In March 2018 the European Medicines Agency endorsed new measures to avoid in utero valproate exposure. Subsequently, updated valproate regulations published by the Medicines and Healthcare products Regulatory Agency (MHRA)1 contraindicate the use of valproate medicines in girls or women of childbearing age unless they participate in the Pregnancy Prevention Programme. Participants must be fully informed of the risks of valproate use in pregnancy, sign a Risk Acknowledgement Form each year, have an annual specialist review, and adhere to a highly effective (pregnancy rate of <1%) but invasive contraception. Valproate is widely prescribed in general practice for a range of indications including epilepsy, bipolar affective disorder, and migraine. This article will argue that there are exceptional circumstances, and personal and practical implications, that have not been adequately considered in the MHRA regulations on valproate prescribing.
TERATOGENIC RISK
Valproate is a known serious teratogen associated with a risk of major congenital malformations (MCM). Large observational studies of national pregnancy registers have identified MCM rates between 6.7% and 10.3%.2–5 Some of the malformations associated with intrauterine valproate exposure include hypospadias, congenital heart defects, neural tube defects, and orofacial clefts. In addition to the MCM risk there is an increased association with neurodevelopmental, cognitive, and behavioural disorders.
Both MCMs and the neurodevelopmental concerns appear to have a clear dose-dependent relationship.3,4,6 It is also recognised that a family history of MCMs or neurodevelopmental problems respectively contribute substantially to the risk in an individual. Thus, although the MHRA guidance emphasises a risk of around 10% for MCMs, and ≤40% of adverse neurodevelopmental outcomes, for some women on low …
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