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

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.