In utero beta-2-adrenergic agonists exposure and risk of epilepsy: A Danish nationwide population-based cohort study

Abstract

Purpose: To examine the association between maternal use of beta-2-adrenergic agonists (β2AAs) and the risk of epilepsy in offspring.

Methods: A nationwide retrospective cohort study was performed based on Danish registries. Children of mothers who used β2AAs during pregnancy were allocated to the exposed group and other children to the unexposed group. The outcome was a diagnosis of epilepsy. Cox regression was performed to estimate the hazard ratios (HRs) of epilepsy after adjusting for parental and children factors. To evaluate confounding by indication, we extended the exposure time window from 2 years before pregnancy and stratified the analyses by maternal asthma, in particular analyses by trimesters.

Results: The exposed children had a 1.24-fold risk of epilepsy (HR = 1.24, 95% confidence interval [CI]: 1.12, 1.38). Compared with no prenatal exposure from 2 years before pregnancy through delivery, the HR was 1.11 (95% CI: 1.01, 1.22) in children of mothers with β2AAs use only before pregnancy, 1.28 (95% CI: 1.09, 1.50) only during pregnancy, and 1.23 (95% CI: 1.07, 1.41) both before and during pregnancy. The increased risk was only observed in children of mothers with β2AAs use in the first (HR = 1.33, 95% CI: 1.01, 1.75) or second trimesters (HR = 1.35, 95% CI: 1.05, 1.74), but not the third trimester.

Conclusions: In utero exposure to β2AAs, particularly in the first or second trimesters, may be associated with an increased risk of epilepsy. It may partly be due to the indication of β2AAs use, but a direct effect of β2AAs cannot be ruled out.

Keywords: asthma; beta-2-adrenergic agonists; epilepsy; pharmacoepidemiology; pregnancy.