Antiseizure medications during pregnancy linked to neurodevelopmental risks in children

Children born to mothers who take antiseizure medications to manage seizures and psychiatric conditions during pregnancy may face increased risks of neurodevelopmental conditions, according to new data from researchers at Drexel's Dornsife School of Public Health.

The current work -- using data from more than three million children from the United Kingdom and Sweden, including 17,495 who were exposed to antiseizure medications during pregnancy -- found that children exposed to the antiseizure drug lamotrigine in utero were at no additional risk for autism or intellectual disability compared with those exposed to other antiseizure medications. However, children exposed to valproate, topiramate, and carbamazepine were linked to specific neurodevelopmental issues. The findings were published this month in the journal Nature Communications.

However, the absolute risk of neurodevelopmental outcomes in offspring is low, the researchers caution, regardless of antiseizure drug regimen. Compared to children unexposed to antiseizure medications, those exposed to the drug topiramate during pregnancy were 2.5 times more likely to be diagnosed with intellectual disability, which raises their risk to 2.1% by age 12. In comparison with other drugs available, the authors found very little data suggesting that the drug lamotrigine in pregnancy increases the risk of neurodevelopmental issues in offspring.

Our findings suggest that while certain medications may pose some risk, lamotrigine may be a less risky option. Active monitoring of any antiseizure medication is critical to ensure safety and effectiveness, particularly during pregnancy."

Brian K. Lee, PhD, co-senior author, professor, Dornsife School of Public Health

This study contrasts earlier studies in that it did not find a statistically significant link between topiramate or levetiracetam and ADHD in children, regardless of whether the birthing parent had an epilepsy diagnosis.

According to the researchers, the data does not argue against use of antiseizure medications in patients who benefit, but rather encourages these patients to have a conversation with their doctor to determine if their course of treatment is most appropriate for them.

"Decisions should be made that are tailored to individual patients," said co-lead author Paul Madley-Dowd, PhD, a research fellow at the University of Bristol. "Stopping antiseizure medications can cause individual harm and harm to offspring, so these conversations always need to happen with a clinician."

This study supports findings from previous research that link the antiseizure drugs valproate, topiramate, and carbamazepine with neurodevelopmental diagnoses in offspring, such as autism, intellectual disability and ADHD. Previous studies in smaller populations also link in utero exposure of these drugs with neurodevelopmental outcomes in offspring, such as ones linking topiramate and intellectual disability, and those associating valproate and lower IQ.

The study utilized data on drug prescriptions in the United Kingdom, and dispensation and self-reported data on drug use in Sweden, as well as electronic health records data for diagnoses. The authors conducted a sibling analysis to help minimize the influence of other factors, such as severity of diagnosis and underlying genetics, that may influence the results.

"The link between these drugs and children's neurodevelopmental outcomes is there, even if the risk isn't much higher than it is in the unexposed population," said co-lead author Viktor H. Ahlqvist, a postdoctoral researcher at Karolinska Institutet. "If you're pregnant or trying to become pregnant, and taking one of these medications, it may be worth talking with your physician to make sure you're taking the best medicine for your needs, while minimizing risk to future children."

Despite the study's large sample size, the authors say patients could benefit from further research from multiple countries on safety of these drugs as the landscape of options available to patients changes.

In addition to Lee, Madley-Dowd and Ahlqvist, other authors included co-senior authors Cecilia Magnusson from the Karolinska Institutet and Dheeraj Rai from the University of Bristol, and collaborators from Drexel University, Pennylvania State University, London School of Hygiene and Tropical Medicine, University College London, University of Bristol, and the Karolinska Institutet.

The study was funded by the National Institutes of Health (1R01NS107607).