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

    Prescrire International
    |December 23, 2009
    PubMed

    Insights

    Valproic acid in pregnancy poses significant teratogenic risks, including birth defects and developmental issues in children. Women of childbearing age should avoid this antiepileptic, especially during pregnancy.

    Area of Science:

    • Neurology
    • Teratology
    • Developmental Pediatrics

    Background:

    • Valproic acid is a widely prescribed antiepileptic drug.
    • Previous studies suggest potential risks associated with valproic acid use during pregnancy.

    Purpose of the Study:

    • To synthesize current evidence on the teratogenicity and developmental effects of valproic acid exposure in utero.
    • To provide updated guidance for clinicians regarding valproic acid use in women of childbearing age and during pregnancy.

    Main Methods:

    • Review of numerous follow-up studies and cohort studies on pregnancies in women with epilepsy.
    • Analysis of reported malformations and neurodevelopmental outcomes in children exposed to valproic acid in utero.

    Main Results:

    • Valproic acid is associated with a higher risk of malformations compared to other antiepileptics, particularly at doses exceeding 1000 mg/day.
    • Specific malformations include neural tube defects (1-2%), urogenital, craniofacial, and digital abnormalities, cardiac disorders, and limb defects.
    • In utero exposure to valproic acid detrimentally affects intelligence, language, and behavior in school-aged children.

    Conclusions:

    • Valproic acid should be avoided throughout pregnancy and by women of childbearing potential not using effective contraception.
    • For women on valproic acid therapy planning pregnancy, treatment should be reassessed, aiming for the minimum effective dose and initiating folic acid supplementation.

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