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,  = 0.63), with substantial heterogeneity (I = 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,  = 0.46, I = 95.6%); ORs of paternal antiseizure medication-related neurodevelopmental disorders were higher in cross-sectional (n = 3) vs. cohort studies (n = 3) ( < 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.