Fathers’ Valproate Use Not Linked To Child Development Disorders

What was studied

This study looked at whether children had a higher chance of neurodevelopmental disorders if their father used valproate during the 3 months before conception, which is the time period used in the study to represent spermatogenesis.

Researchers used nationwide health data from Sweden and Norway and included all singleton live births from 2007 to 2020 at 22 weeks of pregnancy or later. They compared children whose fathers filled prescriptions for valproate only during that 3-month window with children whose fathers filled prescriptions for only lamotrigine or levetiracetam during the same period. The study included 1,588 valproate-exposed children and 3,093 comparison children in Sweden, and 463 valproate-exposed children and 1,109 comparison children in Norway. The children were followed from age 1 through 2022 for diagnoses such as autism spectrum disorder, ADHD, intellectual disability, and psychological development disorders.

What they found

Compared with paternal use of lamotrigine or levetiracetam, paternal use of valproate during the 3 months before conception was not associated with an increased overall risk of neurodevelopmental disorders in children. The pooled adjusted estimate was 1.06 (95% CI 0.81 to 1.22). The same general pattern was reported for autism spectrum disorder, ADHD, intellectual disability, and psychological development disorders, although some estimates were imprecise. Findings were also consistent in dose-response analyses and when the analysis was restricted to fathers with epilepsy.

Limits of the evidence

This was an observational study, so it cannot establish that paternal valproate has no effect; it can only show that this study did not find an increased risk in this comparison. The study relied on prescription fills, which do not guarantee the medicine was actually taken. Some results, especially for specific disorders like intellectual disability, were based on fewer cases and had wide confidence intervals, so smaller increases or decreases in risk cannot be ruled out. The comparison was with fathers taking other anti-seizure medicines, not with fathers taking no medicine, and the findings come from Sweden and Norway, so they may not apply the same way in all settings.

For families and caregivers

This study may be reassuring because it did not find an increased risk of neurodevelopmental disorders in children of fathers who used valproate before conception, compared with fathers using lamotrigine or levetiracetam. It may matter for families because regulators have raised concerns and placed restrictions on paternal valproate use. Still, this is one study, and treatment decisions should balance seizure control and other health needs with the available evidence.

What to watch next

More large studies in other settings could help clarify these findings further, especially for specific outcomes such as autism spectrum disorder and intellectual disability.

Terms in this summary

valproate

A medicine used to treat epilepsy and some other conditions.

spermatogenesis

The process of making sperm; in this study, exposure was measured during the 3 months before conception.

neurodevelopmental disorders

Conditions that affect brain development, learning, behavior, or attention.

autism spectrum disorder

A developmental condition that affects social communication and behavior.

ADHD

Attention-deficit/hyperactivity disorder, which can affect attention, activity level, and impulse control.

cohort study

A study that follows groups of people over time to compare outcomes.

adjusted hazard ratio

A statistical measure researchers use to compare risk between groups while accounting for other factors that may affect the result.

confidence interval

A range that shows how uncertain an estimate is; a wide range means more uncertainty.