The study, led by researchers at the University of Bristol, Drexel’s Dornsife School of Public Health in the US and the Karolinska Institutet in Sweden, used data from more than three million children from the UK and Sweden, including 17,495 who were exposed to anti-seizure medications during pregnancy.
The research also found children born to mothers who take anti-seizure medications to manage seizures and psychiatric conditions during pregnancy may face increased risks of neurodevelopmental conditions, such as autism, intellectual disability and ADHD. Children exposed to valproate, topiramate, and carbamazepine were linked to specific neurodevelopmental issues. However, the researchers caution that the absolute risk of neurodevelopmental outcomes in offspring is very low, regardless of the anti-seizure drug course of treatment.
For example, those exposed to the drug topiramate before birth were 2.5 times more likely to be diagnosed with intellectual disability, which raises their risk by 1.2 per cent by age 12 compared to children not exposed to anti-seizure medications. 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.
Brian Lee, Professor of Epidemiology in the Dornsife School of Public Health, and the study’s co-senior author, said: “Patients need to know that the absolute risk of neurodevelopmental outcomes from these drugs is generally low. Our findings suggest that while certain medications may pose some risk, lamotrigine may be a less risky option, but active monitoring of any anti-seizure medication is critical to ensure safety and effectiveness, particularly during pregnancy.”
The data does not argue against use of anti-seizure medications in patients who benefit, the researchers explain, but rather encourages these patients to have a conversation with their doctor to determine if their course of treatment is most appropriate for them.
Dr Paul Madley-Dowd, Research Fellow in Medical Statistics and Health Data Science at the University of Bristol and the study’s co-lead author, added: “Decisions should be made that are tailored to individual patients. Stopping anti-seizure medications can cause individual harm and harm to offspring, so these conversations always need to happen with a clinician.”
The current study contrasts to earlier findings in that it found no link between topiramate or levetiracetam and ADHD in children, regardless of whether the birthing parent had an epilepsy diagnosis.
The current study supports findings from other studies that link the anti-seizure drugs valproate, topiramate, and carbamazepine with specific neurodevelopmental diagnoses in offspring. 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 used data on drug prescriptions in the UK, 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 minimise the influence of other factors, such as severity of diagnosis and underlying genetics, that may influence the results.
Dr Viktor Ahlqvist, Postdoctoral Researcher at the Karolinska Institutet, and the study’s co-lead author, explained: “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. 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 minimising 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 Professor Lee, Drs Madley-Dowd and Viktor Ahlqvist, other authors included co-senior authors Professor Cecilia Magnusson from the Karolinska Institutet and Professor Dheeraj Rai from the University of Bristol, and collaborators from Drexel University, Pennsylvania State University, London School of Hygiene and Tropical Medicine, University College London, University of Bristol, and the Karolinska Institutet.
Paper
‘Antiseizure medication use during pregnancy and children’s neurodevelopmental outcomes’ by Paul Madley-Dowd et al. in Nature Communications [open access]