Summary: Children born to women with epilepsy who were treated with certain antiepileptic drugs during pregnancy show higher rates of behavioral difficulties as they grow, according to a recent prospective study.
Source: Wiley
Study Finds Increased Behavioral Problems in Children Prenatally Exposed to Common Antiepileptic Drugs
A new prospective study published in Epilepsia evaluated behavioral outcomes in school‑age children whose mothers had epilepsy and used a single antiepileptic drug (monotherapy) during pregnancy. The study highlights differences in behavioral profiles among children prenatally exposed to valproate (VPA), carbamazepine (CBZ), lamotrigine (LTG), and levetiracetam (LEV) and emphasizes the need for routine developmental and behavioral monitoring of these children.
Study design and measures
This Dutch prospective observational study was carried out in collaboration with a European pregnancy registry network. Researchers invited families and ultimately collected behavioral questionnaires for 181 children aged 6 to 7 years whose mothers had taken one of four antiepileptic drugs during pregnancy: valproate (26 children), carbamazepine (37), lamotrigine (88), and levetiracetam (30). For most participants, both parents completed validated parent‑report instruments: the Child Behavior Checklist (CBCL) and the Social Emotional Questionnaire (SEV). These tools assess a broad range of emotional, social, and attention‑related behaviors and can identify clinically relevant problems that warrant further assessment or intervention.
Key findings
Overall, the study found a higher-than-expected proportion of children with clinically relevant behavioral problems across all four drug exposure groups when compared with population norms. Rates of parent‑reported behavioral problems were 32% for VPA, 14% for CBZ, 16% for LTG, and 14% for LEV.
After adjusting for potential confounding factors, children exposed prenatally to valproate had significantly higher levels of social difficulties compared with those exposed to lamotrigine or levetiracetam. Valproate‑exposed children also showed more attention problems than levetiracetam‑exposed children. Comparisons between lamotrigine and levetiracetam revealed different patterns: lamotrigine exposure was associated with higher attention‑deficit scores yet lower anxiety scores compared with levetiracetam.
Interpretation and clinical implications
These findings reinforce earlier concerns about the neurodevelopmental risks associated with prenatal exposure to certain antiepileptic drugs, particularly valproate. Importantly, the study shows that behavioral concerns are not limited to a single medication: clinically relevant problems were identified in children across all four medication groups, although the pattern and severity of difficulties varied by drug.
Clinicians and families should be aware of these potential risks when counseling women of childbearing age who require antiepileptic treatment. The results support informed decision making about medication choice and underscore the value of individualized risk‑benefit discussions, especially for women planning pregnancy or who become pregnant.
Recommendations for monitoring and support
The authors advise routine screening of children who were prenatally exposed to antiepileptic drugs for behavioral and social difficulties during early school years and beyond. Regular monitoring can enable early identification of attention‑related, social, or emotional problems so that appropriate interventions—educational supports, behavioral therapies, or family‑focused strategies—can be offered in a timely fashion. The study also emphasizes considering family and environmental factors alongside medication exposure when planning follow‑up and interventions, as these may provide additional, practical starting points to help parents manage or reduce child behavioral problems.
Study details and citation
Original research: Open access. Title: “Behavioral problems in children of mothers with epilepsy prenatally exposed to valproate, carbamazepine, lamotrigine, or levetiracetam monotherapy.” Authors: Yfke Huber‑Mollema, Frans J. Oort, Dick Lindhout, Roos Rodenburg. Journal: Epilepsia. DOI: 10.1111/epi.15968
Conclusion
This prospective study strengthens the evidence that prenatal exposure to several commonly prescribed antiepileptic drugs is associated with elevated rates of parent‑reported behavioral problems in early school‑aged children. While valproate showed the strongest associations with social and attention problems, other drugs also demonstrated increased rates of clinically relevant behaviors. Regular screening and early support for exposed children, together with careful medication counseling for women with epilepsy, are important steps to mitigate long‑term impacts on behavior and development.
Source: Wiley
Media Contacts:
Penny Smith – Wiley
Image Source:
The image is credited to Author Roos Rodenburg, Ph.D.