Clinical manifestation of prenatal exposure to valproic acid using case reports and epidemiologic information

The present study includes 28 patients prenatally exposed to valproic acid (VPA) monitored by the Spanish Collaborative Study of Congenital Malformations (ECEMC), from April 1976 to December 1988. Among the 28 cases, 15 (53.6%) were exposed only to VPA and 13 (46.4%) to VPA plus other anticonvulsant drugs. The clinical manifestations observed in those prenatally exposed only to VPA, are compared with the abnormalities observed in those with prenatal exposure to VPA plus other anticonvulsant drugs. To better define the spectrum of clinical manifestation of the prenatal exposure to VPA we used, besides our clinical observations and those from the literature, all available epidemiological data. We consider that a "valproate embryofetopathy (VPEF)" could exist, because different anomalies have been observed in children prenatally exposed to VPA in monotherapy. A facial phenotype of VPA exposure has been reported, and epidemiologic studies have shown an increased risk for congenital defects. However, from a review of published cases as well as those in the present study, it appears that the spectrum of VAE in monotherapy may not include oral clefts.