European Journal of Clinical Pharmacology

, Volume 65, Issue 12, pp 1259–1264 | Cite as

Montelukast use during pregnancy: a multicentre, prospective, comparative study of infant outcomes

  • Moumita SarkarEmail author
  • Gideon Koren
  • Sanjog Kalra
  • Angela Ying
  • Carlo Smorlesi
  • Marco De Santis
  • Orna Diav-Citrin
  • Meytal Avgil
  • Sharon Voyer Lavigne
  • Matti Berkovich
  • Adrienne Einarson
Pharmacoepidemiology and Prescription



Montelukast (Singulair) is a selective leukotriene receptor antagonist (LTRA) indicated for the maintenance treatment of asthma. Currently, there are limited prospective, comparative studies in the literature examining the safety of montelukast use in pregnancy.


The primary objective of this study was to determine whether exposure to montelukast during pregnancy increases the rate of major malformations above the 1–3% baseline risk or the rate of other adverse effects.


Pregnant women taking montelukast were enrolled in the study from six teratogen information services around the world. These women were compared to two other groups of women: (1) disease-matched, who used inhalers for a similar indication and (2) women not diagnosed with asthma and not exposed to any known teratogens. The primary outcome was major malformations and secondary endpoints included spontaneous abortion, fetal distress, gestational age at birth and birth weight.


Out of 180 montelukast-exposed pregnancies, there were 160 live births including three sets of twins, 20 spontaneous abortions, 2 elective abortions and 1 major malformation reported. The mean birth weight was lower (3,214 ± 685 g) compared to controls [3,356 ± 657 (disease-matched) and 3,424 ± 551 (exposed to non-teratogens), P = 0.038] and the gestational age was shorter [37.8 ± 3.1 weeks (montelukast) and 37.6 ± 4.4 (disease-matched) versus 39.3 ± 2.4 weeks (exposed to non-teratogens), P = 0.045]. About 25% of the newborns had fetal distress, a higher rate than controls (P = 0.007). However, upon sub-analysis of women who continued the drug until delivery, only birth-weight difference (304 g) remained significant.


Montelukast does not appear to increase the baseline rate of major malformations. The lower birth weight in both asthma groups is most likely associated with the severity of the maternal condition.


Asthma Malformations Pregnancy Montelukast Preterm delivery Low birth weight 


  1. 1.
    Dombrowski MP (2004) Asthma during pregnancy. Am Coll Obstet Gynecol 103:5–12Google Scholar
  2. 2.
    Kwon HL, Triche EW, Belanger K, Bracken MB (2006) The epidemiology of asthma during pregnancy: prevalence, diagnosis, and symptoms. Immunol Allergy Clin North Am 26:29–62CrossRefPubMedGoogle Scholar
  3. 3.
    Frezzo T, McMahon CL, Pergament E (2002) Asthma and pregnancy. IL Teratogen Inf Serv 9(2):1–5Google Scholar
  4. 4.
    Källén B, Rydhstroem H, Aberg A (2000) Asthma during pregnancy – a population based study. Eur J Epidem 16:167–171CrossRefGoogle Scholar
  5. 5.
    Tamási L, Somoskövi A, Müller V, Bártfai Z, Acs N, Puhó E, Czeizel AE (2006) A population-based case-control study on the effect of bronchial asthma during pregnancy for congenital abnormalities of the offspring. J Asthma 43(1):81–86CrossRefPubMedGoogle Scholar
  6. 6.
    Murphy VE, Clifton VL, Gibson PG (2006) Asthma exacerbations during pregnancy: incidence and association with adverse pregnancy outcomes. Thorax 61:169–176CrossRefPubMedGoogle Scholar
  7. 7.
    Alexander S, Dodds L, Armson BA (1998) Perinatal outcomes in women with asthma during pregnancy. Obstet Gynecol 92:435–440CrossRefPubMedGoogle Scholar
  8. 8.
    Källén B, Otterblad Olausson P (2007) Use of anti-asthmatic drugs during pregnancy. 2. Infant characteristics excluding congenital malformations. Eur J Clin Pharm 63(4):375–381CrossRefGoogle Scholar
  9. 9.
    Demissie K, Breckenridge MB, Rhoads GG (1998) Infant and maternal outcomes in the pregnancies of asthmatic women. Am J Respir Crit Care Med 158:1091–1095PubMedGoogle Scholar
  10. 10.
    Sheiner E, Mazor M, Levy A, Wiznitzer A, Bashiri A (2005) Pregnancy outcome of asthmatic patients: a population-based study. J Matern Fetal Neonatal Med 18:237–240CrossRefPubMedGoogle Scholar
  11. 11.
    Acs N, Puho E, Banhidy F, Czeizel AE (2005) Association between bronchial asthma in pregnancy and shorter gestational age in a population-based study. J Matern Fetal Neonatal Med 18:107–112CrossRefPubMedGoogle Scholar
  12. 12.
    Jana N, Vasishta K, Saha SC, Khunnu B (1995) Effect of bronchial asthma on the course of pregnancy, labour and perinatal outcome. J Obstet Gynaecol 21:227–232Google Scholar
  13. 13.
    Tan KS, Thomson NC (2000) Asthma in pregnancy. Am J Med 109:727–733CrossRefPubMedGoogle Scholar
  14. 14.
    Merck Research Laboratories (2006) Seventh annual report on exposure during pregnancy from the Merck Pregnancy Registry for SINGULAIR (montelukast sodium) covering the period from U.S. approval (February 20, 1998) through May 22, 2006. Merck Research Labs, West Point, PA.
  15. 15.
    Gluck JC, Gluck PA (2005) Asthma controller therapy during pregnancy. Am J Obstet Gynecol 192(2):369–380CrossRefPubMedGoogle Scholar
  16. 16.
    Spector SL for the Anti-leukotriene Working Group (2001) Safety of anti-leukotriene agents in asthma management. Ann Allergy Asthma Immunol 86:18–22PubMedGoogle Scholar
  17. 17.
    American College of Obstetricians and Gynecologists and the American College of Allergy, Asthma and Immunology (2000) Position statement: the use of newer asthma and allergy medications during pregnancy. Ann Allergy Asthma Immunol 84:475–480Google Scholar
  18. 18.
    Bakhireva LN, Jones KL, Schatz M, Klonoff-Cohen HS, Johnson D, Slymen DJ, Chambers CD (2007) Safety of leukotriene receptor antagonists in pregnancy. J Aller Clin Immunol 119(3):618–625CrossRefGoogle Scholar
  19. 19.
    Källén B, Otterblad Olausson P (2007) Use of anti-asthmatic drugs during pregnancy. 3. Congenital malformations in the infant. Eur J Clin Pharm 63(4):383–388CrossRefGoogle Scholar
  20. 20.
    Finer LB, Henshaw SK (2006) Disparities in rates of unintended pregnancies in the United States. Perspect Sex Reprod Health 38(2):90–96CrossRefPubMedGoogle Scholar
  21. 21.
    Einarson A, Pistelli A, DeSantis M, Malm H, Paulus WD, Panchaud A, Kennedy D, Einarson TR, Koren G (2008) Evaluation of the risk of congenital cardiovascular defects associated with use of paroxetine during pregnancy. Am J Psychiatry 165(6):749–752CrossRefPubMedGoogle Scholar
  22. 22.
    Holmes LB (1999) Need for inclusion and exclusion criteria for the structural abnormalities recorded in children born from exposed pregnancies. Teratology 59(1):1–2CrossRefPubMedGoogle Scholar
  23. 23.
    Freedman B, Koren G (2002) Reliability of maternal reporting in identifying major congenital malformations. Vet Hum Toxicol 44(3):180–181PubMedGoogle Scholar
  24. 24.
    Bakhireva LN, Schatz M, Jones KL, Chambers CD (2008) Asthma control during pregnancy and the risk of preterm delivery or impaired fetal growth. Ann Allergy Asthma Immunol 101:137–143PubMedCrossRefGoogle Scholar
  25. 25.
    Ziegler A (2005) Asthma management during pregnancy. J Arkan Med Soc 102(1):20–24Google Scholar
  26. 26.
    Schatz M, Dombrowski MP, Wise R, Thom EA, Landon M, Mabie W et al (2003) Asthma morbidity during pregnancy can be predicted by severity classification. J Aller Clin Immunol 112:283–288CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Moumita Sarkar
    • 1
    • 7
    Email author
  • Gideon Koren
    • 1
  • Sanjog Kalra
    • 1
  • Angela Ying
    • 1
  • Carlo Smorlesi
    • 2
  • Marco De Santis
    • 3
  • Orna Diav-Citrin
    • 4
  • Meytal Avgil
    • 4
  • Sharon Voyer Lavigne
    • 5
  • Matti Berkovich
    • 6
  • Adrienne Einarson
    • 1
  1. 1.The Motherisk ProgramTorontoCanada
  2. 2.Servicio di Tossicologica PerinataleFirenzeItaly
  3. 3.Telefono RossoRomeItaly
  4. 4.Israel Teratogen InformationJerusalemIsrael
  5. 5.Connecticut Pregnancy RisklineWest HartfordUSA
  6. 6.Tel Aviv UniversityTel AvivIsrael
  7. 7.Division of Clinical PharmacologyThe Hospital for Sick ChildrenTorontoCanada

Personalised recommendations