Prenatal exposure to Antiseizure Medications for all indications and the risk of neurodevelopmental disorders in offspring: a nationwide population-based cohort study in South Korea

PURPOSE: Antiseizure medications (ASMs) are used during pregnancy for both epilepsy and non-epilepsy indications, yet the neurodevelopmental safety of prenatal ASM exposure remains uncertain, particularly in Asian populations. We evaluated the risk of neurodevelopmental disorders (NDDs) following in utero ASM exposure using a nationwide Korean database. METHODS: This population-based cohort study (2009-2021) used the Korea National Health Insurance Database to identify 3663,052 mother-infant pairs. ASM exposure was defined as ≥1 prescription between the last menstrual period and delivery. Using 1:5 propensity score matching to balance baseline covariates, we estimated adjusted hazard ratios (aHRs) for autism spectrum disorder (ASD) and intellectual disability (ID). RESULTS: After matching, 9587 ASM-exposed and 47,935 unexposed mother-infant pairs were included; among ASM users, 48.2% had epilepsy. Prenatal ASM exposure was associated with significantly increased risks of ASD (aHR 1.57; 95% CI 1.15-2.15) and ID (aHR 2.40; 95% CI 1.80-3.19). A dose-response pattern was observed, with higher risks for duotherapy (ID: aHR 3.23; 95% CI 1.79-5.83) than for monotherapy (ID: aHR 1.74; 95% CI 1.24-2.45). Prolonged exposure and later pregnancy recognition were associated with the highest risks. Among single-trimester exposures, first-trimester-only exposure showed the strongest association with composite outcomes. CONCLUSION: In this nationwide Korean cohort, prenatal ASM exposure was associated with dose-dependent risks of ASD and ID. These findings underscore the importance of preconception counseling and early pregnancy management for all women receiving ASMs, beyond those with epilepsy.