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Valproic Acid in Epilepsy

Pregnancy-Related Issues

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Abstract

Valproic acid (sodium valproate) is widely used as a first-line antiepileptic agent. As with many antiepileptic drugs, there are a number of consequences associated with the use of valproic acid in women of child-bearing potential. Most pregnancies have a favourable outcome in women with epilepsy, and these women should not be discouraged from becoming pregnant. Unlike many other antiepileptic drugs, valproic acid has no significant pharmacokinetic interactions with the steroid hormones used in oral contraceptives. During pregnancy, the major risks to mother and child result from loss of seizure control on the one hand, and an elevated risk of major congenital malformations due to antiepileptic drug treatment on the other. In particular, an elevated risk of major congenital malformations associated with valproic acid use has been a consistent finding in studies of patient registries and several large case series. In addition, developmental delay, characterised by low verbal IQ, has also been reported in children exposed to valproic acid in utero, although the relative risk is not precisely known. For these reasons, pregnancies in women being treated with valproic acid need to be planned, and the benefit-risk ratios associated with continuing valproic acid or changing treatment need to be discussed with the patient. When treatment with valproic acid is the most appropriate treatment to achieve optimal seizure control, a number of measures can be implemented to minimise risk to the fetus. These include the use of the lowest possible effective dose of valproic acid in monotherapy (ideally <1000 mg/day), appropriate folic acid supplementation and close antenatal monitoring. Regular counselling is a prerequisite for informed planning of pregnancies and optimisation of the probability of a healthy outcome. Future research on valproic acid and pregnancy should involve risk assessment in large, population-based prospective studies.

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Acknowledgements

Funding for editorial assistance for the preparation of this article was provided by Sanofi-Aventis, the manufacturer of valproic acid.

Dr Pierre Genton has received lecturing and consultancy fees from Sanofi-Aventis, Novartis, GlaxoSmithKline, UCB and Janssen-Cilag over the past 5 years. He has also received a research grant from UCB and participated in the ‘Access to Medication’ international programme of Sanofi-Aventis in developing countries.

Dr Franck Semah has received lecturing and consultancy fees from Sanofi-Aventis, Novartis, GlaxoSmithKline, Pfizer, UCB and Janssen-Cilag over the past 5 years.

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  1. Centre Saint-Paul, Hôpital Gastaut, 13258 Marseille 09, Marseille, France

    Pierre Genton

  2. Neurology Department, Hôpital Sainte-Anne, Paris, France

    Franck Semah

  3. Service Hospitalier Frédéric Joliot, CEA, Orsay, France

    Franck Semah

  4. Universitätsklinik für Neurologie, Medizinische Universität Innsbruck, Innsbruck, Austria

    Eugen Trinka

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Genton, P., Semah, F. & Trinka, E. Valproic Acid in Epilepsy. Drug-Safety 29, 1–21 (2006). https://doi.org/10.2165/00002018-200629010-00001

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