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DOI: 10.1111/tog.

12048 2013;15:2415
The Obstetrician & Gynaecologist
Review
http://onlinetog.org

Asthma in pregnancy
a,b c,
Michelle H Goldie RM, Chris E Brightling PhD FRCP *
a
Honorary Research Associate, Institute for Lung Health, Department of Infection, Immunity & Inflammation, Clinical Sciences Wing, University
Hospitals of Leicester, Leicester LE3 9QP, UK
b
Former Specialist Midwife, Leicester Royal Infirmary, Leicester LE1 5WW, UK
c
Professor of Respiratory Medicine & Honorary Consultant Physician, Institute for Lung Health, Department of Infection, Immunity &
Inflammation, Clinical Sciences Wing, University Hospitals of Leicester, Leicester LE3 9QP, UK
*Correspondence: Professor Chris E Brightling. Email: ceb17@le.ac.uk

Accepted on 8 September 2012

Key content Learning objectives


 Asthma is a common condition that affects ~10% of pregnant  Comprehensive overview of asthma in pregnancy.
women.  Review asthma management in pregnancy.
 Pregnancy worsens asthma control in one-third of women,
Ethical issues
improves it in one-third and has no effect on one-third. 
 Poor asthma control has adverse effects upon maternal and fetal
Are women appropriately counselled on the pregnancy risks of
asthma?
outcomes.  Are doctors aware of the safety of routine asthma treatments in
 Good asthma management to maintain control is important in line
pregnancy?
with national guidelines.
 Standard therapy with inhaled corticosteroids with or without the Keywords: asthma / b-agonists / corticosteroids / pre-eclampsia /
addition of short and long-acting b-agonists can be used in pregnancy
pregnancy.

Please cite this paper as: Goldie MH, Brightling CE. Asthma in pregnancy. The Obstetrician & Gynaecologist 2013;15:2415.

conversely asthma can affect pregnancy. Importantly, the


Introduction
British Thoracic Society/Scottish Intercollegiate Guideline
Asthma affects an estimated 235 million people worldwide Network (BTS/SIGN) asthma guideline on the management
and the burden is likely to rise substantially in the of asthma apply in pregnancy and good asthma control
next few decades.13 The condition causes about 239 000 during pregnancy is critical.7
deaths per year (0.4% of all deaths due to disease) and
results in a large burden of disability. The total cost of
asthma in Europe is estimated to be 17.7 billion Box 1. Triggers for asthma
per annum.2
Asthma is a chronic inflammatory disease of the airways,  Allergens, such as house dust mite, pollen, etc.
which is characterised by intermittent episodes of wheeze,  Smoking
 Exercise
shortness of breath, chest tightness and cough, which are
 Occupational exposure
often worse at night. It is a variable disease where  Pollution
inflammation and structural changes can occur in the  Drugs, such as aspirin, b-blockers
airway in response to certain stimuli or triggers (Box 1).3,4  Food and drinks such as dairy produce, alcohol, peanuts and orange
juice
This causes airway hyper-responsiveness and variable
 Additives such as monosodium glutamate and tartrazine
airflow obstruction leading to the symptoms described.  Medical conditions, such as rhinitis and gastric reux
Patients suffer from flare-ups or exacerbations of their  Hormonal, such as premenstrual conditions and pregnancy
disease either in response to an acute infection, which is
usually viral in origin, or due to poor control of their
airway inflammation.
Breathlessness in pregnancy
The prevalence of asthma in pregnant women is 412%,
making it the most common chronic condition in Breathlessness is the sensation of feeling out-of-breath or
pregnancy.5,6 Pregnancy can affect asthma control and unable to catch your breath. A healthy respiratory rate is

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Asthma in pregnancy

1220 breaths/minute at rest. A persistent respiratory rate


Box 3. Physiological factors affecting asthma in pregnancy
at rest >24 breaths/minute is abnormal. Breathlessness in
pregnancy is extremely common and may reflect either  Increase in free cortisol levels may protect against inammatory
the normal anatomical and physiological changes that triggers.
occur in pregnancy, or anxiety, or may be a consequence  Increase in bronchodilating substances (such as progesterone) may
of an underlying pathology. Therefore, in a woman with improve airway responsiveness.
 Increase in bronchoconstricting substances (such as prostaglandin
known asthma the cause of increased breathlessness may F2a) may promote airway constriction.
not be due to asthma. Similarly, in a woman not  Placental 11b-hydroxysteroid dehydrogenase type 2 decreased
diagnosed as asthmatic new incident asthma can be the activity is associated with an increase in placental cortisol
cause of breathlessness, albeit rarely. The causes of concentration and low birthweight.
 Placental gene expression of inammatory cytokines may promote
breathlessness to be considered in pregnancy are shown low birthweight.
in Box 2.  Modication of cell-mediated immunity may inuence maternal
response to infection and inammation.

Box 2. Main differential diagnoses in pregnant women with dyspnoea

The effects of asthma on pregnancy


 Anxiety
 Hyperventilation Where risks have been reported the data on the effects of
 Dysfunctional breathing
asthma on pregnancy outcomes is conflicting.1214 This is
 Respiratory disease:
asthma probably due to differences in study designs, asthma severity
chest infection and/or pneumonia and its management in different studies and inadequate
thromboembolic disease consideration of potential confounders. There are limited
interstitial lung disease, e.g. sarcoid or secondary to a connective
tissue disorder
data on how asthma control prior to pregnancy influences
pneumothorax pregnancy outcomes, although in one casecontrolled study
amniotic uid embolism of two-thousand women, poor asthma control and disease
 Cardiac disease: severity prior to pregnancy were associated with an elevated
arrhythmias
ischaemic heart disease
risk of hypertension in pregnancy.15 This is consistent with
cardiomyopathy previous studies that have demonstrated an association
 Endocrine disease: between asthma and hypertension during pregnancy,8 and
diabetes mellitus leading to hyperventilation in the setting of two large, multicentre, prospective studies that found in
acute ketoacidosis
acute thyrotoxicosis women with daily asthma symptoms16 or impaired lung
 Haematological: function17 there was an increase in hypertension. In contrast,
chronic anaemia a systematic review that included nearly one thousand
acute haemorrhage
women found that asthma exacerbations were not
 Renal disease:
hyperventilation to compensate for metabolic acidosis secondary associated with an increased risk of pre-eclampsia.8,13
to acute renal failure Recent evidence suggests that airway hyper-responsiveness
a hallmark of asthma may be a predictor of pre-eclampsia
and points to a mechanistic common pathway of mast cell
airway smooth muscle cell interactions.18
The effects of pregnancy on asthma Retrospective and prospective studies have demonstrated
The severity of asthma during pregnancy remains that women with asthma have a higher frequency of caesarean
unchanged, worsens or improves in equal proportions.8 section than women without asthma.8 Intrauterine growth
Box 3 describes physiological factors that affect asthma restriction or low birthweight were observed in retrospective
during pregnancy. In severe disease, asthma control is more studies but this has not been replicated in large prospective
likely to deteriorate (~60%) than in mild disease (~10%).9,10 studies. However, low birthweight is associated with measures
Exacerbations are most common between 24 and 36 weeks of poor asthma control such as persistent daily symptoms or
of pregnancy.9,11 Respiratory viral infections were the most poor lung function.16,17 and in women not using inhaled
frequent triggers of exacerbations (34%), followed by poor corticosteroids.12 Similarly in a systematic review, of nearly
adherence to inhaled corticosteroid therapy (29%).9 one thousand women, asthma exacerbations during
Therefore, during pregnancy women with asthma need to pregnancy increased the risk of low birthweight compared
be closely reviewed throughout pregnancy, irrespective of to women with asthma without exacerbations and women
disease severity. without asthma.13

242 2013 Royal College of Obstetricians and Gynaecologists


Goldie and Brightling

Figure 1. Guidelines from British Thoracic Society/Scottish Intercollegiate Guidelines Network for asthma treatment steps. SR=slow releasing; BDP
= beclomethasone dipropionate equivalent. Reprinted from BTS/SIGN British Guideline on the Management of Asthma, 2008, revised 2012 with
permission from The British Thoracic Society

Taken together these data do support the view that asthma asthma treatment step 3 or above (Figure 1) need to be
severity and poor asthma control are associated with adverse managed by both a respiratory physician and obstetrician to
outcomes in pregnancy, although it is important to note that optimise asthma control.
in most women with well-controlled asthma there are no or
minimal additional risks. Box 4. Pregnancy issues

 Poorly controlled asthma confers an increased risk to the mother


Management of stable asthma in and fetus.
pregnancy  Asthmatic women are more at risk of low birthweight neonates,
preterm delivery and complications such as pre-eclampsia, especially
The management and treatment of asthma are generally the in the absence of actively managed asthma treated with inhaled
same in pregnant women as in non-pregnant women and in corticosteroids, although the increased risk is very small in women
men.7 The intensity of antenatal maternal and fetal with well-controlled asthma.
surveillance should be based on the severity of asthma, i.e.  There is no contraindication to most rst-line treatments for asthma
when used in pregnancy.
current need for therapy, symptom control, exacerbation  Smoking cessation is an important part of general obstetric advice,
frequency including high-dose corticosteroid usage and but is important in asthma to reduce symptoms and the efcacy of
hospitalisation and lung function, for example, peak flow inhaled corticosteroids is reduced in asthmatics who smoke.
 Exacerbations of asthma should be managed in line with current
and spirometry together with the risk of fetal complications.
guidelines from British Thoracic Society/Scottish Intercollegiate
The general principles of asthma management in pregnancy Guidelines Network.
are summarised in Box 4. Women with moderate to severe

2013 Royal College of Obstetricians and Gynaecologists 243


Asthma in pregnancy

Nonpharmacological management monitored throughout pregnancy both as part of routine care


and because pregnancy might affect the pharmacokinetics
Education is the cornerstone of asthma management and needs of theophylline. Theophylline usage has decreased in
to include understanding of the condition and its asthma due to alternative therapies but still has a place in
management, trigger avoidance, asthma control, adequate asthma management.
use of devices, and the importance of adherence to medication In some asthmatics disease control can only be achieved
together with the construction of personal action plans. with oral corticosteroids and systemic therapy are required to
Systematic reviews have reported that education and manage acute severe or life-threatening exacerbations. In
action plans lead to improvements in asthma control and epidemiological studies oral corticosteroids have been shown
reduction in the need to seek emergency medical help and to increase the risk of fetal cleft lip or palate in the first
hospital admissions. trimester.23 However, this increased risk is small (<0.3%).
Therefore, oral corticosteroids should still be prescribed
Pharmacological treatment
when required but should be used with caution and only
There are concerns held by mothers and their healthcare when there is a clear clinical need.
providers about the potential adverse effects of asthma drugs Leucotriene modifiers are increasingly used in mild to
on their babies and themselves. In pregnancy women reduce moderate asthma and have a good safety profile. Animal
their use of inhaled corticosteroids by 23% and short-acting studies show no teratogenicity with montelukast.5 However,
b2-agonists by 13% for stable therapy and oral corticosteroids there is a paucity of data in pregnancy. Therefore, due to lack
for exacerbations by 54%.19 This change in adherence by of data in pregnancy it is prudent to substitute leucotriene
women is mirrored by doctors who are more reluctant to modifiers with an inhaled corticosteroid prior to conception
prescribe corticosteroids both initially and on discharge to or at the beginning of pregnancy alone or in combination
pregnant women than to nonpregnant women.20 with a long acting b2-agonist.
It should be emphasised that it is safer for women to use Anti-IgE is the only biological therapy available for
asthma therapy in pregnancy to achieve and maintain good asthma.24 Its effects on pregnancy are unknown. This
control than to have uncontrolled asthma.16 Systematic therapy should only be prescribed in specialist tertiary
reviews report consistently that inhaled corticosteroids, asthma centres and although it is not recommended
short or long-acting b2-agonists and theophylline do not during pregnancy, it needs to be considered in light of the
increase the risk of maternal or neonatal outcomes riskbenefit ratio on an individual patient basis, as with all
such as pre-eclampsia, fetal congenital malformations, therapies in those with very severe disease. Immuno-
low birthweight or preterm delivery.21 Therefore, good suppressant therapy such as methotrexate and cyclosporine
asthma control remains the aim throughout pregnancy. are contraindicated in pregnancy, but in non-pregnant
Pregnancy may modify the pharmacodynamics and individuals are sometimes used particularly as oral
pharmacokinetics of some medications, but this effect is corticosteroid sparing agents in severe asthmatics.
small and the dose and regimen of asthma medications rarely
need to be changed in pregnancy. Inhaled corticosteroids are
Management of asthma exacerbations in
the standard anti-inflammatory therapy for asthma. They are
pregnancy
safe in pregnancy,21 and importantly, several studies have
reported that inhaled corticosteroids reduce the risk of Asthma exacerbations are managed as per the BTS/SIGN
asthma exacerbations during pregnancy.21 guidelines,7 which include the use of oral corticosteroids,
Likewise, prospective, observational, and casecontrol nebulised b2-agonists and oxygen as well as other additional
studies have shown that short-acting b2-agonists are safe supportive care dependent upon severity.
during pregnancy.21 By contrast, few data exist on
long-acting b2-agonists used alone or in combination with
Asthma: labour and delivery
inhaled corticosteroids during pregnancy. However, in the
limited studies to date, salmeterol and formoterol did Asthma does not usually affect labour or delivery with less
not cause fetal malformations, preterm delivery, or low than a fifth of women experiencing an exacerbation during
birthweight.16 The safety of long-acting b2-agonists labour,8 and severe or life-threatening exacerbations are very
prescribed alone in the absence of inhaled corticosteroids rare. Prostaglandin F2a (for example, Hemabate, Pfizer Ltd.,
has been questioned with respect to asthma control and thus Sandwich, UK) can cause bronchospasm and needs to be
they should always be used together with an inhaled used with caution, whereas prostaglandin E2 (for example,
corticosteroid, ideally in a combination product.7 Prostin, Pharmacia Ltd., Sandwich, UK) is not associated
Theophylline is safe in pregnancy at recommended with bronchospasm. Box 5 outlines the key points for
doses.22 Importantly, serum theophylline levels need to be women with asthma during labour.

244 2013 Royal College of Obstetricians and Gynaecologists


Goldie and Brightling

3 Global Initiative for Asthma (GINA). Global Strategy for Asthma


Box 5. Peripartum issues Management and Prevention, 2006 (2010 update) [http://
www.ginasthma.org].
 Acute, severe or life-threatening exacerbations of asthma during 4 Brightling CE, Gupta S, Sutcliffe A, Amrani Y. Immunopathogenesis of
labour are extremely rare. severe asthma. Curr Pharm Des 2011;17:66773.
 Women who have been on regular oral steroids may require 5 Rey E, Boulet LP. Asthma in pregnancy. BMJ 2007;334:5825.
hydrocortisone during labour. 6 Kwon HL, Belanger K, Bracken MB. Asthma prevalence among pregnant
 Ergometrine, Syntometrine and prostaglandin may cause and childbearing-aged women in the United States: estimates from
bronchoconstriction and should be used with caution. national health surveys. Ann Epidemiol 2003;13:31724.
7 British Thoracic Society/Scottish Intercollegiate Guideline Network.
British Guideline on the Management of Asthma (2008). Thorax
Asthma: postpartum and breastfeeding 2008;63(Suppl 4):121.
8 Murphy VE, Gibson PG. Asthma in pregnancy. Clin Chest Med
In the postpartum period there is not an increased risk of 2011;32:93110, ix.
asthma exacerbations and within a few months after delivery a 9 Murphy VE, Gibson P, Talbot PI, Clifton VL. Severe asthma exacerbations
during pregnancy. Obstet Gynecol 2005;106:104654.
womans asthma severity typically reverts to its pre-pregnancy 10 Schatz M, Dombrowski MP, Wise R, Thom EA, Landon M, Mabie W,
level.5 Few data are available on the safety of asthma drugs in et al. Asthma morbidity during pregnancy can be predicted by severity
breastfed neonates, but in general the same medications classication. J Allergy Clin Immunol 2003;112:2838.
11 Stenius-Aarniala BS, Hedman J, Teramo KA. Acute asthma during
deemed safe in pregnancy can be continued and those with a
pregnancy. Thorax 1996;51:4114.
negative or an uncertain safety profile should be avoided. 12 Murphy VE, Gibson PG, Smith R, Clifton VL. Asthma during
Non-steroidal anti-inflammatory drugs (NSAIDs) for pregnancy: mechanisms and treatment implications. Eur Respir J
analgesia are to some degree contraindicated in asthma and 2005;25:73150.
13 Murphy VE, Clifton VL, Gibson PG. Asthma exacerbations during
may cause bronchospasm but in women without intolerance
pregnancy: incidence and association with adverse pregnancy
to NSAIDs they can be used. outcomes. Thorax 2006;61:16976.
Primary care physicians can manage most women with 14 Gluck JC, Gluck PA. Asthma controller therapy during pregnancy. Am J
asthma, but women with severe disease, particularly if Obstet Gynecol 2005;192:36980.
15 Martel MJ, Rey E, Beauchesne MF, Perreault S, Lefebvre G, Forget A,
systemic corticosteroids are considered, need to be et al. Use of inhaled corticosteroids during pregnancy and risk of
managed by respiratory physicians. pregnancy induced hypertension: nested casecontrol study. BMJ
The World Health Organization recommends that women 2005;330:230.
should exclusively breastfeed for at least 6 months.25 Whether 16 Bracken MB, Triche EW, Belanger K, Saftlas A, Beckett WS, Leaderer
BP. Asthma symptoms, severity, and drug therapy: a prospective
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detract from the overwhelming benefit of breastfeeding. 17 Schatz M, Dombrowski MP, Wise R, Momirova V, Landon M, Mabie W,
et al. Spirometry is related to perinatal outcomes in pregnant women
with asthma. Am J Obstet Gynecol 2006;194:1206.
Conclusion 18 Siddiqui S, Goodman N, McKenna S, Goldie M, Waugh J, Brightling CE.
Pre-eclampsia is associated with airway hyperresponsiveness. BJOG
Asthma is a widespread condition that affects ~10% of 2008;115:5202.
pregnant women. Poor asthma control has adverse effects 19 Enriquez R, Wu P, Grifn MR, Gebretsadik T, Shintani A, Mitchel E,
upon maternal and fetal outcomes. Good asthma et al. Cessation of asthma medication in early pregnancy. Am J Obstet
Gynecol 2006;195:14953.
management to maintain control is therefore important 20 Cydulka RK, Emerman CL, Schreiber D, Molander KH, Woodruff PG,
and standard therapy with inhaled corticosteroids with or Camargo CA, Jr. Acute asthma among pregnant women presenting to the
without the addition of short- and long-acting b-agonists emergency department. Am J Respir Crit Care Med 1999;160:88792.
21 Schatz M, Dombrowski MP, Wise R, Momirova V, Landon M, Mabie W,
may be used in pregnancy.
et al. The relationship of asthma medication use to perinatal outcomes.
J Allergy Clin Immunol 2004;113:10405.
Disclosure of interests 22 Dombrowski MP, Schatz M, Wise R, Thom EA, Landon M, Mabie W,
MG has no conflicts of interest. CEB receives grant income et al. Randomized trial of inhaled beclomethasone dipropionate versus
theophylline for moderate asthma during pregnancy. Am J Obstet
and consultancy fees via his Institution from
Gynecol 2004;190:73744.
GlaxoSmithKline, AstraZeneca, MedImmune, Novartis, 23 Park-Wyllie L, Mazzotta P, Pastuszak A, Moretti ME, Beique L,
Chiesi and Roche/Genentech. Hunnisett L, et al. Birth defects after maternal exposure to
corticosteroids: prospective cohort study and meta-analysis of
epidemiological studies. Teratology 2000;62:38592.
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2013 Royal College of Obstetricians and Gynaecologists 245

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