Valproate exposure during spermatogenesis carries no harm in offspring

Exposure to valproate during spermatogenesis does not appear to put infants at risk of congenital malformations or neurodevelopmental disorders, including autism spectrum disorder, according to a study.

Researchers used data from the Danish Medical Birth Register and identified 1,235,353 singletons (51.4 percent boys) born between 1997 and 2017. Of these, 1,336 children were born to fathers who had filled prescriptions for valproate during spermatogenesis (ie, 3 months prior to conception).

Outcomes included congenital malformations in the first year of life and neurodevelopmental disorders during the follow-up.

The median follow-up was 10.1 years for valproate-exposed children and 10.3 years for valproate-unexposed children. Major congenital malformations in the first year of life were documented in 43,903 children (3.6 percent), while neurodevelopmental disorders were diagnosed in 51,633 children (4.2 percent) during follow-up.

Compared with the unexposed group, the valproate-exposed group showed no increase in the risk of major congenital malformations (adjusted relative risk [ARR], 0.89, 95 percent confidence interval [CI], 0.67–1.18) and neurodevelopmental disorders (adjusted hazard ratio [AHR], 1.10, 95 percent CI, 0.88–1.37), including autism spectrum disorder (AHR, 0.92, 95 percent CI, 0.65–1.30).

The findings persisted in dose-response and sibling analyses, analysis restricted to children of fathers with epilepsy, analysis that used children with paternal lamotrigine exposure as active comparator, and analysis that used children with paternal exposure to valproate only before spermatogenesis as a negative control exposure).