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A study published in JAMA Network Open looks at parental valproate use and neurodevelopmental disorders in offspring.
Dr Channa Jayasena, Associate Professor in Reproductive Endocrinology at Imperial College London and Consultant in Reproductive Endocrinology and Andrology at Imperial College Healthcare NHS Trust, Imperial College London, said:
“Valproate is a drug which has been used for decades to treat epilepsy. A retrospective study recently been reported that children conceived when their dad was taking Valproate were more likely than normal to have NDD. However, a flurry of further studies has emerged, each finding different results. For instance, a large retrospective study in 90,000 men (Mbizvo et al, Nature Comms 2025) failed to observe any association between paternal valproate and NDD; in contrast, the current study found an increased risk. Data from over 5000 Scandinavian were analysed if their dad had taken valproate or another drug for epilepsy without concerns about causing NDD in babies. The authors found that 4-5% of babies with dads taking valproate had NDD, but only 2-3% had NDD when dads were taking the other drugs for epilepsy. When adjusting for other factors, they found that the increased risk of NDD from valproate about 50% higher than with other drugs for epilepsy. However, all studies have error, so the excess risk might be as low has 9%. Observational studies are unable enough to prove that valproate causes NDD. However, it is extremely difficult to design clinical trials which might cause harm to an unborn baby. Furthermore, drugs for epilepsy work in the brain, so it is scientifically plausible that they could affect NDD. On the other hand, other factors like older paternal age and certain occupations are established risk factors for NDD.
“In summary, I really don’t think we know if valproate causes NDD, but there are potential risks. I still think it is premature to suggest that couples should avoid pregnancy while the male partner is on valproate. Men taking valproate should certainly not stop taking the medication (which would be dangerous), but speak to their specialist if they have concerns, and want to explore alternative medications.”
Prof Allan Pacey, Professor of Andrology at the University of Manchester, said:
“This is a large and comprehensive study conducted across three countries in Scandinavia that suggests that a father’s exposure to Valproate may increase the risk of neurodevelopmental disorders in their children.
“Valproate is a commonly used and relatively cheap medication to control epilepsy and bipolar disorders. Whilst it has been known to be of concern for child health if taken by women during pregnancy, it has been unclear whether the same is true if it is taken by fathers. This study attempts to fill that knowledge gap.
“The approach taken by the authors to answer this question is impressive. They took data from registries in three Nordic countries and used rigorous selection criteria to identify men who are only taking anti-epilepsy drugs as a monotherapy. They then link this with child health records of any children born. The results suggest that children born to men who take Valproate are at a higher risk of neurodevelopmental disorders compared to men who are taking other medications to control their epilepsy and bipolar disorders.
“However, as the authors of the study point out, the findings should be interpreted with caution. Although the study was large, there is still some statistical uncertainty about the result. In my opinion, the result is not sufficiently robust for all men of reproductive age to be switched from Valproate to another type of medication. But if would be fathers are worried, they should discuss this with their doctor who can advise them appropriately.
‘Paternal Valproate Use and Neurodevelopmental Disorder and Congenital Malformation Risk in Offspring’ by Sandrine Colas et al. was published in JAMA Network Open at 16:00 UK time on Monday 10th November 2025.
DOI: 10.1001/jamanetworkopen.2025.42581
Declared interests
Prof Allan Pacey: “Allan Pacey is a member of the Cryos International External Scientific Advisory Committee, he also undertakes consultancy for Carrot Fertility, and in the last two years has delivered educational lectures for IBSA Institut Biochemique SA, and Mealis Group but all monies were paid to the University of Manchester. He is also the co-chair of the UKNEQAS Reproductive Sciences Advisory Committee, is a member of the Advisory Boards for the Progress Educational Trust (Charity Number 1139856) and the Science Media Centre (Charity Number 1140827) and Patron of the Fertility Alliance (Charity Number 1206323 (all unpaid). He is a member of the Guidelines Development Groups for the National Institute for Health and Care Excellence, and the World Health Organisation (again all unpaid).”
Dr Channa Jayasena: No conflicts