The effect of antiepileptic drugs on intrauterine growth is reviewed from the Center for Human Molecular Genetics, Nebraska, and the University of Newcastle upon Tyne, UK. The differentiation of drug effects from those of the genotype of the exposed infant is important in the phenotypic expression of any dysmorphism. In a large Swedish study of 963 infants, with data collected prospectively over 3 periods, from 1973 to 1997, carbamazepine had the greatest negative effect on fetal body growth, although the degree was minor.

In a cohort of 400 women with epilepsy studied prospectively in Northern England, fetal malformations in 5% were significantly more common than among the local population. Less than 50% planned their pregnancy, because of failed oral contraceptive, 71% were still having seizures, and 157 of 252 questioned admitted incomplete drug compliance. A follow-up of 105 infants in the Northern English cohort identified 23 developmentally delayed infants, 7 severe.

In Nebraska, a susceptibility gene for valproate-induced anomalies in the mouse has been identified, syntenic with the short arm of human chromosome 16. [1]

COMMENT. This review is important because the teratogenic potential of newly approved antiepileptic drugs has not yet been determined, and their introduction has not replaced that of conventional therapies.