Antiseizure medication use during pregnancy and neonatal growth outcomes: A systematic review and meta-analysis

Abstract

Aims: We aimed to systematically synthesize the current published literature on neonatal growth outcomes associated with antiseizure medication (ASM) use during pregnancy.

Methods: We searched seven databases, from inception to 23 March 2022. We investigated small for gestational age (SGA) and low birth weight (LBW) as primary outcomes and birth weight, birth height, cephalization index and head circumference as secondary outcomes. The primary analysis included pregnant people exposed to any ASM compared with unexposed pregnant people. Subgroup analysis included ASM class analysis, within epilepsy group analysis and polytherapy compared to monotherapy.

Results: We screened 15 720 citations and included 65 studies in the review. Exposed pregnant people had a significantly increased risk of SGA relative risk (RR) 1.33 (95% CI 1.18 to 1.50, I² 74%), LBW RR 1.54 (95% CI 1.33 to 1.77, I² 67%), and decreased birth weight with a mean difference (MD) of -118.87 (95% CI -161.03 to -76.71, I² 42%) g. A non-significant risk change in birth height and head circumference was observed. In subgroup analysis, ASM polytherapy, within epilepsy and ASM class analysis were also associated with an increased risk of SGA and LBW.

Conclusions: This meta-analysis demonstrates that pregnant people exposed to ASMs have a significantly increased risk of adverse fetal growth outcomes including SGA and LBW and decreased birth weight compared to unexposed pregnant people. Polytherapy was associated with higher risks compared to monotherapy. Additional studies are warranted on specific ASM risks.

Keywords: antiepileptic medication; antiseizure medications; birth outcomes; epilepsy; fetal safety; low birth weight; small for gestational age.