Children born to mothers who use antiseizure medications for managing seizures and psychiatric conditions during pregnancy may face heightened risks of neurodevelopmental disorders, according to new research from Drexel University’s Dornsife School of Public Health. The study analyzed data from over three million children in the United Kingdom and Sweden, including 17,495 who were exposed to antiseizure medications in utero.
Published in the journal Nature Communications, the findings indicate that while exposure to the antiseizure drug lamotrigine does not appear to increase the risk of autism or intellectual disability compared to other antiseizure medications, other drugs such as valproate, topiramate, and carbamazepine are associated with specific neurodevelopmental issues.
The researchers emphasize that the overall risk of neurodevelopmental outcomes remains low, regardless of the antiseizure medication regimen. Specifically, children exposed to topiramate during pregnancy were found to be 2.5 times more likely to be diagnosed with intellectual disability, raising their risk to 2.1% by age 12. In contrast, the study found little evidence suggesting that lamotrigine 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,” said Brian K. Lee, PhD, co-senior author and professor at the Dornsife School of Public Health. “Active monitoring of any antiseizure medication is critical to ensure safety and effectiveness, particularly during pregnancy.”
This study diverges from previous research by not establishing a statistically significant link between topiramate or levetiracetam and attention deficit hyperactivity disorder (ADHD) in children, regardless of whether the birthing parent had an epilepsy diagnosis.
The researchers clarify that their findings do not discourage the use of antiseizure medications in patients who benefit from them. Instead, they advocate for discussions between patients and healthcare providers to evaluate the appropriateness of their treatment plans. “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.”
The study supports earlier findings that link valproate, topiramate, and carbamazepine to neurodevelopmental diagnoses such as autism, intellectual disability, and ADHD. Previous smaller studies have also associated in utero exposure to these drugs with adverse neurodevelopmental outcomes.
Utilizing data on drug prescriptions from the UK and self-reported drug use data from Sweden, along with electronic health records for diagnoses, the authors conducted a sibling analysis to mitigate the influence of confounding factors such as the severity of the mother’s condition and underlying genetics.
“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,” noted 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 discussing with your physician to ensure you’re on the best treatment for your needs while minimizing risks to future children.”
Despite the study’s large sample size, the authors call for further research across multiple countries to assess the safety of these medications as treatment options evolve.
Conclusion
In addition to Lee, Madley-Dowd, and Ahlqvist, the study included contributions from co-senior authors Cecilia Magnusson of Karolinska Institutet and Dheeraj Rai from the University of Bristol, along with collaborators from Drexel University, Pennsylvania State University, London School of Hygiene and Tropical Medicine, University College London, and the Karolinska Institutet.
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