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. 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.