First-trimester asthma controller medication use and major congenital malformation risk in offspring of women with asthma: A nationwide population-based cohort study

Abstract

Background: Evidence regarding the safety of asthma controller medications (particularly montelukast) for the fetus remains insufficient and controversial.

Objective: We sought to comprehensively evaluate the association between first-trimester use of 5 common asthma controller regimens and the risk of major congenital malformations in the offspring of women with asthma.

Methods: We conducted a population-based cohort study using data from the AMerican PREGNANcy Mother-Child CohorT (AM-PREGNANT) from 2003 to 2021, which primarily comprises individuals with private insurance coverage in the United States. Singleton live births to mothers with asthma were included. Exposure was based on first-trimester prescription fills for asthma controller medications. The outcomes included major congenital malformations overall, organ-specific malformations, and 2 specific defects.

Results: We identified 44,435 eligible pregnancies. Compared with the no asthma controller medication group, none of the 5 controller medication groups (montelukast monotherapy, inhaled corticosteroid [ICS] monotherapy, ICS + long-acting β₂-adrenergic agonist [LABA] combination, montelukast + ICS combination, montelukast + ICS + LABA combination) was associated with an increased risk of major congenital malformations. The montelukast + ICS combination group was associated with an increased risk of cleft palate and/or lip compared with the no asthma controller medication group, but the number of events was limited (<5).

Conclusions: Among pregnant women with asthma, first-trimester exposure to any of the 5 common asthma controller regimens in this study was not associated with an increased risk of major congenital malformations. Further studies are needed to confirm the association between the montelukast + ICS combination regimen and the risk of cleft palate and/or lip.

Keywords: Asthma; inhaled corticosteroids; long-acting β(2)-adrenergic agonists; major congenital malformations; montelukast; pregnancy.