NICU

Handbook
2022

Department of Pediatrics
UNIVERSITY OF WISCONSIN
SCHOOL OF MEDICINE AND PUBLIC HEALTH

135
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The guidelines in this handbook are suggestions and a starting point
for management of newborns in NICU supervised by neonatology
providers. They are not intended, nor should they ever be used,
as a substitute for careful evaluation of our patients and thoughtful
diagnostic and therapeutic plans. Direct in-depth discussion with a
member of neonatal supervisory team must occur for individualized
patient care. Please consult a textbook of neonatology for more in-
depth pathophysiology, differential diagnoses and management
issues.

Nina Menda, MD

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 Table of Contents

1. Definitions and Outcomes 1

a. Common NICU abbreviations 1
b. Meriter survival data 1

2. EPIC in NICU 2
a. Dot phrases and navigators 2
b. Medication order entry 3

3. Common NICU Guidelines 5

a. Wisconsin newborn screen 5
b. Immunizations 5
c. Discharge readiness 7
d. Discharge with NGT feeds 10

4. NICU Procedures 12
a. Intubation and medications 12
b. Umbilical catheters 14
c. Lumbar puncture 17

5. Neonatal Resuscitation 18

6. Management of Micropremie 22

7. Screening for Hypoglycemia

in Newborn Nursery 28

8. Respiratory System 32
a. Delivery room management of RDS 32
b. Ventilator management 34
c. Extubation checklist 41
d. Bronchopulmonary dysplasia 41
e. Use of steroids 42
9. Acid Base Balance 43
10. Fluids, Electrolytes and TPN 47
a. Nutritional components 48
b. Electrolytes and minerals 50

11. Enteral Nutrition 54

a. Feeding protocols 55
b. Drug to avoid during lactation 58
c. Special considerations 58
d. Vitamin and iron supplements 62

12. Necrotizing Enterocolitis 64

13. Hyperbilirubinemia 69
a. Bilirubin management for ≥ 35 wks. 69
b. Phototherapy guideline for < 35 wks. 73
c. Direct hyperbulirubinemia 77

14. Cardiovascular System 79

a. Shock 79
b. Arrhythmias 84
c. Patent Ductus Arteriosus 87
d. Persistent Pulmonary Hypertension 89
15. Hematology 93
a. Transfusion guidelines 95
b. Anemia of prematurity 95
c. Thrombocytopenia 97

16. Infectious Disease 99

a. Neonatal Sepsis 99
b. HSV 104
c. Hepatitis B 104
d. GBS protocol 104
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17. Central Nervous System 107
a. Neonatal seizures 107
b. IVH and PVL 112
c. Apnea and bradycardia in newborn 113
d. HIE and Hypothermia protocol 114

18. Neonatal Kidney 125

a. Management of Hydronephrosis 126
b. Evaluation and treatment of UTI 126

19. Neonatal Opioid Withdrawal Syndrome(NOWS) 129

20. Retinopathy of Prematurity 132

21. Metabolic Disease in Newborn 138

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 Chapter 1: Definitions and Outcomes
Nina Menda, MD

Vital Statistics: Definitions

• Perinatal Period From 28 weeks to 7th day of life
• Preterm birth Birth prior to 37 completed weeks
• Late preterm birth Birth between 34 and 36 6/7 weeks
• Term birth Birth from 37 to <42 weeks
• Post term birth Birth from 42 weeks or greater
• Low birth weight Less than 2500 grams
• Very low birth wt (VLBW) Less than 1500 grams
• Extremely low birth wt (ELBW) Less than 1000 grams
• SGA/LGA <10%/<90th%
• IUGR Intrauterine fetal growth <10% for GA
• Fetal death Death after 20 weeks of gestation
• Neonatal death Death prior to 28 days of age
• Infant death Death up to one year of age

2019 US Births Statistics

• Total births 3,747,540
• Total Preterm Births (<37 wks) 10.2%
• Early Preterm Births (<34 wks) 2.8%
• Low birthweights 8.3%

Meriter Survival Data

Statistics collected from Meriter NICU from 2015-2020
Gestational Age at Birth Percent Survival
23 weeks 60%
24 weeks 76%
25 weeks 94% Reference: National Center for
26 weeks 80% Health Statistics, CDC 2019.

27 weeks 93% FastStats - Births and Natality

28 weeks 96% (cdc.gov)

29 weeks 94% Vermont Oxford Network-Nightingale

30 weeks 99% Database
31 weeks 97%
32 weeks 99%1
 Chapter: 2 NICU EPIC Survival Kit
(UPH-Meriter Epic)
Adam Bauer, MD; Ann Ebert, PharmD; Kate Hirsch, NNP

1. Dot phrases for notes:

a. Progress note: .NICUPROGRESS
b. History and Physical: .NICUADMISSION
c. Neonatal Encephalopathy Exam: .HIEEXAM
d. Delivery: .NICUDELIVERY
e. Transport: .NICUTRANSPORT, .NICUTRANSPORTBRIEF
f. Interim Summary: .NICUINTERIM
g. Inpatient Consult: .NICUCONSULT
h. Substance Abuse Counseling: .NICUMARIJUANABF, .NNNCONSULTMETHADONE
i. Procedures: .NICUINTUBATION,.NICUUMBILICAL,.NICULUMBAR,.NICUPICC,
.NICUCHESTTUBE, .NICUPAL, .NICUARTERIALPUNCTURE, .NICUTHORACENTESIS,
.NEWBORNCIRCUMCISION
j. Discharge Summary: .NICUDISCHARGE
2. Dot phrases for labs:
.NICUCBC .NICUBILI .NICUNUTRITION
.NICUDEXI .NICUWBLYTES .NICUBMP
.NICUCBG .NICUCULTURES .NICUABG
.NICUVBG .NICUCORDBLOOD .NICUCRP
.NICUHISTOGRAM .NICUWBHGBHCT .NICUABGTEMPCORRECTED

3. Deliveries
a. Fill in APGARS and resuscitation information under the Delivery Summary tab
located on the left side in mother’s chart. The two sections that should be filled
out by the Neonatal Provider attending the delivery include Resuscitation and
Assessment.
b. Write a delivery attendance note (.NICUDELIVERY)for any baby that is not
admitted to the NICU. If you attend the delivery and admit the baby, the NICU
admission note will contain that information and a separate delivery attendance note
is not required.

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4. Admission
a. Use the Neo Admission Navigator (tab on left of screen) to do admission
orders
b. Go to the Dosing Weight tab and enter the birth weight in the Drug
Calculation Weight section
c. Go to the Med Reconciliation tab
d. Click on Problem List to enter problems for a patient
e. Click on New Orders for Floor
f. Under Order Sets, you can set as Favorites the following Order Sets that
can be helpful orders:

MHM NICU Admission

NICU Feeding Panel NICU Intubation Meds
MHM NICU Lumbar Puncture
MHM NICU Mechanical Ventilation
MHM NICU Non-Invasive Mechanical Ventilation
MHM NICU Cooling
MHM NICU Prepare and Transfuse Blood Products
MHM NICU Discharge
MHM Newborn Admission
MHM Neonatal Circumcision
MHM Newborn Withdrawal
g. Update information in the NICU Signout (under Shared Patient Lists)

5. Order Entry
a. Use Manage Orders (tab on left screen) to enter orders during Rounds
b. For IV fluid orders: use the pseudonym “NICUIV” – this will give you an
abbreviated list of IV solutions built for NICU patients (Under the Facility List
tab).

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 c. Use the pseudonym “NICU MOR” for morphine options (both PO and IV) that
are specific to NICU patients.
d. Orders for starter TPN can be entered and modified by providers
e. The unit pharmacist will enter orders for fat emulsion when started and will
order and modify all custom TPN orders when needed.
f. Contact the unit pharmacist for any questions relating to order entry and for
guidance with finding the correct product.
6. Transfer
a. Use the Neo Transfer Navigator to transfer patients from the Newborn Nursery
to the NICU and vice versa. Select Med Reconciliation to reconcile transfer
orders
7. Discharge
a. Use the Neo Discharge Navigator (tab on left of screen) and select Med
Reconciliation to reconcile discharge orders
b. Order the follow up appointments through the Neo Discharge Navigator
8. Important Reminders:
a. To access the mother’s chart, go to the Summary tab on the left of the screen
and then click the mother’s name
b. Labs should either be entered as “Routine” or “STAT”

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 Chapter 3: Common NICU Guidelines
Elizabeth B. McBride, MD

A. Admissions
• All babies born <35 wks GA or <2000 g must be admitted to NICU
• Admissions should be staffed with the neonatal provider (APP, hospitalist, fellow,
neonatologist)
B. Wisconsin Newborn Screen
All Infants:
– Collect an initial specimen at 24-48 hr of life
– Collect another specimen at 48-72 hr of life on infants initially tested at <24 hr of age
– Always try to collect the initial specimen prior to a blood product transfusion
Infants with a birth weight <2,200 g
– Collect a repeat specimen at 14 days of age
– Collect another specimen at 30 days of life or discharge, whichever comes first, and
monthly there after until3monthsofageoruntil discharge.
Infants with a birth weight ≥ 2,200 g and GAB > 34 weeks
– Collect a repeat specimen at 30 days or just before discharge or at one
month of age, if hospital stay is longer than one month
Transfused infants
– Collect initial specimen before transfusion, if possible
– If specimen is collected before transfusion and less than 24 hours of age,
repeat testing at 48-72hrs of life and another at 60 days of life (at least >14
days from previous transfusion)
– If initial specimen was collected post-transfusion, testing should be done at 60 days of
life (at least>14daysfromprevioustransfusion)
– Always list date of most recent transfusion on specimen collection card
At discharge:
– Always collect a specimen at discharge unless the previous specimen was collected
within 7 days of discharge.
Before transfer
– Collect a specimen before transfer, if possible
– Inform receiving hospital of specimen collection status
C. Immunizations
All immunizations require parental permission
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 – Hepatitis B vaccine
• <2 kg at birth– give at one month of age or prior to discharge, whichever
comes first
• ≥2 kg at birth – administer as soon as medically feasible after birth
– Other standard immunizations are given when baby is 2 months old and
relatively stable. (Hib, Prevnar, Hep B, Polio, DTaP)
– During RSV season (November thru April) Palivizumab (Synagis®)
prophylaxis should be given prior to discharge to:
• All babies ≤ 28 6/7 weeks
• Chronic lung disease of prematurity, < 1 yo, and birth < 32 weeks 0 days’
gestation and required supplemental oxygen for at least 28 days after birth
• Chronic lung disease of prematurity, between 1 yo and 2 yo who required at
least 28 days of supplement oxygen after birth and who continues to require
supplemental oxygen, chronic diuretic therapy, or chronic systemic steroid
therapy
• Infants <1yo with congenital heart disease with any of the following:
– Congestive heart failure on medication
– Moderate to severe pulmonary hypertension
– Cyanotic heart disease in consultation with cardiologist
– Infants undergoing cardiopulmonary bypass
– Infants who receive cardiac transplantation
• Infants with congenital abnormalities of the airway or neuromuscular disease that
compromises handling of respiratory secretions.
• Profoundly immunocompromised infants
• Infants with Cystic Fibrosis < 24 months at beginning of RSV season
• Infants with interstitial lung disease < 24 months at beginning of RSV season
D. Hearing Screen: Perform within 90 days. Must be prior to discharge. Should
also be done after completing phototherapy.
• If refers on repeat testing & baby is < 7 days old
– Send salivary CMV PCR
– Request Meriter Family Liaison or Postpartum HUC to schedule repeat
hearing screen in Meriter outpatient lactation clinic
• If refers on repeat testing & baby is > 7 days old
– Ensure salivary CMV PCR sent
– Enter referral either to:
• Audiology for an appointment in 2 weeks (1-3 hrs, may require sedation)
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 • UW Speech & Hearing Free Clinic with Amy Hartman; (608) 262-3951
E. Updating parents, Primary Care Provider (PCP) and Obstetrician
– Use NICU phone number 608-417-6215. Call through paging 608-262-2122, provide
parents phone number to operator and ask operator to call
– For UW or Meriter PCPs, consider Healthlink or Meriter Epic inbox message
– Parents: Parents of NICU patients should be updated either in person or by phone.
• On admission
• Any major change in patient’s status: Immediately.
• Critical status: Daily.
• During convalescence: Twice per week.
• Prior to discharge: To assess that parents are fully prepared to take care of their infant
• Phone etiquette: When calling a parent on phone, do not leave any medical
information on voicemail or with a relative. Advise parents to call immediately if
emergency or when available for routine update.
– PCP:
• Once identified, notify PCP about NICU admission of the patient
• Update at least every 2 weeks during NICU stay (unless PCP requests differently)
• Call prior to discharge with summary of hospital course
• Call in the event of patient’s death
– Obstetrician: Notify the obstetrician if the infant dies and give brief summary.
They will follow the mother post-partum and they should know about this event
F. Discharge Management
Discharging a high-risk infant requires significant preparation by the family and
the NICU team. The goal is to prepare the family with education and training
during infant’s hospital stay such that they are ready to take care of their infant
when infant is physiologically stable and ready for discharge.
1. Discharge Planning
• Hearing Screen
• Car seat challenge w/in 72 hrs of discharge for infants with any of the following
criteria:
• born <37 weeks gestation
• birth weight <2500 g
• discharging on home oxygen
• hypotonia (T21, congenital neuromuscular disorder, etc.)

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• Congenital heart disease screen
• Circumcision if requested
• CPR for parents
• Head circumference and length measured on the day of discharge
• When applicable, add “Home going Nutrition Plan” formulated by Sally Norlin
and print hospital growth chart for PCP and the family

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 2. Evidence of Physiologic Stability and Medical Readiness for Discharge
• Minimum Requirements in Each Category

GA GA GA >35 weeks
<30 weeks 30-35 weeks >7 days of age*
Thermoregulation
Number of days in open
2 days 2 days 1 day
crib
Feedings
Number of days on
home nutrition with
adequate weight gain 3 days 2 days 2 days
and/or taking
acceptable
10 gm/kg/day OR 10 gm/kg/day OR
What is adequate
Maintaining Maintaining growth
weight gain?
growth percentile percentile
Cardiorespiratory Stability
Breathing room air
3 3 2
without any device
Days off caffeine
without significant
7 7 5
cardiopulmonary
events
Days free of non-
feeding related
cardiorespiratory 5 days 3-5 days 2-3 days
events requiring
stimulation
*Not applicable for infants >35 weeks and ≤7 days old

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3. Follow-up Appointments
Patient must have all follow up appointments scheduled and recorded in the
discharge summary.
• PCP: 1-3 days after discharge
• All subspecialty clinics (ask subspecialist about timing)
• Developmental follow-up:
– Waisman Center Newborn Follow-up Clinic
• All neonates <28 weeks and/or birth weight <1500gm.
• Any infant with significant developmental concerns and all infants with NGT
feed.
• Neurologic abnormalities, HIE, multiple congenital anomalies
• Schedule as soon as possible (typically multi-week wait)
– Meriter Developmental Assessment Clinic:
• Infants 28-32 weeks or at risk for developmental delays
• Evaluation is done by RN, speech therapist, and OT
• Seen at corrected age of 6, 18 and 30 months
– Great Results After Discharge “GRAD” Program
• Provide nutritional recommendations to the PCP and family during the
transition from hospital to home
• Criteria for referral to the program include infants born<326/7weeks
or with a birth weight <1500 grams
• 1st appointment within 2 weeks following discharge. (up to 3 appts)
• Evaluation by nutritionist and lactation consultant
4. Discharge of Infant with Bridled Nasogastric Tube (NGT) Feedings
– Bridle is inserted & attached to NGT to reduce risk of tube dislodgement, but
does not eliminate
• If tube dislodgement occurs during business hours, replace in peds GI clinic

• If tube dislodged overnight, contact peds GI on-call but may have to go to UW

ED
– Infants may be candidates if PMA > 40 weeks & > 40% PO intake for at least 5-7
days
– Order “bridle order bundle” & enter “NG tube fed newborn” on problem list
• Charge RN or NICU CNS place bridle bedside (AMT Microbridle Pro 5- 6 clip fits

6.5F NG)
• XR to confirm NGT position

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– Consultation with SLP & pediatric GI required
• Weekly weight checks with PCP or GRAD Clinic

• out-patient follow-up w/ SLP 1-2 weeks after discharge

• peds GI 4 weeks after discharge

– Consult with Case Management for ENFit syringes & other home supplies
– Enter .bridledischarge & home-going feeding plan from NICU
nutritionist in discharge summary
– Monitor for 48 hours after bridle placement
• PO intake may decline in 1 24 hrs post-placement
st

• Duoderm on columella & Aquaphor to nares can help reduce risk, but monitor

for septal irritation

• parents to perform independent care session

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 Chapter 4: NICU Procedures
Julie Kessel, MD
Must write a procedure note in the patient’s chart after completing a procedure.
A template is available for each of the NICU procedures.
A. Intubation
• Tube for tracheal aspirate gram stain and culture
Equipment
• Suction catheter: Use 6-10 F catheter
• Sterile gloves
• Bag and mask, check mask size
• Blow-by Oxygen(5-10 L)
• Laryngoscope and blade
–Term = “1” blade
–Pre-term = “0” blade
–Extreme prematurity = “00” blade
• Endotracheal tube
ETT size based on weight and gestational age
Tube Size Weight Gestational Age
2.5 < 1000 g < 28 wks.
3.0 1000-2000 g 28-34 wks.
3.5 2000-3000 g 34-38 wks.
4.0 > 3000 g > 38 wks.

ETT position at the lip = Nasal-tragal length + 1

• ETT boneandtapes (prepared by nursing)

–CO2 detector
–Stylet (optional)

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Medications for Non-Emergency Intubation in the NICU
A. Infants with IV access
Pharmaco-
Medication Dose Route Notes
dynamics
Morphine 0.05-0.1 IV Onset: 1-5 min • Longer duration than
mg/kg Duration: 3-5 hours Fentanyl
• Use with caution for in-out
surfactant (INSURE)
Midazolam 0.1 IV Onset: 1-5 min • May use when considering
mg/kg Duration: 20-30 min In-Out Surfactant (INSURE)
Atropine 0.02 IV Onset: 1-2 min • No minimum dose is
mg/kg Duration: 15-60 min required
Optional Agents
Rocuronium 0.6 IV Onset: 1-5 min • Use only if needed
mg/kg Duration: 30-60 min • Attending Neonatologist
must be “in-house”
B. Infants with No IV access
Pharmaco-
Medication Dose Route Notes
dynamics
Morphine 0.1 IM Onset: 15-30 min • Longer duration than
mg/kg Duration: 3-5 hours Fentanyl
• Use with caution for in-out
surfactant
0.3 NG/ Onset: 30-60 min
mg/kg PO Duration: 3-5 hours
Midazolam 0.1 IM Onset: 1-5 min • Use for in-out surfactant
mg/kg Duration: 2 hours (INSURE)
0.2 Intra- Onset: 1-5 min • Use with intranasal
mg/kg nasal Duration: 30-60 min atomization device

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 Surfactant when indicated
– 2.5 ml/kg via ETT (Curosurf® first dose; subsequent doses 1.25 ml/kg every 12 hrs)
– Give in one aliquot via ETT catheter followed by bagged or ventilator breaths
Complications
• Acute
– Tracheal/hypopharyngeal perforation
– Hemorrhage
– Laryngeal edema
– Vocal cord injury
• Chronic
– Glottic/subglottic stenosis
– Subglottic granuloma/cyst

B. Umbilical Catheters Indications

a). Umbilical Arterial Catheter
1. Frequent measurements of blood gases
2. Continuous measurement of arterial blood pressure
3. Infusion of maintenance fluids
4. Access for exchange transfusion
5. Resuscitation (UVC preferred)
b). Umbilical Venous Catheter
1. Resuscitation
2. Exchange transfusion
3. Intravenous fluids and nutrition (≥ D15)
4. IV medication infusions. e.g. Dopamine, Morphine
Contraindications
1. Evidence of vascular compromise of legs or buttocks (For UAC)
2. Peritonitis
3. NEC
4. Omphalitis
5. Omphalocele/gastroschesis
6. Acute abdomen
Duration
1. UAC/UVC should be removed after DOL 7-10 due to increased risk of infection

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Equipment
• Procedure cart
– One located in each wing of NICU behind nurses’ desk
• Soft infant restraints for wrists and ankles per nursing
• Hat, mask, sterile gown and gloves
• Sterile drapes
• Sterile umbilical catheter tray
– Contains forceps, scalpel, umbilical cord tie, dilators, needle driver,
scissors, hemostats
• Use surgical forceps for ELBW
• One three-way stopcock for each line being placed
• One sterile 10 mL syringe for each line being placed
• Red syringe connector to transfer saline from unsterile syringe to sterile
syringe
• Chlorhexadine swabs
• Tubes/culture bottle for labs
• Umbilical venous catheters size
– 3.5 French for infants < 1200 gm.
– 5.0 French for infants > 1200 gm.
• Umbilical arterial catheter size
– 3.5 French for infants > 500 grams
– May use 2.5 French for infants < 500 grams

Determine catheter insertion length

• UAC length
1. 3 x Birth Wt. (kg) + 9
2. 1.5 times length of shoulder to umbilicus measurement
3. Catheter tip should be between T6-T9
4. On x-ray UAC goes caudally into the iliac arteries before
heading cranially in the aorta
• UVC length
1. 1.5 x Birth Wt. (kg) + 6
2. 2/3 length of shoulder to umbilicus measurement
3. Catheter tip should be 0.5-1 cm above the diaphragm, T8-T9
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 Path of umbilical artery
and important landmarks

Complications
Umbilical Artery Catheter
• Malposition: Vessel perforation, peritoneal perforation, false aneurysm,
misdirection into internal or external iliac arteries
• Vascular accident: thrombosis, embolism/infarction, vasospasm, hypertension,
air embolism, loss of extremity
• Equipment related: Transection of catheter, break in catheter
• Other: hemorrhage (including disconnection of UAC), infection, NEC
• b). Umbilical Vein Catheter
• Malposition in heart or great vessels: Cardiac arrhythmia, pericardial
effusion, thrombotic endocarditis, hemorrhagic infarction of lung
• Malposition in portal system: NEC, hepatic necrosis (thrombosis of hepatic vein or
infusion of hypertonic solution into liver
• Infection
• Thromboembolism
• Other: Perforation of peritoneum, portal hypertension, pneumo-pericardium

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C. Lumbar Puncture Equipment
• Procedure cart
• Sterile gloves, mask, hat, gown
• Neonatal Lumbar Puncture Tray
– Contains 1 spinal needle, 4 CSF collection tubes, drapes, syringe, needle,
lidocaine, gauze and band-aid
• Chlorhexadine Swabs
• Extra spinal needles: 22 gauge, 1 inch needles
• Patient labels to place on specimen tubes after CSF collection
• Label each tube following the procedure with a patient label and number
tubes in order they were collected
– Tube 1 = CSF PCR BioFire Film Array
– Tube 2 = CSF gram stain and culture
– Tube 3 = CSF Glucose, protein
– Tube 4 = CSF cell count and differential
– Heel stick or venous tube for serum glucose
Complications
• Hypoxemia from knee-chest positioning
• Infection
• Bleeding: Spinal hematoma (consider platelet count)
• Spinal cord injury/spinal nerve injury
• Intraspinal epidermoid tumor from epithelial tissue introduced into spinal canal
herniation

D. Thoracentesis Equipment:
• Sterile gloves

• Chlorhexadine or betadine swabs

• 25 g butterfly or 18-22 angiocath

• 3-way Stopcock

• 20 ml syringe
Complications
• Pulmonary laceration
• Pneumothorax
• Hemothorax
• Wrong location – due time out to confirm Right vs left
• Puncture diaphragm/spleen/liver

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 Chapter 5: Neonatal Resuscitation
Adam Bauer, MD
Apgars:
• Given at 1 and 5 minutes
– Repeat every 5 minutes until 20 minutes of life if the score is less than 7 at five minutes.
SIGN 0 1 2
Color Blue or Pale Acrocyanotic Completely Pink
Heart Rate Absent <100 bpm >100 bpm
Reflex irritability No Response Grimace Cry or Active
Withdrawal
Muscle Tone Limp Some Flexion Active Motion
Respiration Absent Weak Cry; Good, Crying
Hypoventilation

• Infants <35 weeks

– Initiate resuscitation with 30% blended oxygen and adjust as needed
• Infants ≥35 weeks
– Initiate resuscitation with 21% and adjust as needed
• All infants requiring prolonged PPV or if you’re considering intubation (or
LMA) should have EKG leads placed
• All infants should have pulse oximetry with probe on right upper
extremity (wrist/hand) if:
– Evidence of cyanosis
– Needs oxygen, CPAP, or PPV
CPAP/PEEP
• Use T piece from Panda warmer or Neopuff
• Start at 5 mmHg
PPV Positive Pressure ventilation
• Give 40-60 breaths per minute
• Start with PIP at 20
• Consider placing OG if PPV for more than few minutes

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Chest Compressions
• Thumbs between the nipple line and the xiphoid process
• Compress to a depth of 1/3 of the anterior-posterior diameter of the chest
• 90 compressions + 30 breaths in one minute
– “One–and Two–and Three–and–Breathe–and”
Endotracheal Intubation
• Tube depth (cm at the lip) = Nasal-tragal length + 1
• Tube size
– <1 kg/<28 weeks = 2.5 mm
– 1-2 kg/28-34 weeks = 3.0 mm
– >2 kg/>34 weeks = 3.5 mm
• Use CO2 detector to determine if intubation is successful. It will change
from purple to yellow (note: If there’s no cardiac output, the color will not
change. Also, contamination from esophageal fluids may cause color
change).
LMA
• Use size 1 for neonates > 2kg
• Inflate cuff after placement with 2-4 ml of air
Medications
• Normal saline 10 mL/kg over 5-10 minutes,
• Epinephrine 0.1 mg/mL (flush with 3mL normal saline)
– Via ETT 1 mL/kg (0.1mg/kg)
– Via UVC/IV0.2mL/kg (0.02mg/kg)
Delayed Cord Clamping
• Cord clamping should be delayed for 60 seconds for most term and
preterm infants. Exclusions include abruption, bleeding placenta previa,
cord avulsion.
Special Circumstances
• Infants <29 weeks (see Micropremie Section)
• Pneumothorax
– 18-20 gauge needle (angiocath or butterfly) into fourth intercostal

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 space at the anterior axillary line or the second intercostal space at the
mid-clavicular line
Cord Gases
• Consider obtaining if prolonged/significant resuscitation, abnormal tone,
peripartum abnormalities
– Normal pH >7.2 (7.15-7.38), pCO2 <60 mmHg (35-70), pO2 > 20, base
excess < -10 (-2 to -9)
– Abnormal: pH <7.0 or base excess ≥12 at risk for neonatal
encephalopathy and may qualify for whole body cooling (see HIE
Section)
References:
1. AAP Textbook of Neonatal Resuscitation 8th Edition

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 Chapter 6: Micropremie Care Manual
Infants < 29 weeks Gestational Age (GA)
Nina Menda, MD & Claudette Adegboro, MD

Goal: To increase survival without morbidity for infants born < 29 wks GA.

A. Pre-Delivery
i. Set up for double lumen UVC and single lumen UAC in the NICU
admission room Use NS for flush, but do not use heparin flush
ii. Pre-order IVF with heparin for both umbilical lines. RN may set up D10W for PIV
iii. Set IVF rates for total of 80 ml/kg/day
iv. T-piece (TP) resuscitator settings: FiO2 0.3 and 20/5
v. Team assignments: NICU provider (APP, fellow), neonatologist, charge nurse,
resident, respiratory therapist, admitting RN
B. Delivery Room
a. Delayed cord clamping
i. Discuss and plan delayed cord clamping for 30–60 seconds with OB provider
b. Airway management by fellow, APP or neonatologist
i. Resuscitation to follow NRP & Meriter Algorithm
ii. Start with NCPAP+5, stabilize with appropriate-sized mask and TP
iii. Recommend Intubation and surfactant for all infants < 25 wks GAOR
< 500gms
iv. For all micropremies, if intubated in DR, obtain CXR in NICU prior to
surfactant administration
c. Respiratory Therapist
i. Apply F&P Flexitrunk, and connect to BCPAP or NIPPV with ventilator
ii. For intubated infants: start volume ventilation following surfactant
administration
d. Charge nurse:
i. Thermal mattress, plastic wrap & hat for thermoregulation; follow algorithm
ii. Apply cardiac leads and SpO2 monitors
iii. Prior to intubation: measure length from nose to tragus +1cm for depth of
ETT
iv. Weigh the infant, measure head circumference and apply tortle
• If 22-23 weeks, do NOT use Tortle due to skin fragility
22
C. NICU Admission
a. Admitting RN
i. Obtain weight if not done in DR
ii. Check temperature
iii. Ensure proper head placement
iv. Place cardiorespiratory monitor
b. Providers
i. Prioritize Lungs over Lines
ii. Intubate and give surfactant to:
• Infants < 25 wks GA OR infants < 500 gms at birth
• For all micropremies requiring ≥ 30% oxygen on admission,
consider placing PIV to infuse D10 Wat 80 ml/kg/d before
surfactant administration
iii. Umbilical lines efficiently placed by a skilled NICU provider
• UVC: Obtain blood glucose and start IVF immediately,
prior to X-ray confirmation; the second lumen must be
heparin locked
• Draw all admission labs from UAC or UVC during umbilical
line placement
• If lines are not placed within 30 minutes of starting, must call
neonatologist for assistance
Participate in Delivery room brief and post golden-hour debrief

D. Open Lung Policy

a. Load with caffeine and start maintenance caffeine on admission
b. First week: avoid hypocapnea and hypercapnia with goal pCO2 = 45-55
c. After first week: Permissive hypercapnia; Goal pCO2 50-60
d. Surfactant administration:
i. All infants < 25 wks GA OR < 500 gms: intubated in DR & CXR and surfactant in
NICU
ii. All infants requiring ≥ 30% oxygen at admission or for ≥ 30 minutes
iii. Forinfants≥25 wks, consider INSURE

23
 iv. Give 2nd dose if: >12 hr from first AND < 48-72 hr of age AND > 30% oxygen
e. Ventilator Strategies: Initial Settings
i. Volume targeted ventilator: TV 6-7 ml/kg, R 40, PEEP 5-6, IT 0.35
ii. High Frequency Jet Ventilation:

• Obtain blood gas 30 min after converting to HFJV

• Obtain CXR 45-60 min after converting to HFJV
• See High Frequency Jet Ventilation Guideline for further details
iii. Non-Invasive: Provide support with BCPAP (PEEP 5-6 cm H2O) or NIPPV
f. Extubation readiness:
i. Ventilator settings:
Volume ventilation: FiO2 ≤ 0.3, VT ≤ 6ml/kg, PEEP ≤ 8
OR HFJV: FiO2 ≤ 0.3, MAP ≤ 9, rate 240
OR SIMV: FiO2 ≤ 0.3, rate ≤ 25, PIP ≤ 18, PEEP ≤ 8
ii. pH ≥ 7.25, pCO2 ≤ 55
iii. Successful 3 min ET-CPAP trial

E. Brain Care
a. For infants < 25 wks GA, do not extubate for first 72 hrs
b. To consider treatment of hypotension with fluid bolus and/or
inotrope during first 72 hrs, infant must have two or more of the
following:
i. Persistent HR > 160/min
ii. Metabolic deficit > 8
iii. Lactate > 4
iv. Capillary refill > 4 sec
v. Urine output < 1 ml/kg/hr for infants > 24 hr of age
c. Feeds every 2 hrs until on full feeds and 29 weeks PMA OR by
two weeks of age, whichever is later
d. Limit to 2 full assessments per care session and ask for help with containment
during assessment

24
 e. Maintain head in midline position for 72 hrs; no prone positioning for 72 hrs

F. Nutrition Support
a. Initiate colostrum feeds as soon as available
b. Remove central line when feeds ≥ 120 ml/kg/day

G. Family Integration
a. Integrate parents in infant’s care
b. Encourage parents to participate in daily rounds
c. Discuss timing of kangaroo care on rounds

25
26
27
 Chapter 7: Screening for Hypoglycemia in Newborn Nursery
Elizabeth Goetz, MD

Transient hypoglycemia after birth is normal in full term, healthy newborns.

However, hypoglycemia has been associated with poor developmental outcomes.
Because hypoglycemia is typically asymptomatic in newborns, babies at high risk for
hypoglycemia are screened in the first 12-24 hours of life.

Management of Hypoglycemia in the Newborn Nursery

Screen per Patient Care Policy #34: Hypoglycemia in Birthing Center Infants

Babies with symptomatic hypoglycemia require immediate evaluation.

Symptoms of Hypoglycemia
Lethargy Vital sign instability Apnea
High pitched cry Cyanosis /Pallor Seizures
Irritability Sweating Hypotonia
Jitteriness Poor feeding Respiratory distress

Asymptomatic babies who require screening for hypoglycemia

• Screen IDM and LGA infants for first 12 hours of life
• Screen SGA infants, infants < 2500 gm and infants < 37 weeks for first 24 hours of life
• One time screen if Apgars <4 at 1 minutes or, <7 at 5 minutes of life, temperature
< 97.4, maternal beta blocker, IUGR or exposure to steroids within 2 weeks of delivery

Low blood sugars (<40 in first 4 hours of life and <45 4-24 hours of life) are treated
with the hypoglycemia treatment bundle which includes warming, feeding, and
dextrose gel

Hypoglycemia can be treated with 4 total hypoglycemia treatment bundles in the

newborn nursery. If baby has a low blood sugar after 4 hypoglycemia bundles the baby
should be transferred to the NICU for further management.
28
Management of Hypoglycemia in NICU

Plasma glucose homeostasis requires glucogenesis and ketogenesis to maintain normal rates
of fuel use. Neonatalhypoglycemiaoccurswithimpairedglucogenesisandketogenesis. As
glucose is an essential source of cerebral energy, prolonged hypoglycemia can result in
adverse neurologic sequelae.

Etiology
A. Causes of transient hypoglycemia
• Perinatal stress, asphyxia, hypothermia
• LGA and/or IDM, polycythemia
• Sepsis, shock
• Maternal meds: terbutaline, chlorothiazide, labetalol, propranolol
• Exchange transfusion
B. Decreased glycogen storage
• IUGR/SGA: Must monitor pre-feed blood sugar when infant coming off IVF
and with any change of feeds to lower calories.
• Premature and post mature infants
C. Causes of persistent hypoglycemia
• Hyperinsulinism: Beckwith-Wiedemann Syndrome, Islet cell adenoma, beta cell
hyperplasia, Nesidioblastosis
• Hormone Deficiencies: GH, Glucagon, cortisol, thyroid hormone
• Defects of CHO metabolism: Glycogen storage disease type I, Galactosemia,
Fructose intolerance, Fructose 1, 6 diphosphate deficiency
• Defects in amino acid metabolism: MSUD, Tyrosinosis, Propionic acidemia,
Methylmalonic acidemia
• Defects in fatty acid metabolism: Medium and long chain fatty acid deficiency

29
Treatment
A. Asymptomatic hypoglycemia
• Early and frequent feeds
• Follow hypoglycemia management guidelines for starting IVF
B. Symptomatic and persistent hypoglycemia
• Monitor glucose level closely
• Start IVF: D10W 60-80 ml/kg/d (GIR = 4-6 mg/kg/min)
• Maintain blood glucose >50-60 mg/dl
• Consider bolus of D10W 2 ml/kg (200 mg/kg) if persistently <40 mg/dl followed
by infusion
• Monitor GIR(mg/kg/min) = Dextrose concentration (gm/100 ml) x rate(ml/hr)
6 x weight (kg)
D10W has 10 gm/100 ml
• Need central line if dextrose concentration >12.5%
• If stable, start enteral feeds and increase calories as tolerated
• Once three preprandial blood glucoses > 60 mg/dl, begin weaning IVF. Suggested
weaning protocol: wean IVF by 2 ml/hr if blood glucose > 70 mg/dl; wean IVF
by 1 ml/hr for blood glucoses 60-69 mg/dl; hold current rate of IVF for blood
glucoses 50-59 mg/dl; Notify provider for blood glucoses < 50 mg/dl.
• If no improvement, endocrine and metabolic consults and w/u
• Pharmacologic: For persistent hyperinsulinemic hypoglycemia: cornstarch,
diazoxide and octreotide have been used.
Work up for persistent hypoglycemia, in order of priority:
• Blood sugar, Insulin, Growth hormone, Cortisol
• Serum ketones, CBG, Lactate, Ammonia
• Glucagon, T4, TSH
• Consider metabolic work up: Free fatty acids, alanine, amino acids, uric acid

30
31
 Chapter 8: Respiratory System
Dinushan Kaluarachchi, MD, Heather Becker, RRT-NPS

A. Respiratory Distress in Newborn

• Etiology
Pulmonary Causes
• Transient tachypnea of newborn
• Hyaline membrane disease
• Meconium aspiration
• Air leak syndromes: Pneumomediastinum, pneumothorax, PIE, pneumopericardium,
pneumoperitoneum
• Neonatal pneumonia
• Pulmonary hypoplasia: Idiopathic, agenesis of lung. Secondary to CDH,
oligohydramnios, renal agenesis
• Congenital pulmonary lymphangiectasia
Extrapulmonary causes
• Sepsis
• Cardiovascular disorders: Congenital heart disease, PPHN, Hypotension
• Metabolic disorders: Hypoglycemia, Hyperthermia, Metabolic acidosis
• Neuromuscular disorders
– Brain: Asphyxia, hemorrhage, infection
– Spinal cord: trauma, Werdnig-Hoffmann disease
– Nerves: injury (Phrenic nerve)
– Myasthenia gravis
• Mechanical-restrictive problems
– Airway obstruction: Choanal atresia, micrognathia, laryngeal web,
tracheomalacia, vascular ring, cystic hygroma, mediastinal masses
– Rib cage anomalies: Thoracic dystrophies, generalized bone disease, skeletal
dysplasia’s
– Diaphragmatic disorders: Phrenic nerve injury, CDH, abdominal distension
– Pleural effusion or chylothorax
• Hematologic disorders: Polycythemia, anemia

32
 B. Surfactant
Indication
• Respiratory Distress Syndrome
• Meconium Aspiration Syndrome
• Congenital Pneumonia
Mechanism of Action
• Reduces alveolar surface tension
• Decreases opening pressure
• Provides alveolar stability
• Enhances alveolar fluid clearance
Criteria
• Infants requiring > 30% oxygen delivered by positive pressure using either nasal
CPAP or an ET tube.
• Diagnosis of RDS on CXR
• If you have a baby meeting these criteria at 6 hours, you should give surf within
an hour meeting the criteria.
Dosage (Curosurf)
• 2.5 ml/kg/dose intratracheally for first dose. Subsequent doses 1.25 ml/kg q 12 hrs
(maximum dosage 5 ml/kg)
• Repeat surfactant dose if ≥ 12 hours from first dose AND ≤ 48 hours of age AND
30% FiO₂
Initial management of Respiratory Distress in Delivery Room
<29 wks. 29-34 6/7 wks. ≥ 35 wks.
Starting FiO₂2= 21-30% Starting FiO₂2= 21-30% Starting FiO₂2= 21%
Follow Micro preemie Apply CPAP ± rate in DR Apply CPAP ± rate in DR
DR guidelines Interface: Mask
Give surfactant if Intubated Give surfactant if Intubated Give surfactant if Intubated
and concerns for RDS and concerns for RDS
Meriter NICU: Oxygen Saturation Parameter
Patient Status Oxygen Saturations Goals Oxygen Saturation Alarm

Preterm <37 Wks. 90-94% 88-95%

Preterm ≥37 Wks. ≥95% 92-98%
All infants in room air ≥95% 92-100%

33
C. Ventilation Support
Ventilation types
• High Flow Nasal Cannula
• Delivers heated and humidified gas such as oxygen, air, or nitric oxide for infants
requiring support with low positive airway pressure.
• Infants weaned from CPAP are typically started on heated humidified high
flow cannula at 2 LPM and later weaned to room temperature humidified
cannula when on ≤1 LPM
• Recommended flowrates should be initiated between 2-6 Lpm. The flowrate
can be titrated to provide a variable level of positive distending pressures.
• Infants can PO feed on 2LPMandlowerrespiratorysupport
• Indications: Bronchopulmonary Dysplasia, Respiratory Distress Syndrome, Transient
Tachypnea of the Newborn, Apnea of prematurity, Failure to wean from NIV
support (CPAP and/or NIPPV), Nasal and/or upper airway congestion/anomalies
• Nasal Continuous Positive Airway Pressure (NCPAP)
• Recommended intervention in delivery room for all infants <29 wks.
• For older infants, this is the first intervention for worsening respiratory distress
despite nasal cannula oxygen.
• Start at 5-8 cm H2O and adjust as needed
• NIPPV (Nasal Intermittent Positive Pressure Ventilation)
• Nasal ventilation with higher level of support
• Recommend in premature infants with apnea
• Initial settings: Rate 40, PIP 18-20, PEEP 5-8, IT 0.35
• NAVA and NIV NAVA (Neurally Adjusted Ventilatory Assist)
• NAVA delivers assist in proportion to and in synchrony with the baby’s respiratory
efforts, specifically depolarization of the diaphragm. These efforts are reflected by the
Edi (electrical activity of the diaphragm) signal.
• A low or absent Edi signal may be due to hyperventilation, sedation,
muscle relaxants, neural disorders or the catheter being too deep
• Edi max=force of the diaphragm contraction during inspiration
• Edi min=force required to maintain FRC at the end of exhalation
• Peak Pressure = NAVA level x (Edi peak – Edi Min) + PEEP
• Initial NAVA settings
– Initial NAVA level of 1.5-2 cmH2O/uV – Optimize the NAVA level according
to Edi Max which is targeted between 5-15 uV. Max NAVA level 4
cmH2O/µV.
34
 • Management of Infants on NAVA
– If Edi max is < 5 uV, decrease the NAVA level
– If Edi max is >15 uV, increase the NAVA level
– If Edi min is > 2 uV, increase PEEP
– Initially set the same PEEP as the previous ventilator settings.
– Initial apnea time is set for 5 seconds. If baby is apneic or desaturating, decrease
the apnea time to 2-3 seconds.
– Initial Backup settings: PC 10 above PEEP, PEEP 6-8, Rate 40, It 0.35s
• NIV NAVA: Consider increasing the PEEP when transitioning from invasive to
NIV NAVA to maintain adequate MAP.
• Contraindications: insufficient/absent respiratory effort, anomaly (atresia, severe
CDH), phrenic nerve injury, congenital myopathy, MRI scanning (remove catheter
before scan)
• Conventional Ventilation
Indications
• Persistent respiratory acidosis with pH ≤ 7.10 and PaCO2 >60
• Severe hypoxemia (arterial PaO2 < 50-60) despite a highFiO2 (40-70%)
• Significant apnea or increasing work of breathing

Volume Ventilation mode: APV/CMV (Adaptive Pressure Ventilation/Controlled

Mandatory Ventilation)
Initial Ventilator Settings
Volume 4-6 ml/kg
PEEP 5-6
I-time 0.35
RR 30-50

• APV should be combined with CMV because this mode supports all
spontaneous breaths. APV/CMV is associated with more stable expired
VT, better oxygenation and reduced tachypnea when compared with
synchronized intermittent mandatory ventilation APV/SIMV.
• If ETT leak > 50% consider larger ETT
• APV mode not recommended if ETT leak > 40%. Consider changing to Pressure
ventilation mode.
• May set upper PIP limit

35
 • As the infant improves the PIP will gradually go down while the targeted tidal
volume stays the same. Thus, infant weans naturally. When PIP is low (14-16),
consider extubation.
• A trial of extubation may be considered when the patient is consistently
over breathing the set ventilator rate without increased work of
breathing and both MAP & FiO₂ have dropped to acceptable levels.
MAP 8-10 & FiO₂ < 35%.

Pressure Ventilation Mode: P-SIMV (Pressure-Synchronized Intermittent

Mandatory Ventilation)
Initial Ventilator Settings
RDS Normal Lung
PIP 18-20 12-16
PEEP 5-6 4-5
I-time 0.35 0.3
RR 30-40 20-40
Pressure Support (PS) 8-10 6-8
Evaluate chest rise and increase PIP if chest rise is inadequate

Ventilation Goals Based on Disease Process

pH pCO₂
RDS ≥ 7.25 45-55 (60)
50-65 (<7d)
BPD/Air leak ≥ 7.25 55-70 (≥7d)
PPHN ≥ 7.40-7.55 35-50
Management for infants on ventilator:
To Improve Ventilation (↓PaCO2)
Action Effect Risk
↑RR ↑Minute ventilation, ↓PaO
2
↑MAP
↑PIP or ↑Volume ↑FRC, ↑TV , ↑MAP, Air leaks, BPD
↓IT ↑ET ↓PaO2

36
To Improve Oxygenation (increase PaO2)
Action Effect Risk
↑FiO2 ↑PaO2 BPD with prolonged exposure, ROP
↑PEEP or ↑CPAP ↑Intrapulmonary Hyperinflation with ↑CO
2
shunt, ↑FRC, ↑MAP Air leaks
↓Venous return and cardiac output
↑PIP or ↑Volume ↑FRC, ↑MAP, ↑PIP Air leaks; BPD
↑IT ↑MAP Air leaks; BPD
↓Venous return and cardiac output
↑CO2 retention 2° to ↓E time

Pulmonary functions and equations

• Tidal Volume (TV): Amount of gas inspired n a single spontaneous breath
or delivered through an endotracheal tube during a single cycle of the
ventilator.
• Minute Ventilation = Rate (IMV) x Tidal Volume (TV)
• Rate is affected by IT and ET
• Tidal Volume is influenced by PIP, PEEP, pulmonary resistance and pulmonary compliance
• Oxygenation Index (OI) = (MAP x (FiO2 x 100))/PaO2
• MAP = (IT x PIP) + (ET x PEEP)
IT + ET
ET = Expiratory time IT = Inspiratory time

High Frequency Oscillatory Ventilation (HFOV)

• Uses small tidal volumes (usually less than anatomic dead space) and rapid
respiratory rates at frequencies between 400 to 2400 breaths/min
• High frequency oscillators are air vibrators with piston pumps or vibrating
diaphragms with active inspiration and expiration phase.
• Pressure oscillations within airway produce tiny tidal volumes around a constant
mean airway pressure, maintaining lung volume.
• Advantages-delivers lower proximal airway pressures and possibly reduces
ventilator related lung injury
• TV is determined by the amplitude(∆P) of the airway oscillations, which in
turn is determined by stroke of the device producing oscillations.
37
 • Hz=number of oscillations/min,
1 Hz = 60 bpm
∆P
• Decreasing Hz prolongs inspiratory
MAP
time, thereby increasing TV
• Oxygenation is controlled by MAP,
FiO2
• Ventilation is controlled by ∆P, Hz
TIME
Indications
• Respiratory failure unresponsive to conventional ventilation
1. Inadequate oxygenation despite high FiO2 and MAP
2. Inadequate ventilation despite high PIP
• Air Leak Syndromes: pneumothorax, pulmonary interstitial emphysema
• Atelectasis

Improve oxygenation Improve ventilation

↑FiO2 ↑Amplitude
↑MAP (in increments of 1-2) ↓Hertz

Complications of HFOV
• Hyperinflation and barotraumas
• ↓venous return →↓cardiac output → hypotension →↓renal perfusion (↓UOP)
• Edema
• ↑need for sedation
• Difficult to perform physical exam

High Frequency Jet Ventilation (HFJV)

• HFJV is pressure-limited, and time cycled with adjustable PIP and Rate
• Inspiratory Time (IT) is kept as short as possible (0.02 sec.)
• Exhalation is passive

38
 • Delivers small tidal volumes (Vt) (1-2 ml/kg) at rapid rates (240-600 bpm) via
special Et tube adaptor (Life port adaptor) with built-in nozzle.
• Connecting the Life port adaptor to a patients ET tube enables tandem use of
conventional mechanical ventilation (CMV) (Hamilton G5 vent)
• Monitored Servo-controlled driving pressure (Servo Pressure) is used to detect
changes in lung compliance and resistance.
• Jet rate changes are made in increments of 60 bpm and is independent of the Jet
Vt. Lowering Jet rate allows for a longer expiratory time and helps avoid gas
trapping.
• Jet PIP primarily regulates PaCO₂
• CMV vent PEEP is the main contributor t mean airway pressure (MAP).
• CMV vent rate (sigh breaths) reverse atelectasis.
Indications
• Preventative lung protection strategy in infants < 25 weeks or < 500 grams.
• Strongly consider Jet ventilation for infants < 26 weeks or < 750 grams.
• Rescue therapy for air leak syndromes such as pulmonary interstitial
emphysema, pneumothorax, lung hyperinflation, & air trapping.

Recommended Initial HFJV Settings

Pt Population Jet Rate Jet PIP Jet I.T. PEEP

22-23 wk GA 300 bpm 24-26 0.02 seconds 5
24-25 wk GA 360 bpm 22-24 0.02 seconds 5

Management Strategies

• HFJV delta P (PIP-PEEP) is the primary determinant of PaCO₂. HFJV I-time and
Rate are secondary.
• Resting lung volume (FRC supported by set PEEP) and mean airway pressure
(MAP) are crucial determinants of PaO₂

39
 Settings When to Raise When to Lower
HFJV PIP To decrease PaCO₂ To increase PaCO₂
To eliminate inadvertent
HFJV Rate To decrease PaCO₂ PEEP or hyperinflation
When oxygenation is
PEEP To improve oxygenation adequate

Complication of HFJV
• Atelectasis → Add sigh breaths or increase PEEP
• Hypotension → Decrease PEEP and PIP to decrease MAP
• Hyperinflation → Decrease PEEP and PIP or decrease Jet rate
Complications of ALL Assisted Ventilation
• Air leak: Pneumomediastinum, pneumothorax,
PIE, pneumopericardium,
pneumoperitoneum
• ETT complications: displacement, dislodgement, obstruction,
atelectasis, palatal groves, subglottic stenosis
• Tracheal lesions: erosion, granuloma, perforation, necrotizing tracheobronchitis
• Infection: pneumonia, septicemia
• Impaired cardiac function
• CLD/BPD
• Oxygen toxicity
• Miscellaneous: Intracranial hemorrhage, PDA, ROP, delay in enteral
feedings, complications of parenteral nutrition
Inhaled Nitric Oxide (iNO):
• Pulmonary vasodilator that facilitates perfusion of alveoli and can improve gas
exchange and oxygenation.
• Indications: hypoxic respiratory failure despite optimal ventilator
management, PPHN, meconium aspiration syndrome, pneumonia, and
idiopathic pulmonary hypertension, differential pre and post SpO2
• Inhaled nitric oxide can be given in conjunction with any oxygen system
having 2 liters of oxygen or greater including: high flow nasal cannula,
CPAP, NIPPV, conventional ventilation, and HFOV.
40
 • Initial setting: 20 ppm of iNO
• Weaning: Can decrease nitric oxide by 5 ppm when FiO2is within a desired
range. Once weaned to 5 ppm, then wean by 1 ppm.
• Due to the short half-life, nitric oxide should never be abruptly
stopped. Wean slowly and be aware of a rebound effect.
• Consider monitoring methemoglobin levels daily while on iNO
Extubation Checklist:
Infants must meet following criteria
• Minimum Ventilator settings:
Volume: FiO2 ≤0.3, Rate ≤ 25, VT ≤ 6 ml/kg, PEEP ≤ 6
Pressure: FiO₂ ≤ 0.3, Rate ≤ 25, PIP ≤ 18, PEEP ≤ 6
NAVA level <0.5, FiO2 ≤ 0.3, PEEP ≤ 6
HFJV: Jet PIP ≤ 20, Jet Rate 240-300, Jet MAP 7-8, FiO₂ 0.03
• Safe airway
• pH ≥ 7.25, pCO2 ≤ 55
Peri-Extubation Dexamethasone for Neonates
• To assist in success of extubation for infants at high risk for airway
edema and obstruction and prevent reintubation
• Recommended regimen:
– 0.1 -0.25 mg/kg/dose IV q8h x 3 doses - begin 4 hr prior to extubation
– Infant must be ≥ 7 days of age
• Data not supportive of use for:
– Low risk for airway edema and obstruction
– Subglottic stenosis
– Post-extubation atelectasis
• Use with caution in patients with respiratory or systemic infection
Management of Bronchopulmonary Dysplasia (BPD)
• Permissive hypercapnia (pH ≥ 7.25 and pCO₂ 55-70)
• Ensure adequate caloric intake for weight gain-infants with BPD have
increased basal metabolic rates: May need 130-150 kcal/kg/day
• Fluid restriction:130-150 ml/kg/day
• Diuretics

41
• Bronchodilators
• Systemic steroid: DART protocol
– Use to facilitate extubation in vent-dependent infants
– Do not use in infants less than 2 weeks of age
– Dosing regimen: (IV or PO)
• 0.075 mg/kg/dose q12h x 6 doses, THEN
• 0.05 mg/kg/dose q12h x 6 doses, THEN
• 0.025 mg/kg/dose q12h x 4 doses, THEN
• 0.01 mg/kg/dose q12h x 4 doses, THEN STOP
– Inhaled steroid options:
• Budesonide 0.25-0.5 mg BID by nebulization
• Fluticasone 110 mcg BID by inhalation
• Possible adverse effects: hyperglycemia, hypertension, hypokalemia,
hypocalcemia, cessation of linear growth

Pulmonary Hypertension Screening Guidelines for Preterm Infants

(see Cardiology section for algorithm)

References:
1. Kair LR, Leonard DT,.Anderson JM and Med. Bronchopulmonary Dysplasia.
Pediatrics in Review 2012;33;255. DOI: 10.1542/pir.33-6-255
2. Bestic ML and.Reed MD. Common Diuretics Used in the Preterm and Term
Infant: What’s Changed? Neoreviews 2012;13;e410. DOI: 10.1542/neo.13-7-e410
3. Doyle LW, et al. DART Study Investigators. Low-dose dexamethasone facilitates extubation
among chronically ventilator-dependent infants: a multicenter, international,
randomized, controlled trial. Pediatrics.
2006;117
4. Schmidt B, Whyte R, Asztalos E, Moddemann D, Poets C, et al (COT Group).
Effects of Targeting Higher vs Lower Arterial Oxygen Saturations on Death or
Disability in Extremely Preterm Infants. JAMA. 2013;309(20):2111-2125

42
 Chapter 9: Acid Base Balance
Ashleigh N. Rushing, MD and C. Lydia Wraight, MD

A. Blood Gases
• pH, pCO2, pO2 are measured directly
• HCO3-, O2 saturation are calculated
Normal Blood Gas Values
pH 7.35-7.45
pCO2 35-45*
HCO3 22-26
Base Excess -1 to -3
* For infants ventilated > 7 days, permissive hypercapnea (pCO2 45-60) is
accepted to decrease barotrauma.
• Acid-base balance is maintained with buffers

HCO3 + H H2CO3 H2O + CO2

B. Interpretation of blood gases

• Step 1: Is the pH acidic or basic?
pH < 7.35 Acidosis
pH > 7.45 Alkalosis

• Step 2: Is the disturbance respiratory or metabolic? Look at pCO2.

– Respiratory = pH and pCO2 change in opposite directions
– Metabolic = pH and pCO2 change in the same direction
Acidosis Alkalosis
pH pCO2 pH pCO2
Respiratory ↓ ↑ ↑ ↓
Metabolic ↓ ↓ ↑ ↑

43
 • Step 3: Is there compensation?
• Compensation occurs to bring the pH closer to normal when the derangement is
chronic, it will not correct the pH to normal.
Acute Compensation
pCO2 HCO3 pCO2 HCO3

Respiratory Alkalosis < 40 normal < 40 low

Respiratory Acidosis > 40 normal > 40 high
Metabolic Alkalosis normal > 26 > 40 > 26
Metabolic Acidosis normal < 22 < 40 < 22
• Step 4: Is there an anion gap?
Anion Gap = [Na+] – ([Cl-] + [HCO3])

– Normal anion gap < 15 mEq/L

C. Respiratory Acidosis
• Most common cause of acidosis
• Poor ventilation results in CO2 retention (CO2 is high)
D. Respiratory Alkalosis
• Often iatrogenic, resulting from hyperventilation (ie we are giving the baby
more support than they need)
E. Metabolic Acidosis
• Results from excess acid production or increased loss of base.
• Normal anion gap:
• Renal: Immaturity, Renal Tubular Acidosis, Obstruction, Dysplasia
• GI: Diarrhea, Short Gut
• Endo: Congenital Adrenal Hyperplasia
• High Protein Formula
• Administration of Cl- containing compounds:
44
 – TPN, NH4Cl, CaCl2 especially in ELBW
• Compensation of respiratory alkalosis

• Increased anion gap:

• Lactic acidosis: Shock with poor tissue perfusion and oxygenation
• Acute renal failure
• Inborn errors of metabolism: Organic acidemias, mitochondrial
disorders, glycogen storage disease (type 1), galactosemia
• Toxins
• Systemic effects of Metabolic Acidosis:
• Pulmonary vasoconstriction (Pulmonary hypertension)
• Decreased myocardial contractility
• Respiratory compensation: Increased work of breathing
• CNS damage with severe acidosis
• Management
• Treat the underlying cause when possible
• TPN associated mild acidosis may be treated with decreasing chloride
and increasing acetate for a few days.
• Volume expansion if signs of hypovolemia
– Excessive volume expansion is poorly tolerated in presence of
decreased myocardial contractility
– May use normal saline, packed RBCs or FFP as appropriate
• Pharmacologic options
• NaHCO3
• Only use when infant has excellent ventilation
• Risks of NaHCO3 administration
o Acute expansion of intravascular volume with risk of IVH
o Shift of Hgb dissociation curve to left (↑ binding of O 2to
Hgb)
45
 o Increased Na load and increased CO2
• THAM – an organic buffer
• Can consider with severe acidosis with Na overload and high
CO2/poor ventilation
• Associated with risk of apnea and hypoglycemia and is not as
effective

F. Metabolic Alkalosis
• Commonly iatrogenic, resulting from diuretic use (ex: furosemide)
• Other etiologies:
• Loss of gastric fluid: large gastric aspirates, emesis or diarrhea with Cl– loss
• Compensation for chronic respiratory acidosis
• Excessive administration of alkali (acetate in TPN)
• Management
• Replace Cl- deficit, remove any acetate in TPN
• Replace ongoing fluid and electrolyte losses
• Adjust ventilator if respiratory acidosis

References:
1. Brodsky, D. and Martin, C. Acid Base Balance. Neonatology Review 3rd Ed.
2020.Vol 4: 34-3.

46
 Chapter 10: Fluids, Electrolytes and Parenteral Nutrition (PN)
Ann Ebert, Pharm D
General Information
The overall goal for infant nutrition is to mimic in-utero growth rate
• Fetal Growth
24-28 weeks 18 gm/kg/d
≥ 28weeks 16 gm/kg/d
• From 24 weeks to term; as total body percentage
– water decreases from 87 to 71%
– protein increases from 8.8 to 12%
– fat increases from 1 to 13.1%
• Growth goal for preemie: 15-20 gm/kg/day
Calculation of Fluid Requirements
• Three principals
1. Maintenance
2. Replacement of deficit
3. Replacement of ongoing water loss
• Ongoing water loss
– Insensible water loss (IWL)
– Urinary loss
– Stool loss
– Gastric losses
– Chest tube/ wound loss
• Insensible Water Loss
– Mostly from skin and respiratory tract.
– Gestational age is inversely proportional to insensible water loss.
– Elevated body temperature, radiant warmer
– Gastroschisis, omphalocele, myelomeningocele and phototherapy may increase
IWL
Total caloric requirement:
• Enteral feeds ~110-130 kcal/kg/day
• Parenteral nutrition ~90-100kcal/kg/day

47
 • Combined parenteral and enteral nutrition ~100-120 kcal/kg/day
• Need a minimum of 60 kcal/kg/day + 2.5-3.5gm/kg/d of protein for
positive nitrogen balance
Parenteral Fluids and Nutrition
1. Fluid volume:
• Fluid requirement on first day of life
– Goal is to prevent dehydration, fluid overload and hypoglycemia
Components Term (ml/kg/d) Preterm (ml/kg/d)
Maintenance 20 ±25
IWL 15 ±30
Urine 20 ±20
Stool 10 ±20
Total 65 ±80
– Suggested total fluid intake on Day 1 of life
Weight (gm) < 750 750-1000 1000-2500 >2500
Fluid (ml/kg/d) 80-100 80 60-80 60

• Determining the amount of fluid to be administered as TPN

– Decide the total daily fluid needed (ml/kg/day)
– Subtract other drips and IV fluids
– Subtract enteral feeding volume (if applicable)
– Example: 1.2kg infant
Total daily fluid = 120 ml/kg/day rate = 6 ml/hr
UAC present rate = 1 ml/hr (subtract)
Dopamine drip rate = 0.5 ml/hr(subtract)
Remaining amount for TPN + fat rate = 4.5 ml/hr (90 ml/kg/day)

Key points for infants born < 2000 gm:

• For IV fluids
– Initiate starter PN (D10W + 3% amino acids + heparin) ASAP after birth
– Starting at 80-100 ml/kg/day will give 2.4-3 gm/kg/day of protein
48
 – Add fat emulsion within the first 36 hours of life (consult with pharmacist)
– Transition to custom PN when clinically appropriate (consult with pharmacist)
• Total fluids after first day
– If normal homeostasis, increase total fluid intake by 20 ml/kg/day until
goal of 130-150 ml/kg/d is reached
– Decrease total fluids if: Signs of CHF, poor urine output, hyponatremia
– Increase total intake if: Increased urine output, high IWL, hypernatremia
– Monitor hydration status: body weight, urine output (I/O’s), HR, BP, Labs:
Electrolytes, urine specific gravity
2. Macronutrients
A. Protein
• Supplied as crystalline amino acids
• Contains 40-50% of essential amino acids (cysteine, taurine, tyrosine,
methionine)
– Goal intake equals:
• 4 gm/kg/day – infants less than 35 weeks’ gestation
• 3.5 gm/kg/day – infants 35-37 weeks’ gestation
• 3 gm/kg/day – infants greater than 37 weeks’ gestation
• Calories = 4 kcal/gm
• Management of metabolic acidosis coincident with TPN
• Do not exceed 3.5-4 g/kg/day amino acids
• May need to add acetate 2-3 mEq/kg/day to TPN
B. Fat
• 20% lipid emulsion issued to supply calories from fat
– Intralipid® consists of soybean oil (with glycerin and egg lecithin)
– SMOF lipid® consists of soy, MCT, olive and fish oils and is used for infants
at increased risk for developing cholestasis
• Calories = 9 kcal/gm (or 2 kcal/ml with 20% fat emulsion)
• Usual maximum is 3 g/kg/day
• Maintain lipid calories ≤ 50%-60% of total calories
• Very small premature infants develop evidence of essential fatty acid
deficiency (EFAD) in less than a week
• It is safe to administer in a peripheral IV line
49
 • Areas of concern with the infusion of fat emulsions include:
– Hyperlipidemia
– Consider checking TG levels with advancement, particularly in VLBW
– Cholestasis (increasing direct bili with minimal PO intake): change infant to
SMOF lipid product if not already on it.
C. Carbohydrate
• The balance of non-protein calories is provided as IV dextrose
• Calories = 3.4 kcal/gm
• Hepatic glycogen mobilization has been estimated at 4-8 mg/kg/min
• Most neonates requiring PN will tolerate an initial glucose infusion rate (GIR)*
of 6-8 mg/kg/min (Dextrose 8.6-11.5g/kg/d)
• ELBW infants may need lower infusion rates (2-6 mg/kg/min) due to
hyperglycemia
• Monitor for hyperglycemia and glucosuria
• Increase dextrose infusion in 1-3 gm/kg/day increments to a goal of 15-18
gm/kg/day (if needing full parenteral nutrition)
• GIR*(mg/kg/min) = Dextrose concentration x rate(ml/hr)
6 x weight (kg)
• D10W has 10gm/100ml
• Conversion: mg/kg/min x 1.44 = gm/kg/day
3. Electrolytes and Minerals
A. Sodium
• Normal serum level 135-145 mEq/L
• Maintenance sodium requirement = 2-4 mEq/kg/day
• Hypernatremia(Na > 145)
– Increase total fluid intake by 10-30 ml/kg/d
– Remove or decrease Na in IVFs
• Hyponatremia (Na < 130)
– Decrease total fluid intake
– Increase Na supplement
• Growing preemie may need 5-8 mEq/kg/d Na supplements

50
B. Chloride
• Normal level 96-110 mEq/L
• Supplement 2-3 mEq/kg/d (balanced with other anions- P and acetate)
C. Potassium
• Normal serum level: 3.5-5.5 mEq/L (higher with hemolyzed specimen)
• Begin supplementing when good urine output and the serum
potassium is within normal limits
• Maintenance potassium requirements = 1-2 mEq/kg/day
• Hyperkalemia
– Tall, peaked T waves, prolonged PR interval, wide QRS
– Acute treatment-calcium gluconate, + hyperventilation, sodium
bicarbonate (1 mEq/kg)
– Chronic treatment-albuterol, furosemide, insulin + glucose
D. Calcium
• Normal serum level: 6-11 mg/dl
• Ionized Ca: - 0.9-1.5 mmol/L in preemie (3.7-6 mg/dl)
-1.15-1.4 mmol/L in term infant (4.5- 5.5 mg/dl)
• Ca accretion in fetus 25 wk-term is 90-120 mg/kg/d
• It is presently impossible to safely provide sufficient calcium in PN
solutions to approximate in-utero accretion
• Parenteral supplementation is 2-3 mEq/kg/d
• Limit calcium in peripheral lines (Extravasations can cause tissue necrosis)
• High concentrations of calcium and phosphatein PN may lead to precipitation
• For acute, symptomatic hypocalcemia:
– 10% calcium gluconate 50-100 mg/kg –
E. Phosphorus
• Normal serum level: 4.5-9 mg/dl
• Parenteral supplement 1- 2 mmol/kg/day
• SGA infants may be severely hypophosphatemic and may need additional
supplement
F. Magnesium
• Normal serum level: 1.6-2.2 mg/dl

51
 • A maintenance magnesium requirement is not known but is
reported to be 0.2-0.5 mEq/kg/d
• Delay adding f mom was on MgSO4 – assure normal infant Mg level
before adding
• May need to remove if infant is anuric.
G. Acetate
• Acetate is rapidly metabolized to bicarbonate and is added to PN
solutions when the infant has evidence of metabolic acidosis
• Requirement varies between 0-3 mEq/kg/day
• The amount that can be added to the PN solution is dependent on
the amounts of Na+, K+, and phosphorus
4. Vitamins
• Exact intravenous vitamin requirement is not known for premature infants.
• Give 2 ml/kg for babies < 2.5 kg and 5 ml/day for infants ≥ 2.5kg
5. Trace Elements
• Trace elements are provided in the PN solution based on infant need and
discretion of the pharmacist ordering the solution
• For short term PN patients, zinc is the only essential agent dosed at 400
mcg/kg/day
• Infants who remain on TPN for > 2 weeks with little enteral intake
• should have selenium2 mcg/kg/day added to the TPN solution.
Other Considerations:
A. Peripheral Vein PN
– Limit calcium
– Glucose concentrations should not exceed 12.5%
– Osmolarity should be < 900-1000 mOsm/L
B. Cessation of PN
– PN infusion is gradually replaced by enteral feedings by decreasing the rate of PN
infusion as feedings increase and modifying the composition based on enteral intake
– Fat emulsion is discontinued when infant is tolerating 80-100 ml/kg/day of

52
 enteral feeds and complete cessation of PN when tolerating 100-120
ml/kg/day of enteral feeds. – Refer to feeding guidelines
C. The NICU pharmacist will enter the PN order and a progress note into EPIC
daily after consultation with the medical team.
D. Monitoring Parameters
– Baseline assessments should include serum electrolytes and blood glucose
– Serum triglyceride should be monitored more closely in extremely low birth weight
infant.
– Infants who are expected to remain on parenteral nutrition≥1 week,
or who are severely SGA should have a baseline nutritional panel
checked (T/D bilirubin, LFT’s (AST, ALT, GGT), Ca+, P, Mg, alkaline
phosphatase, triglyceride, albumin, BUN, and creatinine) and
repeated at 1-2 week intervals while continuing to receive parenteral
nutrition.

References:
1. Pediatric Nutrition Handbook, eighth edition, 2020 AAP, Nutrition of the
Preterm Infant pp. 113-142.
2. Viaardingerbroek H, et al Initial nutritional management of the preterm infant.
Early Hum Dev 2009 85(11): 691-5.
3. William Oh, Fluid and Electrolyte management, Neonatal Perinatal Medicine,
Mosby, Seventh edition.
4. Corkins MR, ed The A.S.P.E.N. Pediatric Nutrition Support Core Curriculum,
2nd Ed, Silver Spring, MD: ASPEN; 2015.

53
 Chapter: 11 Enteral Nutrition
Sally Norlin, MS,RD,CLC
General Guidelines
• Follow feeding protocols appropriate for infant’s birth wt.
• Standardized feeding practices have been associated with earlier attainment of full
enteral feeding, reduced rates of morbidities, including NEC, and optimized feeding
practices can improve growth and neurodevelopmental outcomes.
• Early introduction of small volume or “trophic” feedings, ranging from 10-20
mL/kg/day, should be considered for all VLBW infants, even when critically ill or
labile following birth. Not harmful and no increased incidence of NEC.
• Maternal breast milk is the preferred source of nutrition. Colostrum is administered in
the order it was pumped as oral immune therapy (OIT), 0.05 mL- 0.5 mL to the
buccal cavity every few hours, and is used as available for the earliest enteral
feedings.
• When own mother’s breast milk (EBM) is not available, donor breast milk
(DBM) should be used for infants born < 2000 g or < 34 weeks. Furthermore, any
infant whose parent/caregiver/s intend to provide human milk may receive
DBM.
• Nutritional needs of the preterm infant exceed those amounts in human milk,
particularly for protein, calcium and phosphorus. Human milk fortifiers are used to
correct these nutritional inadequacies.
• Soy formulas are not recommended for preemies due to poor availability
of calcium and phosphates.
• Feeding intolerance can present with frequent episodes of emesis or
green bilious emesis. Any infant demonstrating these symptoms should
have an immediate abdominal exam. An abdominal X-ray should be obtained
if any abnormal findings are found on exam.

Benefits of Colostrum
• Colostrum is secreted during the early days post-birth when paracellular
pathways between the mammary epithelium are open and permit transfer of high
molecular weight components.
• Compared to mature milk colostrum has high content of lactoferin,
Oligosaccharides, secretory IgA, anti-inflammatory cytokines, growth factors,
soluble CD14, antioxidants and other protective components

54
 • Initial feedings of colostrum stimulate rapid growth in the intestinal mucosal surface
area, facilitate the endocytosis of protein and induce many digestive enzymes.
• OIT has been associated with reduced rates of sepsis, transfers IgA and lactoferrin
to the infant, and may contribute to the infant’s microbiome.
Growth Goals
• The overall goal for preterm infant nutrition is to mimic in –utero growth.
• Preterm growth charts in EMR: Fenton (boys and girls) – 2013
o Weight, length and Head circumference for age
o Hover plot point for exact % and Z score
• First goal: regain birth weight after initial diuretic phase within 7-14 days of life.
• Growth phase goal: once infant is gaining after initial diuresis, goal is to at least
maintain wt for age % / Z score. The average grams /day wt gain required to at
least maintain metrics in growth phase will vary depending on age and gender.
Additional wt gain or “catch up growth” may or may not be prescribed. Overall
growth goals should be individualized based on medical course and nutritional
history.
• Contact NICU RD for individualized goals if growth concerns.

Recommended enteral energy and protein intakes

Infant age (wk.) Energy goals (kcal/kg/d) Protein goals (g/kg/d)

Preterm < 34 0/7 110-150 3.5-4.5
Late preterm 120-135 3-3.2
34 0/7-36 6/7
Term > 37 0/7 105-120 2-2.5

NICU Feeding Protocol

1. Provide colostrum as soon as it is available, ideally within 2 hours of birth.
2. Initiate trophic feeds on day of life 1-2 in infants without GI anomalies
3. If sufficient colostrum is not available after a minimum of 24 hours, consider
using Donor EBM.
4. Calculate feeding volume with birth weight until infant surpasses birth weight
after initial diuretic phase.
5. Use HMF to fortify human milk.
6. Schedule every 3 hour feeds.

55
Advance feedings per the birth weight based tables below:
< 500 g BW Infants
Feeding Day Total Daily Comments
Feeding Volume
1 10 mL/ kg/day
2 10 mL/kg/day
3 20 mL /kg/day
4 20 mL/ kg/day
5 40 mL/ kg/day
6 60 mL /kg/day
7 80 mL/ kg/day
8 100 mL/kg/day
9 100 mL /kg/day Fortify to 24 cal/oz
10 120 mL/kg/day Consider removing IV access
11 140 mL/kg/day
12 150-160 mL/kg/day

501- 1000 g BW INFANTS

Feeding Day Total Daily Feeding Comments
Volume
1 10 ml/kg/day
2 20 ml/kg/day
3 40 ml/kg/day
4 60 ml/kg/day
5 80 ml/kg/day
6 100 ml/kg/day
7 100 ml/kg/day Fortify to 24 cal/oz
8 120 ml/kg/day Consider removing IV access
9 140 ml/kg/day
10 140-160 ml/kg/day = GOAL

56
 1001 - 2000 g BW INFANTS
Type Volume Comments
Trophic feeds 20 ml / kg/day x 1-2
days
Post trophic feeding Increase by 30 -40 ml / -If cueing, may nipple
progression kg/day above
Fortification Fortify to 24 cal/ oz -Do not increase feeds
once tolerating 100-120 on fortification day
ml /kg/day -May consider d/c IV
fluids/nutrition when
feeds at least 100 ml /
kg/day
Goal feeds 140 -160 ml / kg/day

Donor Human Milk:

• Criteria for use:
– All infants born < 34 weeks, < 2000 g bw or with provider concern for
gut perfusion.
– ANY infant outside of criteria if their parent/s intend to provide breastmilk
• If sufficient colostrum is not available after 24 hours, consider using DBM.
• Signed consent is required.
• Criteria for considering discussion with parents about discontinuation of DBM
– Infant is 34 weeks or 1 week old, whichever comes later
– At provider’s discretion in the setting of poor growth
– Parent/Caregiver’s feeding plans for post – discharge should be
considered.

Liquid Protein Fortifier (LPF)

• Extensively hydrolyzed liquid protein (1 g protein = 6 ml or 0.167 gm/ml)
• Purpose is to achieve goal protein intake and used primarily in VLBW, fluid
restricted or donor human milk fed infant.
• LPF is part of feeding order dosed @ 0.5 ml / 25 ml (standard dose) or 1 ml/
25 ml. This will add 0.5-1.0 gm. of protein /150ml of feeds
57
 Feeding Practice: Special Considerations

Transfusions: PRBCs transfusion when patient has stable hemodynamics.

• Stop feeds 2-3 hours before starting transfusion
• Transfuse over 3 hours, maintain NPO
• Hold feeds for 2-3 hours after end of transfusion
• Restart at same feeding volume
• Patient should not miss > 2 feeds due to transfusion
During pharmacotherapy for treatment of PDA
• No need to reduce or withhold advancing feeds

How to restart feeds (Stopped for any reason)

Duration Starting Volume of Fortification Feeding Advance

of NPO Feeds
<24 hr. Same as last feed Same as last Continue per protocol
feed
24-72 hr. 50% of last feed Same as last To full previous
feed volume in 24-48 hr.*
Continue per protocol
4-7 days 50% of last feed Unfortified Feeding protocol using
current wt.
>7 days Beginning of feeding Unfortified Per feeding protocol
protocol using
current weight
*Fortification may be delayed if necessary
Transitioning to homegoing nutrition plan
• Consider transitioning to homegoing nutrition plan once infant is taking >
50% orally with no other significant barriers to discharge.
• NICU RD may assist with involving parents in decision making about
homegoing nutrition plan that involves fortification of breastmilk or formula.
• Parent/Caregiver/s who plan on breast feeding should be encouraged to offer
the breast as often as they are available and infant is cueing.
• When available, a homegoing nutrition plan should be copied and pasted
from NICU clinical nutrition note into D/C summary for the pediatrician.

58
 NON- SURGICAL GERD GUIDELINE
* Symptoms that may be associated with GERD
GI- Regurgita�on,Spi�ng,Emesis,Abdominaldistension
Symptoma�c* GERD and > 36 weeks PMA Cardiorespiratory Spells
Somatosensory–Irritability,Back arching, Crying, Grimace
Aerodiges�ve-Sneezing,Coughing,Choking,Wheezing,Stridor,Feeding or swallowing problems

Consider 2-4 weeks pHF, eHF or maternal

elimina�on diet for breas�eeding infant
Not improved
Spit Ups formula + 5 mL EBM x 3 day trial –OK to BF Nutri�on consult (maternal diet hx &
educa�on)

Improved
No improvement
Improved OR
Spit ups formula mixed 1:1 with EBM- OK to BF
Diet not indicated

Symptoms return Improvement sustained

Spit ups formula + 5 mL EBM

(Meier, ~ 10 mL/kg/day has Con�nue management
benefits ) Consider medica�on
Post D/C Nutri�on follow up
– OK to BF Improved

59
60
References:
1. Morgan J, Bombell S, McGuire W. Early trophic feeding versus enteral fasting for very
preterm or very low birth weight infants. Cochrane Database Syst. Rev 2013.
2. Oddie SJ,Young L,McGuire W. Slow advancement of enteral feed volumes to
prevent necrotising enterocolitis in very low birth weight infants. Cochrane
Database of Syst. Rev. 2021.
3. Ferreira, D., Oliveira, A., Leves, D., de Bem, E., Fatureto, G., Navaroo, N., Afonos,
N., Santiago, F., Mineo, J., Sopelete, M., Martinez, F., Neto, M., & Abdallah, V.
(2019). Randomized controlled trial of oropharyngeal colostrum administration in
very-low-birth-weight preterm infants. Journal of Pediatric Gastroenterology and
Nutrition, 69(1), 126-130.
4. PediatricNutrition Handbook,Eighth edition,2019. AAP,Nutritionofthe
Preterm Infant,pg 113-162
5. Koletzko B, Poindexter B,Uauy R. Nutritional Care of Preterm Infants, Scientific Basis
and practical Guidelines, World Rev Nutr Diet. Basel, Karger,2014,vol 110.
6. Breastfeeding and the Use of Human Milk SECTION ON BREASTFEEDING Pediatrics
2012;129;e827; originally published online February 27, 2012; DOI:
10.1542/peds.2011-3552
7. Sapsford A , Smith C. Enteral nutrition In: Groh- Wargo S, Thompson M, Cox JH,
eds. Pocket Guide to Neonatal Nutrition. 2nd ed. Chicago, IL: Academy of Nutrition
and Dietetics; 2016: 76-124.
8. Rosen R, Vandenplas Y, Singendonk M, Cabana M, DiLorenzo C, Gottrand F, Gupta
S, Langendam M, Staiano A, Thapar N, Tipnis N, Tabbers M.J Pediatr Gastroenterol
Nutr. 2018 Mar;66(3):516-554

61
 Vitamins and Iron Supplements
Ann Ebert, Pharm D and Sally Norlin, MS,RD

Vitamin D
• Start on term and preterm infants when tolerating enteral feeds.
• Dose is according to the total daily intake volume.

400 units* 200 units* D/C when

EBM + HMF 24 <200 ml/day >200 ml/day >400 ml/day
EBM + HMF 22 <350 ml/day >350 ml/day >700 ml/day
Similac Special <200 ml/day >200 ml/day >400 ml/day
Care 24
Neosure <400ml/day >400 ml/day >800 ml/day
Term formula <500 ml/day >500 ml/day >1000 ml/day
EBM (Exclusively Daily If less than half the Never
or partially) feeds are EBM.
* Concentration is 400 units/ml
Iron
• Term infants do not need routine iron supplement
• For infants < 37 weeks at birth or term SGA .
– Start when on at least 60 mL/kg/day of feeds and approximately 2 weeks of age.
– Standard dosing of iron for inpatients = 3 mg/ 0.2 ml. (Give
3 mg dose 1-3 times per day based on patient need)
– If on erythropoietin = 6 mg /kg/day
– Iron fortified formulas (@ ~ 150 ml/ kg/ day) provide ~ 2 mg/kg/day

Multivitamin with Fe
• Each 1 ml provides 11 mg iron and 400 IU Vit D
• Can be used in lieu of separate Vit D and Fe supplements in the premature or SGA infant
• Give 1 ml/day or 0.5 ml 1-2 times/ day based on patient need
62
 Formula Analysis
Nutrient AAP- MBM MBM MBM Similac Similac MBM Similac Similac
per Preterm Term w/HMF Special Special Care w/ Neosure Term
kg/d - CL- HP Care- -30 Neosure formula
24, HP
Kcal/oz 20 20 24 24 30 24 22 20
Preterm 100 ml/kg 100 ml/kg 100 ml/kg 100 ml/kg 100 ml/kg 100 ml/kg 100 ml/kg 100 ml/kg
Kcal/kg 110-130 67 68 80 80 100 80 73 68
Protein(g) 3.4-4.4 1.4 1.0 2.44 2.68 3.0 1.5 2.08 1.4
CHO (g) 7-20 6.6 7.2 8.0 8.1 7.8 8.7 7.5 7.6
Fat (g) 5.3-8.4 3.9 3.9 4.0 4.4 6.7 4.7 4.1 3.7
Calcium 100-220 25 28 121 146 183 44 78 53
(mg)
Phosphorus 60-140 13 14 67 81 101 24 46 28
(mg)
Iron (mg) 2-4 0.12 0.03 0.47 1.46 1.83 0.32 1.34 1.2
Zinc (mg) 1.4-2.5 0.34 0.12 1.31 1.22 1.52 0.31 0.89 0.51
Sodium 3-5 1.1 0.8 1.6 1.5 1.9 1 1.07 0.7
(mEq)
Potassium 2-3 1.5 1.4 2.9 2.7 3.4 1.9 2.7 1.8
(mEq)
Osmolality 290 286 450 280 325 340 250 310

*Pediatric Nutrition Handbook, 8th Edition. American Academy of Pediatrics, 2019 *Neofax, accessed on line 3/2022

63
 Chapter 12: Necrotizing Entercolitis
Henry Zapata Galarza, MD; and Eileen Cowan, MD
• Inflammation of the bowel wall leading to necrosis
• Most common GI emergency in preterm infants
• Affects 1-3 per 1000 live births
– >90% of cases occur in infants ≤ 1500 grams
– Occurs in 1-7% of infants ≤ 1500 grams
– Affected term infants may have experienced asphyxia or have congenital heart
disease including PDA (due to impaired intestinal perfusion)
• High risk until 35-36 weeks postmenstrual age
• Most commonly affects the distal ileum and proximal colon
Pathophysiology
• Unknown but hypothesized to be multifactorial
– Mucosal intestinal injury (hypoxia/ischemia) + enteral nutrition +
abnormal bacterial colonization → activation of inflammatory cascade →
further bowel injury, invasion of bacteria into bowel wall → bowel necrosis
• Risk Factors
– Prematurity
– Enteral feeds
– Intestinal ischemia: Clinically significant PDA, IUGR, birth
asphyxia, CHD, exchange transfusion, indomethacin, maternal
cocaine abuse
– Absence of maternal antenatal steroid treatment
– Recent blood transfusion, particularly of cells that are not type specific.
Some evidence to suggest the anemia itself predisposes to NEC, not the actual
transfusion
– Prolonged antibiotic usage – impacts on microbiome of GI tract
– Abdominal wall defects
– Use of H2 blockers
Measures to Prevent NEC
• Feedings
– Use human milk (EBM or DBM for high-risk patients)
– Disciplined approach with NICU feeding protocols
• Limit use of antibiotic therapy
• Hold feedings 3 hours before and 3 hours after blood transfusion
• Do not use H2 blockers or PPIs until ≥ 35 weeks CGA

64
Clinical Presentation
• Temperature instability, lethargy, increased apnea/bradycardia/desaturation episodes
• Abdominal distension/tenderness/firmness, feeding intolerance with emesis
(usually bilious), bloody stools, abdominal wall discoloration
• Laboratory: neutropenia, thrombocytopenia, coagulation abnormalities (platelet
consumption), metabolic acidosis, electrolyte abnormalities, glucose instability
• Radiographic: ileus, dilation and thickening of bowel loops, fixed and/or dilated
loop(s) of bowel, pneumatosis intestinalis, portal venous gas, free air

Modified Bell Staging Criteria for NEC

Systemic Abdominal Radiographic
Stage
signs signs signs
I Temperature Gastric residuals, mild
Normal or
(Suspected instability, apnea, abdominal distention,
mild ileus
NEC) bradycardia, lethargy occult blood in stool
Prominent abdominal
Ileus, dilated
IIA distension +
Same bowel loops, focal
(Mild tenderness, absent
as above pneumatosis
NEC) bowel sounds, grossly
intestinalis
bloody stools
Extensive pneumatosis
IIB Mild metabolic Abdominal wall
intestinalis, early
(Moderate acidosis and edema & tenderness
ascites, + portal
NEC) thrombocytopenia + palpable mass
venous gas
Hypotension,
IIIA respiratory & Worsening wall
Prominent ascites,
(Advanced metabolic acidosis, edema & erythema
fixed bowel loops
NEC) oliguria, DIC, with induration
mechanical ventilation
IIIB Evidence of perforation
(Advanced Shock (tense abdomen, Free Air
NEC) bluish discoloration)

65
 Differential Diagnosis
• Spontaneous intestinal perforation (SIP): usually in terminal ileum or colon
– Mostly in VLBW infants
– Distinguished from NEC by absence of pneumatosis, hypotension and abdominal
distention; can occur in the first week of life (earlier than NEC); independent of
feeding
• Cow’s milk protein allergy: rare in preterm; rarely occurs before 6 wks of age
• Infectious enteritis
• Anal fissures resulting in rectal bleeding
Management*
• NPO, replogle to low intermittent suction
– After 7-14 days* feeds should be started gradually
• Serial abdominal circumferences and serial abdominal examinations (both imaging
and physical exam)
• Maintenance IVFs until TPN can be started
• Labs: CBC with differential, CRP, blood gas, electrolytes, glucose, blood culture,
consider coagulation studies
– Repeat labs every 6-12 hours (except blood culture) until infant clinically stable
– Cultures positive in only 20-30% of cases
• Radiographs: APKUB & left lateral decubitus (for free air)
– Repeat every 6-12 hours for first 24-48 hours
– Abdominal US: to assess for pneumatosis, fluid collections, bowel wall
thickness and peristalsis
• Broad-spectrum antibiotics to include anaerobic coverage*
– Usually ampicillin or vancomycin, cefotaxime or gentamicin, and metronidazole
– Treat for 7-14 days
• Monitor and manage homeostasis, DIC, and respiratory status as needed
• Pediatric Surgery Consult especially with x-ray or US diagnosis of NEC
(*See “Wisconsin State Guideline for Staging and Management of NEC)
Prognosis
• 27-63% of cases need surgical intervention (laparotomy with resection or
peritoneal drain)

66
 • Mortality: Overall 20-30%; Increases after perforation to 35-55%
• Survivors have a high prevalence of adverse GI sequelae (9-36% have strictures,
short gut, TPN cholestasis)
– Also increases risk of adverse neurodevelopmental outcomes

Reference
1. Neu J, Walker AW. Necrotizing Enterocolitis. NEJM. 2011; 364 (3) 255-64.
2. Chu A, Hageman JR and. Caplan MS. Necrotizing Enterocolitis: Predictive Markers
and Preventive Strategies. Neoreviews 2013; 14; e113. DOI: 10.1542/neo.14-3-
e113
3. Kim JH, Abrahms SA. Diagnosis, Management and Prevention of necrotizing enterocolitis
in newborns. UpToDate, 2018.

http://www.uptodate.com/contents/prevention-of-necrotizing-enterocolitis-in-
newborns

https://www.dynamed.com/condition/necrotizing-enterocolitis-19

67
Wisconsin State Guideline for Staging and Management of NEC

68
 Chapter 13: Hyperbilirubinemia
Michael A. Porte, MD & Nicole Baumann-Blackmore, MD
Neonatal hyperbilirubinemia is common and occurs in up to 80% of all newborns.
Approximately 5-10% of newborns will require phototherapy, while a much smaller
percentage will require more intensive therapies such as exchange transfusion. It is
important to understand the risk factors for developing severe hyperbilirubinemia
and the treatment guidelines based on these risk factors.
Risk Factors for Severe Hyperbilirubinemia in Infants ≥ 35 Weeks’ Gestation
• Major risk factors
– Pre-discharge TSB level in the high-risk zone (Fig 2)
– Jaundice observed in the first 24 hours
– Blood group incompatibility with positive direct Coombs test
– Other known familial hemolytic disease (G6PD, spherocytosis, etc.)
– Gestational age 35-36 wk.
– Previous sibling received phototherapy
– Cephalohematoma or significant bruising
– Exclusive breastfeeding, particularly with poor feeding or excessive
weight loss
– Asian race
• Minor risk factors
– Pre-discharge TSB or TcB level in the high intermediate-risk zone
– Gestational age 37-38 weeks
– Macrosomic infant
– Male gender
• Low risk group
– TSB or TcB level in the low-risk zone
– Gestational age ≥ 41 wk.
– Exclusive bottle feeding
– Discharge from hospital after 72 hours

69
 Risk Zone as a Predictor of Hyperbilirubinemia
Newborns Who Subsequently
TSB Newborns Total
Developed a TSB Level > 95th
Before Discharge = 2840 n (%)
Percentile, n (%)
High-risk zone(>95th percentile) 172 (6.0) 68 (39.5)
High intermediate-risk zone 356 (12.5) 46 (12.9)
Low intermediate-risk zone 556 (19. 6) 12 (2.26)
Low-risk zone 1756 (61.8) 0

70
 Nomogram for designation of risk in 2840 well newborns at 36 or more weeks’ gestational age with birth
weight of 2000g or more or 35 or more weeks’ gestational age and birth weight of 2500 g or more based on the
hour-specific serum bilirubin values.

71
Ten Commandments for Preventing and Managing Hyperbilirubinemia:
1. Promote and support successful breastfeeding
2. Measure TSB if clinical jaundice before 24 hours
3. If TcB is elevated, must confirm with TSB
4. Recognize that visual diagnosis of jaundice is unreliable
5. Interpret all TSB levels according to infant’s age in hours
6. Do not treat late preterm as a term infant; they are at a much higher risk.
7. Determine the need for repeat bilirubin levels and safety for hospital
discharge based on the 24 hour screening bilirubin level
8. Provide parents with information about newborn jaundice
9. Plan follow-up based on time of discharge and the risk assessment
10. When indicated, treat the newborn with phototherapy or exchange transfusion

Indirect Hyperbilirubinemia
Etiology:
• Concentration from dehydration
• Increased production
– Blood group incompatibility: Rh, ABO, minor subgroup
– RBC defects: spherocytosis, elliptocytosis, pyruvate kinase or G6PD
deficiency, thalassemia
– Extravascular blood: cephalohematoma, bruises
– Polycythemia
– Sepsis or UTI
• Increased enterohepatic circulation
– Bowel obstruction, ileus
– Breast milk jaundice
• Decreased excretion
– Prematurity
– Hypothyroidism
– Hepatocellular dysfunction
– Galactosemia, tyrosinemia
– Drugs (aspirin, sulfa)
– Crigler-Najjar syndrome
– Gilbert syndrome

Initial Work-up for bilirubin in high risk zone and/or requiring phototherapy:
72
 • Total and Direct bilirubin
• Document maternal antibody status and send cord blood for infant’s Type and
Coombs
• Hematocrit and reticulocyte count: evidence of hemolysis
• Smear: Spherocytosis, fragmented RBCs with hemolysis (heel stick will be a false
positive)
• Consider screen for sepsis and/or UTI
• Consider G6PD, thalassemia and pyruvate kinase screen
• If hyperbilirubinemia occurs after two weeks of age, obtain results of
newborn screen and consider testing for thyroid dysfunction (TSH, free T4)
Management:
• Consider supplementing feeds to decrease enterohepatic circulation or
starting IVFs to improve urine output and increase bilirubin excretion
Phototherapy
• First line of treatment for management of hyperbilirubinemia in a newborn
• Can be a high-intensity bilirubin blanket (for babies in the newborn nursery) to
multiple banks of overhead lights depending on the bilirubin level
• Use total bilirubin. Do not subtract direct bilirubin from the total.
• For infants > 35wks: Follow AAP guidelines and bilirubin charts (see pages 69 &
70)
• For infants < 35wks and <7 days:
Initiate Phototherapy Exchange Transfusion for
infants without neurologic
findings
Gestational Age Total Serum Bilirubin Total Serum Bilirubin
(Week) (mg/dl) (mg/dl)
<28 0/7 5-6 11-14
28 0/7-29 6/7 6-8 12-14
30 0/7-31 6/7 8-10 13-16
32 0/7-33 6/7 10-12 15-18
34 0/7-34 6/7 12-14 17-19

73
 – Use postmenstrual age for phototherapy. For example, when a 29 0/7
week infant is 7 days old, use the TSB level for 30 0/7 weeks.
– Use lower range of listed TSB levels for infants at greater risk of
bilirubin toxicity:
• Lower gestational age
• Rapidly rising TSB (rate of rise >0.2 mg/dL/hour)
• Significant bruising
• Clinically unstable

IVIG & Albumin Infusions for Hypoalbuminemia:

• IVIG: 1 gm/kg over 2-4 hours
• May be useful for hyperbilirubinemia associated with hemolysis
• Albumin: 10-20 ml/kg of 5% Albumin
• Studies have shown conflicting levels of efficacy but may be used on a
case-by-case basis
Exchange transfusion for Hyperbilirubinemia: Goal is to prevent kernicterus and
bilirubin-induced neurologic dysfunction (BIND)
• For infant ≥ 35 weeks GA, follow AAP guidelines
• Also indicated when infant has signs of kernicterus or BIND regardless of
TSB level
• For infants < 35 weeks and without neurologic findings, use table above

74
Guidelines for phototherapy in infants of 35 or more weeks’ gestation.
Note: levels shown are approximations.

75
Guidelines for exchange transfusion in infants of 35 or more weeks’ gestation.
Note: levels shown are approximations.

76
Exchange transfusion
• Goal: To remove antibodies and bilirubin
– Before exchange, send baby’s blood for metabolic screen, G6PD screen,
and Hgb electrophoresis
– Request fresh blood (< 3 days)
– Should be double volume (removes 87% of baby’s RBCs, infants >35
weeks have blood volume of 85 mL/kg)
– Aliquots should be no more than 5% of blood volume in a single pass
– Length of exchange procedure would be about 2 hours
• Complications of exchange
– Arrhythmia, cardiac arrest
– Hypoglycemia, hypocalcemia, hyperkalemia
– Necrotizing Enterocolitis
– Portal vein thrombosis or other thromboembolic events
– Thrombocytopenia
• Review detailed protocol for this procedure

Direct Hyperbilirubinemia (if TsB <5, any direct bilirubin >1 mg/dL. If TsB >5, any
direct bilirubin >20% of total)

Etiology
• Prolonged TPN use
• Anatomic Obstruction
– Biliary atresia and/or choledochal cyst
– Alagille syndrome
– Biliary sludge in preterm infants
– Tumor/mass
• Infections
– CMV
– Enterovirus
– HSV
– Parvovirus
– UTI
– Sepsis
– Toxoplasmosis
– Congenital syphilis

77
 • Genetic/Metabolic
– Alpha-one antitrypsin deficiency
– Cystic fibrosis
– Galactosemia
– Zellweger syndrome
– GALD

Diagnosis & Management:

• Liver ultrasound
• LFTs, including GGT
• GI consult
• Consider HIDA scan
• Discuss with nutrition and pharmacy about reconstituting trace elements in
TPN
• Consider ursodiol

References:
1. Management of hyperbilirubinemia in the newborn infant 35 or more
weeks of gestation. AAP Subcommittee on Hyperbilirubinemia.
Pediatrics. 2004;114(1):297.
2. Anderson et al, "Neonatal Indirect Hyperbilirubinemia", NeoReviews,
November 2020, 21:11, e749.
3. Pillai, et al, "Pathogenesis and Management of Indirect Hyperbilirubinemia in
Preterm Neonates Less than 35 weeks...", NeoReviews, May 2020, 21:5,
e298.
4. Bhutani, "Jaundice due to Glucose-6-Phosphate-Dehydrogenase
Deficiency", NeoReviews, March 2012, 13:3, e166.
5. Mintjens et al, "Neonatal Hyperbilirubinemia and Cholestasis",
NeoReviews, September 2021, 22:9, e622.
6. Loomes, "Approach to Evaluation of Cholestasis in Neonates and Young
Infants", Up To Date, online, 2021.

78
 Chapter 14: Cardiovascular System
Megan Derrer, MD & Nathan Lepp, MD

A. Shock
Definitions
Shock
– Insufficient organ perfusion to meet tissue metabolic needs, leading to tissue
hypoxia, acidosis, metabolic derangements and cell death
Hypotension:
- BP lower than expected range for age
- Hypotension does not necessarily mean that an infant is in shock
– There is no BP threshold below which intervention to increase BP has been
shown to improve outcomes
– A combination of low BP with clinical signs of poor perfusion appears to be more
strongly correlated with poor outcomes
Symptoms
• Tachycardia, poor perfusion/weak pulse, cold extremities, lethargy, apnea,
tachypnea, metabolic acidosis
Classification of Shock
• Hypovolemic Shock
– From blood loss-antenatal or postnatal
– Post-operative due to capillary leak and third spacing of
intravascular volume
o Can also be seen in sepsis
• Drug Induced Hypotension
– Magnesium sulfate, beta blockers (Labetalol), nitroprusside,
narcotics, barbiturates
• Cardiogenic Shock
• Cardiac failure – impaired filling, ventricular emptying, and/or
contractility
– Birth asphyxia, CHD, metabolic abnormalities, arrhythmia,
cardiomyopathy, obstruction to venous return

79
 • Distributive shock (including septic shock)
– Inadequate relative intravascular volume secondary to
vasodilation
– Septic shock due to release of endotoxins which lead to
vasodilation
– Also have capillary leak with third spacing due to endothelial
injury
- Anaphylaxis
- Vasodilators
- Adrenal insufficiency
• Neurogenic Shock
– Birth asphyxia and IVH
• Shock in extreme prematurity
– Due to hypovolemia, inability to regulate vascular tone, immature
catecholamine response, IVH, adrenocortical insufficiency
– Usually respond better to inotropes than to volume administration
– PDA can cause transient hypotension

Stages of Shock

Stage Pathophysiology Mechanisms Change in

vitals/lab
values
Compensated Heart, brain, Vasoconstriction Tachycardia
lungs, kidney stimulated by -Stable BP
perfusion acidosis/catecholami -Normal HCO3
maintained, ne release/decreased and lactate
reduced flow stimulation of
to less vital baroreceptors à
organs decreased urine
output
Uncompensated Decreased Continuation of the - Increased
Reversible perfusion to all above tachycardia-BP
organs begins to fall
-HCO3 -
80 decreases
Lactate
 Uncompensated Cellular Release of cellular Extreme
Irreversible dysfunction mediators that lead to tachycardia à
and acidosis further reduced bradycardia
secondary to perfusion, injury to the -Severe
ischemia à endothelium, activation decrease in BP
cellular death of coagulation cascade -Severe
decrease in
HCO3
-Severe
increase in
lactate
Diagnosis
• CBC with differential
• Blood culture
• ABG, lactate
• Electrolytes, glucose, calcium
• Newborn transfusion work-up
• Chest x-ray, echocardiogram, and head ultrasound
Treatment
• Treat underlying abnormalities
• To improve hypotension:
– Volume expansion
• Normal saline bolus 10 ml/kg over 10-30 minutes
• Consider blood products for volume expansion
• Low hematocrit
• Bleeding
• Electrolyte abnormalities that may be sensitive to additional
dextrose or sodium
• Colloids associated with increased mortality
• May worsen cardiogenic shock
• Medications for hypotension

81
 Adverse
Medication Dose Mechanism Notes
Effects
Dopamine
1-5 receptor Preferred
mcg/kg/min Increases renal inotrope in
blood flow Tachycardia, neonates esp.
arrhythmias, for <1500 gm.
Dopamine
Dopamine 5-15 tissue ++Chronotrope
and β1 and
mcg/kg/min α receptors ischemia
(only use in +Inotrope
central IV)
SVR effect is
α receptors dose dependent
15-20
mcg/kg/min Systemic
vasoconstriction

β1>>β2 Tachycardia, Better than

hypotension dopamine in
Increase with presence of
2-20 contractility, hypovolemia
Dobutamine myocardial
mcg/kg/min decreases SVR , cutaneous dysfunction
+Chronotrope vasodilation,
arrhythmia, Less effect on
tissue heart rate
ischemia
+Inotrope
β1 & β2 Hyperglycemi
0.1-0.3
mcg/kg/min Vasodilation, a, Most potent
Increases tachycardia, vasopressor
Epinephrine contractility increased
++Chronotrope
lactate,
α receptors arrhythmias, +Inotrope
0.3-1
Vasoconstriction tissue
mcg/kg/min
, increases HR ischemia,
hypokalemia

82
 Stress dosing: Increases the
expression of Hyperglycemia,
1 mg/kg/ Use for
Hydro- adrenergic GI perforation/
dose q8 hr. unresponsive
cortisone receptors in the hemorrhage, hypotension
Physiologic vascular wall infection,
dosing = enhancing vascular cardiac Do not use with
1 mg/kg/day reactivity to other hypertrophy indomethacin
q8-12 hr. vasoactive
substances

Vasopressin 0.01 hr – 0.04 Vascular effects via Hypertension, Vasoconstrictive

units/kg/hr G protein coupled electrolyte effects
V1a abnormalities, predominate in
(vasoconstriction fluid overload IV infusion
via IP3 pathway)
and V2 receptors Minimal
(vasodilation via chronotropic and
cAMP) in inotropic effects
cardiovascular
system
Milrinone Loading dose PDE-3 inhibitor  Hypotension, Dosing
50 mcg/kg over increased arrhythmias extrapolated
15 minutes intracellular cAMP, from older
increased infants and
Maintenance myocardial children
0.3-0.75 intracellular
mcg/kg/min calcium, and May potentiate
increased uptake of diuretic effects
calcium after
systole Does not
increase
myocardial
oxygen
consumption

83
B. Hypertension (see also Chapter 18, Neonatal
Kidney) Definition
• Systolic/diastolic BP >95th percentile in right upper extremity
– Term infant >90/60
– Preterm infant >80/50
Etiologies
• Renal artery or aortic thrombosis
• Primary renal disease
• Obstructive uropathy
• Coarctation of the aorta
• Endocrine disorders: hyperthyroidism, CAH (11-betaOH)
• Medications: theophylline, corticosteroids, pancuronium
• BPD
• Pain, agitation, drug withdrawal
Diagnosis
• Four extremity BPs-evaluate for coarctation
• Labs
– UA, Urine culture
– Urine Protein / Urine creatinine (Normal <1)
– Electrolytes, creatinine, BUN
– Plasma renin activity, aldosterone
– TSH, free T4
• Imaging
– Abdominal/Renal ultrasound with Doppler studies
– Echocardiogram
Treatment
• Nephrology consult to determine appropriate medication
– Usually start with a calcium channel blocker (isradipine)
–
C. Arrhythmias
Complete Heart
Block
• Seen with maternal connective tissue disorders (i.e. SLE) who have anti-SSA (Ro)

84
 or anti-SSB (La) antibodies
• Can lead to hydrops fetalis
• Treatment
– Only necessary if symptomatic
– Generally symptomatic if HR < 55 bpm
– Atropine, isoproterenol, pacemaker
Supraventricular Tachycardia
• HR 230-330 bpm with decreased variability (fixed R-R interval)
• Increased risk with CHD (Ebstein’s anomaly, L-TGA),WPW
• Acute Treatment
– Unstable-synchronized cardioversion
• Start with 0.5 J/kg, increasing by 0.5 J/kg to max 2 J/kg
– Stable
• Vagal maneuvers-gag reflex, ice to the face, knees to chest
• Adenosine
- 50 mcg/kg rapid IV push followed by rapid saline flush
• Via PIV with 3 way stop cock for rapid flush
- Increase by 50 mcg/kg every 2 minutes to max dose of 250 mcg/kg
- Causes transient AV node block-have ECG running and defibrillator nearby

D. Congenital Heart Disease (CHD)

• VSD-most common CHD
• Transposition of the great arteries-most common CHD presenting in the first
week of life
• HLHS-second most common in the first week of life and the most common
cause of mortality in the first year of life
• Tetralogy of Fallot-most common CHD presenting after the first week of life
Diagnosis
• Four extremity blood pressures
• Pre- and post-ductal O2 saturations (CHD screen)
• Chest x-ray-evaluate heart size and pulmonary vascular markings
• ECG
• ABG-evaluate for metabolic acidosis and hypoxemia
• Echocardiogram

85
Clinical Presentation
• Respiratory Distress: VSD, PDA, ASD, TAPVR, truncusarteriosus(TA)
• Murmurs
• Systolic
- Holosystolic – VSD
- Ejection – aortic/pulmonic stenosis or obstructed outflow tract
- Click – aortic/pulmonic stenosis or truncus arteriosus
• Blowing
- Valve regurgitation
• Diastolic *always pathologic
- Aortic/pulmonic regurgitation, tricuspid/mitral stenosis, increased
flow across tricuspid/mitral valves
• Continuous
- PDA, AV fistula, venous hum, collateral vessels, truncus
arteriosus, aortopulmonary window
• Gallop
- Decreased ventricular compliance and high-flow states
• Cyanosis – bluish discoloration of the tissues when deoxygenated hemoglobin
in the capillary >3g/dL
• Appearance of cyanosis depends upon the total amount of
deoxygenated hemoglobin, not ratio of deoxygenated to oxygenated
blood
• Cyanosis with normal or increased pulmonary blood flow: TGA, TA, DORV
• Cyanosis with decreased pulmonary blood flow: TOF, tricuspid atresia,
pulmonary atresia/stenosis, Ebstein’s anomaly
• Differential Cyanosis - >10% difference in pre/post-ductal saturations
- Lower body more cyanotic than upper body – R to L ductal shunting
with increased PVR
- Seen in coarctation of the aorta, pulmonary hypertension, interrupted
aortic arch
• Reverse differential cyanosis
- Upper body more cyanotic than lower body
- Seen with dTGA + coarctation of the aorta, pulmonary hypertension,
86
 or interrupted aortic arch
• Shock: TAPVR with obstruction, HLHS, critical aortic stenosis, interrupted aortic
arch, coarctation of the aorta

Management
• IV access; UAC, UVC, PICC line
• Prostaglandin E1
– For ductal-dependent lesions
– Dose: start at 0.01-0.02 mcg/kg/min for known ductal dependent lesions or
lesions presenting soon after birth
- If presenting several days after birth, consider starting at 0.5-1
mcg/kg/min
– Side effects: apnea (may be treated with caffeine), fever, leukocytosis,
cutaneous flushing, bradycardia, hypotension, hypoglycemia,
hypocalcemia
– Long-term causes reversible cortical proliferation of the long bones, and gastric
outlet obstruction
• Generally avoid supplemental oxygen as this causes pulmonary vasodilation and
will increase pulmonary blood flow at the expense of systemic blood flow
– Maintain oxygen saturations around 75-80% = Qp/Qs of 1
– Qp/Qs = (SaO2-SvO2)/SpvO2-SpaO2)
• Ratio of pulmonary to systemic blood flow
• Cranial ultrasound, renal ultrasound
• Genetic testing

E. Patent Ductus Arteriosus in Preterm

infants Clinical Presentation
• Murmur-LUSB, systolic or continuous
• Hyperactive precordium, bounding pulses, palmar pulses
• Widened pulse pressure (> 30 mmHg)
• Worsening respiratory distress
• Hepatomegaly, cardiomegaly
– Neither individual clinical trials nor meta-analyses have
demonstrated that closing PDA results in improved long-term
outcomes in preterm infants

87
– Trend toward a more conservative approach to PDA management

PDA Guideline UnityPoint-Meriter and AFCH

88
F. Persistent Pulmonary Hypertension Diagnosis
• Pulmonary hypertension should be considered in a term/post-term infant with
cyanosis
• Associated with fetal distress, RDS and meconium aspiration syndrome
• Pre-ductal and post-ductal saturations differ significantly (>10%)
• Desaturation with stimulation, crying
• S2 is loud with diminished split, murmur of tricuspid regurgitation
• Chest x-ray-decreased pulmonary vascular markings
• Echocardiogram
– PDA with R → L shunting
– Flattening of the interventricular septum
– Bulging of the atrial septum
– Pulmonary pressures determined using TR velocity
Treatment
• Minimize handling
• Surfactant-for RDS or meconium aspiration
• Sedation/paralysis
• Supplemental oxygen as needed to maintain saturations within goal range:

89
 Dilates pulmonary vasculature
• Correct acidosis: Acidosis leads to pulmonary vasoconstriction
• Inhaled Nitric oxide: See Respiratory Chapter
• Sildenafil
• Inotropic agents to increase systemic pressures (decreasing shunting)
• ECMO – consider if oxygenation index (OI) is > 35 for 5-6 hrs
OI = mean airway pressure x FiO2 x 100
PaO2

G. Miscellaneous
Electrocardiogram
• Differs from the adult
• RV dominance with right axis deviation
• T wave inversion in V1-V4 after 48-72 hours of age is normal
–If T wave inversion is not present consider RVH
• RSR’ in right precordial leads is normal as long as QRS interval is <10 msec
over normal intervals
• QTc interval
–QT/square root of the previous R-R interval
–<0.47 normal in first week of life
–<0.45 normal from 1 week to 6 months of age
Equations
• Shortening Fraction = LV diastolic diameter – LV systolic diameter x 100
LV diastolic diameter
– Normal is 28-40%
• Ejection Fraction = LV end-diastolic volume – LV end-systolic volume x 100
LV end-diastolic volume

90
 • Cardiac Output = Stroke volume x Heart rate
– Stroke volume is affected by preload, afterload, and contractility
– In the neonate the CO is more dependent on heart rate

Pulmonary Hypertension Screening guideline for preterm infants

91
References:
1. Use of antihypotensive therapies in extremely premature infants, Beau Batton et al, NICHD,
Pediatrics, 2013;131;e1865
2. Park MK, Salamat M. The Pediatric Cardiology Handbook, Fourth Edition. 2010
3. The Management of Hypotension in the Very-Low-Birth-Weight Infant: Guideline for Practice. Glenview,
IL: National Association of Neonatal Nurses; 2011
4. Satpute MD, et al. Cardiovascular instability after patent ductus arteriosus ligation in preterm
infants: the role of hydrocortisone. J Perinatol. 2012;32(9):685-689.
5. Mitra, Souvik, et al. “Association of placebo, indomethacin, ibuprofen, and acetaminophen with
closure of hemodynamically significant patent ductus arteriosus in preterm infants: a systematic
review and meta-analysis.” JAMA 319.12 (2018): 1221-1238.
6. Brodsky, D and Martin, C. Neonatology Review. 2nd ed., Hanley and Belfus, Inc., 2010.
7. Bondi DS and Ohler KH. Vasopressin and hemodynamic effects on neonates. NeoReviews (2017)
18 (8) e460-e571 NeoFax

92
 Chapter 15: Hematology
Pamela Kling, MD & Henry Zapata Galarza MD
A. Anemia
• Anemia-Blood Loss
• Obstetrical-abruption, placenta previa, umbilical cord trauma
• Immediate (vs. delayed) umbilical cord clamping
• Feto-maternal hemorrhage
• Twin-twin transfusion syndrome
• Internal hemorrhage-IVH, subgaleal hemorrhage, cephalohematoma,
adrenal hemorrhage, subcapsular hematoma of liver
• Iatrogenic-lab tests
• Anemia-Increased RBC destruction
– Hereditary RBC disorders-G6PD, hereditary spherocytosis,
thalassemia
– Immune hemolysis-Rh/ABO incompatibility
– Acquired hemolysis-infection, drugs
• Anemia-Decreased RBC production
– Anemia of prematurity
– Aplastic or hypoplastic anemia
– Bone marrow suppression-parvovirus, rubella
– Nutritional anemia-iron deficiency
• Anemia-Physiologic
– Normal nadir at 6-8 weeks in term infant
– Delayed clamping or cord milking can minimize the Hgb at the
nadir
– Earlier for preterm infant (4-6 weeks)
– Preterm infant nadir is lower than term infant (Hgb of 9 versus 11).
Anemia Initial Work-up
• Must be completed before transfusion
• CBC with platelets
• Reticulocyte count
• Peripheral smear (spherocytes, ABO incompatibility; nRBC, Rh disease)
• Type/Coombs on mother and infant
• Kleihauer-Betke on mother (looking for fetal RBCs)
93
Additional Tests
• RBC enzyme studies: G6PD and pyruvatekinase
– G6PD-may be falsely negative during acute process due to increased
enzyme activity in reticulocytes
• Hemoglobin electrophoresis (newborn screen)
• Head or abdominal ultrasound
Management
• Consider transfusion guidelines from Iowa Study: Low Threshold vs. (High Threshold):
Less IVH in High group, better long-term outcome in girls in Low.
Hematocrit Other Clinical/Lab data
<7-10 Stable child > 1 wk old, asymptomatic, RA or NC,
(<21-30) NCPAP with FiO2<40%, Room air, & retic <4%
<28 (<38) Mild lung disease, NC/CPAP/NPSIMV with FiO2>40%,
or major surgery >21%
<11-13 Hb Critically ill, severe lung disease in first
(<33-39 Hct) week or major surgery
Any Hct Acute blood loss & signs of shock
• Draw first newborn screen prior to transfusion
• Neonatal Transfusion workup (NTW; aka-Type and screen) only needs to be
completed once during the admission, up to 4 months of age
• Transfuse with 15-20 ml/kg of CMV negative, irradiated, type specific pRBCs.
– Irradiation inactivates donor lymphocytes reducing GVHD, but increases
potassium concentration of packed cells and reduces the half-life of stored
blood.
– Some centers used leukocyte-reduced/filtered blood in place of CMV negative
blood. This also reduces CMV transmission.
– Transfusion of 15-20 ml/kg will raise the Hct about 10%
– Transfusion of pRBCs causes bone marrow suppression
– Hold feedings, before & during transfusion per guidelines in the
feeding protocol chapter
– Note: At UW AFCH pRBCs are not type-specific and have higher Hct., so
transfuse up to 15 ml/kg/d in one installation.

94
 Special Transfusions
• Double-Volume Exchange Transfusion
– Indications-hemolytic disease of the newborn
• Volume to be exchanged = 2[infant’s blood volume (ml/kg) x weight (kg)]
• Blood volume estimates: term = 80 ml/kg; preemie = 90 -100 ml/kg
• Partial Exchange Transfusion
– Indications
• Polycythemia, Significant anemia with normal blood volume
• Volume to be exchanged if wanting to lower Hct =
(Blood volume x wt) x (observed Hct –desired Hct)
Observed Hct
• Volume to be exchanged to increase Hct =
(Blood volume x wt) x (desired Hct – observed Hct)
Hct of pRBCs

B. Anemia of Prematurity Etiology

• Reduced erythrocyte half-life
• Iatrogenic losses from phlebotomy
• Hemo-dilution due to increasing body mass
• Relative deficiency of erythropoietin
– Site of Epo production shifts from liver to kidney
– Liver less sensitive to hypoxia, thus protection from polycythemia in fetus

Prevention
• Delayed umbilical cord clamping is indicated to prevent anemia/iron deficiency
• Possible Exceptions: abruption, cord avulsion, monochorionic twins, or extremely
poorly controlled diabetes

Management
• Minimize phlebotomy losses (obtain only relevant lab tests that can
change clinical care, use ABL point of care if possible).

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IV Iron Sucrose (do not use IV Iron Dextran) to prevent Anemia of Prematurity
• Use with premature/SGA patients with prolonged NPO status (usu. surgical)
• Start at 14 days of life (3 mg/kg IV iron sucrose over 4 hrs once weekly)
• Monitor vital signs during transfusion, tachycardia, tachypnea, BP may fall
• If not tolerating, stop infusion & consider premedicating for next dose
• Monitor CBC, plus Ferritin or reticulocyte Hb after 2 wks
• Switch to oral iron 6 mg/kd/d when feeds are tolerated
• Target Ferritin 70-100 ng/mL (µg/L) or target reticulocyte Hb 29-35 pg
• If Ferritin <100: dose IV iron weekly. If 101-199: IV iron every other week
• If Ferritin 200-249: dose IV iron every 4 weeks. If >250: stop IV iron sucrose

ESA (rEpo and Darbepoietin) to Prevent Transfusions

• RBC-stimulating doses are neuroprotective in retrospective studies
• rEpo: 250-300 U/kg SQ or IV, 3 times weekly until 34-35 wks gestation or later
if Hct <28 and on respiratory support
• Consider with premature/small surgical infants with prolonged NPO
• Begin either rEpo or Darbepoietin at approx. 2 weeks of life
• Consider dosing in some ELBW micropremie infants, esp. <850 g BW
• Begin either rEpo or Darbepoietin within 24-48 hours of life
• Darbepoietin: 10 mcg/kg SQ or IV once weekly until 34-35 wks gestation
• If Hb does not rise by 1 g/dL after 4 weeks, increase dose by 25%
• If Hb rises >1 g/dL after 4 wks, consider decreasing dose by 25%
• Stop ESA if Hb >15 g/dL or Hct >45%
• Do not stop ESA for transfusion or with infection work up
• Must give iron with ESA
• Start oral Iron 6 mg/kg/d if tolerating 60 mL/kg/day enteral feeding
• If NPO/unable to take oral iron in 1st wk, IV iron sucrose 3 mg/kg/wk
• Consider stopping oral or IV iron X 1-2 wks post transfusion.
• Target Ferritin 70-100 ng/mL (µg/L) or target reticulocyte Hb 29-35 pg
• If Ferritin <100: dose weekly. If 101-199: every other week
• If Ferritin 200-249: dose every 4 weeks. If >250: stop IV iron sucrose–
Term infants (unless SGA, late preterm, or < 2500 g)
• No need for routine iron dosing until later in life
– Iron fortified formulas (@150 ml/kg/day) provide ~2 mg/kg/day
– Standard concentration of iron for inpatients = 3 mg/0.2 mL

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 • Give 3 mg dose 1-3 times per day based on patient need
– Multivitamin drops with iron provide 10 mg iron/1 mL
– Continue iron until 12 months of age.
– Hold oral iron for 2 wks after transfusion, unless on ESA (hold for 1 wk)
• Blood transfusion (PRBC) may be needed (see Transfusion Guidelines).
• Check Ferritin at 28 days before immunizations: Should be ≥70ng/mL
See IV Iron/Erythrocyte Stimulating Agents Clinical Guidelines

C. Thrombocytopenia
Etiology
• Increased Platelet Destruction
– Autoimmune – maternal ITP, maternal autoimmune disease (SLE)
– Neonatal Alloimmune – due to human platelet antigen 1, 3, or 5
– Placental insufficiency – ex. Preeclampsia or chronic hypertension
– Sepsis/NEC/Perinatal asphyxia – DIC
– Drug-induced – heparin, antibiotics
• Decreased Platelet Production
– TORCH

Platelet transfusions

Clinical Characteristics Platelet Count

Stable term infant or premature >7 days <25,000

<28 wks, <7 days, risk for IVH <50,000

Prior significant <50,000

hemorrhage/surgery
Hemorrhage Transfuse

• Transfuse at any level in presence of active bleeding

• Platelets short shelf life, may need to put on hold for some, delays up to 4-6 hrs.
• Transfuse 10-20 ml/kg of CMV negative, irradiated platelets over 2-3 hrs

Other Blood Products

• FFP transfusion:
97
 – Indications – bleeding, DIC, vitamin K deficiency, Factor IX deficiency
– Components – All clotting factors, fibronectin, gamma-
globulins, albumin, plasma proteins

• Cryoprecipitate
– Indications – Factor VIII deficiency, von Willebrand disease
– Components – Factor VIII, vWF, fibrinogen, factor XIII, fibronectin

Statistics about Safety of Blood Supply; ARC 2004

HIV 1:2,000,000 HBV 1:250,000–500,000
HCV 1:2,000,000 HTLV 1:640,000
WNV 1.5/1000, 3/100,000 HAV 1:1,000,000
Malaria 1:1,000,000 Bacterial RBC– 1:1:500,000; Platelet–1:1000-2000

Reference:
1. Curley A, et al. PlaNeT2 MATISSE Collaborators. Randomized Trial of
Platelet-Transfusion Thresholds in Neonates. N Engl J Med. 2019 Jan
17;380(3):242-251
2. Widness JA. Pathophysiology of Anemia During the Neonatal Period, Including
Anemia of Prematurity. Neoreviews. 2008;9;e520
3. Committee on Obstetric Practice, Timing of Umbilical Cord Clamping After
Birth. Obstetrics & Gynecology. 2012;120;1522-1526.
4. Bell EF. Arch Dis Child. 2021doi:10.1136/archdischild-2020-320495.

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 Chapter: 16 Infectious Disease
Nina Menda, MD

Neonatal Sepsis
Risk Factors for early sepsis
• Prematurity and low birth weight
• Five minute Apgar<6, need for resuscitation at birth
• Premature ROM
• Prolonged ROM >18 hours prior to delivery
• Maternal peri-partum fever
– post-epidural fevers do not increase risk for infection
• Chorioamnionitis
• Maternal GBS (especially GBS bacteriuria)
• Previous sibling with GBS sepsis
• Multiple gestation

Early vs Late Onset

• Early onset sepsis
– Occurs in the first 7 days of life
– Most common organisms GBS, E. coli, Listeria
– Neonatal Sepsis Risk Score for infants ≥ 34 weeks gestational age
• https://neonatalsepsiscalculator.kaiserpermanente.org/
• Information needed: CDC incidence of Early-Onset Sepsis, Gestational age,
Highest maternal antepartum temperature, ROM (hours), GBS status,
Intrapartum antibiotic use
• Risk stratified analysis based on physical exam of neonate
– Antibiotic time out at 24-36 hours to discuss stopping antibiotics if
all cultures negative
• Late onset sepsis occurs at 7-89 days of life
– Increased risk with foreign bodies (central lines, ETT, etc.)
– Most common organism is coagulase negative staph, but other
common organisms are S. aureus, GBS, Klebsiella and Enterococcus

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Evaluation for infection
• Obtain blood culture and a CBC with manual differential
• In healthy infants neutrophil counts initially rise over first 6-12 hours,
peak at 12-18 hours and then decrease over the next 24-48 hours.
I:T ratio = Immature (bands+metas+myelos+promyelocytes)
Immature neutrophils + mature neutrophils
– Concerning if > 0.2-0.3
• For late onset – obtain a UA, urine culture and consider lumbar puncture
– If blood culture is positive a lumbar puncture must be done
• Chest x-ray if respiratory symptoms present
– CBC/D at 12 and 24 hours of age, or after onset of symptoms
• If concerns for HSV follow guidelines
• CMV is by salivary PCR, order for all SGA or head circumference < 3%

Treatment
• Ampicillin and gentamicin – most commonly used as empiric treatment
for early onset sepsis and rule out sepsis coverage
o Ampicillin: covers GBS, Listeria and some E. coli
 Always start with meningitic dosing (100 mg/kg/dose)
o Gentamicin: covers gram-negative organisms
 May have synergistic effect with ampicillin
o Cefotaxime (third generation): occasionally used in place of
gentamicin
 Covers some gram-positive and most gram-negative
organisms
 Better CSF penetrance than gentamicin
o Vancomycin
 Commonly used for late onset sepsis, especially if there is a
central line.
 Necessary for multi-drug resistant coagulase negative
staphylococcus
o Acyclovir: When HSV is suspected

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Treatment: Empiric Therapy
• Early onset: < 7 days at time of presentation
o Ampicillin AND Gentamicin if low suspicion for meningitis
o Ampicillin AND Cefotaxime if high suspicion for meningitis, CSF
Gram stain positive
• Late onset: > 7 days at time of presentation
o Ampicillin and Gentamicin
o If central line present, start Vancomycin and Gentamicin
• Duration of therapy at least 7 days after first negative blood culture

Meningitis Diagnosis
• Lab evaluation
• Blood culture, CBC with differential
• CSF culture/Gram stain
• CSF Biofire PCR
– Increased CSF WBC
(> 20-30 WBC/microL with predominance of neutrophils)
– Elevated CSF protein concentration
(> 150 mg/dl in preterm and > 100 mg/dl in term)
– Decreased CSF glucose concentration
(< 20 mg/dl in preterm and < 30 mg/dl in term)

Meningitis Treatment
– GBS: Ampicillin or Penicillin, add Gentamicin until documented sterility; Complete
14 day course after negative repeat CSF culture
– Ecoli: Cefotaxime; Complete 21 day course after repeat negative CSF culture
– CONS: Vancomycin, Consider rifampin for synergy; Complete 14 day course after
repeat negative CSF culture
• Narrow antibiotic spectrum once susceptibilities known

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Maternal Diagnosis of Chorioamnionitis (CAM) or Intrapartum Infection (IAI)

102
Starting Dose Recommendations
Ampicillin 100 mg/kg/dose
Vancomycin 10-15 mg/kg/dose
Cefotaxime 50 mg/kg/dose
PMA Postnatal age Dosing interval Postnatal age Dosing Interval
(weeks) (days) (hr) (days) (hr)
< 30 0-28 12 0-14 18
> 28 8 > 14 12
30-36 0-14 12 0-14 12
> 14 8 > 14 8
37-44 0-7 12 0-7 12
>7 8 >7 8
> 44 ALL 6 ALL 6

Gentamicin
PMA (weeks) Postnatal age (days) Dose (mg/kg) Dosing Interval (hr)
< 30 0-7 5 48
8-28 4 36
> 28 4 24
30-34 0-7 4.5 36
>7 4 24
> 34 ALL 4 24

Fungal Sepsis Prophylaxis

• Prophylactic fluconazole for 22-23 wk GA infants
• Infants ≤ 1000 grams birth weight with central lines are ONLY given prophylactic
fluconazole (3 mg/kg every 72 hours) if they are on systemic antibiotics for > 3
days
Streptococcus agalactiae (GBS)
• Gram positive diplococciinchains
• Acquired during passage through the vaginal canal, by ascending infection following
rupture of membranes, person-to-person, and via breast milk.

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 • Causes early and late onset sepsis in infants
• Intrapartum antibiotic prophylaxis (IAP) of GBS positive mothers has dramatically
reduced the incidence of early onset GBS sepsis
– IAP does not prevent late-onset GBS sepsis
• Once GBS is confirmed antibiotic therapy should be narrowed to Penicillin G

Herpes Simplex Virus (HSV)

• HSV infection of the neonate is fairly uncommon but with potentially
devastating consequences.
• More than 75% of infants who contract HSV are born to mothers with no
prior history of clinical signs of genital herpes.
• Transmission occurs in utero, intrapartum (85%) or postpartum.
• Risk factors: Maternal primary infection, prolonged rupture of membranes, mode
of delivery (vaginal > C-section), disrupted integrity of mucocutaneous barriers (e.g.
scalp electrode) and prematurity
• Three forms of disease in neonates: Disseminated, CNS disease (+/- skin lesions),
Skin, Eye, Mouth (SEM) disease
• Disseminated disease presents earliest(DOL 4-10), SEM(DOL 6-9) and
CNS disease presents latest (DOL 10-18)
• Consult AAP RedBook for most recent recommendations

Hepatitis B
• Infants born to Hepatitis B positive mothers should receive hepatitis B vaccine
and HBIG within 12 hours after birth
• If maternal hepatitis B status is unknown infants should receive hepatitis B vaccine
within 12 hours after birth
– Infants < 2000 grams: HBIG should be given within 12 hours after birth if
maternal status cannot be determined
– For infants ≥ 2000 grams: HBIG can be given up to 7 days after birth
• For infants< 2000gramswith Hepatitis B positive or unknown mothers the vaccine
dose given at birth does not count towards the 3 dose vaccination schedule.
• Infants< 2000gm at birth should receive hepatitis B vaccine prior to discharge
from the hospital or at one month of age, whichever is earlier
• Infants≥ 2000gm at birth should receive hepatitis B in the first 24 hours of life

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A. Neonatal Urinary Tract Infection: Incidence dependent on GA

105
References:
1. Newman TB, et al. Interpreting Complete Blood Counts Soon After Birth in
Newborns at Risk for Sepsis. Pediatrics 2010; 126: 903-909.
2. Sass L. Group B Streptococcal Infections. Pediatrics in Review 2012;33;219. DOI:
10.1542/pir.33-5-219
3. Plosa EJ, Esbenshade, JC Fuller MP and -Hendrik Weitkamp J. Cytomegalovirus
Infection. Pediatrics in Review 2012;33;156. DOI: 10.1542/pir.33-4-156
4. Chu A,.Hageman JR,Schreiber M and Alexander K. Antimicrobial Therapy and
Late Onset Sepsis. Neoreviews 2012;13;e94. DOI: 10.1542/neo.13-2-e94
5. Puopolo, Karen M., et al. "Management of neonates born at≥ 35 0/7
weeks’ gestation with suspected or proven early-onset bacterial
sepsis." Pediatrics 142.6 (2018).
6. Management of Neonates With Suspected or Proven Early-Onset Bacterial
Sepsis Richard A. Polin and the COMMITTEE ON FETUS AND NEWBORN
Pediatrics 2012;129;1006; originally published online April 30, 2012; DOI:
10.1542/ peds. 2012-0541
7. Guidance on Management of Asymptomatic Neonates Born to Women With
Active Genital Herpes Lesions David W. Kimberlin, Jill Baley, COMMITTEE
ON INFECTIOUS DISEASES and COMMITTEE ON FETUS AND NEWBORN
Pediatrics 2013;131;e635. Red Book 2017 Report of the Committee on
Infectious Diseases.
8. Risk-Based Approach to the Management of Neonatal Early-Onset Sepsis.
Kuzniewicz MW, Puopolo KM, Fischer A, Walsh EM, Li S, Newman TB, Kipnis P,
Escobar GJ. A Quantitative, JAMA Pediatrics 2017 Apr 1;171(4):365-371.
9. Bacterial meningitis in infants. Ku LC, Boggess KA, Cohen-Wolkowiez M. Clin
Perinatal. 2015 Mar; 42(1):29-45.

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 Chapter 17: Central Nervous System
Megan Berube, MD and Jamie Limjoco, MD

A. Neonatal Seizures
• Neonatal seizures more often present with subtle symptoms
– Apnea, lip smacking, tongue thrusting, tonic eye deviation, leg pedaling,
cyanotic spells, autonomic dysfunction
– Focal rhythmic flexion of extremity or distal joint (wrist/hand, ankle/foot)
– Generalized tonic-clonic seizures are rare
– Electroclinical dissociation (subclinical seizures) is common
Differential Diagnosis
• Hypoxic-ischemic encephalopathy
– Most common etiology of neonatal seizures
• Cerebral vascular
– Intracranial hemorrhage
• Intracerebral/parenchymal, intraventricular, subarachnoid, subdural
– Arterio-venous malformation (AVM)
– Stroke: arterial or venous
• Congenital CNS malformations
– Agenesis of corpus callosum
– Polymicrogyria
– Lissencephaly
– Schizencephaly
– Hemimegancephaly
– Focal cortical dysplasia
– Holoprosencephaly
– Subcortical band heterotopia (gray matter heterotopia)
• Metabolic
– Hypoglycemia
– Hypocalcemia/ Hypomagnesemia
– Hypo/Hypernatremia
– Pyridoxine dependency
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 – Inborn errors of metabolism – amino acidopathies, organic acidopathies
• Infection
– Meningitis
– TORCH
• Drug Toxicity
– Withdrawal-barbiturates, benzodiazepines, opioids (heroin, methadone)
– Maternal anesthetics-accidentally injected into fetal scalp during delivery
• Neurocutaneous Disorders
– Tuberous Sclerosis (gene: TSC1, TSC2)
– Incontinenta Pigmenti (gene: IBKKG)
– Sturge-Weber (gene: GNAQ)
• Neonatal Onset Epilepsy Syndromes
– Benign familial neonatal epilepsy (days 2-3, remission in 1 to 12 mo)
• Autosomal dominant: KCNQ2, KCNQ3, SCN2A
– Benign nonfamilial neonatal epilepsy (“fifth day fits”)
– Early myoclonic encephalopathy
– Early infantile epileptic encephalopathy (Ohtahara’s syndrome)
– Malignant migrating partial seizures of infancy (rare)
Work up for Seizures
• History
– Maternal history – drug use, IDM, infection
– Delivery history – birth trauma, hypoxic events
• PE
– Signs of trauma – bruising, petechiae
– Dysmorphic features/congenital anomalies
– Neurologic status
• Labs
– Blood sugar
– Electrolytes, calcium, magnesium
– CBC with differential, blood culture
– Blood gas, ammonia-if concerns for inborn error of metabolism
– Consider UA/Urine Culture and CSF studies
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• Continuous video EEG, aEEG*
• Imaging
– Ultrasound – best for IVH in preemie, may miss intracranial bleed in term
infants (subdural or subarachnoid hemorrhage)
– CT scan – good for concerns of intracranial bleeding in term infants
– MRI – best for structural anomalies and hypoxic-ischemic injury
*Monitoring with Amplitude-Integrated EEG (aEEG)
- aEEG is a bedside tool used to monitor brain function and identify
seizure activity. Most common electrode placement includes biparietal
(P3 and P4) and central leads (C3 and C4). Hydrogel, cups or needles can
be applied to the scalp for monitoring.
- Classification
- Continuous (lower margin >5µV and upper margin 10-25µV)
- Discontinuous (lower margin<5µV and upper margin >10µV)
- Burst Suppression (lower margin <5µV and upper margin >25µV)
- Low Voltage (lower margin<5µV and upper margin <5µV, variability)
- Flat (lower margin<5µV and upper margin <5µV, isoelectric)
- Seizures present as a sudden onset of rhythmic activity lasting >10sec
- Lower and upper margins appear like continuous “humps”
- Artifacts such as patting, oscillator use, hiccups, EKG can mimic
seizure appearance on aEEG

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110
Seizure Treatment
• Correct electrolyte disturbances
• Anticonvulsants

Levetiracetam (Keppra)
1st Loading dose: 50 mg/kg
2nd Loading dose if ongoing seizures: 50 mg/kg
Maintenance dose: 25 mg/kg BID
Desired blood levels: not established
Adverse effects: none known in neonates (reports of irritability,
behavioral dysregulation in older children receiving high doses)

Phenobarbital
1st Loading dose: 20 mg/kg
2nd Loading dose if ongoing seizures: 10 mg/kg
Maintenance dose: 2.5 mg/kg BID
Desired blood levels: 20-40 mcg/ml
Adverse effects: Can cause respiratory depression, hypotension

Vimpat (Lacosamide)
1st Loading dose: 10 mg/kg
2nd Loading dose if ongoing seizures: 5-10 mg/kg
Maintenance dose: 5 mg/kg BID, then increase to 10mg/kg BID
Desired blood levels: not established
Adverse effects: asymptomatic bradycardia and/or prolonged PR interval, can
consider 12 lead EKG

Fosphenytoin
1st Loading dose: 20 PE/kg
(PE: phenytoin equivalents)
2nd Loading dose if ongoing seizures: 10 PE/kg
Maintenance dose: 4-8 PE/kg/day
Desired blood levels: 6-15 mcg/ml
Adverse effects: arrhythmias, bradycardia, hypotension

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B. Intraventricular Hemorrhage
• Periventricular bleeding from the subependymal germinal matrix in preemie
– Bleeds in term infants are from choroid plexus
• Germinal matrix involutes around 36 weeks gestation
• 90% of IVH occurs in the first 3 days of life
– 50% in first 24 hours
– May progress in the first 5-7 days
Papile’s classification:
– Grade 1: Isolated germinal matrix hemorrhage
– Grade 2: Intraventricular hemorrhage without dilatation of the ventricle
– Grade 3: Intraventricular hemorrhage with ventricular dilatation
– PVHI: periventricular hemorrhagic infarction represented by intra-
parenchymal echodensity (formerly known as Grade IV)
Risk Factors:
– Prematurity < 30 wks gestation
– Perinatal asphyxia, Birth Trauma
– Rapid fluctuations in blood pressure
– Shock
– PDA
• Antenatal steroids are protective
Diagnosis:
– Head Ultrasound (HUS)
• Guidelines from American Academy of Neurology
– Screen all infants less than 30 weeks gestation
– First ultrasound at 7-14 days of age
– Repeat ultrasound at 36-40 weeks PMA or discharge
– Consider term equivalent age MRI for infants with history of abnormal HUS
C. Periventricular Leukomalacia
• Cystic lesions in corticospinal white matter adjacent to the lateral ventricles
– Due to repeated hypoxic-ischemic events from cerebral hypoperfusion in the
neonatal period
– Hypoxic injury causes necrotic cell death
• Seen most commonly in premature infants
• Leads to long-term neurodevelopmental disability
– Spastic diplegic cerebral palsy

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 D. Apnea
Apnea: Absence of breathing for >20 seconds or short pause (>10 sec)
associated with oxygen desaturation or bradycardia
Periodic Breathing: Cyclic pauses inbreathing for ≤ 10 secs followed by
a series of rapid, shallow breaths
Bradycardia:
• For infants < 30 wk: HR <100/min for >10 sec
• For infants ≥ 30 wk: HR <80/min for >10 sec
Practical tips:
• Apnea of prematurity: Typical onset is 2-3 days in preemies <34 weeks’ gestation
• Apnea in a full-term infant is never physiologic
• Apnea on first day of life is abnormal, search for causes other than prematurity

Causes of Apnea and Bradycardia by Gestational Age

All ages Premature Infant Full term infant
Sepsis Apnea of prematurity Cerebral infarction
Meningitis PDA Polycythemia
Hypoxia HMD Drug Withdrawal
Aspiration NEC
GER PV-IVH
Pneumonia Anemia of prematurity
Posthemorrhagic
Cardiac disorder
Hydrocephalus
Post-extubation
Polycythemia
atelectasis
Seizures
Cold Stress
Metabolic imbalance
Airway malformations
CNS malformations
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Approach to Apnea & Suspicion of Reflux
• Most spells are not temporally linked to reflux
• Usually apnea precedes the reflux when temporally linked
• Only 3% of spells preceded by reflux
Interventions for Apnea:
1. Positioning: Optimize left side down and prone.
2. Continue bolus feeds (every 3 hours). No strong evidence that continuous drip feeds
will decrease apnea/bradycardia/desaturation spells.
3. Consider thickening feeds using commercial reflux formula (see Reflux Guideline)
4. No evidence to support changing/decreasing maintenance caffeine dose (no evidence
to support caffeine worsening reflux)
5. Anti-reflux medications should be used with caution, and if no difference is observed
in frequency or severity of spells after 5-7 days of therapy, consider discontinuation.

References:
1. Olson DM. Neonatal Seizures. Neoreviews 2012;13;e213DOI:10.1542/neo. 13-4-e213.
2. Donna M. Ferriero MD. Neonatal Brain Injury. N Engl J Med 2004;351:1985-95.
3. Volpe JJ, Inder TE, Darras BT, de Vries LS, du Plessis AJ, Neil JJ, Perlman JM. (2018)
Volpe’s Neurology of the Newborn, 6th edition. Elsevier.

Hypoxic Ischemic Encephalopathy

• Incidence = 3-5/1000 live births
• Mortality up to 60%
• Generally occurs after event of perinatal asphyxia
– Event is not always easily recognized
Perinatal Asphyxia
• ACOG and AAP “Neonatal Encephalopathy and Neurologic Outcome, 2nd
Edition” 2019
• Asphyxia
• Marked impairment of gas exchange leading, if prolonged, to
progressive hypoxemia, hypercapnia, and significant metabolic
acidosis.
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 • Describes a process of varying severity and duration rather than
an end point.
• Should not be applied to birth events unless specific evidence of
markedly impaired intrapartum or immediate postnatal gas
exchange can be linked to neurologic illness in the neonate.
• Perinatal Asphyxia
• Profound metabolic or mixed acidemia (pH <7.0 on umbilical
arterial blood gas)
• Persistence of an Apgar score of 0-3 for >5 minutes
• Neurologic manifestation in the immediate neonatal period
(seizures, encephalopathy)
• Evidence of multi-organ dysfunction in the immediate neonatal
period

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Neonatal Encephalopathy Exam (Modified Sarnat Score)

Level of Encephalopathy

Normal/None Mild Moderate Severe

1 – Hyperalert or
1. Level of 0 – Normal/ irritable
2 – Lethargic 3 – Stupor or coma
Consciousness Alert (responsive to
minimal stimuli)
2. Spontaneous 2 – Decreased
0 – Normal ----- 3 – No activity
Activity activity
2 – Flexion of
0– 1 – Mild flexion of
distal joints or
3. Posture Predominantly distal joints 3 – Decerebrate
complete
flexed (fingers, wrist)
extension
4. Tone 2a – Hypotonia 3a – Flaccid
0 – Strong 1 – Slightly
(focal or general)
flexor tone in increased tone
2b – Hypertonia 3b – Rigid
all extremities in extremities
(focal or general)
5. Primitive 0 – Strong, 1 – Weak, 2 – Weak and 3 – Absent
Reflexes1: coordinated, coordinated uncoordinated,
Suck easy to elicit and/or bite

0 – Complete 1 – Exaggerated 2 – Incomplete 3 – Absent

Moro

6. Autonomic 0 – Normal 1 – Mydriasis 2 – Myosis 3 Deviated/unequal,

System1: (dilated), (constricted), dilated, or fixed/
Pupils reactive reactive nonreactive to light

0 – Normal: 1 – Tachycardia: 2 – Bradycardia: 3 – Variable

Heart Rate 100 – 160 bpm >160 bpm <100 bpm

0 – Normal: 1 – Tachypnea, 2 – Periodic 3a – Apnea, requires

Respiration regular Hyperventilation breathing on-going PPV or
respirations intubation, and has
spontaneous breaths
3b – Apnea, requires
on-going PPV or
intubation, and
does not have
spontaneous breaths

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 Documenting the Neonatal Encephalopathy Exam (.HIEEXAM)
Contribution: Megan Berube, MD

1. Level of consciousness: 0- Normal/Alert; 1- Hyperalert or irritable, responsive to minimal

stimuli; 2- Lethargic; 3- Stupororcoma
2. Spontaneous activity: 0- Normal;2- Decreased activity; 3- No activity
3. Posture: 0- Predominantly flexed; 1- Mild flexion of distal joints (fingers, wrist);
2- Flexion of distal joints or complete extension; 3-Decerebrate
4. Tone: 0- Strong flexor tone in all extremities; 1 – Slightly increased tone in extremities
2a- Hypotonia (focal or general); 2b- Hypertonia (focal or general); 3a- Flaccid; 3b- Rigid
5. Primitive reflexes:*
Suck: 0- Strong, coordinated, easy to elicit; 1- Weak, coordinated; 2- Weak and
uncoordinated, and/or bite; 3- Absent
Moro: 0- Complete; 1- Exaggerated; 2- Incomplete; 3- Absent
6. Autonomic system:*
Pupils: 0- Normal; 1 – Mydriasis (dilated), reactive; 2 – Myosis (constricted), reactive; 3-
Deviated/unequal, dilated, or fixed/nonreactive to light
Heart rate: 0- Normal (100-160 bpm); 1- Tachycardia (>160 bpm);
2- Bradycardia (<100 bpm); 3- Variable
Respiration: 0- Normal; 1 – Tachypnea, hyperventilation; 2- Periodic breathing;
3a – Apnea, requires on-going PPV or intubation, and has spontaneous
breaths; 3b – Apnea, requires on-going PPV or intubation, and does not have
spontaneous breaths
*For Primitive Reflexes (Suck, Moro) and Autonomic System (Pupils, Heart Rate, Respirations), the
item with the highest score determines the level of encephalopathy.
Total categories with score of 0 = ____
Total categories with score of 1 = ____
Total categories with score of 2 = ____
Total categories with score of 3 = ____
• Neonate has a normal encephalopathy exam if he/she has scores of 0 in all six
categories.
• Neonate has mild encephalopathy if he/she has < three categories with a score of 2 or
3, but has a score of 1, 2, or 3 in at least one category.
• Neonate has moderate encephalopathy if he/she has a score of 2 in three or more
categories.
• Neonate has severe encephalopathy if he/she has a score of 3 in three or more
categories

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Neonatal Encephalopathy Exam Definitions

1. Level of consciousness:
a. Hyperalert - Full wakefulness with eyes open/staring but decreased frequency of
blinking/tracking. Spontaneous motor activity normal or decreased with lowered
threshold to all stimulus types.
b. Irritability – Lowered threshold with excessive response to all stimulus types. Can
be seen with varied states including hyperalert, lethargy, and obtundation.
c. Lethargy - Slightly delayed but complete response to stimuli with slightly increased
threshold for eliciting responses and decreased spontaneous movement
d. Obtundation - Delayed and incomplete responses with markedly increased
threshold to all sensory stimuli and little or no motor activity
e. Stupor - No spontaneous eye opening and tactile stimulation elicits poorly sustained
eye opening. Responds only to strong, noxious stimuli. Absent gag, corneal reflex.
f. Coma- No eye opening with vigorous tactile stimulation.
2. Spontaneous activity:
a. Decreased spontaneous activity- Decreased frequency or amplitude
of spontaneous facial and extremity movements.
b. Absent spontaneous activity - Movements absent.
3. Posture:
a. Distal flexion - Fingers, toes in strong flexion; incomplete extension of fingers
when stroked on dorsal surfaces. Thumbs flexed, adducted, opposed across palms
(i.e."corticalthumbs").
b. Decerebrate posturing - Head, neck, and back are arched in extension (opisthotonos),
elbows are extended, wrists are pronated, and hips are adducted.
4. Tone (remove positioning barriers for accurate examination of tone):
a. Hypotonia - Focal or generalized decreased resistance to passive movement.
Associated with greater extension of the extremities than normal.
b. Hypertonia - Focal or generalized increased resistance to passive movement.
Associated with greater flexion of the extremities than normal.
c. Flaccid - "Flat on the mat" appearance. May be associated with frog-leg posturing
with arms and hips/legs lying in abduction.
d. Rigidity - "Lead pipe" feel of extremities, severe hypertonia with extreme resistance to
passive movement. Does not depend on imposed speed or threshold of movement.
Unilateral contraction of antagonist or agonist muscle groups can occur with rigidity,
but the limb does not tend to return to a fixed posture or extreme joint angle. May
be associated with exaggerated deep tendon and tactile reflexes.
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5. Primitive Reflexes:
a. Weak suck – Some sucking noted, but it is not as vigorous or sustained as it
should be. A pacifier or gloved finger can be easily pulled from the mouth.
b. Absent suck – No sucking or root reflex elicited.
c. Bite-Insertion of pacifier or gloved finger into mouth elicits neonate to
“clampdown” or bite object. No sucking motion elicited.
d. Moro- The Moro reflex is elicited by holding the baby's head and shoulders off
the mat with arms held in flexion on chest. While supporting the head and
neck, the examiner suddenly lets the head and shoulder drop while releasing the
arms. The arms should fully abduct and extend, then return towards midline
with the hand open and the thumb and index finger forming a “C” shape. An
incomplete Morois marked by absence of any component or any asymmetry in
movements. Incomplete Moro reflex often extends irregularly but typically does
not return to midline.
e. Absent Moro- Absence of any reflexive activity (see above for method of
eliciting Moro reflex).
6. Autonomic System:
a. Dilated pupils (mydriasis) - Normal pupil size for term newborns is 3.9 mm
+/- 0.8 mm. Dilated pupils are larger than this even in bright light.
b. Constricted pupils (miosis) - Normal pupil size for term newborns is 3.9 mm
+/- 0.8 mm. Constricted or pinpoint pupils are smaller than this even in dim light.
c. Unequal; Fixed; Dilated; Poor light reflex pupils - Pupils that are not normally
symmetrically aligned or symmetrically dilated, are fixed in position, or that do not
accommodate (constrict) in the presence of light.
d. Tachycardia- Resting heart rate > 160 beats per minute.
e. Bradycardia- Resting heart rate of< 100beats per minute, typically 80-90
beats per minute. Only occasional increases to 120+ beats per minute are
noted.
f. Variable heart rate - Resting heart rate varies considerably without a consistent
baseline.
g. Periodic breathing - Three or more respiratory pauses of three seconds or
longer separated by normal breathing for less than 20 seconds. Often
associated with shallow breathing pattern.
h. Apnea- Absence of airflow and respiratory effort lasting 20 seconds or longer.
Apnea may also be present if a respiratory pause is shorter than 20 seconds
but is associated with heart rate change or oxygen desaturation.

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Therapeutic Hypothermia Protocol
 1. Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head cooling with mild
systemic hypothermia after neonatal encephalopathy: multicentre randomised trial.
The Lancet 2 0 0 5 ;365:663-70.
2. Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia
for neonates with hypoxic-ischemic encephalopathy. The New England
journal of medicine 2005;353:1574-84.
3. Lommen CM, Pasman JW, van Kranen VH, et al. An algorithm for the automatic
detection of seizures in neonatal amplitude-integrated EEG. Acta paediatrica
(Oslo, Norway : 1992) 2007;96:674-80.
4. Silverstein FS. Do seizures contribute to neonatal hypoxic-ischemic brain injury?
The Journal of pediatrics 2009;155:305-6.
5. Malin GL, Morris RK, Khan KS. Strength of association between umbilical cord
pH and perinatal and long term outcomes: systematic review and meta-analysis.
BMJ 2010;340:c1471-c.
6. Meyn DF, Jr., Ness J, Ambalavanan N, Carlo WA. Prophylactic phenobarbital and
whole-body cooling for neonatal hypoxic-ischemic encephalopathy. The Journal of
pediatrics 2010;157:334-6.
7. Sarkar S, Barks JD. Systemic complications and hypothermia. Seminars in fetal &
neonatal medicine2010;15:270-5.
8. Thoresen M, Hellstrom-Westas L, Liu X, de Vries LS. Effect of hypothermia on
amplitude-integrated electroencephalogram in infants with asphyxia. Pediatrics
2010;126:e131-9.
9. van Laerhoven H, de Haan TR, Offringa M, Post B, van der Lee JH. Prognostic
tests in term neonates with hypoxic-ischemic encephalopathy: a systematic
review. Pediatrics 2013;131:88-98.
10. Shankaran S, Barnes PD, Hintz SR, et al. Brain injury following trial of
hypothermia for neonatal hypoxic-ischaemic encephalopathy. Archives of
Disease in Childhood 2012.
11. Bonifacio SL, deVries LS, Groenendaal F. Impact of hypothermia on
predictors of poor outcome: How do we decide to redirect care? Seminars in
fetal & neonatal medicine 2015.
12. aEEG graphic provided by NCC – National Certification Corporation
 Initial Management of Newborns with Myelomeningocele
Bermans Iskandar, MD Lisa McLennan, RN

Pre-Operative Care
1. The attending neurosurgeon should be notified as soon as the ob/gyn has selected
a delivery date/time. UW/AFCH Pediatric Neurosurgery: 608-263-9585.
2. On day of admission and once baby is delivered, the neurosurgery resident (AFCH
or Meriter) or attending who performed prenatal visit should be notified.
Immediately after birth:
3. Initial care should be taken in keeping the myelomeningocele (MMC) defect clean
and moist. Immediately after birth cover defect with sterile Telfa and then layer
with wet 4x4 gauzes. Telfa should be left in place until surgery but wet sterile
gauzes can be changed as needed to keep area moist. This non adherent dressing
can be kept in place by covering with a steri-drape or loosely wrapping Kerlix
around abdomen.
4. Care should be taken to prevent contamination or exposure of MMC area, protect
from soiling with a plastic flap (steri drape).
5. Perform initial measurement of head circumference.
6. Prophylactic antibiotic coverage should be started with broad spectrum coverage
(Ampicillin + Gentamicin recommended) which should be continued for 48 hr.
post op.
7. Infant must be nursed and kept prone to prevent injury to the exposed neural
tissue.
8. If infant has not voided within first hours of birth, bladder ultrasound/straight
catheterization must be performed. Notify Urology
9. Arrange for transfer to AFCH NICU in consultation with Neurosurgery and
Neonatologist.

For more information, go to: https://workspaces.uconnect.wisc.edu/display/nicuunitres/

Policies+and+Clinical+Practice+Guideline/MyelomeningoceleNeonatalProtocol
 Chapter 18: Neonatal Kidney
Matthew Harer, MD & Dan Gorski,MD
A. Neonatal Hypertension
• BP Measurement
a. Technique- Optimal cuff size is 2/3 the length of limb segment and 75% of limb
circumference
• Protocol for BP measurement in hypertensive infants
a. Measure 1.5h after a feed or intervention
b. Infant lying supine, taken on RIGHT upper arm
c. Place cuff and wait 15 min before measures
d. Optimal if infant is asleep
e. 3 successive readings at ~ 2 min intervals, average of these values
• Incidence
a. 0.3-3% of Neonatal patients
b. Risk Factors: history of UAC, BPD, history of AKI, IVH, PDA
• What is abnormal?
(>95th%tile) a. 26-32 weeks
PMA – 83/55 b. 32-36 weeks
PMA – 87/65 c. 36-44 weeks
PMA – 105/68
d. For full table: HTN in infancy, Peds Nephro, 2012:27
• Initial Work-up
a. Urine analysis(+/- culture)and Urine protein
b. CBC,BMP, Calcium
c. Renal ultrasound with Doppler
d. Upper/Lower BPs
e. Consider the following dependent on the situation
– Thyroid studies
– Echocardiography
– Aldosterone, renin, cortisol
– Abdominal ultrasound
– VCUG 125
B. Fetal hydronephrosis: Most common prenatal abnormality
Definition - Prenatal identification of dilation of the upper urinary tract

Causes Grading
Ureteropelvic or ureterovesical Mild < 10 mm dilation
junction obstruction
Posterior urethral valves Moderate > 10 mm dilation
Vesicoureteral reflux Severe > 15 mm dilation

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C. Renal Tubular Acidosis: The most encountered RTA in premature
neonates is transient proximal RTA which resolves as the infant ages
Test Type I Type II (Proximal) Type IV
Urine pH High > 6.5 High > 7.0 Low < 5.5
Potassium Low Low High
Nephrocalcinosis Yes
Defect Reduced H+ Impaired HCO3 Impaired cation
secretion reabsorption exchange
Association Fanconi Syndrome Pseudohypo-
aldosteronism
Treatment Bicarbonate Bicarbonate

E. Neonatal Acute Kidney Injury

• Prevalence - 30% of all patients in the NICU have AKI(50% of <29weekpreterms)
• Etiology – Primarily prerenal, congenital anomalies like PUV can cause post-renal
• Definition – neonatal KDIGO definition – most commonly used
Stage Serum Creatinine (sCr) UOP over 24 hours
1 sCr increase by 0.3 within 48 hours OR sCr > 0.5 but < 1 mL/kg/hr
increase by 1.5-1.9x baseline in 7 days
2 sCr increase by 2-2.9x baseline in 7 days > 0.3 but < 0.5 mL/kg/hr
3 sCr above 2.5 OR < 0.3 mL/kg/hr
sCr increase by >3x baseline in 7 days

• Work-up for AKI - Renal Ultrasound, BMP,UA, U Osm, U creatinine/sodium

• Treatment: Supportive care – Support BP, minimize fluid overload, avoid NTX meds
• Consult Peds Nephro for stage 2 or 3 injury, follow-up as outpatient

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 Test Prerenal AKI Intrinsic AKI
BUN/Cr ratio > 30 < 20
FENa (%) < 2.5 > 3.0
Urinary Na < 20 > 50
Urinary Osm > 350 < 300
Specific Gravity > 1.012 < 1.014
Response to Volume Challenge Improved UOP No change in UOP

F. Helpful formulas:
a. FeNa (%) = (PCr x UrNa / PNa x UrCr) x 100
i. Avoid single measurement
ii. Very variable in the 1st week in preterm infants
b. Renal failure index(RFI) = (UrNa/UrCr) x 100
c. Hyponatremia correction:
i. (desired Na – actual Na) x 0.6 (kg)

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 Chapter 19:
Neonatal Opioid Withdrawal Syndrome (NOWS)
Ann Ebert, Pharm D

Definition: Due to withdrawal from in-utero opioid exposure

- Occurs in infants with chronic exposure to opioids in utero-maternal. Opioid
use is frequently accompanied by use of other substances such as nicotine,
alcohol, benzodiazepine, and marijuana
- CNS irritability in infants can also occur following exposure to nicotine and SSRIs
Clinical Presentation
• Signs of abstinence occur in 60%-80% of infants exposed to opiates
• Symptoms can begin within 24 hours of birth for short acting opiates and
within 3-7 days for longer acting drugs, like methadone.
• Neurologic signs: hypertonia, excessive suck, tremors, hyperreflexia,
irritability, high-pitched cry, poor sleep, rarely seizures
• Autonomic dysfunction signs: yawning, sneezing, nasal stuffiness, low-grade
fever, sweating, skin mottling
• Gastrointestinal signs: diarrhea, vomiting, poor feeding, poor weight
gain
Eat -Sleep-Console Assessment
• Begin ESC assessment at 24 hours of life
• Assess after feeding/cares (~ every 3-4 hours)
• If infant experiences withdrawal symptoms, a caregiver huddle will be called to
discuss
• Pharmacologic therapy may be indicated if enhanced sensitive care guidelines are
not working to control symptoms
Treatment
• Non-pharmacologic (sensitive care) begin ASAP after birth
– Gentle handling, quiet environment, swaddling, pacifier, skin to skin
• Pharmacologic: The goal of pharmacologic therapy is to have the baby feeding well
without vomiting and diarrhea, gaining weight, decreased irritability, and sleeping
between feeds as appropriate for age without undue sedation.
• Refer to ESC algorithm for treatment details

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 • Note: Breastfeeding is contraindicated when women continue to use illicit drugs
such as cocaine, heroin, and marijuana

Reference:
1. Patrick SW, Barfield WD, Poindexter BB; Committee on Fetus and Newborn;
Committee on Substance Use and Prevention. Neonatal Opioid Withdrawal
Syndrome. Pediatrics. 2020;146(5):e2020029074.
2. Grisham, Lisa M. NNP-BC; Stephen, Meryl M. CCRN; Coykendall, Mary R. RNC-
NIC; Kane, Maureen F. NNP-BC; Maurer, Jocelyn A. RNC-NIC; Bader, Mohammed
Y. MD Eat, Sleep, Console Approach, Advances in Neonatal Care: April 2019 -
Volume 19 - Issue 2 - p 138-144
3. Kocherlakota, P.Neonatal Abstinence Syndrome. Pediatrics 2014: 134 (2); e547-e561.
4. Agthe AG, Kim GR, Mathia KB, et al Clonidine as adjunctivetherapy to opioids for
neonatalabstinence syndrome: a randomized, controlled trial. Pediatrics.
2009;123(5):e849-e856
5. McQuenn K, Murphy-Oikonen J. Neonatal abstinence syndrome. N Engl J Med.
2016;375:2468-2475

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131
 Chapter 20: Retinopathy of Prematurity
Nina Menda, MD

• ROP is a multi-factorial condition of abnormal vascularization of developing etinal

vessels occurring in premature infants due to incomplete vasculogenesis of the
retina at the time of birth.
• Leads to retinal detachment and blindness if severe and untreated.
Retinal Vasculature Embryology
• Retinal vasculature begins to develop at 14-15 weeks gestation
• Growth of the vessels begins centrally at the optic disc and grows out
peripherally to the ora serrata
• Retinal vessels develop initially by the process of vasculogenesis and later angiogenesis
• 70% of retinal vasculature present at 27 weeks
• Reaches nasal ora serrata by 36 weeks and the temporal ora serrata by 39-41 weeks
• Preterm birth leads to an avascular zone in the peripheral retina
Epidemiology
• Global health epidemic
• Leading cause of childhood blindness worldwide
• Overall prevalence is between 10-25% in premature infants, while incidence is about
50-70% in infants weighing ≤ 1500 grams at the time of birth.[Incidence of 18-40%
in premature infants in developed countries]
Pathogenesis of ROP
• Phase 1 (Vaso-obliteration)
– Characterized by cessation of normal new retinal vessel growth
– Occurs shortly after birth, following hyperoxia exposure
– Hyperoxia downregulates vascular endoethelial growth factor (VEGF) secretion
• Phase 2(Vaso-proliferation)
– Characterized by retinal neovascularization, fibrosis and detachment
– Fourto sixweeksafterbirth,theretinabecomeshypoxic dueto
inadequate vasculature to nourish it
– Hypoxia upregulates VEGF secretion, and excess VEGF leads to dysregulated
angiogenesis
– Vessels leave the retinal plane and grow into the vitreous leading to
cicatrization, tugging of fibrous scars on the retina and eventual detachment

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Risk Factors
• Prematurity (ROP incidence is inversely proportional to gestational age at birth)
• Prolonged hyperoxia or supplemental oxygen use
• Low birth weight
• Post-natal growth restriction
• Inadequate post-natal nutrition
• Sepsis
• RDS/BPD
• Shock
• Asphyxia
• Hypothermia
• Acidosis
• Vitamin E deficiency

Classification
• Zone=Location of abnormal vascularization
• Clock Hour =Extent
• Stage = Severity

Stage Features of Disease

1 Demarcation line between the vascular and avascular portions of the retina
2 Ridge-like structure between avascular and vascular retina
3 Fragile new vessel proliferation from the ridge into the vitreous gel
4A Partial retinal detachment not involving the macula
4B Partial retinal detachment involving the macula
5 Total retinal detachment

• Plus Disease is defined as a significant retinal vein dilation and arterial tortuosity
• Pre-threshold disease is defined as stage 3 ROP in Zone II or any ROP in Zone I

133
Example of what ophthalmologists document in chart

Right Eye = Stage 2 Zone I/II, 6 clock hours without plus disease
Left Eye = Stage 2/3 Zone II, 12 clock hours with plus disease in one quadrant

Treatment
Most treatments for ROP are targeted for Phase 2 ROP
A. Monitoring of pulse oximetry and judicious use of oxygen
• Monitoring oxygenation using pulse oximetry has become the mainstay of
ROP prevention.
• Controversies surround target SpO2 levels due to concerns of multi-centered
randomized clinical trial (SUPPORT trial) showing increased mortality in low
oxygen saturation target group (85-89%) compared to high (91-95%), despite
reduction in severe ROP.
• Oxygen saturation goals from birth to <37 weeks corrected age (90-94%),
while infants >37 weeks corrected age(>95%)
B. Serial Monitoring : Dilated retinal exams using a binocular indirect ophthalmoloscope
by an ophthalmologist to determine retinal maturity and early detection of ROP to
facilitate early treatment.

134
 C. Laser photocoagulation or cryosurgery
• Current standard therapy for ROP
• Ablates the avascular portion of the retina to reduce hypoxic stimulus from
VEGF production, stopping abnormal vessel growth
• Goal is to prevent retinal detachment
• Patients will still lose some peripheral vision after treatment
• Who should be treated?
– Zone I any stage with Plus disease
– Zone I Stage 3 without Plus disease
– Zone II stage 2-3 with Plus disease
D. Intravitrealbevacizumab(avastin)monotherapyhasshownsignificantbenefitfor
Zone I stage 3 disease in a RCT. Bevacizumab is a monoclonal antibody against
VEGF. It is an intravitreal injection, used in premature infants with severe ROP
and has shown significant promise in the treatment of ROP.
• There is concern for systemic absorption of Avastin, which may result in pan-VEGF
blockade which may interfere with angiogenesis in other developing organs. There is
insufficient long term data on efficacy and safety.
Prognosis
• Up to 80% of ROP will resolve spontaneously or regress
• Less than 6% require any treatment
• 3% or less will become blind from ROP

135
 Screening Eye Exams
Nina Menda, MD

AAP/Meriter Guidelines
• All infants with a birthweight ≤ 1500 grams, or gestational age at birth of≤ 30 weeks
• Select infants with birth weight 1500-2000 grams or gestational age at birth of
• 30 weeks with an unstable clinical course and at higher risk for ROP
as determined by attending neonatologist
• In most cases, ROP exams will begin at a PMA of 31 weeks or a
chronological age of 4 weeks, whichever is longer.
• **As an exception, infants born at < 25 weeks gestation should be
considered for earlier initiation of ROP screening at 6 weeks chronological
age based on severity of comorbidities to identify and treat posterior ROP (severe
form that is aggressive with rapid progression)

Timing of Initial ROP Exam

Gestational Age at Birth, Age at Initial Exam in Weeks
Completed Weeks
Postmenstrual Chronological
22** 31 (28**) 9 (6**)
23** 31 (29**) 8 (6**)
24** 31 (30**) 7 (6**)
25 31 6
26 31 5
27 31 4
28 32 4
29 33 4
30 34 4
Older gestational age, high-risk factors 4

136
• Discontinuation of examinations
o PMA 45 weeks with no Pre-threshold disease
o Progression of vascularization in zone III without previous ROP in zone
I or II
o Mild and regressing of ROP in zone III
o Full retinal vascularization

References:
1. AAP Policy Statement. Screening Examination of Premature Infants for
Retinopathy of Prematurity. Pediatrics 2013;131:189-195. doi: 10.1542/peds.
2012-2996.
2. Smith, L.E., Pathogenesis of retinopathy of prematurity. Semin Neonatol, 2003.
8(6): p. 469-73.
3. Mezu-Ndubuisi, O.J., In Vivo Angiography Quantifies Oxygen-Induced
Retinopathy Vascular Recovery. Optometry and Vision Science, 2016. 93(10): p.
1268.
4. Silva RA and. Moshfeghi DM. Interventions in Retinopathy of Prematurity.
Neoreviews 2012;13;e476. DOI: 10.1542/neo.13-8-e476.
5. Phelps DL. Retinopathy of Prematurity. Pediatrics in Review. 1995; 16: 50-56.
6. Gilbert, C., Retinopathy of prematurity: A global perspective of the epidemics,
population of babies at risk and implications for control. Early Human
Development, 2008. 84: p. 77-82.
7. Good, W.V., Final results of the Early Treatment for Retinopathy of Prematurity
(ETROP) randomized trial. Trans Am Ophthalmol Soc, 2004. 102: p. 233-48;
discussion 248-50.
8. SUPPORT Network, S.S.G.o.t.E.K.S.N.N.R., et al., Target ranges of oxygen
saturation in extremely preterm infants. N Engl J Med, 2010. 362(21): p. 1959-69.
9. Owen LA, Morrison MA, Hoffman RO, YoderBA, DeAngelis MM. Retinopathy
of prematurity: A comprehensive risk analysis for prevention and prediction of
disease. Vavvas DG, ed. PLoS ONE. 2017;12(2):e0171467.
doi:10.1371/journal.pone.0171467.
10. Helen a. Mintz-Hittner, Kathleen Kennedy. Efficacy of Intravitreal Bevacizumab
for stage 3+ retinopathy of prematurity. NEJM 2011; 364:603-15.

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 Chapter 21: Metabolic Disorders in Newborn
Sarah Trinh, MD and Lydia Wraight, MD

Overview
• Heterogenous group of disorders that typically present after 48 hours of life
and after the initiation of feedings
• Often associated with hypoglycemia, hyperammonemia, and acidosis
• Presentation in the newborn period includes lethargy, emesis, poor feeding,
hypotonia, tachypnea, temperature instability, seizures, coma, and apnea
• Always consider in a newborn who is being evaluated for sepsis
• May have family history of unexplained neonatal deaths
• Consanguineous matings (most are autosomal recessive)
Diagnosis
• Initial labs
– Blood glucose
– Arterial blood gas
– Lactate (arterial sample)
– Electrolytes (look for acidosis and aniongap)
– Ammonia (arterial sample, place immediately on ice)
– Liver function tests
– Urine ketones and reducing substances
– Newborn screen
• Diagnostic labs
– Plasma amino acids (amino acidopathies, urea cycle disorders)
– Urine organic acids (fatty acid oxidation disorders, amino acidopathies)
– Plasma acylcarnitine (fatty acid oxidation disorders, organic acidemias)
– Serum carnitine (fatty acid oxidation disorders, organic acidemias,
carnitine deficiency)
Hyperammonemia
• Medical emergency
• Treatment:
– Stop all feeds and discontinue all proteinintake
– Provide IV hydration with D10W

138
 – Correct electrolyte disturbances
– Consult a metabolic specialist
– Promote an anabolic state with lipids
– IV arginine HCL, sodium benzoate, sodium phenylacetate
– Peritoneal or hemodialysis if above therapies are not effective
– Monitor for increased intracranial pressure

Galactosemia
• Presentation: Progressive vomiting and lethargy, jaundice, encephalopathy,
hepatomegaly
• Associated with E. coli sepsis
• Diagnosis: NBS, urine reducing substances
• Treatment: soy formula, galactose free diet

Table 1. Inborn Errors of Metabolism Associated With an Acute Crisis

Diagnostic Clues
Primary Secondary Suggested Disorders
Acidosis ± Hypoglycemia Various Organic Acid Disorders
± Lactic Acidosis
± Ketosis
± High ammonia
Increased Anion gap (AG)
Significant Lactic Acidosis Mitochondrial disorders, Pyruvate
Normoglycemia dehydrogenase deficiency,
Alpha-ketoglutarate dehydrogenase
deficiency, Pyruvate carboxylase
deficiency
Sig. lactic acidosis Glycogen storage type I,
Hypoglycemia Fructose-1, 6-bisphosphatase deficiency
Normal AG Renal tubular acidosis
Normal
lactate
No ketosis

139
 Hyperammonemia Alkalosis or normal pH Urea cycle disorders
Normal lactate
Reye-like illness Fatty acid oxidation defects
(hypoglycemia, elevated
LFTs, no ketones)
Acidosis Various organic acid disorders
± Lactic acidosis
± Ketosis
± Hypoglycemia
Increased AG
Hypoglycemia Acidosis Various organic acid disorders
± Ketosis
± Lactic acidosis
± high ammonia
Increased AG
Hepatomegaly Glycogen storage disorders
± Lactic acidosis
No acidosis or ketosis Hyperinsulinemia
No Lactic acidosis Fatty acid oxidation defects
Hyponatremia Adrenal insufficiency
Hypotension
Signs of liver Tyrosinemia
failure Glycogen storage disease type IV
Galactosemia
Niemann Pick type C

Table 2. Characteristic of common Inborn Errors of Metabolism

Disorder Fatty Acid Amino- Organic Urea Cycle
Oxidation acidopathies Acidemias (pro- Disorders (OTC
Disorders (MSUD, PKU, pionic acidemia, deficiency)
(MCAD, tyrosinemia) methylmalonic
LCHAD, SCAD) acidemia)

140
 Key Hypoketotic No acidosis, Metabolic acidosis Hyperamonemia,
Finding Hypoglycemia Nml + AG, hypogly, Resp alkalosis
ammonia, hyperammonemia No acidosis
elevations in
specific AAs

Key Test Acylcarnitine Plasma amino Urine organic Plasma amino

Profile acids acids acids
Supple- Carnitine Profile Urine organic Acylcarnitine Urine organic
mental acids profile acids
Tests
Signs/ Presents MR, lethargy, Vomiting, Lethargy,
Symptoms 6 mos-2 yr. coma, liver lethargy, vomiting,
VLCAD/LCHAD failure end organ coma
dysfunction, be-
-rhabdomyolysis
gins with feeds
-cardiomyopathy
-hypotonia, SIDS
Acute D10, early IVFs Dextrose, D10, early IVFs, D10, early IVFs,
Treatment special TPN, no protein, sodium
insulin +/- bicarbonate benzoate,
phenylacetate,
arginine, insulin,
dialysis
Chronic Low fat diet, Low protein Low protein diet, Low protein diet,
Treatment avoid prolonged diet, supplemental supple- mental
fasts, nighttime supplemental formula, carnitine, formula, phenyl
feeds when sick, formula liver transplant acetate, arginine,
carnitine liver transplant

References:
1. Gregory M. Rice, Robert D. Steiner. Inborn Errors of Metabolism (Metabolic Disorders). Pediatrics in
Review. 2016;37;3.
2. Brodsky & Martin. Neonatology Review 3rd Ed. Vol 4. Inborn errors of metabolism. 2020

131
Disorder Fatty Acid Amino- Organic Urea Cycle
Oxidation acidopathies Acidemias (pro- Disorders (OTC
Disorders (MSUD, PKU, pionic acidemia, deficiency)
(MCAD, tyrosinemia) methylmalonic
LCHAD, SCAD) acidemia)
Key Hypoketotic No acidosis Metabolic acidosis Hyperam-
Finding Hypoglycemia or hyperam- with anion gap, monemia
monemia, hypoglycemia, w/o
elevations in hyperammonemia acidosis,
specific amino respiratory
acids alkalosis
Key Test Acylcarnitine Plasma amino Urine organic Plasma amino
Profile acids acids acids
Supple- Carnitine Profile Urine organic Acylcarnitine Urine organic
mental acids profile acids
Tests
Signs/ Presents MR, lethargy, Vomiting, Lethargy,
Symptoms 6 mos-2 yr. coma, liver lethargy, vomiting,
VLCAD/LCHAD failure end organ coma
dysfunction, be-
-rhabdomyolysis
gins with feeds
-cardiomyopathy
-hypotonia, SIDS
Acute D10, early IVFs Dextrose, D10, early IVFs, D10, early IVFs,
Treatment special TPN, no protein, sodium
insulin +/- bicarbonate benzoate,
phenylacetate,
arginine, insulin,
dialysis
Chronic Low fat diet, Low protein Low protein diet, Low protein diet,
Treatment avoid prolonged diet, supplemental supple- mental
fasts, nighttime supplemental formula, carnitine, formula, phenyl
feeds when sick, formula liver transplant acetate, arginine,
carnitine liver transplant
By taking care of a
newborn
we make a difference
that lasts a lifetime!
–Neena Shah, MD

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