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Teratogenicity of antiepileptic drugs

Torbjörn Tomson1, Dina Battino2, Emilio Perucca3

  • 1Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Current Opinion in Neurology
|January 22, 2019
PubMed
Abstract

Insights

Antiepileptic drugs (AEDs) carry risks for fetal development, including major congenital malformations (MCMs). Valproate poses the highest risk, while lamotrigine, levetiracetam, and oxcarbazepine are associated with lower MCM prevalence.

Area of Science:

  • Pharmacology
  • Teratology
  • Neurodevelopmental Toxicology

Background:

  • Antiepileptic drugs (AEDs) are commonly prescribed to women of childbearing potential.
  • Prenatal exposure to AEDs can lead to various adverse fetal outcomes.
  • Understanding the comparative teratogenicity of AEDs is crucial for risk-benefit assessment.

Purpose of the Study:

  • To review and compare the teratogenic risks of different antiepileptic drugs (AEDs).
  • To focus on major congenital malformations (MCMs), intrauterine growth restriction, and neurodevelopmental effects.
  • To inform rational AED selection and counseling for women of childbearing potential.

Main Methods:

  • Review of prospective registries and meta-analyses data.
  • Analysis of dose-dependent risks for major congenital malformations (MCMs).
  • Evaluation of cognitive and behavioral outcomes following prenatal AED exposure.

Main Results:

  • Valproate demonstrates the highest risk for MCMs, while lamotrigine, levetiracetam, and oxcarbazepine show the lowest prevalence.
  • The risk of MCMs is dose-dependent for several AEDs, including valproate, phenobarbital, phenytoin, carbamazepine, and lamotrigine.
  • Prenatal valproate exposure is linked to cognitive impairments and autistic traits, potentially mitigated by periconceptional folate supplementation.

Conclusions:

  • The risk of adverse fetal effects varies by AED type and dosage.
  • While MCM risks are concentrated in the first trimester, developmental effects can persist throughout pregnancy.
  • Current data enable evidence-based counseling and rational AED selection for women of childbearing potential.

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