Prenatal exposure to valproic acid during pregnancy and limb deficiencies:A case-control study

We conducted a case-control study using data from the Spanish Collaborative Study of Congenital Malformations (ECEMC) on the relationship between pren atal exposure to valproic acid (VPA) and the presence of limb deficiencies in newborn infants. Among a total of 22,294 consecutive malformed infants ( once we excluded genetic syndromes) and 21,937 control infants with specifi ed data on antiepileptic drugs during gestation, 57 malformed infants and 1 0 control infants were exposed to VPA during the first trimester of pregnan cy, Of the total of malformed infants exposed to VPA, 36.8% (21/57) present ed with congenital limb defects of different types (including overlapping d igits, talipes, clubfoot, clinodactyly, arachnodactyly, hip dislocation, pr e- and postaxial polydactyly, etc.), three of them having limb deficiencies . The result of the case-control analysis shows a risk for limb deficiencie s of odds ratio = 6.17 [confidence interval (CI) 1.28-29.66, P = 0.023], af ter controlling for potential confounder factors. If are consider that in o ur population the prevalence at birth of this type of defect is 6.88 per 10 ,000 livebirths (95% CI 6.43-7.36) we can estimate that the risk for women treated with VPA of having a baby with limb deficiencies would be around 0. 42%. The limb deficiencies in the three patients exposed to VPA were the fo llowing: the first case was a newborn infant with hypoplasia of the left ha nd, the second patient was a newborn infant with unilateral forearm defect and hypoplastic first metacarpal bone in the left hand, and the third patie nt presented with short hands with hypoplastic first metacarpal bone, absen t and hypoplastic phalanges, retrognathia, facial asymmetry, hypospadias, t eleangiectatic angioma in skull, and hypotonia. (C) 2000 Wiley-Liss, Inc.