Valproic Acid Monotherapy in Pregnancy and Major Congenital Malformations

This large case–control study used a European database to assess associations between first-trimester valproic acid monotherapy and 14 malformations reported previously to be linked to valproic acid use in early pregnancy. Valproic acid monotherapy was associated with significantly increased risks for 6 of the 14 malformations, including spina bifida, atrial septal defect, cleft palate, hypospadias, polydactyly, and craniosynostosis, as compared with no antiepileptic-drug use or use of other antiepileptic drugs. Valproic acid monotherapy was associated with significantly increased risks for 6 of 14 malformations, including spina bifida, atrial septal defect, cleft palate, hypospadias, polydactyly, and craniosynostosis, as compared with no antiepileptic-drug use or use of other antiepileptic drugs. Valproic acid, which has been used for the treatment of seizure for more than 30 years, has long been recognized as a teratogen. Maternal exposure to valproic acid monotherapy during the first trimester was first linked to an increased risk of congenital spina bifida in the 1980s 1 – 6 ; subsequent studies confirmed this increased risk and also suggested increased risks of other major congenital malformations. 7 , 8 Recently, the American Academy of Neurology recommended avoidance of valproic acid during pregnancy if possible. 9 However, if treatment with valproic acid has been providing good seizure control, it can be difficult to change the . . .