EMA Update: Valproate and Paternal Risk of Neurodevelopmental Disorders

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) concluded that evidence linking valproate medications to neurodevelopmental disorders in children conceived by treated men is inconsistent. Because a causal role remains uncertain, PRAC recommended maintaining 2024 precautionary measures for male patients until a larger study is completed in 2028.

Why are precautions still in place for men using valproate?

PRAC decided to keep existing precautions for male patients to manage a potential risk of neurodevelopmental disorders (NDD) in children conceived during the three months before conception. These measures were first implemented in 2024.

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The committee noted that while recent data is inconsistent, uncertainty persists regarding whether valproate or other factors, such as a father’s pre-existing medical condition, cause these disorders. Valproate medications are used to treat epilepsy and bipolar disorder, and in some member states, they are used for migraine prevention.

Did You Know? Valproate medications are used for epilepsy and bipolar disorder, and in certain member states, they are also indicated for the prevention of migraines.

What evidence led to the current uncertainty?

The current uncertainty stems from conflicting study results. In January 2024, a post-authorization safety study (PASS) using databases from Denmark, Norway, and Sweden suggested an increased risk of NDD in children of men treated with valproate compared to those treated with levetiracetam or lamotrigine.

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However, a July 2025 signal based on a Danish national register study did not suggest an increased risk. According to PRAC, most retrospective observational studies have not found an increased risk of NDD. The committee attributed these differing results to variations in study design, including the types of patients enrolled and how pre-existing medical conditions were handled.

Expert Insight: Samantha Carter notes that the conflict between the 2024 PASS study and the 2025 Danish data highlights the difficulty of isolating medication effects from paternal health history. The decision to maintain precautions despite inconsistent data suggests a conservative approach to patient safety while awaiting definitive evidence.

What happens next for patients and doctors?

PRAC recommended updating product information, healthcare professional guides, and guides for male patients to reflect the latest NDD data. These updates ensure that both providers and patients have access to current findings.

A larger study designed to address previous limitations is currently underway. According to the committee, results from this study are expected to be available in 2028. The current precautionary measures may remain in effect until those findings are finalized.

Frequently Asked Questions

What are neurodevelopmental disorders (NDD)?
According to the source, NDDs are developmental problems starting in early childhood, including autism spectrum disorders, intellectual disabilities, communication disorders, ADHD, and movement disorders.

When were the precautionary measures for men first introduced?
The measures were implemented in 2024 to manage potential risks during the three months prior to conception.

When will more definitive data be available?
A larger study is currently in progress and is expected to be completed in 2028.

How do you feel about the balance between precautionary medical warnings and evolving scientific data?