Risk of Autism Spectrum Disorder According to the Dose and Trimester of Exposure to Antiseizure Medications: A Systematic Review and Meta-Analysis

Background The association between prenatal exposure to antiseizure medications (ASM) and autism spectrum disorder has been documented. This study sought to examine and synthesize evidence from studies that have evaluated these associations, with particular focus on the trimester of pregnancy and dosage of exposure. Methods PubMed, Embase, and PsycINFO databases were searched following strict inclusion/exclusion criteria. 10 studies were recruited involving children born to mothers with epilepsy who took ASM during pregnancy as cases, and those with epilepsy who did not take any ASM in pregnanc. Results The relative risk of developing ASD among children exposed to valproic acid (RR, 3.90 [95% CI: 2.36–6.44]), was twice higher than that of carbamazepine (RR, 1.65 [95% CI: 0.62–4.37]), or lamotrigine (RR, 1.60 [95% CI: 0.77–3.32]) The trimester of exposure and dosage of ASM administered were inconsistent. Conclusion In summary, prenatal exposure to ASM increased the risk of developing ASD in children. The relative risk was twice as high in those exposed to valproic acid compared to those exposed to carbamazepine or lamotrigine. Trimester of pregnancy and dosage of ASM used by the mothers were not consistent .