicitis. infants and young children. All irreducible ingui-
The diagnosis and management of gastroenteritis is nal hernias should be assumed to be strangulated. In
­discussed in Chapter 20.2. practice, the vast majority of so-called irreducible her-
nias can be reduced manually by skilled hands (see
Malabsorption Chapter 9.1).
In the majority of malabsorption syndromes vomiting
is not a feature. Vomiting can be a presenting symptom
in some children with coeliac disease (gluten enteropa- Vomiting in older children
thy; see Chapter 20.3).
Vomiting in older children is usually associated with
Intussusception infection, particularly viral or bacterial infection of the
respiratory and gastrointestinal tracts. Nevertheless,
Vomiting commences early in intussusception and is there are some other less frequent, but important,
the most consistent symptom. The general features, causes of vomiting.
diagnosis and treatment have been discussed above. The possibility of an intracranial neoplasm should
always be considered in a child with unexplained vom-
iting. There may be signs of increased intracranial
pressure with midline cerebellar tumours, tumours
Clinical example
involving the fourth ventricle, and tumours involv-
Tim, a previously well 22-month-old infant, ing the pons or medulla. Initially, vomiting tends to
suddenly became unwell with onset of occur in the morning before breakfast. There may be
vomiting and a temperature of 38.5 °C. remissions for several days but the vomiting invariably
Within 12 hours he started passing frequent, returns.
loose motions. Associated with this he appeared to have
bouts of abdominal pain. On the second day the vomiting
stopped but the diarrhoea persisted at a rate of more than Migraine
eight stools per day. On presentation to the emergency
department, Tim's weight was 13.6 kg, compared with In the older child, the association of severe paroxysmal
14.5 kg 3 weeks previously. He was clinically assessed to be frontal headache with pallor and vomiting is suggestive
5–8% dehydrated and was treated with an oral rehydration of migraine (see Chapter 17.5). A ­positive family his-
solution via a nasogastric tube. A provisional diagnosis of tory is common. In the younger child, attacks of pallor
acute gastroenteritis was made. His temperature gradually or vomiting may be the only symptom. The diagnosis
settled over 24 hours and oral feeds were introduced once
rehydration was complete. His stools returned to their normal
of migraine is made on clinical history but, where it
pattern after 5 days. Rapid stool testing for rotavirus antigen is difficult to exclude an intracranial s­ pace-occupying
was positive. lesion clinically, cerebral computed tomography may
713
be required.
 20.1 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

Acute appendicitis and peritonitis Cyclical vomiting syndrome

In acute appendicitis in childhood, vomiting is a fre- Cyclical vomiting is a clinical syndrome of persistent
quent early symptom but is usually preceded by periodic vomiting of childhood. The severity varies,
pain. The general features of appendicitis have been but ketosis and metabolic acidosis may develop rap-
described above. In the young child (under 5 years), idly. The aetiology is unknown and attacks usually
vomiting with or without diarrhoea may be the only cease spontaneously. Children with cyclical vomit-
apparent symptom. Physical examination in this age ing are often tense and anxious, and may develop
group can be difficult and unreliable; the child will migraine or psychosomatic disease later in life.
prefer to lie still, as movement worsens the pain. This However, cyclic vomiting syndrome is a diagnosis of
pain and the fear of its exacerbation by palpation may exclusion; it is essential to exclude other important
make the child appear uncooperative. It is only by causes of ­recurrent vomiting, such as intermittent
repeated examination of the abdomen and an ongoing volvulus from malrotation, neurological causes and
high index of suspicion that the diagnosis will be made metabolic disease.
before widespread peritonitis has developed.

Poisoning
Vomiting and respiratory and circulatory collapse in
Practical points
a previously well child should raise the possibility of
poisoning (see Chapter 5.3). Non-accidental poison- • Intussusception, the primary surgical cause of abdominal
pain between 3 and 12 months of age, usually presents
ing is becoming more frequent. with vomiting, abdominal pain, pallor and lethargy.
• Although appendicitis may occur at any age, it is rare in
Psychological causes of vomiting preschool children; in this age group its presentation may
be atypical, making early diagnosis a challenge.
Psychogenic vomiting may occur in any age group. • Recurrent abdominal pain commonly occurs in children;
It can be associated with attempts to force-feed a toddler it is often benign and self-resolving. Warning signs of a
significant underlying organic cause include weight loss,
or schoolchild, after punishment, and as an attempt to
night pain, pain worse with movement and bile-stained
avoid situations perceived as threatening, such as going vomiting.
to preschool or school. Almost any stressful ­situation • Vomiting is a very non-specific symptom in infancy and
may precipitate vomiting in a tense or anxious child. early childhood, and may indicate infection.
The absence of abnormal physical signs will be a feature.

714
 Infective diarrhoea and 20.2
inflammatory
bowel disease
Jeremy Rosenbaum, George Alex

The basic pathological mechanisms causing diarrhoea to severe infection causing life-threatening diarrhoea
include osmotic, secretory and inflammatory pro- because of pre-existing malnutrition and poor access
cesses (Table 20.2.1). Often more than one mechanism to primary care. Similarly, Indigenous Australian chil-
occurs simultaneously resulting in diarrhoea. dren require hospitalisation due to rotavirus gastroen-
Diarrhoea is defined as a measured stool volume teritis about three to five times more commonly than
greater than 10 mL per kg per day. Both the consis- non-Indigenous children.
tency of the stool (loose or watery) and frequency The mucosal damage caused by rotavirus (Fig. 20.2.2)
(usually more than three stools in a 24-hour period) occurs primarily in the small intestine. It results in vil-
are important defining features of diarrhoea. lus destruction and loss of digestive enzymes found
Acute diarrhoea usually lasts less than 10 days and on the tips of villi. This causes impaired digestion of
can have a major impact on the individual's fluid and carbohydrates, impaired intestinal absorption of fluid
electrolyte status. The commonest cause of acute and electrolytes, and fluid loss from the intestine. The
diarrhoea in children is an enteric infection (acute need for structural repair places considerable nutri-
gastroenteritis). This can be driven by all three of the tional demands on malnourished children. Repeated
pathological mechanisms mentioned above. asymptomatic reinfection helps maintain immunity.
Chronic diarrhoea is defined as symptoms being The other major viral cause of hospital admissions
present for more than 2–3 weeks. This requires fur- is the enteric adeno family of viruses. Norovirus is also
ther investigation as several important causes such as implicated in winter outbreaks of vomiting. Other less
inflammatory bowel disease need to be excluded to common viruses, such as calicivirus, astrovirus and
avoid possible systemic complications and negative other small viruses, have also been implicated in gastro-
effects on the nutritional state of the child. This can enteritis requiring hospitalization. Cytomegalovirus
also have a significant effect on the nutritional state of (CMV) enteritis should be considered in immunocom-
a child (see Chapter 20.3). promised patients.

Bacterial and parasitic gastroenteritis

Acute gastroenteritis Bacteria cause fewer episodes of acute gastroenteri-
tis in developed countries than viruses. The main
Viral gastroenteritis
causes of bacterial infection are Campylobacter jejuni,
Rotavirus infection (Fig. 20.2.1) is the most common Salmonella spp., Shigella spp. and various types of
cause of acute gastroenteritis in children worldwide, Escherichia coli, each accounting for a small percent-
with a peak incidence between 6 and 24 months of age. Clostridium difficile, known to cause pseudomem-
age. It is also a major cause of mortality in developing branous colitis following systemic antibiotic therapy,
countries and is responsible for the majority of cases is usually hospital-acquired and becoming increas-
where hospital admission is required. In Australia, ingly resistant to first line treatment options.
before routine infant rotavirus immunization was In developing countries, E. coli (enterotoxigenic,
introduced in 2007, approximately 10 000 children enteropathogenic and enteroinvasive), Shigella spp.
aged under 5 years were hospitalized each year due to and Entamoeba histolytica are especially important:
rotavirus infection, 115 000 visited a general practitio- E. coli because of the large number of episodes it
ner, 22 000 required an emergency department visit causes, Shigella because it causes prolonged, debil-
and, on average, one Australian child died each year itating illness and antibiotic-resistant strains are
from the complications of dehydration and shock. emerging, and Entamoeba because it causes severe life-
Since 2007, these numbers have fallen dramatically. threatening dysentery. These organisms are rarely
Infants in developing countries are more susceptible acquired in industrialized countries. 715
 20.2 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

Table 20.2.1 Classification of diarrhoea

Osmotic Secretory Inflammatory

Clinical features Ceases when enteral feeding Continues when enteral Presence of blood and
is ceased feeding is ceased mucus in the faeces

Stool volume < 200 mL/day > 200 mL/day Variable, usually < 200 mL/day

Faecal sodium < 60 mosmol/L 90 mosmol/L Variable

The parasite Giardia lamblia is a rare cause of

acute dehydrating diarrhoea, but a common cause
of persistent diarrhoea with flatulence and bloat-
ing. It is most common in toddlers and young chil-
dren, and also in their parents and caregivers. It is
also common in people who have travelled o ­ verseas
especially to developing countries where drinking
water supplies may be contaminated. Another parasite,
Cryptosporidium, is another rare cause of acute diar-
rhoea in some infants admitted to hospital and should
be considered in immunocompromised patients.

Clinical features
Acute gastroenteritis is a relatively common cause of
presentation to medical attention, but it should remain
a diagnosis of exclusion, because several systemic dis-
orders and surgical emergencies can present with diar-
rhoea and/or vomiting (Box 20.2.1) and should be
considered in the differential diagnosis.
Fig. 20.2.1 The rotavirus (electron micrograph).

A B
716
Fig. 20.2.2 Scanning electron microscope appearances of (A) normal and (B) rotavirus-infected calf jejunum. Villi are short, the epithelium is
damaged, and crypts are deep. (Courtesy of DGA Hall, Institute for Animal Health, Compton, UK. With permission from Walker et al 1991.)
 Infective diarrhoea and inflammatory bowel disease 20.2
Management
Box 20.2.1 Differential diagnosis of acute diarrhoea and
vomiting in infants and children Once the diagnosis of acute gastroenteritis is made on
thorough clinical history and physical examination,
Enteric infection
the next step is to assess the degree of dehydration
• Rotavirus
• Other viruses
and institute an appropriate plan for rehydration. This
• Bacterial should be combined with nutritional support that aids
• SaImonella spp. the patient during the ­recovery phase.
• Shigella spp.
• Escherichia coli Dehydration
• Campylobacter jejuni
• Protozoa
The risk of dehydration is inversely related to age, with
• Cryptosporidium young infants being at greatest risk because they have a
• Giardia lamblia high surface area : body volume ratio, resulting in increased
• Entamoeba histolytica insensible fluid loss. They also tend to have more severe
• Food poisoning vomiting and diarrhoea than older children and adults.
• Staphylococcal toxin Fluid loss is usually assessed on the basis of percent-
age body weight loss. Physical signs of dehydration are
Systemic infection
• Urinary tract infection
not usually apparent until 4% of body weight is lost.
• Pneumonia The signs of dehydration traditionally described are
• Septicaemia outlined in Box 20.2.2. The three signs that discrimi-
nate best between dehydration and adequate hydration
Surgical condition are deep breathing, decreased skin turgor and poor
• Appendicitis peripheral perfusion.
• Intussusception
• Partial bowel obstruction Electrolyte loss
• Hirschsprung disease
Dehydration is usually isotonic (water and electrolytes
Other being lost in equal amounts). Hypertonic hypernatrae-
• Diabetes mellitus mic dehydration (fluid loss > electrolyte loss) occurs in
• Antibiotic diarrhoea
5–10% of children with acute gastroenteritis, and hypo-
• Haemolytic–uraemic syndrome
tonic hyponatraemic dehydration (electrolyte loss >
fluid loss) can occur if the colon (a major site of sodium
resorption) is out of circuit (e.g. in short gut syndrome).
Symptoms of acute gastroenteritis are watery diar-
rhoea (up to 10–20 stools daily) with or without vom- Box 20.2.2 Assessment of dehydration
iting and fever (to 39–40°C). Vomiting is often the
predominant feature early in the illness, followed by Mild (≤ 5% body weight loss)
diarrhoea. If both occur concurrently, there is an • Dry mucous membranes
• Decreased peripheral perfusion*
increased risk of dehydration. Maintaining hydra-
• Thirsty, alert, restless
tion is easier after the cessation of vomiting. Blood,
mucus and the passage of small frequent bowel actions Moderate (6–9% body weight loss)
accompanied by abdominal pain suggest a diagnosis • Exaggeration of the above
of colitis due to bacterial gastroenteritis (‘bacterial • Lethargic but irritable
dysentery’), amoebic dysentery or, potentially, inflam- • Rapid pulse, normal blood pressure
matory bowel disease. • Sunken eyes, sunken fontanelle
• Oliguria is usually obvious
• Pinched skin retracts slowly (1–2 s)*

Investigations Severe (≥ 10% body weight loss)

• General appearance:
Stool samples should be sent for microscopy, b ­ acterial • Infants: drowsy, limp, cold sweaty, cyanotic limbs, comatose
culture and sensitivities (MC + S). Samples should also • Older children: apprehensive, cold, sweaty, cyanotic limbs
be sent for ova, cysts and parasites (OCP) and viral • Rapid feeble pulse, low blood pressure
studies, which may include enzyme-linked immunosor- • Sunken eyes and fontanelle
bent assay (ELISA), polymerase chain reaction (PCR) • Pinched skin retracts slowly (> 2 s)*
and viral culture. Appropriate treatment should not be • Deep acidotic breathing*
withheld pending results. Sending several stool sam-
ples from different bowel actions increases the positive
* These are the only signs proven to discriminate between 717
hydration and dehydration.
yield of the test and is recommended.
 20.2 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

If corrected too rapidly, hypernatraemic dehy-

Box 20.2.3 An infant of 10 kg estimated at 8%
dration can cause convulsions due to rapid shifts of dehydration has fluid requirements equal to
water into cells. Hyponatraemic dehydration can also
cause significant neurological morbidity and mortality Maintenance 100 × 10 kg = 1000 mL
and, in contrast to the hypernatraemic state, requires Deficit 8% of 10 kg = 800 mL
­vigorous replacement of sodium. Nasogastric rehydra- Total = 1800 mL
tion has a much lower risk of these electrolyte compli- Using oral rehydration the deficit can be replaced in 6 h
rather than 24 h, so in the above example the infant would
cations than intravenous rehydration.
be offered fluid as follows:

Rehydration guidelines First 6 hours

Deficit = 800 mL
See also Chapter 6.1. Maintenance 6/24 of 1000 = 250 mL
Total = 1050 mL (175 mL/h)

No dehydration Next 18 hours

Maintenance 18/24 of 1000 = 750 mL (45 mL/h)
• Nutritional intake and fluids should not be Another simple method that gives about the right answer is
modified and should be encouraged to keep up with to calculate the fluid deficit, double it, and give that volume
ongoing losses, avoiding the need for rehydration over 6–12 h.
via nasogastric or intravenous route.

Mild to moderate dehydration

Rapid nasogastric rehydration
• Oral rehydration solution (ORS) is the cornerstone
• 25ml/kg/hr for 4 hours
of successful rehydration and is recommended
• Suitable for the majority of patients with
globally for the management of acute diarrhoea.
gastroenteritis and moderate dehydration
• The success of ORS is based on the principle
that intestinal sodium transport is enhanced by Slower nasogastric rehydration
glucose transport in the small intestine and that this
sodium-coupled mechanism for glucose transport • Slower rehydration is preferred for the following patients:
remains intact during acute gastroenteritis. • Infants < 6 months
• To facilitate optimal absorption of sodium, glucose • Co-morbidities present.
and water, the sodium and glucose must be in the • Children with significant abdominal pain.
range recommended (Table 20.2.2). • Replacing deficit over first 6 hours and then daily
• Rehydration of deficit should take place over 4–6 maintenance over the next 18 hours.
hours and can be given orally or, if either vomiting
Severe dehydration (≥ 10%)
or fluid refusal is a problem, by nasogastric tube.
Ondansetron can be administered once in this • If circulatory insufficiency is present, intravenous
setting but not in children <6 mo or <8 kg. therapy is required. The usual requirement is to
• If unable to maintain oral intake then maintenance fill the vascular compartment quickly to restore
fluids should be continued either by NGT or circulation. This will require rapid rehydration,
intravenous route with monitoring of potential often using boluses of normal saline (10–20 mL/kg)
ongoing losses during this time. (see Box 20.2.3). by intravenous or intraosseous infusion.

Table 20.2.2 Oral rehydration preparations available in Australia

Na K Cl Citrate Glucose

World Health Organization 90 20 80 10 90

Hydralyte 45 20 45 30 90

Gastrolyte 60 20 60 10 90

718 Repalyte 60 20 60 10 90

Concentration expressed as millimoles per litre (mmol/L).

 Infective diarrhoea and inflammatory bowel disease 20.2
Box 20.2.4 A 10-kg child with 15% dehydration and shock
• Certain types of probiotic may have a modest
effect in acute infective gastroenteritis; however,
Total fluid deficit = 15% of 10 kg = 1.5 L = 1500 mL their routine use is not recommended until further
Assume a total of 40 mL/kg (400 mL) normal saline needed to large-scale trials have been undertaken.
restore circulation • The antiemetic ondansetron is being used increasingly
Remaining deficit = 1500 − 400 = 1100 mL to treat vomiting associated with gastroenteritis. It
Maintenance fluid requirement is 100 mL per kg per should be administered only once in this setting and
day = 10 × 100 = 1000 mL
does not change the natural history of the disease,
Fluid in next 24 h = remaining deficit + maintenance
= 1100 + 1000 = 2100 mL = 90 mL/h but can improve tolerance of enteral rehydration.
Therefore, give 400 mL normal saline quickly, then 90 mL/h 5% It is not recommended for children aged less than
dextrose in N/2 saline with KCl 40 mmol/L for the next 24 h. 6 months or weighing less than 8 kg.

Prevention of acute gastroenteritis

• Once dehydration is corrected and normal
organ perfusion is restored, ORS can be used in A simple and effective method of prevention of this
conjunction with intravenous fluids. The latter is condition is via handwashing when in contact with
rarely required for longer than 24 hours. an index case, as the faecal–oral route is the most
• In severe dehydration, replace deficit over first 6 ­common form of transmission.
hours and then daily maintenance over the next 18 Two live attenuated oral rotavirus vaccines, Rotarix®
hours with regular reviews of losses. and RotaTeq®, have been used in Australia since 2007
• Clinical observations must be highlighted; these to immunize all babies aged 2–6 months. Rotavirus
allow the physician to reassess the patient's state of vaccines are even more valuable in developing coun-
hydration and also help confirm the diagnosis of tries, where the burden of rotavirus disease is far
acute gastroenteritis. higher.
• All patients with dehydration require regular Vaccines against typhoid and cholera infection are
checks on pulse, blood pressure, temperature and also available. Anti-E. coli colostrum tablets are also
respiration. In addition, a strict fluid balance chart available to help prevent the most common type of
must be kept. The child should be weighed on traveller's diarrhoea, and E. coli vaccines are under
admission and, in severe cases, after 6 and 24 hours, development.
with an increase in weight being a reliable sign of
rehydration. However, in some patients, weight may Complications of acute gastroenteritis
not fall even in the presence of severe dehydration,
especially if the child has an ileus, so other signs of Sugar malabsorption
dehydration must also be sought (Box 20.2.4). Sugar malabsorption is commonest in infants less than
6 months of age and presents with persistent diar-
Recommendations on nutritional management rhoea after feeds are reintroduced. With exposure to
In babies and young infants, breastfeeding should con- carbohydrates, stools are often watery, frothy and tend
tinue through rehydration and maintenance phases of to excoriate the buttocks.
treatment. Similarly, formula feeds should be restarted If sugar intolerance is suspected, the napkin should
after rehydration. Use of special formulas or diluted be lined with thin plastic material, or a rectal examina-
formulas is unjustified unless problematic diarrhoea tion should be performed and the fluid stool collected
persists (see complications of acute gastroenteritis). and tested for reducing substances. It is pointless to
test solid stool material.
To test for lactose intolerance, mix 5 drops of liquid
Pharmacotherapy
stool with 10 drops of water and add a Clinitest tablet.
• Infants and children with acute gastroenteritis A positive test of more than 0.5% indicates lactose or
should not be treated with antidiarrhoeal agents. glucose malabsorption, but not sucrose, which is not a
• Antibiotic treatment may be indicated in ­reducing sugar.
non-typhoid Salmonella gastroenteritis in infants Diarrhoea due to lactose malabsorption resolves
(especially those aged < 3 months) and children who rapidly on a lactose-free diet, which should be con-
are immunocompromised or who are systemically tinued for approximately 4 weeks. A very small
unwell. It may also be indicated in C. jejuni proportion of infants continue to have diarrhoea
­
infection in compromised hosts and Yersinia despite the exclusion of lactose and sucrose. Under
enterocolitica in children with sickle cell disease. these ­circumstances, a carbohydrate-free feed is given
• Pathogens for which antimicrobial therapy is temporarily, with g­lucose and fructose (different 719
indicated include Shigella, Entamoeba histolytica transport ­mechanisms across the enterocyte) added to
and Giardia lamblia. tolerance.
 20.2 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

Children may experience the same symptoms,

Clinical example c­linical presentations, complications and response
to treatment as adults with IBD, but often with
Tim, a previously well 22-month-old infant, more aggressive disease characteristics. This chapter
suddenly became unwell with vomiting and
will highlight some of the features of IBD that have
fever (38.5°C). Within 12 hours he started
passing frequent, loose motions. Associated
­particular importance to the paediatric patient.
with this he appeared to have bouts of abdominal pain.
On the second day the vomiting stopped but the diarrhoea
Crohn's disease
persisted at a rate of more than eight stools per day. On
presentation to the emergency department, Tim's weight Crohn's disease is a lifelong condition that can present
was 13.6 kg, compared with 14.5 kg 3 weeks earlier. He was in several ways with variable involvement of any length
clinically assessed to be 5–8% dehydrated and was treated
of the gastrointestinal tract from mouth to anus. The
with an oral rehydration solution via a nasogastric tube.
A provisional diagnosis of acute gastroenteritis was made.
disease causes transmural, granulomatous inflamma-
His temperature gradually settled over 24 hours and oral tion of affected areas, interspersed with normal areas.
feeds were introduced once rehydration was complete. His Numerous genes have been implicated in contributing
stools returned to their normal pattern after 5 days. Rapid to this complex disease including NOD2 (also called
stool testing for rotavirus antigen was positive. CARD15), a gene that is involved in the regulation of
intestinal epithelial cells, which are important in their
role as mucosal barrier. Many other genes have been
associated, but none in causation. Further advances
Practical points in genetics will undoubtedly contribute to our under-
standing in the years to come.
Acute gastroenteritis The disease can be classified broadly into inflamma-
• Commonly caused by viruses and self-limiting. tory, fistulizing or stricturing disease:
• Assess dehydration carefully and correct appropriately, but • Upper gastrointestinal Crohn's disease
reassess constantly. (oesophageal, gastric and small bowel) may present
• Not all children with diarrhoea and/or vomiting have as nausea, vomiting, abdominal pain, diarrhoea
gastroenteritis; be wary of other conditions that may mimic it.
and/or weight loss.
• Proper hand-washing is the best measure to avoid
transmission. • Colonic involvement presents with passage of
• Rotavirus vaccines are safe and effective. blood or mucus per rectum.
• Perianal involvement includes skin tags, fissures,
fistulas and abscesses.
• Oropharyngeal involvement includes orofacial
granulomatosis (lip and gum swelling) and
Inflammatory bowel disease recurrent mouth ulcers.
Chronic diarrhoea is defined as the presence of diar- • Extraintestinal manifestations include growth
rhoea for more than 2–3 weeks. It can follow a bout retardation, anorexia, fatigue, delayed puberty,
of acute gastroenteritis, but usually begins insidiously. erythema nodosum, arthritis, clubbing, decreased
Many causes of chronic diarrhoea are associated with bone mineral density, hepatitis and uveitis.
malabsorption of nutrients and are dealt with in detail Crohn's disease can have an insidious onset with
in Chapter 20.3. patients often having a prodrome of several months
Inflammatory bowel disease (IBD) constitutes prior to the diagnosis being made. Patients may be
Crohn's disease and ulcerative colitis (UC). These con- referred by their local doctor for non-specific abdomi-
ditions should be considered in the differential diagno- nal pain or other specialty units for consideration of
sis of patients with chronic diarrhoea, particularly with Crohn's disease; for example, haematology for iron
blood and mucus, once infectious agents have been deficiency anaemia, endocrinology for growth retarda-
excluded. The incidence of inflammatory bowel disease tion or pubertal delay, and rheumatology for arthritis.
has increased in recent years and Australia has among
the highest rates reported in the world. Current opin- Ulcerative colitis
ion regarding aetiology favours the hypothesis that IBD
results from a complex interaction between immunologi- UC is characterized by continuous inflammation of
cal, genetic and environmental factors. There is a positive the colon including the rectum. It involves only the
family history of IBD in up to 20% of cases. The micro- lining of the intestine (unlike Crohn's disease which
biota of the gut and its interaction with the host's immune affects all layers of the intestinal wall). As the inflam-
system has been the focus of much attention recently with mation continues, the mucosa of the intestine begins
720
its importance becoming increasingly apparent. to slough off, leaving pits (ulcerations). UC can ­present
 Infective diarrhoea and inflammatory bowel disease 20.2
acutely or insidiously with a prodrome of several Treatment
months. If there is a short history of colitic symptoms,
Treatment strategies for IBD often depend on the
it is essential to exclude infectious agents. Children
extent and severity of disease at the time of presen-
with UC usually present with lower abdominal pain,
tation. Medications are selected based on tolerance
urgency, tenesmus, diarrhoea and rectal bleeding.
and side-effect profile. Adherence considerations
Additionally:
are important, e­specially in adolescent patients, as
• systemic symptoms are less marked than in Crohn's
perceived treatment failure can potentially lead to
­
disease
unnecessary treatment escalation.
• the child can develop extra-intestinal manifestations
of disease such as arthritis and sclerosing
cholangitis Aminosalicylates
• pyoderma gangrenosum occurs more commonly in
UC, but is still rare. 5-Aminosalicylates (5-ASAs) can be used both orally
and topically (as enemas) to manage colonic ­disease in
UC. They are often used in mild UC to achieve remis-
Investigations sion and as maintenance therapy.
Several laboratory tests will support the diagnosis of
IBD. These include anaemia, thrombocytosis, raised Corticosteroids
erythrocyte sedimentation rate (ESR), hypoalbumi-
naemia, and the presence of white and red blood cells • Used in the dose range of 1–2 mg/kg prednisolone
on stool microscopy; however, endoscopy and biopsy for moderate to severe UC or Crohn's disease,
are the ‘gold standard’. usually for a 2–3-month period with a gradual dose
Antibody testing can help differentiate Crohn's reduction.
disease from UC. Anti-Saccharomyces cerevisiae • Can adversely affect growth and have many
antibody (ASCA) positivity and anti-neutrophil unpleasant cosmetic and systemic side-effects.
cytoplasmic antibody (p-ANCA) negativity suggest • Associated with decreased bone mineral density
Crohn's disease, and vice versa. However, these tests and contribute to osteoporosis risk.
are not accurate enough to use for screening or diag- • Corticosteroids such as budesonide have fewer
nostic purposes. side-effects and are particularly useful for ileal and
Gastroscopy and colonoscopy (with ileoscopy) right-sided colonic disease, but are expensive, thus
is essential, taking biopsies at all levels of the gut, preventing their widespread use.
whether or not there is macroscopic disease. Biopsies • Steroid enemas are helpful in the management of
from a normal-appearing stomach or duodenum may distal colonic and rectal inflammation.
contain granulomas, making the diagnosis of Crohn's • The minimum amount of steroids is used in
disease more likely. Pathological findings above the order to avoid their numerous side effects and
ileum exclude the diagnosis of UC. complications.
Magnetic resonance imaging (MRI) is a very use-
ful way of visualizing the small bowel for evidence of
Exclusive enteral nutrition
disease and has less radiation exposure in comparison
with the previously favoured barium follow-through. • Utilizes polymeric and/or elemental feeds, which
Occasionally, computed tomography (CT) is very are equally effective but are generally not palatable
­useful in identifying abscesses and gut perforation. and may require nasogastric infusion. All other oral
Ultrasound is safe and cheap and can provide help- intake is ceased during this treatment, which usually
ful information about bowel wall thickness and abcess lasts 6–8 weeks.
formation for example. • Provides a similar remission rate to corticosteroids
Wireless capsule endoscopy is a relatively new and in the treatment of childhood Crohn's disease
­evolving technology that is also inflammatory mark- (not UC) and improves growth and inflammatory
ers such as being used increasingly to image the small markers.
bowel mucosa, allowing more accurate mapping of • Exact mechanism of effect is unknown but
disease distribution and activity. generally thought to exert its beneficial effects
Faecal markers of inflammation such as, faecal by avoiding certain dietary antigens/substrates,
calprotectin, are a new way of measuring intestinal alterations in gut flora, enterocyte nutrition and
inflammation and are slowly becoming part of routine modulation of endogenous growth factors.
clinical practise. These tests may also have a future role • Maintaining compliance with this treatment
in differentiating functional from i­nflammatory bowel strategy is difficult, so discontinuation is a major
721
conditions. cause of treatment failure.
 20.2 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

Immunomodulators Surgery
Thiopurine drugs such as azathioprine and 6-mercap­ Up to 80% of patients with long-term Crohn's disease
topurine/6MP are now a mainstay of treatment for will require surgery at some stage during their d­ isease.
IBD. They are effective for maintaining remission but This may be to treat a stricture, abscess or fistula.
not for inducing remission. They can be used in steroid- Unfortunately surgery will not prevent recurrence of
dependent children with either UC or Crohn's disease, the disease, so it is important to maintain a conserva-
but take 12–14 weeks to be clinically effective. They tive approach to bowel resection. Nutritional deficien-
can cause nausea, pancreatitis and myelosuppression, cies can result from resection of a significant length
and patients must be monitored. Methotrexate is also of small bowel, especially if the terminal ileum is
used as a maintenance agent; it can be administered involved. Appropriately timed surgery in children with
orally and subcutaneously, which can be useful if com- Crohn's disease may accelerate growth and advance
pliance is a problem. puberty, allowing a reduction in drug therapy.
In contrast to Crohn's disease, only a minority of
patients with UC require surgery during the course of
Biologicals
their lifetime. However, the impact of a colectomy and
The anti-tumour necrosis factor (TNF)-α class of drugs stoma can be significant, especially during c­ hildhood
are very effective at inducing and maintaining remis- and adolescence when physical and psychological
sion in both adults and children. In the past, several growth and development are taking place. There are
issues limited use of these drugs in children, including several reasons to consider colectomy or subtotal
cost, adverse effects such as severe allergic reactions, colectomy in patients with UC, including fulminant
and concern over long-term safety. However, their use ­colitis not responding to therapy, toxic megacolon,
is becoming more frequent for several r­ easons, includ- severe growth or pubertal failure, and/or disabling
ing more severe disease, failure of other m ­ edications chronic symptoms. Total colectomy results in a perma-
and increasingly impressive safety data. These agents nent ileostomy but cures the individual of their d
­ isease
are traditionally administered intravenously at ­regular and associated risks. Another option is a subtotal
time intervals (8-weekly) although some newer agents ­colectomy and ileal pouch–anal anastomosis (IPAA).
have different dosing schedules and administration This procedure is associated with p ­ouchitis (50%),
methods. Tolerance or resistance to anti-TNF-α treat- increased stool frequency and faecal ­incontinence in
ment can develop in some patients, and the manage- some cases.
ment of treatment failure in this population group is a
challenge and the focus of much research. Cancer risk
There is an increased risk of cancer in IBD, which is
Other pharmacological treatments greatest in children with UC, particularly those with
• Antibiotics such as metronidazole and ciprofloxacin pancolitis for more than 10 years. It is increased fur-
are useful in perianal and colonic Crohn's disease. ther in persons with coexisting sclerosing cholangitis.
Metronidazole has been shown to reduce recurrence Population-based studies demonstrate that the
rates at the anastomotic site following resection. risk of colorectal cancer is 5.7 times that of the gen-
• Tacrolimus and cyclosporin, are sometimes used eral population in both UC and Crohn's colitis, but
in the most severe disease or for rescue therapy in patients with Crohn's disease that spares the colon do
acute fulminant colitis. not have an increased risk.
Endoscopic screening is indicated after 8–10 years
Immunosuppression of disease. Unfortunately, as we are seeing younger
Patients with IBD are often on one or more of these patients in increasing numbers, cancer surveil-
immunosuppressant medications. Therefore, they are lance is becoming increasingly relevant to paediatric
at increased risk of infection and are vulnerable to gastroenterologists.
opportunistic infections, such as CMV, tuberculosis To avoid colonic cancer, patients with longstand-
or fungal infection. This must be considered during a ing extensive colitis face either prophylactic colectomy
febrile illness especially. These patients may also have or regular surveillance colonoscopy. Neither option is
reduced host response to immunizations whilst on perfect; a more reliable, cheaper process of screening
these therapies. would be ideal.

722
 Infective diarrhoea and inflammatory bowel disease 20.2

Clinical example Practical points

Sarah presented at the age of 14 years with a
Inflammatory bowel disease
3-month history of recurrent abdominal pain
and diarrhoea. Her stools were described • Potentially a multisystem chronic relapsing disease.
as watery with variable amounts of blood • Assessment of the distribution of the disease may require
multiple modalities (i.e. endoscopy and biopsy and
and mucus. Clinical examination revealed mild pallor
imaging modalities).
and, on abdominal examination, there was tenderness
in both the left and right iliac fossa. Blood tests revealed • Treatment is individually tailored, based on the site and
severity of disease.
a microcytic anaemia (haemoglobin 90 g/dL and mean
corpuscular volume (MCV) 69 fL) and an ESR of 25 mm/h. • Be aware of long-term malignant risk, especially in ulcerative
colitis, and also side-effects of various medications used.
Stool microscopy showed both red and white blood cells.
Repeated stool cultures for viruses and bacteria, and testing
for Clostridium difficile toxin, were negative. At colonoscopy,
there was a pancolitis and a normal ileum. A provisional
diagnosis of ulcerative colitis was made, subsequently
supported by the histopathology. Sarah was treated initially
with high-dose steroids and was later maintained on
sulfasalazine, with good clinical response.

723
 20.3 Chronic diarrhoea and
malabsorption
Shoma Dutt, Edward O'Loughlin

Malabsorption can be defined as the failure to absorb intolerance. History of overseas travel is important, as
nutrients. A wide range of intestinal, pancreatic and some unusual infections, such as amoebic dysentery,
hepatic disorders can be associated with malabsorp- can cause chronic bloody diarrhoea.
tion. To understand how one approaches the problem The nature of the loose stool is important to ascertain,
of malabsorption in the clinical setting, an understand- as it provides important clues to the pathophysiology and
ing of the normal physiology of nutrient digestion and thus aetiology. Diarrhoea can be thought of in terms of
of salt, water and macronutrient and micronutrient fatty stools (steatorrhoea), watery diarrhoea (osmotic
absorption is essential. This information is available in because of carbohydrate malabsorption or secretory
general physiology texts. disorders) and bloody diarrhoea. Box 20.3.1 provides a
differential diagnosis of chronic diarrhoea and malab-
sorption categorized by the nature of the stool.
Diagnostic approach Assessment of general health is important, as many
gastrointestinal disorders exhibit extraintestinal manifes-
A large number of children have loose stools without tations. Cystic fibrosis (see Chapter 14.6), Shwachman
having underlying gastrointestinal disease. In young syndrome and immunodeficiency disorders (see
children this is called ‘toddlers’ diarrhoea’. A major clin- Chapter 13.2) are associated with infections, particularly
ical challenge is to differentiate well children with loose sinopulmonary infections. Delayed pubertal develop-
stools from children who have gastrointestinal disease. ment can accompany many chronic disorders but is par-
The diagnosis of the majority of children with mal- ticularly prevalent in Crohn's disease (see Chapter 20.2).
absorption can be established with thorough clinical Family history may be of note. Cystic fibrosis, pri-
assessment, stool examination and simple ancillary tests. mary disaccharidase deficiencies and abetalipopro-
teinaemia are recessively inherited. Coeliac disease
Clinical assessment
and inflammatory bowel disease are more frequently
Initial assessment can reveal whether a child is ill. If observed in first-degree relatives.
so, immediate evaluation will be required. In the well Physical examination includes assessment of growth,
child, a ‘wait and see’ approach may be more reward- nutritional status and pubertal development. Plotting
ing than immediate investigation. percentile charts is mandatory. A child who is growing
Malabsorption does not present as malabsorption normally is unlikely to be suffering from serious gastro-
per se. Rather, individuals with malabsorption can intestinal disease. Plotting longitudinal measurements,
present with a wide array of symptoms and ­physical if available, is very important as it may give clues to the
signs (Table 20.3.1). Diarrhoea is the most com- onset of disease and could indicate the diagnosis. Other
mon presentation and may be accompanied by loss physical signs of malabsorption and specific nutritional
of appetite, decreased physical activity, lethargy and deficiencies include: loss of muscle bulk and subcutane-
growth failure. Children with coeliac disease may have ous fat; peripheral oedema (hypoproteinaemia); bruising
decreased appetite, and are often cranky and irrita- (vitamin K deficiency); glossitis and angular stomatitis
ble. In contrast, children with pancreatic insufficiency (iron deficiency); finger clubbing (cystic fibrosis, Crohn's
often develop a voracious appetite. In children with disease, coeliac disease); skin rashes in coeliac disease
failure to thrive, a detailed dietary history is required. (dermatitis herpetiformis) and inflammatory bowel
Occasionally, parents manipulate the child's diet in ­disease (erythema nodosum, pyoderma gangrenosum);
an attempt to control the diarrhoea, which can lead and ­specific skin disorders associated with zinc, ­vitamin
to significant dietary insufficiency with attendant A and essential fatty acid deficiencies (Fig. 20.3.1). Rickets
weight loss. Assessment of the age of introduction is ­uncommon in our community, although biochemical
of various foods into the diet may give insight to the vitamin D deficiency is quite common and is prevalent in
underlying diagnosis. Onset of ­symptoms 3–6 months patients with malabsorption, such as in cholestatic liver
after the introduction of wheat products suggests the disease, and coeliac disease. It is important to examine
­possibility of coeliac disease. Onset shortly after the carefully as there are many extraintestinal m ­ anifestations
724
introduction of cow's milk s­ uggests cow's milk protein of gastrointestinal disease and malnutrition.
 Chronic diarrhoea and malabsorption 20.3
Table 20.3.1 Some symptoms and signs of nutrient Box 20.3.1 Differential diagnosis of chronic diarrhoea
deficiencies and malabsorption categorized according to
type of stool
Nutrient Symptom or sign of deficiency
STEATORRHOEA
Protein Growth failure
Pancreatic insufficiency
Muscle wasting
• Cystic fibrosis
Hypoproteinaemic oedema
• Shwachman syndrome
Fat Weight loss • Chronic pancreatitis
Muscle wasting • Malnutrition (developing world)
Manifestation of deficiency of vitamins • Isolated lipase deficiency
A, D, E, K
Inadequate bile salt concentration
Carbohydrate Weight loss • Biliary atresia
Salt/water Electrolyte disturbances • Cholestatic syndromes
Growth failure (chronic salt deficiency) • congenital
Dehydration (acute loss) • acquired
• End-stage liver disease
Vitamins
• Bacterial overgrowth syndrome
A Night blindness
• Bile salt malabsorption (ileal resection)
Skin rash
Dry eyes (xerophthalmia) Inadequate absorptive surface
D Rickets • Coeliac disease
Hypocalcaemia • Surgical resection (short gut syndrome)
K Bruising (coagulation defects) • Milk protein intolerance
E Anaemia • Immunodeficiency
Peripheral neuropathy
B12 Megaloblastic anaemia Enterocyte defect
Irritability • Abetalipoproteinaemia
Hypotonia
Defective lymphatic drainage
Peripheral neuropathy
• Intestinal lymphangiectasia
Folate Megaloblastic anaemia
• Constrictive pericarditis
Irritability
Minerals WATERY DIARRHOEA
Iron Microcytic anaemia Osmotic
Delayed development Disaccharidase deficiency
Calcium Rickets • Lactase
Irritability • Sucrase–isomaltase
Seizures glucose–galactose malabsorption
Zinc Diarrhoea Excessive intake
Skin rash (mouth, perineum, fingers • Sorbitol
and toes) • Fructose
Poor growth
Abnormal water and electrolyte transport
Congenital electrolyte transporter defects
• Congenital chloride diarrhoea
Stool examination • Congenital sodium diarrhoea

Stool examination is very simple and provides very impor- infection

tant information. The presence of numerous white and mucosal disease
red cells indicates colitis. This is usually due to bacterial • Coeliac disease
• Milk protein intolerance
or parasitic infection, to chronic i­nflammatory disorders
• Inflammatory conditions (inflammatory bowel
of the large bowel, or to milk protein intolerance when disease)
identified in infants. Leukocytes are not increased in the • Immunodeficiency disorders
stool of i­ndividuals with small bowel or pancreatic dis- • Autoimmune enteropathy
ease. Cysts of parasites such as Giardia lamblia indicate
bile salt malabsorption
giardiasis.
• Congenital
Oil droplets seen on stool microscopy are always • Ileal resection
abnormal outside the newborn period and usually indi-
cate fat maldigestion, as occurs with pancreatic insuf- bacterial overgrowth syndromes
• Gastrointestinal motility disorders
ficiency, for example in cystic fibrosis. Mucosal disease,
• Anatomical (blind loop) 725
such as coeliac disease, in general does not interfere
 20.3 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

discussion will provide a systematic approach to the

Box 20.3.1 Differential diagnosis of chronic diarrhoea
and malabsorption categorized according to
child with malabsorption and diarrhoea based on the
type of stool—Cont'd type of stool, i.e.:
• fatty
BLOODY DIARRHOEA • watery or
Infection • bloody.
• Bacterial Some illustrative cases will be provided and a sum-
• Parasitic
mary of this approach can be seen in Figure 20.3.2.
INFLAMMATORY BOWEL DISEASE Fatty diarrhoea (steatorrhoea)
• Crohn's disease
• Ulcerative colitis The differential diagnosis of fat malabsorption is
• Milk protein intolerance quite wide ranging (see Box 20.3.1); however, if one
understands the normal physiology of fat digestion
and absorption, the differential diagnosis is much
less daunting. Conditions that cause steatorrhoea can
also be associated with protein maldigestion and/or
malabsorption, although symptoms most commonly
relate to the malabsorption of fat. The presence of fat
in the stool is also more readily observed than protein.

Clinical example

Mary was 9 months old. She presented with

poor weight gain, chronic diarrhoea and
a history of recurrent respiratory illnesses,
including one admission at age 3 months with
‘bronchiolitis’. Loose stools were found each time her nappy
was changed. On occasion her mother had noted oil drops in
the stool. Despite the poor weight gain, Mary had an excellent
Fig. 20.3.1 Exfoliative rash of zinc deficiency. appetite and was described as a voracious eater. She
consumed a mixed diet, including infant formula, appropriate
for age. Cereal was introduced at age 6 months. Mother also
with fat digestion because pancreatic function is usually
commented that she tasted salty when she kissed Mary.
normal. Mucosal disease interferes with the absorption On examination, Mary was found to be a thin wasted girl.
of triglyceride products. These products are observed Her height was on the 50th percentile and her weight was
as fatty acid crystals on polarizing microscopy. less than the 3rd percentile. She had mild finger clubbing,
The presence of carbohydrate in the stool can be peripheral oedema, pallor of the tongue and palmar
detected with Clinitest tablets. This is a commercially creases, but no signs of chronic liver disease. There was
available bedside test in which the ­reaction between no abdominal distension of note, although she had a fine
scaling rash over her trunk. Respiratory examination was
stool sugars such as lactose causes a colour change when normal. No other abnormal physical signs were present.
added to the tablets. Greater than 500 mg/dL (0.5%) Results of investigations included haemoglobin 85 g/L
indicates carbohydrate malabsorption. Measurement (normal range 110–140) with a normocytic normochromic
of stool electrolytes and o­ smolality in the stool water film, normal white cell count and differential; albumin 24 g/L
is also a very useful test. When the sum of the stool (normal range 34–44) and normal liver function test results.
electrolytes (i.e. sodium + potassium + chloride + Stool microscopy revealed copious fat droplets. Three-day
faecal fat excretion estimation demonstrated an output of
bicarbonate) equals measured osmolality, a secretory
35% of ingested fat (normal < 7% of intake).
diarrhoea is present. If the sum of the electrolytes is Mary's diarrhoea was due to fat malabsorption, as
substantially less than the measured osmolality (> 100 evidenced by her mother's observation of fat droplets in
mosmol/L), this indicates an osmotic diarrhoea. the stool.
Mary's sweat test demonstrated a sweat chloride of
80 mmol/L (a result > 60 mmol/L is diagnostic of cystic
Malabsorption with chronic fibrosis). Genetic testing indicated that she was homozygous
ΔF508 (the commonest mutation), consistent with her
diarrhoea relatively severe symptoms. Introduction of pancreatic
exocrine replacement therapy, a high-fat diet and vitamin
Diarrhoea is the most common presentation of mal- supplements alleviated her diarrhoea and eventually
absorption. Diarrhoea can be defined as increased corrected Mary's failure to thrive, anaemia and skin rash.
726
­frequency, fluidity and volume of stool. The following
 Chronic diarrhoea and malabsorption 20.3
Fatty stool Watery stool Bloody stool

Fat globules Fat acid crystals

(triglycerides) (free fatty acid Clinitest1 Stool microscopy
Reducing sustances2 Red blood cells
Stool pH White blood cells
Osmotic gap3

Lipase deficiency Mucosal disease

or Mucosal damage,
Liver disease e.g.
(resulting in reduced • coeliac disease Osmotic diarrhoea Secretory diarrhoea Colitis
bile sallts) • short bowel +ve stool reducing –ve reducing IBD
syndrome substances substances Milk intolerance
Osmotic gap > 100 Osmotic gap < 50 Invasive infection

1 Sweat test for CF Small bowel biopsy

2 Assess degree of for histology
fat malabsorption Small bowel biopsy, Secretagogue (VIP) Imaging
e.g. mucosal Congenital transport Colonoscopy and
• formal 3 day faecal disaccharidases defect biopsy
balance study Manipulation of Infection
• breath test dietary CHO with Malabsoption
monitoring bile salts

Fig. 20.3.2 Algorithm for investigation of patient with chronic diarrhoea. 1, Stool collection must be fresh as stool osmolality increases
after excretion due to continued bacterial fermentation of faecal carbohydrates (breastfed infants can exhibit up to 0.5% reducing
substances). 2, Sucrose is a non-reducing sugar, and not measurable as a reducing substance unless hydrolysed by boiling or acid.
3, Osmotic gap in stool fluid = Serum osmolality (280) − [2 × ([Na] + [K])]. CF, cystic fibrosis; CHO, carbohydrate; IBD, inflammatory bowel
disease; VIP, vasoactive intestinal polypeptide.

Fat and protein digestion and absorption pancreatic proteases. These are secreted as inactive
precursors. Chymotrypsin is converted to trypsin by
Ingested fat in the form of triglycerides, cholesterol
the action of the small intestinal enzyme enterokinase.
and phospholipids is, to a large extent, digested in
Activated trypsin further activates chymotrypsin and
the lumen of the small intestine and absorbed in the
other proteases, such as carboxypeptidase. The prod-
jejunum. This requires bile salts, which form micelles
ucts of protein hydrolysis are amino acids and oligo-
and solubilize the fat; pancreatic enzymes, such as
peptides. The latter are further hydrolysed to mono-,
lipase and co-lipase, which digest the fat; and an intact
di- and tri-peptides by brush border hydrolases and
intestinal mucosa, which is required for absorption
are absorbed by specific membrane transporters. Di-
of the products of digestion. Following digestion in
and tri-peptides undergo hydrolysis to amino acids
the micelles, breakdown products diffuse across the
in the cytoplasm of the enterocyte. Isolated protein
enterocyte apical membrane and are reconstituted
maldigestion/malabsorption is extremely rare. It usu-
in the cell into chylomicrons. These are small pack-
ally occurs in association with malabsorption of other
ets of triglyceride, phospholipid and cholesterol that
macronutrients.
associate with carrier proteins, such as β-lipoprotein,
essential for cellular trafficking of the chylomicrons.
After the chylomicrons are reconstituted, they exit the
Fat malabsorption
mucosa into the lymphatic system and subsequently
pass into the systemic circulation. Some small-chain Diseases of the pancreas and the small intestine are
triglycerides can bypass this system and enter the por- the usual causes of steatorrhoea in children. Chronic
tal venous system directly. liver disease may cause steatorrhoea but this is in the
Protein digestion begins in the stomach by the action setting of severe and obvious liver disease (such as the
of pepsin and acid. However, most protein hydrolysis patient who is cirrhotic and jaundiced) and is not usu-
727
occurs in the lumen of the jejunum by the action of ally a diagnostic problem.
 20.3 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

Steatorrhoea causes bulky stools and can lead to Malabsorption in cystic fibrosis frequently results
other nutritional deficits. Fat is responsible for approx- in malnutrition and there may be symptoms and signs
imately 40% of caloric intake in the Western diet. Thus, of specific nutrient deficits such as hypoalbuminaemic
fat malabsorption can lead to failure to thrive due to oedema, night blindness due to vitamin A deficiency,
an energy-deficient diet. Some vitamins are f­ at-soluble or skin rash due to essential fatty acid deficiency.
and require normal fat digestion for their absorp- Median life expectancy is 30 years, with death usually
tion. These include A, D, E and K. Thus patients with from respiratory failure or haemorrhage from portal
steatorrhoea may also develop signs of fat-soluble
­ hypertension and oesophageal varices.
vitamin deficiency, as described above. Essential fatty Many mutations have been identified in the CFTR.
acids such as arachidonic acid are also malabsorbed in Depending on what part of the channel is affected by the
patients with pancreatic malabsorption. A scaling skin mutation, the phenotype can vary from mild to severe
rash is one physical manifestation of essential fatty disease. Individuals with milder mutations have milder
acid deficiency. lung disease and do not usually have malabsorption, as
Pancreatic and intestinal diseases associated with pancreatic function is normal (pancreatic sufficient).
fat malabsorption can also result in protein and car- Newborn screening:
bohydrate maldigestion/malabsorption. Thus it is not • can detect cystic fibrosis in the neonatal period
uncommon to find a mixed picture of malabsorption. • involves measurement of immunoreactive
Protein maldigestion/malabsorption results in hypo- trypsinogen and/or CFTR mutations
proteinaemia. The main physical manifestations are • is the commonest mode of presentation when it is
growth failure, peripheral oedema and ascites. performed.
In children with the severe phenotype who are missed
by screening, or in countries where screening is not
Pancreatic disease
performed, presentation is usually in the first year
Cystic fibrosis with chronic diarrhoea and failure to thrive, with or
See also Chapter 14.6. without respiratory symptoms. In milder phenotypes,
Cystic fibrosis: patients may not present until adult life with respira-
• is the commonest cause of pancreatic tory disease or infertility.
malabsorption in the Caucasian population Diagnostic investigations for cystic fibrosis are:
• has an incidence in the population of approximately • raised sweat sodium and chloride (‘sweat test’) –
1 per 2000 simplest and cheapest
• is an inborn error in epithelial chloride secretion – • CFTR mutation analysis.
cystic fibrosis transmembrane conductance Treatment is usually undertaken in a tertiary referral
regulator (CFTR). multidisciplinary clinic and involves:
Organs affected include: • physiotherapy, inhalation therapy and antibiotics
• gastrointestinal tract and liver for chest disease
• sinopulmonary tract • pancreatic enzyme supplements
• pancreas • nutritional support and fat-soluble vitamin
• exocrine portion of the sweat glands supplementation
• vas deferens • specific therapy may be required for the other
• sweat duct (CFTR absorbs rather than secretes intestinal/liver complications.
chloride in this organ).
Shwachman syndrome
Because of the fluid and salt transport defects, patients
The features of Shwachman syndrome are:
with cystic fibrosis produce more viscous secretions in
lung, gut, pancreas and vas deferens, leading to: • agenesis of the pancreatic acinus
• chronic suppurative lung disease • short stature
• nasal polyps • dysplasia of the metaphysis of the long bones
• pancreatic insufficiency (approximately 85% of • cyclical neutropenia.
There is no specific diagnostic test; treatment includes
patients)
pancreatic enzyme replacement and ­ treatment of
• intussusception
infections.
• meconium ileus and distal intestinal obstruction
syndrome Chronic pancreatitis
• infertility Causes of chronic pancreatitis include:
• raised sweat sodium and chloride, which can lead to • protein energy malnutrition
heat prostration in warmer climates. • hereditary pancreatitis (SPINK1, PRSS and CFTR
Chronic liver disease will develop in 10–15% of chil- gene mutations)
728
dren with cystic fibrosis. • idiopathic fibrosing pancreatitis (rare).
 Chronic diarrhoea and malabsorption 20.3
Small bowel disease • The older child with:
Coeliac disease (gluten enteropathy)
• growth failure
Coeliac disease is a disorder characterized by intes-
• chronic diarrhoea
tinal injury induced by the cereal protein gluten.
• iron deficiency
Gluten is a glycoprotein found in wheat, barley
• Positive antibody screening (now the commonest
form of assessment leading to diagnosis).
and rye, and, to a lesser extent, oats. In suscepti-
Examples of antibodies used to screen when there is
ble individuals, the ingestion of gluten induces a
suspicion of coeliac disease include:
cell-mediated injury of the intestinal mucosa result-
ing in severe villous atrophy, crypt hyperplasia and
• anti-gliadin
infiltration of the epithelium with lymphocytes
• anti-endomysial
(intraepithelial lymphocytes). In Western countries,
• anti-tissue transglutaminase
the incidence of coeliac disease in the general popu-
• deamidated anti-gliadin antibodies.
Anti-endomysial and anti-tissue transglutaminase anti-
lation may be as high as 1 in 70, although not all
bodies have a sensitivity and specificity greater than 95%
affected individuals develop the classical manifesta-
in clinical trials but probably less in the clinical setting.
tions of coeliac disease. At risk populations include
These are mostly immunoglobulin (Ig) A-based tests and
individuals with type 1 diabetes mellitus, a positive
a false-negative result may occur with IgA deficiency
family history of coeliac disease and other autoim-
(the deaminated anti-gliadin antibody is IgG based).
mune disease (thyroiditis, hepatitis), and syndromes
However, it is important to note that these are screening
such as trisomy 21 and Turner syndrome. A chang-
tests only. There is a close association with human leu-
ing pattern in the presentation of coeliac disease has
kocyte antigen (HLA) DQ2 and DQ8 phenotypes. HLA
been noted with the advent of accurate screening
DQ2 and DQ8 typing may be useful in assessing the risk
serological tests.
of coeliac disease in close family members. These phe-
Modes of presentation include:
notypes are common in the general population and can-
• ‘Classical’ coeliac disease (Fig. 20.3.3):
not be used to diagnose coeliac disease. However, their
• between 9 and 18 months of age
absence makes coeliac disease very unlikely.
• anorexia, weight loss, abdominal distension and
The following are important points in the approach
wasting
to the diagnosis of coeliac disease in childhood:
• chronic diarrhoea with or without iron
deficiency anaemia, hypoproteinaemic
• Small bowel biopsy is mandatory for the diagnosis
(Fig. 20.3.4).
oedema, fat-soluble vitamin deficiency
(vitamins A, D, E, K)
• Small bowel biopsy should be performed while the
patient is on an unrestricted diet.
• There is no place for an empirical trial of a gluten-
free diet.
• Definitive diagnosis is important, as treatment is a
lifelong gluten-free diet.
The patient should be monitored for a clinical response
to treatment with a gluten-free diet, and antibody titres
should be expected to fall with response.
Enterocyte defect
Abetalipoproteinaemia is a recessively inherited defect
in chylomicron assembly. Patients develop steator-
rhoea early in life with:
• fat-soluble vitamin deficiencies
• low serum cholesterol and triglyceride levels.
Small bowel biopsy reveals fat-laden enterocytes.
Impaired lymphatic drainage
Obstructed lymphatic drainage prevents chylomicrons from
migrating from the gut to the systemic circulation. The main
cause is intestinal lymphangiectasia. This can lead to:
• fat malabsorption
Fig. 20.3.3 Typical physical appearance of a young child
• low serum cholesterol and triglyceride levels
with coeliac disease. Note the protuberant abdomen, buttock • hypoproteinaemia and lymphopenia (loss of lymph
and shoulder girdle wasting and oedema of the lower limbs. into gut lumen)
729
(Courtesy of Professor K. Gaskin.) • abnormal mucosal biopsy.
 20.3 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

Fig. 20.3.4 Micrographs of normal intestine (left) demonstrating normal crypt villus structure, and coeliac disease (right) with marked
crypt hyperplasia and villous atrophy.

Other causes of reduced mucosal surface and reduced Watery diarrhoea

contact time
Carbohydrate digestion and absorption
Miscellaneous inflammatory and surgical conditions
can lead to loss of absorptive surface or reduced contact Dietary carbohydrates are primarily starch (polysac-
between chyme and the mucosa. Such conditions include: charides, amylose and amylopectin), disaccharides
• milk protein intolerance (severe) (sucrose, in table sugar; lactose, in milk) and some
• infections such as rotavirus infection monosaccharides such as fructose.
• severe immunodeficiency disorders Starch polymers are large molecules composed of
• autoimmune enteropathy long chains of glucose. These chains are broken down
• short gut syndrome (surgical removal) by the action of salivary and pancreatic amylase, which
• motility disorders causing very rapid intestinal transit. release a disaccharide (amylose), trisaccharide (malto-
triose) and a series of branched oligosaccharides
(α-limit dextrins). These molecules are further digested
Clinical example by the brush border enzymes, sucrase–isomaltase and
George was 9 years old. He presented with glucoamylase, to the monosaccharide glucose.
a 6-month history of intermittent bloating, The disaccharides sucrose and lactose are metabo-
abdominal pain and diarrhoea up to 6–7 times per lized by disaccharidases on the intestinal brush bor-
day. He had lost 1 kg in weight in the past 2 months. der. Sucrase breaks sucrose down to glucose and
He reported that dairy products such as milk and ice-cream made fructose, and lactase breaks down lactose into glucose
his symptoms worse. He had no past history of significant illness. and galactose. Glucose and galactose are absorbed
George was the oldest son of Greek migrants. His mother reported
by the enterocyte sodium–glucose co-transporter
that she could not drink milk, as it made her feel sick.
On examination, George was well looking. His weight was (SGLT), which absorbs the monosaccharides in an
on the 50th percentile and his height on the 10th percentile. energy-dependent fashion. Fructose is absorbed by
­
There was no abdominal distension, organomegaly, signs of facilitated diffusion (non-energy-dependent) by glu-
chronic liver disease or evidence of nutritional deficiency such cose transporter type 5 (GLUT-5).
as anaemia or peripheral oedema. Examination of his anus
did not reveal any evidence of perianal disease.
Investigations included a normal full blood count, differen­ Carbohydrate malabsorption
tial white cell count and erythrocyte sedimentation rate (ESR).
The presence of non-absorbed osmotically active
The C-reactive protein level was less than 1 g/L. Lactose
breath hydrogen measurement following oral ingestion of nutrients in the gut lumen results in osmotic retarda-
50 g lactose increased 100 parts per million above baseline tion of water absorption, leading to watery diarrhoea.
levels within 60 minutes of ingestion of lactose (normal rise This is referred to as osmotic diarrhoea. Osmotically
20 parts per million), indicating lactose intolerance. active compounds are usually low-molecular-weight
George was diagnosed as having lactose intolerance. compounds such as monosaccharides and disaccha-
His history suggested ontogenic lactase deficiency. This rides. Osmotic diarrhoea is usually due to maldiges-
was confirmed by small bowel biopsy, which demonstrated
tion and/or malabsorption of carbohydrates, but can
normal morphology, and by disaccharidase measurement,
which revealed very low lactase activity but normal sucrase be caused by the ingestion of laxatives such as sorbi-
and maltase activities. Treatment was a low-lactose diet. tol or magnesium chloride. Unabsorbed carbohydrate
730
present in the lumen of the large bowel is fermented to
 Chronic diarrhoea and malabsorption 20.3
short-chain fatty acids such as butyrate. This results in • milk protein enteropathy
a highly acidic stool, which can cause perianal exco- • small bowel bacterial overgrowth syndrome
riation. The colon can absorb the anionic forms of • immunodeficiency disorders
these acids in exchange for bicarbonate, causing a mild • autoimmune enteropathy.
hyperchloraemic acidosis. Monosaccharide transporters are less susceptible to
While stating the obvious, it is important to appreci- injury because, unlike disaccharidase enzymes, they
ate that one cannot malabsorb a nutrient that has not are deeply embedded in the brush border membrane.
been ingested. Thus, it is useful to obtain a dietary his- However, severe enteropathies can occasionally result
tory in patients suspected of osmotic diarrhoea. One in monosaccharide malabsorption. Examples include:
needs to ascertain the nature of the carbohydrates • congenital villous atrophy (which presents in
being ingested, and in some instances the age of intro- newborns)
duction of the carbohydrate, which can then be com- • severe postinfectious enteritis
pared with the age of onset of symptoms. For example, • milk protein intolerance
the onset of osmotic diarrhoea commensurate with the • autoimmune enteropathy.
introduction of fruit into the diet suggests the diagno- Monosaccharide malabsorption is life-threatening and
sis of congenital sucrase–isomaltase deficiency. requires a level of care found only in tertiary paediatric
centres. The treatment is to remove the offending car-
Disaccharidase deficiencies and monosaccharide bohydrate from the diet and substitute an ­alternative.
malabsorption In acquired disorders, treatment may also be required
for the primary mucosal disease.
Congenital
Ontogenic lactase deficiency:
• occurs in most of the non-Caucasian population of Disorders of fluid and electrolyte transport
the world
In the normal child approximately 5 litres (depend-
• is dominantly inherited ing on size!) of fluid and electrolytes enters the
• is physiological (due to the disappearance of upper gastrointestinal tract per day. One litre is
lactase)
ingested and the remaining volume is from normal
• presents in late childhood. secretions into the lumen. The majority of this fluid
Ingesting lactose causes diarrhoea, bloating, excessive
is absorbed before reaching the colon. Stool weights
flatus and weight loss. Treatment is a low-lactose diet.
range from 75 to 150 g per day, of which approxi-
Congenital sucrase–isomaltase deficiency is caused
mately 75% is water. Small increases in stool water,
by inactivating mutations in the sucrase–isomaltase as little as 30–40 mL daily, are enough to produce
gene. These mutations: diarrhoea.
• are recessively inherited Water is absorbed by osmosis through aqua-
• lead to similar symptoms as for lactase deficiency porins and paracellular pathways in the mucosa.
with the ingestion of sucrose
Electrolytes are absorbed by a variety of active
• cause onset of symptoms at the time of weaning transport or passive transport processes. Anions
when fruit is introduced to the diet.
such as chloride and bicarbonate can be absorbed
Treatment is a low-sucrose diet.
or actively secreted. This varies according to the
Congenital monosaccharide malabsorption refers to region of small or large i­ ntestine. Regulation of gas-
defective glucose/galactose malabsorption. Features are: trointestinal fluid and electrolyte transport is closely
• mutations in SGLT1 integrated by humoral and neural factors involved
• recessively inherited in fluid and electrolyte homeostasis. Abnormal
• present in the neonatal period. fluid and electrolyte transport can be due to inher-
Treatment is substitution of fructose for glucose–
ited defects in specific electrolyte transporters, but
galactose.
more commonly it is due to mucosal damage or
inflammation.
Acquired
Except for ontogenic lactase deficiency, acquired dis- Congenital
orders are much more common than inherited defi- Congenital sodium diarrhoea and congenital chlo-
ciencies. Lactase is more susceptible to injury than ride diarrhoea are rare inherited disorders of Na/H
sucrase. exchange and Cl/HCO exchange, respectively. They
Causes of disaccharidase deficiencies include: cause:
• viral gastroenteritis • diarrhoea in utero, which results in polyhydramnios
• coeliac disease • profuse diarrhoea, obvious from birth
731
• chronic giardiasis • systemic electrolyte disturbances.
 20.3 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

Acquired
Isolated water and salt malabsorption is very rare in
childhood in the developed world. However, defective
salt and water transport can contribute to diarrhoea in:
• disorders that damage or inflame the mucosa of
small or large intestine
• bile salt malabsorption (bile acids irritate the colonic
mucosa and act as potent stimulants of secretion).
Excessive salt and water loss in the stool may lead to
dehydration and electrolyte disturbances. Treatment
may require salt and water replacement in addition to
treatment of the underlying disease.

Bloody diarrhoea (see also Chapter 20.2) Fig. 20.3.5 Microscopic appearance of leukocytes in a stool
Chronic bloody diarrhoea is usually caused by inflam- smear. The large dark structures are polymorphonuclear
leukocytes; the small round objects are red blood cells.
matory disorders of the colon such as:
• milk colitis in infants
• infections, such as with bacteria or parasites B12 complex moves to the ileum where it is absorbed into
• inflammatory bowel disease in older children. The the enterocytes by carrier-mediated transport. On entry
two major forms are: into the enterocyte, vitamin B12 is separated from intrin-
• ulcerative colitis sic factor and subsequently exits the enterocyte into the
• Crohn's disease. circulation bound to transcobalamin, which carries the
Blood is not always obvious in the stool. However, the vitamin to sites distant from the intestine.
presence of leukocytes on stool microscopy (Fig. 20.3.5)
indicates the presence of colitis. Malabsorption of fluid
and electrolytes by the inflamed colonic mucosa is a
Clinical example
major factor contributing to diarrhoea. Malabsorption
of nutrients is uncommon in milk colitis and inflam- John was 9 months old. He presented with a
matory bowel disease. In contrast, excessive blood and 6-week history of poor weight gain, irritability
protein loss from the inflamed intestinal mucosa can and pallor. His mother was also concerned
cause iron deficiency anaemia and hypoproteinae- about his development. He was able to sit but
mic oedema. This is called protein-losing enteropathy, could not pull himself to standing. His language had not
progressed from babbling, which was in stark contrast to
and can be assessed by measuring stool α1-antitrypsin
his older sibling, who had several single words at this age.
levels. John had a poor appetite but no diarrhoea. He was originally
breastfed and his mother ingested a normal diet during
pregnancy and lactation.
Nutrient malabsorption with little On examination, John was a pale irritable boy. He had
moderate abdominal distension but no organomegaly. He
or no diarrhoea could sit up unsupported but was mildly hypotonic and would
not weight-bear. There were no focal neurological signs.
Children present with symptoms and signs of nutrient Investigation results included: haemoglobin 65 g/L (normal
deficiency with little or no accompanying diarrhoea. range 120–150) with a megaloblastic blood film, serum B12
This is often due to dietary insufficiency (e.g. inade- 50 pmol/L (normal range 120–600) and red blood cell folate
quate iron intake), but can sometimes be due to mal- 350 nmol/L (normal range 200–1000). A Schilling test revealed
absorption of the specific nutrient. urinary excretion of ingested radioactive vitamin B12 (after
parenteral administration of a non-radioactive flushing dose
of 1 mg vitamin B12) of 1% (normal 8%), with no enhancement of
Vitamin B12 urinary excretion with the addition of intrinsic factor.
Vitamin B12 is ingested in animal protein and is liberated John's Schilling test result suggested a defect in the ileal
by pepsin in the stomach. In the stomach, the free vita- vitamin B12 transporter, as the test was abnormal and did
not recover with the addition of intrinsic factor. His age of
min B12 binds to a binding protein (R protein) that has
presentation and lack of previous intestinal surgery suggest a
greater affinity for the vitamin than intrinsic factor (car- congenital defect. His symptoms and megaloblastic anaemia
rier protein). Intrinsic factor is produced by epithelial corrected with administration of parenteral vitamin B12.
cells in the gastric mucosa. The vitamin B12–R protein
complex moves to the duodenum where trypsin cleaves
the complex, releasing free vitamin B12, which then Both congenital and acquired disorders can lead to
732
binds to intrinsic factor. The intrinsic factor–­vitamin vitamin B12 malabsorption.
 Chronic diarrhoea and malabsorption 20.3
Congenital disorders Miscellaneous nutrients
Congenital defects in: Calcium
• ileal vitamin B12 transporter Calcium absorption occurs in the duodenum and
• intrinsic factor proximal jejunum and is largely under the regulation
• transcobalamin of vitamin D:
can lead to vitamin B12 malabsorption and deficiency.
• Hypocalcaemia can be associated with a wide
This usually presents in the second 6 months of life,
variety of digestive disorders affecting intestinal
after the vitamin B12 accumulated during intrauterine
calcium uptake or the biosynthesis and availability
life is exhausted.
of vitamin D (see Chapter 19.5).
Symptoms are due to megaloblastic anaemia and
• It commonly presents with tetany of the fingers and
the central nervous system effects of deficiency. Babies
occasionally seizures.
born to vegan mothers (who ingest no animal product
and thus can themselves be vitamin B12-deficient) and
weaned on to a vegan diet can present with a similar pic- Zinc
ture, although usually in the first 6 months, as they are
Zinc is absorbed by the small intestine. Zinc deficiency
deficient from birth. Dietary history is important to dif-
can be due to:
ferentiate between dietary deficiency and malabsorption.
• low breast milk zinc levels in solely breastfed
Acquired disorders infants
• an inherited defect in zinc absorption
Acquired disorders that lead to B12 malabsorption are: (acrodermatitis enteropathica)
• surgical resection of the ileum • conditions associated with steatorrhoea
• atrophic gastritis • intestinal inflammatory disorders.
• gastric surgery Zinc deficiency can cause diarrhoea but the most dra-
• autoimmune pernicious anaemia (blocking matic manifestation is an erythematous scaly rash on
antibodies to intrinsic factor) the fingertips and around the perineum and mouth
• pancreatic insufficiency (failure to hydrolyse (see Fig. 20.3.1).
vitamin B12–R protein)
• small bowel bacterial overgrowth (competition for
vitamin B12 by bacteria).
Magnesium
Magnesium is absorbed in the proximal small intes-
Iron tine. Magnesium malabsorption leading to deficiency
Iron absorption occurs in the duodenum and proximal can be:
jejunum. An apical enterocyte carrier called the diva- • inherited (primary hypomagnesaemia)
lent metal cation transporter mediates uptake into the • secondary to other conditions leading to
enterocyte. Iron is exported to the circulation via a malabsorption.
basolateral process that has not yet been fully defined. Hypomagnesaemia causes similar symptoms to cal-
In non-breastfed children, only 5–10% of dietary iron is cium deficiency.
absorbed. The efficiency of iron absorption is greater in
breastfed infants because the iron carrier transferrin is Isolated protein malabsorption
present in breast milk. Iron absorption is finely regulated
Enterokinase deficiency:
at the level of the enterocyte so that absorption does not
exceed requirements. Excessive iron accumulation can • is a very rare disorder
lead to multiple organ damage (haemochromatosis). • presents with diarrhoea, growth failure and severe
hypoproteinaemia.
Iron deficiency is the commonest nutritional defi-
ciency in humans and is usually due to:
• inadequate dietary intake Amino acids
• excessive gastrointestinal blood loss (bleeding
Defective amino acid absorption due to mutations in
lesions or inflammation).
amino acid transporters can occur in:
Acquired disorders • Hartnup disease
Iron deficiency anaemia can occasionally be the primary • cystinuria
presenting feature of small intestinal disease such as: • lysinuric protein intolerance.
• coeliac disease These defects are rare disorders affecting amino acid
• milk protein intolerance transport in gut and kidney, and in other organs in
733
• Crohn's disease. the last case. They do not involve gastrointestinal
 20.3 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

symptoms and there are no nutritional consequences In patients with carbohydrate maldigestion/malab-
because of compensatory absorptive mechanisms for sorption, the following might be indicated:
peptide and amino acid absorption. • breath hydrogen testing – challenge with the
carbohydrate of interest (e.g. lactose)
• small bowel biopsy/mucosal disaccharidase activities
• occasionally with monosaccharide malabsorption
Summary of the diagnostic inpatient dietary manipulation with close
observation of stool output.
approach to suspected In patients with bloody diarrhoea (if stool culture is
malabsorption negative for pathogens) consider:
Initial clinical assessment and stool examination will • gastroscopy and colonoscopy
suggest the diagnosis in most children. Stool micros- • biopsy of small bowel and colon
copy and measurement of stool-reducing substances • sometimes radiology looking for inflammatory
can be performed in the clinician's office and are read- bowel disease in jejunum/ileum.
ily available ‘bedside’ tests. If the diagnosis is not Sometimes highly specialized investigations are
immediately obvious, the clinician will be in a position required to establish the diagnosis of some disorders.
to investigate a limited differential list with simple and
well-directed diagnostic tests.
In patients with steatorrhoea, the following will Practical points
be useful but are not necessarily indicated for every
patient: • Diagnosis is not by exclusion.
• full blood count and differential white cell count • A thorough history, physical examination and stool
examination will suggest the diagnosis in most disorders.
• serum triglycerides/cholesterol
• Simple well-directed investigations usually confirm the
• sweat test clinical diagnosis.
• small bowel biopsy • There is no such thing as a ‘malabsorption workup’.
• X-ray of long bones.

734
 Gastro-oesophageal 20.4
reflux and Helicobacter
pylori infection
Paul Hammond, Geoffrey Davidson

This chapter discusses gastro-oesophageal reflux (GOR), work together to generate LOS pressure. The current
a very common clinical problem in infants and children, understanding of LOS function suggests that a pres-
and Helicobacter pylori, an infectious agent that colo- sure of 5–10 mmHg above intragastric pressure is suf-
nizes the stomach in more than 50% of the world's pop- ficient to maintain an antireflux barrier. Transient
ulation. H. pylori infection is acquired in early childhood lower oesophageal sphincter relaxation (TLOSR) is
but its disease manifestations usually do not occur until the major mechanism responsible for GOR in infants,
adulthood. It is possible there may be a relationship children and adults. A TLOSR is defined as an abrupt
between the two, and this will be discussed. decrease in LOS pressure unrelated to swallowing or
oesophageal body peristalsis.
Abdominal straining, which occurs frequently in
Gastro-oesophageal reflux infants, probably exacerbates GOR only when there is
simultaneous TLOSR, because both LOS tone and the
GOR can be defined as the spontaneous or involun- crural diaphragm are inhibited. The neuroregulation
tary passage of gastric content into the oesophagus. of TLOSR is controlled via a vagovagal reflex. Feeding
The origin of the gastric content can vary and includes is a potent stimulus for TLOSR, evidenced by the
saliva, ingested food and fluid, gastric secretions, and fact that, in children with GORD, TLOSRs increase
pancreatic or biliary secretions that have first been from four per hour in the fasting state to eight per
refluxed into the stomach (duodenogastric reflux). hour in the fed state.
Gastro-oesophageal reflux disease (GORD) can be Normal oesophageal body peristalsis facili-
defined as significant symptoms or damage arising as tates clearance of refluxed material including acid.
a result of GOR. The difference between physiologi- Disordered peristalsis can lead to prolonged acid
cal reflux and GORD is often blurred by the anxiety exposure and oesophageal damage.
engendered in parents, particularly first-time par- The role of gastric emptying in the pathophysiology
ents, by symptoms such as vomiting and irritability. of GORD is not clear. Delayed gastric emptying could
Physiological reflux manifested by spilling, regurgi- exacerbate GOR by prolonging gastric distension and
tation and occasional vomiting is seen in more than increasing the frequency of TLOSRs. There are some
60% of healthy infants by 4 months of age, resolves in children at the severe end of the GORD spectrum in
the majority by 12 months and rarely leads to GORD. whom delayed gastric emptying may be an issue, espe-
Conservative management is important, particularly cially those with neurological or respiratory disease.
in an otherwise healthy infant, so as not to label the
condition as a disease state when in fact it is not.
The symptoms of GORD in children aged 3–18 Clinical manifestations
years range in frequency from 1.8% to 22%, and are
more refractory and associated with complications There are many causes of regurgitation and vomiting
such as pain, vomiting, haematemesis, oesophagitis, in infants and children, both within the gastrointesti-
stricture, growth failure, swallowing difficulties, respi- nal tract and external to it. The more common causes
ratory symptoms and apnoea. are outlined in Box 20.4.2.
Regurgitation can be defined as effortless spilling
of gastric content that is usually benign. Vomiting, on
Pathophysiology (Box 20.4.1)
the other hand, is a forceful emptying of gastric con-
The main barrier to GOR is the pressure gradient tent that should always be explained. The content of
across the lower oesophageal sphincter (LOS) which is the vomitus is important because of the likely cause,
formed by the intrinsic LOS (thickened smooth mus- as is the age at onset. Bile staining implies small bowel
cle of the lower oesophagus) and the extrinsic striated obstruction and should be examined immediately.
735
muscle of the crural diaphragm. Both components Blood staining implies ulceration or gastritis.
 20.4 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

More ­ serious complications include apnoea, acute

Box 20.4.1 Pathophysiological mechanisms of ­gastro-
oesophageal reflux in infants, children and adolescents
life-threatening events and recurrent chest disease
­secondary to aspiration. Chronic cough without asso-
• Delayed volume clearance ciated lung disease is unlikely to be reflux-related.
• Impaired primary or secondary peristalsis Older children, usually over the age of 8 years, can
• Reduced pressure wave amplitude describe common symptoms such as heartburn, chest
• Increased occurrence of GOR pain, and a sick or sour taste in the mouth, implying
• Transient LOS relaxation
refluxate. Some younger children may complain of a
• Straining
• LOS sphincter hypotonia
hot feeling in the chest, abdomen or throat.
• LOS pressure drift GORD is a common problem in neurologically
• Delayed gastric emptying impaired children and, although regurgitation is the
most likely symptom, problems such as recurrent chest
LOS, lower oesophageal sphincter. disease, feeding difficulties and food refusal, anaemia,
Modified from Davidson GP, Omari TI 2001 Pathophysiological weight loss and behavioural changes can all be mani-
mechanisms of gastroesophageal reflux disease in children.
Curr Gastroenterol Rep 3:257–262.
festations of GORD.
There are many potential extra-oesophageal man­
ifestations of GORD; these are highlighted in
Table 20.4.1 highlights the symptoms suggestive of Table 20.4.2 and need to be considered as they may
GORD in infants and children. Symptoms do vary be the only presenting symptom or sign. Ear nose and
according to age. Infants more frequently regurgi- throat manifestations such as otitis media, sinusitis and
tate but have also been shown to have reflux-related dental erosions are now being recognized. Although a
neurobehavioural symptoms including irritability, link between many extra-oesophageal manifestations
crying, fussiness and back-arching but not gagging. and GORD has been identified, causality has not been
proven, and data supporting improvement in symp-
toms with GORD treatment are sparse.
Box 20.4.2 Causes of regurgitation and vomiting in
infants and children
Eosinophilic oesophagitis
Gastrointestinal tract
• Oesophagus
This condition has been widely recognized only in the
• Achalasia past decade. Eosinophilic oesophagitis is distinguished
• GOR from GORD by the presence of abundant eosinophils
• Foreign body in the oesophageal mucosa. Their presence had previ-
• Congenital defects ously been thought to be due to acid reflux. The den-
• Stomach sity of eosinophils in the mucosa (< 5 per high-power
• Pyloric stenosis
microscopy field in GORD and > 20 per high-power
• Peptic ulcer disease/gastritis
• Duodenum
field in eosinophilic oesophagitis) defines the differ-
• Malrotation ence between these two conditions, although there can
• Duodenal ulcer be a large overlap in symptoms.
• Superior mesenteric artery syndrome Symptoms include dysphagia with solid food, food
• Small intestine/colon impaction, epigastric pain and vomiting. Food allergy
• Infectious diarrhoea is present in more than 60% and at present the only
• Intussusception
proven effective therapy is strict avoidance of the
• Soy or cow's milk protein intolerance
• Meconium ileus offending allergen(s). Topical steroids seem capable of
• Inflammatory bowel disease inducing remission if a food allergy is not identified.
• Appendicitis
• Other organs
• Hepatitis Diagnostic tests
• Gallbladder disease Physiological GOR should be diagnosed on clini-
• Pancreatitis
cal grounds; diagnostic tests are not required. There
Extra-intestinal disorders is no single test for the diagnosis of GORD. If there
• Generalized sepsis are symptoms or signs of pathological reflux, such as
• Rumination pain, growth failure or respiratory symptoms, then
• Intoxications further testing is required (Fig. 20.4.1). The test used
• Intracranial lesions (e.g. tumour, hydrocephalus) will depend on the age of the child, the types of test
• Adrenal insufficiency
available, and the type and severity of symptoms. The
736 • Metabolic disorders
most commonly used tests are outlined in Box 20.4.3.
 GASTRO-OESOPHAGEAL REFLUX AND HELICOBACTER PYLORI INFECTION 20.4
Table 20.4.1 Symptoms suggestive of gastro-oesophageal reflux disease in infants and children

Infants Children

Vomiting
Gastrointestinal Feeding difficulties Waterbrash
Failure to thrive Nausea
Malnutrition Dysphagia
Cow's milk protein intolerance
Respiratory Cough, stridor Chronic cough
Cyanotic episodes
Apnoea
Acute life-threatening events

Acid reflux
Gastrointestinal Apnoea, cyanotic episodes Heartburn
Colic, irritability Oesophageal obstruction
Sleep disturbance Dysphagia, odynophagia
Flexion patterns after feeds Night waking
Hiccoughs Haematemesis
Iron deficiency
Respiratory Apnoea, cyanotic episodes
Stridor
Neurobehavioural Sandifer syndrome
Seizure-like events (similar to infantile spasms)

refluxate. It can also be used to evaluate gastric empty-

Table 20.4.2 Potential extra-intestinal manifestations of
gastro-oesophageal reflux disease ing and to document aspiration due to reflux.

Pulmonary Ear, nose and throat Other

Upper gastrointestinal endoscopy and biopsies
Asthma Chronic cough Dental erosions
Chronic Laryngitis Non-cardiac Endoscopic examination of the upper gastrointestinal
bronchitis Hoarseness chest pain tract is indicated in GORD with complications such as
Bronchiectasis Pharyngitis Sleep apnoea chest or epigastric pain, heartburn, haematemesis or
Pulmonary fibrosis Sinusitis persistent unexplained iron deficiency.
Pneumonia Vocal cord granuloma Unlike in adult medicine, oesophageal biopsies form
Recurrent granuloma
an important part of the diagnostic strategy in GORD
Adapted from Richter JE 2000 Extraesophageal in children. They can support a reflux aetiology and
manifestations of gastroesophageal reflux disease. An exclude other less common causes of oesophagitis,
overview. Am J Gastroenterol 95:51–53. such as infection (cytomegalovirus, herpes simplex
virus, candidiasis), Crohn's disease or eosinophilic
oesophagitis.
Barium oesophagraphy (‘barium swallow’)
This is the most commonly used but least sensitive
24-hour intra-oesophageal pH monitoring
test for the diagnosis of GOR. It is useful for detect-
ing structural abnormalities such as pyloric steno- This provides an assessment of oesophageal acid
sis, malrotation and strictures, and may be useful in exposure. In the majority of infants with GOR,
the assessment of swallowing function or aspiration. this test is not required and it should be carried
Children with persistent vomiting are most likely to out only if it will alter diagnosis, treatment or out-
require this test. come. Current indications for its use are outlined in
Box 20.4.4.
This is not a simple test and should be carried out
Radionuclide scintigraphy
only in a specialist centre, as many factors need to be
Radioactive 99Tc–sulphur colloid is added to an age- considered, including pretest preparation, insertion
appropriate liquid meal and can be used as a direct and positioning of the catheter, symptom assessment
737
measure of reflux. It has the benefit of measuring all and analysis of results.
 20.4 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

History and examination

Physiological reflux (GOR), GORD

e.g. regurgitation,
vomiting, irritability

Persistent symptoms Atypical symptoms,

e.g. chest disease,
asthma, apnoea

e.g. vomiting, e.g. excessive irritability,

failure to thrive abdominal/chest pain,
haematemesis

Reassurance,
thickened No
Diagnostic evaluation
feeds, posture, response
antacids

Barium swallow Upper gastrointestinal Gastro-oesophageal

endoscopy scintiscan
pH monitoring
Normal Abnormal Chest X-ray
Normal Oesophagitis Bronchoscopy
Tracheal aspirate
Symptoms Treat Appropriate
resolve management pH monitoring Treat
and/or trial of
therapy

Fig. 20.4.1 Algorithm for diagnostic approach to gastro-oesophageal reflux disease (GORD). (Modified from Youssef NN, Orenstein SR
2001 Clinical Perspectives in Gastroenterology Jan/Feb: 11–17.)

Oesophageal manometry and multi-channel

Box 20.4.3 Commonly used diagnostic tests for gastro-
oesophageal reflux disease
intraluminal impedance
Oesophageal manometry is rarely needed clinically in
• Barium oesophagraphy
the diagnosis of GORD in children but may be use-
• Upper gastrointestinal endoscopy and biopsies
• Radionuclide scintigraphy (milk scan) ful prior to fundoplication in children with a sus-
• 24-hour intra-oesophageal pH monitoring pected motility disorder. It also has a place in children
• Oesophageal manometry and multi-channel intraluminal with swallowing difficulties and in the diagnosis of
impedance achalasia.
Multi-channel intraluminal impedance measures
the flow of liquid (acid and non-acid) or gas in the
oesophagus and thus has an advantage over pH moni-
toring, which recognizes fluid flow only with a pH < 4.
It is a relatively new technique and its role in clinical
Box 20.4.4 Current indications for 24-hour intra- practice is still being evaluated. In young infants and
oesophageal pH monitoring children it is likely to become the ‘gold standard’ for
• Diagnose occult reflux in:
delineating an association between reflux and a par-
• unexplained recurrent pneumonia ticular symptom such as apnoea, cough or irritability.
• patients with bradycardia, apnoea Recently both the North American and European
• non-gastrointestinal symptoms caused by reflux, such Societies for Paediatric Gastroenterology, Hepatology
as stridor, laryngeal symptoms, atypical chest pain, and Nutrition have advocated the use of combined pH/
severe irritability multi-channel intraluminal impedance in investigating
• Assessment of adequacy of medical therapy in cases of
symptoms such as excessive crying, distressed behav-
738 severe intractable GORD
iour, apnoea and apparent life-threatening events.
 GASTRO-OESOPHAGEAL REFLUX AND HELICOBACTER PYLORI INFECTION 20.4
Diagnostic approach to gastro-oesophageal
Box 20.4.5 Treatment approach to gastro-oesophageal
reflux disease reflux disease
The diagnostic approach depends largely on the nature
General
and severity of symptoms and the presence or absence
• Reassurance
of complications. In the otherwise healthy infant • Positioning
whose main symptoms are vomiting or regurgitation, • Thickened feeds
parental reassurance is all that is required. Drug therapy
If symptoms persist despite simple therapies such • Antacids
as posture and formula thickening, barium oesophag- • H2-receptor antagonists
raphy should be carried out to exclude an anatomical • Proton pump inhibitors
Continuous nasogastric feeds
abnormality such as stricture, gastric outlet obstruc-
Surgery
tion or malrotation.
Infants presenting with acid reflux-related symptoms
suggestive of oesophagitis require endoscopy and biop-
sies. In infants with atypical symptoms, the approach is General measures
more difficult, but initially aspiration needs to be con- These include reassurance, positioning and thicken-
sidered. Barium oesophagraphy, chest X-ray and a gas- ing feeds. The importance of reassurance in relation
tro-oesophageal scintiscan may provide support for this to the otherwise healthy infant cannot be overstated.
diagnosis. Referral to a respiratory physician may also It is important to avoid numerous dietary changes,
be indicated for bronchoscopy and computed tomogra- unnecessary investigations and multiple drug thera-
phy (CT). Combined 24-hour pH/impedance monitor- pies, which are often recommended by others or tried
ing is now more widely available and will detect evidence by parents.
of GOR and also possible symptom association. Previously the only posture proven scientifically to
be effective was the prone position, but this is no longer
recommended because of the increased risk of sudden
Clinical example
infant death syndrome (see Chapter 3.10). New evi-
Sophie, the 7-month-old daughter of Greek dence suggests that laying children on their left side fol-
parents, presented with a history of recurrent lowing a meal significantly reduces regurgitation and
haematemesis, with bright and altered blood the frequency of TLOSRs. Feed thickening has also
noted in regurgitated fluid and also dark stains been shown to reduce symptoms of regurgitation and
on bibs and pillow. She was generally quite happy and vomiting by reducing the height by which the refluxate
thriving, although clinically a little pale. She did not have any
comes up the oesophagus. There are now commercially
evidence of abdominal tenderness.
In view of the recurrent bleeding and the possibility of
available infant formulas that contain thickening com-
oesophagitis or gastritis, an upper gastrointestinal endoscopy pounds. The risk is that the attenuation of overt symp-
was carried out. This showed macroscopically ulcerative toms may mask complications of GORD.
oesophagitis but normal stomach and duodenum. Sophie
was treated with omeprazole 10 mg 12-hourly, and after 4 Prokinetic drugs
weeks the bleeding had stopped clinically and the spilling had
also decreased. A repeat endoscopy 8 weeks later showed No prokinetic agents have been shown to be beneficial
macroscopic healing but still histological evidence of moderate and thus none can be recommended at present.
oesophagitis. Sophie remained on omeprazole for a further 4
months but following a trial off therapy her symptoms recurred
and she underwent a Nissen fundoplication. When reviewed
Acid suppression
at the age of 2 years she was well and asymptomatic. This is effective in reduction of symptoms due to acid
irritation of the oesophagus. Acid suppressing agents are:
• Antacids. In infants with mild symptoms suggestive
Treatment approach (Box 20.4.5)
of heartburn such as irritability between feeds, a
The ideal therapy would include the use of a drug that trial of 0.5–1 mL per kg per dose 3–6 times a day
specifically reduces the frequency of TLOSRs, but this may be worthwhile. Antacids have only a brief
is currently not available. Baclofen is a γ-aminobutyric duration of action and a response can be noted
acid (GABA) agonist frequently used to reduce muscle within several days; if not then do not persist.
spasms, particularly in children with neurological hand- • H2-receptor antagonists. Ranitidine has proved the
icap. It has been shown to reduce TLOSRs as well as most effective, in doses often higher than used in
both acid and non-acid reflux in adults and children, adults. It does have rare serious adverse effects such
but its side-effects preclude it from routine use in clini- as fulminant hepatic failure. The dose recommended
739
cal practice. is 2–3 mg per kg per dose 2–3 times a day.
 20.4 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

• Proton pump inhibitors. These are the most potent children. This may work, not by acting as a valve or
acid-suppressing agents and are used when acid- increasing LOS pressure, but by decreasing TLOSRs
related symptoms fail to respond to other therapies. due to reduction in the fundal surface area. Fundal
They are superior to H2-receptor antagonists distension is an important trigger for TLOSRs.
in efficacy because of their ability to maintain
intragastric pH > 4 for longer periods of time and
Summary
to inhibit meal-stimulated acid secretion. They
are often used as first-line treatment where more It is important to realize that only a small proportion
complete acid suppression is required, for example of children with GOR go on to develop GORD. For
in chronic respiratory disease, neurologically most infants, symptoms resolve completely before
disabled children and repaired tracheo-oesophageal 12 months of age. Unfortunately, many of these chil-
fistula. In the older child with typical symptoms dren are overdiagnosed and overtreated. It is equally
such as regurgitation and heartburn, response to a important that those with continuing symptoms are
short course of a proton pump inhibitor supports recognized and treated effectively.
GORD as the underlying aetiology.
• Omeprazole has been most extensively studied in
adults and children. It is used in doses ranging
from 0.7 to 3.5 mg/kg once daily, just before the Practical points
first meal of the day. Twice-daily dosing may
be indicated in certain situations such as severe Gastro-oesophageal reflux (disease)
oesophagitis, peptic stricture, persistent nocturnal • GOR in infants is usually a benign, self-limiting condition.
reflux symptoms and extra-oesophageal GORD. • Reassurance and minor interventions such as posture and
feed thickening often suffice.
There may be a role for ‘as required’ therapy • GORD always requires further assessment and possibly
for symptom control where there are infrequent investigation.
symptoms and damage is not an issue. Although • GORD has a number of extra-oesophageal manifestations
widely used for infantile irritability, recent studies that need to be considered.
do not support clinical benefit. • Proton pump inhibitor therapy should be first-line therapy
for treatment of GORD.
Continuous feeding
Children with intractable vomiting and growth failure
may respond to continuous nasogastric tube or gas- Helicobacter pylori infection in
trostomy feeding, with catch-up growth, and surgery
may be avoided. Transpyloric feeding using a nasoje- children
junal or gastrojejunal tube may rarely have a role, par- Helicobacter pylori is the commonest bacterial patho-
ticularly in small infants. gen in humans, infecting more than 50% of the
world's population. This infection (initially called
Surgery Campylobacter pylori), discovered in 1982 by Warren
The Nissen fundoplication is the most common surgi- and Marshall in Australia, ranks as one of the most
cal procedure; the indications are shown in Box 20.4.6. important medical discoveries of the last century.
It is now typically carried out laparoscopically in They cultured the organism from the gastric antrum
of adults with peptic ulcer disease. It meets Koch's
postulates as a human pathogen causing chronic active
Box 20.4.6 Indications for anti-reflux surgery in children gastritis. H. pylori is usually acquired in the first
2 years of life, but the disease consequences rarely
Absolute
• Acute life-threatening event or chronic lung disease due to arise in childhood.
aspiration
• Continuing severe oesophagitis or oesophageal ulceration
despite adequate therapy Epidemiology
• Intractable vomiting with growth failure secondary to GOR
Socioeconomic differences are the most important
Relative predictor of H. pylori infection prevalence in any pop-
• Oesophageal stricture secondary to GOR ulation group. In developed countries the prevalence
• Severe asthma or respiratory disease unresponsive to in children seems to be declining, but there is vari-
therapy ability in the burden of infection with higher levels in
• Family choice to avoid long-term regular acid suppression
immigrants and Indigenous populations. This is par-
740 • Persistent symptoms with oesophagitis or growth failure
ticularly the case in Aboriginal children, where at least
 GASTRO-OESOPHAGEAL REFLUX AND HELICOBACTER PYLORI INFECTION 20.4
80% are infected. This is similar to developing coun- Genetic analysis of H. pylori has demonstrated
tries, where up to 80% of children are infected by the strains with certain virulence factors, such as vacuolat-
age of 2 years, with a lower prevalence in breastfed ing cytotoxin (Vac A), and cytotoxin-associated genes
infants. In developed countries, only 10% of all chil- (cagA, cagE). In adult ulcer disease there is a correla-
dren are infected by the age of 10 years. tion between cagA positivity and peptic ulcer, but this
The route of transmission is probably similar to that is less clear in children. A study has shown a strong
of other enteric pathogens, being faecal–oral, oral–oral correlation between disease severity and the cagE gen-
or gastric–oral. H. pylori has been detected in vomitus, otype in children.
saliva, faeces, on children's dummies, and also in con-
taminated water, and food prepared with contaminated
Gastrointestinal infection (Box 20.4.8)
water. The housefly has been implicated as a vector.
The spread of infection within families is high, most Gastritis
probably from infected mother to child, although there H. pylori colonization of gastric mucosa in children is
is also evidence of father to child and sibling to sib- almost always associated with gastritis, which resolves
ling spread, especially in households with high infec- with eradication of the organism. Endoscopy can be
tion rates in all family groups. Risk factors for H. pylori negative and biopsy is essential for diagnosis, although
infection in children are shown in Box 20.4.7. on occasions nodular antral hyperplasia can be seen
The natural history of H. pylori infection in child- and is diagnostic of infection.
hood remains obscure. A significant finding has been
Duodenal ulcer
spontaneous clearing and reacquisition of gastric infec-
H. pylori gastritis is found in 90% of children with duo-
tions in preschool children, as spontaneous eradication
denal ulcers. Ulcers heal faster if anti-H. pylori ther-
does not appear to occur in adults. Although H. pylori
apy is given, compared with acid suppression alone.
infection rates are decreasing, particularly in developed
Importantly, ulcers tend not to recur if the infection is
countries, atopy is increasing. Within populations, the
successfully eradicated.
frequency of atopy is less in H. pylori-infected individ-
uals, a finding that warrants further research. Gastric ulcers
H. pylori infection as a cause of gastric ulcers is much
Helicobacter pylori-associated disease less common in children than adults, probably reflect-
ing the fact that the majority are secondary to systemic
General
causes.
In the past, gastric and duodenal ulcers in ­children
Gastric adenocarcinoma
have been described as primary or secondary.
The epidemiological association between H. pylori
Secondary ulcers, which are more common in younger
infection and gastric cancer has been judged by the
children (less than 10 years of age), are caused by sys-
World Health Organization to be sufficiently strong
temic stresses such as trauma, burns, septic shock, cor-
for it to classify H. pylori as the first bacterium to be
ticosteroids or non-steroidal anti-inflammatory drugs.
a human carcinogen. H. pylori-induced gastric cancer
Primary ulcers, which usually occur in older children,
has not been reported in children, but this associa-
give rise to symptoms similar to those in adults, with
tion may influence a decision regarding whether to
epigastric nocturnal abdominal pain and vomiting, and
treat or not.
often a positive family history of peptic ulceration. It is
now clear in this latter group that the disease is due to
H. pylori infection of gastric mucosa.
All H. pylori strains produce urease, which is thought Box 20.4.8 Consequences of Helicobacter pylori infection
to be important in the inflammatory reaction in the
stomach and also in maintaining the ideal submucous Gastrointestinal
environment for the organism. The urease reaction is • Gastritis
also exploited in a number of diagnostic tests. • Duodenal ulcer
• Gastric ulcer
• Gastric adenocarcinoma
Box 20.4.7 Risk factors for Helicobacter pylori infection • Gastric lymphoma and MALT lymphoma

• Poor socioeconomic status Extragastric

• Household crowding • Gastro-oesophageal reflux
• Ethnicity • Iron deficiency anaemia
• Migration from high prevalence areas • Short stature
• Infected parent, particularly mother
• Contaminated water MALT, mucosa-associated lymphoid type. 741
 20.4 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

Gastric lymphoma and MALT lymphoma

Box 20.4.9 Diagnostic tests for Helicobacter pylori
Sero-epidemiological studies support an associa-
tion between longstanding H. pylori infection and Endoscopic
lymphoma and mucosa-associated lymphoid type • Biopsy and histology
(MALT) lymphomas. Eradication of H. pylori has • Rapid urease test
resulted in regression of MALT lymphoma in some • Bacterial culture
cases. Both of these tumours are rare in children.
Indirect tests
Recurrent abdominal pain • Serum antibody (IgA, IgG)
In adults, a link between non-ulcer dyspepsia (pos- • Stool culture/stool antigen
sibly the equivalent of recurrent abdominal pain • 13C-urea breath test
in childhood) and H. pylori has been suggested by
a recent meta-analysis of a large number of con-
trolled studies. A comparable study in children with i­ndirect identification of infection but has only a 50%
recurrent abdominal pain does not support an asso- positive predictive value in children.
ciation. The major problem with studies in children The 13C-urea breath test is currently the best non-
is the lack of a standardized, validated, reproduc- invasive diagnostic test for H. pylori infection in
ible symptom assessment instrument. It is possible ­children. It has a greater than 95% positive and nega-
that there is a subset of children in whom H. pylori- tive predictive value. The principle of the test is out-
induced gastritis is responsible for recurrent abdom- lined in Figure 20.4.2. Urea can be labelled with either
inal pain, but more information is required. The radioactive 14C or stable isotope 13C. In children and
current consensus is that recurrent abdominal pain women of childbearing age, the 13C-urea breath test is
of childhood is not an indication to test for H. pylori recommended. Serology, although commercially avail-
infection. able, is frequently unreliable and cannot distinguish
between past and present infection. Of the other non-
Extra-gastric disease invasive tests under trial the most promising is the use
of a monoclonal antibody to detect H. pylori antigen
Gastro-oesophageal reflux in faeces.
It is postulated that certain H. pylori strains cause The aim of testing is not to detect the presence of
decreased acid production and atrophic gastritis and infection but to find the cause of clinical symptoms,
that, with eradication of H. pylori, acid rebound and therefore the important question is who should be
occurs, causing GORD. This is a controversial area in tested (Box 20.4.10).
adults, whereas there is contrasting evidence in chil-
dren supporting a potential link between the pres-
ence of H. pylori and increased acid production and
GORD. *CO2 breath
Iron deficiency/growth stunting
Iron deficiency has been described in growth-retarded
adolescents with H. pylori infection. Eradication of
H. pylori infection corrected the deficiency and led to
growth improvement. The current consensus is that
testing for H. pylori infection should be considered in
*CO2
children with refractory iron deficiency anaemia where
no other cause is found.
A large Australian study has shown a relationship
NH2
between small-for-gestational-age infants and mater-
nal H. pylori infection. Growth delay in height and *CO2
Urease
weight has also been shown in H. pylori-infected chil- *C=O *CO2+NH2
blood in
dren, but this may be biased by socioeconomic status. H.pylori
NH2

Diagnostic tests (Box 20.4.9)

Endoscopy and biopsy is the only method that can
provide evidence of disease activity such as gastritis
742 or an ulcer. Urease testing of biopsy material gives Fig. 20.4.2 The principle of the 13/14C-urea breath test.
 GASTRO-OESOPHAGEAL REFLUX AND HELICOBACTER PYLORI INFECTION 20.4
Box 20.4.10 Who should be tested for Helicobacter pylori Box 20.4.11 Who should be treated for Helicobacter
infection? pylori infection?

Yes • Children with duodenal and gastric ulcers and proven H.

• Endoscopic/radiologically proven gastric or duodenal pylori infection
ulcers • Children with histologically proven infection with
• Confirmation of eradication of H. pylori infection gastrointestinal symptoms
• Children with gastric lymphoma and proven H. pylori
No infection
• Recurrent abdominal pain without ulcer disease • Children with atrophic gastritis with intestinal metaplasia
• Asymptomatic children and proven H. pylori infection
• Children in families with history of gastric cancer or ulcer • Children with refractory iron deficiency and proven H.
disease pylori infection

Treatment
The discovery of H. pylori as the cause of primary Addition of probiotics to H. pylori eradication
peptic ulceration and gastric ulcers has dramatically regimes has led to decreased complication rates and a
changed their management, because eradication of the modest increase in eradication rates.
organism cures the disease and prevents recurrence. The burden of illness and socioeconomic costs of H.
This has meant that peptic ulcer disease is now a cur- pylori-related illness is considerable, making the devel-
able condition, virtually eliminating the need for long- opment of a prophylactic vaccine to prevent infection
term or destructive surgery. or a therapeutic vaccine to eliminate existing infection
If endoscopy is indicated to investigate organic dis- desirable, but to date no vaccine is available.
ease and H. pylori is found, the child should receive
treatment (Box 20.4.11); however, if no ulcer is found
the patient/parents should be informed that H. pylori
eradication may not relieve the symptoms. Clinical example
The traditional treatments of peptic ulcer do not A 10-year-old Vietnamese child, Than, who
eradicate H. pylori infection, and current treatment had lived in Australia since birth, presented
in children advocates a combined regimen using two with a long history of recurrent epigastric pain
antibiotics and a proton pump inhibitor, based on that woke him from his sleep at night. His
adult treatment regimens. Bismuth subsalicylate-based appetite was described as poor. There was a family history
treatment is possibly more effective, but access to this of peptic ulcer disease. Examination revealed a thin child
on the 3rd percentile for weight and 25th centile for height.
treatment in Australia and other countries can be
Epigastric tenderness was present. The signs and symptoms
difficult. suggested peptic ulcer disease, and at endoscopy antral
The currently recommended first-line treatment nodular hyperplastic gastritis was noted, as well as an ulcer
is a combination of a proton pump inhibitor, clar- in the first part of the duodenum. Histological examination
ithromycin and amoxicillin twice daily for 7 days. showed evidence of H. pylori infection. Treatment with triple
Metronidazole can be substituted for either amoxi- therapy (clarithromycin, amoxicillin and omeprazole) for
cillin or clarithromycin, but there is a high resistance 1 week led to resolution of symptoms within 4 weeks. Six
weeks after stopping therapy a 13C-urea breath test was
to this drug and its use may lead to treatment failure.
carried out and was negative, confirming eradication. At
Failure of eradication leads to the use of second-line review 12 months later, Than was well and his height and
options, which may include bismuth subsalicylate in a weight were on the 25th percentile.
triple or quadruple therapy regimen.

743
 20.5 Liver diseases Wolfram Haller, Winita Hardikar

The liver plays an indispensable role in whole-

Introduction body energy homeostasis and provides the neces-
Liver disease is relatively infrequent in childhood. sary enzymatic repertoire for numerous catabolic
Early recognition is, however, crucial, as the timing of and anabolic pathways. The main functions of the
diagnosis has a significant impact on the outcome of liver are:
many liver disorders. Chronic liver conditions result in • synthesis of a large number of proteins
a high burden of care for children and their families. (e.g. clotting factors and albumin)
This chapter aims to promote an understanding of • production and excretion of bile
the basic concepts of normal liver function, to introduce • detoxification and metabolism of endogenous
the concept of biochemical pattern recognition of liver toxins and exogenous drugs
disease, and to enable appropriate differential diagnosis • processing of nutrients – the liver is the central
and investigations in the child with suspected liver injury. regulator of intermediary metabolism
• immune function
• fluid balance
• regulation of growth and other endocrine functions.
Normal liver anatomy
and function
In evaluating liver disease, it is useful to think of Pattern recognition in acute
the liver as being composed of two morphological
and functional subunits. Injury to either compart-
and chronic liver dysfunction
ment gives rise to a specific pattern of symptoms Assessment of liver dysfunction in the child is part
and liver test abnormalities. The first subunit is the of a diagnostic process involving a thorough clinical
parenchymal compartment consisting of hepatocytes, history, clinical symptoms and signs, and a complete
the carriers of anabolic and catabolic enzymes, and panel of ‘liver function tests’ (see below). The integra-
­non-hepatocytic parenchymal cells. The latter include tion of these results will allow further categorization
­stellate cells, important for production of fibrous tis- of the disease process. Depending on which morpho-
sue under ­disease conditions, and the Kupffer cells, logical and functional compartment is affected, liver
resident mononuclear leukocytes fulfilling a crucial
­ disease can be primarily hepatocellular (parenchymal),
role in processing antigens that enter the liver through biliary (cholestatic) or mixed hepatocellular–biliary,
the portal vein. The second subunit is the biliary com- and can finally lead to failure of synthetic and detoxi-
partment consisting of the canalicular and biliary fication function. Allocation of laboratory tests to a
system. This system carries bile produced by the hepa- disease pattern results in more targeted investigations
tocytes into the bowel, but is also actively involved in (Fig. 20.5.1).
resorption of various solutes. Bile acids, comprising
12% of bile, are required for the normal absorption
Laboratory patterns of liver dysfunction
of fat and ­fat-soluble vitamins in the intestinal lumen.
Blood supply to the liver is predominantly via the The actual term ‘liver function tests’ is a misnomer:
portal vein (70%), channelling intestinal nutrients not all measurements (e.g. alanine aminotransfer-
towards the liver. The remaining 30% is provided by ase (ALT), aspartate aminotransferase (AST)) actu-
the hepatic artery, which supplies oxygen-rich blood ally assess the function of the liver, whereas others
to the parenchymal and biliary compartments. The (e.g. international normalized ratio (INR)) will not
bile ducts are sensitive to reduced arterial flow and be obtained on request of ‘liver function tests’ on a
may become damaged if hepatic arterial flow is inter- biochemistry form. For practical purposes, the liver
rupted. Blood flows out of the liver via the hepatic function tests can be divided into four categories, as
veins, which connect to the inferior vena cava. described below.
744
 Liver diseases 20.5
Infectious

Disease Diagnostic test

Hepatitis A HAV-IgG/IgM
Hepatitis B HBsAG
Ant-HBc
Hepatitis C Anti-HCV
EBV Serology
PCR

Immunologic UTI Serology Drug toxic

Sepsis PCR
Disease Diagnostic test Disease Diagnostic test
Autoimmune Total IGG Paracetamol Serum level
hepatitis ANA
Antiepileptics Stop medication
SMA (type 1)
± liver biopsy
LKM (type 2) Antibiotics
Contraceptives

Mainly
hepato
cellular
Immunologic Vascular

Disease Diagnostic test Disease Diagnostic test

Sclerosing pANCA Right heart Echocardiography
cholangitis US abdomen failure
MRCP Pattern Budd Chiari CT angiography
of liver syndrome
dysfunction
Hepatic artery US abdomen
thrombosis CT angiography

Mainly biliary Mixed

Obstructive Metabolic

Disease Diagnostic test Disease Diagnostic test

Cholelithiasis US abdomen alpha1 AT FeA1AT level
Sludge deficiency Pi type
Coledochal cyst US abdomen Haemo- Ferritin
MRCP chromatosis Transferrin
saturation
Biliary atresia US abdomen Wilson’s disease Coeruloplasmin
Liver biopsy Opthalmology
Alagille syndrome X-ray spine Cystic fibrosis Immunoreactive
Ophthalmology trypsin
Liver biopsy Sweat test

Fig. 20.5.1 Diagnoses and investigations according to the predominant pattern of liver dysfunction. ANA, anti-nuclear antibody; AT,
antitrypsin; CT, computed tomography; EBV, Epstein–Barr virus; HAV, hepatitis A virus; HBc, hepatitis B core antigen; HBsAg, hepatitis B surface
antigen; HCV, hepatitis C virus; Ig, immunoglobulin; LKM, liver/kidney microsomal antibody; MCS; microscopy, culture, sensitivity; MRCP,
magnetic resonance cholangiopancreatography; pANCA, perinuclear anti-neutrophil cytoplasmic antibody; PCR, polymerase chain reaction;
Pi, protease inhibitor; SMA, anti-smooth muscle antibody; US, ultrasonography; UTI, urinary tract infection.

745
 20.5 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

Markers of hepatocellular dysfunction: ALT, AST and filtered in the kidneys (dark urine). The lack of
bilirubin in the intestine results in pale (acholic) stools.
ALT is a cytosolic enzyme; AST can be found in both
Determination of conjugated bilirubin is the most
cytosolic and mitochondrial compartments. Both
important test in any jaundiced patient. A conjugated
catalyse a chemical reaction called ‘transamination’ –
bilirubin fraction of more than 20% of total bilirubin
hence the term transaminases. Hepatocyte damage
is called conjugated hyperbilirubinaemia and indicates
resulting from infections, drugs, toxins, immunologi-
liver disease and impaired bile flow (cholestasis). Lack
cal or ischaemic insults can result in leakage of these
of bile flow also leads to retention and blood accumula-
enzymes into the circulation. The levels of ALT and
tion of bile acids and other components of bile. It is not
AST do not correlate well with the severity of liver
known which of these components is the main mediator
damage; for example, low levels of transaminases can
of the intense pruritus seen in chronic cholestasis.
be seen in advanced parenchymal necrosis in acute liver
failure. ALT is more specific for hepatocellular injury
than AST, as the level of AST is also increased in Markers of synthetic dysfunction: albumin, INR
­cardiac or skeletal muscle damage as well as in haemol-
Albumin is the most abundant protein produced by the
ysis. If there is an isolated rise in ALT or AST, consider
liver with a half-life of 3 weeks. Serum concentrations
extrahepatic causes, such as muscle disease or coeliac
therefore change slowly in response to acute alterations of
disease.
synthesis (e.g. in acute liver failure), although albumin is a
good marker of chronic synthetic failure. The specificity of
a low albumin level is, however, limited as a marker of liver
Markers of biliary dysfunction/cholestasis: ALP,
dysfunction. Albumin synthesis is also low in situations of
GGT, conjugated bilirubin, serum bile acids
longstanding low protein intake (malnutrition), inflam-
Alkaline phosphatase (ALP) is an enzyme of uncertain matory conditions (as a negative acute-phase protein),
physiological function. Blockage of bile flow leads to and can also be lost in the urine (renal disease) or through
de novo production within the bile duct ­epithelium and the intestine (protein-losing enteropathy). The liver synthe-
to a rise in serum levels, which takes a few days. ALP sizes the majority of coagulation proteins, some of them
levels may therefore be normal in acute biliary obstruc- with the help of vitamin K as a co-factor (factor II, VII,
tion. The specificity of ALP is limited, as it is also IX, X). Liver synthetic function can therefore be assessed
found in other tissues including bone, intestine and through measurement of the INR. Because most clotting
kidney. ALP concentration is therefore often increased ­factors have a shorter half-life than albumin (factor VII, 6
in growing children, particularly rapidly growing ado- hours), the INR is useful in assessing short-term changes
lescents. If there is confusion, the origin of the ALP in synthetic liver function. In general, an abnormal INR
(i.e. liver or bone) can be tested in the ­laboratory by can be attributed to synthetic liver dysfunction if it does
determining the so-called isoenzymes. not improve 6 hours after a dose of vitamin K.
γ-Glutamyltransferase (GGT) is a more sensitive and
specific test for biliary disease, and its level increases
Markers of impaired hepatic detoxification:
with biliary obstruction or inflammation. GGT is also
ammonia, lactate
induced by certain medications; therefore, if there is
an isolated rise in GGT levels, take a full drug history. Ammonia is a product of protein catabolism. The liver
Bilirubin is the end-product of enzymatic haem break- plays a crucial role in metabolizing this neurotoxic solute.
down, a component of haemoglobin. This unconjugated In situations of acute or chronic liver failure, increased
bilirubin is lipid-soluble, can cross membranes such as concentrations of ammonia may play an important role
the blood–brain barrier and is therefore toxic, partic- in the development of hepatic encephalopathy. Lactate
ularly in small infants. Conjugation of the b ­ ilirubin is an important carrier of energy in the fasting state and
to glucuronide in the liver makes it w ­ ater-soluble and is either oxidized in the citric acid cycle or used as a sub-
allows excretion (via a transport protein in the cell strate for gluconeogenesis in the liver. Consequently,
membrane) into the small bile ducts, called canalic- liver dysfunction leads to a slowing of these metabolic
uli. The conjugated bilirubin then drains through the pathways and to accumulation of lactate within the
common bile duct into the duodenum. Damage to the bloodstream. Lactate is therefore a useful marker of
transmembranous transport of conjugated bilirubin pronounced acute and chronic liver dysfunction.
(e.g. hepatocellular insult) or blockage of the b ­ iliary
drainage system (e.g. due to gallstones or biliary atre-
Clinical signs of liver dysfunction
sia) impairs bile flow, leading to a clinical phenotype
called c­holestasis. The water-soluble conjugated bili- A thorough history and clinical examination are essen-
rubin flushes back into the bloodstream (conjugated tial to guide the diagnostic approach in a child with
746
hyperbilirubinaemia), is deposited in the skin (jaundice) suspected liver disease. When trying to identify the
 Liver diseases 20.5
cause of liver disease, it is useful broadly to catego- storage (fat, glycogen or other storage disease),
rize children into infants versus older children, acute malignancy (hepatoblastoma, leukaemia), infection
versus chronic liver disease, and biliary (cholestatic) (abscess), inflammatory infiltration (infectious and
versus hepatocellular injury. Of course, there will be autoimmune hepatitis, drug toxicity) or blockage
significant overlap, but the categories are described in of biliary outflow. The liver can feel soft and often
detail below and in Table 20.5.1 and Fig. 20.5.1. tender in the acute setting as a consequence of
The major clinical symptoms and signs of acute and capsular stretching, or hard, firm and irregular
chronic liver dysfunction are (Fig. 20.5.2): in situations of chronic liver insult. Acute biliary
• Jaundice due to impaired bile flow is associated obstruction can result in referred right shoulder pain.
with pale stools, steatorrhoea, dark urine and • Splenomegaly is typically seen acutely with
pruritus as described above. infectious hepatitis, acutely and chronically with
• Hepatomegaly can be a consequence of congestion metabolic storage diseases, but can also reflect
with blood (obstruction of venous outflow), chronic portal and splenic vein congestion in the
expansion of the parenchymal compartment by setting of portal hypertension (see below).

Table 20.5.1 Clinical and aetiological categories of liver disease in childhood

Time of presentation
Mode of
presentation Infancy Older child

Acute Infectious Infectious

• urinary tract infection • viral hepatitis (A, B, E, rarely C)
• bacterial sepsis • non A–E hepatitis
• congenital (TORCH) Biliary/obstructive
Biliary/obstructive • cholelithiasis
• inspissated bile (sludge) Metabolic
• cholelithiasis • Wilson's disease (acute-on-chronic)
Metabolic • mitochondrial disease
• galactosaemia Drug-induced
• hereditary fructose intolerance • paracetamol
• Niemann–Pick C disease • antibiotics
• fatty acid oxidation defect • antiepileptics (e.g. valproate)
• mitochondrial disease • contraceptives
Ischaemic
• neonatal asphyxia
Immunological
• neonatal haemochromatosis

Chronic Biliary/obstructive Infectious

• extrahepatic biliary atresia • hepatitis B/C
• Alagille syndrome • non-A–E hepatitis
• choledochal cyst Biliary/obstructive
Metabolic • sclerosing cholangitis
• α1-antitrypsin deficiency • choledochal cyst
• cystic fibrosis Drug-induced
• tyrosinaemia type 1 • methotrexate (e.g. chemotherapy)
• glycogen storage disease Metabolic
• Niemann–Pick C disease • α1-antitrypsin deficiency
• mitochondrial disease • cystic fibrosis
• Wilson’s disease
• non-alcoholic fatty liver disease
• tyrosinaemia type 1
Immunological
• coeliac disease
• autoimmune hepatitis
• sclerosing cholangitis
Cardiac
• congenital heart disease (+ right ventricular failure) 747
 20.5 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

Scleral icterus Feeding difficulties

Palmar erythema Muscle wasting

Clubbing Malnutrition

Portal hypertension Cholestasis

- Hepatomegaly - Jaundice
- Splenomegaly - Pruritus
- Dilated abdominal - Pale stools
veins - Dark urine
- Umbilical hernia - Steatorrhoea
- Ascites - fat-soluble vitamin
- Hydrocele deficiency

Peripheral oedema Hypotonia

Fig. 20.5.2 Clinical signs of the child with liver disease: an 8-month-old infant with end-stage liver disease due to extrahepatic biliary
atresia and failed Kasai portoenterostomy.

• Encephalopathy – mental alteration in the setting of vascular outflow branch of the liver (posthepatic:
acute/chronic liver dysfunction is thought to result Budd–Chiari syndrome, veno-occlusive disease).
from an accumulation of toxins not processed The high pressure within the portal vein transmits to
by the failing liver. Encephalopathy is graded the rest of the splanchnic vasculature and results in
according to severity. This is, however, not so distension of small venules within the oesophageal,
straightforward in children, where irritability can gastric and anal capillary bed, leading to varices.
reflect many other factors such as hunger or lack of Haematemesis following rupture of oesophageal
sleep. Early symptoms are reversal of the day/night varices can be the life-threatening first manifestation
and awake/asleep pattern in addition to irritability, of portal hypertension, whereas recurrent episodes
inconsolability or unusually aggressive behaviour. of melaena or iron deficiency anaemia can be a
Lethargy and sleepiness are late signs of hepatic more insidious sign. Splenic enlargement leads to
encephalopathy in the child. hypersplenism; a low platelet count can thus be a
• Skin changes include palmar erythema, facial useful indirect sign of advanced chronic liver disease.
telangiectasia, spider naevi, dilated abdominal veins
and clubbing, mostly reflecting chronic and severe
liver damage with portal hypertension.
• Portal hypertension is a result of increased resistance Liver disease in the neonate
to blood flow into the liver and can be due to
blockage of the inflow branch itself (extrahepatic:
and infant
portal vein thrombosis), parenchymal scarring Jaundice is extremely common in the healthy term neo-
of the liver in chronic liver disease (intrahepatic: nate, affecting more than 50% of newborns. About
748
cirrhosis) or as a consequence of obstruction of the 5–10% of infants are still jaundiced beyond 3 weeks
 Liver diseases 20.5
of age, a condition called prolonged jaundice. It is Bacterial sepsis and congenital infection are ­certainly
crucial to distinguish those children with unconju- one of the more common causes of liver ­dysfunction
gated hyperbilirubinaemia due to benign breast milk in the young neonate, a septic and TORCH (toxoplas-
jaundice, haemolysis, blood group incompatibility or mosis, rubella, cytomegalovirus, herpes simplex and
inherited conjugation disorders from those with con- HIV) screen should therefore be part of the workup.
jugated hyperbilirubinaemia. The latter is commonly Splenomegaly and skin rashes can be additional clini-
associated with liver disease, and hence conjugated cal cues in congenital infections. Congenital infections
and unconjugated bilirubin levels should be deter- can also, however, present with prolonged jaundice
mined in any child with severe or prolonged jaundice (see below) later in the neonatal period.
beyond 2 weeks of age. Common causes of neonatal Metabolic liver disease is another important disease
and infant liver disease are summarized in Table 20.5.1. complex to consider. Clinical deterioration typically
Manifestation of neonatal liver disease can be acute, occurs after a honeymoon period of a few days dur-
chronic or acute-on-chronic. ing which toxic metabolites reach a critical blood level.
Taking a detailed history is crucial. Important Episodes of hypoglycaemia can further support the
details and relevance of parental and infant history are diagnosis of a liver-based metabolic disease.
summarized in Table 20.5.2. Galactosaemia is a typical example of an autoso-
mal recessively inherited inborn error of metabo-
lism. It is rare, with an incidence of about 1 in 40 000.
The acutely unwell neonate and infant with
The lack of an enzyme, galactose-1-phosphate uri-
liver disease
dyltransferase (Gal-1-PUT), leads to blockage of
The neonate and infant have a limited array of ­galactose breakdown and to accumulation of the toxic
clinical responses to severe illness, irrespective of
­ metabolite, galactose-1-phosphate (Gal-1-P) after a
aetiology. Significant liver disease should therefore be few days of breastfeeding. Towards day 7 of life the
considered in the setting of any acutely unwell infant. ­newborns display increasing feeding difficulties, vom-
A full set of liver function tests should be performed. iting, j­aundice, lethargy and/or irritability. Laboratory
Mixed patterns of hepatocellular and biliary dysfunc- investigations will show a mixed laboratory pattern
tion (with or without synthetic dysfunction) are com- of liver dysfunction. There may be associated Gram-
mon; ­however, there will usually be a ­predominant negative sepsis (e.g. Escherichia coli). Withdrawal of
category. lactose-containing feed (including breast milk) will
­

Table 20.5.2 Clinical history in the infant with liver disease

Parents Infant

History Consider History Consider

Consanguinity Metabolic Low birth weight TORCH, metabolic

Miscarriages, early deaths Metabolic Vitamin K prophylaxis Vitamin K deficiency in cholestatic child

Pruritus/jaundice during Metabolic Pale stool colour Biliary obstruction (e.g. in biliary atresia)
pregnancy

Maternal illness during TORCH Irritability Early encephalopathy

pregnancy

Maternal intravenous Hepatitis B, C Lethargy Late encephalopathy, hypoglycaemia,

drug use hyperammonemia

Maternal hepatitis Hepatitis B, C Slow weight gain Malabsorption secondary to cholestasis

Family history of Autoimmune

autoimmune disease

Dysmorphic features in Alagille syndrome

parents 749
 20.5 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

improve symptoms rapidly. Cataract, female infertil- Abnormal clotting studies are often related to vitamin
ity and developmental delay are common long-term K deficiency on the background of longer-standing
issues. Untreated, galactosaemia leads to liver failure fat-soluble vitamin malabsorption, and are correct-
and death. However, a more chronic cholestatic course able with vitamin K supplementation. Early diag-
of disease is also seen. nostic workup is crucial. Therefore, in any child with
A significant number of inherited conditions jaundice beyond 2 weeks of age, stool colour has to
affecting lipid, fatty acid, amino acid and ammo- be assessed and conjugated bilirubin should be deter-
nia metabolism, as well as oxidative phosphorylation mined. The approach to the infant with conjugated
(mitochondriopathies), share the clinical phenotype jaundice is summarized in Fig. 20.5.3.
of galactosaemia. Further workup should therefore Chronic infant liver diseases affecting the biliary
include the determination of urine organic acids, compartment include extrahepatic biliary atresia and
amino acids and succinylacetone as well as plasma Alagille syndrome. Extrahepatic biliary atresia is char-
amino acids in the acutely unwell neonate. acterized by progressive inflammation and oblitera-
tion of the extrahepatic and intrahepatic biliary tree,
leading to impaired bile flow and secondary dam-
Chronic liver disease in the infant
age to the parenchymal compartment. The cause is
The infants falling into this category typically pres- unknown. Affected babies are typically born at term,
ent with prolonged or new-onset jaundice beyond appropriate for gestational age with no significant fail-
2–3 weeks of age, displaying predominantly clinical ure to thrive in the early stages of disease. Pale stool
signs of cholestasis with pale stools and dark urine, colour and prolonged jaundice can be seen early in the
but otherwise being clinically well. Baseline labora- course of disease, but are often overlooked. Firm hep-
tory investigations typically show a predominant bil- atosplenomegaly and failure to thrive will evolve later
iary pattern (conjugated hyperbilirubinaemia) with in the disease. Left untreated, biliary atresia will lead
only mild to moderate hepatocellular dysfunction. to cirrhosis and death within the first 2 years of life.

Evaluation of neonatal
conjugated hyperbiliruninemia

Screen for biliary obstruction

– abdominal ultrasound
(fasting ≥ 3 hours)
Examine stool colour

Collapsed gall bladder Collapsed gall bladder Collapsed gall bladder

+ pale stool + pale stool + pale stool

Sludge, gallstones Screen for infections

Liver biopsy
– ursodesoxycholicacid – urine/blood culture
– ± ERCP/stone removal – TORCH screen

Biliary atresia Screen for metabolic causes

– colangiogram – alpha1 AT level/Pi type
Choldochal cyst – + kasai surgery – immunoreactive trypsin
– surgery – urine reducing sugars
– urine succinylacetone
No biliary atresia Screen for endocrine causes
– 9am cortisol
– thyroid function testS

750 Fig. 20.5.3 The approach to the child with conjugated hyperbilirubinaemia. AT, antitrypsin; ERCP, endoscopic retrograde
cholangiopancreatography; Pi, protease inhibitor, TORCH, toxoplasma, others, rubella, cytomegaly, herpes.
 Liver diseases 20.5
Early diagnosis and treatment is crucial, and hence bil-
iary atresia needs to be excluded on an urgent basis
in any newborn with conjugated hyperbilirubinae-
mia. There is no single laboratory test to confirm bili-
ary atresia. Fasting liver ultrasonography often shows
a small, collapsed gallbladder, whereas liver biopsy
has some characteristic features. The final diagno-
sis is made with an intraoperative injection of con-
trast medium into the gallbladder (cholangiography).
At the same time, the first-line treatment, the Kasai
hepatoportoenterostomy, is performed. This opera-
tion restores bile drainage through attachment of a
bowel loop to the cut surface of the liver, slows the
progression of cirrhosis and development of end-
stage liver failure, and thereby delays the need for liver
transplantation.

Clinical example

Lilah, a 6-week-old breastfed infant, presented

with ongoing jaundice from infancy and pale
stools but was feeding well. Liver function tests Fig. 20.5.4 X-ray of the thoracic spine with ‘butterfly vertebrae’
showed a predominantly cholestatic picture with on multiple levels (arrows).
raised conjugated bilirubin and GGT levels. Ultrasonography
showed a small contracted gallbladder despite 4 hours of
fasting. The α1-antitrypsin level was normal, and liver biopsy
showed features consistent with biliary atresia. Operative j­ aundice and the complications of longstanding
cholangiography did not identify any extrahepatic biliary ­cholestasis. Liver function tests often show a mixed
tree. Lilah underwent a Kasai operation, which resulted in hepatocellular and biliary picture. Serum levels of α1-
some biliary drainage. She was able to continue to grow antitrypsin are low. A diagnosis can be established by
with the help of fortified feeds and fat-soluble vitamin serum protein electrophoresis confirming the abnor-
supplementation. By the age of 7 years, Lilah developed mal protein – protease inhibitor ZZ (PiZZ) phenotype.
end-stage liver disease and underwent liver transplantation.
The majority of infants clear jaundice spontaneously
early during infancy, whilst the hepatitic laboratory
pattern persists. A significant number of patients are
Alagille syndrome is a rare autosomal dominant therefore diagnosed later in life following the inciden-
condition also presenting with prolonged jaundice. tal finding of hepatomegaly or raised transaminase
Associated clinical features include a triangular facies, levels. A minority of patients develops liver failure
butterfly vertebrae on spinal X-ray (Fig. 20.5.4), requiring liver transplantation within the first 2 years
posterior embryotoxon on eye examination and
­ of life.
­pulmonary valve stenosis. Refractory failure to thrive
and severe pruritus are frequent late complications.
Ultrasound images of the liver and biliary tree can be
normal or indistinguishable from biliary atresia. Liver
Liver disease in the older child
biopsy confirms the diagnosis, displaying a paucity of The diagnosis of liver disease in the older child is
bile ducts. A subset of patients develop chronic liver often incidental following detection of hepatomeg-
­failure needing liver transplantation. aly or abnormal transaminases on routine exami-
Chronic infant liver disease affecting predominantly nation and blood testing, unless the child presents
the parenchymal compartment includes a number of already clinically jaundiced. Similar to the infant,
metabolic diseases, of which α1-antitrypsin deficiency clinical history (Table 20.5.3), symptoms, physical
is the most common . This is an autosomal recessive examination and liver function tests help to catego-
genetic disorder in which the defective synthesis of rize the disease into a predominantly hepatocellular
α1-antitrypsin leads to its retention within the liver or biliary pattern with an acute, chronic or acute-on-
cell, causing chronic hepatocellular damage. The clin- chronic presentation. A range of possible diagnoses
ical presentation in the infant can again be indistin- with acute and chronic presentation is summarized
751
guishable from that of biliary atresia with prolonged in Table 20.5.1.
 20.5 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

Table 20.5.3 Clinical history in the older child with liver disease

Parents Child

History Consider History Consider

Consanguinity Metabolic Travel in endemic areas Hepatitis A, E

Miscarriages, early deaths Metabolic Surgery, piercing, transfusion Hepatitis B, C

Pruritus/jaundice during pregnancy Metabolic Medication (recent new) Drug-induced

Maternal intravenous drug use Hepatitis B, C Rash, arthralgia Drug-induced or autoimmune

Family history of coeliac disease, Autoimmune Metabolic, e.g.

inflammatory bowel disease, rheumatoid New-onset behavioural changes Wilson's disease
arthritis Developmental delay Niemann-Pick C disease
Mitochondriopathy

The older child with acute liver dysfunction with acute hepatocellular and synthetic injury – even
if intake of paracetamol is denied. Nausea, vomiting
Older children falling in this category often present
and abdominal pain are common. Laboratory inves-
with a phenotype of new-onset jaundice and abdomi-
tigations reveal a predominantly hepatitic picture
nal pain.
together with often pronounced synthetic dysfunction.
In the setting of acute-onset abdominal and right
N-Acetylcysteine therapy should be started as early as
shoulder pain, vomiting and pale stools, biliary obstruc-
possible, ­particularly when the amount and timing of
tion is likely. Abdominal examination is often inconclu-
paracetamol intake is unclear.
sive; sometimes a distended and tender gallbladder can be
Sodium valproate, an antiepileptic drug, can cause
felt. Laboratory investigations display a predominantly
a similar pattern of acute synthetic liver failure,
biliary pattern of liver function test results. Pancreatic
­particularly in the child with pre-existing mitochon-
lipase concentration is commonly increased due to
drial disease. Drug reactions involving liver dysfunc-
ongoing blockage of the distal bile ducts. Diagnosis is
tion f­ollowing other drugs, such as antibiotics, are
confirmed with abdominal ultrasonography, which may
typically less acute and can be accompanied by blood
demonstrate a dilated biliary tree, an incarcerated stone
eosinophilia, arthralgia and skin rash.
in the common bile duct, sludge or stones within the
gallbladder, or a c­ holedochal cyst. Treatment may con-
sist of endoscopic stone removal (endoscopic retrograde
The older child with chronic liver dysfunction
cholangiopancreatography, ERCP) or surgery.
Infectious hepatitis is an important differential diag- Autoimmune hepatitis should be considered in any child
nosis. Abdominal pain, vomiting, general malaise and, with abnormal liver function test results. It is a chronic
sometimes, fever are present. The degree of symptoms disease of the parenchymal compartment of the liver.
in addition to cholestasis is variable and dependent The liver is enlarged and inflamed following infiltra-
on the age of the child, with younger children being tion with inflammatory cells. The affected child can be
less symptomatic. Laboratory investigations display a asymptomatic at presentation, display symptoms of
mixed pattern of hepatocellular and biliary features. acute liver disease with laboratory signs of synthetic fail-
Ultrasonography may reveal an enlarged or echogenic ure, or take a more insidious course with intermittent
liver, a normal biliary tree, often a thickened gallblad- jaundice, loss of energy, abdominal pain and arthral-
der wall, portal lymph nodes and a variable degree of gia. An important laboratory feature is the discrepancy
splenomegaly. Diagnosis is confirmed with serological between a high total serum protein and a low–normal
testing (see Fig. 20.5.1). albumin concentration, reflecting the polyclonal produc-
The clinical spectrum of drug toxicity/drug-induced tion of immunoglobulins. Serum autoantibodies allow
liver disease is very variable. A good clinical history further classification of the disease into type 1: anti-
is crucial. Paracetamol overdose is an example of nuclear antibody/anti-smooth muscle antibody-positive
acute and dose-dependent drug toxicity causing pro- (ANA/SMA+) and liver/kidney microsomal antibody
found hepatocellular damage and synthetic dysfunc- type 2-positive (LKM-2+). The diagnosis is confirmed
tion. Determination of serum paracetamol levels by liver biopsy. Treatment involves immunosuppressive
752
should be part of the diagnostic workup in every child medications such as c­ orticosteroids and azathioprine.
 Liver diseases 20.5
should not automatically be attributed to ‘fatty liver
Clinical example disease’. Other causes of chronic liver disease have to
be considered if there are any other clinical warning
Troy was a 2-year-old boy, previously well, signs or if raised transaminases do not normalize after
who developed vomiting and diarrhoea, and
a period of lifestyle changes (e.g. 6 months).
was noticed to be jaundiced. Liver function test
results showed a predominantly hepatocellular
picture with ALT and AST > 1000 units/L and raised serum
proteins. Serology for hepatitis A, B and C was negative,
α1-antitrypsin level was normal, but the LKM autoantibody
Clinical example
level was significantly raised. A presumptive diagnosis of
Sarah was a well adolescent who had liver
autoimmune hepatitis type 2 was made and liver biopsy
function tests prior to commencing therapy for
confirmed evidence of piecemeal necrosis. Troy was treated
acne. The test results showed a mildly abnormal
with corticosteroids, with a significant improvement in his
hepatocellular picture. On further questioning,
transaminase levels. Because of the severity of the initial
it was discovered that Sarah had been adopted from Bosnia
presentation, he was commenced and maintained on
and that her biological mother was thought to have used
azathioprine while the steroids were weaned. He remains
intravenous drugs. Sarah underwent testing and was found
well 11 years after presentation.
to have hepatitis C infection. She was counselled regarding
transmission of blood-borne viruses and was considered for
pegylated interferon and ribavirin therapy to eradicate the
virus. Depending on the genotype of the virus, successful
Wilson's disease is an important differential diag- eradication can occur in 40–80% of patients.
nosis to autoimmune hepatitis. It is a rare autosomal
recessive disorder presenting beyond 4 years of age.
A defective copper-transporting protein leads to reten-
tion of copper within the hepatocyte. Intracellular
copper overload leads to hepatocellular dam-
Liver failure
age. Once the liver is saturated with copper, copper The described mechanisms of acute or longstanding
­accumulates in other organs such as the brain, heart, damage to the hepatocellular and biliary compart-
kidneys and bone marrow. As in autoimmune hepati- ment can all lead to temporary or irreversible liver fail-
tis, the affected child can be asymptomatic, or present ure. The paediatric definition of liver failure relies on
with symptoms of acute liver dysfunction or chronic laboratory features, including hepatocellular injury
­
liver disease. Behavioural changes at school or at home with raised levels of transaminases and synthetic failure
as a consequence of cerebral copper deposition may be with coagulopathy (INR ≥ 2.0), uncorrectable by intra-
reported. An additional clinical feature is the Kayser– venous vitamin K administration. Jaundice and hepatic
Fleisher ring, a circular area of copper deposition in encephalopathy are not prerequisites to establish the
the periphery of the cornea seen on slit-lamp examina- diagnosis. Liver failure may be acute (i.e. in someone
tion. No single diagnostic test is available for Wilson's with no underlying liver disease) or acute on chronic
disease, but, in addition to the clinical features above, (i.e. decompensation of liver dysfunction in someone
diagnosis can be supported by a low serum caerulo- with an underlying liver disease). Unfortunately, the
plasmin level, increased urine copper excretion or a underlying chronic liver disease may have been previ-
high concentration of copper within a liver biopsy. ously unrecognized until the presentation with liver
Treatment aims to remove copper from the body, for failure. Every effort should be made to establish a
instance with chelating agents (d-penicillamine) or by ­diagnosis in order to tailor treatment appropriately and
interfering with copper absorption through the entero- allow recovery of liver function when possible.
cytes (zinc). Patients with an acute presentation often In contrast to other end-stage disease states where
need liver transplantation. replacement and supportive therapies exist (dialysis
Non-alcoholic steatohepatitis (NASH) is b ­ ecoming in renal failure, cardiac assist devices in heart f­ailure,
an increasing issue in Western countries. It is asso- ­ventilatory support in respiratory failure), there is no
ciated with the metabolic syndrome (obesity and comparable device for liver failure in routine ­clinical
­hyperinsulinism, hyperlipidaemias and h ­ ypertension). use. Treatment is mostly supportive: providing adequate
Mild liver function abnormalities usually improve fol- nutrition, preventing fat-soluble vitamin d
­ eficiency and
lowing lifestyle changes and weight loss. Untreated, treating complications such as sepsis, encephalopathy,
NASH can lead to cirrhosis and liver f­ ailure. Obesity- ascites or variceal bleeding. The only life-saving treat-
related liver disease is best treated by a m
­ ultidisciplinary ment for refractory acute or chronic liver failure is
team which includes an endocrinologist, dietitian, liver transplantation. Outcome is excellent with 5- and
physiotherapist and psychologist. As ­
­ childhood 10-year survival rates beyond 80%. Lifelong immuno-
753
­obesity is so common, abnormal transaminase levels suppressive treatment is generally required.
 20.5 GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

Practical points

• ‘Liver function tests’ do not include markers of key liver • Pale stools are difficult to detect. Examine infant stool colour
functions such as synthesis (i.e. INR) and detoxification (i.e. yourself.
lactate, ammonia). These are important and need to be • Acutely ill infants who are jaundiced are likely to have
requested separately. serious infections or metabolic disorders. Apart from a
• Abnormal liver function test results including INR must be septic screen, urgent investigations should include a full
repeated to determine the rate of progress of disease. panel of liver function tests plus creatine kinase.
In the setting of the child with abnormal INR and raised • In children, encephalopathy is a late sign in the setting of
transaminases: give vitamin K and check INR 6 hours liver dysfunction. Carefully note drowsiness and irritability in
afterwards. This helps to distinguish vitamin K deficiency the infant, and aggression or unusual behaviour in the older
from liver failure. child.
• Any newborn with jaundice persisting beyond the first
2 weeks of age must have the conjugated bilirubin fraction
measured and the stool colour examined.

754
 21
PART

SKIN DISORDERS

755
 21.1 Skin disorders Maureen Rogers, Rod Phillips, Li-Chuen Wong

Infective disorders presenting with pustules

Neonatal skin conditions
• Staphylococcal infection – particularly impetigo
Many of these conditions will be described below, (which more often presents with vesicles); a
but the manner of their presentation in the neonatal common site is near an infected umbilical stump.
period will be emphasized in this initial section. • Candida – multiple widespread small pustules
which soon rupture producing a circular lesion with
Pustular lesions in the neonate peripheral scale.
• Herpes simplex – grouped, often coalescing,
There are many conditions that present in the neona- pustules; often evolve from initial vesicular
tal period with pustules or pustule-like lesions. Some lesions. Particularly on presenting part (so
of these are benign and transient and of no systemic usually the head). This may be associated with
significance; however, many potentially serious infec- severe neurological disease (see below and also
tions can present with similar pustular lesions and it is Chapter 11.4).
vital to exclude infection rapidly in any pustular erup- • Varicella – usually initially vesicles, which may
tion in a neonate. become pustular. Unlike chickenpox in older
children, the lesions are often seen in the same stage
Sterile benign transient pustular disorders of development.
• Many other organisms including Listeria
• Toxic erythema of the newborn – widespread red monocytogenes, Pseudomonas aeruginosa and
macules each surmounted by a papule or pustule; Haemophilus influenzae can cause sepsis and
onset in the first 2 days of life and disappearance pustules.
by the end of the first week.
• Transient neonatal pustular dermatosis – onset at
Blistering lesions in the neonate
birth of flaccid pustules that dry out in 48 hours,
leaving post-inflammatory hyperpigmentation in As indicated there is overlap between pustular and blis-
dark-skinned infants. tering disorders in the neonatal period. Several condi-
• Infantile acropustulosis – crops of spontaneously tions may present with blisters and then become pustular.
resolving pustules on the hands and feet that occur The term vesicle refers to a small blistering lesion.
during the first few months of life.
• Eosinophilic pustular folliculitis of the scalp –
Infections
recurrent groups of pustules on a red base on
the scalp in early infancy; later they may occur • Herpes simplex – grouped coalescing vesicles,
elsewhere. particularly on presenting part (so usually the
• Pustular miliaria or sweat duct occlusion rash – head); rupture to produce deep, punched out,
short-lived pustules in amongst more typical erosions.
red papules of miliaria (heat rash), occurring • Varicella – usually initial vesicles which soon evolve
particularly on the face, scalp and upper trunk. into pustules.
• Bullous impetigo – flaccid blisters which soon
rupture to produce large superficial spreading
Benign transient lesions simulating pustules
erosions (Fig. 21.1.1).
• Milia – firm, white papules especially on the face, • Staphylococcal scalded skin syndrome – widespread
which extrude in early weeks of life; these are erythema followed by superficial erosions,
sebaceous retention cysts. commencing in flexural areas and around the
• Sebaceous hyperplasia – yellow papules on the nose, mouth; may be transient blistering.
which resolve in early weeks. • Congenital syphilis – blisters mainly in buttock area.
756
 Skin disorders 21.1

Fig. 21.1.1 Bullous impetigo with flaccid blisters and spreading Fig. 21.1.3 Incontinentia pigmenti with a linear array of blisters
erosions. and pustules.

Conditions with possible systemic implications stigmata of disease, including brown Blaschko-
distributed lesions, patchy alopecia and partial
• Zinc deficiency – blistered and crusted lesions anodontia. Infant may have early seizures.
around mouth, nose and in napkin area.
• Epidermolysis bullosa – blistering in areas of Purpura in the neonate
trauma; may be mucosal blistering and breathing
problems. This may be due to the early presentation of any cause
• Bullous ichthyosis – blisters and erosions on the base of childhood purpura (see below), but particular
of a bright red skin; skin thickens in early days. causes in the neonate are mentioned here.
• Mastocytosis – blisters on the background of • Systemic congenital infections – including rubella,
localized brownish lesions or a diffuse leathery skin cytomegalovirus, toxoplasmosis, herpes simplex.
with a peau d'orange appearance. • Haemolytic disease of the newborn – for example
• Langerhans cell histiocytosis – vesicles, erosions and with Rhesus incompatibility.
purpuric crusted lesions (Fig. 21.1.2); may be self- • Malignancy – including neuroblastoma,
limiting or can progress to, or reappear as, a serious Langerhans cell histiocytosis, leukaemia.
malignant disease. May be associated lytic bone • Iatrogenic injury – including birth trauma,
lesions and hepatomegaly. extravasation of drugs, arterial injury during
• Incontinentia pigmenti – a linear arrangement of catheterization.
blisters, particularly on the limbs (Fig. 21.1.3),
following the lines of Blaschko (see below). Red, scaly rashes in the neonate
An X-linked recessive disease, so presents or young infant
predominantly in girls. The mother may have late A number of important conditions can present with
diffuse redness and variable scaliness in the neo-
nate; affected infants often have major problems with
temperature regulation and fluid balance, and may
­seriously fail to thrive.
• Seborrhoeic dermatitis – dull red erythema with a
greasy, yellow scale involving particularly the scalp,
centrofacial area and all flexures, major and minor.
The scale may be absent in the flexures, and secondary
monilia is common. Usually asymptomatic and
self-limiting after the early months of life. Responds
to weak steroids and anti-monilial agents. In cases
in which there is a failure to respond to appropriate
treatment, or the presence of any brownish scale
or purpura, the possibility of Langherhans cell
Fig. 21.1.2 Langerhans cell histiocytosis with crusted purpuric histiocytosis, which also occurs in the ‘seborrhoeic
papules. areas’, must be considered.
757
 21.1 Skin disorders

• Atopic dermatitis – rarely this condition presents in pigmentation of the sclera of the ipsilateral eye. It is
very early infancy with a widespread red, scaly and most common in Oriental individuals and is present
itchy rash. These patients often have food allergies at birth in over 50% of cases. It is a permanent lesion.
and will go on to develop difficult long-term Associated sensorineural deafness is reported, and
disease. very rarely these lesions may be complicated in adult
• Ichthyoses – some of these conditions present life by development of malignant melanoma.
with the child covered in a shiny, red membrane
Congenital melanocytic naevi (CMN)
that peels off in the early weeks of life to leave a
These occur at birth as raised verrucous or lobulated
red scaly skin. Some commence with a dramatic
lesions of varying shades of brown to black, sometimes
degree of redness and scale without the membrane.
with blue or pink components, with an irregular margin
An early possible complication is hypernatraemic
and often growing long dark hairs. They may become
dehydration. The high metabolic state may lead
increasingly hairy with time. Giant-sized lesions may
to failure to thrive. Some are associated with
produce considerable redundancy of skin and often
neurological abnormalities.
occur in a ‘garment’ distribution on the trunk and adja-
• Metabolic disorders – a red, scaly rash can occur
cent limbs. In patients with large naevi an eruption of
in neonates with inherited carboxylase deficiencies
smaller, but essentially similar, lesions may occur dur-
and essential fatty acid deficiency secondary to
ing the first few years of life. Malignancy in giant naevi
any severe malabsorption. The former may be
can occur in childhood and the incidence over a life-
associated with severe acidosis and coma.
time is possibly of the order of 2%. In medium and
• Immunodeficiencies – patients with severe
small lesions the risk is much lower and any develop-
combined immune deficiency (SCID) and other
ment of malignancy is always post-pubertal. When
immunodeficiencies may present with a widespread,
large lesions occur over the axial spine, and in particu-
red, scaly rash in the neonatal period or early
lar when multiple satellite lesions are present, there is
infancy. In some cases this represents a congenital
a risk of intracranial lesions, both melanocytic involv-
graft-versus-host disease.
ing the meninges and structural in the posterior cranial
• Staphylococcal scalded skin syndrome – after
fossa, which may be further complicated by obstructive
the blistering and erosive phase there may be a
hydrocephalus. CMN over the lower spine may be asso-
striking scaly and crusted rash, still on a residual
ciated with a tethered cord (Fig. 21.1.4). Neuroimaging
erythematous background.
is required in all these patients.
• Congenital candidiasis – usually presents with small
pustules, but as they resolve a widespread scaly red
rash can ensue.

Birthmarks and other naevoid conditions

Some naevoid conditions are not present till some time
after birth, despite being ‘programmed’ from birth.
These will be included in this section.

Pigmented birthmarks
Mongolian spot
These are flat, blue or slate-grey lesions with poorly
defined margins. They may be single or multiple and
occur particularly on the lumbosacral area, although
the shoulders, upper back and other areas may be
involved. They are found in over 80% of Oriental and
black infants and in up to 10% of white infants, par-
ticularly those of Mediterranean origin. They usually
fade considerably by puberty, but may remain unal-
tered throughout life.
Naevus of Ota
This is a patchy blue–grey discoloration of the skin of
the face, particularly on the cheek, periorbital area and Fig. 21.1.4 Congenital melanocytic naevus over the
758
brow. It is usually unilateral and often there is a ­similar lumbosacral area.
 Skin disorders 21.1
Naevoid pigmentary disorders ­ ypopigmented; it usually occurs in otherwise healthy
h
These are flat areas of hyperpigmented or hypopig- children but can be associated with endocrine dis-
mented skin, obvious at or very soon after birth. They eases. Leprosy is another important cause of acquired
occur in characteristic patterns – either segmental, or hypopigmented lesions.
whorled and streaky following the lines of Blaschko
(Fig. 21.1.5). These lines represent the tracks taken
by genetically identical cells in the embryo and are a
Epidermal naevi
marker for genetic mosaic patterns. The lesions usu-
ally have rather irregular edges. Sometimes the condi- Epidermal naevi arise from the basal layer of the
tion is extensive, resembling a marble cake, and both embryonic epidermis, which gives rise to skin append-
hypopigmented and hyperpigmented lesions are pres- ages as well as keratinocytes. These naevi have been
ent in the one individual. These lesions usually occur classified, according to the tissue of origin, into kera-
as isolated phenomena but may be associated, as part tinocytic, sebaceous and follicular types. They can
of certain mosaic phenotypes, with neurological, skel- involve any area of skin. They may be present at birth
etal and other abnormalities. One syndrome with or appear in the first few years of life; subsequently
hyperpigmented lesions and skeletal abnormalities is they may simply grow with the patient or new areas
McCune–Albright syndrome. of involvement may become evident. On the scalp and
Important in the differential diagnosis of brown face the naevi have a yellowish colour, due to promi-
lesions are the café-au-lait spots of neurofibromato- nent sebaceous glands, and present as a hairless, often
sis, which are rarely present at birth, are more rounded linear, plaque, usually flat in infancy and childhood
in shape, and which continue to increase in num- and becoming verrucous at puberty. Lesions elsewhere
ber. In the differential of hypopigmented lesions are are usually dark brown but are occasionally paler
the ash leaf-shaped white spots of tuberous sclerosis. than the normal skin. They occur as single or multiple
These also often appear after birth. Vitiligo, which can warty plaques or lines, often arranged in a linear or
occur at any age, is totally depigmented rather than swirled pattern (Fig. 21.1.6).

759
Fig. 21.1.5 Lines of Blaschko.
 21.1 Skin disorders

after 10 months is unusual. After a stationary

phase, signs of involution begin, with the
appearance of grey areas that enlarge and coalesce.
The tumour becomes softer and less bulky and
then disappears in 90% of cases by 9 years of age.
Residual skin changes at the site may persist.
• Deeper haemangiomas may occur alone or beneath
a superficial lesion (Fig. 21.1.7). The overlying skin
is normal or bluish in colour. As they resolve, they
soften and shrink, and most disappear completely.
Complications of haemangiomas. Although many
haemangiomas resolve without sequelae, significant
complications can occur.
• Incomplete resolution – redundant tissue, residual
telangiectasia, scarring following ulceration.
Fig. 21.1.6 Epidermal naevus with brown, warty lesions
following the lines of Blaschko.
• Ulceration – inevitable scarring, full-thickness tissue
loss on ‘edge structures’ (lip, lid, ala), cicatricial
ectropion from scarring of eyelids, cicatricial alopecia.
It is now clear that the linear and swirled patterns • Obstruction of vital structures:
taken by epidermal naevi follow the lines of Blaschko • Large eyelid lesions can obstruct vision producing
and that all epidermal naevi can be explained on the amblyopia. Lesions that press on the globe, even
basis of genetic mosaicism, with each type of naevus without obstructing vision, can cause astigmatism
representing the cutaneous manifestation of a differ- and a degree of amblyopia.
ent mosaic phenotype. In most patients the naevus is • Lesions around the nares can lead to difficulty in
the only detectable manifestation, but in some patients breathing during feeding.
there are associated abnormalities in other organ sys- • Large, or painfully ulcerated, lesions of the lip
tems, particularly skeletal, neurological and ocular. can lead to problems with sucking.
Skeletal abnormalities occur particularly with large • Haemangiomas of the larynx can cause stridor
naevi of keratinocytic type on the limbs, and neurolog- followed by complete obstruction and represent
ical and ocular abnormalities with large or centrally a medical emergency. A ‘beard’ distribution
located naevi of sebaceous type on the head. haemangioma is a marker for possible laryngeal
involvement and these patients should be
Vascular birthmarks investigated with a lateral airways X-ray even
These can be divided into haemangiomas, which are pro- when stridor is not present.
liferative vascular tumours, and vascular malformations,
representing fixed collections of dilated abnormal vessels.
Haemangiomas
Presentation and terminology. Haemangiomas usually
appear just after birth, undergo a fast growth phase
and then, over a long period, tend to resolve sponta-
neously. All infantile haemangiomas, whether super-
ficially or deeply located in the skin, have the same
structure, being composed in the early stage of prolifer-
ating masses of endothelial cells with occasional lumina
and later, as they resolve, of large endothelium-lined
spaces. The terms capillary, cavernous and capillary–
cavernous are misleading and should be abandoned in
favour of the simple term haemangioma. However, the
terms superficial and deep remain useful.
• Superficial haemangiomas usually appear in the
first weeks of life as an area of pallor, followed by
a telangiectatic patch. They then grow rapidly into
a lobulated, well demarcated, bright red tumour.
Rapid growth continues over the first 6 months of Fig. 21.1.7 Combined deep and superficial haemangioma with
760
life; the growth rate then slows and further growth ulceration.
 Skin disorders 21.1
Some haemangiomas do not respond to propranolol,
Clinical example and propranolol does not help heal ulcerated lesions
and might worsen ulceration. This is a new treatment
Harriet was born with a blanched area of skin and needs continuing evaluation.
bilaterally on the lower face, extending under
the chin. A week later there was a tracery
of telangiectases and over the subsequent
Vascular malformations
3 weeks bright red, raised dots appeared in the area, These are collections of dilated abnormal vessels, clas-
gradually coalescing into an extensive red haemangioma. sified according to the vessels of origin. All vascular
When the baby was 4 weeks old her mother noticed that malformations are present at birth (although occa-
Harriet's breathing had become noisy when feeding. sionally not evident) and grow only in proportion to
Urgent referral to investigate the stridor was followed by the growth of the child. They show no tendency to
a lateral airways X-ray, which demonstrated narrowing
involution. The most appropriate terminology refers
in the subglottic area. Endoscopy confirmed subglottic
haemangioma. The infant was admitted to hospital and to the component vessels and many outdated terms
observed carefully. Oral propranolol was commenced. After (in brackets below) can be abandoned:
1 day the stridor had gone and the birthmark was less angry- Capillary malformation (port wine stain). This pres-
looking. A tracheostomy was not needed. The propranolol ents as a flat purple stain, most commonly on the face,
treatment was continued over an 8-month period during but it may occur anywhere. When it involves the upper
which there was considerable fading and shrinking of lid and central forehead it may be a part of Sturge–
the haemangiomata. Harriet remained free of respiratory
Weber syndrome, associated with glaucoma, cerebral
symptoms.
calcification and seizures. Careful ophthalmological
assessment and follow-up, and neuroimaging are indi-
cated in patients with this presentation.
Possible associations of haemangiomas Venous malformation (varix). This presents as a
• Lumbosacral lesions – tethered spinal cord. bluish tumour that empties with pressure and when
• Perineal segmental lesions – abnormalities of the elevated, and fills when dependent; phleboliths may
genitalia and lower urogenital and gastrointestinal develop within it and be seen on ultrasonography or
tracts. X-ray.
• Large segmental facial lesions – posterior cranial Lymphatic malformation (lymphangioma, cystic
fossa malformations, abnormalities of heart, aorta hygroma). This may be macrocystic, microcystic, or
and other major arteries, and ocular abnormalities. a combination of both. Macrocystic lesions are deep
• Multiple small cutaneous haemangiomas – and present as skin-coloured tumours, often with
haemangiomas in the liver, brain and other internal bruising; rarely these lesions become clinically appar-
organs; high-output cardiac failure. ent only when bleeding into them occurs. Microcystic
Appropriate imaging studies should be performed in lesions are deep or superficial and present on the skin
all patients with these presentations. as groups of haemorrhagic vesicles or warty lesions.
Management of haemangiomas. Simple observation Arteriovenous malformation. This presents as a
and reassurance while awaiting natural resolution is pulsatile skin-coloured or erythematous lump. These
the ideal approach for most haemangiomas. always need experienced assessment and management
Ulceration should be managed with a combination because of the significant risk of expansion and prob-
of topical anaesthetic, topical antibiotic, dressings lems such as pain and bleeding, particularly at puberty.
and/or oral antibiotics as appropriate. Other mixed malformations. Some are very com-
Systemic treatments should be considered for lesions plex and associated with limb hypertrophy. Klippel–
with anticipated long-term appearance problems, an Trenaunay syndrome is a capillary–venous–lymphatic
alarming growth rate, ulceration in areas where seri- malformation with limb hypertrophy; Parkes–Weber
ous complications could ensue (e.g. lips), interference syndrome is a capillary–arteriovenous malformation
with vital structures and severe bleeding. The first-line with limb hypertrophy and risk of ulceration from the
systemic treatment has been high-dose oral predniso- shunting.
lone to try to slow or stop growth. This is associated
with predictable steroid side-effects, limiting its use
Moles (acquired melanocytic naevi)
to more serious cases. More recently, oral proprano-
lol has been used as initial treatment. This change These usually first appear after the age of 1 year and
has occurred because propranolol appears to be more increase in number throughout childhood. They com-
effective at stopping growth and hastening involution mence as brown or black macules, some of which
in many haemangiomas and has a better side-effect become raised and enlarge laterally as they develop.
profile. Unlike the situation with oral steroids, pro- They are usually of uniform colour and well circum-
761
pranolol may shrink lesions that have ceased growing. scribed. The risk of melanoma arising from acquired
 21.1 Skin disorders

melanocytic naevi is very low (less than 0.1%); mela- dysfunction. These problems can be prevented by early
noma almost never occurs in childhood so their pro- magnetic resonance imaging (MRI) and surgical cor-
phylactic removal in young patients is not justified. rection. Congenital lesions that have been associated
with underlying spinal problems include haemangio-
Halo naevi
mas, capillary malformations, lipomas, dimples, sinuses,
A depigmented halo may occur around a melanocytic
congenital melanocytic naevi and hairy patches.
naevus; the lesion may appear inflamed and often disap-
pears, leaving a white spot, which may eventually repig-
ment. This is a completely benign change. Although
often apparently isolated, the condition can occur in the Cutaneous infections and
setting of vitiligo (Fig. 21.1.8) and may in some patients infestations
indicate a predisposition to this condition.
Viral exanthems
Dysplastic or atypical naevi
A subtype of acquired melanocytic naevi with char- This term refers to the cutaneous manifestation of
acteristic clinicopathological features is a marker for a viral illness (enanthem is the manifestation in the
an increased risk of developing malignant melanoma. mouth).
Atypical naevi differ from more typical moles by being The patterns may be:
larger (more than 5 mm in diameter), having irregular • specific – where the appearance of the exanthem
and indistinct margins and irregular tan-brown colou- enables a clinical diagnosis of the causative virus.
ration, often with an erythematous component. They • non-specific – where the same pattern of exanthem
are predominantly macular, sometimes with a cen- may be caused by many different viruses.
tral elevated portion. They may appear in childhood
as small, typical-appearing naevi, which after puberty Specific patterns
develop the atypical features. Characteristic dysplastic The aetiological virus can usually be identified clin-
naevi may appear on the scalp in childhood. The final ically from the pattern of rash in the following
confirmation is based on the finding of some or all of situations:
a constellation of histopathological features. Patients • Chickenpox – scattered vesicles, pustules and dark
with multiple dysplastic naevi should be observed fre- crusts; lesions occur in crops (see Chapter 12.1).
quently and monitored with serial photography. Any • Herpes zoster – vesicles and pustules following the
such naevus showing significant alteration should be distribution of sensory nerves (see Chapter 12.1).
removed immediately. • Herpes simplex – see below.
• Erythema infectiosum – caused by a parvovirus
Lumbosacral birthmarks B19, presenting with a slapped cheek appearance
followed by a lacy erythematous rash mainly on the
Congenital lesions over the lumbosacral area may be limbs (Fig. 21.1.9) (see Chapter 12.1).
associated with occult spinal abnormalities such as a
• Mollusca – caused by a pox virus (see below).
tethered cord. These spinal anomalies may not cause
• Hand, foot and mouth disease – due to one of the
problems until later in childhood, when they can pres- Coxsackie group of enteroviruses; presents with
ent insidiously with irreversible bladder, bowel or limb pustules and purpuric lesions limited to hands and
feet with oral blistering.

762 Fig. 21.1.8 Halo naevus in a patient with vitiligo. Fig 21.1.9 Lacy erythematous lesions of erythema infectiosum.
 Skin disorders 21.1
Non-specific patterns Conditions that may mimic viral exanthems, or which
viral exanthems may mimic, include:
Each of these patterns may be produced by a wide
• Drug reactions – urticarial, macular, papular or
variety of viruses, and the same virus may produce
erythrodermic exanthems. History of exposure and
many different patterns of exanthem.
timing are helpful in differentiation. An allergic
The viruses usually involved are: reaction to ampicillin is more common in patients
• Enteroviruses with Epstein–Barr virus infection.
• Adenoviruses • Kawasaki disease – macular, urticarial,
• Hepatitis A and B viruses erythrodermic exanthems. An erythematous rash
• Epstein–Barr virus accompanied by oedema of the palms and soles is
• Cytomegalovirus often prominent in Kawasaki disease. Other early
• Human herpesvirus (HHV) 6 and HHV7 features include prolonged high fever, conjunctivitis,
• Parvovirus (can produce non-specific as well as redness, swelling or ulceration of mucosal surfaces,
specific rashes). and enlargement of lymph nodes. Desquamation of
The patterns include: the hands and feet, especially of the digit tips, is a
• Urticarial exanthems – raised erythematous lesions later finding.
that may be annular or figurate; itch is variable • Meningococcal septicaemia – purpuric exanthem
and the pattern changes from hour to hour. In (see Chapter 12.3). Small purpuric spots and
young children there may be a central non-palpable larger stellate areas of purpura developing central
purpuric element that resolves over several days necrosis. Associated with high fever and shock.
rather than hours, leading to misdiagnosis as • Scarlet fever – papular exanthem, erythrodermic
erythema multiforme. In children under 6 years exanthem. There is significant fever, strawberry
old, more than 90% of cases of urticaria are caused tongue, a rough consistency to the rash, and later
by a viral illness. peeling of palms and soles.
• Macular exanthems – these are composed of flat • Staphylococcal and streptococcal toxic shock –
red spots of variable size, sometimes becoming erythrodermic exanthems. Accompanied by a high
confluent. These are usually widespread and are fever and significant manifestations of shock.
characteristically difficult to differentiate from • Rickettsial infections – macular, papular or purpuric
allergic reactions to drugs. In general the occurrence exanthems.
of lesions in a linear distribution along scratch • Miliaria or heat rash – micropapular exanthem
marks, exaggeration in areas of sunburn or previous or purpuric exanthem in a thrombocytopenic child
skin disease, and the presence of lymphadenopathy with miliaria.
favour a viral over a drug aetiology. • Systemic juvenile chronic arthritis – macular,
• Papular exanthems – papules, which are raised papular and urticarial exanthems. An erythematous
erythematous lesions, may be few or multiple and maculopapular rash is often seen in this condition.
vary in size from tiny pinpoint lesions to 0.5–1.0 cm This rash usually has a salmon-pink colour and tends
in diameter. A linear distribution of groups of to come and go, being particularly evident at the time
lesions is commonly seen and the limbs are usually when the fever is at its height. It may also be urticarial.
affected more than the trunk. • Food-induced urticaria – urticarial exanthems.
• Purpuric exanthems – enteroviruses are the • Guttate (small spot) psoriasis – micropapular
commonest causes of purpuric exanthems. exanthem.
Clearly the most important condition to be
differentiated is meningococcal septicaemia. The
purpuric lesions caused by enteroviruses tend to Molluscum
be small petechial macules but larger, angulated This is a poxvirus infection that is uncommon under
lesions sometimes occur. 1 year of age and occurs particularly in the 2–8-years age
• Vesicular and/or pustular exanthems – these lesions group. The spread of lesions is enhanced in warm water
start as vesicles but often, as in varicella, become and outbreaks occur among children who swim together
pustular and an admixture of lesions is seen. or share baths or spas. Further spread of mollusca in the
The lesions are often concentrated mainly on the individual is also encouraged by being in warm water.
limbs. The buttocks are another common site of
involvement.
Clinical features
• Erythrodermic exanthems – these are rare, with
widespread erythema and variable scaling. They are Typical lesions are spherical and pearly white with
particularly difficult to differentiate from bacterial a central umbilication, but they may vary from tiny
toxic reactions and drug reactions. 1-mm papules to large nodules over 1 cm in diameter. 763
 21.1 Skin disorders

They occur on any part of the skin surface, with com- Management
mon sites being the axillae and sides of the trunk, the
Various forms of treatment are available; they depend
lower abdomen and the anogenital area. Rarely they
on the area, the type of wart and the age of the
occur on the eyelids, where they may cause conjunc-
patient. Because spontaneous disappearance is com-
tivitis and punctate keratitis. Mollusca on the face in
mon, aggressive treatment is often inappropriate.
school-aged children are visually unsightly and should
Treatments include:
be treated.
A secondary eczema often occurs around lesions,
• Keratolytic wart paints (e.g. salicylic acid, lactic
acid and collodion) – for common warts and
particularly in atopic children.
plantar warts.
Secondary bacterial infection may occur, producing
crusting, redness and pus formation. However, these
• Retinoic acid preparations – for facial plane warts.
same changes may be seen during spontaneous reso-
• Podophyllotoxin and imiquimod – for anogenital
warts, used under strict supervision.
lution, which occurs in most children within several
months, leaving normal skin or tiny, varicella-like scars.
• A 20% formalin solution – for plantar warts,
combined with serial paring.
• Cautery or diathermy – useful for lesions on the lips
Management or anogenital area but elsewhere recurrence is fairly
frequent following their use and there is also a risk
Each lesion lasts for only weeks and, if the child is kept
of producing a painful scar, particularly over the
out of heated pools and spas and has showers rather
joints of digits or on the palms or soles.
than baths at home, the proliferation is curbed and the
• Liquid nitrogen cryotherapy – a successful method
number of lesions usually decreases quickly. If these
of dealing with common warts that is useful for
measures are adhered to rigidly, treatment is rarely
older children.
required:
• Oral cimetidine has recently been demonstrated
• Mollusca are often resistant to chemical therapies
to be a useful treatment in some cases of multiple
but cantharidin and potassium hydroxide may
refractory warts in young children.
sometimes be effective when applied under strict
• Topical immunotherapy – creating sensitization
guidelines.
with 2% diphencyprone (DCP) followed by
• The most definitive treatment is deroofing of the
application to the warts of a diluted DCP solution
lesion with a 21-gauge cutting-edged needle and
or cream will cause an inflammatory reaction,
wiping out the contents.
which may hasten resolution of the lesions.
• With multiple small lesions in a young child,
spontaneous resolution should be awaited but,
if the lesions are troublesome because of their Dermatological presentations
site, surrounding eczema or frequent secondary of herpes simplex
infection, removal under nitrous oxide sedation Herpes simplex virus (HSV) infections are extremely
may be considered. common in children, and serological studies confirm that
• Treat any secondary eczema. more than 90% of the population have been infected by
the time of reaching adulthood. The commonest type is
Warts HSV1, although HSV2 is more important in adulthood,
being the major cause of genital herpes. Several distinct
These are benign tumours caused by infection with a presentations are recognized in childhood.
variety of papilloma viruses of the papova group:
• The common wart (verruca vulgaris) occurs
particularly on hands, knees and elbows. Intrauterine herpes simplex
• Plane or flat warts, 1–3-mm, pink or brown, barely • Cutaneous lesions include blisters and erosions,
raised papules, occur on the face and often spread sometimes in a dermatomal distribution, and
along scratch marks or cuts. irregular, often linear scars.
• Plantar warts occur particularly over pressure • Other features are microcephaly, short digits,
points on the soles and can be differentiated from cardiac abnormalities and a variety of ocular
calluses by a loss of skin markings over the skin abnormalities.
surface.
• Warts at mucocutaneous junctions often have a
Neonatal herpes simplex
filiform or fronded appearance.
• Anogenital warts may be acquired from maternal • The skin lesions are grouped blisters, localized
infection during delivery but their presence in older initially on the presenting part, usually the head,
764
children raises the suspicion of sexual abuse. with the onset usually between the fourth and eighth
 Skin disorders 21.1
days of life. The eruption may become widespread,
with individual lesions a few millimetres across
coalescing to produce large erosions.
• A rapid immunofluorescence test on material from
the blister base enables a diagnosis within a few
hours.
• Assess immediately for other organ involvement,
of which the most potentially devastating is
neurological.
• Immediate treatment with intravenous aciclovir is
indicated.

Primary herpetic gingivostomatitis

The child is systemically unwell with a high fever
and there is severe swelling, erosion and bleeding of
the gums and the anterior part of the buccal mucosa.
Spread to the lips and the facial skin often occurs.
There may be considerable soft tissue swelling and Fig 21.1.11 Herpes simplex on a finger with grouped, intact
prominent lymphadenopathy. If swallowing is impos- pustules.
sible, the child will require admission for hydration.
Recurrent cutaneous herpes simplex
Primary cutaneous herpes simplex
Recurrent herpes simplex of the face, particularly
• Can occur anywhere on the body, depending on the around the lips (herpes labialis), is common in child-
source of infection, as painful grouped blisters or hood. As in adults, various factors, including fever and
pustules (Fig. 21.1.10) on an erythematous base that sun exposure, may reactivate the virus. Recurrent her-
soon break to produce erosions or crusted lesions. pes can occur at any site.
• Often there is local swelling and regional
lymphadenopathy, and the child may be febrile. Disseminated herpes simplex
• When a primary lesion occurs on the thick skin (eczema herpeticum)
of a finger, the blisters do not break easily and
intact, grouped pustules last for several days, often This occurs as a complication of atopic eczema and in
misdiagnosed as a bacterial abscess (Fig. 21.1.11). immunosuppressed patients. It may originate from a
• When primary herpes simplex occurs in the napkin primary or recurrent infection or from external rein-
area it presents as a severe erosive napkin rash. fection. Spread is both on the surface of the skin and
This is usually contracted from a herpes lesion also by haematogenous dissemination. The lesions are
on the lip of a carer, directly or via the hands, but vesicles or pustules 2–4 mm across, which may spread
occasionally occurs as a result of sexual abuse. with alarming rapidity and have a tendency to coales-
cence to produce geographically shaped erosions with
scalloped edges (Fig. 21.1.12). If there are more than
a very few lesions, the patient should be hospitalized.
Secondary bacterial infection should be treated with
oral antibiotics, and saline or tap-water packs used to
relieve discomfort and dry out the lesions. In severe
cases, systemic aciclovir is indicated.

Indolent ulceration in the immunosuppressed

patient
An unusual presentation of herpes simplex in immu-
nosuppressed patients is as a chronic, slowly growing
ulcer, often with rather overhanging edges. The out-
line is usually irregular, reminiscent of the geographi-
cal shapes produced by coalescing lesions in the more
Fig. 21.1.10 Primary herpes simplex with coalescing, grouped typical forms of herpes simplex. It requires systemic
765
pustules. antiviral therapy.
 21.1 Skin disorders

• Impetigo is often superimposed on other skin

diseases such as insect bites, scabies, pediculosis and
atopic eczema.
• Staphylococcal impetigo does not scar, but deep
streptococcal lesions may do so.
• Post-inflammatory pigmentation can occur,
particularly in dark-skinned patients.

Management
• Saline bathing may be used to dry out the lesions.
• Avoid direct contact of the lesions with the skin of
other children.
Fig. 21.1.12 Disseminated herpes simplex in an atopic child, • A swab for culture and sensitivity testing should
with coalescing lesions. always be taken.
• Topical mupirocin may be successful for localized early
Impetigo disease. In general, oral antibiotics should be used.
• For bullous impetigo, flucloxacillin or cefalexin is
Impetigo is a bacterial infection caused by Staphylococcus the treatment of choice.
aureus, group A streptococcus or a combination of • If the lesions are strongly suggestive of a
these organisms; it occurs in two forms, bullous and streptococcal origin or when a group A
non-bullous (or crusted). streptococcus is isolated, the patient should
be treated with penicillin or a first-generation
cephalosporin and be watched for 8 weeks for signs
Clinical features
of glomerulonephritis.
• Bullous impetigo is always due to staphylococci.
Painless blisters arise on previously normal skin
Staphylococcal scalded skin syndrome
and increase rapidly in size and number, soon
rupturing to produce superficial erosions with a
peripheral brown crust. The erosions continue to Clinical example
expand, sometimes clearing centrally to produce
annular lesions. As they dry they may assume a At the age of 13 months Oscar developed
conjunctivitis. Oral amoxicillin was prescribed by
shiny brown-lacquer-like surface.
his general practitioner. Four days after starting
• Non-bullous impetigo may be due to either this treatment Oscar developed a red, macular
organism or to a combination. The lesions begin rash on his face and in the groin and axillary areas. He was
with a small, transient vesicle on an erythematous febrile and irritable, and screamed when his mother tried
base. The serum exuding from the ruptured vesicle to pick him up. The rash was diagnosed as a drug reaction
produces a thick soft yellow crust, below which and the antibiotic was ceased. The red rash continued to
there is a moist superficial erosion (Fig. 21.1.13). spread and flaccid blisters appeared in the groin, with the
skin lifting off easily. A Gram stain from the blistered groin
The deeper the erosion, the more likely the lesion
skin demonstrated no organisms. By this time the result
is to be of streptococcal origin. from the conjunctival swab had returned, demonstrating
Staphylococcus aureus insensitive to penicillin but sensitive
to flucloxacillin, which was commenced immediately. The
rash worsened over the next 12 hours, with sheeting off
of skin all over the body, most marked around mouth and
in axilla, groin and neck-fold. The child was brought to a
paediatric emergency department, where a diagnosis of
staphylococcal scalded skin syndrome was made and
intravenous flucloxacillin was started. Over the next 4 days
the redness settled, the blisters dried out, and Oscar became
comfortable and cheerful. He was discharged on oral
flucloxacillin for a further 4 days.

Staphylococcal scalded skin syndrome is a widespread

blistering disease caused by the epidermolytic toxin
produced by certain strains of Staphylococcus aureus,
766
Fig. 21.1.13 Crusted lesions of non-bullous impetigo. most often of phage group 2, types 70/71 or 51 but
 Skin disorders 21.1
occasionally of phage group 1. This toxin produces a Boils (furuncles)
superficial splitting of the skin, with the level of split
Boils are cutaneous abscesses, centred on hair follicles,
being high in the epidermis. Clinical disease occurs
caused by certain species of coagulase-positive S. aureus.
when a sufficient toxin load is produced from infection
with these organisms.
Clinical features

Clinical features • Local predisposing factors are cutaneous injury,

friction and sweating.
The commonest sites of infection are the umbilicus • Episodes are often recurrent and many patients with
(in neonates), the nose, nasopharynx or throat, the recurrences are found to carry furuncle-producing
conjunctiva and deep wounds. strains of S. aureus in nostrils, axilla or groin, or to
The condition commences with a macular erythema, have had close contact with someone who does.
initially on the face and in the major flexures, and then
becoming generalized. The skin is exquisitely tender
Management
and the child draws back from contact. After 2 days
flaccid bullae develop and the skin wrinkles and shears • Early lesions should be treated with warm
off. The exfoliation is most marked in the groin, neck- compresses and oral flucloxacillin or cefalexin.
fold (Fig. 21.1.14) and around the mouth, and may • For older lesions that have matured and pointed,
involve the entire body surface, but mucosae remain incision and drainage may occasionally be indicated
uninvolved. in conjunction with the use of antibiotics.
The child is usually febrile but, because of the super- • Chronic and recurrent furunculosis should be
ficial level of the split, fluid loss is rarely significant. treated with a course of antibiotics of several
The erosions crust and dry and heal with desquama- weeks' duration. While the patient is on antibiotics,
tion over the next 4–8 days, leaving no sequelae. all clothing, towels and bed-linen that have
Cultures from skin and blister fluid are usually neg- contacted the affected areas should be washed in
ative. Cultures should be obtained from any area of hot water. Attempts should be made to deal with
obvious infection but, if none is apparent, from the the carrier state in the patient and/or close contacts.
nasopharynx and throat. Washing of the groin, axilla and hands with an
antiseptic soap can help, as can topical nasal
antibiotics such as mupirocin. An oral rifampicin
Management
and fusidic acid combination has also been
• Nurse the child naked on a non-stick material and successful in reducing carriage.
handle as little as possible.
• Avoid topical agents in the early stages. Streptococcal perianal disease
• Flucloxacillin is the treatment of choice and is
usually given intravenously. This is a distinctive perianal eruption due to group A
• Analgesia is often necessary in the early stages. β-haemolytic streptococcus (GABHS):
• Emollients are useful once the skin dries and • Peak incidence is in children aged 3–4 years, but it
desquamation commences. may occur in infants.
• The child complains of pain on defecation and
often refuses to open the bowels.
• Bright blood is frequently seen on the stool. A
bright pink erythema extends from the anal rim,
which is often fissured and macerated, 2–3 cm out
from the anus; the skin is tender but not indurated.
• Lymphangitis and lymphadenopathy are absent.
• There may be an associated GABHS balanitis or
vulvovaginitis.
• Diagnosis is established by culture, on blood agar,
of GABHS from a swab of the perianal skin.
• The treatment of choice is oral penicillin V 50 mg per
kg per day in four divided doses, combined with the
use of topical mupirocin twice daily. Recurrences are
very frequent without this combined therapy, which
Fig. 21.1.14 Staphylococcal scalded skin disease with extensive should be continued for 10 days. Erythromycin is
767
erythema and exfoliation. appropriate in penicillin-allergic patients.
 21.1 Skin disorders

Tinea
This is an infection due to dermatophyte fungi; the
source of the fungus is an animal (e.g. dog, cat, guinea-
pig, cattle), the soil or another human. Tinea occurs
on any part of the skin surface and can involve hair
and nails.

Clinical features and diagnosis

• Classical features of tinea on the general body skin
are itchy, annular or geographical erythematous
lesions studded with papules or pustules, with a
tendency to central clearing and a superficial scale
(Figs 21.1.15 & 21.1.16).
Fig. 21.1.16 Multiple annular lesions of tinea.
• Tinea is often unilateral and always asymmetrical,
whereas eczema and psoriasis, which it may
resemble, are often symmetrical in distribution.
• Between the toes, maceration with a thick white at lengths of up to 2–3 mm, but in an individual
scale is the main finding, and an annular lesion may case all the hairs break at the same length. The
extend on to the dorsum of the foot. inflammation varies from mild erythema and a
• Nail tinea produces a white discoloration and fine, dandruff-like scale to a pustular carbuncle-like
crumbling of the nail plate with an accumulation of lesion (kerion).
subungual debris. • A Wood's light (an ultraviolet lamp) is useful in
• On the soles there are deep-seated blisters or the diagnosis of some varieties of scalp tinea,
pustules that dry to produce brown crusts. with the infected hairs fluorescing bright green.
• On the scalp there is a characteristic combination Other varieties of scalp tinea produce no typical
of alopecia and inflammation with the hair loss fluorescence and the Wood's light has no place in
being due to breaking of the hair shafts. Depending the diagnosis of tinea on the skin surface.
on the pattern of hair invasion by the fungus, the • The diagnosis of tinea is confirmed by
hairs are either broken off flush with the scalp or scraping hairs or scales on to a slide, adding
20% potassium hydroxide and examining the
specimen microscopically. Septate branching
hyphae are seen in skin scales, and spores are
found in hair. The fungus can be cultured on
appropriate media.

Management
• Topical antifungals may be satisfactory for small,
localized patches of tinea on the skin.
• Oral griseofulvin is the treatment of choice for
longstanding or severe cutaneous tinea and hair
tinea. This fat-soluble drug is best taken after
meals, preferably with a glass of milk. For hair
tinea, a 3-month course is optimal but shorter
treatments of 4–8 weeks may be adequate for
cutaneous tinea.
• Nail tinea is not responsive to topical treatment
and is treated with oral terbinafine.

Tinea versicolor
This is an infection with Pityrosporum species, which
are part of the normal skin flora. It occurs mainly
in tropical and temperate zones, and usually affects
768
Fig. 21.1.15 Annular lesion of tinea. ­adolescents and young adults.
 Skin disorders 21.1
Clinical features and diagnosis Scabies
• Presents as well-demarcated, asymptomatic or Scabies is due to Sarcoptes scabei, an eight-legged,
slightly itchy macules with a fine, branny scale oval-shaped mite less than 0.5 mm in length. The dis-
that is often obvious only on light scratching of ease is transmitted by close physical contact, with
the lesions. Primary macules 1–10 mm in diameter transmission by fomites being exceptional. A small
coalesce into larger patches. number of mites burrow into the skin in certain sites,
• Lesions occur in two colours – red–brown, particularly between the fingers, the ulnar border of
especially in the fair-skinned, and hypopigmented the hand, around the wrists and elbows, the anterior
in darker-skinned children (Fig. 21.1.17). axillary fold, nipples and penis and, in infants, the
• The hypopigmented form must be differentiated palms and soles.
from vitiligo, where the depigmentation is total and
scale is absent, and pityriasis alba, where lesions
are less well demarcated and some erythema may Clinical features and diagnosis
be seen.
The pathognomonic primary lesion, a typical burrow,
• In young children it often presents with only facial
may not be seen with the naked eye, but is more easily
lesions, and almost invariably a parent or older
identified with a dermatoscope. It is a 2–3-mm long,
relative will have tinea versicolor in the typical
curved grey line with a vesicle at the deeper end.
distribution.
Other lesions that mark the sites of burrows are
• Diagnosis is confirmed by microscopic
small blisters or papules, larger blisters on the palms
examination of skin scrapings to which 20%
and soles of infants (Fig. 21.1.18), scratch marks, sec-
potassium hydroxide has been added. Grape-like
ondary eczema and secondary bacterial infection.
clusters of spores and short fragments of thick
Eczema or impetigo in the target areas for scabies
mycelia are seen.
should always raise suspicion of this disease, as should
blisters on the palms and soles of infants.
Often more prominent than the evidence of burrows
Management
is the so-called secondary eruption of scabies. This
• Untreated, the condition is persistent, although presents as multiple, very pruritic, urticarial papules,
some improvement may occur in winter. which are soon excoriated. They occur particularly on
• The treatment of choice is with topical imidazole the abdomen, thighs and buttocks.
creams.
• With the depigmented form, therapy deals with
the scale but sun exposure is required for full
repigmentation.
• In widespread disease in adolescents, oral
ketoconazole once weekly for 6 weeks is effective.

Fig. 21.1.17 Pale lesions of tinea versicolor in a dark-skinned Fig. 21.1.18 Scabies in an infant with pustules on the sole of 769
child. the foot.
 21.1 Skin disorders

Large inflammatory nodules may form part of the with ­ excoriations and also eczematization and
secondary eruption, occurring particularly on covered ­secondary infection, which may mask the underlying
areas, especially on axillae, scrotum, penis and but- infestation. Permethrin shampoos are effective pedicu-
tocks. They may, however, be very widespread, pro- licides but may not destroy ova, and a repeat applica-
ducing diagnostic difficulties. They may persist for tion after a few days is recommended to kill further
months after effective scabies treatment. hatched lice. Removal of nit cases with a fine comb is
The diagnosis of scabies is usually a clinical one easier if the chitin is softened by a prior application
but can be confirmed by demonstration of the mite. of vinegar.
A burrow, which may be softened by the application
of 20% potassium hydroxide, is scraped and the mate-
Pediculosis corporis (body lice)
rial is smeared on a slide for microscopic examination.
Burrows may be more easily identified by rubbing a This is rare in children except in severely overcrowded
thick, black marking pen over suspicious areas and conditions with poor hygiene. The organism infests
wiping with an alcohol swab, leaving a burrow out- bedding and clothing, and the nits are not found on
lined with ink. the human host. The lice hatch with body warmth
and puncture the skin, producing very itchy, small,
red papules with haemorrhagic puncta. Spots of
Management
dried blood may be found on the clothing and bed-
• All close contacts should be treated simultaneously linen. Treatment is directed towards removal of the
with the patient, whether or not they have organisms from materials with hot water laundering
symptoms. and hot ironing or the use of a hot electric dryer.
• 5% permethrin cream is the treatment of choice
and should be applied to all body surfaces from
Pediculosis pubis (pubic lice, crab lice)
the neck down, and left on overnight on two
consecutive nights. This treatment should be This is mainly an adult disease. The pubic louse has as
repeated a week later. The application duration its normal habitat the anogenital area, but in children
should be reduced to 6 hours in extremely young it is particularly seen on the eyelashes. Eyelash infesta-
infants. tion in children may occur from innocent close contact
• Bedclothes and clothing should be washed in the with an affected adult. Pediculosis of the eyelashes is
normal way with no disinfection required. best treated with petroleum jelly applied thickly twice
• An irritant dermatitis may follow scabies treatment, a day for a week.
particularly in atopic children, and may require
emollients and topical steroids once the miticide
Arthropod bites
therapy is fully completed.
• Persistent nodules may respond to topical Patients with arthropod bites present to a dermatologist
corticosteroids but painting with a coal tar solution in two situations: the severe local allergic reaction and
is preferable for the very resistant ones. the more chronic hypersensitivity condition called ‘pap-
ular urticaria’. The arthropods most encountered are
mosquitoes, sandflies, fleas and grass mites. The distri-
Pediculosis
bution of the bites helps to suggest the causative agent.
Human lice are six-legged arthropods without wings,
grey in colour or brown–red when engorged with
Severe local reactions
blood. The body louse and the head louse have a thin
body, 2–4 mm long and three similar pairs of legs; the • Include blisters, purpura, and cellulitis and
pubic louse is wider and shorter, and the second and lymphangitis even in the absence of secondary
third pair of legs are larger than the first, producing infection.
a crab-like appearance. The ova (nits) appear as oval, • As the lesions are extremely itchy, scratching occurs,
grey–white, 0.5-mm specks, attached by a firm chitin leading to secondary eczematization and secondary
ring to hairs or clothes. infection.

Pediculosis capitis (head lice) Papular urticaria

This is a common infestation, often occurring in epi- • A very common condition in children, particularly
demics in schools. The occipital area of the scalp between 10 months and 4 years.
770
is involved preferentially and may be the only site • In a child who has been sensitized by previous
affected. The condition is itchy, leading to ­scratching exposure, the bite produces an itchy urticarial (hive-like)
 Skin disorders 21.1
weal, which is succeeded by a firm itchy papule that
lasts for many days.
• The weal and papule usually show a central
punctum and the papule may be surmounted by a
tiny blister.
• The persistence and severity of the condition are
explained by the fact that new bites by the same
species will often cause a recrudescence of activity
in resolving lesions.
• Secondary infection and eczematization from
scratching also contribute to the chronicity of the
condition, which may plague the child through an
entire summer.
Management involves avoidance of insect attack, Fig. 21.1.19 Flexural lesions of atopic dermatitis.
with the use of insect repellents, insecticides, protec-
tive clothing and changes in activities, which clearly
Complications
are difficult in an active child. Wrapping the affected
areas in wet dressings overnight as soon as new bites Patients with atopic eczema may develop secondary
occur is helpful in reducing the itch and preventing bacterial infection that presents either as yellow crust-
scratching, which leads to the secondary eczema and ing impetigo or folliculitis, or simply as worsening
infection. Topical corticosteroids will improve the eczema. Mollusca are common and atopic patients are
secondary eczema and have some effect in damp- at risk of developing severe widespread herpes simplex
ening the severity of the actual bite reaction, but infections. The usual childhood immunizations are
must not be used for prolonged periods. Oral anti- quite safe. Severe eczema can lead to failure to thrive.
biotics are required if there is significant secondary Psychosocial and behavioural problems may occur in
infection. severe cases as a result of the continual discomfort,
onerous treatment and restrictions on the child's life.
The whole family suffers as a result.

Dermatitis Differential diagnosis

Atopic dermatitis (atopic eczema)
• Genetic ichthyoses of various types can lead to a
Note: the terms dermatitis and eczema are often used very dry, scaly, and sometimes red skin. In many
synonymously. of these patients only the skin is abnormal but
Atopy is a genetically determined disorder with an associated abnormalities in some types include
increased tendency to form immunoglobulin (Ig) E cryptorchidism, neurological abnormalities,
antibody to inhalants and foods, and increased suscep- developmental delay, deafness and cataracts.
tibility to asthma, allergic rhinitis and atopic eczema. • Immunodeficiency syndromes of various types can
This eczema may begin at any age, but 75% of patients be associated with dermatitis, and may resemble
show the first signs by 6 months. atopic dermatitis. The condition is usually refractory
to treatment and there may be other features such as
recalcitrant infections, diarrhoea or haematological
Clinical features
abnormalities to suggest an alternative diagnosis.
The characteristic clinical features are a general- • Phenylketonuria may present with an eczematous rash.
ized dryness and a tendency to lichenification or • Boys with hypohidrotic ectodermal dysplasia, an
thickening of the skin, pruritus, and excoriations X-linked disorder, may be more prone to dry skin
and patches of acute, subacute or chronic eczema. and eczema; associated abnormalities include
Involvement of the whole cutaneous surface may deficient hair growth, dentition and sweating, and a
occur but the predominant areas are the face in tendency to develop respiratory tract infections.
infants, extensor aspects of the limbs as the child
begins to crawl, and the limb flexures in older chil-
Management
dren (Fig. 21.1.19). In severe cases the whole skin
may be erythematous, and in these patients white Explanation and education
dermographism is often a prominent feature; this The most important aspect of the management of
indicates that the condition is likely to be unstable atopic eczema is explanation of the condition to the
771
and difficult. patient or parents. The family should understand that
 21.1 Skin disorders

the child has been born with an inherently dry, irri- bandaged on with a crepe bandage, and a net material
table skin and that this will be a lifelong tendency. is used to hold the dressings in place. The procedure
Although the skin does become more stable with time, is repeated three times a day. These dressings cool the
it will always require extra care. It is essential to talk in skin down, reduce itching, physically prevent scratch-
terms of control rather than cure, otherwise the family ing, increase the hydration of the skin and enhance
search for an endpoint after which care will no longer the penetration of topical steroids. This treatment is
be required and this is an unrealistic expectation. The usually effective in clearing the eczema in 3–4 days. If
condition should be explained as a multifactorial dis- dressings are required for longer periods, the cortico-
order as it must be appreciated that, just as there is no steroid should be used only once a day. Particular care
‘cure’, there is no single ‘cause’. should be taken with infants.

Avoidance of irritants Systemic therapy

Factors that will often irritate the atopic skin should If significant bacterial infection occurs, a swab should
be discussed. Woollen material in direct contact with be taken and oral antibiotics used. Nocturnal sedation
the skin is a major irritant; apart from the child's is often valuable during severe episodes but daytime
own clothing it is important to remember the par- sedation should be avoided; antihistamines are the
ent's clothing, carpets, blankets, stroller and car seat preferred sedatives. Although they may be essential for
covers, furniture and toys. Shiny nylon materials and associated diseases, oral corticosteroids should never
some acrylics irritate but cotton–polyester mixtures be instituted for the eczema itself; a severe rebound can
are usually well tolerated. Sand contact is often trou- occur on their withdrawal and after several courses the
blesome, especially with prolonged close contact as in eczema can become very unstable. Eczema that contin-
playing in a sandpit. Chlorinated water may aggravate ues to be widespread and difficult to manage despite
but this is variable. Soap in excess and bubble baths all these measures may require oral immunosuppres-
over-dry the skin, and many perfumed and ‘medi- sion with azathioprine or ciclosporin, or narrow-band
cated’ products, disinfectants and strong cleansers ultraviolet B therapy.
cause irritation.
Dietary manipulation
Dealing with dryness No alteration should be made to the patient's diet
Bath oils and oatmeal-containing products are use- unless the atopic eczema has failed to respond to con-
ful and prevent the defatting of the skin that bathing ventional therapy properly carried out. There is only a
can induce. It is essential to find a suitable moisturizer small group of patients with unstable eczema with an
that can be applied all over twice a day, whether or associated urticarial element in whom dietary factors
not there is active eczema. Glycerine 10% in Sorbolene are of major significance; skin-prick tests are useful
cream is useful in many cases, but more or less greasy in this group to give a guide for dietary manipula-
preparations are available to suit individual patients tion, which should be instituted only by those with a
and climatic conditions. Urea-containing products full understanding of the nutritional requirements of
sting broken skin and are unsuitable. young children.

Topical corticosteroids Dust mite allergy

These are an essential part of treatment. In general, This is important in a selected group of patients.
ointment bases are preferred because they are more In these children the eczema is usually particularly
emollient than cream bases. Nothing stronger than troublesome on the face and neck. The family should
1% hydrocortisone should be used on the face or in be given details of dust mite reduction strategies,
the axillae or groin. Medium-strength fluorinated which may be of limited value.
corticosteroids are usually adequate for lesions on
the trunk and limbs; the stronger preparations are
Discoid eczema
rarely required. These preparations are best used
three times a day and ceased as soon as the eczema • In children this is often a manifestation of a
is clear. combined atopic and psoriatic diathesis.
• Well-defined patches of acute eczema occur in a
Wet dressings strikingly symmetrical distribution. In infants the
These are useful in severe widespread eczema. A water- commonest sites are the upper back and the tops
based emollient is applied all over; a corticosteroid of the shoulders; in older patients the extensor
cream (rather than ointment in this case, because cream aspects of the limbs are particularly involved. The
is more water-miscible) is applied to the areas of active lesions may be very thick and exudative and they
772
eczema; sheeting soaked in tap water is applied and are very itchy.
 Skin disorders 21.1
• Discoid eczema should be distinguished from tinea • Initially there may be much oedema, especially
and impetigo, which are less symmetrical, and on the face (Fig. 21.1.20), and cellulitis is often
classical psoriasis, which is rarely moist. suspected; however, the child is afebrile and the
• Management involves emollients and topical area is itchy rather than painful.
steroids as for atopic dermatitis, with the continued • The condition may be spread beyond areas of
use of emollient helping to prevent recurrences. initial contact as a result of retention of allergen on
clothing and under the nails.
• A strong topical steroid may be adequate for
Pityriasis alba localized areas but a short course of oral steroids is
This condition probably represents a very mild eczema, usually indicated.
which, however, produces a striking post-inflamma-
tory depigmentation. The condition is more common
in atopics, and occasionally some areas will show ery- Clinical example
thema and more definite eczematous changes. It is
rarely troublesome unless the child has darker skin, Harry, aged 4 years, presented with a
making the patches more visible. swelling and redness around one eye. It was
diagnosed by the ophthalmology registrar
• Appears as poorly defined, slightly scaly,
as preseptal orbital cellulitis, the child was
hypopigmented patches occurring particularly on admitted to hospital and intravenous antibiotics were
the face and the upper arms. started. It was remarked that a lack of fever and pain was
• The mild irritation and signs of mild eczema unusual in a child with cellulitis. The next day the area was
respond to emollients and weak topical more swollen and some blistering had occurred. Harry was
corticosteroids, but the hypopigmentation may be noted also to have multiple linear blistered red lesions on
very persistent and require sun exposure over a his arm. Harry's mother told the registrar that Harry's best
friend from the preschool had similar lesions on the arms
prolonged period before repigmentation is complete.
and face, which had been diagnosed by a dermatologist
• The condition should be differentiated from vitiligo, as a plant contact dermatitis. The history obtained was that
where there is total depigmentation and no scale, the preschool garden had been landscaped by parents over
and from tinea versicolor, which is rare on the face, the previous weekend and the two children carried Robyn
has very well demarcated lesions and has a very fine Gordon grevilleas in the car for planting. Harry's antibiotics
branny scale. were ceased and he was discharged from hospital on
a 5-day course of oral steroids. The swelling resolved in
2 days, and in 6 days all the rash had disappeared. The
Allergic contact dermatitis following weekend the Robyn Gordon grevilleas were
removed from the preschool.
• The commonest causative agents in Australia are
Rhus and a variety of grevilleas, including Robyn
Gordon, Ned Kelly and Hookerana. Other occasional causes of allergic contact der-
• The dermatitis is usually severe and blistering often matitis in children include iodine (e.g. wound care,
occurs. ­antisepsis for operative field) (Fig. 21.1.21) , nickel
• It often occurs in a streaky pattern where the plant (e.g. press-studs on clothing, belt buckles), and topical
has brushed against the skin.

Fig. 21.1.20 Allergic contact dermatitis due to contact with Fig. 21.1.21 Allergic contact dermatitis from iodine used for 773
grevillea. preoperative skin preparation.
 21.1 Skin disorders

­ edications (e.g. antihistamine cream), and lime juice

m • Ulcerated nodules – occur most often in the vulval
(where sun exposure is also required; see photosensi- area in a situation of a constant urinary leak in the
tivity, below). presence of major congenital anomalies.
• ‘Frog plaster’ napkin rash – due to the accumulation
of faeces and, to a lesser extent, of urine under the
Napkin rashes
plaster used in cases of developmental dysplasia of
These various causes often occur in combination, and the hip; usually of a mixed erosive and ulcerated
the management of most napkin rashes involves a nodule type.
weak topical steroid, an anti-monilial agent and fre-
quent napkin changes.
Other causes

Common causes • Psoriasis – produces a bright red, glazed, clearly

marginated, napkin rash (Fig. 21.1.23). This may
• Seborrhoeic dermatitis – presents as a dull red develop into the condition called ‘napkin psoriasis’.
rash covering most of the napkin area, sometimes A few small scaly spots occur on the trunk above
with a greasy yellow scale, although this is the psoriatic napkin rash, followed by a sudden
characteristically absent in this moist area. explosion of typical psoriatic lesions on scalp, face
• Monilia – manifested as a thick, white material deep and all over the trunk. The infant is well and the
in the folds and as small annular lesions with an condition is usually asymptomatic. The eruption is
overhanging white macerated scale at their margin. self-limiting in a few weeks.
• Irritant dermatitis from urine and faeces – irritant • Impetigo – presents as small, pus-filled blisters that
dermatitis due to urine affects mainly the convex quickly rupture and expand into large superficial
surfaces, with relative sparing of the flexures; erosions, usually asymptomatic.
irritation due to faeces particularly affects the natal • Herpes simplex – punched-out 3–8-mm individual
cleft. Napkin dermatitis is rarely caused by irritant erosions that coalesce to form geographical-shaped
or allergic reactions to laundering products. lesions; considerable swelling is usually seen and
• Miliaria – sweat duct occlusion may occur alone or there is associated lymphadenopathy and fever.
in combination with other elements. This presents • Staphylococcal scalded skin syndrome – may present
as small red papules, which are very transient, so in the napkin area with a very painful bright red
the pattern varies considerably from hour to hour. rash with superficial blistering.
• Congenital syphilis – perianal erosions and moist
warty lesions may be seen in early infancy, with
Variants of common types
erythema on the palms and soles, fever, failure to
• Gluteal granulomas – occur on top of a pre-existing thrive and hepatosplenomegaly.
napkin rash as purplish nodules that tend to be oval • Kawasaki disease – often presents in the napkin
in shape, following the lines of the skin folds. area with a tender red scaly rash in a febrile,
• Erosive napkin rash – occurs in the perianal and natal irritable child.
cleft area, and usually follows a period of diarrhoea. • Langerhans cell histiocytosis – produces a severe
It is seen in infants with lactose intolerance or other napkin rash with a brownish scale, erosions and
causes of malabsorption (Fig. 21.1.22). purpuric spots, unresponsive to standard napkin

774
Fig. 21.1.22 Erosive napkin dermatitis. Fig. 21.1.23 Psoriasis in the napkin area with glazed erythema.
 Skin disorders 21.1
rash treatment. A scaly, papular eruption on the • Pustular psoriasis and psoriatic arthropathy are
scalp or trunk may also appear. Fever, diarrhoea, extremely rare in children.
polyuria and hepatosplenomegaly may be present. • There is a particular type of well-marginated,
• Zinc deficiency – produces a well-marginated bright red napkin rash, described above, that is a
shiny rash rather similar to psoriasis, but with a marker for psoriasis.
characteristic dark peripheral scale. Similar lesions are • Many therapies used in adults are inappropriate
present around the mouth and nose. These patients in children. In general, psoriasis in children
are usually irritable and alopecia may be present. is better treated with tars than topical
• Biotin and essential fatty acid deficiencies – can corticosteroids. No treatment can alter the course
cause a rash similar to that of zinc deficiency. of the condition.
• HIV infection – can present as severe, erosive
napkin dermatitis, which may be secondarily
Photosensitivity in children
infected.
Photosensitivity may be manifested by exaggerated
sunburn, sometimes with blistering, or another rash
Psoriasis
appearing in a light-exposed area. There are many
Psoriasis is an hereditary disease; it is probably an causes and some are briefly reviewed here.
autosomal dominant condition with variable pen- • Phytophotodermatitis – contact with a phototoxic
etrance. It commences during childhood in 30% of agent (e.g. lime juice, perfumes) followed by sun
patients. It may present in the typical adult form of exposure causes an exaggerated sunburn reaction.
large erythematous plaques, with a thick, silvery- • Drug reactions – rare in children.
white scale, predominantly on the knees, elbows, but- • Polymorphous light reaction – may produce
tocks and scalp, but certain differences are seen in recurring erythematous, itchy vesicles and papules
childhood disease: mainly located on the cheeks, ears, upper anterior
• Plaques are usually smaller and with a finer scale chest and exposed limbs. The onset of the eruption
(Fig. 21.1.24). may be delayed for 1–2 days after sun exposure,
• A particularly common presentation is acute but the distribution of the lesions and history of
guttate psoriasis with the eruption of tiny papules exacerbation in the summer are typical.
in a widespread distribution. The eruption is often • Solar urticaria – a transient urticarial rash
preceded by an intercurrent illness, particularly a appearing immediately after sun exposure on
streptococcal throat infection. exposed areas.
• The face and intertriginous sites are commonly • Connective tissue diseases
affected in children. • Lupus erythematosus – the skin lesions of
• Children presenting with vulvitis, balanitis and systemic lupus erythematosus (SLE) include a
perianal itching may be found to have psoriasis. characteristic butterfly distribution over both
In these areas the typical scale is absent and the cheeks and the base of the nose. Patchy lesions
condition presents as a glazed erythema, often with may also present over the light-exposed areas of
fissuring. ears, neck and limbs. In acute SLE, erythematous
• Nail involvement is usually absent or minimal with macules are also seen about the nail-beds, on the
minor pitting. tips of the fingers, the toes, and on the palms of
the hands and soles of the feet.
• Dermatomyositis – an erythematous rash that
is distributed over the extensor surfaces of the
joints, particularly over the knuckles, elbows and
knees, is characteristic of dermatomyositis. In
addition, most children with this disorder show
a violaceous facial rash and periorbital oedema.
Worsening of the condition after sun exposure
is typical and some patients show a more
widespread scaly red rash in light-exposed areas.
• Genetic photosensitive disorders – most very rare,
but commoner ones include:
• Erythropoietic protoporphyria – pain in feet
sometimes without much to see, sometimes
associated with swelling, redness and blistering; 775
Fig. 21.1.24 Psoriatic plaques with fine scale. later scarring. May lead to hepatic damage.
 21.1 Skin disorders

• Albinism – dilution or absence of pigmentation;

poor vision, photophobia and nystagmus. Blistering disorders
The differential diagnosis of blistering in children
includes the following (most of these have been
described elsewhere in this chapter). Other causes are
Purpura covered in the neonatal section.
The differential diagnosis of purpura in children • Infections
includes the following: • HSV
• Trauma – accidental or as part of child abuse; in the • Varicella and other viral exanthems
latter, bruises of different ages and at unusual sites • Bullous impetigo
may be seen. • Staphylococcal scalded skin syndrome
• Thrombocytopenia – purpura in association • Trauma – for example, burn; chemical or thermal
with a low platelet count is often associated (accidental or abusive)
with bruising and signs of bleeding elsewhere. • Contact dermatitis – for example, plants, iodine
Idiopathic thrombocytopenic purpura is the most • Blistering with photosensitivity
common cause (see Chapter 16.2). Children need • Phytophotodermatitis
to be examined and investigated for leukaemia, • SLE, dermatomyositis
pancytopenia, splenomegaly, and drug- • Porphyrias
induced thrombocytopenia or aplastic anaemia • The erythema multiforme (EM), Stevens–Johnson
(chloramphenicol, anti-thyroid medications). syndrome (SJS), toxic epidermal necrolysis (TEN)
• Coagulation disorders – such as haemophilia; spectrum – hypersensitivity reactions
there may be a history of joint pain or swelling, or • EM – target lesions, with peripheral erythema
bleeding from other sites. and central blistering and necrosis; occasional
• Infections – cause vascular damage moderate mucosal involvement. Main cause is a
• Purpuric viral exanthems especially due to recent herpes simplex infection.
enteroviruses (see above) • SJS – severe mucosal blistering and erosions.
• Bacterial infections: an unwell febrile child with Usually minor skin involvement. Main cause is a
purpura should be treated for meningococcal Mycoplasma infection.
septicaemia without waiting for the results of • TEN – severe widespread sheeting off of skin,
investigations. Septicaemia from Haemophilus severe mucosal involvement. Main cause is drugs.
influenzae, streptococci, staphylococci and • Chronic bullous disease of childhood – an
some Gram-negative organisms may also cause immunological bullous disease with widespread
purpura. Less extensive, but diagnostically blisters occurring in rosette patterns.
useful, are the purpuric lesions of subacute
bacterial endocarditis, typhus and typhoid Erythema nodosum
fever.
• Rickettsial infections such as typhus and, in Erythema nodosum can occur at any age and pres-
Australia, Ross River virus. ents initially as subcutaneous erythematous lesions,
• Vasculitis – in children mainly Henoch–Schönlein mainly on the anterior lower legs, that may progress to
purpura (see Chapters 16.2, 18.2). This is quite extensive bruise-like lesions. Erythema nodosum may
common in childhood. Purpuric lesions on the legs be idiopathic or associated with chronic streptococ-
and buttocks may be the only finding in Henoch– cal disease, pulmonary or other tuberculosis, Crohn's
Schönlein purpura, or there may be associated disease, chronic gastrointestinal infections, sarcoidosis
abdominal pain, arthritis or renal involvement. and Mycoplasma infection. It may also be secondary
These patients must be followed for months for the to a number of drugs.
development of nephritis.
• Langerhans cell histiocytosis – the various rashes
that occur in this condition characteristically have a
purpuric element.
Hair loss in children
• Glucocorticoid excess – causes skin fragility, which There are two major types of hair loss (alopecia):
leads to easy bruising and bleeding. diffuse and patchy. The commonest cause of diffuse
• Scurvy – irritability, bone pain, gum sponginess alopecia is telogen effluvium, and the main causes
and bleeding may also be present. Wrist X-rays are of patchy alopecia are tinea, alopecia areata and
diagnostic. trichotillomania.
776
 Skin disorders 21.1
Diffuse alopecia Hirsutism
• Telogen effluvium – high fever causes a large number Increased pubic or axillary hair in young children
of hairs to enter the resting or telogen stage of the hair may be due to adrenal, gonadal or central nervous
cycle prematurely; 2–3 months later these are inevitably system disease, and requires investigation. Hirsutism
shed. The hairs have a club-shaped end, visible as in adolescent females may be an isolated finding or
a white dot with the naked eye. New hairs appear may be seen with obesity and amenorrhoea in poly-
immediately in the empty follicles. The condition may cystic ovary syndrome. Cushing syndrome, mild con-
continue for several months but is fully reversible. genital adrenal hyperplasia, virilizing adrenal and
• Some other causes: ovarian tumours, and thyroid dysfunction may cause
• drugs hirsutism.
• malnutrition
• iron deficiency
• various aminoacidurias Acne and acneiform rashes
• hereditary hair shaft abnormality syndromes
• congenital atrichia Some degree of acne is common on the face and upper
• alopecia as a part of other genetic syndromes. trunk during puberty and may be the first sign of
puberty. Acne, particularly if severe, can lead to sig-
Patchy alopecia nificant depression in adolescents and is a risk factor
for suicide. Both the depression and the acne need to
• Tinea – combination of inflammation of varying be recognized and treated.
degree and broken hairs.
• Alopecia areata – autoimmune disease with areas of
total hair loss and no obvious inflammation; there Clinical features
may be some short, so-called ‘exclamation mark’, Acne affects mainly the forehead and face, but can
hairs at the edges. involve neck, shoulders and upper trunk. Early lesions
• Trichotillomania – hair twisting or plucking; include blackheads, whiteheads and papules. In more
hairs broken at different lengths, usually no severe cases there may be pustules or inflammatory
inflammation. cysts that can lead to permanent scarring.
• Some other causes:
• hair cutting as a form of artefactual skin disease
• traction from tight hair styles Management
• infections – boils, erysipelas, herpes simplex, If acne begins before puberty, look for androgen
herpes zoster, tick bites excess, glucocorticoid excess or precocious puberty.
• localized scleroderma (morphoea). If the morphology or distribution is atypical, consider
drug-induced acne or tuberous sclerosus (in which
facial angiofibromas may mimic acne).
Excessive hair in children Acne is treatable. No person with acne should just
be told it is an inevitable part of adolescence. Effective
Hypertrichosis is increased hair that is not in an andro-
acne therapies are now available and should be used to
gen-dependent distribution. Hirsutism is excessive hair
control the disease.
as a result of hyperandrogenism and occurs in a male-
For mild disease, the treatment is topical benzoyl
pattern distribution.
peroxide 2.5–5%, a topical keratolytic such as ada-
palene, and topical antibiotics, either erythromycin or
Hypertrichosis
clindamycin. These can be used singly or in combination.
Generalized hypertrichosis (increased hair in all areas) Improvement occurs over 1–2 months, not within days.
may be an isolated finding or may be related to: Treatment of moderate acne often involves the addi-
• inherited syndromes, including Hurler and De tion of oral antibiotic therapy (e.g. doxycycline) for
Lange syndromes 3–6 months. Oral hormone therapy can help female
• medications, especially minoxidil, phenytoin and patients.
ciclosporin If antibiotics and topical treatment have not
• gastrointestinal disease, including coeliac disease resulted in satisfactory clearing within 3–6 months,
• hypothyroidism oral isotretinoin is indicated. Provided pregnancy is
• anorexia nervosa avoided, this is safe and highly effective. Isotretinoin
• porphyria; look for photosensitivity and blisters. is also indicated if there is scarring or cyst formation.
777
 21.1 Skin disorders

Recurrent mouth ulcers Practical points

These are generally due to aphthous stomatitis. Such
ulcers are usually small and resolve in a few days. • Purpuric rashes require immediate assessment to exclude
Recurrent mouth ulcers can also be seen in: life-threatening conditions such as meningococcal
disease.
• Iron, folate or vitamin B12 deficiency. Apparent cellulitis that is itchy, occurs in a well, afebrile
•
• Gastrointestinal disorders – coeliac disease, Crohn's child and begins to blister on the second day suggests
disease and ulcerative colitis are all associated allergic contact dermatitis to a plant.
with mouth ulceration. Recurrent abdominal pain, • A bright red, well marginated napkin rash suggests
intermittent diarrhoea and failure to thrive may be psoriasis.
present. • Widespread chronic eczema is usually associated with
• Connective tissue disorders – patients with Behçet's systemic complications including psychosocial and growth
problems.
disease usually present in late childhood with ulcers
• Painful defaecation, bright blood on the stool and a
at one site (mouth or genitals) and it may be many bright red rash in the immediate perianal area point to
years before a second site is involved. SLE and streptococcal perianal infection.
juvenile rheumatoid arthritis may cause recurrent • Herpes simplex lesions are grouped and coalesce forming
mouth ulcers. geographical-shaped erosions with a scalloped edge.
• Immunodeficiency states, human immunodeficiency
virus (HIV) infection.
• Malignancy – lymphoma and histiocytosis can
present with non-healing mouth ulcers.

778
 22
PART

ENT, EYE AND

DENTAL DISORDERS

779
 22.1 Ear, nose and throat
disorders
Elizabeth Rose

Paediatric otolaryngologists see children with mucosal and so difficult to see, and it becomes v­ ertical with
diseases of the upper aerodigestive tract (ears, nose, growth. At birth there is only one ­mastoid air cell (the
oral cavity, pharynx and larynx), airway obstruction, antrum), but there is rapid pneumatization after this.
and pathologies of communication. The paediatric larynx is higher in young children
The common problems include: than in adults, and the epiglottis may be seen on
• foreign bodies, in any of these areas tongue protrusion. The larynx is cone-shaped, so the
• otitis media, both acute and chronic subglottis is the narrowest part and therefore prone
• hearing loss, both conductive and sensorineural, to damage and stenosis in prolonged intubation. The
and congenital and acquired laryngeal cartilages are soft and tend to collapse in.
• rhinosinusitis and its complications The larynx grows rapidly until the age of 3 years,
• tonsillitis and suppuration in the neck and then slows before another rapid growth at puberty;
• obstructive sleep apnoea the vocal cords lengthen and the angle of the cartilages
• noisy and obstructed breathing, especially in infants. change, and this accounts for the voice changes that occur.

Growth and development Trauma and foreign bodies

Young children can place, inhale or ingest a variety
In infants the face is relatively small compared with the
of foreign bodies into each orifice. Small batteries
cranium, and elongation occurs with mandibular and
become moist and erode mucosa and cartilage, so need
maxillary growth as the permanent teeth erupt, from
to be removed urgently.
about 6 years of age. This coincides with development
of the eustachian tube, as it becomes more v­ ertical
and functions more efficiently. During this time there The ear
is also growth and maturation of the immune system,
A foreign body may be wedged in the canal; if this is
with enlargement of the tonsils and adenoids; these
vegetable matter, it can expand and cause pain. If not
increase in size until the age of about 7 years, and then
removed easily with a head-light and wax curette, it is
start to involute (Fig. 22.1.1).
best to remove under anaesthesia or sedation to avoid
Infants are obligate nose-breathers until approxi-
further trauma, especially to the TM.
mately 5 months, when they are able to mouth-breathe.
Trauma from a long or sharp foreign body can
The nose is small with considerable airway resistance
­perforate a TM, and perforation may also result from
and this explains why infants have difficulty breathing
a direct hit on the ear. If kept dry, these usually heal
and feeding with a cold.
spontaneously.
If there is obstruction at the back of the nose with
Bleeding from the ear occurs with skull-base
choanal atresia, intervention is needed in the newborn
­fractures, and may contain cerebrospinal fluid (CSF).
period, especially if the obstruction is bilateral.
These should be allowed to heal with minimal inter-
The paranasal sinuses also develop with facial
vention, to avoid contaminating the CSF. The child
growth. The ethmoid and maxillary sinuses are p ­ resent
should be examined for nystagmus, hearing loss and
at birth; the sphenoid sinus is aerated at 5 years and
facial nerve injury.
the frontal sinus at 10 years of age. This has impor-
An audiogram is performed to identify o ­ ssicular
tant implications for the complications of acute
and inner ear damage in all cases of trauma and
sinusitis: ethmoid sinusitis can develop intraorbital
perforation.
­complications from infancy, but intracranial extension
from frontal and sphenoid sinusitis is rare under the
The nose
age of 10 years.
The temporal bone contains the outer, middle and A foreign body in the nose may present as unilateral
inner ears. The inner ear is adult size at birth. In the new- rhinorrhoea with an offensive odour; this resolves once
780
born the tympanic membrane (TM) is more h ­ orizontal the foreign body is removed. This may be accomplished
 Ear, nose and throat disorders 22.1
cough and persistent or recurrent pneumonia. A chest
X-ray may show ipsilateral hyperinflation from entrap-
ment of air behind the foreign body, but there is a low
threshold for performing bronchoscopy if there is a his-
tory of choking and no radiological signs. The bron-
Size

choscopy is performed under general anaesthesia using

a rigid, ventilating bronchoscope and telescopic forceps.

The ear
Congenital abnormalities
0 3 6 9 12
Age (years) Differences in the shape and size of the pinna are com-
mon. Corrective surgery is performed after the age of
Fig. 22.1.1 Adenoidal size in relation to age. Redrawn with
5 years, when the pinna is near adult size.
permission from Dhillon RS, East CA, 2006 Ear, Nose and Throat
and Head and Neck Surgery: An Illustrated Colour Text, 3e. With
There is an association of pinna deformity and mid-
permission from Elsevier. dle ear abnormalities; the hearing is tested and appro-
priate intervention with hearing aids may be needed.
Often the loss is conductive and the child can be fitted
with the child sitting upright and supported against a with a bone-conduction hearing aid.
parent's chest. The nose is sprayed with anaesthetic/ Major deformities of microtia (small ear) and anotia
decongestant and the foreign body is removed by (absent ear) are managed in interdisciplinary clinics
­placing a wax curette behind it and ­pulling it forwards. with plastic surgeons to determine timing for surgery,
Trauma to the nose is common from falling on to a both to correct deformities and to improve hearing, by
table or step, or sports injury. There is often swelling either a tympanoplasty or bone-anchored hearing aid.
and bruising initially, and an assessment for deformity
may be needed after this has settled. An assessment
of the airway and possible septal haematoma should Otitis media
be performed immediately, as it quickly becomes an
Otitis media is inflammation or infection of the muco-
abscess and pressure on the cartilage causes necrosis
periosteal lining of the middle ear, and includes the
and saddle-nose deformity.
mastoid ear cells and the eustachian tube (ET). There
is a spectrum of disease from mild and reversible to
Pharynx and oesophagus chronic and destructive.
A child with a pharyngeal foreign body such as a fish • A child with acute otitis media (AOM) usually
bone may present with drooling and can point to the presents following a cold with severe pain and
site; a bone is often lodged in the tonsil and can be fever, and may have otorrhoea. Infants and young
readily seen and removed. children may not localize well and present with
If a foreign body is further down or in the oesopha- fever, irritability and sometimes vomiting.
gus the child will have dysphagia and regurgitation of • Otitis media is common in the first year of life, and
saliva, and will need general anaesthesia for removal. 75% of children have had at least one episode by the
Trauma from running with a stick, pencil or other toy age of 3 years. Recurrent otitis media is defined as at
in the mouth is common. If it involves the soft p ­ alate, least three episodes in 6 months or four in 12 months.
flexible nasopharyngeal examination is ­performed to It is most common in autumn and winter as viral
ensure there is no injury in the retropharynx, as there infections cause obstruction of the nose and ET.
is the possibility of air and infection tracking down to • The three common causative organisms are
the mediastinum. Small punctures of the soft palate Streptococcus pneumoniae, Haemophilus influenzae
will heal well, but if there is a large flap, or the injury (non-typeable) and Moraxella catarrhalis.
is on the free edge of the soft palate, it is sutured under • The complications of AOM include TM perforation,
general anaesthesia. facial paralysis, mastoiditis, intracranial spread
including meningitis and abscess formation, and
sigmoid sinus thrombosis.
Larynx and bronchi
• A child with mastoiditis has often had symptoms for
A child with an inhaled foreign body in the airway may days before the ear starts to protrude, with erythema
present in the immediate period with choking, gasping and swelling over the mastoid process. The treatment
781
and cyanosis, or may have problems later with wheeze, is surgical drainage and antibiotic therapy.
 22.1 ENT, EYE AND DENTAL DISORDERS

• With unresolved inflammation and eustachian tube • Biofilms (blankets of bacteria in a low metabolic
obstruction there may be damage and retraction state and enclosed by a polymeric matrix) may
of the TM, with erosion of the ossicles. Retraction contribute, and the organisms are similar to those
pockets form and accumulate keratinizing stratified that cause AOM.
squamous epithelium, known as a cholesteatoma. • There is no evidence that treatment with decongestants,
This causes bone erosion and usually presents antihistamines, nasal steroids or alternative medications
with intermittent otorrhoea with hearing loss. will improve the resolution of MEE.
Cholesteatoma may also be congenital and present • The hearing changes in COME are often mild
as a white mass (‘pearl’) behind an intact TM. This (10–15 dB worse) but there is a wide range, and the
may be an incidental finding. criteria for what is a significant loss are uncertain.
There are some recognized risk factors for otitis media: • Long-term studies indicate that for children with
• Race – Australian aboriginal children and some normal development there are no sequelae for
Native Americans (Inuit, Apache and Navajo). language development from COME.
There are differences in the eustachian tube and
immunological response, but socioeconomic factors
are also important. Clinical example
• Craniofacial abnormalities – including cleft palate
and Down syndrome. Thien Phuoc is 4 years old and this winter he
has had a lot of colds and two episodes of
• Genetic – both anatomical and immunological.
AOM. He often ignores his mother or asks her
There are recognized environmental factors, and fami- to repeat what she has said, but she says he
lies can help control these: speaks clearly in Vietnamese. On examination, he has fluid
• Reduce contact with people with upper respiratory in both ears. As there is concern about his hearing
infections, especially large-group childcare centres. Thien Phuoc should have an audiogram, but if it is near the
• Avoid tobacco smoke both during and after pregnancy. end of winter this can be delayed until summer as his mother
• Breastfeed for at least 6 months, preferably 12 months. is not concerned about his speech, and the fluid may resolve
spontaneously. If he has persistent middle ear effusions in
If bottle-fed, prop the baby up as milk can reflux into
summer with a conductive hearing loss, then discussions
the ear if lying flat, causing inflammation. about whether to insert tubes should start. It may be difficult
• Avoid pacifiers/dummies; this is possible from for health workers to determine whether there is a speech
inadvertent sharing in childcare centres. delay in a child who does not speak English.
• Vaccination with the polyvalent pneumococcal
vaccine reduces the incidence of AOM by 8%.
Diagnosis and management of otitis media
Clinical example • The diagnosis is often difficult to make as the child
may be uncooperative, the ear canals are small, and
Maisie is 15 months old; she has a fever and is wax may block the view. In infants it may not be
crying. She has purulent rhinorrhoea, a bulging
possible to make an accurate diagnosis owing to the
left ear drum and fluid in the right ear. Her
management includes pain relief and, as she slope of the TM.
is less than 2 years old, an antibiotic – usually amoxicillin. If • The difference between AOM and COME is based
not clinically improved in 2 days she should be reviewed to on clinical grounds of irritability, fever and pain in
determine whether the acute infection has resolved; if not, acute infection, compared with no symptoms apart
she should be changed to a β-lactamase-stable antibiotic from hearing loss if there is chronic fluid.
such as amoxicillin–clavulanate. After this acute infection
• In AOM the TM is bulging with loss of the
Maisie might have fluid in her middle ears for some weeks,
without having infection.
prominence of the handle of the malleus.
• In COME the TM is drawn in and the handle of
the malleus is much more prominent.
• The use of pneumatic otoscopy to evaluate mobility
Chronic otitis media with effusion (COME)
of the TM is very useful in determining the
This is commonly known as ‘glue ear’. ‘Chronic’ presence of middle ear fluid (Fig. 22.1.2).
implies duration of at least 3 months. There is persis- • All children with pain should be given adequate
tent fluid in the middle ear, usually after AOM, which analgesia.
is asymptomatic apart from hearing loss. The term • Many older children with AOM will not need
middle ear effusion (MEE) designates fluid in the ear, antibiotic therapy and their pain will be better
without reference to the aetiology or duration. within 2 days with symptomatic therapy.
782 • COME can be present for 3 months and still resolve • There are groups of children who should be
spontaneously. considered for antibiotic treatment:
 Ear, nose and throat disorders 22.1
Otoscopic view Lateral section through tympanic
membrane – middle ear

Pars flaccida
Posterior mallear fold
Chorda tympani
Short process of malleus
Long process of incus
Stapedius tendon
Normal Lenticular process of incus
Manubrium of malleus
Umbo
Round window niche
Pars tensa
Promontory of cochlea

Bulging of entire
pars flaccida
and
pars tensa

Bulging
Manubrium obscured

Very prominent posterior

mallear fold and short
process of malleus

Severe Tympanic membrane on incus

retraction and stapedial tendon
(atelectasis)
Manubrium of malleus
severely retracted
posterosuperiorly

Tympanic membrane
touching promontory

Fig. 22.1.2 Otoscopic view. (Redrawn with permission from Bluestone CD, Stool SE, Alper CM et al (eds) 2003 Pediatric otolaryngology,
4th edn. WB Saunders, Philadelphia, Ch. 10. © Elsevier.) In the normal ear anatomical features such as the manubrium (handle) of the
malleus and sometimes the long process of the incus are readily seen. In AOM the TM bulges out with loss of the prominence of the
handle of the malleus. With severe retraction of the TM the manubrium is very prominent and is more horizontal. The TM may drape
onto the incus and stapes.

• children aged 2 years and under as they • children with known immunosuppression
are more likely to develop suppurative • Indigenous children
complications and are not able to describe their • children with cochlear implants.
symptoms • The standard antibiotic therapy for AOM is oral
• severe disease with possible complications, amoxicillin for 5 days. Cefuroxime is an alternative
783
including perforation if there is a penicillin allergy.
 22.1 ENT, EYE AND DENTAL DISORDERS

• If there is no improvement in pain within 2 days the A genetic cause may also be non-syndromic, the most
child should be reviewed, and if the infection is not common being abnormalities of the connexin proteins.
resolving consider changing to a β-lactamase-stable
Acquired
antibiotic such as amoxicillin–clavulanate.
• Prenatal, e.g. intrauterine cytomegalovirus (CMV)
• Otorrhoea in children with chronic TM
infection.
perforations or who have ventilation tubes in place
• Perinatal, e.g. hypoxia, prematurity, high bilirubin
can often be managed with local therapy. The
(kernicterus).
mucus and pus is mopped out with tissue spears
• Postnatal, e.g. meningitis, head injury.
and topical quinolone antibiotic drops are instilled,
as they are not ototoxic.
Management
• For children with recurrent AOM, antibiotic
prophylaxis gives some benefit, but there may be • Referral to Australian Hearing for hearing aids and
gastrointestinal side-effects as well as a risk of early intervention.
accelerated bacterial resistance, especially in the • If the hearing loss is greater than 45 dB in the better
childcare setting. ear, apply for the Carer Allowance payment from
• In children with COME who do not have other Centrelink.
problems, start with observation, and request The investigations performed depend on the wishes of
a hearing test if there is no improvement after the parents. Some are not ready for genetic testing and
3 months. Surgical intervention with middle-ear counselling at the time of diagnosis, but request refer-
ventilation tubes should be considered if there is: ral at a later time.
• known language delay • Electrocardiography (ECG) to check for prolonged
• learning/intellectual problems QT interval, seen in Jervell and Lange-Nielson
• significant hearing loss syndrome.
• visual impairment in addition to hearing loss • Imaging of the inner ear at some stage. If the
from COME child has profound or total hearing loss, imaging
• damage to the TM with retraction pockets, to is performed to determine whether there are inner
prevent permanent ossicular erosion. ears and nerves; both computed tomography (CT)
• Children with a conductive hearing loss who and magnetic resonance imaging (MRI) are needed
are not able to have surgery may be referred to for cochlear implant surgery.
Australian Hearing for assessment for a • If there is mild or moderate loss, the imaging
bone-conduction hearing aid. is performed when the child is about 5 years old and
able to lie still, unless there is deterioration before this.
Hearing loss • The main abnormality looked for is widening of
the vestibular aqueducts, as this is associated with
Newborn hearing screening is now universal in progressive hearing loss if there is head injury.
Australia, and the aim is to have completed the hearing • Ophthalmology consultation to check for vision
evaluation by 3 months of age and to have ­hearing aids problems but also to look for possible causes such
fitted by 6 months, to maximize speech and l­anguage as Usher syndrome (with retinitis pigmentosa).
acquisition.
There are many agencies offering early interven-
tion, and integrated kindergartens and schools for Clinical example
­hearing-impaired children. Families are given a folder
and information outlining the choices available to them. Halil is a 6-month-old baby who was born at 27
weeks' gestation; he had a prolonged stay in the
Aetiology neonatal intensive care unit with ventilation for
lung disease, and sepsis requiring intravenous
It is not always possible to determine the cause, but antibiotics. His parents are non-consanguineous and there
the possibilities include: genetic and acquired factors. is no known family history of hearing loss. He was referred
from the infant hearing screening programme and objective
Genetic audiology confirmed that he has severe sensorineural
These may be syndromic: hearing loss in both ears. It is probable that the hearing loss
• Autosomal dominant, e.g. Waardenburg syndrome is related to the perinatal problems of prematurity, hypoxia
with pigment alterations in the hair and eyes. and sepsis. Halil should be referred for hearing aids, and
it is likely that he will have sufficient hearing with these to
• Autosomal recessive, e.g. Usher syndrome (with develop speech and language. He should also be referred
retinitis pigmentosa), Pendred syndrome (with to ophthalmology to check his eyesight, and to the genetics
goitre), Jervell and Lange-Nielsen syndrome (with clinic when his parents are ready.
784
arrhythmias).
 Ear, nose and throat disorders 22.1
• There may be a progressive hearing loss, with • In CRS, topical saline sprays or lavage and nose-
normal hearing at birth. If parents or teachers are blowing is usually all that is needed, but in severe
concerned about the hearing, or there is a delay in cases consider investigations for allergies, immune
speech and language, the child should be referred deficiencies and adenoid hypertrophy.
for an audiogram. • Sinus surgery is rarely indicated except for
management of suppurative complications;
however, in CRS adenoidectomy may be effective,
especially if there is associated nasal obstruction
The nose and chronic snoring.
See Figures 22.1.3 and 22.1.4.
Respiratory infection
During the course of an acute respiratory infection
Epistaxis
there is nasal obstruction/congestion and rhinorrhoea,
which starts as thin, becomes mucoid, then purulent, This is common and often results from a combina-
then mucoid again and returns to thin secretions. tion of infection and trauma (nose-picking). It is more
Colds last for 10 days, and most preschool children likely if there is a haematological disorder with low
have about 10 colds per year. platelets or a bleeding diathesis.
Inflammation of the nose (rhinitis) and the sinuses Most bleeding comes from the anterior septum, and
(sinusitis) usually coexist and are difficult to differenti- in the short term can be controlled by pressure on the
ate clinically, so the term used is rhinosinusitis. nasal septum for 10 minutes.
• Acute rhinosinusitis (ARS) lasts for between If there is crusting, the main treatment is appli-
10 days and 4 weeks. cation of an antibiotic ointment and avoidance of
• Chronic rhinosinusitis (CRS) lasts for more than trauma.
12 weeks. If there is recurrent bleeding, this is managed
• CRS is common, and the predisposing factors are: with application of silver nitrate using topical local
• exposure to viruses, especially in the childcare anaesthesia, although in younger children a general
setting ­anaesthetic may be needed.
• mucociliary dysfunction and immunoglobulin Nasopharyngeal angiofibroma is a rare tumour that
deficiencies, although there are usually other occurs in adolescent males and presents with severe
infections as well epistaxis and nasal obstruction; the diagnosis is made
• allergic rhinitis, including inhaled and ingested by nasendoscopy, or by CT with contrast.
allergens.
• Tumours in the nose, such as rhabdomyosarcoma,
may also present with chronic rhinorrhoea.
The oropharynx
Management Acute sore throat
• In ARS, symptomatic therapy is all that is required. This is a common problem and may be caused by:
Nasal saline drops and sprays are effective for • viruses including rhinovirus, influenza and
eliminating oedema and secretions, and for children parainfluenza, and Epstein–Barr virus
older than 3 years topical nasal steroid sprays are • bacteria, especially Streptococcus pyogenes
safe and effective for reducing rhinorrhoea. • fungi, including Candida albicans, especially if
• Cultures from the nose do not correlate well immunosuppressed.
with pathogens within the sinuses, so are not Tonsillitis is a clinical diagnosis based on:
recommended. • the child presents with sore throat, fever and
• Plain X-rays of the sinuses are usually not useful. dysphagia
• CT of the sinuses may be requested if there is • inflammation is confined to the tonsils and there
a poor response to therapy, or if suppurative may be exudate on them
complications are suspected. This should be with • enlarged tender cervical lymphadenopathy
contrast to demonstrate abscess formation in the • the absence of coryza and cough, which would
orbit, extradural space or brain. indicate a viral upper respiratory illness.
• Antibiotics are considered if: The throat should also be examined for possible sup-
• the illness is severe purative complications:
• suppurative complications are suspected • peritonsillar (quinsy) abscess
• there is also bronchitis or otitis media • associated trismus (difficulty opening the mouth) 785
• there are prolonged symptoms. • displacement of the tonsil medially
 22.1 ENT, EYE AND DENTAL DISORDERS

Sudden onset of two or more symptoms, one of which At any point

should be either nasal blockage/obstruction/congestion Immediate referral/hospitalization
or nasal discharge: anterior/postnasal drip; ± frontal • Periorbital oedema
pain/pressure, ± reduction or loss of sense of smell • Displaced globe
Examination: anterior rhinoscopy • Double vision
X-ray/CT not recommended • Ophthalmoplegia
• Reduced visual acuity
• Severe unilateral or bilateral frontal headache
• Frontal swelling
• Signs of meningitis or focal neurological signs
Symptoms for less Symptoms persistent
than 5 days or or increasing after
improving thereafter 5 days

Common cold Moderate Severe Hospitalization

Nasal endoscopy
Culture
Imaging
IV antibiotics
Asthma and/or surgery
Symptomatic relief Non-toxic Toxic, severely ill
Chronic bronchitis

Hospitalization
No Yes Oral antibiotics
IV antibiotics

Oral amoxicillin
Symptomatic relief No effect in 48 h
can be considered

Hospitalization

Fig. 22.1.3 Evidence-based scheme for children with acute rhinosinusitis. CT, computed tomography; IV, intravenous. (Reproduced
with permission from Fokkens W, Lund V, Mullol J 2007 Rhinol Suppl 20:103.)

• parapharyngeal abscess, often with swelling in the recommendation to avoid antibiotic therapy may
pharynx and neck change in the future.
• retropharyngeal abscess When indicated, the recommended antibiotic therapy
• suppurative lymph nodes in the neck. is penicillin V for 10 days.
Throat cultures are usually not needed and may be inac- Suppurative complications in the pharynx usually
curate, as it is possible to be a carrier of Streptococcus require:
pyogenes and not have infection. • evaluation with CT or MRI
Antibiotic therapy is usually not necessary unless: • intravenous antibiotics
• there is a suspected suppurative complication • surgical drainage as there is a risk of:
• the child is immunosuppressed • spontaneous rupture and aspiration into the
• the child is Indigenous or a Pacific Islander, as these lungs
children are more likely to develop rheumatic fever • spread into the mediastinum
• at present, strains of Streptococcus pyogenes • thrombosis or erosion of major vessels in the
that cause rheumatic fever are rare, but the neck.
786
 Ear, nose and throat disorders 22.1
Two or more symptoms, one of which should be either Consider other
nasal blockage/obstruction/congestion or nasal diagnosis
discharge: anterior/postnasal drip; ± facial pain/pressure, Unilateral symptoms
± reduction or loss of sense of smell Bleeding
Examination: anterior rhinoscopy Crusting
X-ray/CT not recommended Cacosmia

Orbital symptoms
Periorbital oedema
Displaced globe
Frequent Double or reduced
Not severe exacerbations vision
Ophthalmoplegia

Severe frontal
headache
Frontal swelling
Treatment Signs of meningitis
Allergy + No systemic disease Immunodeficiency
not necessary or focal
neurological signs

Systemic symptoms
Topical steroids Antibiotics Treat systemic
Nasal douching/lavage 2–6 weeks disease if possible
± antihistamines

Urgent investigation
and intervention
Review after
4 weeks

Improvement No improvement No improvement

Continue treatment Consider surgery

Reduce to minimum
possible

Fig. 22.1.4 Evidence-based scheme for children with chronic rhinosinusitis. CT, computed tomography. (Redrawn with permission
from Fokkens W, Lund V, Mullol J 2007 Rhinol Suppl 20:104.)

Obstructive sleep apnoea

Clinical example
This is airway obstruction resulting in temporary
Vasuki is 10 years old and in grade 4 at school. apnoea while sleeping with pauses greater than
She has had recurrent tonsillitis every 6–8 weeks 6 seconds, respiratory effort, restless sleep and
since she was in kindergarten. With each illness awakenings.
she has a sore throat with exudate on the The child is often hard to wake in the morn-
tonsils and cervical lymphadenopathy, and misses 3–4 days ings and has daytime somnolence. There may
from school. It is not likely that Vasuki will improve as she has
be poor school performance, or a younger child
had recurrent tonsillitis for 6 years, and she misses several
days from school each time. She would probably benefit may be thought to have a developmental delay. In
from tonsillectomy. severe cases there is failure to thrive and even cor
pulmonale.
787
 22.1 ENT, EYE AND DENTAL DISORDERS

Predisposing features are: See Figure 22.1.5 for the differential diagnosis of
• tonsil and adenoid hypertrophy stridor.
• craniofacial disorders
• neurological impairment/hypotonia
• obesity. Aetiology in infants
Congenital
Indications for tonsillectomy and • Laryngomalacia – also called ‘floppy larynx’. The
adenoidectomy baby has high-pitched inspiratory stridor and
on awake flexible nasendoscopy there is an
There are several reasons why a child might bene- omega-shaped larynx and the aryepiglottic folds
fit from tonsillectomy and adenoidectomy. Caution fall in on inspiration. This usually improves by
must be taken when removing adenoids to examine 12–18 months, but rarely the obstruction is severe
for structural or functional problems with the palate, with failure to thrive, and the child needs surgery with
as removal of the adenoids may cause velopharyngeal a supraglottoplasty to remove redundant mucosa.
insufficiency with nasal escape of air and indistinct • Webs and cysts
speech. • Subglottic stenosis
• recurrent tonsillitis – at least seven episodes in • Bilateral vocal cord paralysis, associated with
1 year. Many children starting in kindergarten abnormalities such as the Arnold–Chiari
and school have a year of tonsillitis and the malformation in the central nervous system, but
next year will be improved, so observation over may also be idiopathic.
2 years or more is warranted. A good guide is the
severity of each episode and whether the child Acquired
has missed more than 2 weeks from school in • Subglottic stenosis – with good neonatal care
a year. acquired stenosis is uncommon. Severe cases
• obstructive sleep apnoea require tracheostomy and later laryngotracheal
• recurrent quinsy reconstruction.
• biopsy for possible malignancy, especially • Subglottic haemangioma – this usually becomes
lymphoma. symptomatic in the first few months of life and
then, like other haemangiomas, involutes. The
Indications for adenoidectomy only infant can have severe obstruction, and the current
• Chronic mouth breathing and discomfort standard treatment is with propranolol to avoid the
• Chronic rhinorrhoea and recurrent sinusitis need for a tracheostomy.
• Chronic otitis media with effusion. • Subglottic cysts occur in premature babies who
had prolonged intubation; these are opened in
the operating theatre under general
Noisy and obstructed breathing
anaesthesia.
• Stridor is noisy breathing from narrowing of the • Recurrent juvenile papillomatosis; this is caused
airway at or below the larynx. by human papilloma virus (HPV) and the child
• A child may also have noisy or obstructed breathing presents as a toddler with hoarseness and stridor.
from problems in the: The mainstay of treatment is laser therapy. With the
• pharynx (especially tonsils and adenoids) new HPV vaccine it is hoped that this distressing
• chest (e.g. diaphragmatic hernia) disease will become a disorder of the past.
• abdomen (e.g. a large abdominal mass). • Unilateral vocal cord paralysis may occur after
• Inspiratory stridor is usually from extrathoracic surgery in the neck and chest (congenital heart
pathology. disease, tracheo-oesophageal fistula and thyroid
• Expiratory stridor is from intrathoracic surgery) and causes a hoarse voice, but rarely
pathology. airway obstruction.
Features of upper airway obstruction include:
• stridor Aetiology in older children
• tachypnoea, tachycardia, chest retraction
• cyanosis. • Acute laryngotracheobronchitis (croup)
There may also be: • Epiglottitis (which is uncommon now with the
• a weak cry H. influenzae type B vaccine)
• recurrent aspiration • Foreign body
• recurrent or prolonged croup. • Retropharyngeal abscess.
788
 Ear, nose and throat disorders 22.1
Noisy breathing

Stertor Stridor

Adenotonsillar Inspiratory
Expiratory
hypertrophy or biphasic
Macroglossia
Micrognathia
Choanal atresia

Hoarse voice Normal voice Afebrile Febrile

Foreign body
Afebrile Febrile Afebrile Febrile Bronchiolitis
Bronchial asthma

Vocal cord Croup Laryngomalacia Retropharyngeal

paralysis Supraglottitis Subglottic stenosis abscess
Respiratory Subglottic
papillomatosis haemangioma
Laryngeal
cyst/web
Laryngeal cleft

Fig. 22.1.5 Differential diagnosis of stridor in children. (Redrawn with permission from Ludman H, Bradley PJ (eds) 2007 ABC of Ear,
Nose and Throat, 5th edn. John Wiley, Chichester, p56.)

Assessment
Assessment of the child requires careful history and Practice points
examination. Investigations may include:
• flexible awake endoscopy, to assess vocal cord • A child with an inhaled foreign body may present with
unilateral wheeze or unresolved pneumonia.
mobility, and look for other cysts, oedema, webs
• If there is concern about a child's hearing or speech and
• radiology, which may include: language development, an audiogram should be performed,
• chest X-ray even if the child passed the newborn screening hearing test.
• barium swallow, to assess for a vascular ring • In many children with epistaxis there are crusts and
• MRI/magnetic resonance angiography (MRA) of infection in the nose and antibiotic ointment can treat both
the chest for possible vascular anomalies the infection and the bleeding.
• ultrasonography or MRI of the brain for Arnold– • Tonsillitis is a clinical diagnosis in a child with sore
throat, fever, dysphagia, exudate on the tonsils, cervical
Chiari malformation
lymphadenopathy and the absence of coryza and cough.
• echocardiography • The most common cause of stridor in newborn babies is
• bronchoscopy under general anaesthesia, if no laryngomalacia.
other cause is found.
789
 22.2 Eye disorders Susan Carden, James Elder

Examination of the eyes should be included in all a­ cuity, and forced preferential looking tests may be
general medical paediatric checks because it is only more appropriate.
through timeliness of diagnosis of ophthalmic The vision should be tested for each eye individually.
­pathology that the best vision can be achieved. Repeat the test on another occasion if the test results
seem inaccurate.
The notation for documenting visual acuity is often
based on the Snellen fraction (e.g. 6/6). Most visual
Development of vision acuity tests use standard distances of 3 or 6 m between
At birth, an infant has a visual acuity of approximately ­subject and chart. The numerator of the Snellen f­ raction
6/120 and by 12 months this has improved to about is the distance from the chart, whereas the denominator
6/12. This rapid development is the result of ­retinal indicates which line on the chart was the smallest to be
maturation, myelination of the visual pathways, the seen. If the vision is poor, the subject should be brought
ability to accommodate (change the focal length of the closer to the chart. The vision then may be recorded as
eye) and maturation within the visual cortex. The mat- 2/18 or 1/60, etc., depending on how close the subject is
uration of vision occurs probably until 14 years of age, to the chart and which line is read.
with the most rapid phase being in the first 2 years, and
subtle changes occurring after 8 years of age. What level of vision is abnormal?
An infant who is not fixing and following must be
examined further and investigated.
Measurement of vision In an older child, a vision of worse than 6/9 is a rea-
sonable cut-off for referral. In addition, a difference in
in children visual acuity between the two eyes of two or more lines
Asking a parent ‘Does your child see well?’ or ‘How indicates the need for further assessment.
well do you think your child sees?’ often gives useful
information about an infant's visual function. If a
­parent expresses concern about an infant's vision, take
note, as this concern is often well founded. Assessment of a child with
An understanding of normal visual behaviour is a possible eye problem
vital to estimating visual function in infancy. At birth,
History
when alert, an infant should be able to fix on a face
briefly. By 6 weeks of age most infants smile in a visu- Prematurity, perinatal difficulties (e.g. birth asphyxia),
ally responsive fashion to a face. At this age the infant significant syndromes (e.g. Down syndrome) and other
will also be able to follow a face or light. By 6 months sensory impairment (e.g. deafness) are all associated
of age an infant can actively follow objects in the with an increased risk of eye disease. Common child-
visual environment. Comments on an infant's ability hood eye problems such as strabismus and refractive
to ‘fix’ and/or ‘follow’ are very useful qualitative mea- errors have a familial tendency, although the precise
sures of vision. Forced preferential looking tests are genetics are not well understood. Finally, the parents'
used to measure vision quantitatively. perception of a child's visual function is important,
Picture-naming tests can be done by children between particularly if there is concern that the vision is poor.
2 and 3 years of age, and single letter-matching tests are
within the abilities of most 3–4-year-olds. The standard
Examination
Snellen chart test is generally not performed well until
the child is between 5 and 6 years of age. As with any paediatric medical examination, obser-
Children with specific language delay or intellec- vation of the child in the environment of the waiting
tual delay will have difficulty with some tests of visual room, walking towards your clinical room and in the
790
 Eye disorders 22.2

Fig. 22.2.1 Retinoblastoma. ‘White’ light reflex in left pupil.

Fig. 22.2.2 This infant has prominent epicanthic folds, giving rise
to the appearance of misaligned eyes. This is pseudostrabismus.
Note that the corneal light reflections are symmetrical. Cover
clinical room is generally the key to diagnosis. Observe testing failed to reveal misalignment of either eye.
whether the child smiles at a face, looks around the
room or follows moving objects.
Systematic examination of the eye involves dividing fix on an object while the observer determines which
the areas into three: external (eyelids, eyelashes and eye appears to be misaligned. The eye that appears to
periorbital region), anterior segment (cornea, pupil, be fixing on the object (and not misaligned) is then cov-
iris and lens) and posterior segment (vitreous cavity, ered while the apparently misaligned eye is observed.
optic nerve and retina). If strabismus is present, a corrective movement of the
Most eyelid, eyelash and ocular surface abnormal- misaligned eye will be seen as this eye takes up fixation
ities can be detected by observation. Many intraoc- on the object of regard (Fig. 22.2.3). If no movement
ular abnormalities can be detected by examination is seen, the eye is uncovered.
of the ‘red reflex’. This is the red to orange colour The cover test is then repeated, covering the other
seen within the pupil when the line of illumination eye this time; the eye that is not covered is again
and observation are approximately coaxial (that is, observed for a corrective movement and, if present,
the same). This situation is most easily obtained by strabismus is confirmed. The test can be repeated
observing the child's eye with a direct ophthalmo- as many times as necessary. If no movement is seen
scope from a distance of about 1 m. The light reflex following repeated covering of either eye, then stra-
for each eye can be compared. A dull or absent red bismus is not present. Care must be taken to allow
reflex indicates an opacity, such as a cataract, in the the child to fix with both eyes open before covering
normally clear media of the eye. A white reflex results either eye, otherwise normal binocular control may
from an abnormally pale reflecting surface within the be prevented and a small latent squint (phoria) may
eye, such as a white retinal tumour (retinoblastoma; be detected. Latent squints are normal variants and
Fig. 22.2.1) Although these intraocular disorders are are of no significance.
rare, they are important in terms of the severe effect
on vision or threat to life.

Misalignment of the eyes

Strabismus or squint occurs in 3–4% of children.
Observation will confirm the presence of a large-
angle strabismus. However, a broad nasal bridge
or ­prominent epicanthic folds will mimic milder
degrees of strabismus, especially in younger infants.
This condition is known as pseudostrabismus
(Fig. 22.2.2). The epicanthic folds cover the sclera
on the medial aspect of the globe, while the lateral
sclera is easily visible. This creates the appearance
of misalignment, particularly when the child looks Fig. 22.2.3 Cover test. First the child's attention is attracted with
laterally. Examination of the symmetry of corneal a toy (top). Then the eye that appears to be looking directly at
the toy is covered and the other eye is observed for a refixation
light reflections will aid in determining whether
movement (bottom). In convergent squint there will be an
there is an esotropia (in-turning of the eyes) or only outward movement of the uncovered eye (pictured), and in
pseudostrabismus. divergent squint there will be an inward movement of the eye.
A cover test is a reliable method of detecting strabis- If no movement is detected, the test should be repeated but
mus. The cover test is done by first getting the child to covering the other eye first.
791
 22.2 ENT, EYE AND DENTAL DISORDERS

Occlusion therapy and surgery are the most common

Common eye problems treatments. Children with infantile esotropia need to
in childhood be followed up throughout childhood: approximately
one-third require further surgery, and amblyopia can
Amblyopia occur despite adequate eye alignment.
Amblyopia, the cortical response to abnormal input
from the eyes and manifest as reduced visual acuity Intermittent divergent strabismus (exotropia)
in one or both eyes, results from refractive (spectacle)
error (in one or both eyes), strabismus or from depri- While exotropia can occur in infancy, it is more com-
vation (e.g. cataracts). Amblyopia usually responds to mon from 18 months of age. It is often more noticeable
treatment if detected in a timely fashion. Detection on distance fixation and may be associated with mon-
of amblyopia is one of the major reasons for rou- ocular closure in bright light. Amblyopia is less com-
tine visual screening in childhood as the earlier it is monly associated with exotropia than with esotropia
detected the more chance there is that treatment will because the deviation is intermittent and, presumably,
be successful. when the eyes are straight n­ ormal visual development
Refractive errors cause a poorly focused image to be proceeds. In some cases the divergence becomes more
transmitted from the retina to the cortex. Such input ­constant and surgery may be undertaken to improve
does not stimulate normal cortical development and alignment.
amblyopia results.
Strabismic (misaligned) eyes each send a different Accommodative esotropia
view of the world to the cortex. If the brain ‘paid
This occurs in children who are excessively ‘long-
attention’ to the image from each eye, diplopia would
sighted’ (hypermetropic). To overcome hypermetropia
ensue. However, the immature visual cortex is capable
and focus a clear image on the retina, accommoda-
of ignoring the image from one eye. Eventually the
tive effort is used. Accommodation consists of the
cortex may suppress the input from a deviating eye,
combination of changing focal length of the lens
with resulting amblyopia.
together with convergence of the eyes (so that both
Treatment of amblyopia involves the correction of
are directed at the near object of regard). Thus,
any focusing errors with appropriate spectacles and
in children with excessive hypermetropia there is
forcing the brain to use the amblyopic eye by depriv-
increased focusing and at times excessive conver-
ing the brain of clear input from the better-seeing eye.
gence; a c­onvergent squint (esotropia) appears as a
This is commonly done with a patch. Unfortunately,
result of the increased accommodative effort used by
realigning strabismic eyes is not enough to overcome
these children. Accommodative esotropia can be com-
amblyopia secondary to strabismus.
pletely or ­partially corrected by prescribing glasses
that compensate for the appropriate amount of hyper-
Strabismus metropia. Amblyopia, sometimes in both eyes, is often
A squint or misaligned eye is frequently associated with seen in association with an accommodative esotropia.
amblyopia. Childhood strabismus is often the result Occlusion therapy may be required. If glasses only
of failure of binocular control at a cortical level. Less partly correct the esotropia, surgery may be indicated
commonly it is the result of cranial nerve lesions or to obtain optimal alignment.
extraocular muscle disease. In most children, strabis-
mus is not associated with neurological or ­intellectual
problems. However, children with widespread c­ entral Clinical example
nervous system abnormalities have an increased
risk of developing strabismus. Down syndrome is a A 3-year-old girl presented with a history
of a worsening inward turn of her left eye
good example of this, with an approximately 10-fold
over 4 months. The cover test confirmed a
increased risk of developing strabismus. left convergent squint and the red reflex
The following is a brief description of frequent pat- was normal in each eye. Subsequent assessment by an
terns of strabismus seen in childhood and an outline ophthalmologist confirmed the findings and the girl's
of their management. visual acuities were 3/3 in the right eye and 3/9 in the
left, with refraction showing that she was hypermetropic.
When seen 4 months later she was wearing glasses and
Infantile esotropia had been patching her right eye for 2 hours a day. Her
eyes were straight to cover test, her left eye vision was
This is a large-angle convergent squint seen before improving and strabismus surgery was less likely to be
6 months of age. Strabismic amblyopia is common appropriate.
792
in infantile esotropia, but refractive errors are rare.
 Eye disorders 22.2
Refractive errors Nasolacrimal duct obstruction
Common refractive errors include hypermetropia, Obstruction of one or both nasolacrimal ducts is a com-
myopia and astigmatism. These are the result of mon problem during infancy. It can present as a watery
defects in the focusing components of the eye (the and sticky eye in the first few weeks of life. Despite the
optics of the eye). Hence, any defect in the shape of persistent discharge, the eye is ‘white’ and not red or
a surface of the eye can cause a refractive error: an inflamed. An inflamed eye suggests an alternative diag-
abnormality of corneal curvature (a frequent cause nosis such as conjunctivitis. If the obstruction persists,
of astigmatism), abnormalities of lens power and the lower lid may become red and sometimes slightly
axial length of the eye that is too long (causing myo- scaly as a result of prolonged skin irritation.
pia) or too short (causing hypermetropia). Children The differential diagnosis includes trauma, conjunc-
rarely complain of poor vision related to refractive tivitis and infantile glaucoma. These conditions are
error. Children with poor vision, due to any signifi- described below.
cant refractive error, often hold objects of regard very Most congenital nasolacrimal duct obstructions
closely. resolve spontaneously during the first year of life.
Significant refractive errors can be equal in both Persistence after 1 year of age is generally an indica-
eyes or they can be different in each eye (anisometro- tion for probing of the duct under general anaesthesia.
pia). Bilateral equal refractive errors can cause ambly-
opia in both eyes, whereas anisometropia can lead to
unilateral amblyopia. Trauma
Vision screening in preschool children aims to detect
Trauma to the eye may be physical (blunt or sharp)
silent, significant, refractive errors that are amenable
thermal, electromagnetic or chemical.
to treatment. Amblyopia becomes less amenable to
Direct blunt trauma to the eye may cause disruption
treatment the older a child becomes.
of iris blood vessels (leading to a hyphaema, i.e. blood
If a refractive error is suspected in a young child
in the anterior chamber of the eye), iris tears (irido-
because of strabismus or poor visual acuity, objective
dialysis), dislocation of the lens, rupture of the choroid,
testing with cycloplegic retinoscopy is required. If a
retinal haemorrhages and, rarely, rupture of the sclera.
child is prescribed glasses, these should be worn the
Gross inspection of the eye will reveal most injuries.
majority of the time. Occlusion therapy with a patch
Choroidal and global rupture may be suspected on the
is a frequent mainstay of treatment and needs to be
basis of the nature of the injury and associated poor
monitored very carefully to avoid under-patching or
vision. Referral to an ophthalmologist is necessary for
over-patching (reverse amblyopia).
confirmation of the injury and further management.
Surface trauma can be diagnosed with the help of flu-
orescein staining and a cobalt blue light. It is helpful to
instil local anaesthetic drops at the beginning of the exam-
Practical points ination. Areas of epithelial abrasion will f­luoresce green.
If a round ulcer and/or vertical linear abrasions are seen,
Vision assessment and strabismus suspect a subtarsal foreign body. The upper lid should be
• Parental assessment of their infant child's vision is often everted and any subtarsal foreign bodies can be removed
very accurate; if they are concerned their child is not
seeing, you should be concerned also.
with a moistened c­otton-bud. Superficial trauma is
• Carefully observe the child's visual behaviour before treated with antibiotic ointment and daily review until any
actively examining the child. Red reflexes can be observed epithelial defect (ulcer or abrasion) has healed.
from a distance. Urgent referral is required if an abnormal If the cornea or sclera has been penetrated, intra-
red reflex is found. ocular contents can prolapse out through the wound.
• Vision screening programmes aim to detect silent, In such cases, the iris and pupil may appear distorted
significant refractive errors in children. Children under
or the anterior chamber may be shallower than nor-
7 years of age rarely complain of poor vision relating to a
refractive error (reduced visual acuity). mal. Any patient with a suspected penetrating eye
• Strabismus is a common cause of amblyopia. injury must be referred to an ophthalmologist. During
Suspected cases of strabismus should be referred transport of the patient, the eye should be protected
to an ophthalmologist for further assessment and with a cone that does not exert any pressure on the eye.
management. If vomiting is likely, an antiemetic should be given to
• Cover testing is a helpful method to diagnose strabismus. ­prevent further prolapse of intraocular tissue.
• Amblyopia can often be treated effectively with glasses Thermal injuries to the eyes are uncommon because
and/or occlusion therapy if it is detected in a timely
manner. An optimal time is at about 3 years of age (or closure of the eyelids tends to protect the eyes. With time,
earlier). facial burns may cause cicatricial scarring that interferes
793
with lid function, leading to exposure and drying of the
 22.2 ENT, EYE AND DENTAL DISORDERS

eye's surface. If a primary thermal injury to the eye is Conjunctivitis

suspected, fluorescein dye should be used to detect any
Conjunctivitis may be infective, allergic or due to
ulceration. If ulceration is found, treatment with antibi-
chemical irritation. The main symptoms are itch,
otic ointment and regular review is important.
pain, irritation or a gritty sensation. The main signs
Radiation injuries to the eye are generally the result
are epiphora (watering), discharge, and erythema of
of medical radiation therapy for facial or ocular neo-
­conjunctiva and lids. The relative prominence of dif-
plasia. Typical complications can be cataract, dry eye
ferent symptoms and signs varies with the cause of the
syndrome, radiation retinopathy and optic neuropa-
conjunctivitis (Table 22.2.1).
thy. These changes are seen some considerable time
Ophthalmia neonatorum is bacterial conjuncti-
after the irradiation.
vitis contracted during delivery from the maternal
Chemical burns to the eye in childhood are poten-
birth canal. It can be due to Neisseria gonorrhoeae
tially very serious, especially if the chemical is alkaline.
or Chlamydia trachomatis. These are serious dis-
Burns may occur with accidental access to a domestic
eases that both cause conjunctivitis with copi-
cleaning agent, many of which are alkaline in nature.
ous discharge and marked erythema. Gonococcal
Strong alkali will denature and dissolve p ­ rotein and
conjunctivitis can cause perforation of the cor-
penetrate deeply into the cornea. Acids tend to coag-
nea, resultant loss of vision and generalized sepsis.
ulate the corneal structures and this often prevents
Chlamydial conjunctivitis can also lead to a gener-
deeper penetration of the acidic chemical into the
alized sepsis and pneumonia. Microbiological diag-
eye. Immediate first aid should consist of copious
nosis is required urgently, and conjunctival swabs
­irrigation with water at the site of the accident and this
and scrapings need to be done. Antibiotic treatment
should be continued for at least 10 minutes. Following
often requires topical and systemic measures for the
adequate irrigation, all patients with chemical burns
infant, and systemic treatment of the mother and
of the eye should be referred to an ophthalmologist.
her partner(s).
Bacterial conjunctivitis occurring outside the first
few weeks of life in children is usually the result of rel-
Practical points
atively innocuous organisms (e.g. Staphylococcus spp.
and Haemophilus spp.) Microbiological investigation
Blocked tear ducts and eye injury
is not usually indicated and a broad-spectrum topical
• Most congenital blocked tear ducts resolve spontaneously
by 1 year of age. antibiotic should be prescribed (e.g. chloramphenicol,
• Inspection with the addition of local anaesthetic drops framycetin sulphate, neomycin).
and fluorescein staining will enable the diagnosis of most Viral conjunctivitis is common at all ages. The dis-
physical trauma to the eye. charge from viral conjunctivitis is often less than
• All chemical injuries to the eye should be regarded as with bacterial conjunctivitis. Viral conjunctivitis is
serious and require copious irrigation.
frequently associated with upper respiratory tract
­

Table 22.2.1 Signs and symptoms of conjunctivitis

Cause of conjunctivitis Symptoms Signs

Viral Moderate discomfort Moderate epiphora

Mild discharge
Mild to moderate erythema

Bacterial Moderate to severe discomfort Moderate epiphora

Copious discharge
Moderate to severe erythema

Allergic Excessive blinking and eye rubbing Mild to moderate epiphora

Stringy discharge
Mild erythema

Chemical Pain intense Severe epiphora

Mild discharge
Moderate to severe erythema

The descriptions in this table are intended to be a guide; there may be considerable variation and overlap in the signs and
794 symptoms of conjunctivitis from different causes.
 Eye disorders 22.2
i­nfection ­symptoms. Treatment usually involves eye
toilets and prevention of the sharing of towels in the Practical points
family.
Allergic conjunctivitis is common in children of all Conjunctivitis and chalazia
age groups and empirically seems to be worsening as • Neonatal conjunctivitis may be sight-threatening and
the climate changes. Children tend to complain of itch a threat to the newborn infant's health. Immediate
much less than adults but will often be noted to rub their investigation with appropriate treatment is needed.
eyes vigorously. Many children may present only with • Children do not always complain of itchiness with allergic
conjunctivitis. Excessive blinking may be the key to the
excessive blinking and may have been thought to have a
diagnosis.
tic. House-dust mite, grass and other plant pollens are
• Most chalazia are not infected, and redness and swelling
common allergens that precipitate allergic conjunctivi- is the result of sterile inflammation. Consequently topical
tis. Therapy depends on the severity of the symptoms. and oral antibiotics are of little use in treatment. Most
If mild, cold compresses may be all that is needed. For chalazia resolve spontaneously.
more severe symptoms, topical eye-drop mast cell sta-
bilizers are helpful. In more persistent and severe cases,
topical steroid preparations may be indicated. Topical
Ptosis
steroids should be used only under the supervision of
an ophthalmologist because of the risk of side-effects, Ptosis, also called blepharoptosis, is a droopy upper
including cataract, glaucoma and keratitis. eyelid and results from innervational or muscular
defects of the levator superioris or Müller muscles.
Innervational defects include third cranial nerve palsy,
Horner syndrome (sympathetic nervous system) and
Clinical example myasthenia gravis. Congenital ptosis is the commonest
A 4-year-old boy presented with a 12-hour type of ptosis in children, and is caused by a defect in
history of a red and watery eye. He complained the levator superioris muscle. Ptosis can cause ambly-
of pain and his parents had not observed any opia in young children. This is usually the result of
discharge. Examination revealed a red eye occlusion of the visual axis. On occasion, ptosis is a
with no obvious trauma or foreign body on the surface of cosmetic concern; surgical correction can be offered in
the eye. After topical local anaesthetic drops had been many cases.
instilled, fluorescein staining demonstrated a round ulcer
on the upper part of the cornea. Eversion of the upper
eyelid revealed a small foreign body. It was removed with a
moistened cotton-bud. The ulcer was treated with antibiotic Learning difficulties
ointment and healed in 1 day.
Learning difficulties are common in school-aged chil-
dren. Affected children are often sent for an ophthal-
mic examination to rule out a disorder of vision. It
Lid infections and inflammation is uncommon to find a cause, although allergic eye
disease (in particular vernal allergic eye disease) is
These are common in children and most arise in the
an increasing cause of poor concentration. It is com-
skin appendages of the eyelids (lash follicles and mei-
monly assumed that there may be a visual abnormal-
bomian glands). Infection of a lash follicle is called a
ity that contributes to, or even causes, the learning
stye. Unless there is significant secondary erythema
difficulty. This assumption is ill-founded and arises
of the surrounding lid, topical and systemic antibi-
because vision is obviously involved with activities
otics are not indicated. Occasionally, severe preseptal
such as reading and writing. Children with learning
cellulitis will follow a focal lid infection and systemic
difficulties are no more or less likely to have visual
(often intravenous) antibiotics will then be needed for
problems than children without evidence of learning
treatment.
problems. Rather than expending effort on therapies
Inflammation of a meibomian gland is known as a
for perceived ocular abnormalities, parents should be
chalazion. This is the result of inflammation due to
encouraged to take an educational approach to their
blockage of the duct of the gland, rather than infection.
child's learning difficulties.
A chalazion will appear as a lump in the substance of
the lid. It can be inflamed in appearance. Warm com-
presses may give symptomatic relief and help drainage.
Visual handicap
Chalazia may persist for many months. Some will dis-
charge their contents through either the conjunctiva or Visual handicap in childhood may be the result of ocu-
the skin. Occasionally, surgical drainage is indicated for lar and/or cortical visual abnormalities, and may be
795
a persistently inflamed and large chalazion. associated with other abnormalities, such as deafness,
 22.2 ENT, EYE AND DENTAL DISORDERS

motor defects and intellectual deficits. Intervention r­ eadily by inspection of the red reflex with the direct
and support for a particular child needs to be planned ophthalmoscope.
after a thorough assessment of the child's visual and There are numerous causes of congenital c­ataract,
associated handicaps. From a purely visual point of including: hereditary (dominant, recessive and X-linked);
view, interventions may include mobility training, low metabolic (e.g. galactosaemia); association with ­systemic
vision aids, such as magnifiers and closed-circuit tele- syndromes (e.g. Down syndrome); and congenital
vision, and training in alternative means of commu- infection (e.g. rubella embryopathy). Many, especially
­
nication, such as Braille and the use of a computer unilateral cataracts, are idiopathic.
to write.
The presence of an additional handicap, such as deaf- Retinoblastoma
ness or an intellectual deficit, compounds the situation
This is a rare childhood cancer arising within the
and necessitates skilled intervention over many years.
­retina. Sporadic and hereditary forms are recognized.
The sporadic form is the result of two separate muta-
tions that negate the action of the retinoblastoma (Rb)
gene within a single retinoblast cell, and thus is always
Other important eye problems in unilateral (see Fig. 22.2.1). The hereditary form arises
childhood when the first of these two mutations occurs in one
Rb gene within a germ cell (most often a sperm). The
These are mentioned briefly because prompt recogni-
second mutation occurs within the retinoblast. As all
tion enables early treatment and optimal out­comes.
retinoblasts descended from an affected germ cell have
the first mutation, by chance more than one retino-
Poor vision in infancy blastoma will usually develop and hence the hereditary
form is often, but not always, bilateral.
This first comes to attention when a child fails to
Retinoblastoma often presents with leukocoria
achieve normal milestones of visual development
(white pupillary reflection – the white tumour is seen
(see Measurement of vision in children, above). If the
immediately behind the lens), strabismus, poor vision,
cause of severe visual impairment is within the eye,
or a known family history of retinoblastoma. Prompt
sensory nystagmus will develop by 3–4 months of age.
recognition is vital as early treatment will increase the
This nystagmus is often slow and somewhat pendular
possibility of preserving vision and life. With current
rather than jerky in appearance, due to its immaturity.
treatments the 5-year survival rate for this childhood
Severe visual loss due to cortical visual impairment
cancer is about 98%.
tends not to cause nystagmus.
Causes of poor vision in infancy include:
Glaucoma
• cataracts
• albinism Glaucoma in infancy presents with a cloudy and
• retinal colobomas enlarged cornea (buphthalmos) with associated epiph-
• infantile glaucoma ora (watery eye) and photophobia (see Fig. 22.2.4).
• congenital retinal dystrophy It may be unilateral or bilateral, and is usually an
• retinoblastoma isolated ocular abnormality. If unrecognized it will
• delayed visual maturation result in severe and untreatable visual loss over weeks
• cortical visual impairment.
Prompt recognition is vital as there may be a treatable
cause (e.g. cataracts) and, even if no treatment is pos-
sible, early and appropriate intervention minimizes the
negative effects of severe visual impairment on general
development.

Cataract
A cataract is any opacity within the lens. Bilateral
congenital cataracts will often cause poor vision in
infancy, whereas unilateral congenital cataract may
go unrecognized as one eye has normal vision. Both Fig. 22.2.4 Congenital glaucoma. The left eye has a corneal
bilateral and unilateral congenital cataracts are diameter larger than that on the right eye, a hazy cornea, and is
treatable if diagnosed early. Cataracts are detected watery.
796
 Eye disorders 22.2
to months. Surgical treatment, aimed at increas- Regular screening of at-risk infants (birth
ing the drainage of aqueous fluid out of the eye, is weight < 1500 g or gestation < 32 weeks) by an ophthal-
indicated as in most instances, medical therapy with mologist enables timely detection of significant ROP
anti-glaucoma medication is usually a temporizing or before retinal detachment ensues. Retinal ablation with
­adjunctive measure. laser surgery greatly reduces the risk of the develop-
ment of retinal detachment and subsequent blindness.
Colobomas
Juvenile chronic arthritis
A coloboma is a defect resulting from failure of com-
plete fusion of the embryonic fissure of the developing Childhood chronic arthritis is associated with inflam-
eye between the fourth and sixth week of gestation. If mation of the iris (iritis or anterior uveitis). Those at
the optic nerve or macular area of the retina is involved, particular risk are young girls with oligoarticular juve-
vision will be affected significantly. An iris coloboma nile chronic arthritis who are antinuclear antibody
may or may not be present in association with a ­visually positive, although it also occurs in other presentations
more important posterior pole coloboma. of juvenile arthritis. The iritis that occurs in these
­children is painless and chronic, and may, if untreated,
cause cataract and glaucoma. Periodic assessment
by an ophthalmologist will detect early uveitis. The
Practical points mainstay of uveitis treatment is topical steroid drops.
Glaucoma can be associated with the disease and also
Further important considerations with steroid treatment. Regular review by an ophthal-
• Learning difficulties are seldom the result of eye problems. mologist is important.
• Examine the red reflexes of all infants suspected of having
poor vision and all infants with strabismus. An abnormal
red reflex may be due to retinoblastoma and urgent Down syndrome
referral is mandatory.
• Think of congenital glaucoma if a child has one eye that Down syndrome is associated with an approximately
is bigger than the other. Then look for coexisting clouding 10-fold increased risk of developing eye problems
of the cornea and seek a history of a watery eye and during childhood when compared with the aver-
photophobia. age incidence. Blocked tear ducts and blepharitis are
­significant problems. Squint, nystagmus, poor vision,
refractive error, keratoconus, cataract and anoma-
lous optic nerve heads can frequently be found. An
The eye in paediatric systemic increased index of suspicion for eye problems should
disease be maintained for children with Down syndrome.

The following is a brief account of the common ocular

features of some paediatric systemic diseases. Physical child abuse
Non-accidental injury may involve the eye. Direct
Extreme prematurity trauma to the eye or eyelids will be obvious on
Marked prematurity gives rise to eye problems by inspection. Violent shaking of a small child is often
interfering with the orderly development of retinal ­associated with the development of retinal haemor-
blood vessels. This disorder is known as retinopathy rhages and a severe closed brain injury. Although not
of prematurity (ROP). Mild ROP is seen in 30–50% pathognomonic of child abuse, the presence of retinal
of infants weighing less than 1250 g at birth and then haemorrhages is highly suggestive of abuse in cases of
regresses without ill effect on vision. In some infants unexplained severe brain injury in a young child.
the ROP progresses and a fibrovascular proliferation
develops within the eye that detaches the retina, with
Diabetes mellitus
resultant loss of vision.
Excess oxygen administration to premature infants Insulin-dependent diabetes mellitus (type 1) is increas-
has been known since the 1950s to be a cause of severe ing in frequency in childhood. Screening for eye com-
ROP. Curtailment of oxygen use to amounts sufficient plications occurs regularly in adults. Severe diabetic
to limit respiratory and neurological sequelae has eye disease is uncommon in childhood because the
greatly reduced the incidence of blinding ROP, but has diabetes is usually kept under strict control. In cases
not completely prevented it, particularly as infants of where the control is poor, regular eye checks can be
even lower gestation survive. commenced early (e.g. at 6 years of age). In ­developing
797
 22.2 ENT, EYE AND DENTAL DISORDERS

countries, where medical treatment may be erratic

and blood sugar level control is poor, severe dia- Summary
betic eye disease (cataracts, retinal haemorrhages It is important for the paediatrician to become familiar
and ­neovascularization) can occur before the age of with examination of children's eyes and to incorporate
10 years. Significant retinal abnormalities are seen in a this into their general medical examination technique.
small number of diabetic children in mid to late ado- Timely diagnosis of ophthalmic problems is essential
lescence, particularly if the disease was of early onset so that a referral to an ophthalmologist can rapidly
and control is poor. initiate sight-saving treatment.

798
 Teeth and oral cavity 22.3
disorders
Nicky Kilpatrick, Kerrod Hallett

The oral cavity can be considered the gateway to the the mandible and the upper incisors protrude, creating
body. It is the start of the alimentary tract and is inte- an increase in ‘overjet’, this is known as a class II mal-
grally involved in the initial phases of digestion. The occlusion. Conversely, in those cases where the man-
oral cavity consists of teeth sitting in sockets in the dible is relatively prognathic and the upper front teeth
alveolar processes of the maxillary and mandibular develop behind the lower ones, the result is a class III
bones supported by a fibrous sling known as the peri- malocclusion, or reverse overjet.
odontal ligament. The oral cavity is lined by a com- These malocclusions may result from growth anom-
bination of attached gingival tissue (gums) and more alies in either or both jaws and may be complicated
generalized mucous membranes. As with the rest of further by the pattern of eruption of the dentition,
the body, the oral cavity is susceptible to both develop- size of the teeth and other external influences such as
mental and acquired disorders that can occur in isola- thumb-sucking. Recognizing malocclusions is impor-
tion or as part of more general medical conditions or tant not only in determining the need for and nature
genetic syndromes. of treatment, but also in diagnosing growth disorders
It is becoming increasingly well recognized that oral and in syndrome identification, as jaw discrepancies
health plays a significant role in maintaining good gen- are common in such conditions.
eral health and wellbeing. This chapter will, therefore,
summarize the key features of normal oral develop-
ment and highlight the common disorders that affect
Practical points
both the teeth and their supporting structures. It will
also identify the oral manifestations of some of the
more common paediatric diseases. • Eruption times vary widely.
• Provided the sequence of eruption of the teeth is in order
(central incisors before lateral incisors, etc.), delays per se
are not a cause for concern.
Development • Asymmetrical eruption, particularly of the permanent
incisors, should be reviewed by a dentist in order to check
Teeth start to form from the fifth week in utero and that there is no obstruction (such as an extra tooth) to the
may continue until the late teens or early twenties with eruption of the appropriate tooth.
the eruption of the third permanent molars (or wis- • The simultaneous presence of primary and permanent teeth
during the mixed dentition phase is generally not a problem.
dom teeth) (Table 22.3.1). The first tooth to erupt is
• Premature loss of primary teeth can be a sign of
usually a lower central incisor at around 7 months of underlying systemic disease and should be reviewed by a
age. By the age of 2.5 years most children will have paediatric dentist.
a complete primary dentition consisting of 20 teeth:
8 incisors, 4 canines, 8 molars. At around the age of
6 years, the primary incisors become mobile and fall
Teething
out. Most people have 32 permanent teeth, the first
of which to erupt is usually the lower first permanent Teething is a normal process by which an infant begins
molars at around 6 years of age. The period that fol- to cut their first teeth (primary dentition). A variety
lows, referred to as the mixed dentition phase, is highly of symptoms can accompany teething, including sen-
variable. sitive and painful gums, mouth ulceration, drooling,
Permanent upper incisors are usually more promi- feeding difficulties, lack of sleep, fevers, diarrhoea
nent than their predecessors; this allows the mandi- and crying. There is no scientific evidence that any of
ble to grow forward and encourages the development these symptoms is directly related to tooth eruption;
of what is described as a normal occlusion – a class I nevertheless, they are commonly reported and can
occlusion. Variations of the norm are common par- cause significant distress to the child and anxious par-
ticularly in the anteroposterior dimension, and cause ent. Similarly there is no evidence base to support any
changes to the relationship between the upper and particular management strategy. The use of chilled
799
lower incisors. When the maxilla is forward relative to teething rings, hard sugar-free rusk biscuits and f­ inger
 22.3 ENT, EYE AND DENTAL DISORDERS

Table 22.3.1 Summary of the eruption times for primary and permanent teeth

Primary dentition (months after birth)

Central incisors Lateral incisors Canines First molars Second molars

6–12 9–16 16–23 13–19 23–33

Permanent dentition (years of age)

Central incisors Lateral incisors Canines First premolars Second premolars First molars Second molars Third molars

6–8 6.5–8.5 9–13 9.5–11.5 10–13 5.5–7.0 11–13 17+

pressure appears to help. Over-the-counter teething Eruption cysts

preparations are of limited use. Not only do many
contain choline salicylate and significant amounts
• A blue or clear swelling overlying the crown of
an erupting tooth, most frequently in the incisor
of ethanol, which are contraindicated in very young
region of the maxilla.
infants, but also repeated use can cause ulceration of
the gums. Some lidocaine-based gels are thought to be
• Eruption is slightly delayed and discomfort or pain
may occur.
slightly more effective and may be mildly antiseptic.
Mildly increased temperature can be managed with
• Management is symptomatic only. Surgical
intervention is contraindicated.
systemic oral medication, but temperatures of 38°C
and above, or other serious symptoms (e.g. convul-
sions), should not be ascribed to teething and should
Natal and neonatal teeth
be assessed independently.
• Present in 1 in 3000 births, or erupt in the neonatal
period – usually in the lower incisor region.
• Most are prematurely erupted normal primary teeth,
Developmental anomalies but some may be ‘supernumerary’ or extra teeth.
A few developmental anomalies occur in the newborn • Can interfere with breastfeeding (nipple trauma).
or very young child. As it is unusual for infants to be • Can cause an ulceration under the tongue in
seen by a dental health professional, it is important breastfed infants, called Riga–Fede disease, that
that the medical practitioner examine the oral cavity often necessitates tooth removal.
periodically and refer to a paediatric dentist as appro- • Removal is commonly indicated to alleviate
priate. Amongst the more common are Epstein pearls, parental anxiety and is simple (using topical local
Bohn nodules, eruption cysts and natal teeth. anaesthesia and a haemostat). Suggest checking vitamin
K-dependent coagulation factors before removing teeth.

Oral alveolar developmental cysts

Developmental defects of enamel
Epstein pearls
Teeth start forming from the fifth week in utero. Any
• Whitish-yellow nodules appear on the roof of the disturbance in metabolism can cause damage to, or
mouth in a neonate. even the death of, the sensitive enamel-forming cells
• Composed of trapped epithelial remnants during (the ameloblasts). Such a disturbance will leave a per-
palatal fusion. manent developmental defect on the tooth surface which
• The cysts usually burst and disappear by 90 days. will be apparent as a loss of tooth substance (hypopla-
sia) or a deficiency in the quality of the enamel (hypo-
mineralization) once the tooth erupts. Such defects in
Bohn nodules
enamel have in the past been related to:
• Multiple 1–5-mm creamy nodules on the outer • prenatal events such as maternal rubella virus
surface of the alveolar ridges (normally shed or cytomegalovirus (CMV) infection, maternal
in utero). syphilis and pregnancy toxaemia
• Composed of epithelial remnants. • natal events such as prematurity, hypoxia and
• Sometimes mistaken for prematurely erupting teeth. hyperbilirubinaemia
800 • No treatment indicated as the contents discharge • postnatal events – measles virus infection,
spontaneously by the third month. gastrointestinal disease and hypoparathyroidism.
 Teeth and oral cavity disorders 22.3
The first permanent molars (the so-called 6-year-old
molars) and incisors are particularly susceptible to Acquired disorders of the teeth
enamel defects as they are developing at the time of Dental caries
birth. Children with other health issues such as con-
genital heart disease or cerebral palsy are more likely Dental caries (decay) remains one of the most common
to have developmental defects of their teeth, possibly chronic diseases in childhood, and recent epidemiologi-
as a result of systemic illness, fevers and periods of cal data show that disease prevalence and severity in
hypoxia in infancy and early childhood. Early iden- childhood is increasing. As with many diseases, there
tification of these defects is important as the quality are considerable inequalities in terms of caries experi-
of the tooth enamel is compromised; the teeth may be ence with around 80% of all decay being experienced
sensitive, particularly to oral hygiene measures, and by just 20% of children. It is therefore important to
more likely to develop decay. identify children at high risk of developing decay and
target them for proactive prevention. Given the fact
that very few preschool-aged children are seen by a
dental health professional, responsibility lies with med-
Clinical example ical and nursing professionals to identify infants at risk
of developing decay and to refer to a paediatric dentist
Miranda, now aged 2 years, was born normally for appropriate anticipatory preventive advice.
at term with a normal birth weight. Since then Dental caries (or decay) is an infectious disease
she has demonstrated slow developmental
milestones and mild hemiplegia with no
caused by the presence of certain bacteria, predomi-
obvious cause. Dental examination revealed a caries-free nantly mutans streptococci (MS), in the oral cavity.
primary dentition, which, however, had chronologically The MS metabolize sugars and starches to produce
distributed enamel hypoplastic (developmental) defects, acids; this lowers the pH of the oral cavity and pro-
affecting the teeth at 4–7 months in utero. On questioning, motes loss of minerals from the tooth surface.
the grandmother had recorded in her diary the dates when Minerals in the saliva, including calcium, phosphate
her daughter had a severe viral infection and was in bed for
and fluoride, are re-deposited on the tooth surface
several days.
Antibodies to CMV were detected on testing. CMV was
once neutral pH is restored (normally after about
the presumptive cause of the enamel defects and possibly 20 minutes). This process is dynamic and as long as
also of the mild neurological defect and hemiplegia. This minerals are replaced the tooth surface remains sound
diagnosis helped early planning for future care. These and intact. If, however, the drop in pH is prolonged
enamel defects can increase the risk of developing dental and/or frequent, there will be a net loss of minerals
caries as the surface of the teeth are often more porous and leading to a weakening and eventual breakdown (cavi-
retain plaque, and they can be quite sensitive. Such teeth
tation) of the tooth surface. The early sign of mineral
can be protected with a tooth-coloured adhesive material
and the parents should be encouraged to assist Miranda loss is characterized by pre-cavitated or ‘white spot’
with her oral hygiene and to maintain regular dental visits. lesions (Fig. 22.3.1A), usually around the necks of the
teeth where the MS tend to colonize the oral biofilm

Fig. 22.3.1 (A) Typical appearance of an early carious lesion. The white spot lesion represents demineralization of the enamel caused
by the presence of bacterial plaque creating an acidic environment. If left unmanaged, the white area will continue to demineralize until
cavitation occurs (B) If identified early enough, remineralization of the enamel is possible through exposure to topical fluoride (particularly 801
toothpaste) and other calcium-based products such as casein phosphopeptide–amorphous calcium phosphate (CPP-ACP).
 22.3 ENT, EYE AND DENTAL DISORDERS

(known clinically as dental plaque) on the teeth. Early Fluoride

identification of these pre-cavitated lesions is impor- Fluoride is the single most effective way to protect
tant because they signal the need for proactive preven- teeth from decay. It acts in two ways: it can enhance
tive measures to encourage remineralization. If the the ability of teeth to resist demineralization caused
disease does progress to cavitation, restorations (fill- by intraoral acids, and it can also inhibit oral bacterial
ings and crowns) are necessary to rehabilitate func- enzymes to reduce the conversion of sugars to acids.
tion and aesthetics. However, the latter effect is relatively small in compari-
Early childhood caries (ECC – historically also son to its biochemical modification of the structure of
referred to as nursing-bottle caries, baby-bottle tooth enamel.
decay, and many other terms) is a distinct form of Fluoride can be delivered both systemically and
dental caries affecting preschool-aged children. ECC topically. Fluoridation of the water supplies allows for
is particularly virulent, causing massive destruction both effects. Water ingested during development of the
to the primary dentition in children as young as 14 teeth allows fluoride to be incorporated into the devel-
months of age (Fig. 23.3.1B). At birth, MS do not oping dental enamel. However, it is as a topical agent
inhabit the oral cavity; however, the earlier colo- that water has its most beneficial effect as low-dose
nization occurs, the greater the risk of ECC. The fluoride comes into frequent contact with the teeth
most common source for transmission of MS has before being ingested. As such, water fluoridation is
been shown to be the primary caregiver, usually the considered a very cost-effective public health inter-
mother. Poor maternal oral health coupled with inap- vention. However, many homes in rural and remote
propriate feeding behaviours such as prolonged on- areas do not enjoy ‘town water’ and so miss out on the
demand breastfeeding, particularly through the night advantages of water fluoridation. The other common
after 18 months of age, and putting a child to sleep source of fluoride comes in the form of toothpaste.
with a bottle, places an infant at high risk of develop- In Australia and New Zealand (and most parts of
ing ECC. Medical practitioners, paediatricians and Europe) there are two common strengths of fluoride
maternal child health nurses are all in a strategically toothpaste; most adult toothpastes contain around
good position to identify individuals at risk of devel- 1000 parts per million (ppm) fluoride, whereas child
oping ECC (Table 22.3.2). toothpastes contain lower concentrations of fluoride,
around 400 ppm. Early exposure to fluoridated tooth-
paste is very effective in preventing caries as the newly
Prevention of dental caries
erupted immature tooth surface is highly susceptible
Strategies to prevent dental caries should start as soon to the beneficial maturation effect of fluoride. The use
as the first primary teeth erupt (Table 22.3.3). of additional fluoride supplements (tablets or drops)

Table 22.3.2 Common risk factors for dental caries

Risk factor Influence

Fluoride exposure Exposure to fluoridated water source and the regular use of fluoridated toothpaste are two key
factors that reduce caries risk

Sugar exposure Infant feeding habits are very important, with frequency of exposure being most relevant. High risk
associated with prolonged bottle-feeding and on-demand night-time breast feeds (> 18 months of age)

Family oral health history Poor parental oral health places child at risk of decay as cariogenic bacteria can be transmitted to
infants from their primary caregiver (usually the mother)

Social and family practices Poor, Indigenous, ethnic and migrant groups have higher levels of dental disease

Medical history Medically compromised children are at greater risk of dental decay, the impact of which on their
general health can be considerable. They are also less likely to receive appropriate treatment

Saliva flow Children with reduced salivary flow are at significant risk of developing caries as the acids in the
oral cavity cannot be diluted, buffered and cleared effectively. Examples of such children are those
taking specific medications for management of asthma, those with ADHD, childhood cancer, or
with certain head and neck tumours managed by radiotherapy

802 ADHD, attention-deficit/hyperactivity disorder.

 Teeth and oral cavity disorders 22.3
Table 22.3.3 Summary of caries preventive strategies

Factor Strategy

Fluoride A smear of child's fluoridated toothpaste should be applied regularly to an infant's teeth within
6 months of their eruption
Teeth should be brushed twice a day with nothing to eat or drink after the night-time brushing
Parents should supervise tooth-brushing until around 8 years of age
The use of additional fluoride supplements (tablets or drops) is no longer recommended due to the risk
of unsupervised ingestion

Diet Reduce the frequency of intake of sweetened foods and drinks, particularly between mealtimes
Avoid on-demand feeding through the night-time
Limit sugary snacks to meal times when salivary flow is optimal
Avoid sugary snacks close to bedtime
Increase water intake for hydration

Dental attendance Parents should be encouraged to take their infant to a dental professional within 6 months of the
eruption of their first teeth
Regular monitoring by a dental professional should continue into adulthood

Remineralizing products Products containing fluoride concentrates and calcium phosphopeptides are available through dental
practitioners. These promote remineralization of early carious lesions (e.g. Tooth Mousse®; GC
Corporation, Itabashi-ku, Tokyo, Japan)

is no longer recommended in Australia and New limiting sugary snacks/drinks to meal times, when sali-
Zealand, but varies around the world. Advice regard- vary flow is optimal, will optimize the buffering capac-
ing the appropriate use of fluoride prescription should ity of the saliva.
be sought from the local paediatric dentists and/or
Remineralization products
professional bodies.
Recently new products have been developed that contain
Oral hygiene measures casein phosphopeptide–amorphous calcium phosphate
In comparison to early and effective ­tooth-brushing (CPP-ACP). These products, as either a chewing gum
with fluoridated toothpaste, other oral hygiene mea- (Recaldent®; Cadbury Japan Limited, Adams Division)
sures are relatively less important for children. or a topical cream (Tooth Mousse®; GC Corporation,
Flossing, although useful for adults in the prevention Itabashi-ku, Tokyo, Japan), act as a reservoir for cal-
and control of both caries and periodontal disease, is cium phosphate, maintaining a state of supersaturation
difficult for children as it requires a high level of man- around the tooth with respect to calcium and phos-
ual dexterity. In those at high risk of caries, parents phate, thereby depressing the demineralization of tooth
can be shown how to floss between the primary molars tissue and promoting its remineralization. These prod-
after tooth-brushing with a fluoridated toothpaste, ucts can be used in conjunction with fluoride products
which will optimize the topical effects of fluoride. such as toothpaste, as they act synergistically to pro-
Mouth rinses may be a useful adjunct to routine care mote remineralization in the oral cavity. With the excep-
and are starting to gain a foothold in preventive den- tion of individuals with milk protein allergy, they are
tistry. However, at this stage they are best prescribed safe and effective. These products are currently available
by a dental professional and should not be viewed as only through dental surgery outlets, but are being used
an alternative to effective tooth-brushing. increasingly, particularly in individuals who continue
to develop caries despite optimal fluoride exposure.
Diet
In addition to encouraging optimal exposure to fluo-
ride, providing advice on healthy dietary practices that
Fluorosis
reduce the length of time that the saliva pH is below
the threshold 5.5 for enamel demineralization will also High serum levels of fluoride can produce a develop-
reduce the risk of caries development and progression. mental abnormality of enamel maturation known as
At all ages, diet modification to reduce the frequency fluorosis. Mild cases appear clinically as a white fleck-
of intake of both sugary foods and drinks is impor- ing or linear opacity of the enamel; more severe cases
tant. In particular, children put to bed and allowed to can have quite marked brown mottling. When recom-
sleep with a nursing bottle are likely to develop decay. mending fluoride strategies, the risks of developing
803
As children get older, encouraging water drinking and fluorosis (which potentially can create minor ­aesthetic
 22.3 ENT, EYE AND DENTAL DISORDERS

challenges in the permanent dentition) need to be

weighed against the risk of developing dental car- Clinical example
ies and all its potential sequelae. Discussion between
a paediatric dentist and the family is important in Jimmy, aged 3 years and 6 months, presented
with his mother because he had been crying
order to optimize prevention but reduce unwanted
when he ate or drank at the daycare centre.
side-effects. Recently his mother had noticed that he
sometimes woke up at night crying because of the pain in
his mouth. On being asked about his health, his mother
Dental abscesses
reported that he had seen a heart doctor at the children's
If dental caries is undiagnosed, untreated or treated hospital because he had a ‘hole in the heart’. She also
inappropriately, it can cause pain, systemic infection acknowledged that Jimmy still took a bottle of milk to bed
at night and that she sometimes put a little of his favourite
and abscesses. In the primary dentition an abscess can
chocolate powder in the milk to help him sleep.
be superficial, pointing beneath the gum usually on the Oral examination confirmed the presence of early childhood
cheek side of the tooth, and often relatively unpainful. dental caries with extensive decay involving the incisor teeth in
Alternatively and more seriously, an infection from both upper and lower jaws as well as the upper first primary
a necrosed tooth can spread into the deeper soft tis- molars, with some white areas of early enamel demineralization
sue planes and lymph nodes (Fig. 22.3.2). Cellulitis on the recently erupted second molars. In addition, his gums
is accompanied by systemic illness, high fever, facial were slightly inflamed and there were widespread deposits
of white furry plaque over his teeth and gums.
swelling and often limited mouth opening. In the
From the history of spontaneous pain, particularly at night,
upper jaw this can cause closure of the eye, whereas in it was apparent that the decay was well advanced and
the lower jaw it can compromise the airway as the sub- involved the nerve (pulp) of at least some of the teeth. The
mandibular and sublingual spaces become involved. In presence of generalized plaque deposits around the teeth
most cases a simple clinical examination will identify and gums suggested that tooth-brushing did not happen
the affected tooth; however, an orthopantomogram is regularly, if at all. In addition to posing a risk of bacteraemia
useful to confirm the diagnosis. Once the infection has (and hence for endocarditis in Jimmy who had a pre-existing
cardiac history), the presence of gingivitis also suggested
reached this stage, extraction as soon as possible (often
that he was not receiving the optimal benefits to be gained
under general anaesthesia) is usually the best course from regular topical fluoride exposure.
of action. Management was in two stages. First, the immediate
relief of pain and elimination of infection was performed by
the removal of all pulpally involved teeth and the restoration
Practical point of non-pulpally involved teeth; this was completed under
general anaesthesia. Prophylactic antibiotic cover is no
longer recommended for this child, but proactive preventive
• When presented with any facial swelling, consider a advice was required and provided at ongoing outpatient
dental cause as part of the differential diagnosis. appointments. This advice included recommending (and
demonstrating) tooth-brushing using an adult fluoridated
toothpaste (1000 ppm). This should be done by Jimmy's parents
twice a day, and at the same time to stop immediately the
night-time use of the infant feeding bottle. Finally, information
was provided to Jimmy's mother on the particular importance
of good oral health for people with congenital heart disease.

Oral health for children who have other health-care

needs is often not high on the list of parental priorities.
Close cooperation is necessary between doctors, pae-
diatricians and paediatric dentists to assist parents of
such children in appreciating the importance of oral
health for their child and to provide advice on how
to minimize potential future problems. It is never too
early to start to talk about teeth.

Fig. 22.3.2 An example of the potential sequelae following the

failure to treat a carious lower primary molar in a 4-year-old boy. Trauma
The necrotic tooth has become infected and resulted in cellulitis,
pus tracking extraorally, and systemic illness. Treatment includes Almost a third of children will experience dental
intravenous antibiotics, extraction of the tooth and drainage of injury to either their primary or permanent teeth. The
804
the abscess. peak ages are between 18 months and 3 years when
 Teeth and oral cavity disorders 22.3
infants are learning to walk and prone to falling, and Injury to the primary teeth can, in some instances,
again in early teens when they (boys in particular) are affect the development of the underlying permanent
participating in more adventurous games and sports. successor. Primary teeth are never re-implanted as
Most injuries in children are accidental in nature as this too can have a detrimental effect on the perma-
opposed to adults, where fights and traffic accidents nent successor; however, parents can be reassured that
are not uncommon. early loss of primary incisors has no lasting effect on
Dental injuries can affect the teeth, bone and soft speech, function or appearance.
tissues, or any combination of the three, with inju-
ries to the teeth and lacerations of the tongue and lips
Permanent dentition
being the most common. Jaw fractures are relatively
uncommon in children and not covered further here. Injuries to the permanent dentition range from a small
tooth fracture to complete loss (avulsion) of multiple
teeth and significant soft tissue lacerations. Injuries
Primary dentition
to the permanent dentition are often missed or incor-
Injuries to the primary dentition most commonly rectly diagnosed. Appropriate emergency management
involve displacement of the upper primary incisors of traumatized teeth impacts significantly on the ulti-
from their sockets with or without some soft tissue mate outcome of the injury.
lacerations (Fig. 22.3.3). In general, infants are very
resilient and parents are often more stressed than the
affected child.
Practical points

Practical points • All injuries should be carefully examined intraorally.

• Ideally an avulsed permanent tooth should be replanted
immediately, if possible.
• Check that there are no other signs of injury such as limb
fractures or head injury. • Irrespective of the degree of seriousness of the injury,
trauma to the permanent dentition should be referred
• Refer to an appropriate dental professional.
promptly (by telephone) to a dental professional.
• If the displacement is mild and not affecting function
(i.e. the child can bring their teeth together), regular
monitoring may be appropriate.
• If the tooth is more severely displaced, it should be
removed, under either local or general anaesthesia Unless replaced immediately, the long-term progno-
depending on the age of the child and nature of the injury. sis for an avulsed permanent tooth is guarded. Given
• An avulsed primary tooth is never repositioned. that this rarely occurs, the avulsed tooth should be
handled as little as possible and stored in milk. The
child should be referred by telephone immediately to
an emergency dental provider. Direct contact with the
dentist will ensure that they are prepared to accept
the child for treatment, hence avoiding further delays.
Often this will be a paediatric dentist or hospital-based
dental unit.
Dental management of displaced teeth usually
involves repositioning accompanied by placement of
a thin wire splint bonded to the affected and some
unaffected teeth to stabilize the injury for several
days. In some cases further endodontic (root canal)
therapy may be required and treatment can continue
for many years after the initial injury. In many cases
the prognosis for retaining traumatized teeth in the
long term is very good. However, avulsion and severe
intrusion injuries, particularly those with additional
Fig. 22.3.3 Tooth displacement injuries such as this occur bony fractures, do not have a good prognosis in the
commonly in the primary dentition. These teeth create long term. The aim of treatment in these cases is
interference when this child tries to close his teeth together. In
the primary dentition one does not try to reposition the teeth as
often to retain a child's natural teeth through adoles-
this may cause further damage to the permanent successor, the cence so that once growth is complete the permanent
crowns of which are located close to the apices of the primary prosthetic replacement of the compromised teeth can
805
tooth roots. Removal of these teeth is the best treatment. be considered.
 22.3 ENT, EYE AND DENTAL DISORDERS

Non-accidental injury (child abuse)

Table 22.3.4 Potential sources of acid responsible for
Orofacial trauma is commonly reported in cases of dental erosion
child abuse. Bruising and laceration of lips and alve-
Extrinsic Intrinsic
olar mucosa, damage to teeth, alveolar bone frac-
tures, finger and bite marks on face and neck are Dietary Gastro-oesophageal reflux
all frequent signs of child abuse. These result from • citrus fruits and juice • infancy
slapping, punching, hand over mouth, forcible feed- • carbonated drinks (including • early childhood
‘diet’ products) Cyclical vomiting
ing with spoon or fork, and forcible intrusion or
• sports drinks Eating disorders
removal of a feeding bottle, dummy or toy from • wine • bulimia nervosa
the mouth. Tears to the upper midline fraenum in Environmental/occupational Rumination
­pre-ambulatory infants is highly suspicious, and oral • swimming (poorly regulated
bruising and palatal contusion can be seen in cases pool water)
of sexual abuse. Oral signs should not be neglected • nutrition regimes for elite
when considering the possibility of child abuse, and athletes
Lifestyle
an intraoral examination should form part of routine
• recreational drugs
surveillance. Medications
• topical effect – aspirin,
vitamin C, phenylketonuria
supplements, nebulized
Dental erosion asthma medications without
spacer
Dental erosion is defined as a chronic localized loss • systemic effect on
of dental hard tissue, chemically etched away from the ­saliva – asthma, ADHD,
tooth surface without bacterial involvement (which ­antidepressants,
differentiates it from caries, which is bacterial in aeti- ­anticholinergic medications
• ethanol-containing
ology). Many young children show wear of their pri-
­mouthwashes
mary incisors but more worrying is the fact that almost
one-third of adolescents have significant wear of their ADHD, attention-deficit/hyperactivity disorder.
permanent teeth as well. The appearance of erosive
tooth wear is quite characteristic, but challenging for
most non-dental professionals to diagnose. There is a
general loss of lustre from the surface enamel, thin-
The role of the medical practitioner in managing
ning and chipping of the upper incisors, and there
dental erosion is to be aware of the risk factors, to pro-
may be smooth exposed dentine, pulpal exposure and
vide generic preventive advice (Table 22.3.5) and to
sensitivity.
refer the child to a dentist for ongoing monitoring. If
As with dental caries, the aetiology is multifac-
caught early enough, little active dental treatment will
torial but is associated with an increased exposure
be required; however, if significant tooth tissue loss
of the teeth to acid (Table 22.3.4). These non-bac-
occurs in the young permanent dentition, pain and
terial acids may be extrinsic (essentially dietary) or
aesthetic considerations may mean that restorative
intrinsic (from the gastric tract). Children with dys-
treatment is required.
phagia and other conditions associated with abnor-
mal muscle tone tend to have more gastric reflux
and are more likely to have dental erosion. In addi-
tion, children with muscle spasticity tend to grind
their teeth which, superimposed upon the softening Acquired disorders of the soft
caused by acidic erosion, can lead to rapid tooth tissues
tissue loss.
Bleeding gums
Gingivitis is the most common cause of bleeding
gums. Gingivitis is a non-specific inflammation of
Practical point the gingival tissues (gums) that reflects the bacterial
challenge to the host when dental plaque accumu-
lates. Dental plaque is a complex biofilm that starts to
• Any child with a history of gastric reflux should be counselled
as to the potential for erosive tooth tissue loss, and advised accumulate around the teeth immediately after tooth-
806 to seek dental review. brushing. It consists of 70% microorganisms and 30%
food debris, and if brushing is ineffective the gums
 Teeth and oral cavity disorders 22.3
Table 22.3.5 Strategies to prevent dental erosion

Factor Strategy

Reducing acid exposure Inform patients of types of food and drink that have greatest erosive potential
Consumption of still/non-carbonated drinks as an alternative
Limiting the intake of acidic foods/drinks to mealtimes
Advocate consumption of a neutral food immediately after a meal (e.g. cheese)
Rinsing mouth out after acid exposure (i.e. after episode of vomiting), but delay brushing
teeth immediately after the exposure as this increases wear of tooth tissue

Optimizing salivary function Increased water intake

Use of water bottles in schoolbags
Advise use of sugar-free chewing gum to enhance salivary flow

Enhancing resistance to erosion Suitable products include: neutral fluoride mouthwashes, Recaldent® chewing gum and
Tooth Mousse®

organize a subclinical inflammatory response within Danlos syndrome) and immunocompromised individ-
2 days that will become clinically apparent by 10 days. uals (e.g. those with cyclic neutropenia), children and
The characteristic signs of chronic gingivitis include adolescents do not experience periodontal disease.
red inflamed gums that bleed when brushed and that
can deteriorate to a point where there is bleeding on
Oral ulceration
eating and, in some cases, even spontaneous bleeding
(Fig. 22.3.4). Gingivitis is easily reversed with appro- Ulceration of the oral cavity is often a sign of under-
priate oral hygiene practices to remove the plaque. lying systemic disease and, if present, treatment of
If certain anaerobic organisms predominate in the the oral lesions will be essentially symptomatic whilst
subgingival biofilm, gingivitis may progress to perio­ the underlying disorder is attended to appropriately.
dontitis in which the inflammatory mediators and A careful history and examination should be com-
cytokines destroy the underlying supporting tissues. pleted in order to assist with the diagnosis.
This can lead to significant bone loss around the teeth,
which become mobile and may ultimately be lost. There
is a high degree of individual susceptibility to peri-
odontal disease, with certain subgroups with a com- Practical points
promised immune response being particularly prone
to destructive periodontal disease (e.g. individuals
• Take a good history of:
with Down syndrome). Fortunately, with the exception • general health status including appetite, weight loss, fever
of some rare connective tissue disorders (e.g. Ehlers– • the ulcers, including frequency, position, duration, stimuli.
• Complete a thorough examination of:
• general health, including appearance, weight,
psychological state, signs of inflammatory bowel disease
• oral cavity, including location, size, appearance, obvious
traumatic aetiology.
• Useful special tests – full blood screen, full blood count
(FBC), erythrocyte sedimentation rate (ESR), iron, serum B12,
folate, as well as markers for inflammatory bowel disease.

Infections
The most common oral infection seen in children is
primary herpetic gingivostomatitis (Fig. 22.3.5). The
signs are of a systemic viral infection with fever, las-
situde, lack of appetite and very sore oral cavity with
Fig. 22.3.4 The appearance of plaque-induced gingivitis. Note
the build-up of soft white bacterial plaque associated particularly with
characteristic painful ulcerated gingival tissues as well
the gingival margins. Good oral hygiene not only reduces the bacterial as occasionally on the tongue and buccal mucosa.
load but, if using fluoridated toothpaste, increases exposure of Other viral infections can involve the oral cavity includ- 807
the underlying enamel to the protective benefits of fluoride. ing hand, foot and mouth disease, and chickenpox.
 22.3 ENT, EYE AND DENTAL DISORDERS

to form an ulcer with a crater-form base that heals

slowly over 8–10 days. Aphthous ulcers may be of
minor or major type and may be associated with
stress; however, they may also be associated with an
underlying iron or folate deficiency.
Treatment
Aphthous ulcers are difficult to manage and rarely is
treatment totally successful. Chlorhexidine gluconate
or a tetracycline–nystatin combination mouth rinse
along with diligent tooth-brushing help relieve pain
and control secondary infection. Other strategies for
aphthae include topical anaesthetics, systemic anal-
gesics, and topical anti-inflammatories including ste-
roids. However, these medications, at best, will reduce
Fig. 22.3.5 The early appearance of primary herpetic the duration of the ulcer experience rather than cure it.
gingivostomatitis. The gums become fiery-red, covered with
fluid-filled blisters that later burst and ulcerate. Typically the
Haematological causes
child presents with fever and dehydration requiring supportive
medical care. Children suffering from an underlying haematological
disorder, including neutropenia and leukaemia, can
Treatment experience oral ulceration. Children with leukaemia
Treatment is symptomatic, involving fluids and analge- may present initially with bleeding gums in the absence
sia and encouraging the parents to maintain oral hygiene of poor oral hygiene. Those with cyclic neutropenia, in
to prevent secondary bacterial infection of the ulcers. particular, experience cyclical bouts of severe gingivi-
tis accompanied by significant periodontal bone loss,
resulting in premature loss of both primary and later
Trauma
permanent teeth. Children with this condition need
Single ulcers located in specific sites around the oral regular review and management by a paediatric den-
cavity can be caused by both physical and chemi- tist or periodontist in order to try to slow the process.
cal trauma. Use of a toothpick to relieve food pack-
ing between teeth can cause ulceration interdentally,
Gastrointestinal causes
and the placement of an aspirin tablet directly on to
the buccal gum in order to relieve toothache has been As the oral cavity is the start of the gastrointestinal
known to produce a nasty chemical ulcer. In most cases tract, it is common that disorders affecting the rest of
of traumatic ulcer, the aetiology will be relatively clear; the tract can present in the mouth. Individuals with
however, it is important to bear in mind the potential inflammatory bowel conditions such as Crohn's dis-
for self-inflicted injury. Particularly in instances of ease, coeliac disease and ulcerative colitis may experi-
apparently random and repeated episodes of traumatic ence oral ulceration. In addition, those with Crohn's
ulceration, there may be an associated condition involv- disease can have other significant oral manifestations,
ing insensitivity to pain such as Riley–Day syndrome. often described as orofacial granulomatosis, including:
• marked lip enlargement, together with enlargement
Treatment of the buccal mucosa
Treatment involves the elimination of the irritant, such
• alveolar mucosal erythematous granulomatosis in
as a fractured filling or poorly contoured orthodontic the anterior regions of the maxilla
appliance, or cessation of the injurious behaviour.
• large, linear ulceration in the buccal mucosa
posteriorly.
Aphthous ulcers These oral findings can occur on their own, or together
with anal fissuring, genital swelling and gastrointesti-
In many situations an obvious aetiology is not forth-
nal changes.
coming. These are referred to as aphthous ulcers.
Fortunately they are relatively uncommon in chil- Treatment
dren, as they are difficult to treat. They are non- If there are any concerns about gastric symptoms
infective, extremely painful ulcers, occurring most (e.g. weight loss, blood in the stools), the child should
commonly on the labial and buccal mucosa and be referred to a paediatrician (or paediatric gastro-
tongue borders. A prodromal burning sensation enterologist) and paediatric dentist for a combined
808
precedes breakdown of an initially white papule
­ evaluation.
 Teeth and oral cavity disorders 22.3
Dermatological causes problems are relatively simple to prevent and manage
if diagnosed early, close collaboration between the
Oral ulcers occur in many of the rarer dermatological
general health-care providers (medical practitioner,
conditions such as epidermolysis bullosa, pemphigus
paediatrician or nurse) and the dental care provider is
and pemphigoid. However, these conditions are usually
essential. Identifying an appropriate ‘dental home’ for
diagnosed from their more general manifestations
children with special health-care needs is important
rather than their oral symptoms.
so that these complex children have access to timely
and appropriate oral health care. Many general den-
tists are not comfortable managing children with spe-
Malignancy
cial health-care needs, whereas paediatric dentists are
Oral malignancy is rare in children; however, single, trained specifically in this area.
persistent, large ulcers that have no obvious traumatic
aetiology and are not associated with acute systemic
Medications
illness should be viewed with suspicion and referred
for investigation to a paediatric dentist/maxillofacial Many children with special health-care needs are on
surgeon. multiple medications for prolonged periods of time.
There is an increased risk of developing caries associ-
ated with the long-term use of sugar-based liquid med-
Gingival swellings
ications. As many of the common liquid medications
Swelling of the gingival tissues can be congenital or are ‘over-the-counter’ formulations, parents should be
acquired, although the former are relatively rare. warned to check that, where possible, they purchase a
Individuals with any of the mucopolysaccharidosis sugar-free brand of medications such as cough linctus
disorders may have very enlarged gums, often to the or analgesic.
extent that teeth fail to erupt or are ectopically dis- Given the high prevalence of asthma, particu-
placed. Similar disruption to the developing dentition larly in Australia and New Zealand, a suggested asso-
can occur in individuals with vascular anomalies, such ciation between asthma medication (particularly
as a lymphangioma, that may affect both soft and hard β2-agonist inhalers) and dental erosion/caries is rele-
tissues of the jaws. vant. This association appears to be more of a prob-
Of the acquired causes of gum enlargement, drugs lem in adults than in children, and one large study in
are most commonly implicated – most specifically the children showed no such association. There are theo­
anti-seizure medication, phenytoin, and the immuno- retical reasons why this might occur, for example:
suppressant cyclosporin A. The latter has been widely chronic ­mouth-breathing from associated allergic rhi-
used in organ transplant protocols, and in children has nitis ­leading to mouth dryness; a higher incidence of
caused significant aesthetic and psychological prob- gastro-oesophageal reflux, which may result in more
lems as the gums enlarge in an unsightly fashion and acid in the oral cavity; an acidic base to some nebu-
teeth are covered in excess gum tissue. The advent lizer solutions. The use of both spacers and oral rins-
of tacrolimus as an alternative to cyclosporin A has ing with water afterwards will minimize the potential
improved significantly the quality of life of these chil- oral health risks, which should not be viewed as a con-
dren by reducing not only the gum overgrowth but also traindication to positive asthma prevention.
the hirsutism. Most of the enlargement resolves once
the causative drug is stopped. Other more localized
Congenital heart disease
swelling of the gingival tissues includes giant cell gran-
uloma, histiocytosis and lymphoma, and, although Children with congenital heart defects (CHD) are pre-
rare, such swellings are of obvious clinical significance disposed to infective endocarditis (IE), which is associ-
and should be reviewed by a paediatric dentist. ated with high morbidity and mortality. Traditionally
attention has focused on the risk of developing IE fol-
lowing bacteraemia associated with dental treatment,
with the resultant implementation of aggressive pro-
Children with special health-care phylactic antibiotic regimens. However, the lack of
substantive evidence that preoperative antibiotics are
needs effective in preventing IE, coupled with the realiza-
Children with significant medical conditions, develop- tion that bacteraemia originating in the oral cavity
mental disabilities and craniofacial disorders face mul- occurs daily (resulting from chewing, tooth-brushing,
tiple health issues, amongst which is often an increased etc.), has led to a dramatic rethinking of the guidelines
risk of dental disease, coupled with barriers in access- for prophylactic antibiotic usage in individuals with
809
ing appropriate dental services. Given that many dental CHD; see the UK National Institute for Health and
 22.3 ENT, EYE AND DENTAL DISORDERS

Clinical Excellence (NICE) guidelines (http://guid-

ance.nice.org.uk/CG64). Practical points
Recommendations regarding antibiotic cover vary
widely around the world, and it is important that clear, • Every child with a special health-care need should have
concise and consistent information is provided to a regular dentist familiar with the implications of their
families regarding this issue. When taking their child medical history.
to a dental professional, parents should be provided • Good communication between paediatricians and paediatric
with written confirmation of the child's cardiac sta- dentists will optimize health outcomes for individuals and
their families.
tus together with a clear indication of the risk of IE
• The specific prescription of sugar-free alternatives should
and the need for prophylaxis endorsed by their car- be part of routine clinical practice.
diologist. This will facilitate the smooth provision of • Parents of children with a congenital heart defect should
appropriate dental care and minimize the unnecessary be provided with written confirmation of their child's
prescription of antibiotics. Educational resources exist cardiac status with respect to endocarditis.
for parents in most paediatric cardiology units; these • Standard protocols for prophylactic antibiotic cover should
should be reviewed regularly and informed by contem- be followed when a child with a significant congenital
heart defect requires any invasive dental procedure
porary evidence (http://www.rch.org.au/emplibrary/
(protocols can be accessed at: http://www.rch.org.au/
cardiology/dentalheart.pdf). Finally, irrespective of cardiology/health-info.cfm?doc_id=3482).
antibiotic regimen, emphasis should be placed on opti-
mizing the oral health of children with CHD and thus
reducing the need for dental intervention and minimiz-
ing the risk of additional exposure to infection.

810
Index

Note: Page numbers in italics refer to boxes, figures and tables.

A Acute bacterial tonsillitis 471–472, 472 Adolescent-focused interventions 85

Acute confusional migraine 627 Adoption 316
ABC (mnemonic) life support steps Acute disseminated encephalomyelitis Adrenal androgens 659
200–204, 524 (ADEM) 388, 410–411, 411 Adrenal insufficiency 712
ABCDE (mnemonic) primary assessment Acute gastroenteritis 715–719 Adrenaline 218, 431
steps 194–198, 195, 199 clinical features 716–717, 717 Adrenarche, premature 671
Abdomen complications 719 Adrenomyeloneuropathy (AMN) 325
examination 30, 32–33, 224, 337 dehydration 717, 717 Adulthood
imaging 242–245 electrolyte loss 717–718 disease 348
mass 243, 244 investigations 717 obesity 81
trauma 243, 245 management 717 transition to 27
Abdominal pain nutrition 719 Aedes aegypti 417–418
0-3 months 706 pharmacotherapy 719 Age, developmental
4-12 months 706–707 prevention 719 bone 660
childhood, acute 707–710, 710 rehydration guidelines 718, 718, 718, 719 consultation 24
imaging 242 Acute head trauma 237–238, 237 examination 34
recurrent (RAP) 710–711, 742 Acute kidney injury 652, 652 immune response at different 90
refugees 158 Acute leukaemia 569–572 immunodeficiency 440
right upper 246 Acute liver disease 747, 749–750, 752 neurodegenerative disorders 601
Abdominal wall defects 278, 377–379 Acute lymphoblastic leukaemia (ALL) 568, self-care 138
Aboriginal and Torres Strait Islanders 50–56 569–572, 570, 571 sleep duration 150
beliefs, health/illness 52–53 Acute myeloid leukaemia (AML) 568, 569, sudden unexpected death in infancy (SUDI)
defined 50 571–572, 571 126
health care/cultural safety 50–51 Acute myopathies 608 susceptibility to infection 90
history/disadvantage/health 53–54 Acute nephritis 649 viral pneumonia 502
kinship family 54–55, 54 Acute neuromuscular junction disorders 607 Ageing, features of 297–298
language/communication styles 55–56 Acute neuropathies 605–606 Ages and Stages Questionnaires (ASQ) 39
mortality 51–52 Acute otitis media (AOM) 473, 781–784 Age-specific risks, maternity 282, 282
population 51 Acute promyelocytic leukaemia (APML) 571, β2-Agonists, chronic asthma 487
specific infections 423, 424 572 AIRE gene 450
Abscesses Acute respiratory infections see Upper Airway
dental 804, 804 respiratory tract infections (URTIs) ABC steps 201–202, 201
intracranial 632 Acute rhinosinusitis (ARS) 785, 786 ABCDE steps 194, 199
perianal 272, 273 Acute sinusitis 472 abnormalities, structural 493–494
Absence epilepsy 585–586, 588 Acute sore throat 785–786 imaging 240–242
Absorptive surface 725 Acute viral bronchiolitis 503–504 lower abnormalities, congenital 506
Abuse see Child abuse Adenoidectomy 788 malacia 493–494
Acanthosis nigricans 81, 81, 694–695 Adenosine (A) 289 obstruction 358–360, 359, 788
Accessory navicular bone 254 Adenosine triphosphate (ATP) 230–231, 291, stenosis 494
Accommodative esotropia 792 324 Alagille syndrome 750–751, 751
Acetazolamide 633 Adenoviruses 392, 502–503 Alanine aminotransferase (ALT) 744, 746
Acetretin 286–287 Adherence 26, 693 Albendazole 420, 423
N-Acetylcysteine therapy 752 Adjunctive treatment 400 Albinism 776
Achondroplasia 310 Adolescence 130–140 Albumin 746
Acid suppression 739–740 adolescent idiopathic scoliosis 258, 258, Albuterol 431
Acidosis 259 Alcohol 285
lactic 300, 320–321, 321 burden of illness 131–132, 133 Alkaline phosphatase (ALP) 746
metabolic 230–231, 231, 320, 345, 524 chronic illness 137–140 Alkalosis 231, 231
see also Ketoacidosis clinical approach 134–137 Allergens 428
Acne 777 defined 130 identification 430, 430, 433
Acquired aplastic anaemia 546–547 development 130–131, 131, 170–171 triggers 433
Acquired hyperthyroidism 676–677 early 130 Allergen-specific IgE (ASE) 428, 430
Acquired hypothyroidism 673–675 examination 34 Allergic contact dermatitis 773–774, 773, 776
Acquired immune deficiency syndrome gynaecology 142–148 Allergic rhinitis 429
(AIDS) 20–21 health 18 Allergy
adolescence 131–132 jaundice 246 asthma 483, 510
global context 16, 18, 19 late 131 cough 510
see also Human immunodeficiency virus (HIV) medicolegal context 133–134 see also Atopy
Acquired melanocytic naevi 758–762 mid- 130–131 Alma Ata Declaration (1978) 19
Acquired red cell aplasia 547 nutrition 69 Alopecia 776–777
Actinomyces spp 503 obesity 78–82, 84–88 Alopecia areata 777
Activated charcoal 210 poisoning 209 Alport syndrome 650
Activated protein C (APC) 566, 566 pregnancy 147 Altered conscious state, imaging 238
Active immunity 89 psychiatric disorders 183, 187–191 Alternative/complementary therapies 181–182,
Acute angle-closure glaucoma 634 risk/protective factors 132, 133 599
Acute anterior horn cell disorders 604 Scheuermann's condition 260 Amblyopia 792
Acute appendicitis 242, 243, 707–709, 714 slipped capital femoral epiphysis 260, 260 Amenorrhoea
differential diagnosis 709, 709 transition to adult care 27 primary 143
Acute asthma 487, 487 see also Pubertal development variation secondary 144–145, 145 811
 INDEX

American Academy of Pediatrics 152 Anxiolytics 186–187 Atropine 213

Amino acids malabsorption 733–734 Aorta, coarctation 527, 530–531, 530 Attention difficulties 168, 179–182, 180
Aminophylline 487 Aortic stenosis 527, 530 Attention-deficit/hyperactivity disorder
Aminosalicylates 721 Apgar scores, newborn 331, 331 (ADHD) 13, 170, 174, 179–182
Amitriptyline 629, 631 Aphthous ulcers 808 co-morbidities 180, 690
Ammonia 746 Aplastic anaemia 542–548, 546 defined 179
Amoebiasis 419, 420 acquired 546–547 management 180–182
Amoxicillin 405, 537, 743 Apnoea 360 outcomes 182
Amoxicillin-clavulanic acid 501 of prematurity 342 prevention 182
Amphetamines 211 Appendicitis see Acute appendicitis sleep 150
Amphotericin 399 Aqueduct stenosis/atresia 620 Atypical antipsychotics 188
Anaemia 540–557 Arachnoid cysts 632 Atypical dysmenorrhoea 146
blood transfusion 556–557, 557 Arnold–Chiari malformation 617–618, 618, Atypical mycobacterial infection 505
clinical presentations 540–541, 541 620 Atypical naevi 758–759
defined 540, 541 Arteriovenous malformation 761 Auscultation 519–522, 519, 520
investigations 542, 543, 544, 545 Arthritis Australia New Zealand Food Standard
physiology 540 headaches 634 Code 64
prematurity 345 see also Chronic inflammatory arthritis; Australian Bureau of Statistics (ABS) 45
specific disease entities 542–556, 546 Juvenile idiopathic arthritis (JIA) 2005 Child Care Survey 4
Anal agenesis 337 Arthropod bites 770–771 Australian Childhood Immunisation Register
Anal fissure 272 Arthropod-borne encephalitis viruses 411–412 (ACIR) 13
Analgesia 338–339 Artificial insemination by donor (AID) 316 Australian Developmental Screening Test
Anaphylactoid purpura 565–566, 565 Ascariasis 420, 421 (ADST) 39
Anaphylaxis 436, 436 Ascaris spp 419, 421, 423 The Australian Immunisation Handbook
Ancylostoma duodenale 420, 421 Ascaris lumbricoides 419, 420 (NHMRC) 91, 92
Androgen therapy 546 Aseptic meningitis 410 Australian Indigenous Health InfoNet 53
Anencephaly 278, 613, 614 Aspartate aminotransferase (AST) 744, 746 Australian Institute of Family Studies 114
Aneurysms 632 Asperger's disorder 185 Australian Institute of Health and Welfare
Angelman syndrome 110 Aspergillus spp 451–452, 503, 514 (AIHW) 51–52
Angiotensin-converting enzyme (ACE) Asphyxia 330, 330 Australian National Asthma Council
inhibitors 525, 610–611, 654 accidental 125 488, 489
Anion gap 231 Aspiration 357 Australian National Child Protection
Ankles 598 lung disease 510–511 Framework 114, 114
rolling in 252, 253 pneumonia 492–493, 493 Australian paralysis tick 214
Ankyloglossia 338 Aspirin 628 Australian Red Cross Blood Service (ARCBS)
Anogenital warts 764 Asplenia 96 556, 557
Anorectal malformations 377, 378 Association, defined 303 Australia's Health 2010 (AIHW) 51
Anorexia nervosa 190 Asthma 429, 432–433, 482–490 Autistic spectrum disorders 184, 184
Antacids 739 acute 487, 487 Autoimmune haemolysis 555–556
Anterior fontanelle 336 age of onset 482 Autoimmune haemolytic anaemia 543
Anterior horn cell disorders 604–605 burden 482 Autoimmune hepatitis 752
acute 604 chronic 487–488 Autoimmune myasthenia gravis 607
chronic 604–605, 604 classification 484, 486 Autoimmune polyendocrinopathies
Anthrax 502 clinical features 484 (APECED) 450
Anthropometry 62, 84 cough/allergy 510 Automatisms 588
Antibiotics defined 482 Autosomal dominant inheritance 298, 299
ataxia telangectasia (AT) 450 examination 484, 485 Autosomal recessive inheritance 298, 298
bacterial meningitis 404, 405 history 484 AVPU (mnemonic) method 197
bone/joint infections 399 inhaler devices 490 Azathioprine 462, 721, 752
duration 399 investigations 485–487, 486
group B streptococcus (GBS) 373 management 487–489, 488, 489, 490
hyper-IgE syndrome 451 obesity 80, 80 B
infective endocarditis (IE) 537, 809–810 pathogenesis 482–483, 483
inflammatory bowel disease (IBD) 722 prognosis 490 Bacillus (Bacille) Calmette–Guérin (BCG)
urinary tract infection (UTI) 640, 642 Asylum seekers see Refugees vaccine 95, 161, 416
Antibody deficiencies 445–448 Ataxia telangectasia (AT) 450 Baclofen 598
Antibody-mediated haemolysis 555–556 Ataxic cerebral palsy 595 Bacterial disease
Anticipation, genetics 296 Atelectasis 354 bronchitis (PBB), protracted 511
Anticoagulation 566, 633 Athetosis 595 gastroenteritis 715–716
Anticonvulsants (antiepileptics) 588, 591–592 Atomoxetine 181 invasive 414–415
harmful effects 285–286 Atopic dermatitis 429, 431–432, 437, 758, overgrowth syndromes 725
neural tube defects 619 771–773 pneumonia, uses 502
pregnancy 286 Atopic eczema 771–773 tonsillitis, acute 471–472, 472
side-effects 591, 592 Atopy 426–438 Bacterial meningitis 402–410
Antidiuretic hormone (ADH) 223–224, assessment 427, 429 aetiology 403
227–228, 233–234 burden of disease 426 antibiotics 404, 405
Antidotes 211, 211 complications 434–438 cerebral imaging 407
Antiepileptics see Anticonvulsants defined 426 chemoprophylaxis 408
Antifungal therapy 450 examination 426–427, 429 clinical presentation 403–404, 404
Antihistamines 434 history 426–427, 428 complications 406–407
Antipsychotics 188 immunodeficiency 439 diagnosis 404, 405
Antiretroviral therapy (ART) 416 investigations 428, 430 environment 402
Antithrombin 566, 566 management 428–430, 430, 431 epidemiology 402
α1-Antitrypsin deficiency 496 pathogenesis 426, 427 fluid replacement 233–234, 233
Anti-tumour necrosis factor (TNF)-α 721–722 prevalence 426, 427 genetics 402
Antivenom 217–218 prevention 428 outcome 407
Ants 214 specific disorders 430–434 pathogenesis 403, 403
Anus 272 Atrial septal defect (ASD) 527, 528, 528 polysaccharide capsule 402
Anxiety disorders 176–177 Atrioventricular septal defect (AVSD) prevention 407–408
812 middle childhood 186–187 528–529, 529 recurrent 410
 INDEX

Bacterial meningitis (Continued) Birthdates 164 Breath-holding attacks 589–590

risk factors 403 Birthmarks 758–762 Breathing 199
special circumstances 408–409 Biting 169 ABC steps 202–203, 202
treatment 406 Bladder ABCDE steps 194–196, 195, 199
tuberculous 405, 409 abnormalities 645, 646 efficacy of 196
Bailey scale 40 neuropathic 617 effort of 195–196, 196
Balanitis 266 Blantyre Coma Score 417 inadequacy effects 196
Balanitis xerotica obliterans (BXO) 266, Bleeding disorders 558–567 noisy/obstructive 788–789, 789
267–268 coagulation disorders 561–565, 563, 566 periodic 342
Ballard score 338 diagnosis 558–560 problems see Respiratory distress
Balloon atrial septostomy 534 gums 558, 806–807, 807 see also Respiratory system
Bariatric surgery 87 history 558–559 British Thoracic Society 488, 489
Barium oesophagraphy (‘barium swallow’) investigations 560, 560 Brodie abscess 393
737 physical examination 559 Bronchi 781
‘Barker’ hypothesis, nutrition in utero 63 platelet disorders 560–561, 561 Bronchiectasis 511–512, 511
Barlow test 256, 256 vascular defects 565–566 Bronchiolitis obliterans 493, 493
Barmah Forest virus 423 BLES (bovine lipid extract surfactant) 353 Bronchitis (PBB), protracted bacterial 511
Battered baby syndrome 113 Blistering disorders 776 Bronchodilators 487
Becker muscular dystrophy 611 neonates 756–757 Bronchomalacia 493–494
Beckwith–Weidemann syndrome 359–360 Blood film, examination 542, 543 Bronchopulmonary dysplasia (BPD) 492
Beclomethasone 431 Blood gas monitoring 353 Brucella spp 502
Bees 214 Blood loss, anaemia 556 Bruising 117
Behaviour problems 185–186 Blood pressure 518–519, 519 BTK gene deficiency 445–447
associations, obesity 82–83 Blood transfusion 556–557, 557 Budesonide 431
consultation 30 Bloody diarrhoea 725 Bulimia nervosa 190
health 13–14 ‘Blueberry muffin’ rash 366 Bullous ichthyosis 757
history 28 Blue-ringed octopus 214 Bullous impetigo 756, 757, 766
management 181, 181 ‘Bobath’ therapy 599 Bullying 170
metabolic causes 323 Body fluid composition 222–224, 223, 223 Burden of disease 10–12, 11
obesity 83, 85, 86 Body lice 770 Burkholderia cepacia
sleep problems 149–150, 151 Body mass index (BMI) 62, 75, 76, 77 cystic fibrosis (CF) 514
suicidal 176, 176 Body water distribution 223 pneumonia 502
Behaviours, health 13–14 Bogalusa Heart Study 80 Burkholderia pseudomallei 423
Beliefs, health/illness 52–53 Bohn nodules 800 Burns 100, 232–233
Benign focal epilepsies of childhood 586–587, Boils 767
586, 588 Bone
Benign occipital epilepsy 586 age 660 C
Benign rolandic epilepsy (benign childhood marrow aspirate 570, 570, 571, 571
epilepsy with centrotemporal spikes) mineral disorders 696–703 Caesarean sections 334
586, 586 osteosarcoma (OS) 577–578 Café-au-lait spots 759
Benzimidazoles 423 scan 397 Calcium 696, 697, 698
Benzodiazepines Bone/joint infections 393–401, 424 channel blockers 211
antidotes 211 clinical presentation 394–395 malabsorption 733–734
bipolar disorder (BD) 188 diagnosis 395–398 Campylobacter spp 459
focal seizures 588 differential diagnosis 395 Campylobacter jejuni 447, 605–606, 715, 719
generalized tonic-clonic seizures microbiology 393–394 Campylobacter pylori see Helicobacter pylori
588 pathogenesis 393, 394 Cancer 568–580
myotonic, atonic, tonic seizures 588 prognosis 400 acute leukaemia 569–572
schizophrenia 189 spinal infection 400 aetiology 568, 569
Beta cells, autoimmune destruction 687 surgical management 399–400 brain/central nervous system tumours
Beta-blockers 211 treatment 399–400 572–574, 573, 573
Betamethasone (Diprosone) 142 Bone-marrow transplantation 569 incidence 568, 569
Bicarbonate 230–231, 232 anaemia 445, 546, 546 inflammatory bowel disease (IBD) 722
‘Bicycle training wheels’ metaphor 135 chronic granulomatous disease (CGD) 452 lymphoma 574–577
Bile acids 746 vaccines 96 management 568–569
Bile salt 725 Wiskott–Aldrich syndrome (WAS) 450 palliative care 580
Bilharzia (schistosomiasis) 161, 419–421, Bordetella pertussis 504 rare tumours 579
420 pneumonia 502 sarcomas 577–579
Biliary dysfunction 746 Borrelia spp 459 therapy effects 579
Bilirubin Botulinum antitoxin 607 treatment 569
conjugated 746 Botulinum toxin A 598 Candida spp 450, 451–452, 503, 756
encephalopathy 350–351 Bow legs 252, 253 Candida albicans 536, 785
synthesis 348, 349 Bowel Candidiasis, congenital 758
Binet scale 107 action, newborn 339 Capillary malformations 761
Biological considerations, refugees 163 neuropathic 617 Capillary naevi 335
Biological drugs 721–722 obstruction 711 Capital femoral epiphysis, slipped 260, 260
Biotin deficiency 775 see also Inflammatory bowel disease (IBD) Caput 335
Bipolar disorder (BD) 188 Box jellyfish sting 214, 219–220 Carbamates 211
Birth 167 Brain Carbamazepine
attendants 331 malformations, metabolic causes 323 epilepsy 587–588, 589
weight 12, 341, 594–595 structural abnormalities 588–589, 588 focal seizures 588
Birth defects 276–279 tumours 572–574, 573, 573 generalized tonic-clonic seizures 588
causes 276, 277 Branchial remnants 274 pregnancy 286
diagnosis 278 Breast milk 71, 349, 350 seizures 592
frequency 277–278, 278 Breastfeeding 60, 63–64, 63, 129, 167 Carbohydrates 65, 67
genetics 276–277 common problems 64 malabsorption 730–731
multiple 278 initiation 64 Carbon monoxide 211
prevention 279 Breasts Cardiac problems
registers 278–279 development, asymmetrical 671 arrhythmias 125, 323
structural types 276 examination 30 cancer therapy 579
813
 INDEX

Cardiac problems (Continued) Child abuse (Continued) Chronic immune thrombocytopenic

catheterization 522–524 inter-agency child protection 115–116, purpura 561
failure see Heart failure 120 Chronic inflammatory arthritis 453, 454
impulse, palpation 519 mandatory reporting 114 associated disorders 459
pain, imaging 240 overview 115 frequency 453
prematurity 342–343 prevalence 115 investigations 456, 457
wheezing 494–495, 494 see also Physical abuse symptoms 453
Cardiology imaging 240 Child Care Survey (ABS 2005) 4 Chronic inflammatory demyelinating
Cardiomyopathy 323, 535–536 Child Growth Standards (WHO) 69 peripheral neuropathy (CIDP) 606
Cardiovascular system Child health 4–5 Chronic kidney disease 652–653
complication, obesity 80, 80, 81 descriptors 5, 5 Chronic liver disease 744–748, 750–751, 750,
examination 32 determinants 5, 6 752–753
Carotid bruit 521 factors influencing 4–5 laboratory patterns 744–746
Cascade testing 315 inequity 6–7, 8, 15–16, 39, 47 symptom patterns 745, 746–748, 747
Cataracts 323, 336, 796 professionals, global health 21, 21 Chronic lung disease (CLD) 346, 597
Cauda equina symptomatology 238 Childcare 3–4 neonatal 358
Cefotaxime 399, 405 Child-focused approach 106 Chronic mucocutaneous candidiasis (CMC)
Ceftazidime 399, 423 Childhood 450
Ceftriaxone 399 abdominal pain 707–710, 710 Chronic myeloid leukaemia (CML) 569, 570
Centers for Disease Control and Prevention autoimmune haemolysis 555–556 Chronic myopathies 608–611
(USA) 95 bacterial meningitis 403 Chronic neuromuscular junction disorders
Central apnoea 362 bleeding 558 607
Central Australia 7 chronic bullous disease 776 Chronic neuropathies 606–607
Central cyanosis 352 developmental approaches 85 Chronic otitis media with effusion (COME)
Central hypoventilation 153 early see Early childhood 782–784
Central nervous system (CNS) growth 659 Chronic pain disorders 465, 465
examination 33 gynaecology 141–142 Chronic pancreatitis 728
tumours 572–574, 573 inborn errors of metabolism (IEM) 318 Chronic recurrent multifocal osteomyelitis
Central pain, imaging 240 liver disease 751–753, 752 (CRMO) 395, 464, 464
Centre Link 48–49 middle see Middle childhood Chronic rhinosinusitis (CRS) 785, 787
Cephalhaematoma 335 nutritional concerns 68–69 Churg–Strauss syndrome 496
Cerebral imaging 407 obesity 78–82, 84–88 Ciclosporin 461, 462, 722
Cerebral oedema 234, 406 referral 414 Circulation
Cerebral palsy (CP) 593–599 six diseases of 382, 383 ABC steps 203–204, 203
aetiology 593–595, 594 skeletal injuries 260–263 newborn 328, 329
associated disabilities 596–597 vomiting 713–714 poisoning 211
classification 595–596 wheezing disorders 495–496, 496 shock 406
examination/investigation 596 see also Adolescence support 524
life expectancy 599 Childhood absence epilepsy 585 Circulation ABCDE steps 195, 196–197, 199
management 597–599 Childhood sensoneural hearing loss (SNHL) assessment 196–197
presentation 596 364 inadequacy effects 197
prevalence 593, 594 Childless lifestyle 316–317 neurological failure 198
Cerebrospinal fluid (CSF) Children's Courts 113 Circumcision 267–268, 337
encephalitis 411 Chlamydia spp 133 bleeding 558
meningitis 404, 405 Chlamydia pneumoniae 495–496 Citrobacter spp 502
seizures 322 Chlamydia trachomatis 370–371 Clarithromycin 743
Cervical spine 99 Chloride 232 Clavicle fractures 261, 337
Cestodes 420 Choledochal cyst 246, 246 Cleft lips 278, 336
Cetirizine 431 Cholestasis 746 Cleft palate 278, 336
CFTR gene 512, 728 Chondromalacia patellae 259–260 Climate change 19
CHALICE (Children's Head injury Chorea 595 Clinical case management 414, 414
ALgorithm for the prediction of Chorionic villus sampling (CVS) 282, 282, Clinical consultation 24–35
Important Clinical Events) 237 284 history-taking 26–29
Charcoal, activated 210 Choroid plexus papilloma 620 note-taking 34–35
Charcot–Leyden crystals 421 Chromosome disorders 306–309, 663–664, as part of therapy 35
Charcot–Marie–Tooth disease 603, 606–607 664 physical examination 29–34, 30
CHARGE association/syndrome 303 22q11.2 deletions 450 planning 24–26
CHD7 gene 303 numerical 306–307 Clinical Practice Guidelines for
Chemical burns, eyes 794 structural 307–309 Adolescent and Youth Depression
Chemotherapy 569 Chromosomes 289, 290–291 (Australia) 187
Ewing sarcoma 578 Chronic anterior horn cell disorders 604–605, Clonazepam 592
Hodgkin disease 575 604 Clonidine 629
lymphoma 574 Chronic arthritis, systemic juvenile 763, 797 Clostridium botulinum 607
Wilm's tumour (nephroblastoma) 577 Chronic asthma 487–488 Clostridium difficile 715
Cherry red spots 323 Chronic bullous disease of childhood 776 Clostridium perfringens 555
Chest Chronic cough 507 Cluster headaches 634
compressions 333 diagnosis/management 507–509, 508, 509, Coagulation disorders 561–565, 563, 566, 758
examination 30, 224, 336–337 509 clotting, abnormal 566
trauma 241 pathophysiology 507 Coarctation of aorta 527, 530–531, 530
Chest wall anomalies, congenital 506 Chronic daily headache (CDH) 630–631 Coccidiomycosis spp, fungal pneumonia 503
Chest X-rays Chronic diarrhoea 244 Cochrane database 628
heart disease 522, 524 differential diagnosis 725 Cochrane reviews 406, 472, 473
respiratory distress 353 malabsorption 725, 726–732, 727 ‘Cocktail party syndrome’ 622
‘Chewing reflex’ 68 Chronic granulomatous disease (CGD) Codman's triangle 578
Chickenpox see Varicella-zoster virus (VZV) 451–452, 451 Coeliac disease (gluten enteropathy) 729, 729,
Child abuse 113–122, 133 Chronic haemolytic anaemia 548 730
clinical management 116–121 Chronic health conditions 133 Cognitive-behavioural therapy (CBT) 186–187,
current concepts 113–114, 114 adolescence 137–140 190–191
health professionals and 122 growth 663 Colchicine 213
814 injuries 261 nutrition 72 Colobomas 797
 INDEX

Combined screening 281 Connective tissue disorders (Continued) Cultural factors

Combined T- and B-cell immunodeficiency systemic lupus erythematosus (SLE) competency 58
448–449 459–460 contact 58–59
Common cold 468, 469 undifferentiated 463 indigenous see Aboriginal and Torres Strait
Common variable immunodeficiency (CVID) vasculitis syndromes 463, 463, 463 Islanders; Maori people
441, 445, 447 Conscious level 197, 197 safety 50–51
Commonwealth Department of Health and altered, imaging 238 Curosurf 353
Ageing 95 decreased 318–319 Cushing syndrome 566
growth hormone guidelines 667 Consent 134 Cutaneous herpes simplex
Communication 55–56 Constipation 178, 709, 709 primary 765, 765
Community factors 166 anal fissure 272 recurrent 765
child abuse services 116 cerebral palsy (CP) 597 Cutis laxa 566
poor child health 19 imaging 242 Cyanide 211
Co-morbidities 182 Consultation see Clinical consultation Cyanosis 196, 522
Comparative genomic hybridization (CGH) Contact dermatitis 773–774, 773, 776 Cyclic progestogens 148
570 Continence issues, refugees 158 Cyclical vomiting syndrome 714
Complement disorders 452 Continuous feeding 740 Cyclophosphamide 462
Complete androgen insensitivity syndrome Continuous oral contraceptive pill Cyclospora cayetanensis 420, 422
143 (OCP) 148 Cyproheptadine 628, 631
Complex IV 324 Continuous positive airway pressure (CPAP) Cystic adenomatoid malformation (CCAM),
Compliance 26 152, 153, 353 congenital 358, 506
Computed tomography (CT) see Imaging ‘Continuum of child protection’ 113 Cystic fibrosis (CF) 507, 512–514
Conduct disorder 174, 185, 185 Contraception 146–147 abdominal pain 709
Conductive Education 599 intellectual disability 147–148, 148 clinical manifestations 513, 513, 513
Confidentiality 133–134, 135 options 146–147 diagnosis 512–513
Congenital adrenal hyperplasia 685 Convention on the Rights of the Child (UN) malabsorption 728
Congenital candidiasis 758 (1990) 19 management 513–514
Congenital chest wall abnormalities 506 Convulsions 406 wheezing 492, 492
Congenital cystic adenomatoid malformation Cooley anaemia 551–552 Cysts
(CCAM) 358, 506 Copy number variations (CNVs) 295 choledochal 246, 246
Congenital diaphragmatic hernia 357 Corticosteroids Dandy–Walker 622, 622
Congenital disorders 125, 255–258 allergic rhinoconjunctivitis 434 dermoid 273
dislocation of hip (CDH) see atopic dermatitis 772 eruption 800
Developmental dysplasia of hip bacterial meningitis 406 hygroma 273, 273, 273, 761
(DDH) chronic neuropathies 606 lung 505
ear abnormalities 781 eczema 771 mucus retention 336
of glycosylation 324–325 epilepsy 584–585 obstructed breathing 788
lower respiratory tract 505–506 inflammatory bowel disease (IBD) 721 oesophageal duplication 495, 496
Congenital dyserythropoietic anaemia juvenile dermatomyositis 461 oral alveolar 800
548, 549 liver dysfunction 752 ovarian 146
Congenital heart disease (CHD) 32, 240, 240, vasculitis 463 ovulation 143
527, 809–810 Corynebacterium spp 502 of parasites 725
Congenital hyperthyroidism 675–676 Co-trimoxazole 420, 423, 445, 452 renal 323, 647, 647
Congenital hypothyroidism 672–673, 673, 674 Cough thyroglossal 273
Congenital infection, bleeding 558 asthma and allergy 510 Cytomegalovirus (CMV) 363–365
Congenital lobar emphysema 358 gastro-oesophageal reflux and aspiration enteritis 715
Congenital malformations 276 lung disease 510–511 Cytosine (C) 289
register 278–279 imaging 240
Congenital melanocytic naevi (CMN) 758, 758 non-specific 509
Congenital monosaccharide malabsorption sinusitis and post-nasal drip 511 D
731 see also Chronic cough; Croup
Congenital muscular torticolis 257 Council of Australian Governments 7 Dandy–Walker syndrome 620
Congenital myasthenic syndromes 607 Counselling 614, 667–668, 670 cysts 622, 622
Congenital myopathies 608, 608 see also Genetic counselling Dantrolene sodium 598
Congenital myotonic dystrophy 611 Courts 116 Death, causes of
Congenital nephrotic syndrome (CNS) Cow's milk 67 1-14 years 8–9, 9
651–652 Coxiella burnetii 502 15-19 years 9–10
of Finnish type (CNF) 651–652 Coxsackie virus 649 see also Mortality rates
Congenital obstructive posterior urethral Crab lice 770 Decompression procedures 633
membranes (COPUMs) 645 Cranial meningocele 614 Decreased conscious state 318–319
Congenital red cell aplasia 545, 547 Craniosynostosis 336 Deformations 276
Congenital scoliosis 257–258 Cranium bifidum 614 Dehydration 224, 225, 717, 718
Congenital sucrase-isomaltase deficiency 731 C-reactive protein (CRP) 395, 400 kidneys 345
Congenital syphilis 367–368, 756, 774 CREST syndrome 462 mild to moderate 717, 718, 718
Congenital talipes equinovarus (club foot) Creutzfeldt–Jakob disease, variant (vCJD) 564 severe 718, 719
257, 257 Crohn's disease see Inflammatory bowel Dengue fever 417–418
Congenital vascular ring 494, 494 disease (IBD) Dengue haemorrhagic fever (DHF) 418
Conjugated bilirubin 348, 746 Cromolyn sodium 431 Dengue shock syndrome (DSS) 418
Conjugated hyperbilirubinaemia 750, 750 Cromones 488 Dental caries 801–803,
Connective tissue disorders 453, 454, 456 Croup 479–480 801, 802
autoimmune haemolysis 555 acute viral 479–480, 481 prevention 802–803, 803
chronic recurrent multifocal osteomyelitis recurrent (spasmodic) 480 Dental issues
(CRMO) 464, 464 Crying 167 abscesses 804, 804
frequency 453 newborn 340 cancer therapy 579
juvenile dermatomyositis 461–462 Cryptococcus spp 503 cerebral palsy (CP) 597
management 457–458 Cryptorchidism 269–270, 269, 270 erosion 806, 806, 807
overlap syndromes (mixed) 463, 496 Cryptosporidiosis 420, 422 refugees 162
photosensitivity 775 Cryptosporidium spp 419, 423, 447, 503, Dentition
scleroderma 462–463, 462 716 permanent 805
Sjögren disease 461 Cryptosporidium parvum 420, 422 primary 805, 805
815
 INDEX

Denver II 39 Diagnostic and Statistical Manual of Mental Disorders of sexual development (DSDs)
Denys–Drash syndrome 651–652 Disorders (DSM-IV) (Continued) (Continued)
Deoxyribonucleic acid (DNA) 289–291 mental health 172, 173, 173 management 685–686
encoded information 289, 290 retardation 107 physical examination 683
function 292 3,4-Diaminopyridine 607 with unambiguous genitalia 685
location 289 Diamond–Blackfan syndrome (DBS) 545, Disruptions 276
Department of Family and Community 547 Disruptive behaviour disorder 185–186
Services (Australia) 48–49 Diaphragm, congenital eventration of 506 Disseminated herpes simplex 765, 766
Depot medroxyprogesterone acetate ­ Diaphragmatic hernia 379 Disseminated intravascular coagulation (DIC)
(Depo-Provera) 144, 147, 148 Diarrhoea 715–722 418
Dermatitis 771–776 bloody 418, 732, 732 Distal bowel obstruction 375–377, 376
allergic contact 773–774, 773, 776 categories 418 Diuretics 525
atopic 429, 431–432, 437, 758, 771–773 chronic 244 DNA technology 312
seborrhoeic 757, 774 classification 715, 716 DNA-based prenatal diagnosis 284
Dermatological factors, oral ulceration 803 dehydration 224 Donor embryo 317
Dermatomyositis 775 diarrhoeal disease 418–419 Donor gametes 316
Dermatophyte infections 437 persistent 418 Dorland's Illustrated Medical Dictionary 475
Dermoid cysts 273 refugees 158 ‘Double bubble’ sign 376
Desmopressin 178 watery 418, 725, 730–732 Down syndrome (trisomy 21) 278, 282, 282
Determinants of health 5, 6 see also Chronic diarrhoea eye problems 797
Development, child 17–18, 36–41 Diarrhoea-associated (D+) haemolytic-uraemic features 109–110, 110, 305–306
adolescence 130–131, 131 syndrome (HUS) 652 genetic counselling 311
age see Age, developmental Diarrhoea-associated disease 652 macroglossia, severe 359–360
assessment 598–599 Diastolic murmurs 520, 521 surgical conditions 375
consultation 28 Diazepam 592, 598 Drooling 597
coordination disorder 112 Diet Drowning 100
delay 111, 238, 440–442 assessment 62 Drug ingestion 559
ear, nose and throat (ENT) 780, 781 dental caries 803 Drug reactions 763, 775
equipment 37–38, 38 diabetes mellitus 690 Drug-related autoimmune haemolysis 555
examination 33 management 86, 86 Drug/substance abuse 47–48, 133, 213–214
history 36–37, 37 manipulation 772 Dryness 772
intellectual 45 obesity 83 DTP (diphtheria, tetanus, pertussis) vaccine
investigations 40–41 Dietary Guidelines for Children and Adolescents 89
normal ranges 37, 37, 38 in Australia (NHMRC) 61 Dual-energy X-ray absorptiometry (DEXA)
outcomes 41 Diethylenetriamine penta-acetic acid (DTPA) 702
parents 36 640, 642, 646 Dubowitz score 338
prematurity 346 Diethylstilbestrol (DES) 287–288 Duchenne muscular dystrophy (DMD) 153,
refugees 163–164 Diffuse disorders 603, 609–611, 610
screening 39 alopecia 777 Ductus-dependent congenital defect 524
stages 24, 166–171 grey matter 601 Duodenal obstruction 375, 376
surveillance 37–39 white matter 601 Duodenal ulcer 741
teeth 799–801, 800 DiGeorge (22q microdeletion) syndrome 110, Duplication 645
see also Pubertal development 188, 305, 307–308, 450 Durie, Sir Mason 57, 60
variation Digits Dust mites 430, 772
Developmental approaches 85 clubbing 513 Dwarf tapeworm 162
Developmental disability 106–112 extra 337 Dyscalculia 112
assessment 39–41 Digoxin 211 Dysentery 418
defined 106 Dihydroergotamine 631 Dyserythropoietic erythropoiesis 548–549,
high-prevalence disorders 111–112 Dihydrotestosterone (DHT) 681–682 549
intellectual impairment 107–111, 109, Dimercaptosuccinic acid (DMSA) 640, 642 Dysgraphia 112
147–148, 148 Diphencyprone (DCP) 764 Dyskinetic cerebral palsy 595
management 106–107 Diphenhydramine 431 Dysmenorrhoea 145
prevalence 106, 107 Diphenoxylate 213 atypical 146
Developmental dysplasia of hip (DDH) Diphtheria 94 Dysmorphic child 303–310
248–249, 255–257, 278 Diplegia 596 chromosomal disorders 306–309
classification 255 Diprosone (betamethasone) 142 common disorders 309–310
diagnosis 256–257, 256 Direct antiglobulin test (DAT) 556 diagnosis 303
risk factors 255–256 Disability 17–18 examination 304, 305
Developmental field defect, defined 303 ABCDE steps 195, 197–198, 199 history 304
Developmental quotient (DQ, GQ) 40 assessment 39–41 investigations 305–306
Dexamethasone 406 intellectual 147–148, 148 metabolic causes 323
Dextrose 228 physical, management 616–617 recognition 304
Diabetes mellitus type 1 687 young people 133 Dysplastic naevi 758–759
clinical presentation 687–688, 688 see also Developmental disability Dystonia 595
co-morbidities 690 Disaccharidase deficiencies 725, 731
complications 690–692 Discitis 400
differential diagnosis 688 Discoid eczema 772–773 E
eye disorders 797–798 Disease
future directions 694 burden of 10–12, 11 Ear, nose and throat (ENT) 780–789
insulin, metabolic effects 687 control/prevention 413 ear 30, 780, 781–785
ketoacidosis 687–689 pattern changes 10 foreign bodies 780–781
management 689–694, 691 Disease-modifying anti-rheumatic drugs growth/development 780, 781
pathogenesis 687 (DMARDs) 457, 464 nose 780–781, 785
Diabetes mellitus type 2 694–695, 694, 694 Dislocations 260 oropharynx 785–789
Diabetic ketoacidosis (DKA) 234 Disorders of sexual development (DSDs) Early childhood
Diagnostic and Statistical Manual of Mental 680–686 caries (ECC) 801, 802, 802
Disorders (DSM-IV) diagnostic categories 683–685 education 3–4
hyperactivity 179, 180 evaluation 682–683 knock knees 253
inattention symptoms 179, 180 history 682–683 poisoning 208
816 learning difficulties 112 investigations 683 psychiatric disorders 183–185
 INDEX

Early infancy 167 Environmental factors Eye disorders (Continued)

Ears see Ear, nose and throat (ENT) influences 166 juvenile idiopathic arthritis (JIA) 456, 457
Eating disorders 83, 158, 190–191 Maori people 59–60 metabolic causes 323
Echo virus, gromerulonephritis 649 obesity 82–83 misalignment 791, 791
Echocardiography 522 refugees 163 systemic disease 797–798
Economic disadvantage 46–47 Enzyme replacement therapy (ERT) 324 Eyelid infections 795
Ectopic bowel mucosa 271 Eosinophilic oesophagitis 736
Ectopic thyroid 273 Eosinophilic pustular folliculitis
Eczema 142, 771 of scalp 756 F
atopic 771–773 Ephedrine 607
discoid 772–773 Epidemic parotitis 472 Fabry disease 324
herpeticum 765, 766 Epidermal naevi 759–760, 760 Face, examination 336
Education Epidermolysis bullosa 757 Face mask, neonatal resuscitation 333
atopic dermatitis 771–772 Epididymo-orchitis 270–271, 271 Facial asymmetry 336
early childhood 3–4 Epilepsies 185, 582–592 Facioscapulohumeral syndrome (FSH) 611
folate intake 619 common 582–590, 583 Faecal parasites 162, 162
myelomeningocele 618 with focal seizures 588–589, 588 Faeces 774
‘Educational diet’ 68 with generalized tonic-clonic seizures Failure to thrive (FTT) 102–105
Edwards syndrome (trisomy 18) 282, 306–307, 587–588, 588 causes 102–103, 103
375 terminology/classification 582, 583 defined 102
Ehlers–Danlos syndrome 566 Epinephrine 218, 431 examination 104
Eisenmenger syndrome 528 Epispadias 268 growth patterns 102, 103
Ejection murmurs 520, 521 Epistaxis 785 history 103–104
Elbow, pulled 263 Epithelial pearls 337 investigations 104–105
Electrocardiography (ECG) 522, 524 Epstein pearls 800 management 105
Electroencephalography (EEG) Epstein–Barr virus (EBV) 471, 575, 649 Falls 100
epilepsy 585–586 Equipment 37–38 Familial hemiplegic migraine 627
sleep 149, 151 Erb's palsy 337 Family 44–49
Electrolytes 223, 229–230 Ergotamine 211, 628 Australian 45–46
loss 717–718 Eruption cysts 800 composition 3
transport disorders 725, 731–732 Erythema infectiosum 387, 387, 762, 762 in distress 46–48
Electromyogram (EMG) 151 Erythema multiforme (EM) 776 emotional/social needs, child 44
Electro-oculogram (EOG) 151 Erythema nodosum 776 extended, at risk 315
Embryo, donor 317 Erythmoid stem cell failure 546, 547–548 family-centred care 48, 85, 106, 599
Embryogenesis 297–298 Erythrocyte sedimentation rate (ESR) 395, history 27
Emergencies 194–199 400 income 3
causes 194, 195 Erythrodermic exanthems 763 intellectual development, child 45
complex 18–19 Erythropoietic protoporphyria 775 kinship 54–55, 54
contraception 146 Escherichia coli (E.coli) physical needs, child 44
management of severe trauma acute gastroenteritis 715 rapport 25
(EMST) 261 bone/joint infection 394 support services 48–49
primary assessment 194–198 haemolytic-uraemic syndrome (HUS) 652 tree 27, 27
reassessment 198 infective endocarditis (IE) 536 workforce participation 46
Emotional factors meningitis 408, 410 Fanconi anaemia 542–546, 547
abuse 115 neonates 371 Fasciolopsis buski 420
adjustment 618 pneumonia 500, 502 Fats 65, 67
distress 133, 597 tropical/developing countries 418–419 digestion/absorption 727
needs, child 44 urinary tract infections (UTI) 639 malabsorption 727–728
refugees 163 Essential fatty acids 775 Fatty acid oxidation effects 319
Enamel defects 800–801 Ethics, genetics 302 Fatty diarrhoea (steatorrhoea) 725, 726–730
Encephalitis Ethnic variations in BMI 77 Febrile seizures 582–584
arthropod-borne 411–412 Ethosuximide 588 Feeding
herpes simplex virus (HSV) 411–412 Ethylene glycol 211 continuous 740
infectious 405, 410–412, 410, 411 Etonogestrel 147, 148 infants 167
Encephalocele 614, 620 European Society for Immunodeficiencies problems, prematurity 345
Encephalopathy 748 (ESID) 442 routes 71–72, 72
Encopresis 178 Ewing sarcoma 577, 578 see also Breastfeeding
Endobronchial tuberculosis 495 EWS gene 578 Feet
Endocrine factors Exanthems 382, 763 accessory navicular bone 254
cancer therapy 579 Exchange transfusion 351 curly middle toes 254, 254
obesity 80, 81, 81 Exogenous surfactant 353 flat 252–254, 254
short stature 664 Exomphalos 271, 278, 377–378, 379 in-toe gait 254–255
tall stature 668 Exotropia 792 puncture wounds 399
Endometrial ablation 148 Expanded Programme on Immunization (EPI) talipes calcaneovalgus 252, 253, 337
Endometriosis 145–146 413, 415 see also Talipes equinovarus
Energy 61, 82 Expiratory grunt 352 Fetal alcohol effects (FAEs) 285
Entamoeba spp 419 Exposure (ABCDE steps) 195, 198, 199 Fetal alcohol syndrome (FAS) 111, 285
Entamoeba dispar 419, 420 Expressed breast milk (EBM) 71 Fetal growth 659
Entamoeba histolytica 419, 420 Extracellular fluid (ECF) 222–224, 223, 230 Fetal surgery 614
gastroenteritis 715, 719 Extrahepatic biliary atresia 750–751 FEV gene 127
Enteral nutrition 721 Extrinsic membrane defects 555–556 Fever
Enterobius spp 423 Eyes imaging 240, 247–248
Enterobius vermicularis 419, 420 examination 30, 224 persistent 407
Enterococci 536 vision 790 rash and 382, 383
Enterocyte defects 725, 729 Eye disorders 790–798 refugees 158
Enterohepatic circulation 348 assessment 790–791 Filatow–Dukes' disease 383
Enteroviruses 371, 391–392 cancer therapy effects 579 Flat feet 252–254, 254
Enthesitis-related arthritis (ERA) 456 common problems 792–797 ‘Floppy’ infant syndrome 612
Enuresis, nocturnal 177–178 examination 790–791, 791 Flucloxacillin 767
Envenomation 214–220, 214 history 790 Fluid balance 329
817
 INDEX

Fluid replacement therapy 222–234 Gastro-oesophageal reflux (GOR) 735–740 Goat's milk 67
acid-base balance 230–231, 231 causes 736 Goitre 273, 677–678
bacterial meningitis 406 clinical manifestations 735–736, 737 Gonadal mosaicism 297
body fluid composition 222–224, 223, 223 diagnosis 736–738, 738, 738, 739 Gower's sign 609, 610
dehydration 224, 225 helicobacter pylori 742 Granulocyte-macrophage colony-stimulating
electrolytes 223, 229–230 pathophysiology 735, 736 factor 546
emergencies 204 treatment 739–740, 739, 740 Grasp reflex 337
ongoing losses 228 Gastroschisis 271, 278, 378–379, 379 Great vessels, malformations 278
requirements 225–228, 226, 227, 228 Gaucher disease 324 Greave's hypothesis 569–570
specific illnesses 231–234, 232 Gavage feeding 525 Grey matter, diffuse disorders 601
Fluid transport disorders 731–732 GAVI Alliance 415 Griffiths scale 40
Flunarizine 628 Gender issues 686 Gross Motor Function Classification System
Flunisolide 431 Gene therapy 445, 450, 452 (GMFCS) 596
Fluorescence in situ hybridization (FISH) 317, General appearance, examination 30 Growth, child 658–671
450, 570 General practitioners 12 assessment 660–662
Fluoride 802–803 Generalized anxiety disorder 186 cerebral palsy (CP) 597
Fluorosis 803–804 Genetic counselling 311–317 consultation 28
Fluoxetine 187, 188, 189, 607 alternatives 316–317 ear, nose and throat (ENT) 780, 781
Fluticasone 431 anaemia 553 genetic factors 658, 659
FMR1 gene 308 burden 315–316 hormonal factors 658–659
FMR2 gene 309 diagnosis 312 nutritional factors 658
Focal segmental glomerulosclerosis 651, 651 emotional impact 317 patterns 102, 103
Folate 549, 619 extended family 315 phases 659–660
Folic acid 286, 619 family history 312–313, 313 poor 119
Food indications 311 prematurity 346
allergy 434–437, 435 predictive testing 315 puberty, delayed 693
fortification 619 process 311–312 refugees 157–159
-induced urticaria 763 for risk 314–315 skeletal variation 252–255
intolerances 435, 436 specialists 311 small for gestational age (SGA) 348, 663
solid 68 Genetic photosensitive disorders 758 stunting 742
Food and Drug Administration (FDA) 178 Genetics 289–302 see also Short stature; Tall stature
Forearm fractures 261, 261, 262 chromosomes 289, 290–291 Growth hormone (GH) deficiency 667
Foreign bodies deoxyribonucleic acid (DNA) 289–292, Growth hormone–insulin-like growth factor I
ear, nose and throat (ENT) 780–781 290 axis (GH–IGF-I) 658–659
inhaled 495, 495 ethics 302 Growth Motor Development Curves 596
vaginal 142 genome function 291–292 Guanidine (G) 289
Forensic assessment 120–121 mutations 295–298, 295 Guillain–Barré syndrome 605–606
Foreskin 266–268, 337 networks 293 Gums
Fractures 260–263 patterns of inheritance 298–301 bleeding 558, 806–807, 807
child abuse 117, 119, 261 regulation 292–293 examination 30
Fragile syndrome 108–109, 109 variation 294–295 Guttate (small spot) psoriasis 763
Fragile X mental retardation protein (FMRP) Genitalia Gynaecology 141–148
108 ambiguous 337, 683–685 adolescence 142–148
Fragile X tremor ataxia syndrome (FXTAS) 309 disorders, unambiguous 685 neonates 141
Fragile X (XA) syndrome 308, 308 examination 30, 33, 337 young girls 141–142
Fragile XE syndrome 309 external 681–682, 682 Gynaecomastia 671
French-American-British (FAB) system 571–572 internal 680–681, 681
‘Frog plaster’ napkin rash 774 Gentamicin 399
Frontal lobe epilepsy (FLE) 589 German measles see Rubella H
Fungal pneumonia 503 Gestation 341
Funnel-web spider bite 214, 219 Gestational age scoring 338 H1N1 influenza pandemic 95
Furuncles 767 Giant cell arteritis 634 H2-receptor antagonists 739
Giardia intestinalis 157–159, 162 Haem synthesis, defective 549, 550–551
Giardia lamblia 419, 420, 447, 716, 719 Haemaethrosis, knee 564
G Giardiasis 419, 420, 725 Haemangiomas 760–761, 760
Gingival inflammation 451–452, 451 associations 761
G6PD enzyme deficiency 554 Gingival swellings 804 complications 760
Gabapentin 588 Gingivitis 806–807, 807 subglottic 478, 478, 493, 788
Gametes 289 Gingivostomatitis, primary herpetic 765, Haematological factors
Gammaglobulin 605–606 808 oral ulceration 808
Gastric adenocarcinoma 741 Glandular fever 390 prematurity 345
Gastric lavage 210–211 Glanzmann disease 561 refugees 160
Gastric lymphoma 742 Glasgow Coma Scale (GCS) 197, 197, 237 Haematopoietic stem cell transplant 572
Gastric ulcers 741 Glaucoma 796–797, 796 Haematuria 247, 648–650
Gastritis 741 Global Initiative for Asthma (GINA) 482, Haemoglobin Barts 552
Gastroenteritis 707, 713 488, 489 Haemoglobin E1β-thalassaemia 552
acute see Acute gastroenteritis Global mortality rates 15, 16 Haemoglobin H disease 552
fluid replacement 231–232 causes 16–17, 17 Haemoglobinopathies 551–553
Gastroenterology, imaging 242–245 complex emergencies 18–19 see also Anaemia
Gastrointestinal (GI) factors effective interventions 19–21 Haemolysis 350, 350, 553–554, 553
bleeding 244–245, 558 progress 17 antibody-mediated 555–556
infection 741–742, 741 Glomerulonephritis 648–650, 649 Haemolytic disease of newborn 757
lesions 712 post-streptococcal 648–649, 649 Haemolytic-uraemic syndrome (HUS) 652
newborn 329–330 Glucocorticoid excess 776 Haemophilia 563–565, 564
oral ulceration 808 Glucose-galactose malabsorption 725 Haemophilus spp 441, 794
prematurity 345 γ-Glutamyltransferase (GGT) 746 Haemophilus influenzae
Gastro-oesophageal reflux disease (GORD) Gluteal granulomas 774 acute otitis media 473
597, 710 Glycol ethers 211 acute sinusitis (rhinosinusitis) 472
cough and aspiration lung disease 510–511 Glycosylation, congenital disorders of cystic fibrosis 514
818 see also Gastro-oesophageal reflux (GOR) 324–325 hyper IgE syndrome 450
 INDEX

Haemophilus influenzae (Continued) Height Human metapneumovirus (HMP) 468

otitis media 781 measurement 31, 31 viral pneumonia 502–503
pneumonia 501 mid-parental (MPH) 660–662 Human papillomavirus (HPV) 136, 788
septicaemia 776 percentile charts 661, 662 Human rhinovirus (HRV) 502–503
skin disorders 756 Helicobacter pylori 735, 740–743 Humerus, supracondylar fracture 261–262, 262
Haemophilus influenzae type b (Hib) 9 abdominal pain 709 Hyaline membrane disease (HMD) 355–356
arthritis 453 associated disease 741–742 Hydranencephaly 619–620
bacterial disease 415 consequences 741 Hydroceles 269, 269, 337
bone/joint infections 394, 399 diagnostic tests 742, 742, 743 Hydrocephalus 597, 620–624, 620
hereditary spherocytosis 555 epidemiology 740–743 clinical diagnosis 621
immunization 90, 94 refugees 157–159, 160, 162 investigations 622–623, 622, 623
meningitis 402, 405, 407, 408, 410 risk factors 741 physical examination 622
vaccine 413 treatment 743, 743 treatment 623–624
Haemorrhagic disease of newborn 565 ulcers 743 Hydrocortisone 218, 431
Hair Hemiplegic migraine 627 Hydrops fetalis syndrome 552
abnormal, metabolic causes 323 Henoch–Schönlein purpura 459, 565–566, Hydroxycarbamide 553
examination 30 565, 649 1α-Hydroxylase deficiency 700
excessive 777 Heparins 211, 566, 566 Hydroxyurea 553
loss 776–777 Hepatic factors Hydroxyzine 431
Hallucinations 625–626 detoxification 746 Hygiene hypothesis 483
Halo naevi 762 examination 338 Hymen, imperforate 141, 143
Hand, foot and mouth disease 471, 762 function, abnormal 246 Hymenolepis nana (dwarf tapeworm) 162, 420
Hartmann's solution 225–226, 226, 232–233 prematurity 345 Hyperactivity 179–182, 180
Head Hepatitis A vaccine 95 Hyperammonaemia 319
examination 30, 33–34, 34, 335–336, Hepatitis B virus (HBV) 94, 162, 373–374 Hyperbilirubinaemia
338 vaccine 91 conjugated 750, 750
large (macrocephaly) 619–624 Hepatitis C virus (HCV) 162, 374 prematurity 345
Head injuries 99 Hepatobiliary factors Hypercalcaemia 701–702, 702
child abuse 118, 119 imaging 246 Hypercalciuria 702
trauma, acute 237–238, 237 obesity 79–80, 80 Hypercoagulable state 651
Head lice 770 Hepatocellular dysfunction 746 Hyperglycaemia 345
Headaches 625–635 Hepatomegaly 747 Hyper-IgE syndrome 450–451
cranial causes 625–633 Herd immunity 90–91 Hyper-IgM syndrome 447
extracranial causes 633–634 Hereditary motor and sensory neuropathy Hyperkalaemia 345
investigations 634–635 606–607 Hypermagnesaemia 703, 703
overrated causes 634 Hereditary spherocytosis 543, 555 Hypermobility disorders 465
unusual childhood 634 Herpangina 471 Hypernatraemia 230, 345
HEADSS (mnemonic) 135–136, 136, Herpes simplex virus (HSV) Hyperphosphataemia 698
145–146 atopic dermatitis 437 Hypertension 653–654, 653, 653, 654, 654
Health childhood 391 imaging 247
behaviours 13–14 dermatological presentations 764–765 portal 748
conceptual framework for Australia 5, 6 encephalitis 411–412 Hyperthyroidism 668, 675–677
inequity 6–7, 8, 15–16, 39, 46–48 napkin rash 774 acquired 676–677
see also Child health neonates 756 congenital 675–676
Health services perinatal 371–372, 372 Hypertrichosis 777
Australian 12–13 stomatitis, primary 471 Hypertrophic pyloric stenosis 278
child abuse 116 Herpes zoster 389, 389, 762 Hypoallergenic diets 69
family support 48–49 Hexachlorophene 208 Hypocalcaemia 696–698, 699
Maori people 58 Hilar lymph nodes, enlarged 495 Hypochondriasis 190
service provision, trends 599 Hips 597–598 Hypoglycaemia 319–320, 320, 321, 345,
Hearing examination 338 692–693, 712
cancer therapy effects 579 inset 255, 255 Hypokalaemia 229
examination 338 see also Developmental dysplasia of hip Hypomagnesaemia 703, 703
loss 784–785 (DDH) Hypomania 188
screening 339 Hirschsprung disease 375–376 Hyponatraemia 227–228, 229–230, 233–234,
Heart Hirsutism 777 345
examination 30, 336–337, 338 Histoplasma spp 503 Hypoparathyroidism, late-onset 697
malformations 278 History-taking 26–29 Hypophosphataemic rickets 700
rate 336 Hitting 169 Hypoplastic left heart syndrome 531, 531
Heart disease 518–525, 526–538 Hodgkin disease 575 Hypospadias 266–267, 268, 278, 337
acquired 535–537 Homicide, sudden unexpected death in infancy Hypotension 225–226
acyanotic defects 526–529 (SUDI) 125 Hypothalamic factors, amenorrhoea 145
assessment 518–522, 519, 519, 520 Hookworm 419, 420, 421–422 Hypothyroidism 672–675
cardiac arrhythmias 537–538 Hospital feeds 71 acquired 673–675
congenital (CHD) 32, 240, 240, 527, Hospitalizations 12 congenital 672–673, 673, 674
809–810 Hospitalized child, nutrition 70–73, 70 Hypotonia 612
cyanotic defects 531–535 Household circumstances 3 Hypotonic fluids 227, 228, 229
heart block 537–538 HOX genes 277 Hypoventilation 153, 360–362, 361
history 518 Human genome 289 Hypovolaemia 204, 651
investigations 522–524 function 291–292 Hypoxia 196
obstructive defects 529–531 Human immunodeficiency virus (HIV) Hypsarrhythmia 584, 584
presenting features 518, 526 adolescence 131–132 Hysterectomy 148
prevalence 518 control 413
treatment 524–525 global context 16, 18, 19
Heart failure infection 19, 416 I
manifestations 197, 522 malnutrition 70
treatment 524 skin disorders 775 Iatrogenic factors, short stature 663
Heart murmurs 337, 520–521, 521, 523 transmission 374 Iatrogenic injury 757
innocent 521–522 tuberculosis (TB) co-infection 416 Ibuprofen 628
Heat rash 763 vaccines 96 Ichthyosis 757, 758
819
 INDEX

Identification of Severe Acute Malnutrition in In vitro fertilization (IVF) 284, 316, 317 Influenza virus 502–503
Infants and Children (WHO) 69 Inattention 168, 179–182, 180 vaccine 95
Idiopathic autoimmune haemolysis 555 Inborn errors of metabolism (IEM) 318–326 Inguinal hernia 268, 269
Idiopathic intracranial hypertension 632–633 acute metabolic decompensation 318–322 strangulated 713
Idiopathic scoliosis 258, 258 diagnosis/genetics 322 Inguinoscrotal region 268–271
IgA nephropathy 649, 649 multisystem disease 322–325, 323 Inhaled foreign body 495, 495
IgE-mediated food allergy 435 neurodegeneration 322, 602 Inhaler devices, asthma 490
non-IgE-mediated food allergy 435–436 newborn screening 325 Inheritance see entries beginning Congenital;
IgG subclass deficiency 448 peri-mortem protocol 325 Genetics
Imaging 236–250 vomiting 712 Inhibitory casts 598
abdomen/gastroenterology 242–245 Incontinence 597 Insecticide-treated bed-nets (ITNs) 417
cardiology 240 Incontinentia pigmenti 757, 757 Inset hips 255, 255
hepatobiliary 246 Indigenous families 47 Inspiratory stridor 336
musculoskeletal 247–250 health inequity, child 6–7, 8, 15–16, 39, 47 Insulin 687, 689, 689
nephrology/urology 246–247 see also Aboriginal and Torres Strait Integrated Management of Childhood Illness
neurology 237–240 Islanders; Maori people (IMCI) 20, 414, 415
pulmonary/airway 240–242 Indolent ulceration 765 Intellectual development, child 45
radiation 236, 237 Induced emesis, poisoning 210 Intellectual disability 107–111, 109, 147–148,
Imipenem 423 Ineffective erythropoiesis 548–549, 549 148
Immersion scalds 117, 118 Inequity, health 6–7, 8, 15–16, 39, 47 Intelligence quotient (IQ) 40, 107
Immigrant families 47 Infancy Inter-agency child protection 115–116, 120
Immune reconstitution inflammatory bacterial meningitis 403 Interferon-γ release assays 161
syndrome (IRIS) 416 developmental dysplasia of hip (DDH) Interleukin-12/interferon-γ axis 452
Immune system 256–257 Intermittent divergent strabismus 792
active immunity 89 early 167 Internal tibial torsion 255
deficiencies, metabolic causes 323 feeding requirements 64 International Classification of Diseases (ICD-10)
dysregulation 456 history 119–120 mental health 172
passive immunity 89 hospital breast milk feeding 71 sleep disorders 151–152
Immune thromocytopenic purpura 560–561, injuries 117–119 sudden infant death syndrome (SIDS) 123
562 late 168 International Classification of Headache
Immunization 89–96, 129 liver disease 747, 748–751, 749 Disorders (ICHD) 626, 627, 630
adverse effects 92–93 meningitis 408–409 International conventions 19, 20
benefits 94, 94 mental health problems 175 International League Against Epilepsy 582
consent 92 mortality rates 7–10, 8 International League of Associations for
disorders and 93 poisoning 208 Rheumatology (ILAR) 454
missed/delayed 93 psychiatric disorders 183–185 International Society for the Study and
newborn 339 referral 414 Prevention of Perinatal and Infant
prematurity 346 skeletal injuries 260–263 Death (ISPID) 124, 128
principles 89–91 swelling 249 International Union of Immunological
questionnaire 92 urinary infection 246, 247 Societies (IUIS) 442, 443
recording 94 vision 796 Intestinal nematodes 424
refugees 160 vomiting 712–713 Intestinal problems, metabolic causes 323
respiratory infections 473, 474 wheezing disorders 491–495, 494 In-toe gait 254–255
schedule 91, 91 see also Premature infant Intoxications 602
side-effects 94, 94 Infant botulism 607 Intracellular enzyme defects 554
special circumstances 95–96 Infant formulas 64–67 Intracellular fluid (ICF) 222, 223
specific considerations 93 composition 64–67, 65 Intracranial haemorrhage 558
status 28 preparation 67 Intracranial hypertension 632–633
Immunization Technical Advisory Group Infantile acropustulosis 756 Intracranial mass lesions 620
(NHMRC) 91 Infantile esotropia 792 Intracranial pressure 632
Immunodeficiency 439–452 Infantile idiopathic scoliosis 258 Intraosseous needles 204, 204
antibiotics 399 Infantile spasms 584–585, 584 Intrapartum antibiotics 373
atopy influence 439 Infections Intrauterine diagnosis 316
clinical features 441 age and susceptibility 90 Intrauterine growth restriction 348
developmental delay 440–442 asymptomatic 644 Intrauterine herpes simplex 764
diagnosis 440 blistering 776 Intrauterine posture 252–255
host factors/resistance 439–440, 440, 441 immunodeficiency 440 Intravenous fluids, respiratory distress 353
investigations 442–444, 446 neonates 756 Intravenous immunoglobulin replacement
meningitis 408–409 nervous system 602 therapy (IVIG) 351, 441
prematurity 440–442 oral 807–808 ataxia telangectasia (AT) 450
primary (PID) 439, 442–445, 443, 445 prematurity 345–346 common variable immunodeficiency (CVID)
secondary 442, 445 route of 90 448
skin disorders 758 sexual contact 119 hyper-IgM syndrome 447
specific disorders 445–452 skin 437 juvenile dermatomyositis 462
treatment 445 systemic 711, 757 vasculitis 463
Immunoglobulin tropical/developing countries 413–424 Intraventricular haemorrhage 343–344
chronic neuropathies 606 see also specific infections Intrinsic membrane defects 554–555
evolution of 440, 441 Infectious diseases 382–392, 383 Intussusception 706–707, 707, 708, 713
Immunoglobulin replacement therapy 445 diarrhoea 424 differential diagnosis 707
X-linked 446–447 encephalitis 405, 410–412, 410, 411 treatment 707
Immunological complications, prematurity mononucleosis 390 Ionizing radiation 287
345–346 myelitis 410–412 Ipecacuanha 210
Immunological memory 439–440 Infective endocarditis (IE) 536–537, 809–810 Ipratropium bromide 487
Immunomodulators 721 Inflammatory bowel disease (IBD) 720–722, Iron
Immunosuppressants 606, 722 725 antidotes 211
Immunosuppression 722, 765 cancer risk 722 deficiency 550–551, 742
Immunotherapy 430, 434 investigations 720–721 malabsorption 733
Impetigo 766, 766, 774 surgery 722 Irritant dermatitis 774
bullous 756, 757, 766 treatment 721–722 Irritants 772
820 non-bullous 766, 766 Inflammatory myopathy 611 Irukandji syndrome 220
 INDEX

Isoimmune haemolysis 555 Lactate 746 Lower respiratory tract infections (LRTIs)
Isolated microscopic haematuria 648 Lactic acidosis 300, 320–321, 321 498–505
Isolated premature menarche 671 Lamotrigine 588, 592 acute viral bronchiolitis 503–504
Isolated protein malabsorption 733 The Lancet 19–20 atypical mycobacterial infection 505
Isolated proteinuria 650 Landau–Kleffner syndrome 583 pertussis (whooping cough) 94, 504–505
Isospora belli 420, 422 Langerhans cell histiocytosis 757, 757, pneumonia 498–503
Isotretinoin 286–287 774–775, 776 pulmonary tuberculosis (TB) 505
Ivermectin 420 Language Lumbar puncture (LB) 404
Aboriginal and Torres Strait Islanders 55–56 Lumbosacral birthmarks 762
delay 169 Lungs
J impairment 111–112, 111 abnormalities, congenital 505–506
second, acquisition 164 examination 30
Jaundice 348–351, 747 Laryngeal obstruction 360 Lung disease 358
adolescence 246 Laryngomalacia 476–477, 477, 788 aspiration 510–511
bilirubin synthesis 348, 349 Laryngotracheobronchitis see Croup cysts 505
breast milk 349, 350 Larynx, foreign bodies 781 non-cystic fibrosis suppurative 492, 492
complications 350–351 Late infancy 168 see also Chronic lung disease (CLD)
evaluation 348, 349 Latent TB infection (LTBI) 160–161 Lyme disease 459
history 348–349 Latin American Group for Primary Lymph nodes
laboratory evaluation 349 Immunodeficiencies (LAGID) 442 enlarged 273
neonates 246, 246 Lead 211 examination 30
pathological unconjugated 350 Learning difficulties 112, 170, 618 tumours 274
physical examination 349 refugees, assessment 163–164 Lymphangioma 761
physiological 349–350, 350 vision 795 Lymphatic drainage 725, 729
treatment 351, 351 Learning theory, sleep 149 Lymphatic malformation 761
Jellyfish stings 214, 219–220 Legislation, child protection 113 Lymphomas 495, 574–577, 742
Joints Legs, bow 252, 253 Lysosomal storage disorders 322–325
bleeding 558 Leigh disease 324
function, maintenance 458 Lennox–Gastaut syndrome 584
pain/dysfunction 459, 459 Lenses, dislocated 323 M
see also Bone/joint infections Leukaemia, acute 569–572
Juvenile absence epilepsy 585 Leukocyte adhesion deficiency (LAD) 452 McCune–Albright syndrome 759
Juvenile chronic arthritis, systemic 763, 797 Leukotriene receptor antagonists 488 Macrocephaly 323, 619–624
Juvenile dermatomyositis 461–462 Levetiracetam 588, 592 Macrocytosis 543–545, 543
Juvenile idiopathic arthritis (JIA) 453–456, 454 Levonorgestrel intrauterine device (IUD) Macroglossia 359–360
associated abnormalities 458 144, 148 Macular exanthems 763
frequency 453 Leydig cells 680 Magnesium 696, 697, 698
outcomes 458 Lice disorders 703, 703
Juvenile myelomonocytic leukaemia (JMML) body 770 malabsorption 733
569 crab 770 Magnesium sulphate 487
Juvenile myoclonic epilepsy 587 head 770 Magnetic resonance imaging (MRI) see
Juvenile myotonic dystrophy 611 Lichen sclerosis 142 Imaging
Juveniles see Adolescence Lid infections 795 Maintenance fluids 227–228, 227, 228
Life events 166–171 Major depressive disorder 187, 187
Life support 200–205, 205, 206 Malabsorption 713, 724–734, 725
K newborn 332 with chronic diarrhoea 725, 726–732, 727
snake bites 218 clinical assessment 724, 725, 726
Kartagener syndrome 512 Li–Fraumeni syndrome 578–579 diagnosis 724–726, 734
Karyotype 289 Limbs with no diarrhoea 732–734
Katser–Fleisher ring 753 examination 30, 337 sugar 719
Kawasaki disease 463, 535, 763, 774 fractures 99 Malaria 16, 161, 416–417, 417
Kempe, Henry 113 reflexes 338 control 413
Kernicterus 350–351 upper 598 Malformations 593–594
Ketoacidosis 687–689 Lines of Blaschko 759, 759, 760 congenital 276, 278–279
diabetic (DKA) 234 Lips, examination 30 Malignancy 496
Ketoconazole 769 Listeria monocytogenes 369, 372, 502, 756 autoimmune haemolysis 555
Ketorolac 631 meningitis 404, 408, 410 neonates 757
Kidneys Liver oral ulceration 803–804
abnormality 645 anatomy 744 second 579
disease, chronic 652–653 trauma 99 see also Cancer
duplication 645 Liver disease 744–754 Malnutrition 69–70
injury, acute 652, 652 acute 747, 749–750, 752 developed world 70
trauma 99 categories 747 developing world 70
Kingella kingae 393, 398 childhood 751–753, 752 MALT lymphoma 742
Kinship family 54–55, 54 chronic see Chronic liver disease Mania 188
Klebsiella spp 500, 639 liver failure 323, 753 Mantoux test 161
Klebsiella pneumoniae 502 neonates/infants 747, 748–751, 749 Manual Abilities Classification System
Klein–Levin syndrome 154 pattern recognition 744–748, 745, 748 (MACS) 596
Klinefelter syndrome 307, 315–316, 658, 668 Lobar emphysema, congenital 506 Maori people 56–60
Klippel–Trenaunay syndrome 761 Location 2–3 children, significance of 57
Knees 598 Locus, terminology 289 cultural competency 58
knock 252, 253 Lomotil 213 defined 57
Koplik's spots 382 London Dysmorphology Database 278, 305 future challenges 60
Kussmaul respiration 687–688 London Neurogenetics Database 305 genetics/environment 59–60
Long QT syndrome 537 health, concepts of 57
Long-acting β-agonists (LABAs) 489 health services 58
L Loratadine 431 historical issues 57–58
Lower oesophageal sphincter (LOS) 735 physical abuse 60
Labial fusion 141 Lower respiratory tract, congenital disorders population statistics 57
Lacosamide 588 505–506 socioeconomic issues 58–59
821
 INDEX

Maple syrup urine disease 319 Methaemoglobinaemia 211 Movement disorders 323
Marfan syndrome 310, 668 Methanol 211 Mucopolysaccharidoses 324
Marrow replacement 546, 548 Methicillin-resistant Staphylococcus aureus Mucosal disease 725
Masses 337 (MRSA) 500–501 bleeding 558
Mast cell stabilizers 434 Methotrexate 461, 464, 721 Mucosal surface 730
Mastocytosis 757 Methylphenidate 181 Mucus retention cysts 336
Maternal inheritance 300, 300 Methylprednisolone (Advantan) 142 Müllerian-inhibiting substance (MIS) 680, 681
Maternal serum screening (MSS) 280 Metoclopramide 628 Multi-channel intraluminal impedance 738
Mean corpuscular volume (MCV) 542 Metronidazole 420, 423, 743 Multidisciplinary teams 39–40, 106, 185,
Measles 94, 382–385, 383, 384 Microarray (array comparative genomic 598–599
MMR (measles, mumps, rubella) vaccine hybridization) 295, 303, 305–306 Multisystem (multifactorial) disease 300–301,
385, 472 Microcephaly 323 301, 314, 322–325, 323
Mebendazole 423 Microdeletion syndrome 110–111 Mumps 94, 472
Meconeum ileus equivalent 709 Micrognathia 359–360, 360 MMR (measles, mumps, rubella) vaccine
Meconium aspiration syndrome (MAS) 357, Micturating cystourethography (MCU) 640, 385, 472
357 644 orchitis 270–271
Meconium exposure 334 Micturition, newborn 339 Muramyl tripeptide (MEPACT) 578
Meconium ileus 376 Midazolam 583–584, 592 Muscle disorders 608–612
Mediastinal masses 495, 496, 496 Middle childhood acute myopathies 608
Medical assessment poisoning 208–209 chronic myopathies 608–611
forensic 120 psychiatric disorders 183, 185–187 infections 424
obesity 83, 83 Middle ear effusion (MEE) 782 Muscle tone, examination 198, 224
Medical Council of New Zealand 58 Midline neck swellings 273 Muscular dystrophies 608–611, 608, 609
Medical Journal of Australia 473 Mid-parental height (MPH) 660–662 Muscular torticolis, congenital 257
Medical Research Council (UK) 618 Migraine 625–629 Musculoskeletal system
Medications 28 aetiology 627–628 disorders 465
Megalencephaly 619 ‘classical’ 625–626 examination 33
Megaloblastic anaemia 548–549 clinical manifestations 625–626 imaging 247–250, 248, 249
Melanoma 14 epidemiology 625 pain 158, 247–248
Meliodosis 423 prognosis 629 swelling 247–248, 249
Membrane defects 554–556 treatment 628–629 trauma 247, 248
Memory, immunological 439–440 types 626–627 Mutation, defined 294
Menarche, isolated premature 671 vomiting 713 Mycobacterial infection, atypical 505
Mendelian disorders 314 Milia 335, 756 Mycobacterium spp 502
Meninges 613 Miliaria 763, 774 Mycobacterium avium 505
Meningitis Milks 67 complex (MAC) 273
aseptic 410 Millennium Development Goals (MDGs) Mycobacterium avium, intracellulare,
viral 405, 410, 410 (2000) 19, 20, 413 scrofulaceum (MAIS) 273
see also Bacterial meningitis Goal 4 - child mortality 20–21 lymphadenitis 273
Meningocele 608, 613, 614 Mitochondrial disorders 319 Mycobacterium intracellulare 505
Meningococcaemia 404, 409 depletion syndrome 324 Mycobacterium scrofulaceum 505
Meningococcal quadrivalent ACW135Y encephalomyopathy (MELAS) 300, 324 Mycobacterium tuberculosis (MTB) 393, 394,
polysaccharide vaccine 95 respiratory chain 324 415–416
Meningococcal septicaemia 763 Mitochondrial DNA (mtDNA) 289, 291 complex 160–161
Meningococcus C 9 maternal inheritance 300, 300 pulmonary tuberculosis 505
Menorrhagia 144, 144 Mixed apnoea 362 wheezing disorders 492
Men's business/Women's business 52 Mixed chromosome pattern 685 Mycoplasma spp 459, 463, 463, 776
Menses Mixed gonadal dysgenesis 685 Mycoplasma pneumoniae 411, 493, 495–496,
delayed onset 143 Mixed (overlap syndromes) connective tissue 501, 502
heavy periods 144, 144 disease (MCTD) 463, 496 Myelomeningocele 613, 614, 616
intellectual disability 147–148, 148 MMR (measles, mumps, rubella) vaccine 385, management 615
irregular periods 144 472 Myocarditis 535
menstrual cycle 142–148 Moles 761–762 Myoclonic epilepsy with ragged red fibers
Mental health problems 47–48, 172–178 Mollusca 762, 763–764 (MERRF) 300, 324
assessment 174 Mongolian spot 758 Myopathy, metabolic causes 323
externalizing 172, 173–174 Monilia 774 Myotonic disorders 611
features 172–174, 173 Monosaccharide malabsorption 731 dystrophy 611
infancy 175 Montelukast 431 myotonia congenita 611
internalizing 172–173 Mood stabilizers 188
management 174–175 Moraxella catarrhalis 472, 473, 781
prevalence 172, 173 Morbidity rates 10–12 N
special issues 176–178 burden of disease 10–12, 11
Mercapto-acetyl-triglycine (MAG3) 642 disease pattern changes 10 Naevoid conditions 758–762
Mercurochrome 208 future directions 14 Naevus of Ota 758
Metabolic factors indigenous children 6–7 Nails, examination 30
acidosis 230–231, 231, 320, 345, 524 Moro reflex 335 Napkin rash 774–775
decompensation, acute 318–322 Mortality rates 2, 6, 7, 11 erosive 774, 774
disorders 125, 758 Aboriginal and Torres Strait ‘frog plaster’ 774
imaging 248 Islanders 51–52 Narcolepsy 153–154
insulin 687 future directions 14 NARP (neurogenic muscle weakness, ataxia,
myopathies 612 global see Global mortality rates retinitis pigmentosa) 324
obesity 81 indigenous children 6–7, 8 Nasal aspirates 499
screening, newborn 339 infant 7–10, 8 Nasal continuous positive airway pressure
Metabolic liver disease 749 Mosaicism, defined 295 (NCPAP) 342
Metabolism Motor disorder 595 Nasal decongestants 434
newborn 329 management 338 Nasal flare 352
see also Inborn errors of metabolism (IEM) severity 596 Nasal mucosa, bleeding 558
Metatarsus adductus 255, 255 Mouth Nasal obstruction 358–359
Metatarsus varus 337 examination 30, 224 Nasogastric feeding 190–191
822 Metformin 87 ulcers, recurrent 778 Nasolacrimal duct obstruction 793
 INDEX

Natal teeth 800 Neurodevelopment Non-steroidal anti-inflammatory drugs

National Aboriginal Health Strategy 52 impairments, prematurity 346 (NSAIDs) (Continued)
National Health and Medical Research small for gestational age (SGA) 348 migraine 628
Council (NHMRC) (Australia) therapy (NDT) 599 pelvic pain 145
breastfeeding 63 Neurofibromatosis 578–579 SAPHO syndrome 464
cultural competency 50 type 1 (NF1) 574 upper respiratory tract infections (URTIs)
dietary guidelines 61 Neurogenic theory, migraine 627 473
energy intake 62 Neurological factors Noonan syndrome 309–310, 309
immunization 91, 91 imaging 237–240 Nordic Conference on Forensic Medicine 127
neural tube defects 619 lesions 406 Norethisterone acetate (NEA) 144
National Immunization Programme for obesity 80, 80 Norrie disease 313, 313
Australian Children (NHMRC) 91 prematurity 343–345 Northern Territory 7, 50
National Institute for Health and Clinical Neuromuscular disorders 603–612 Nose
Excellence (NICE) 809–810 diagnosis 603–604, 604 examination 30
National Survey of Mental Health and Well- respiratory distress 361, 362 see also Ear, nose and throat (ENT); entries
being (Australia) 172, 173, 176 symptoms 603–604 beginning Nasal
National Travel Health Network and Centre Neuromuscular junction disorders 607 Note-taking, consultation 34–35
(UK) 95 acute 607 Nuchal translucency screening 280–281
Necator americans 420, 421 chronic 607 Nuclear genome (nuclear DNA) 289, 290
Neck Neuromuscular scoliosis 258 Nucleotides 289
examination 33–34, 34 Neuropathies Nutrients 61
surgical conditions 272–274 acute 605–606 deficiencies 725
Neck swelling bladder 617 Nutrition 61–74
lateral 273–274, 273 bowel 617 acute gastroenteritis 719
midline 272–273, 273 chronic 606–607 assessment 62–63, 63
Necrotizing enterocolitis (NEC), neonatal fracture 617 breastfeeding 63–64, 63
345, 377 Neutropenia 543–545 deficiency 566
Nedocromil sodium 431 New Zealand wars 58 enteral 721
Neglect see Child abuse Newborn 328–340 growth 658
Neisseria gonorrhoeae 146, 394 breathing problems see Respiratory distress hospitalized child 70–73, 70
Neisseria meningitidis 402, 405, 406, 407, 409, calcaneovalgus foot 253 in utero 63
410, 502 definitions 341, 342 infant formulas/milks 64–67, 65
Nematodes 420, 424 developmental dysplasia of hip (DDH) overnutrition 69
Neonatal lupus syndrome 460, 461 256, 256 refugees 157–159
Neonatal necrotizing enterocolitis (NEC) examination 34, 334–339 requirements 61–62
345, 377 haemolytic disease 757 status 224
Neonates haemorrhagic disease 565 undernutrition 69–70
antibiotics 399 imaging 238 well child 68–69
bacterial meningitis 403 isoimmune haemolysis 555
bleeding 558 neonatal transition 328–330
gynaecology 141 normal checks 339–340 O
health 17, 18 poisoning 208
herpes simplex virus (HSV) 764–765 principles of care 341 Obesity 14, 75–88, 133
imaging 240, 240 screening 325 anthropometry 84
inborn errors of metabolism (IEM) 318, 319 stabilization/resuscitation 330–334, 330, causes 82–83, 82
jaundice 246, 246 332, 333 clinical history 84, 84
liver disease 747, 748–751, 749 statistics 328 complications 78–82, 80
meningitis 408 surgical conditions 375–379 defined 75–77
problems 594 toxic erythema of 756 environmental/behavioural associations
sepsis 369–370 transient tachypnoea (TTN) 355 82–83
skin disorders 756–762 see also Perinatal infections; Premature genetics 82
teeth 800 infant; Small for gestational age (SGA) laboratory investigations 85
vomiting 711–712 NEXUS clinical prediction rule 238 management 84–87, 86
Neoplasms 602 Night terrors 150–151, 151 medical conditions, associated 83, 83
Nephritis, causes 649 NIS genes 673 monogenic forms 82
Nephroblastoma 576–577 Nissen fundoplication 740, 740 outcomes 85
Nephrology imaging 246–247 Nitazoxanide 420, 423 physical examination 84
Nephrotic syndrome 650–652 NKX2.1 mutation 673, 673 physiological basis 82
congenital (CNS) 651–652 Nocardia spp 503 prevalence 77–78
minimal change 650–651, 650, 650 Nocturnal enuresis 177–178 primary prevention 87–88
Nervous system, examination 30 NOD2 gene 720 syndromic forms 82
Neural tube defects (NTD) 613–619 Non-accidental injury see Physical abuse treatment 85–87
antenatal diagnosis 614 Non-alcoholic fatty liver disease (NAFLD) Observation 25, 30, 352, 406
clinical features 614, 614 79–80 Obsessive-compulsive disorder (OCD) 173,
counselling 614 Non-alcoholic steatohepatitis (NASH) 753 173
embryology/pathogenesis 613 Non-epileptic episodic disorders 589–590, middle childhood 186, 186
fetal surgery 614 589 Obstetric emergencies 594
incidence 613 Non-Hodgkin lymphoma 574 Obstructive apnoea 362
management 615, 616–618 Non-intensive mask ventilatory (NIV) support Obstructive jaundice 323
prevention 618–619 153 Obstructive sleep apnoea (OSA) 437, 151–153,
terminology 613 Non-protein-coding genes 292 787–788
Neuroblastoma 575–576 Non-rapid eye movement (NREM) sleep 149, complications 357
Neurocognitive effects, cancer therapy 579 150 Occupational therapists 598
Neurodegenerative disorders 599–602 Non-specific cough 509 Oedema 224
age of onset 601 Non-steroidal anti-inflammatory drugs Oesophageal atresia 278, 375
brain anatomy, distribution 600–601 (NSAIDs) Oesophageal duplication cysts 495, 496
evidence 599–600, 600 arthritis 459 Oesophageal manometry 738
progressive symptoms 600 juvenile idiopathic arthritis (JIA) 457 Oesophagus, foreign bodies 781
systematic reviews 601–602 menorrhagia 144 Oestrogens 659
treatable 602 menstrual management 148 Oligaemia 533
823
 INDEX

Oligoarthritis 453–454, 454 Pancreatic disease 728 Pharyngitis 468, 471

Omeprazole 740 Pancreatic insufficiency 725 streptococcal 471–472, 472
Omphalitis (umbilical sepsis) 271 Pancreatitis 709 Pharynx
Online Mendelian Inheritance in Man Panic disorder 186 examination 30
(OMIM) 314 Pansystolic murmurs 520, 521 foreign bodies 781
Ontogenic lactase deficiency 731 Panton–Valentine leukocidin (PVL) toxin 501 Phenobarbital 588, 592
Opiates 211 Papilloedema 632 Phenothiazine dystonia 211
Optic atrophy, metabolic causes 323 Papular exanthems 763 Phenotype, terminology 278
Optic gliomas 574 Papular urticaria 770–771 Phenylketonuria (PKU) 325
Oral alveolar development cysts 800 Paracetamol 211, 213, 457, 628, 752 Phenytoin 286, 588, 592
Oral contraceptive pill (OCP) 147 Parainfluenza virus 502–503 Phimosis 266, 267–268, 267
contraceptive management 148 Paraphimosis 266, 267 Phosphorus 696, 697, 698
menorrhagia 144 Paraquat 213 Photosensitivity 775–776
pelvic pain 145 Parasites 161–162, 162, 725 blistering 776
Oral hygiene 803 Parasitic infections 419–423, 420 epilepsy 587
Oral rehydration solutions (ORS) 226–227, gastroenteritis 715–716 Phototherapy 351
231–232, 718, 718 treatment 423 PHOX2B gene 153
WHO standards 232, 232 Parasomnias 150–151 Physical abuse 115, 797
Oral ulceration 807–809 Parenteral nutrition 72–73, 74 Maori people 60
Organic acidurias 319 Parents non-accidental injury 249–250, 806
Organisation for Economic Co-operation and child development 36 Physical examination
Development (OECD) 3, 4, 97 health 133 adolescents 137
Organophosphates 211 mid-parental height (MPH) 660–662 bleeding disorders 559
Orlistat 87 support 127–128 clinical consultation 29–34, 30
Oropharyngitis 468 uniparental disomy 293 disorders of sexual development (DSDs) 683
Oropharynx 785–789 see also Family hydrocephalus 622
Orthopaedic problems 252–263, 597–598 Parent's Evaluation of Developmental Status newborn 34, 349
congenital abnormalities 255–258 (PEDS) 39 nutrition 62
injuries 260–263 Parkes–Weber syndrome 761 obesity 84
obesity 79, 80 Paroxysmal torticollis 627 short stature 665, 665, 666
osteochondroses/osteochondritis 259–260 Parry–Romberg syndrome 462 Physical exercise 690
skeletal growth variation 252–255 Parvovirus B19 365–366, 365 fitness 14
Orthotists 598 Passive immunity 89 obesity 83, 86
Ortolani test 256, 256 Past history 27 Physical needs, child 44
Osgood–Schlatter's condition 259, 259 Pasteurella spp 502 Physiotherapists 598
Osler, William 152 Patau syndrome (trisomy 13) 282, 307 Phytophotodermatitis 775
Osteochondritis 259–260 Patchy alopecia 777 Pierre Robin sequence 336, 359–360
Osteochondroses 259–260 Patent ductus arteriosis (PDA) 342–343, Pigeon toeing 254–255
Osteomyelitis 393, 394 527–528, 527 Pigmentary disorders 759, 759, 760
aspirated pus 395–398 Patent urachus 271 naevoid 759, 759, 760
blood/bone culture 397 Patent vitellointestinal duct 271 Pigmented birthmarks 758–759
bone scan 397 PAX-8 mutation 673 Pinworms 142
clinical presentation 394 Pectus excavatum 506 Piperacillin 399
diagnosis 395–398, 396 Pediculosis 770 Pituitary factors, amenorrhoea 145
magnetic resonance imaging (MRI) 398, 398 capitis (head lice) 770 Pityriasis alba 773
plain radiography 397, 397 corporis (body lice) 770 Pityrosporum spp 768
ultrasonography 397–398 pubis (pubic lice) 770 Pizotifen 629, 631
vertebral 400 Pelvic inflammatory disease (PID) 146 Plasmalyte148 solution 226
Osteopenia 597 Pelvic pain 145–146 Plasmaphaeresis 605–606
Osteopetrosis 703 Pelviureteric junction (PUJ) obstruction 646 Plasmodium falciparum 416, 417
Osteoporosis 702, 703 Penicillin G 405 Platelet disorders 560–561, 561
Osteosarcoma (OS) 577–578 Penis 266–268 qualitative 561
Otitis media 781–784 Peptic ulceration 710 Pleural fluid specimen 499
acute 473 Percentile charts 660, 661, 662 Pleuritic pain, imaging 240
diagnosis/management 782–784, 783 Perianal abscess 272 Pluripotential stem cell failure 542–548, 546
Otorrhoea, tympanic membrane (TM) Perinatal infections 363–374 PMP22 gene 606
perforations 784 acute 370–373 Pneumococcal infections 9, 500
Ovarian factors chronic 373–374 pneumonia 499, 499
amenorrhoea 145 modes of acquisition 363, 364 vaccines 95
cysts 146 neonatal sepsis 369–370 Pneumococcus spp 415, 450, 649
torsion 146 organisms, associated 363–369, 364, Pneumocystis spp 447, 449–450
Overnutrition 69 370–374 hyper-IgM syndrome 447
Ovotesticular disorder of sexual development risk assessment 363 severe combined immunodeficiency
685 Perineum 272 (SCID) 448–449, 449
Ovulation 143 Periods see Menses Pneumocystis jiroveci
cyst 143 Periosteum, bleeding 558 common variable immunodeficiency
Ovum, gene mutations 297 Peripheral nerve disorders 605–607 (CVID) 447
Oxcarbazepine 588, 592 acute neuropathies 605–606 protozoal pneumonia 503
Oximetry 196 chronic neuropathies 606–607 Pneumonia 498–503
Oxygen Peritonitis 708, 714 aspiration 492–493, 493
hypoxia 525 Periventricular leukomalacia 344–345 investigations 498–499
supplementary 333 Permanent dentition 805 right lower-lobe 709
treatment 353 Peroxisomal disorders 325 Poisoning 208–214, 714
Persistent femoral neck anteversion 255, 255 antidotes 211
Pertussis (whooping cough) 94, 504–505 common 213, 213
P Pervasive developmental disorders 184–185 diagnosis 209
‘Petit mal’ epilepsy 585 epidemiology 208–209
Pacifiers 129 PH monitoring 737, 738 management 209–213, 210
Palate, examination 30 Phagocytic cell disorders 451–452 prevention 213–214
824 Palliative care 580 Pharyngeal obstruction 359–360, 360 Poisons Information Centre 213
 INDEX

Police services, child abuse 116 Probiotics 232 Pupil size/reactivity 198
Poliomyelitis 94, 604 Prochlorperazine 628 Purpura 762–771, 776
Polyarthritis 455, 455 Productivity Commission 53 exanthems 763
Polycystic ovary syndrome 143, 144, 145 Professionals, health 21, 21 fulminans 566
Polygenic/multifactorial disorders 300–301, child abuse 116–121, 121, 122 neonates 757
301, 314 indigenous peoples 51, 52–54, 55, 56 rash 366
Polymerase chain reaction (PCR) 364–365 interventions 167, 168, 169, 170, 171 Pustular lesions 756
Polymerase (POLG) deficiencies 324 Progestogen-only pills 147 exanthems 763
Polymorphism 294 Progestogen-releasing intrauterine device infective disorders 756
Polymorphous light reaction 775 (IUD) 147 miliaria 756
Polysaccharide capsule 402 Prokinetic drugs 739 simulation 756
Polysomnography (PSG) 151, 152 Promethazine 431, 628 sterile benign transient 756
obstructive sleep apnoea (OSA) 152 Propranolol 533, 628, 629, 631 Pyloric stenosis 232, 712–713, 713
sleep 153 Prostaglandin 524, 535 Pyrantel pamoate 423
Pompe disease 324 Proteins 65, 67 Pyridostigmine 607
Population -coding genes 291, 291 Pyridoxine dependency 590
Aboriginal and Torres Strait Islanders 51 digestion/absorption 727
child statistics 2, 4, 57 translation 291, 292
Port wine stains 761 Proteinuria 650–652 Q
Portal hypertension 748 Proteus spp 502, 639
POSSUM (Physiological and Operative Proteus mirabilis 646 Questions, closing 29
Severity Score for the enUmeration of Proton pump inhibitors 740
Mortality and morbidity) 278 Protozoa 420
POSSUM (Pictures of Standard Syndromes Protozoal pneumonia 503 R
and Undiagnosed Malformations) 305 Protracted bacterial bronchitis (PBB) 511
Postinfectious autoimmune haemolysis 555 Provera 144 Rachitic rosary 700
Post-nasal drip 511 Pseudomonas spp 450, 500, 513, 639 Racial variations in BMI 77
Post-traumatic stress disorder (PTSD) 163, 189 Pseudomonas aeruginosa 394, 447, 502, 514, Radiation 236
Postural torticollis 274 756 background 236, 237
Posture 198 Pseudostrabismus 791, 791 harmful effects 287
intrauterine 252–255 Pseudo-tumour cerebri 632–633 injuries, eyes 794
Potassium 211, 228, 229 Psoriasis 761, 774, 775 Radionuclide scintigraphy 737
Poverty 46–47 guttate (small spot) 763 Radiotherapy 575, 577, 578
Prader–Willi syndrome 110, 188 Psoriatic arthritis 456 Ranitidine 739
Praziquantel 420, 423 Psychiatric disorders 183–191 Rapid eye movement (REM) sleep 149, 150,
Pre-auricular skin tags 336 adolescence 187–191 153–154
Precocious puberty 668, 670–671 infancy/early childhood 183–185 Rapport, establishing 25
Pre-departure medical screening (PDMS) 156 metabolic causes 323 Rashes
Prednisolone 588 middle childhood 185–187 ‘blueberry muffin’ 366
Pregabalin 588, 592 symptoms 183 fever and 382, 383
Pregnancy 145, 167, 595 Psychological factors heat 763
Pre-implantation genetic diagnosis (PGD) abuse 115 neonates 757–758
284, 317 stresses 693 newborn 335
Premature infant 341–346 vomiting 714 refugees 158
causes 341, 342, 343, 344, 344 Psychosocial factors sweat duct occlusion 756
cerebral palsy (CP) 594–595 cancer therapy 579 see also Napkin rash
complications 342–346 forensic 120 Reactive attachment disorders 183–185
eye disorders 797 obesity 78–79, 80, 81–82 Recession 352
immunization 93 screening (HEADSS mnemonic) 135–136, Rectal prolapse 272
immunodeficiency 440–442 136, 145–146 Rectus abdominis, divarication of 337
late preterm 346 short stature 664 Recurrent abdominal pain (RAP) 710–711,
nutrition 72 Psychotropic medication 175 742
Premature menarche, isolated 671 Ptosis 795 management 711
Premature thelarche 670–671 Pubertal development variation 142–143, Recurrent immune thrombocytopenic purpura
Prenatal bleeding 558 669–671 561
Prenatal diagnosis 279–284 asymmetrical breast development 671 Recurrent juvenile papillomatosis 788
genetic conditions 283–284 counselling 670 Red cell aplasia 546, 547–548
indications 281–282 delay 693 acquired 547
screening 280–281 delayed 669, 669 congenital 545, 547
tests 280, 281, 282–283, 282, 283 diagnosis/management 669 Red cell destruction 553–554, 553
Preschool period 169 early normal 669 ‘Red reflex’ 791
common problems 169 growth spurt 660 Redback spider bite 214, 219
food needs 68 gynaecomastia 671 REDCAT (mnemonic) 653
wheezing disorders 491–495, 494 precocious puberty 668, 670–671 Refeeding syndrome 73
Presenting problem treatment 669–670 Referral 25–26, 598–599
acuity 24–25 see also Adolescence Reflex apnoea 362
consultation 26 Pubic lice 770 Reflux oesophagitis 710
Pressure-immobilization first aid 215–218, Public health, pyramid approach 114 Refractive errors 793
217, 219 Pulled elbow 263 Refugees 155
Primary amenorrhoea 143 Pulmonary factors defined 155
Primary ciliary dyskinesia (PCD) 512 air leaks 356 development/learning 163–164
Primary cutaneous herpes simplex 765, 765 atresia 534–535 differential diagnosis 158
Primary dentition, trauma 805, 805 flow murmur 521 health assessment 155–156,
Primary herpes simplex virus (HSV) stomatitis haemorrhage 358 157
471 hypoplasia 357–358 key features 155
Primary herpetic gingivostomatitis 765, 808 imaging 240–242 mental health 163
Primary immunodeficiencies (PID) 439, stenosis 527, 529–530, 529 settlement considerations 164
442–445, 443, 445 Pulmonary tuberculosis (PTB) 160–161, Rehydration 226–227
specific disorders 445–452 415–416, 505 guidelines 718, 718, 718, 719
vaccines 96 Pulses, examination 518, 519 Remineralization products 803
825
 INDEX

Renal factors Royal Australasian College of Physicians Selective dorsal rhizotomy 598
abnormalities, antenatal 646, 647 (RACP) 334, 338 Selective IgA deficiency 448
agenesis 278 Royal Australian and New Zealand College Selective mutism 186
calculi 646 of Obstetricians and Gynaecologists Selective serotonin-reuptake inhibitors (SSRIs)
cysts 323, 647, 647 374 186–187, 188, 189
disease 712 Rubella 94, 285, 366–367, 366, 383, 386–387, Self-management, chronic illness 138
dysgenesis 278 386 Sensory deficit 617
failure, imaging 247 MMR (measles, mumps, rubella) vaccine Separation anxiety disorder 173, 173, 177
function 642 385, 472 Sepsis, imaging 240
osteodystrophy 700–701 Septic arthritis 393, 395
prematurity 345 diagnosis 396, 398
Reproductive system complications 80, 81 S Sequence, defined 303
Reprotox database 288 Sequestration 506
Research, folate intake 619 Sacral agenesis 614 Serotonergic mechanisms, disruption 127
Resilience 166 Sacral dimples/pits 338 Serratia spp 451–452
Respiratory distress 352–362 Sacrococcygeal teratoma 379 Sertoli cells 680
cancer therapy 579 Salbutamol 431 Serum α-fetoprotein (AFP) 613, 614
causes 353–362, 354 Salmonella spp Services see Health services
infections 352, 354, 424, 785, 786, 787 acute gastroenteritis 715 Settings
management, principles of 352–353 antibiotic resistance 415 consultation 25
metabolic causes 323 arthritis 459 treatment 87
symptoms, refugees 158 bone/joints 394 Severe combined immunodeficiency (SCID)
syndrome (RDS) 342, 355–356, 355, 356 gastroenteritis 719 448–449
types 352 pneumonia 502 Sever's condition 259
see also Lower respiratory tract infections tropical/developing countries 415, 417 Sex steroid replacement 686
(LRTIs); Upper respiratory tract Salmonella paratyphi 415 Sexual factors
infections (URTIs) Salmonella typhi 415 abuse 115
Respiratory syncytial virus (RSV) 468, 483, Salter–Harris classification 261, 262 development see Disorders of sexual
502–503 SAPHO syndrome 464 development (DSDs)
Respiratory system Sarcocystis hominis 422 differentiation 680–682
complications 80, 80, 342 Sarcomas 577–579 function 617
examination 32 Sarcoptes scabei 769 intercourse 133
failure 153 Scabies 769–770, 769 Shaken baby syndrome 60
inadequacy effects 196 Scalds 100 Shigella spp 459, 715, 719
newborn 328 child abuse 117 Shigella dysenteriae 418
patterns, neurological failure 198 immersion 117, 118 Shingles 389, 389
rates 195–196, 196, 336 Scalp examination 335–336, 336 Shock, resuscitation 225–226
support 524 Scarlatina 389–390 Shoes 254
Resuscitation 200–207 Scarlet fever 383, 389–390, 390, 763 Short bowel syndrome (SBS) 72, 73
diagnosis 200, 201 Scedosporium prolificans 514 Short stature 662–668, 663
guides 202, 205 Schachman syndrome 728 assessment 664–665
life support 200–205, 205, 206 Scheuermann's condition 260 constitutional delay 663
newborn 330–334, 332, 333 Schistosoma haematobium 419–421 counselling 667–668
ongoing 204–205 Schistosoma mansoni 419–421, 420 examination 665, 665, 666
shock 225–226 Schistosomiasis 161, 419–421, 420 familial (genetic) 663
Retained fetal lung fluid (RFLF) 355, Schizophrenia 188–189 history 665
355 School years 169–170 investigations 666–667
Retinal haemorrhages 323 common problems 170 management 665–666
Retinitis pigmentosa 323 poisoning 208–209 pathological causes 663–664
Retinoblastoma 791, 791, 796 school refusal 176–177 treatment 667
Retinopathy of prematurity (ROP) 346, 797 Scleroderma 462–463, 462 Shunting procedures 633
Retrograde menstruation 145 Scoliosis 257–258, 506, 598 Sickle cell disease 543, 552–553
Retro-orbital bleeding 558 Screening anaemia 399, 552
Reye syndrome 628 combined 281 Sickle trait 552
Rhabdomyosarcoma 578–579 development 39 Sickle-trait–β-thalassaemia 552
Rheumatic heart disease 518, 536 hearing 339 Single nucleotide polymorphisms (SNPs)
Rheumatoid factor-positive maternal serum (MSS) 280 294–295
polyarthritis 456 newborn 325, 339 Single umbilical artery (SUA) 338
Rhinitis, allergic 437 nuchal translucency 280–281 Sinusitis
Rhinoconjunctivitis, allergic 433–434 prenatal diagnosis 280–281 acute 472
Rhinosinusitis 472 psychosocial (HEADSS mnemonic) cough and post-nasal drip 511
Rickets 159, 159, 698, 699–700, 699, 701 135–136, 136, 145–146 recurrent/chronic 437
hypophosphataemic 700 refugees 156, 157, 159, 160–161 Sjögren disease 461
Rickettsial infections 763, 776 Scrotal pathology 270–271 Skeletal disorders 663
Risk factors acute pain 270, 270, 271 Skeletal growth variation 252–255
acceptance 316 oedema, idiopathic 271 Skeletal involvement syndromes 248
developmental stages 166, 167, 168, 169, Scurvy 776 Skin
170, 171 Sebaceous hyperplasia 335, 756 care 617
interpretation 315 Seborrhoeic dermatitis 757, 774 changes 748
pregnancy 167 Secondary amenorrhoea 144–145, 145 examination 30, 33, 224
RNA 291 Secondary immunodeficiency 442, 445 Skin disorders 756–778
mRNA translation 291, 292 Sedentary behaviour, obesity 83, 86 acne 777
transcription 291, 292 Seizure-related headaches 633 bleeding 558, 559
Road trauma 100 Seizures 582–592 blistering 756–757, 776
Roll Back Malaria plan (WHO) 417 assessment 590–591 complications, obesity 80, 81
Rooting reflex 336 imaging 238 dermatitis 771–776
Roseola infantum 383, 385–386 metabolic conditions 319, 322 excessive hair 777
Ross River virus 423 terminology/classification 582, 583 hair loss 776–777
Rotavirus 419, 715, 716 treatment, principles 591–592, 592 infections 424, 437
826
 INDEX

Skin disorders (Continued) Somatic complaints 177 Streptococci (Continued)

infections/infestations 762–771 Somatic mosaicism 297 Group B β-haemolytic 186, 502
lesions 335 Somatic symptoms 176 Group B (GBS) 372–373, 394
metabolic causes 323 Somatization disorder 190 Group C 502
mouth ulcers, recurrent 778 Somatoform disorders 190 perianal disease 767
neonates 756–762 Sore throat, acute 785–786 pharyngitis 471–472, 472
purpura 757, 776 Spasmodic croup 480 toxic shock 388, 763
Slapped cheek disease 387, 387 Spastic cerebral palsy 595 Streptococcus agalactiae 369, 372, 408, 410
Sleep 28 Spastic hemiplegia 596 Streptococcus pneumoniae
development/maturity 149 Spastic quadriplegia 596 acute otitis media 473
environment 128 Spasticity 598 acute sinusitis (rhinosinusitis) 472
infants 167 Special senses, examination 33 bacterial pneumonia 499
newborn 340 Specialized paediatric services 12–13 bone/joints 394
physiology/function 149, 150 Speech impairment 111–112, 111 meningitis 402, 404, 405, 407, 410
position 128 Speech pathologists 598 otitis media 781
Sleep problems 149–154 Sperm, gene mutations 297 vaccine 413
behavioural aspects 149–150, 151 Spider bites 214, 218–219 Streptococcus pyogenes 388, 390, 394, 767
insufficient sleep 153 Spina bifida 278, 613 acute sore throat 785, 786
metabolic causes 323 adults 618 bacterial pneumonia 502
parasomnias 150–151 cystica 613, 614 bacterial tonsillitis 471–472, 472
polysomnography (PSG) 151, 152 management 616 rheumatic fever 786
rare conditions 153–154 occulta 613, 614, 615 Streptococcus viridans 536
spectrum of 151–153 Spinal cord Stridor 475–478, 788, 789
Sleep-disordered breathing 80, 80 imaging 238 acute 476
Sleepwalking 150–151, 151 tethered 617 causes 476–478
Slipped capital femoral epiphysis 260, 260 Spinal deformities 617 differential diagnosis 475–476
Slow virus infection 412 Spinal dysraphism 238–240, 613 imaging 241
Small bowel problems Spinal infection 400 investigations 478, 479
atresias 376, 377 Spinal muscular atrophies (SMAs) 604, 604 persistent 476
disease 729–730 type 1 604–605, 605 physiological principles 475, 476
obstruction, subacute 244 type 2 605 Stroke
perforation 99 Spine, examination 30 imaging 238
Small for gestational age (SGA) 72, 347–348 Spirometry 485, 486 metabolic causes 323
causes/complications 347, 347, 348 Spleen, trauma 99 Stroke-like episodes 300
growth 348, 663 Splenomegaly 559, 747 Strongyloides spp 161–162, 419
prognosis 347–348 Sprintzen (DiGeorge) syndrome 110, 188, 305, Strongyloides fulleborni 422–423
terminology 347 307–308, 450 Strongyloides stercoralis 420, 422–423
treatment 347 Sputum 499 Strongyloidiasis 420, 422–423
Smegma 266, 267 SRY gene 680 Structural airway abnormalities 493–494
Smith–Magenis syndrome 111 Stage 45 disease 576 Subacute sclerosing panencephalitis
SMN1 gene 605 Stanford-Binet scales 40 (SSPE) 385
Smoking 13–14, 473, 474 Staphylococcal infection 756 Subconjunctival haemorrhages 336
passive 502 pneumonia 500–501, 500 Subdural effusion 406–407, 407
-related disorders 13–14 toxic shock 763 Subgaleal haemorrhage 335
smoke-free environments 128 Staphylococcus spp 451–452, 501, 639, 649, Subglottic cysts 788
Snake bites 214, 215 794 Subglottic haemangioma 478, 478, 493, 788
antivenom 217–218 Staphylococcus albus 536 Subglottic stenosis 477–478, 788
management 215–218, 216 Staphylococcus aureus Submental lymph node/abscess 273
Snoring 152–153 atopic dermatitis 437 Subsarcolemmal cytoskeleton 608, 609
SOAP note format 24, 34–35 bacterial disease 415 Substance/drug abuse 47–48, 133, 213–214
Social factors bone/joints 393, 398, 399 Sudden infant death syndrome
adjustment 618 cystic fibrosis 514 (SIDS) 7, 8
history 27 infective endocarditis (IE) 536 mortality rate 124, 124
needs, child 44 pneumonia 500 see also Sudden unexpected death in infancy
phobia 173, 173, 177, 186 recurrent meningitis 410 (SUDI)
refugees 163 scalded skin syndrome 756, 758, 766–767, Sudden unexpected death in infancy (SUDI)
Social Trends 2010 4 767, 774 123–129
Society for Paediatric Gastroenterology, Startle reflex 335 aetiology 124–127
Hepatology and Nutrition STAT3 gene 451 classification 127
European 738 Steatorrhoea (fatty diarrhoea) 725, 726–730 definitions 123–124
North American 738 Steinert disease 611 exogenous stressors 126
Socioeconomic issues 58–59, 83, 502 Stem cell proliferation disorders 542–548, 546 historical perspective 123
Sodium 230 Stem cell transplant 572 incidence 124, 124
Sodium chloride 225–226, 226, 227 Stenosis 278 parent support 127–128
Sodium valproate Stenotrophomonas maltophilia 514 prevention 128–129
absence seizures 588 Sternomastoid tumour 274, 274, 274 procedures 127
epilepsy 587–588 Steroids 464, 487, 488, 633 triple risk model 125, 126
focal seizures 588 Stevens–Johnson syndrome (SLS) 776 Sugar malabsorption 719
generalized tonic-clonic seizures 588 Sticky eyes 336 Suicidal intention/behaviour 176, 176
liver dysfunction 752 Still's murmur 521 Suicidality 136
migraine 629 Stimulants 181 Sumatriptan 628
myotonic, atonic, tonic seizures 588 Stone fish 214 Sun exposure 13–14
pregnancy 286 Stool examination 725–726, 725 Support services, family 48–49
seizures 592 Strabismus 792 Supracondylar fracture, humerus 261–262,
Soft tissue disorders 806–809 Strangulated inguinal hernia 713 262
sarcoma 578–579 Streptococci Supraventricular tachycardia 537
Solar urticaria 775 Group A 415, 500 Surgical conditions 266–274, 375–379
Solid foods 68 Group A β-haemolytic (GABHS) see anus/perineum 272
Somatic (body) cells 289 Streptococcus pyogenes inguinoscrotal region 268–271
827
 INDEX

Surgical conditions (Continued) Tests Transient neonatal pustular dermatosis 756

neck 272–274 batteries 40 Transient tachypnoea of newborn (TTN)
penis/foreskin 266–268 predictive 315 355
umbilicus, abnormalities 271–272, 271 Tetanus 94 Translation 291, 292
Survanta 353 Tethered spinal cord 617 Transposition of great arteries 527, 533–534,
Swaddling 256 Tetralogy of Fallot 527, 532–533, 532 533
Sweat duct occlusion rash 756 Thalassaemias 543, 551–553 Transpyloric feeding 740
Syncope 590 Thelarche, premature 670–671 Trauma 97–101
Syndrome, defined 303 Theophylline 487, 488 abdomen 243, 245
Syndrome of inappropriate ADH secretion Thermal injuries, eyes 793–794 blistering 776
(SIADH) 229 Thermoregulation, prematurity 346 chest 241
Synthetic dysfunction 746 Thomsen disease 611 eyes 793–794
Syphilis, congenital 367–368, 756, 774 Thoracic dystrophies 506 foreign bodies 780–781
Systemic arthritis 455, 455 Thoracic mass, imaging 241–242, 241 head 237–238, 237
Systemic juvenile chronic arthritis 763 Throat see Ear, nose and throat (ENT) musculoskeletal 247, 248
Systemic lupus erythematosus (SLE) 452, Thrombocytopenia 543–545, 560, 561, 776 oral ulcers 808
459–460, 649–650 Thrombocytopenia-absent radius (TAR) organ injuries 99
photosensitivity 775 syndrome 545 paediatric care 97–99
Systems review, consultation 27 Thrombosis 566, 566 prevention 99–100
Systolic murmurs 520–521, 521 Thymidine (T) 289 purpura 776
Thyroglossal cyst 273 refugees 163
Thyroid disorders 672–679 teeth 804–806
T masses 677–678 see also Post-traumatic stress disorder
nodules 678 (PTSD)
Tachypnoea 352 Thyroid hormone 659 Travel bug 414
Tacrolimus 722 Thyroid physiology 672 Travel, vaccines 95
Talipes calcaneovalgus 252, 253, 337 Thyroid transcription factor (TTF) Treaty of Waitangi 57–58
Talipes equinovarus 278, 337 TTF-1 mutation 673 Trematodes 420
congenital 257, 257 TTF-2 mutation 673 Treponema pallidum (syphilis) 367–368, 756,
postural 252 Tibia fracture 262 774
Tall stature 668–669 Ticarcillin 399 TRH receptor gene 673
causes 668 Tinea 768, 768, 777 Trichotillomania 777
diagnosis/treatment 668–669 Tinea versicolor 768–769, 769 Trichuris spp 419
familial factors 668 Tinidazole 420, 423 Trichuris trichiura 419, 420, 422
syndromes causing 668 Tiptoe test 252–253, 253 Tricuspid atresia 534
Tantrums 168, 169, 176, 177 Tobacco see Smoking Tricyclic antidepressants (TCAs) 178, 211
Teamwork 39–40, 106, 185, 598–599 Toddlers 168–169 Trigger thumb 257, 258
Technology, assistive 599 bow legs 253 Trimethadione 286
Teenagers see Adolescence common problems 168–169 Trinucleotide repeat sequence disorders
Teeth metatarsus adductus 255, 255 308–309
acquired disorders 801–804 nutrition 68 Triple risk model 125, 126
anomalies, developmental 800–801 tibia fracture 262 Triple X syndrome 307
cancer therapy effects 579 Toddlers' diarrhoea 724 Triplet repeat mutations 296
dental erosion 806, 806, 807 Todd's paresis 587 Triptans 628, 631
development 799–800, 800 Toes, curly middle 254, 254 Trisomy 13 (Patau syndrome) 282, 307
examination 30 Toilet phobia 178 Trisomy 18 (Edwards syndrome) 282, 306–307,
medications 809 Toilet training 169 375
soft tissue disorders 806–809 Tone 338 Trisomy 21 see Down syndrome
special health-care and 809–810 Tongue Truncus arteriosis 535
teething 799–800 examination 224 TSH-R gene 588
trauma 804–806 tie (ankyloglossia) 338 Tuberculosis (TB) 131–132, 160–161, 415–416,
Television watching 82–83 Tonsillectomy 788 505
Telogen effluvium 777 Tonsillitis 468 control 413
Temper tantrums 168, 169, 176, 177 acute bacterial 472 Tuberculous meningitis 405, 409
Temperature control, newborn 328–329 Epstein–Barr virus (EBV) 471 Tumour lysis syndrome 575
Temporal arteritis 634 Topiramate 588, 592, 629 Tumours
Temporal lobe epilepsy (TLE) 588, 589 TORCH group of organisms 594 brain 572–574, 573, 573
Tension-type headache (TTH) 629–630 Torticollis 274 central nervous system (CNS) 572–574,
Teratogens 284–288 congenital muscular 257 573
access 285 postural 274 imaging 238, 239
dose 285 Total body water (TBW) 222, 223 intracranial 632
exposure, timing 284–285 Toxic epidermal necrolysis (TEN) 776 lymph node 274
genetic susceptibility 285 Toxic erythema of newborn 756 rare 579
important 285–288, 286 Toxicity assessment 569 sternomastoid 274, 274, 274
information services 288 Toxoplasma spp 503 Wilms' 576–577
interaction 285 Toxoplasma gondii 367, 367 Turner syndrome 307, 658, 659, 663–664, 664
paternal exposure 288 Tracheal obstruction 360
requirements 284–285 Tracheo-oesophageal fistula 278
Teratological hip 256 Tramcinolone acetonide 431 U
Terbutaline 431 Tranexamic acid 144, 148
Terfenadine 431 Transcription 291, 292 Ulcerative colitis (UC) see Inflammatory
TERIS database 288 Transferrin isoforms 325 bowel disease (IBD)
Testes Transient erythroblastopenia of childhood Ulcerative pharyngotonsillitis 470–471
malignancy 270–271 (TEC) 547–548 Ulcers
retractile 270, 270 Transient erythroid aplasia 548 aphthous 808
torsion 271 Transient infantile wheeze 491 gastric 741
undescended 269–270, 269, 270, 597 Transient lower oesophageal sphincter indolent 765
Testicular appendix, torsion 271 relaxation (TLOSR) 735, 739 nodules 774
Testosterone 659, 680 Transient neonatal myasthenia gravis 607 oral 807–809
828
 INDEX

Ultrasonography 280 Vagus nerve stimulation 592 Volvulus, malrotation 711, 712
Umbilicus 337 Valproate 188, 587 Vomiting
abnormalities 271–272, 271 Vancomycin 405 acute diarrhoea and 717
discharge 271–272 Varicella-zoster virus (VZV) (chickenpox) bile-stained vomitus 337
granuloma 271 388–389, 388, 762 bilious 243
hernia 271, 271, 272 neonates 756 childhood 713–714
sepsis (omphalitis) 271 perinatal 368–369, 369 infancy 712–713
stump bleeding 558 Varix 761 infection 712
Unconjugated bilirubin 348 Vascular factors neonatal period 711–712
Unconjugated hyperbilirubinaemia 350, access 204 newborn 339–340
351 birthmarks 760–761 non-bilious 243, 245
Undernutrition 69–70 defects 565–566 psychological causes 714
Undervirilized XY child 684 events 594, 594 see also Gastro-oesophageal
Unified airways hypothesis 488 malformations 761 reflux (GOR)
Unilateral pulmonary agenesis 506 Vascular ring, congenital 494, 494 Von Willebrand disease 144, 565
Uniparental disomy 293 Vasculitis 776 Voriconazole 399
United Nations (UN) Vasoconstrictors 434 Vulvovaginitis 142
Convention on the Rights of the Child VATER association 303, 309–310
(1990) 19 Vegan diets 68–69
conventions on child health 19 Vegetarian diets 68–69 W
High Commissioner for Refugees (UNHCR) Velocardiofacial (DiGeorge) syndrome
18 (VCFS) 110, 188, 305, 307–308, 450 ‘W’ position 255, 255
Millennium Development Goals (MDGs) Venoms 214 Waist:height ratio 75
(2000) 19, 20 Venous hum 521–522 Waist circumference 75
Upper gastrointestinal endoscopy 737 Venous malformation 761 Walking reflex 338
Upper limbs 598 Ventilation, mechanical 353 Warfarin 287
Upper respiratory tract infections (URTIs) Ventricular septal defect (VSD) 526–527, 527, Warts 764
468–474 527 WASP gene 449–450
age 469 Ventricular shunts 624 Wasps 214
complications 468, 470 Ventricular tachyarrhythmias 537 Water transport, abnormal 725
identifiable syndromes 468–473 Ventriculoatrial shunt 624 Weight
prevalence 469, 470 Ventriculoperitoneal shunt 623–624 birth 12, 341, 594–595
prevention/treatment 473, 473 Vertebral osteomyelitis 400 change 224
tobacco smoke 473, 474 Very low birth weight (VLBW) 71 for gestational age 341
viral, incubation period 468, 469 Vesicoureteric junction (VUJ) obstruction measurement 31
Urea cycle defects 319 646 newborn 339–340
Urethral valves, posterior 645 Vesicoureteric reflux (VUR) 640, 644–645, overweight see Obesity
Urinalysis 638 644 Werdnig–Hoffmann disease 604–605,
Urinary obstruction 646–647 -associated nephropathy 645 605
management 646–647 Vesicular exanthems 763 Weschler Intelligence Scale 107
Urinary tract abnormalities 644–647 Video-assisted thoracoscopic surgery (VATS) Weschler tests (WPPSI, WISC) 40
Urinary tract infections (UTI) 638–644 501 West syndrome 584–585, 584
asymptomatic infection 644 Vigabatrin 584–585, 588, 592 Western Australian Child Health
diagnosis 638–639, 640 Violence 48, 133 Survey 47
epidemiology 638, 639 see also Child abuse Wet dressing 772
imaging 246–247, 247 Viral exanthems 762–763 Wheezing disorders 491–497
investigations 640–642 Viral gastroenteritis 715, 716 causes 491–496, 494, 496
microbiology 639 Viral hepatitis 162 defined 491
treatment 639–640, 643 Viral meningitis 405, 410, 410 imaging 240
Urine 774 Viral pneumonia 502–503, 503 infection 491–492, 495–496
culture 639, 641 Virilized XX child 684, 684 pathophysiology 491
output, dehydration 224 Viruses 415, 483 see also Asthma
Urology, imaging 246–247 Vision Whipworm 420, 422
Urticaria abnormal 790 White cell count 395, 400
food-induced 763 development 790 ‘White’ light reflex 791
papular 770–771 measurement 790 White matter, diffuse disorders 601
solar 775 see also Eye disorders; Eyes White Men Are Liars – Another Look at
Urticarial exanthems 763 Visual handicap 795–796 Aboriginal–Western Interactions
Uterovaginal agenesis 143 Vital signs (Bain) 55–56
by age 196 Whole bowel irrigation 211
examination 32, 32, 224 Whooping cough 94, 504–505
V respiratory distress 352 Williams syndrome 305–306
Vitamin A 69–70, 286–287 Wilms' tumour 576–577
Vaccines 94–95 Vitamin B 69–70 Wilson's disease 753
administration 92–93 Vitamin B12 68–69, 104–105 Wiskott–Aldrich syndrome (WAS) 442, 445,
development 96 acquired disorders 733 449–450, 559
live virus 93 congenital disorders 733 Wolff–Chaikoff effect 674
requirements 89–90 deficiency 548–549, 602 Workforce participation 46
selection, principles 90–91, 90 malabsorption 732–733 World Health Organization (WHO) 5, 15
sites of administration 92 Vitamin C 68–69, 71 body mass index (BMI) 75
storage 92 Vitamin D 71, 104–105 breastfeeding 60
see also Immunization deficiency 70, 148, 602 guidelines on paediatric care 20
VACTERL association 375 refugees 157, 159–160, 159 Helicobacter pylori 741
Vagina rickets 698, 699, 699 immunization 95
bleeding 141, 142, 337 Vitamin E 71 Integrated Management of Childhood
discharge 142 Vitamin K 339 Illness (IMCI) 20
mucoid discharges 337 Vocal cord oral rehydration solution (ORS) 232,
mucosa skin tags 337 dysfunction 496, 497 232
pain 142 paralysis 788 treatment protocols 414
829
 INDEX

Worms, vaginal pain 142 X-linked dominant inheritance 299–300 Yersinia enterocolitica 719
Wrapping, infants 256 X-linked recessive inheritance Y-linked inheritance 300
299, 299
XXX syndrome 668
X XYY syndrome 668 Z
X chromosomes 289 Zinc
inactivation 297 Y deficiency 724–726, 757, 775
X-linked adrenoleukodystrophy (XALD) 325 malabsorption 733
X-linked agammaglobulinaemia (XLA) Y chromosome 289 Zonisamide 588, 592
445–447 Yersinia spp 459, 502 Zoster immune globulin (ZIG) 369

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