Children born to mothers who take anticonvulsant drugs to manage seizures and psychiatric conditions during pregnancy may face an increased risk 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 UK and Sweden, including 17,495 who were exposed to anticonvulsant drugs during pregnancy — found that children exposed to the anticonvulsant drug lamotrigine in utero did not experience additional risk for autism or intellectual disability compared to those exposed to other anticonvulsant drugs. However, children exposed to valproate, topiramate, and carbamazepine were associated with 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 the anticonvulsant drug regimen. Compared with children not exposed to anticonvulsant drugs, those exposed to the drug topiramate during pregnancy were 2.5 times more likely to be diagnosed with an intellectual disability, which increases the risk to 2.1% by the age of 12 years old. Compared with other available drugs, the authors found very little data to suggest that the drug lamotrigine in pregnancy increases the risk of neurodevelopmental problems in the offspring.
Our findings suggest that while some drugs may carry some risk, lamotrigine may be a less risky option. Active monitoring of any anticonvulsant medication is critical to ensure safety and efficacy, particularly during pregnancy.”
Brian K. Lee, PhD, co-senior author, professor, Dornsife School of Public Health
This study contrasts with previous studies in that it found no statistically significant association between topiramate or levetiracetam and ADHD in children, regardless of whether the birth parent had a diagnosis of epilepsy.
According to the researchers, the data do not support the use of anticonvulsant drugs in patients who benefit, but they encourage these patients to talk with their doctor to determine if their course of treatment is best for them.
“Decisions should be made that are tailored to individual patients,” said co-lead author Paul Madley-Dowd, PhD, a researcher at the University of Bristol. “Discontinuing anticonvulsant medications can cause individual harm and harm to offspring, so these discussions should always be with a clinician.”
This study supports findings from previous research linking the anticonvulsant drugs valproate, topiramate and carbamazepine to neurodevelopmental diagnoses in the offspring, such as autism, intellectual disability and ADHD. Previous studies in smaller populations have also linked in utero exposure to these drugs to neurodevelopmental effects in the offspring, such as those linking topiramate to intellectual disability and those linking valproate to lower IQ.
The study used data on drug prescriptions in the UK and dispensing and self-report data on drug use in Sweden, as well as electronic health record 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 exists, even if the risk is not much higher than in the unexposed population,” said co-lead author Viktor H. Ahlqvist, a postdoctoral researcher at the Karolinska Institutet . “If you are pregnant or trying to become pregnant and are taking one of these drugs, it may be worth talking to your doctor to make sure you are taking the best drug for your needs while minimizing the risk to future children.”
Despite the study’s large sample size, the authors say patients could benefit from further research from multiple countries on the 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 colleagues from Drexel University, Pennylvania State University, the London School of Hygiene and Tropical Medicine, University College London, University of Bristol and Karolinska Institutet.
The study was funded by the National Institutes of Health (1R01NS107607).
Source:
Journal Reference:
Madley-Dowd, P., et al. (2024). Anticonvulsant drug use during pregnancy and child neurodevelopmental outcomes. Nature communications. doi.org/10.1038/s41467-024-53813-1.
