Major malformations with valproic acid

QUESTION: Increasing numbers of pregnant patients are treated with valproic acid, not just for epilepsy, but also for psychiatric conditions. Are there teratogenic risks other than the risk of spina bifida? ANSWER: It has now become evident that valproic acid might cause more than just neural tube defects (NTDs). In a systematic review of all cohort studies intended to answer this question, higher rates of major malformations (and not just NTDs) were found in most studies. The calculated relative risk was 2.59 when compared with other antiepileptic drugs and was 3.77 when compared with risk in the general population. There is compelling evidence that the risk is dose dependent. The risks appear to begin increasing at doses of 600 mg/d and to become more prominent at doses above 1000 mg/d.