Malformations in offspring of women with epilepsy: a prospective study

Epilepsia. 1999 Sep;40(9):1231-6. doi: 10.1111/j.1528-1157.1999.tb00851.x.

Abstract

Purpose: The incidence of malformations among infants of mothers with epilepsy treated with antiepileptic drugs (AEDs) during pregnancy is higher than that found in the general population. The aim of this study was to contribute to providing a definition of the rate of congenital anomalies in the offspring of mothers with epilepsy and to detect possible risk factors.

Methods: Since 1977, 517 pregnancies were followed up at the San Paolo Hospital in Milan by a team of epileptologists and obstetricians. The patients received monthly obstetric and neurologic examinations, and the blood levels of AEDs were tested monthly. During pregnancy the patients underwent ultrasound investigations to evaluate fetal morphology and development. At the time of delivery, the infants were submitted to a standardized examination by a pediatrician, and a more detailed clinical examination was performed on day 5. Malformations were classified as (a) genetic and chromosomic, (b) severe and mild malformations, and (c) deformities.

Results: The overall rate of malformations was 9.7%: of these, 5.3% were structurally severe, 2.2% were mild, 0.4% were chromosomic-genetic, and 1.8% were deformities. No malformation was detected in the 25 untreated patients.

Conclusions: The risks of teratogenicity have been regarded as multifactorial, involving such factors as genetic predisposition, although most prospective studies show that AED-related factors are the primary risk factors for an increased incidence of congenital malformations.

MeSH terms

  • Abnormalities, Drug-Induced / epidemiology*
  • Anticonvulsants / adverse effects*
  • Anticonvulsants / therapeutic use
  • Carbamazepine / adverse effects
  • Carbamazepine / therapeutic use
  • Comorbidity
  • Congenital Abnormalities / epidemiology*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Epilepsy / drug therapy*
  • Epilepsy / epidemiology
  • Female
  • Gestational Age
  • Humans
  • Incidence
  • Infant, Newborn
  • Italy / epidemiology
  • Male
  • Maternal-Fetal Exchange
  • Phenytoin / adverse effects
  • Phenytoin / therapeutic use
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Pregnancy Complications / epidemiology
  • Prospective Studies
  • Risk Factors
  • Valproic Acid / adverse effects
  • Valproic Acid / therapeutic use

Substances

  • Anticonvulsants
  • Carbamazepine
  • Valproic Acid
  • Phenytoin