Paternal exposure to antiseizure medications and offspring outcomes: a systematic review and meta-analysis of observational studies

Introduction: To assess the risk of adverse offspring outcomes related to paternal antiseizure treatment during conception. Methods: We identified studies of offspring outcomes for fathers with vs. without antiseizure medication(s) during conception in Embase/Medline in 01/2025. Study quality was evaluated using the Newcastle-Ottawa-Scale. Our primary outcome was the odds ratio (OR, 95% confidence intervals [95%CI]) of offspring outcomes in fathers with vs. without antiseizure medication(s). A subgroup analysis assessing the study design impact and sensitivity analyses after excluding poor-quality studies, and sequentially each study, were performed. Results: Of the six studies included (k = 6, n = 17,974), two and four were rated as good- and poor-quality studies, respectively. There were no differences regarding risk of major congenital malformations in offsprings with vs. without paternal antiseizure medication(s) (OR = 1.22, 95%CI = 0.55 to 2.68, p = 0.63), with substantial heterogeneity (I2 = 93.0%). In six studies (k = 6, n = 17,604) there were no differences regarding risk of neurodevelopmental disorders in offsprings with vs. without paternal antiseizure medication(s) (OR = 1.21, 95%CI = 0.73 to 1.99, p = 0.46, I2 = 95.6%); ORs of paternal antiseizure medication-related neurodevelopmental disorders were higher in cross-sectional (n = 3) vs. cohort studies (n = 3) (p < 0.001). Conclusions: There is no evidence of elevated risk of adverse outcomes for offsprings with vs. without paternal antiseizure treatment, although heterogeneity was substantial. Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD42025635478.