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


OBJECTIVE
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.
Sarkar
Moumita
M
The Motherisk Program, Toronto, Canada. moumita.sarkar@sickkids.ca
Koren
Gideon
G
Kalra
Sanjog
S
Ying
Angela
A
Smorlesi
Carlo
C
De Santis
Marco
M
Diav-Citrin
Orna
O
Avgil
Meytal
M
Lavigne
Sharon Voyer
SV
Berkovich
Matti
M
Einarson
Adrienne
A
D000085:Acetates / Q000009:adverse effects* / Q000627:therapeutic use*; D000328:Adult; D001249:Asthma / Q000188:drug therapy*; D003521:Cyclopropanes; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D020024:Leukotriene Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011256:Pregnancy Outcome; D011446:Prospective Studies; D011804:Quinolines / Q000009:adverse effects* / Q000627:therapeutic use*; D013440:Sulfides
D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; C093875:montelukast
Immunol Allergy Clin North Am. 2006 Feb;26(1):29-62
16443142
Am J Respir Crit Care Med. 1998 Oct;158(4):1091-5
9769265
J Allergy Clin Immunol. 2003 Aug;112(2):283-8
12897733
J Matern Fetal Neonatal Med. 2005 Oct;18(4):237-40
16318973
J Ark Med Soc. 2005 Jul;102(1):20-4
16032927
J Matern Fetal Neonatal Med. 2005 Aug;18(2):107-12
16203595
Obstet Gynecol. 2004 Jan;103(1):5-12
14704237
Ann Allergy Asthma Immunol. 2001 Jun;86(6 Suppl 1):18-23
11426912
Ann Allergy Asthma Immunol. 2008 Aug;101(2):137-43
18727468
Vet Hum Toxicol. 2002 Jun;44(3):180-1
12046978
J Allergy Clin Immunol. 2007 Mar;119(3):618-25
17336611
J Obstet Gynaecol (Tokyo 1995). 1995 Jun;21(3):227-32
8590358
Am J Obstet Gynecol. 2005 Feb;192(2):369-80
15695974
J Asthma. 2006 Jan-Feb;43(1):81-6
16448971
Thorax. 2006 Feb;61(2):169-76
16443708
Eur J Clin Pharmacol. 2007 Apr;63(4):375-81
17265059
Teratology. 1999 Jan;59(1):1-2
9988874
Obstet Gynecol. 1998 Sep;92(3):435-40
9721785
Eur J Clin Pharmacol. 2007 Apr;63(4):383-8
17279357
Ann Allergy Asthma Immunol. 2000 May;84(5):475-80
10830999
Eur J Epidemiol. 2000 Feb;16(2):167-71
10845267
Perspect Sex Reprod Health. 2006 Jun;38(2):90-6
16772190
Am J Med. 2000 Dec 15;109(9):727-33
11137489
Am J Psychiatry. 2008 Jun;165(6):749-52
18381907