Valproate Use During Spermatogenesis and Risk to Offspring

Valproate Use During Spermatogenesis and Risk to Offspring

2024-06-04 | Jakob Christensen, DrMedSci; Betina B. Trabjerg, MSc; Julie Werenberg Dreier, PhD
This study evaluates the association between paternal use of valproate during spermatogenesis and the risk of congenital malformations and neurodevelopmental disorders in offspring. The study included 1,235,353 singletons born in Denmark between 1997 and 2017, with 1,336 children whose fathers had filled prescriptions for valproate during spermatogenesis. The median follow-up was 10.1 years for valproate-exposed children and 10.3 years for unexposed children. The results showed no significant increased risk of major congenital malformations (adjusted relative risk [ARR] 0.89, 95% CI 0.67-1.18) or neurodevelopmental disorders (adjusted hazard ratio [AHR] 1.10, 95% CI 0.88-1.37) among the exposed children compared to unexposed children. Specific analyses, including dose-response, sibling, and restriction analyses, did not identify increased risks. The findings suggest that paternal use of valproate during spermatogenesis is not associated with an increased risk of congenital malformations or neurodevelopmental disorders, including autism spectrum disorder, among offspring.This study evaluates the association between paternal use of valproate during spermatogenesis and the risk of congenital malformations and neurodevelopmental disorders in offspring. The study included 1,235,353 singletons born in Denmark between 1997 and 2017, with 1,336 children whose fathers had filled prescriptions for valproate during spermatogenesis. The median follow-up was 10.1 years for valproate-exposed children and 10.3 years for unexposed children. The results showed no significant increased risk of major congenital malformations (adjusted relative risk [ARR] 0.89, 95% CI 0.67-1.18) or neurodevelopmental disorders (adjusted hazard ratio [AHR] 1.10, 95% CI 0.88-1.37) among the exposed children compared to unexposed children. Specific analyses, including dose-response, sibling, and restriction analyses, did not identify increased risks. The findings suggest that paternal use of valproate during spermatogenesis is not associated with an increased risk of congenital malformations or neurodevelopmental disorders, including autism spectrum disorder, among offspring.
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