Association of prenatal exposure to antiseizure medication with risk of autism: a systematic review and meta-analysis

Abstract

Background: Antiseizure medications (ASMs) can affect neurodevelopment and cause congenital malformations. Autism spectrum disorder (ASD) is characterized by challenges in communication, behavior, and learning. This study evaluated the association between prenatal ASM exposure and ASD development. Methods: A systematic review and meta-analysis was conducted using PubMed, Scopus, Web of Science, and Cochrane databases to identify studies on fetal ASM exposure and ASD. Hazard ratio (HR) and risk ratio (RR) with 95 % confidence interval (CI) were pooled using a random-effects model. Heterogeneity was assessed using I² statistic. A p-value < 0.05 was considered significant. Results: 10 studies were included in our meta-analysis, comprising 54,747 patients exposed to ASM. Prenatal ASM exposure significantly increased the risk of ASD (HR 1.8082; 95 % CI 1.2616 to 2.5916; P = 0.001; RR 2.0401; 95 % CI 1.7588 to 2.3664; P < 0.0001). Subgroup analyses identified elevated risks with specific ASMs, including carbamazepine (HR 1.2213; 95 % CI 1.0047 to 1.4847; P = 0.045; I² = 0 %), valproate (HR 2.8306; 95 % CI 2.3881 to 3.3550; P < 0.001; I² = 0 %), and oxcarbazepine (HR 1.6141; 95 % CI 1.1500 to 2.2655; P = 0.006; I² = 27 %). Among women with epilepsy, prenatal ASM exposure increased ASD risk (RR 1.4174; 95 % CI 1.2345 to 1.6273; P < 0.0001; I² = 0 %). Conclusions: This meta-analysis showed that prenatal exposure to antiseizures, particularly valproate, carbamazepine, and oxcarbazepine, significantly increases ASD risk. These findings emphasize the need for cautious ASM use during pregnancy.