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Fetal growth restriction and birth defects with newer and older antiepileptic drugs during pregnancy

Gyri Veiby1, Anne Kjersti Daltveit, Bernt A Engelsen

  • 1Department of Clinical Medicine, Section for Neurology, University of Bergen, Bergen, Norway, gyri.veiby@hotmail.com.

Journal of Neurology
|January 23, 2014
PubMed

Insights

Prenatal exposure to antiepileptic drugs can increase risks for fetal growth restriction and birth defects. Topiramate and valproate monotherapy showed significant risks, while other newer antiepileptic drugs had lower malformation rates.

Area of Science:

  • Obstetrics and Gynecology
  • Pediatrics
  • Pharmacology

Background:

  • Antiepileptic drugs (AEDs) are frequently used during pregnancy.
  • Assessing the risks of AEDs for fetal development is crucial for informed clinical decisions.
  • Previous studies have yielded conflicting results regarding AED teratogenicity.

Purpose of the Study:

  • To evaluate the association between prenatal exposure to various antiepileptic drugs and the risks of fetal growth restriction and congenital malformations.
  • To compare risks associated with newer and older generation antiepileptic drugs.
  • To utilize a large, unselected Norwegian birth cohort for robust statistical analysis.

Main Methods:

  • Retrospective cohort study using the Medical Birth Registry of Norway (1999-2011).
  • Inclusion of 2,600 children exposed to AEDs in utero and 771,412 unexposed children.
  • Comparison of outcomes including small for gestational age (SGA) birth weight, microcephaly, and major congenital malformations (MCMs).
  • Internal control group of children born to untreated mothers with epilepsy.

Main Results:

  • AED-exposed children showed a moderate risk of growth restriction.
  • Topiramate exposure was linked to increased risks of microcephaly (OR 4.8) and SGA (OR 3.1).
  • Valproate monotherapy was significantly associated with birth defects (OR 2.5), particularly septal heart defects and hypospadias.
  • Increased risk of major birth defects observed in subsequent pregnancies following valproate use (OR 10.4).
  • Carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, gabapentin, and pregabalin showed low malformation rates.

Conclusions:

  • Topiramate is associated with substantial fetal growth restriction and potentially increased malformation rates.
  • Newer-generation AEDs, excluding topiramate, demonstrate low malformation risks.
  • Valproate monotherapy carries a significant risk of birth defects, especially in cases of repeated pregnancies.
  • Untreated epilepsy in mothers did not increase malformation risk compared to the general population.

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