Asthma Management Handbook

Managing asthma actively during pregnancy

Recommendations

Manage asthma during pregnancy as for asthma in other adults, aiming to maintain the best possible asthma control and to avoid asthma flare-ups.

Note:  The Therapeutic Goods Administration categorises medicines according to safety during pregnancy.

How this recommendation was developed

Evidence-based recommendation (Grade A)

Based on systematic literature review.

Clinical question for literature search:

What are the effects of (1) asthma and (2) asthma treatment on pregnancy outcomes?

(e.g. Does effective asthma control improve pregnancy outcomes [maternal, foetal] in women with asthma? Does poorly controlled asthma [evidenced by exacerbations, acute asthma episodes, emergency visits)] affect pregnancy outcomes in women with asthma? Does asthma treatment affect pregnancy outcomes [maternal, foetal] in women with asthma?)

Key evidence considered:

  • Clifton et al. 20101
  • Moldenhauer et al. 20102
  • Murphy et al. 20063
  • Murphy et al. 20114
  • Namazy et al. 20125
  • Schatz et al. 20016
  • Schatz et al. 20067
  • Silverman et al. 20058

For a pregnant woman with asthma, prescribe preventers, if indicated, just as for other adults, aiming to maintain the best possible asthma control and to avoid asthma flare-ups.

Note: Do not withhold preventer treatment due to pregnancy. Pregnancy is not a contraindication for asthma preventers.

How this recommendation was developed

Evidence-based recommendation (Grade A)

Based on systematic literature review.

Clinical question for literature search:

What are the effects of (1) asthma and (2) asthma treatment on pregnancy outcomes?

(e.g. Does effective asthma control improve pregnancy outcomes [maternal, foetal] in women with asthma? Does poorly controlled asthma [evidenced by exacerbations, acute asthma episodes, emergency visits)] affect pregnancy outcomes in women with asthma? Does asthma treatment affect pregnancy outcomes [maternal, foetal] in women with asthma?)

Key evidence considered:

  • Lim et al. 20129
  • Murphy et al. 20114
  • Silverman et al. 20058

Step up the regimen as necessary to regain or maintain control during pregnancy.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available), with particular reference to the following source(s):

  • Powell et al. 201110

During pregnancy, consider stepping down only if the woman is taking an inappropriately high dose of a medicine.  

Note: Stepping down is not a priority during pregnancy because of the risk of flare-up.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Offer regular review of asthma every 4 weeks during pregnancy. Assess asthma control consistently at each review (e.g. use a validated asthma assessment tool, and use the same tool each time).

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Identify and manage comorbid conditions that may affect asthma control or mimic asthma symptoms (e.g. allergic rhinitis, gastro-oesophageal reflux disease).

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

More information

Effects of pregnancy on asthma control

In Australia the prevalence of asthma in pregnancy is approximately 12%.1112

Most women with asthma experience a change in asthma control while pregnant. Asthma control improves in approximately one in three, and worsens in at least one in three women.13 These changes are unpredictable from woman to woman and from pregnancy to pregnancy.13

During pregnancy, approximately 6% of women with asthma are hospitalised with a severe asthma flare-up.143 In a large Australian cohort of pregnant women, 36% of those with asthma experienced a severe flare-up that required medical intervention, and a further 19% experienced a milder flare-up.3

Although flare-ups occur at any time during gestation, they appear to be more common in the late second trimester.13

Risk factors for flare-ups during pregnancy include1413

  • ‘severe’ asthma (according to older classification based on pattern of symptoms when not treated)
  • nonadherence to preventer medicines
  • viral infections
  • a range of other factors such as obesity and gastro-oesophageal reflux.

In an Australian study, almost one third of women who experienced a severe asthma flare-up during pregnancy reported that they had not been taking their prescribed preventer before the flare-up.15

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Effects of asthma on pregnancy outcomes

Birth weight and related outcomes

Untreated asthma, poorly controlled asthma or asthma flare-ups during pregnancy put mothers and babies at risk:

  • Overall (not taking into account asthma severity or treatment), women with asthma have a higher risk of pre-eclampsia4 and preterm delivery,4 and their infants have a higher risk of low birth weight34 and of being small for gestational age,4 compared with non-asthmatic women.
  • Severe asthma flare-ups (symptoms requiring medical interventions such as hospitalisation, emergency department visits, other unscheduled urgent visits to the doctor, or the use of emergency treatment) during pregnancy increase the risk of low birth weight, compared with infants of women with asthma who do not have any flare-ups during pregnancy.35

Active management of asthma by a health professional reduces the risk of preterm delivery. Among women with asthma that is managed by a health professional, the risk of preterm labour and preterm delivery is not significantly higher than for non-asthmatic pregnant women.4

Inhaled corticosteroid use may reduce the risk of flare-ups during pregnancy.3 Inhaled corticosteroids generally have good safety profiles in pregnant women.8

Although treatment with oral corticosteroids for flare-ups has been associated with low birth weight5 and preterm delivery5 compared with no oral corticosteroid use, it is uncertain whether the effect is due to the treatment itself or to the acute flare-ups.

Congenital malformations

Maternal asthma is associated with increased risk of any congenital malformation, and increased risk of cleft lip with or without cleft palate, but not major congenital malformations or stillbirth.16

The use of bronchodilators and inhaled corticosteroids is not associated with increased risk of congenital malformations.16

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Safety of stepping down treatment during pregnancy

It may not be feasible to step down (e.g. reduce the inhaled corticosteroid dose or cease long-acting beta2 agonist) during pregnancy, because this is usually accomplished over several months while monitoring asthma control.

Several studies have reported deterioration in asthma control after ceasing long-acting beta2 agonist treatment in adults with asthma previously stabilised on inhaled corticosteroid/long-acting beta2 agonist combination.1718 If inhaled corticosteroid/long-acting beta2 agonist combination is replaced by inhaled corticosteroid only, patients should be advised to start taking their old combination inhaler again if asthma worsens within the first few days after switching.

In a woman planning a pregnancy, a failed treatment trial of inhaled corticosteroid alone may demonstrate that she needs to continue taking combination therapy during pregnancy in order to maintain asthma control. 

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Safety of asthma medicines in pregnancy

Published evidence for the safety of asthma medicines during pregnancy is limited mainly to prospective and retrospective cohort studies, and regional or national register databases. Many studies of the safety of asthma medicines in pregnancy have been underpowered.13

Therefore, it is not possible to precisely distinguish the effects on foetuses of asthma treatments from those of maternal asthma; any outcome statistically associated with the use of reliever medicines could be due to either to the medicines or to poor asthma control necessitating reliever use, while any outcome associated with the use of emergency asthma medicines could be due either to the medicines or to the effects of a severe flare-up.

Table. Pregnancy safety categories for asthma and allergic rhinitis medicines Opens in a new window Please view and print this figure separately: https://www.asthmahandbook.org.au/table/show/44

Inhaled corticosteroids

A systematic review of evidence on the safety of regular preventer medicines during pregnancy did not find an association between the use of inhaled corticosteroids during pregnancy and any particular adverse event.9 This finding is consistent with earlier research.13

An adequately powered, large multicenter prospective cohort study found no significant relationships between inhaled corticosteroid use during pregnancy and adverse outcomes such as preterm birth at less than 32 weeks’ gestation, major malformations, low birth weight, and small-for-gestational age infants.19 By maintaining adequate asthma control, inhaled corticosteroid use may protect against low birth weight.1320

Comparison of different formulations and doses

The majority of studies assessing the safety of inhaled corticosteroid use in pregnancy have involved women using budesonide.13  There is insufficient evidence to enable comparison between different inhaled corticosteroids,9 or to make conclusions about ciclesonide (a newer inhaled corticosteroid).9

There is little evidence about safety of different doses of inhaled corticosteroids.9 A study of pregnant women using beclometasone, budesonide or fluticasone propionate found that the rate of congenital malformations among those who used low-to-moderate doses in the first trimester was not higher than for those who did not use inhaled corticosteroids.21 The rate of congenital malformations (mainly musculoskeletal and cardiac malformations) was higher among those who used high doses than those who did not use inhaled corticosteroids.21 However, women who used higher doses of inhaled corticosteroid were older, more likely to have multiple foetuses, and more likely to have severe or uncontrolled asthma.9

The use of high doses of inhaled corticosteroids during pregnancy does not appear to affect foetal adrenal function.22

ICS/LABA combinations

There is insufficient evidence to make conclusions about the combination of inhaled corticosteroids and long-acting beta2 agonists during pregnancy.9

A systematic review of the safety of regular preventer medicines during pregnancy did not find an association between the use of long-acting beta2 agonists during pregnancy and any particular adverse event.9

In a retrospective cohort study of 7376 pregnancies, during which 8.8% women took long-acting beta2 agonists, long-acting beta2 agonist use was not associated with increased risk of low birth weight, preterm birth, or small for gestational age.23

Systemic corticosteroids

Associations have been reported between oral corticosteroid use during pregnancy and preeclampsia, preterm delivery, and reduced birth weight.13 However, it is difficult to separate the effects of the drug from the effects of the flare-up that necessitated its use.13

When systemic corticosteroids are required to manage severe acute asthma during pregnancy, the possible risks are less than the risks of severely uncontrolled asthma, which may result in maternal and/or foetal death.1324

A meta-analysis of cohort studies found an association between the use of oral corticosteroid use and preterm delivery, low birth weight, and small-for-gestational age infants.25 However, use of oral corticosteroids was a marker of severe asthma.25

The use of oral corticosteroids during the first trimester may be associated with a small increase in the risk of oral cleft.26

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Gastro-oesophageal reflux in pregnancy

An estimated 30–50% of pregnant women experience symptomatic gastro-oesophageal reflux disease.27 There is anecdotal evidence that pregnant women commonly develop alkaline reflux, which does not respond to treatment with proton pump inhibitors.

There is little published evidence for the best way to manage gastro-oesophageal reflux (including gastro-oesophageal reflux disease) in women with asthma during pregnancy.

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Allergic rhinitis in pregnancy

The presence of allergic rhinitis is associated with worse asthma control.2829, 30

If continuous treatment is required to manage allergic rhinitis, an intranasal corticosteroid is the first-choice treatment unless contraindicated.31 Budesonide nasal spray is rated pregnancy category A.32

Pregnant women can also experience rhinitis-like symptoms of physiological congestion of nasal mucous membranes, due to pregnancy hormones.

Table. Pregnancy safety categories for asthma and allergic rhinitis medicines Opens in a new window Please view and print this figure separately: https://www.asthmahandbook.org.au/table/show/44

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References

  1. Clifton VL, Hodyl NA, Murphy VE, et al. Effect of maternal asthma, inhaled glucocorticoids and cigarette use during pregnancy on the newborn insulin-like growth factor axis. Growth Horm IGF Res. 2010; 20: 39-48. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19695914
  2. Moldenhauer JS, Lai Y, Schatz M, et al. Influence of maternal asthma and asthma severity on newborn morphometry. J Asthma. 2010; 47: 145-9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20170320
  3. Murphy VE, Clifton VL, Gibson PG. Asthma exacerbations during pregnancy: incidence and association with adverse pregnancy outcomes. Thorax. 2006; 61: 169-76. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2104591/
  4. Murphy VE, Namazy JA, Powell H, et al. A meta-analysis of adverse perinatal outcomes in women with asthma. BJOG. 2011; 118: 1314-1323. Available from: http://onlinelibrary.wiley.com/doi/10.1111/j.1471-0528.2011.03055.x/full
  5. Namazy JA, Murphy VE, Powell H, et al. Effects of asthma severity, exacerbations and oral corticosteroids on perinatal outcomes. Eur Respir J. 2012; 41: 1082-90. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22903964
  6. Schatz M, Harden K, Kagnoff M, et al. Developmental follow-up in 15-month-old infants of asthmatic vs. control mothers. Pediatr Allergy Immunol. 2001; 12: 149-53. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11473679
  7. Schatz M, Dombrowski MP, Wise R, et al. Spirometry is related to perinatal outcomes in pregnant women with asthma. Am J Obstet Gynecol. 2006; 194: 120-6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16389020
  8. Silverman M, Sheffer A, Diaz PV, et al. Outcome of pregnancy in a randomized controlled study of patients with asthma exposed to budesonide. Ann Allergy Asthma Immunol. 2005; 95: 566-70. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16400897
  9. Lim A, Stewart K, Konig K, George J. Systematic review of the safety of regular preventive asthma medications during pregnancy. Ann Pharmacother. 2011; 45: 931-945. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21712513
  10. Powell H, Murphy VE, Taylor RD, et al. Management of asthma in pregnancy guided by measurement of fraction of exhaled nitric oxide: a double-blind, randomised controlled trial. Lancet. 2011; 378: 983-99. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21907861
  11. Clifton VL, Engel P, Smith R, et al. Maternal and neonatal outcomes of pregnancies complicated by asthma in an Australian population. Aust N Z J Obstet Gynaecol. 2009; 49: 619-26. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20070710
  12. Sawicki E, Stewart K, Wong S, et al. Management of asthma by pregnant women attending an Australian maternity hospital. Aust N Z J Obstet Gynaecol. 2012; 52: 183-8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22141407
  13. Murphy VE, Gibson PG. Asthma in pregnancy. Clin Chest Med. 2011; 32: 93-110. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21277452
  14. Ali Z, Ulrik CS. Incidence and risk factors for exacerbations of asthma during pregnancy. J Asthma Allergy. 2013; 6: 53-60. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650884/
  15. Murphy VE, Gibson P, Talbot PI, Clifton VL. Severe asthma exacerbations during pregnancy. Obstet Gynecol. 2005; 106: 1046-1054. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16260524
  16. Murphy VE, Wang G, Namazy JA, et al. The risk of congenital malformations, perinatal mortality and neonatal hospitalisation among pregnant women with asthma: a systematic review and meta-analysis. BJOG. 2013; 120: 812-22. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23530780
  17. Brozek JL, Kraft M, Krishnan JA, et al. Long-acting β2-agonist step-off in patients with controlled asthma: systematic review with meta-analysis. Arch Int Med. 2012; 172: 1365-75. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22928176
  18. Thomas A, Lemanske RF, Jackson DJ. Approaches to stepping up and stepping down care in asthmatic patients. J Allergy Clin Immunol. 2011; 128: 915-924. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3205296/
  19. Schatz M, Dombrowski MP, Wise R, et al. The relationship of asthma medication use to perinatal outcomes. J Allergy Clin Immunol. 2004; 113: 1040-5. Available from: http://www.jacionline.org/article/S0091-6749(04)01149-2/fulltext
  20. Murphy VE, Gibson PG, Smith R, Clifton VL. Asthma during pregnancy: mechanisms and treatment implications. Eur Respir J. 2005; 25: 731-50. Available from: http://erj.ersjournals.com/content/25/4/731
  21. Blais L, Beauchesne MF, Rey E, et al. Use of inhaled corticosteroids during the first trimester of pregnancy and the risk of congenital malformations among women with asthma. Thorax. 2007; 62: 320-328. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2092465/
  22. Ernst P, Suissa S. Systemic effects of inhaled corticosteroids. Curr Opin Pulm Med. 2012; 18: 85-9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22112998
  23. Cossette B, Forget A, Beauchesne MF, et al. Impact of maternal use of asthma-controller therapy on perinatal outcomes. Thorax. 2013; 68: 724-30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23585516
  24. National Asthma Education and Prevention Program. Working Group Report on Managing Asthma During Pregnancy: Recommendations for Pharmacologic Treatment. Update 2004. U.S. Department of of Health and Human Services, National Institutes of Health, National Heart, Lung and Blood Institute, Bethesda, 2005. Available from: http://www.nhlbi.nih.gov/health/prof/lung/asthma/astpreg.htm
  25. Namazy JA, Murphy VE, Powell H, et al. Effects of asthma severity and medication use on prematurity and intrauterine growth: A meta analysis from published data. J Allergy Clin Immunol. 2011; 127: AB153. Available from: http://jacionline.org/article/S0091-6749(10)02550-9/fulltext
  26. Oren D, Nulman I, Makhija M, et al. Using corticosteroids during pregnancy. Are topical, inhaled, or systemic agents associated with risk?. Can Fam Physician. 2004; 50: 1083-5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15455804
  27. Day JP, Richter JE. Medical and surgical conditions predisposing to gastroesophageal reflux disease. Gastroenterol Clin North Am. 1990; 19: 587-607. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2228165
  28. Pawankar R, Bunnag C, Chen Y, et al. Allergic rhinitis and its impact on asthma update (ARIA 2008)–western and Asian-Pacific perspective. Asian Pac J Allergy Immunol. 2009; 27: 237-243. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20232579
  29. Clatworthy J, Price D, Ryan D, et al. The value of self-report assessment of adherence, rhinitis and smoking in relation to asthma control. Prim Care Respir J. 2009; 18: 300-5. Available from: http://www.nature.com/articles/pcrj200937
  30. Price D, Zhang Q, Kocevar VS, et al. Effect of a concomitant diagnosis of allergic rhinitis on asthma-related health care use by adults. Clin Exp Allergy. 2005; 35: 282-7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15784104
  31. National Asthma Council Australia. Managing allergic rhinitis in people with asthma. An information paper for health professionals. National Asthma Council Australia, Melbourne, 2012. Available from: http://www.nationalasthma.org.au/publication/allergic-rhinitis-asthma-hp
  32. AstraZeneca Pty Ltd. Product information: Rhinocort (budesonide for nasal inhalation). Therapeutic Goods Administration, Canberra, 2009. Available from: https://www.ebs.tga.gov.au