Antiseizure medications used in pregnancy linked to neurodevelopmental risks in children

A recent study published in Nature Communications has revealed significant associations between in-utero exposure to certain antiseizure medications (ASMs) and increased risks of neurodevelopmental disorders, including autism spectrum disorder (ASD), intellectual disability (ID), and attention deficit hyperactivity disorder (ADHD).

Study overview

The study analyzed data from 3,182,773 children born in the United Kingdom and Sweden, including 17,495 children exposed to ASMs during pregnancy. Through this cohort, researchers evaluated the risks posed by ASM exposure on offspring neurodevelopment by age 12, adjusting for various confounders like maternal health, socioeconomic status, and prenatal healthcare utilization.

Key ASMs examined included valproate, topiramate, carbamazepine, and lamotrigine. Each was analyzed for its association with specific neurodevelopmental outcomes.

Key findings

• Valproate:
  • Risk of ASD nearly doubled (HR: 1.78).
  • ID risk increased over twofold (HR: 2.56).
  • ADHD risk was significantly elevated, with a prevalence of 6.34% by age 12 compared to 2.5% in unexposed children.
• Topiramate:
  • ID risk doubled (HR: 2.48), translating to an absolute risk increase from 0.92% in unexposed children to 2.14% in exposed children by age 12.
• Carbamazepine:
  • ASD risk increased by 25% (HR: 1.25).
  • ID risk rose by 30% (HR: 1.30).
• Lamotrigine:
  • No significant association with ASD, ID, or ADHD, making it a potentially safer option for women requiring ASM during pregnancy.

Clinical implications

According to the study authors, ASMs are essential for managing epilepsy and certain psychiatric conditions. However, this study underscores the complexity of balancing maternal health needs with potential risks to fetal development. Researchers advocate for preconception planning to explore safer alternatives like lamotrigine, especially for women of childbearing age.

"Our findings highlight the importance of personalized treatment plans, taking into account both maternal and fetal health," wrote the study authors.

Study strengths and limitations

This study’s strengths include its large sample size and the use of comprehensive registry data from 2 countries. Its sibling comparison analysis offers robust control for genetic and environmental confounders, providing strong evidence of the risks associated with valproate, topiramate, and carbamazepine.

However, limitations include reliance on prescription records rather than confirmed medication adherence and potential differences in diagnostic practices between the UK and Sweden.

While the study provides crucial insights, further research is needed to confirm causal relationships and explore the safety of newer ASMs. This is particularly critical as the prevalence of ASM use among women of childbearing age continues to rise.

Reference:

Madley-Dowd, P., Ahlqvist, V.H., Forbes, H. et al. Antiseizure medication use during pregnancy and children’s neurodevelopmental outcomes. Nat Commun 15, 9640 (2024). https://doi.org/10.1038/s41467-024-53813-1