Maternal Use of Anti-asthmatic Drugs and Infant Congenital Malformations

  • Bengt Källén


Most likely there is an association between maternal use of anti-asthmatic drugs and infant congenital malformations. It is not strong and appears rather unspecific as it can be seen after different types of anti-asthmatic drugs and on some different malformation types. It is likely that these effects to a large extent are due to confounding by indication so that they are caused by underlying asthma disease. It is important that women with asthma get necessary therapy during pregnancy and there seems to be little difference in the teratogenic effect of at least most used drugs. For some drug types, available information is limited, e.g., for xanthine derivatives and leukotriene antagonists, and further data are needed. The available information does not indicate any marked risks with these drugs, still less is known about the use of the monoclonal anti-IgE antibody omalizumab.


  1. Alexander S, Dodds L, Armson BA. Perinatal outcomes in women with asthma during pregnancy. Obstet Gynecol. 1998;92:435–40.PubMedGoogle Scholar
  2. Bakhireva LN, Jones KL, Schatz M, Klonoff-Cohen HS, Johnson D, Slymen DJ, Chamgers CD. Safety of leukotriene receptor antagonists in pregnancy. J Allergy Clin Immunol. 2007;119:618–25.CrossRefGoogle Scholar
  3. Blais L, Forget A. Asthma exacerbations during the first trimester of pregnancy and the risk of congenital malformations among asthmatic women. J Allergy Clin Immunol. 2008;121:1379–84.CrossRefGoogle Scholar
  4. Blais L, Beauchesne M-F, Rey È, Malo J-L, Forget A. Use of inhaled corticosteroids during the first trimester of pregnancy and the risk of congenital malformations among women with asthma. Thorax. 2007;62:320–8.CrossRefGoogle Scholar
  5. Blais L, Beauchesne M-F, Lemière C, Eltouh N. High doses of inhaled corticosteroids during the first trimester of pregnancy and congenital malformations. J Allergy Clin Immunol. 2009;124:1229–34.CrossRefGoogle Scholar
  6. Blais L, Kettani F-Z, Elftouh N, Forget A. Effect of maternal asthma on the risk of specific congenital malformations: a population-based cohort study. Birth Defects Res A Clin Mol Teratol. 2010;88:216–22.PubMedGoogle Scholar
  7. Charlton RA, Snowball JM, Nightingale AL, Davis KJ. Safety of fluticasone prescribed for asthma during pregnancy; a UK population-based study. J Allergy Clin Immunol Pract. 2015;3:772–9.CrossRefGoogle Scholar
  8. Demissie K, Breckenridge MB, Rhoads GG. Infant and maternal outcomes in the pregnancies of asthmatic women. Am J Respir Crit Care Med. 1998;158:1091–5.CrossRefGoogle Scholar
  9. Eltony S, Forget A, Blais L. Beta2-agonists use during pregnancy and the risk of congenital malformations. Birth Defects Res A Clin Mol Teratol. 2011;91:937–47.CrossRefGoogle Scholar
  10. Eltony S, Forget A, Beauchesne M-F, Blais L. Risk of congenital malformations for asthmatic pregnant women using a long-acting β2-agonist and inhaled corticosteroid combination versus higher-dose inhaled corticosteroid monotherapy. J Allergy Clin Immunol. 2015;135:123–30.CrossRefGoogle Scholar
  11. Garne E, Hansen AV, Morris J, Zaupper L, Addor M-C, Barisic I, Gatt M, Lelong N, Klungsøyr K, O’Mahony M, Nelen V, Neville AJ, Pierini A, Tucker D, de Walle H, Wiesel A, Loane M, Dolk H. Use of asthma medication during pregnancy and risk of specific malformations: a European case-malformed control study. J Allergy Clin Immunol. 2015;136:1496–502.CrossRefGoogle Scholar
  12. Greenberger PA, Patterson R. Beclomethasone dipropionate for severe asthma during pregnancy. Ann Intern Med. 1983;98:478–80.CrossRefGoogle Scholar
  13. Källén B. Maternal asthma and use of antiasthmatic drugs in early pregnancy and congenital malformations in the offspring. J Pulm Respir Med. 2004;4:166.
  14. Källén B. Maternal use of montelukast in early pregnancy and infant congenital malformations. Pulm Crit Care Med. 2016;1:1–4.CrossRefGoogle Scholar
  15. Källén B, Otterblad Olausson P. Use of anti-asthmatic drugs during pregnancy. 3. Congenital malformations in the infants. Eur J Clin Pharmacol. 2007;63:383–8.CrossRefGoogle Scholar
  16. Källén B, Rydhstroem H, Åberg A. Congenital malformations after the use of inhaled budesonide in early pregnancy. Obstet Gynecol. 1999;93:392–5.PubMedGoogle Scholar
  17. Källén B, Rydhstroem H, Åberg A. Asthma during pregnancy—a population based study. Eur J Epidemiol. 2000;18:167–71.CrossRefGoogle Scholar
  18. Lin S, Munsie JPW, Herdt-Losavio ML, Bell E, Druschel C, Romitti PA, Olney R, The National Birth Defects Prevention Study. Maternal asthma medication use and the risk of gastroschisis. Am J Epidemiol. 2008;168:73–9.CrossRefGoogle Scholar
  19. Lin S, Herdt-Losavio M, Gensburg L, Marshall E, Druschel C. Maternal asthma, asthma medication use, and the risk of congenital heart defects. Birth Defects Res A Clin Mol Teratol. 2009;85:161–8.CrossRefGoogle Scholar
  20. Lin S, Munsie JPW, Herdt-Losavio ML, Druschel CM, Campbell K, Browne ML, Romitti PA, Olney RS, Bell EM, The National Birth Defects Prevention Study. Maternal asthma medication use and the risk of gastroschisis. Pediatrics. 2013;129:e317. CrossRefGoogle Scholar
  21. Liu S, Wen SW, Demissie K, Marcoux S, Kramer MS. Maternal asthma and pregnancy outcome: a retrospective cohort study. Am J Obstet Gynecol. 2001;184:90–6.CrossRefGoogle Scholar
  22. Merck. Pregnancy registry to Singulair®: the 8th annual report 2006. West Point: Merck Research Laboratories; 2007.Google Scholar
  23. Munsie J-PW, Lin S, Browne ML, Campbell KA, Caton AR, Bell EM, Rasmussenn SA, Romitti PA, Druschel CM, The National Birth Defects Prevention Study. Maternal bronchodilator use and the risk of orofacial clefts. Hum Reprod. 2011;26:3147–54.CrossRefGoogle Scholar
  24. Namazy J, Cabane MD, Scheuerle AE, Thhorp JM Jr, Chen H, Carrigan G, Wang Y, Veith J, Andrews EB. The Xolair pregnancy register (EXPECT): the safety of omalizumab use during pregnancy. J Allergy Clin Immunol. 2015;135:407–12.CrossRefGoogle Scholar
  25. Nelsen LM, Shields KE, Cunningham ML, Stoles JM, Bamshad MJ, Eng PM, Smugar SS, Gould AL, Philip G. Congenital malformations among infants born to women receiving montelukast, inhaled corticosteroids, and other asthma medications. Letter to the editor. J Allergy Clin Immunol. 2012;129:251.CrossRefGoogle Scholar
  26. Olesen C, Trane N, Nielsen GL, Sørensen HT, Olsen J, For the EuroMAP Group. A population-based prescription study of asthma drugs during pregnancy: changing the intensity of asthma therapy and perinatal outcomes. Respiration. 2001;68:256–61.CrossRefGoogle Scholar
  27. Sarkar M, Koren G, Kalra S, Ying A, Smorlesi C, De Santis M, Diav-Citrin O, Avgil M, Lavigne SV, Berkovich M, Einarson A. Montelukast use during pregnancy; a multicentre, prospective, comparative study of infant outcomes. Eur J Clin Pharmacol. 2009;65:1259–64.CrossRefGoogle Scholar
  28. Schatz M, Zeiger RS, Harden KM, Hoffman CC, Forsythe AB, Chilingar LM, Porreco RP, Benenson A, Sperling WL, Saunders BS, ED K. The safety of inhaled β-agonist bronchodilators during pregnancy. J Allergy Clin Immunol. 1988;82:686–95.CrossRefGoogle Scholar
  29. Schatz M, Zeiger RS, Hoffman CP, Harden K, Forsythe A, Chilingar L, Saunders B, Porreco R, Sperling W, Kagnoff M, Benenson AS. Perinatal outcomes in the pregnancies of asthmatic women: a prospective controlled analysis. Am J Respir Crit Care Med. 1995;151:1170–4.PubMedGoogle Scholar
  30. Schatz M, Zeiger RS, Harden K, Hoffman CC, Chilingar L, Petitti D. The safety of asthma and allergy medications during pregnancy. J Allergy Clin Immunol. 1997;100:301–6.CrossRefGoogle Scholar
  31. Tamasi L, Somoskövi A, Müller V, Bártfai Z, Acs N, Puhó E, Czeizel AE. A population-based case-control study on the effect of bronchial asthma during pregnancy for congenital abnormalities of the offspring. J Asthma. 2006;43:81–6.CrossRefGoogle Scholar
  32. Tata LJ, Lewis SA, McKeever TM, Smith CJP, Doyle P, Smeeth L, Gibson JE, Hubbard RB. Effect of maternal asthma, exacerbations and asthma medication use on congenital malformations in offspring: a UK population-based study. Thorax. 2008;63:981–7.CrossRefGoogle Scholar
  33. Vasilakis-Scaramozza C, Aschengrau A, Cabral HJ, Jick JJ. Asthma drugs and the risk of congenital anomalies. Pharmacotherapy. 2013;33:363–8.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Bengt Källén
    • 1
  1. 1.Tornblad Institute for Comparative EmbryologyLund UniversityLundSweden

Personalised recommendations