Human Serum Teratogenicity Studied by Rat Embryo Culture: Epilepsy, Anticonvulsant Drugs, and Nutrition

Abstract

Epileptic women have a greater risk for spontaneous abortions and children with birth defects than do nonepileptics. In a unique approach to identifying causes of these problems, whole rat embryos were cultured for 48 h on blood sera from epileptics. In the 1st part of the study, 3 embryos were cultured on each serum sample from 128 different epileptics being treated with either single anticonvulsants or no drug to compare the teratogenicity of these drugs. Sera from subjects receiving either phenobarbital or no drug had comparable frequencies of cultured embryo abnormalities, which were lower than those from subjects taking phenytoin, valproic acid or carbamazepine. In the 2nd phase of the study, attempts to identify causes for serum teratogenicity led to the finding that the abnormalities and reduced embryo growth produced by many samples could be completely overcome by adding vitamins and/or amino acids to the serum. Of 53 samples tested, 32 (60%) were corrected by supplementation (17 of 23 phenytoin, 7 of 9 phenobarbital, 6 of 12 carbamazepine, none of 6 valproic acid and 2 of 3 no drug). Although the results of this study provided a general assessment of drug teratogenicity that agreed with other studies and emphasized the role of nutrition in fetal defects, the importance of individual differences in causes of teratogenicity was also noted.