Effect of folic acid supplementation on congenital malformations due to anticonvulsive drugs

Eur J Obstet Gynecol Reprod Biol. 1984 Nov;18(4):211-6. doi: 10.1016/0028-2243(84)90119-9.


A study was conducted to determine the frequency of malformations among newborn infants of mothers receiving anticonvulsive therapy, with and without supplementation of folic acid. In the retrospective part of the study, the frequency of congenital malformations among the 66 newborn of 24 women who received anticonvulsive drugs without the supplementation of folic acid was 15% (10 children). The defects noted were congenital heart disease, cleft lip and palate, neural tube defects and skeletal abnormalities. Three out of the 10 children were stillborn or died immediately after delivery. In the prospective study of the 22 epileptic women with folic acid supplementation to their anticonvulsive regimen, 33 infants were born alive, without congenital malformations and of normal body weight. The teratogenic activity of anticonvulsant drugs seems to be mediated by interference with folic acid metabolism, and such activity might be influenced by hereditary and environmental factors. When an epileptic woman wishes to become pregnant, it is recommended that folic acid be added to her regimen.

MeSH terms

  • Abnormalities, Drug-Induced / etiology*
  • Abnormalities, Drug-Induced / prevention & control
  • Anticonvulsants / adverse effects*
  • Anticonvulsants / therapeutic use
  • Drug Therapy, Combination
  • Epilepsy / drug therapy*
  • Female
  • Folic Acid / therapeutic use*
  • Humans
  • Infant, Newborn
  • Male
  • Phenytoin / adverse effects
  • Phenytoin / therapeutic use
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Prospective Studies
  • Retrospective Studies


  • Anticonvulsants
  • Phenytoin
  • Folic Acid