Possible valproate teratogenicity

I. Tein and D. L. MacGregor

The teratogenic risk of maternal valproic acid therapy and the prenatal effects on growth and morphogenesis have been difficult to determine, in part, because of the small number of epileptic women who receive valproic acid as the sole anticonvulsant therapy. An increased incidence of open neural tube defects has been suggested and other isolated case reports have noted the presence of certain dysmorphic features. We present a patient whose defects in morphogenesis appear to be associated with valproic acid exposure only, and suggest a clinical phenotype that our patient shares with other children exposed to prenatal valproic acid therapy. Features described previously include dysmorphic facies with hypertelorism, prominent forehead, low flat nasal bridge, low-set or odd-shaped ears, and micrognathia with growth deficiency of prenatal or postnatal onset. A striking and perhaps unique feature in our patient consists of hypoplasia of the lateral margins of the zygomatic arches. We discuss the pharmacokinetics of valproic acid in pregnancy and in the neonatal period.