Congenital malformations due to anticonvulsive drugs.

A retrospective study of congenital malformations in the offspring of 20 women who received antiepileptic drugs during pregnancy is presented. Of 56 births, 9 children (16%) were born with malformations. Four children were born dead or died shortly after delivery. Congenital heart disease, cleft lip with or without cleft palate, neural tube defects, and skeletal abnormalities were the commonest anomalies found. One child had a recognizable pattern of multiple malformations. The increased perinatal mortality was mainly due to congenital malformations and spontaneous hemorrhage. The teratogenic activity of anticonvulsant drugs is mediated by interference with folic acid metabolism, and such activity might be influenced by hereditary and environmental factors. Bearing in mind the importance of anticonvulsant therapy in epilepsy, there is certainly need for an investigation of the problem in a larger and more representative birth population than that described.