Exposure to valproate (Depakote) during pregnancy is associated with an increased risk of which congenital anomaly?

• A. Cleft lip
• B. Spina bifida
• C. Hypospadias
• D. Microcephaly

Answer: (B)

Valproate exposure during pregnancy most strongly increases the risk of neural tube defects, with spina bifida being the classic anomaly. The neural tube forms and closes very early in gestation, and valproate can interfere with folate-dependent processes essential for neural tube closure. This disruption leads to open spinal defects characteristic of spina bifida. While valproate can be associated with other malformations, the link to neural tube defects is the hallmark most frequently tested. Because of this risk, valproate is avoided in pregnancy whenever possible, and if a patient is of childbearing potential, planning often includes safer alternatives and folate optimization.