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Valproic acid: long-term effects on children exposed in utero

FEATURED REVIEW Numerous follow-up studies show that valproic acid is more teratogenic than other antiepileptics. The use of valproic acid should be avoided throughout pregnancy, as well as by women of child-bearing age not using effective contraception.
Full review (4p) in English available for download by subscribers.

Abstract

  • Numerous follow-up studies of pregnancies in women with epilepsy show that valproic acid is more teratogenic than other antiepileptics. The risk of malformations increases with doses above 1000 mg/day.
  • Malformations associated with valproic acid include neural tube defects in 1-2% of exposed children, as well as urogenital, craniofacial and digital abnormalities. Cardiac disorders and limb defects have also been reported.
  • Convergent results of several cohort studies show that exposure to valproic acid in utero has detrimental effects on intelligence, language and behaviour, which appear in school-age children.
  • In practice, the use of valproic acid should be avoided throughout pregnancy, as well as by women of childbearing age not using effective contraception. If a woman is planning pregnancy, the choice of valproic acid should be reassessed with the patient. If valproic acid therapy is maintained, the minimum effective daily dose should be determined and folic acid supplementation initiated.

©Prescrire January 2010

"Valproic acid: long-term effects on children exposed in utero" Prescrire International 2009; 18 (104): 253-257 (pdf, subscribers only).

Download the full review