Valproic acid and fetal abnormality

Abstract

Infants born to women with epilepsy have an increased incidence of fetal abnormality. There are several possible causes for this including inherited factors and the effects of cnvulsions during pregnancy. Some fetal abnormality, however, may be attributed to the teratogenic effects of anticonvulsants, and phenytoin and phenobarbitone are the drugs most commonly blamed for this. Valproic acid and carbamazepine have been recommended in preference to phenytoin and phenobarbitone as anticonvulsants for women of childbearing age. We report 2 cases that may call into question the wisdom of this advice with respect to valproic acid. In each of these 2 cases the mother had taken valproic acid throughout the pregnancy. There are few data on the outcome of pregnancies in which valproic acid was the sole drug taken, but facial, digital and skeletal abnormalities as well as developmental delay have been described. The manufacturers of the drug have collected data on 33 pregnancies in which valproic acid was the sole anticonvulsant. These pregnancies resulted in 25 normal babies, 4 spontaneous abortions, and 4 infants with congenital malformations (2 with meningomyelocoeles, 1 with syndactyly, and 1 with a small ventricular septral defect). Recently 8 participants in the International Clearinghouse for Birth Defects Monitoring Systems reported that valproic acid was associated with neural tube defects in about 1% of fetuses exposed in early pregnancy. We cannot be certain that valproic acid was responsible for the abnormalities in our 2 cases but wish to draw attention to the occurrence of appreciable congenital malformations in 2 infants born to mothers who took valproic acid throughout pregnancy and to the possibility that yet another drug is hazardous for women in their childbearing years.