Clifton and Busuttil.
Obstet Gynecol cases Rev 2015, 2:2
ISSN: 2377-9004
Obstetrics and
Gynaecology Cases - Reviews
Case Report: Open Access
A Case Study of Stillbirth in a Pregnancy Complicated by Asthma
Vicki L Clifton1,2* and Maureen D Busuttil1,3
1
Department of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, Australia
2
Mothers and Babies Research Centre, Hunter Medical Research Institute, University of Newcastle, Australia
3
Emergency Department, Lyell McEwin Health Service, Australia
*Corresponding author: A/Professor V.L. Clifton, Department of Paediatrics and Reproductive Health, Robinson
Research Institute, University of Adelaide, Medical North Building, Level 6, Frome Rd, Adelaide SA 5005, Australia,
Tel: 6128 83038321, Fax: 618 83034099, E-mail: Vicki.clifton@adelaide.edu.au
Newcastle, NSW antenatal clinic during the first trimester, following
Abstract
a previously described protocol [5]. Clinical asthma severity was
Asthma during pregnancy can be complicated by intrauterine rated as mild, moderate or severe using the integrated severity score
growth restriction, preterm delivery and stillbirth. This paper described in the Australian Asthma Management Guidelines [6],
reports the obstetric and respiratory history of a 23 year old
which closely approximate the National Heart, Lungs and Blood
woman whose pregnancy was complicated by asthma and a
severe asthma exacerbation that was associated with a stillbirth Institute Guidelines [7]. Appropriate inhaler use and compliance was
at 34 weeks gestation. The article attempts to link the relationship assessed in the Asthma Management Service [8].
between asthma in pregnancy and adverse fetal outcomes and
therefore highlights the need for multidisciplinary care of pregnant Results
asthmatic women and the increased need for greater awareness
by health professionals and pregnant women of the use of inhaled
Case
corticosteroid (ICS) treatment during pregnancy in combination This is the case of a 23 year old, non-tobacco smoking, marijuana
with an asthma action plan.
smoker with no major social problems except that her partner was
unemployed. This Caucasian woman, gravidity 0, parity 0, at 34
Background weeks gestation presented to the Emergency Department with a
severe exacerbation of asthma. She was a known asthmatic but had
A large North American collaborative project on asthma ceased preventer medications 2 years ago due to a reduction in her
and pregnancy reports that there are no significant differences in symptoms however reported that she had experienced increasing
perinatal outcomes between asthmatic and non-asthmatic women symptoms since her pregnancy. Pregnancy had been complicated
[1]. However, one factor that was not considered in this study was with increasing reflux and heartburn although this was not disclosed
the impact of acute exacerbations on fetal outcome. Our recent in any of her antenatal visits, a mild exacerbation of her asthma at
studies of pregnant asthmatic women identified that those asthmatic 14 weeks and anemia at 30 weeks gestation at which time she was
women who experienced an acute exacerbation during pregnancy commenced on iron replacement. The treatment that was instituted
had a number of adverse outcomes including intra uterine growth for her asthma exacerbation was not documented but her antenatal
restriction, preterm delivery or still birth [2-4]. record showed the use of salbutamol on an as needed basis up to
In this paper the events leading to a stillbirth in a pregnancy twice per day. Early gestation scan reported fetal growth was normal.
complicated by chronic asthma and an acute exacerbation that Prior to her emergency presentation the patient had experienced
occurred during a prospective cohort study of asthmatic women worsening difficulty breathing and had used nebulized salbutamol in
will be described [5]. The case study will highlight the importance the preceding 48 hours and had used 6 x 5mg/ml salbutamol nebules
of asthma management during pregnancy by general practitioners, during the morning before presenting to the emergency department.
obstetricians and respiratory physicians and demonstrate that asthma When she first presented to hospital she was noted to be hypoxic with
is a risk factor during pregnancy that should be seriously considered. saturations of 90% on room air. On examination she was afebrile,
heart rate of 122 and blood pressure of 139/80. There was widespread
Materials and Methods audible wheeze in at inspiration and expiration and her examination
was otherwise unremarkable. Her peak flow was 250 L/min. prior to
Subjects administration of any treatment and was only improved to 280L/min
This case was part of a prospective cohort study that was post treatment with one salbutamol nebulization. She was considered
approved by the Hunter Area Health Service and University of to be too unwell to remain at the local hospital and was transferred
Newcastle Human Research Ethics Committees. Pregnant women to tertiary hospital for specialist care within the obstetric unit. The
with and without asthma were recruited in the John Hunter Hospital, patient was admitted for treatment with intravenous hydrocortisone
Citation: Clifton VL, Busuttil MD (2015) A Case Study of Stillbirth in a Pregnancy
Complicated by Asthma. Obstet Gynecol Cases Rev 2:027
ClinMed Received: January 18, 2015: Accepted: March 23, 2015: Published: March 25, 2015
Copyright: 2015 Clifton VL. This is an open-access article distributed under the terms of
International Library the Creative Commons Attribution License, which permits unrestricted use, distribution, and
reproduction in any medium, provided the original author and source are credited.
Table 1: Maternal characteristics of non-asthmatic and asthmatic subjects that There were no signs of infection or placental insufficiency. The report
had a live birth and case study subject who had a stillbirth
did not attribute a cause of death or an estimated date of demise.
Maternal Characteristics Control Asthmatic Case 1
Total number of subjects 39 184 9 Comment
Asthma is recognized as a risk factor during pregnancy [9-11].
Age(yrs) 28.8 26.2* 23 There are a number of reports that show there is an increased risk
Standard error 0.65 0.39 of stillbirth in asthmatic pregnancies [9,12-15]. Fetal demise in
pregnancies associated with asthma are thought to be caused by
Height(cms) 164.5 164 156.5 the development of maternal alkalosis [14] and reductions in fetal
Standard error 1.2 0.5 oxygenation resulting in fetal hypoxia, hypercapnia and acidosis [16].
Weight at beginning of pregrnancy(kg) 70.2 73.8* 61 The fetal death in this case appears to be related to the effects of a
Standard error 2.8 1.6 severe exacerbation and uncontrolled asthma during pregnancy. The
woman had a history of moderately severe asthma with numerous
Weight durringpregrnancy(kg) 11.2 11.3 15.45 admissions to hospital but had not used ICS for 2 years due to
Standard error 1.1 0.5 improved symptoms however there is evidence from the case record
that she was experiencing asthma symptoms from early pregnancy and
Gravidity 2.6 2.4* 0 yet she received only reliever therapy without the necessary ICS. The
Standard error 0.3 0.12 fetus was small for gestational age supporting that there was growth
restriction due to uncontrolled asthma during pregnancy [15,17].
Parity 1.2 0.9* On admission she was experiencing a severe exacerbation with a
Standard error 0.2 0.1 poor response to salbutamol and received suboptimal treatment. The
recommended treatment for an adult with acute asthma is currently
Gestational age at delivery(weeks) 39 39.2 34 three nebulizations over one hour with supplemental oxygen if
Standard error 0.6 0.2 hypoxia is present [18] in addition to systemic steroid which she did
receive. The combination of growth restriction and maternal hypoxia
%predicted FEV1 96 89.6* 74 would likely have had an adverse effect on the fetus. The death of the
Standard error 2.5 1.6 fetus ,although not reported in the autopsy is likely to have occurred
days prior to its discovery [19,20] towards the end of admission or
FEV1 VC 0.85 0.81* 0.82 within hours after discharge as the ultrasound performed early in
Standard error 0.02 0 her admission showed a live fetus. Fetal movement and a fetal heart
rate were last documented the day after the scan, 3 days before her
Inhaled glucocorticoid intake during discharge. Nursing notes mention attention to fetal heart on the day
pregnancy of discharge yet no heart rate was documented.
First trimester ug/day 0 46.9* 0
Standard error 43.9
The circumstances leading to this death highlight the need for
Second trimester ug/day 0 577.2* 0
close management of asthma during pregnancy with a focus on
Standard error 50.7
specialist respiratory care which includes providing the asthma
Third trimester ug/day 0 638.7* 1000
patient with education in control, management and a crisis plan for
Standard error 51.8
pregnancy [21,22].
Asthma exacerbations are of considerable concern during
Periodic oral glucocorticoid intake during pregnancy due to the adverse effect they have on the fetus [23].
pregnancy No yes yes
Schatz et al. found that of 1739 women with asthma, 20% had a severe
* P<0.05 Student t-Test exacerbation during pregnancy which required medical intervention.
Exacerbations increased with increasing asthma severity, with 52% of
and nebulized salbutamol only as frequently as every 2 hours inspite severe asthmatics having an exacerbation.
of the severity of her asthma. She was not treated with supplemental
oxygen and her saturations remained low between 93 and 96%. She Exacerbations can occur at any time during gestation but tend
also was tachycardic during the first 48 hours of her admission. Fetal to cluster between 17 and 34 weeks gestation with a median of 25
heart was documented but no fetal monitoring was performed. The weeks gestation [2]. Previous studies report similar results [24]. This
laboratory investigations were unremarkable aside from a mild suggests that the most important time to focus on asthma control and
anemia with haemoglobin of 104. Ultrasound was conducted one day maternal self-management skills is early in gestation with continued
after admission and reported an anatomically normal, live fetus with follow up throughout pregnancy.
normal umbilical artery systolic/diastolic flow (Table 1). Inhaled steroid use for the treatment of asthma during pregnancy
Prednisolone (25mg/day) and inhaled beclamethasone significantly reduces the incidence of acute exacerbations during
dipropionate (1000g/day) was commenced on the third day of her gestation [17,25,26], decreases the number of hospital admissions
admission in place of hydrocortisone. By the fifth day her condition [27] and reduces the need for regular use of oral steroid which is
had improved with her PEFR pre and post salbutamol 250/L min and associated with low birthweight [25,28]. Stenius-Aarniala et al. [25]
360/L min respectively. The patient was discharged from hospital concluded that when asthmatic women were carefully managed by
after six days with continuing inhaled and oral steroid as prescribed both obstetricians and respiratory physicians the rate of preterm
in hospital. Fetal heart was noted but the rate not documented on delivery, perinatal death and low birth weight was not significantly
discharge. The patient then returned two days later for a follow up different from the non-asthmatic population. Our previous studies
visit at the antenatal clinic and no fetal heart rate was detectable. are also in agreement with these findings [21,22,29].
Labor was induced two days after fetal demise was detected and a It is impossible to identify a single etiology for stillbirth as there
male fetus was delivered weighing 1940 grams, on the 10th centile for are many potential factors that contribute to a poor outcome for the
birth weight and a placental weight of 372g. It was noted there was fetus. In this particular case, the combination of a low birth weight
thick meconium staining of amniotic fluid. Autopsy reported a grossly fetus, male sex [30], a primigravid pregnancy and low socioeconomic
externally macerated fetus of normal morphology with weights and status [31] could also have contributed to this poor outcome.
measurements consistent with 35 weeks gestation. There was marked However this case study highlights that the presence of chronic
maceration of the internal organs and overlapping of the skull bones. maternal asthma, an acute asthma exacerbation and a male fetus
Clifton and Busuttil. Obstet Gynecol cases Rev 2015, 2:2 ISSN: 2377-9004 Page 2 of 3
further increases the possibility of a perinatal death, especially when III. External fetal examination; a study of 86 stillborns. Obstet Gynecol 80:
593-600.
exacerbations occur in late gestation when fetal demand for oxygen
and nutrients has increased. The use of preventative clinical practices 20. Langley FA (1971) The perinatal postmortem examination. J Clin Pathol 24:
that include asthma education and management in the antenatal 159-169.
setting may reduce the risk of stillbirth in pregnancies complicated 21. Murphy VE, Gibson PG, Talbot PI, Kessell CG, Clifton VL (2005) Asthma
by asthma [22]. self-management skills and the use of asthma education during pregnancy.
Eur Respir J 26: 435-441.
Condensation 22. Powell H, Murphy VE, Taylor DR, Hensley MJ, McCaffery K, et al. (2011)
Management of asthma in pregnancy guided by measurement of fraction of
This paper is an examination of a stillbirth in a pregnancy exhaled nitric oxide: a double-blind, randomised controlled trial. Lancet 378:
complicated by asthma. 983-990.
23. Murphy VE, Clifton VL, Gibson PG (2006) Asthma exacerbations during
Funding pregnancy: incidence and association with adverse pregnancy outcomes.
Thorax 61: 169-176.
National Health and Medical Research Council of Australia
(Grant No. 252438), The Asthma Foundation of NSW, the NSW 24. Gluck JC, Gluck P (1976) The effects of pregnancy on asthma: a prospective
Department of Health and Hunter Medical Research Institute. A/ study. Ann Allergy 37: 164-168.
Prof Vicki Clifton was a recipient of National Health and Medical 25. Stenius-Aarniala B, Piiril P, Teramo K (1988) Asthma and pregnancy: a
Research Council RD Wright Fellowship during the collection of prospective study of 198 pregnancies. Thorax 43: 12-18.
this data (Grant No. 300786). VC salary is currently funded by the 26. Murphy VE, Gibson PG, Smith R, Clifton VL (2005) Asthma during pregnancy:
National Health and Medical Research Council Senior Research mechanisms and treatment implications. Eur Respir J 25: 731-750.
Fellowship (APP1041918). 27. Wendel PJ, Ramin SM, Barnett-Hamm C, Rowe TF, Cunningham FG (1996)
Asthma treatment in pregnancy: a randomized controlled study. Am J Obstet
References Gynecol 175: 150-154.
1. Dombrowski MP, Schatz M, Wise R, Momirova V, Landon M, et al. (2004) 28. Perlow JH, Montgomery D, Morgan MA, Towers CV, Porto M (1992) Severity
Asthma during pregnancy. Obstet Gynecol 103: 5-12. of asthma and perinatal outcome. Am J Obstet Gynecol 167: 963-967.
2. Murphy VE, Gibson P, Talbot PI, Clifton VL (2005) Severe asthma 29. Murphy VE, Gibson PG, Giles WB, Zakar T, Smith R, et al. (2003) Maternal
exacerbations during pregnancy. Obstet Gynecol 106: 1046-1054. asthma is associated with reduced female fetal growth. Am J Respir Crit
Care Med 168: 1317-1323.
3. Hodyl NA, Stark MJ, Scheil W, Grzeskowiak LE, Clifton VL (2014) Perinatal
outcomes following maternal asthma and cigarette smoking during pregnancy. 30. Engel PJ, Smith R, Brinsmead MW, Bowe SJ, Clifton VL (2008) Male sex and
Eur Respir J 43: 704-716. pre-existing diabetes are independent risk factors for stillbirth. Aust N Z J
Obstet Gynaecol 48: 375-383.
4. Clifton VL, Engel P, Smith R, Gibson P, Brinsmead M, et al. (2009) Maternal
and neonatal outcomes of pregnancies complicated by asthma in an 31. Goy J, Dodds L, Rosenberg MW, King WD (2008) Health-risk behaviours:
Australian population. Aust N Z J Obstet Gynaecol 49: 619-626. examining social disparities in the occurrence of stillbirth. Paediatr Perinat
Epidemiol 22: 314-320.
5. Clifton VL1, Giles WB, Smith R, Bisits AT, Hempenstall PA, et al. (2001)
Alterations of placental vascular function in asthmatic pregnancies. Am J
Respir Crit Care Med 164: 546-553.
6. Campaign National Asthma. Asthma Management Handbook. Sydney,
Australia.
7. Health NIO. Guidelines for the diagnosis and management of asthma.
National Heart, Lung and Blood Institute.
8. Barnes NC, Marone G, Di Maria GU, Visser S, Utama I, et al. (1993) A
comparison of fluticasone propionate, 1 mg daily, with beclomethasone
dipropionate, 2 mg daily, in the treatment of severe asthma. International
Study Group. Eur Respir J 6: 877-885.
9. Gelber M, Sidi Y, Gassner S, Ovadia Y, Spitzer S, et al. (1984) Uncontrollable
life-threatening status asthmaticus--an indicator for termination of pregnancy
by cesarean section. Respiration 46: 320-322.
10. Gilchrist DM, Friedman JM, Werker D (1991) Life-threatening status
asthmaticus at 12.5 weeks gestation. Report of a normal pregnancy outcome.
Chest 100: 285-286.
11. Raphael JH, Bexton MD (1993) Combined high frequency ventilation in the
management of respiratory failure in late pregnancy. Anaesthesia 48: 596-
598.
12. Gordon M, Niswander KR, Berendes H, Kantor AG (1970) Fetal morbidity
following potentially anoxigenic obstetric conditions. VII. Bronchial asthma.
Am J Obstet Gynecol 106: 421-429.
13. Bahna SL, Bjerkedal T (1972) The course and outcome of pregnancy in
women with bronchial asthma. Acta Allergol 27: 397-406.
14. Sachs BP, Brown RS, Yeh J, Acker D, Niaraki M (1987) Is maternal alkalosis
harmful to the fetus? Int J Gynaecol Obstet 25: 65-68.
15. Greenberger PA, Patterson R (1988) The outcome of pregnancy complicated
by severe asthma. Allergy Proc 9: 539-543.
16. Cousins L (1999) Fetal oxygenation, assessment of fetal well-being, and
obstetric management of the pregnant patient with asthma. J Allergy Clin
Immunol 103: S343-349.
17. Fitzsimons R, Greenberger PA, Patterson R (1986) Outcome of pregnancy in
women requiring corticosteroids for severe asthma. J Allergy Clin Immunol
78: 349-353.
18. Australia. NAC. Australian Asthma Handbook Version 1.0: National Asthma
Council Australia, Melbourne Website. [http://www.asthmahandbook.org.au,
2014].
19. Genest DR, Singer DB (1992) Estimating the time of death in stillborn fetuses:
Clifton and Busuttil. Obstet Gynecol cases Rev 2015, 2:2 ISSN: 2377-9004 Page 3 of 3
