Skip to main content

Advertisement

SpringerLink
Log in

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

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Background

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.

Objectives

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.

Methods

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.

Results

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.

Conclusions

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Dombrowski MP (2004) Asthma during pregnancy. Am Coll Obstet Gynecol 103:5–12

    Google Scholar 

  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 26:29–62

    Article  PubMed  Google Scholar 

  3. Frezzo T, McMahon CL, Pergament E (2002) Asthma and pregnancy. IL Teratogen Inf Serv 9(2):1–5

    Google Scholar 

  4. Källén B, Rydhstroem H, Aberg A (2000) Asthma during pregnancy – a population based study. Eur J Epidem 16:167–171

    Article  Google Scholar 

  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):81–86

    Article  PubMed  Google Scholar 

  6. Murphy VE, Clifton VL, Gibson PG (2006) Asthma exacerbations during pregnancy: incidence and association with adverse pregnancy outcomes. Thorax 61:169–176

    Article  CAS  PubMed  Google Scholar 

  7. Alexander S, Dodds L, Armson BA (1998) Perinatal outcomes in women with asthma during pregnancy. Obstet Gynecol 92:435–440

    Article  CAS  PubMed  Google Scholar 

  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):375–381

    Article  Google Scholar 

  9. Demissie K, Breckenridge MB, Rhoads GG (1998) Infant and maternal outcomes in the pregnancies of asthmatic women. Am J Respir Crit Care Med 158:1091–1095

    CAS  PubMed  Google Scholar 

  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 18:237–240

    Article  PubMed  Google Scholar 

  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 18:107–112

    Article  PubMed  Google Scholar 

  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 21:227–232

    CAS  Google Scholar 

  13. Tan KS, Thomson NC (2000) Asthma in pregnancy. Am J Med 109:727–733

    Article  CAS  PubMed  Google Scholar 

  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. www.merckpregnancyregistries.com

  15. Gluck JC, Gluck PA (2005) Asthma controller therapy during pregnancy. Am J Obstet Gynecol 192(2):369–380

    Article  PubMed  Google Scholar 

  16. Spector SL for the Anti-leukotriene Working Group (2001) Safety of anti-leukotriene agents in asthma management. Ann Allergy Asthma Immunol 86:18–22

    CAS  PubMed  Google Scholar 

  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 84:475–480

    Google Scholar 

  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):618–625

    Article  CAS  Google Scholar 

  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):383–388

    Article  Google Scholar 

  20. Finer LB, Henshaw SK (2006) Disparities in rates of unintended pregnancies in the United States. Perspect Sex Reprod Health 38(2):90–96

    Article  PubMed  Google Scholar 

  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):749–752

    Article  PubMed  Google Scholar 

  22. Holmes LB (1999) Need for inclusion and exclusion criteria for the structural abnormalities recorded in children born from exposed pregnancies. Teratology 59(1):1–2

    Article  CAS  PubMed  Google Scholar 

  23. Freedman B, Koren G (2002) Reliability of maternal reporting in identifying major congenital malformations. Vet Hum Toxicol 44(3):180–181

    PubMed  Google Scholar 

  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 101:137–143

    Article  PubMed  Google Scholar 

  25. Ziegler A (2005) Asthma management during pregnancy. J Arkan Med Soc 102(1):20–24

    Google Scholar 

  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 112:283–288

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Motherisk Program, Toronto, Canada

    Moumita Sarkar, Gideon Koren, Sanjog Kalra, Angela Ying & Adrienne Einarson

  2. Servicio di Tossicologica Perinatale, Firenze, Italy

    Carlo Smorlesi

  3. Telefono Rosso, Rome, Italy

    Marco De Santis

  4. Israel Teratogen Information, Jerusalem, Israel

    Orna Diav-Citrin & Meytal Avgil

  5. Connecticut Pregnancy Riskline, West Hartford, CT, USA

    Sharon Voyer Lavigne

  6. Tel Aviv University, Tel Aviv, Israel

    Matti Berkovich

  7. Division of Clinical Pharmacology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G1X8, Canada

    Moumita Sarkar

Authors
  1. Moumita Sarkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gideon Koren
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sanjog Kalra
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Angela Ying
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carlo Smorlesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marco De Santis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Orna Diav-Citrin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Meytal Avgil
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sharon Voyer Lavigne
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Matti Berkovich
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Adrienne Einarson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Moumita Sarkar.

Additional information

All the authors guarantee that this is original work, has not been previously published and is not currently under review at another journal. Each has approved the submission of this manuscript to European Journal of Clinical Pharmacology.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sarkar, M., Koren, G., Kalra, S. et al. Montelukast use during pregnancy: a multicentre, prospective, comparative study of infant outcomes. Eur J Clin Pharmacol 65, 1259–1264 (2009). https://doi.org/10.1007/s00228-009-0713-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-009-0713-9

Keywords

Search

Navigation