Valproate (VPA) is one of the most frequently used
antiepileptic drugs (AEDs). Concern has recently been raised regarding VPA medication during pregnancy and teratogenic effects in the offspring. Both
neural tube defects (5, 18, 34) and a constellation of signs termed the
fetal valproate syndrome (1, 12) have been reported.
Benzodiazepines (BZDs) are also widely used and sometimes as effective adjunctives in AED
therapy. Both VPA and BZD have close connections to
GABA transmission. Recently, clinical and epidemiological human studies (26, 27, 37, 39), supported by animal studies (17, 24, 40), have indicated that BZDs may act as human
teratogens. We report on 7 children with congenital malformations, dysmorphism and abnormal neurological signs from birth. The mothers had well controlled primary generalized
absence epilepsy without major
seizures during pregnancy. Five children had been exposed to VPA monotherapy and two children to VPA and BZD combined during the first trimester. Those two infants had
myelomeningoceles and the most pronounced dysmorphism in the group. We propose that these observations indicate a possible amplifying action of BZDs on VPA teratogenicity. Unrecognized BZD use during pregnancies exposed to VPA may be of importance when estimating the teratogenic risks of VPA
therapy.