NEJM Evid
Study finds no increased neurodevelopmental risk from paternal valproate use
The study analyzed more than 1.39 million children from nationwide cohorts in Norway and Taiwan, including 883 offspring exposed to paternal valproate in the 90 days before conception. In crude population analyses, exposed children had higher rates of neurodevelopmental disorders, with hazard ratios of 1.67 in Norway and 1.35 in Taiwan. However, after adjusting for clinical and demographic factors in indication‑restricted and active‑comparator models, associations were no longer seen. Adjusted hazard ratios ranged from 1.02 to 1.22 across analyses, with confidence intervals crossing unity in both countries. Findings were consistent when valproate was compared with lamotrigine or levetiracetam, suggesting no independent link between paternal exposure and neurodevelopmental risk.
Clinical takeaway: For men who require valproate, preconception exposure does not appear to increase the risk of neurodevelopmental disorders in offspring.
Source:
Meng LC, et al. (2026, February 24). NEJM Evid. Valproate Use by Fathers and Risk of Neurodevelopmental Disorders in Children. https://pubmed.ncbi.nlm.nih.gov/41733407/