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Results of a review and meta-analysis suggest there is “no evidence” that children born to fathers treated with valproate are at increased risk of developing neurodevelopmental disorders, such as autism and ADHD.
Publishing their findings in the Journal of Neurology, Neurosurgery and Psychiatry on 12 May 2026, researchers analysed data from patients in Denmark, Norway, Sweden and Taiwan between 1995 and 2025, and compared paternal use of sodium valproate with lamotrigine or levetiracetam and their effects on offspring.
“We have brought together and analysed the best available data from several countries and, overall, we find no increased risk,” the authors wrote.
The researchers identified three eligible studies based on data from Norway and Sweden, Norway and Taiwan, and Denmark.
They found that in the meta-analysis of data from Denmark, Sweden and the first set of Norwegian data, the pooled hazard ratios (HRs) of offspring neurodevelopmental disorders was 1.05 (95% confidence interval [CI] 0.87–1.27; I2=0.0%), compared with 1.03 (95% CI 0.85–1.24; I2=0.0%) in the meta-analysis of data from Denmark, Sweden and the second set of Norwegian data.
In their meta-analysis of data from Taiwan, Denmark, Sweden and the first set of Norwegian data, researchers found that the pooled HR was 1.06 (95% CI 0.88 to 1.27; I2=0.0%), compared with 1.04 (95% CI 0.87 to 1.25; I2=0.0%) in the data from Taiwan, Denmark, Sweden and the second set of Norwegian data.
In September 2024, the Medicines and Healthcare products Regulatory Agency (MHRA) issued advice recommending that male patients and their female partner should use effective contraception during valproate use.
The measures were influenced by study results that showed a possible connection between use of valproate in men and a small increased risk of neurodevelopmental disorders in their children.
Sodium valproate is an anti-seizure medicine used to treat epilepsy; however, babies exposed to it in the womb are at significant risk of developing foetal valproate spectrum disorder, which is the collective name for a variety of disorders and development issues, including spina bifida, autism and malformations of the brain, heart and kidneys.
In January 2024, the MHRA announced a requirement for a two-clinician sign-off for men aged under 55 years taking valproate. Under the measures, two specialists are required to agree that there is no other effective or tolerated treatment, or there are “compelling reasons” that the reproductive risks do not apply.
However, the requirement was changed in February 2025 to only apply to men aged under 55 years being newly initiated on valproate.
Commenting on the review, Tom Shillito, health improvement and research manager at charity Epilepsy Action, said: “It is encouraging to see extensive new research suggesting that men taking valproate aren’t at increased risk of neurodevelopmental disorders in their children, compared to the risks involved with other epilepsy medication.
“We know from the calls we receive to our helpline that many men are concerned about the potential transgenerational effects of sodium valproate. This can sometimes result in them stopping their medication, which can put them at further risk.
“Epilepsy Action has been consistently raising this issue with the MHRA and asking them to reconsider the published regulations. Given this new study, it is time for them to revisit the evidence and give it consideration.”
