Antiepileptic Drug Exposure and Prenatal Outcomes

Exposure to antiepileptic drugs (AEDs) during pregnancy represents a complex balance between maintaining maternal seizure control and minimising risks to the developing embryo and foetus. As the utilisation of both older agents such as valproate and carbamazepine and newer alternatives like lamotrigine and levetiracetam has evolved, large‐scale cohort studies and population registries have elucidated patterns of congenital malformations, growth restriction and neurodevelopmental impairment. Risk profiles differ markedly between drugs, with valproate consistently associated with the highest prevalence of major malformations and adverse neurodevelopmental outcomes in a dose‐dependent manner. Shifts in prescribing practice towards lower‐risk monotherapies have driven measurable declines in birth defects. Nonetheless, concerns regarding subtle cognitive and behavioural sequelae, as well as foetal growth parameters, underscore the need for ongoing surveillance and tailored preconception counselling.

Research from Nature Portfolio

A nationwide cohort analysis in France investigated early neurodevelopmental disorders following in utero exposure to monotherapy with various AEDs. Among over 1.7 million births, children exposed to valproate exhibited a four- to fivefold increased hazard of mental or behavioural disorders by age three, with a clear dose–response relationship and heightened sensitivity when exposure occurred in the second and third trimesters. Pregabalin demonstrated a modest but consistent elevation in risk, whereas other agents showed no significant associations. This work confirms a particularly deleterious profile for valproate and supports prioritising alternatives where clinically feasible.

Antiepileptic Drug Exposure and Prenatal Outcomes publication trend

The graph below shows the total number of articles in antiepileptic drug exposure and prenatal outcomes across all publications each year (not limited to Nature Index journals).

Technical terms

Major congenital malformations: anomalies in the structure of major organs or body parts present at birth.

Neurodevelopmental disorders: conditions affecting brain development leading to cognitive, behavioural or social impairments.

Small for gestational age: birth weight below the tenth percentile for a given gestational age.

Monotherapy vs polytherapy: use of one antiseizure medication compared with multiple concurrent agents.

Teratogenicity: the capacity of a substance to cause birth defects during embryonic or foetal development.

References

1. Risk of Major Congenital Malformations and Exposure to Antiseizure Medication Monotherapy. JAMA Neurology (2024).
2. Prenatal exposure to antiseizure medications and fetal growth: a population-based cohort study from the Nordic countries. The Lancet Regional Health - Europe (2024).
3. Comparative safety of anti-epileptic drugs during pregnancy: a systematic review and network meta-analysis of congenital malformations and prenatal outcomes. BMC Medicine (2017).
4. Association of Prenatal Exposure to Antiseizure Medication With Risk of Autism and Intellectual Disability. JAMA Neurology (2022).
5. Risk of early neurodevelopmental disorders associated with in utero exposure to valproate and other antiepileptic drugs: a nationwide cohort study in France. Scientific Reports (2020).