Comment: valproate dose effects differ across congenital malformations.

Fetal valproate exposure has been associated with the highest risk of congenital malformations among antiepileptic drugs.(1) Valproate's effect is dose-dependent(1) and has been associated with multiple specific malformations.(2,3) Vadja et al.(4) examined data from the Australian Pregnancy Registry (1999-2012 data), which included 1,705 pregnancies with 436 valproate exposures.(4) They found that the use and dosages of valproate have fallen over the last 5 years. The rates of spina bifida and hypospadius in those exposed dropped with reducing dosages of valproate, but the rates of other malformations did not. Mean dosages for malformations were higher for spina bifida (2,000 mg/d) and hypospadius (2,417 mg/d) than all other malformations (1,083 mg/d).