The consequences of valproate exposure in utero.

Abstract

Prospective studies have unequivocally identified that valproate poses an unacceptable risk to the foetus in utero, prompting European and national bodies to issue unambiguous advice to neurologists. In 2014, The European Medicines Agency recommended strengthening the restrictions on the use of valproate in women and girls. The joint task force of International League Against Epilepsy-commission on European affairs and European Academy of Neurology responded with a detailed letter, later published in Epilepsia, which included seven recommendations. The first of which is “Where possible, valproate should be avoided in women of childbearing potential.” In January 2015, the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom issued stringent guidance regarding the prescription of valproate to women of child-bearing potential. The data supporting these statements were based on robust prospective research approximating the risk of major malformations at one in ten, and that four in ten children are at risk of neurodevelopmental disorders. The advice is, therefore, that first valproate should not be used in girls or women of child-bearing potential unless other treatments are ineffective or not tolerated, and second that women of child-bearing potential must use effective contraception during treatment. However, valproate cannot simply be discarded from the panoply of anti-epileptic medications since it remains one of the most efficacious therapies; especially for those patients with genetic generalised epilepsy. In recognition of this recent MHRA guidance states “No-one should stop taking valproate without discussing it first with their doctor and the benefits of valproate treatment must be carefully balanced against the risks.” However, despite the advice offered, there remains much that we do not know about valproate and foetal outcomes. Below we discuss three papers that aim to improve the description of risks to the foetus of valproate exposure including foetal loss, autism spectrum disorder and congenital malformations.