Sodium valproate in pregnancy: what are the risks and should we use a shared decision-making approach?

Abstract

BackgroundDespite significant teratogenic risks, sodium valproate is still widely prescribed in many countries to women of childbearing age, as a mood stabiliser in bipolar disorder and also in epilepsy. The UK has recently banned valproate use in women who are not in a pregnancy prevention programme. Whilst this ruling reflects prevailing clinical practice, it also highlights an ongoing debate about when (if ever) a woman who is or could become pregnant should be allowed to choose to take valproate.Main bodyWe review the benefits and harms of drugs available for bipolar disorder and epilepsy in women of childbearing age, with a particular focus on teratogenic risk. We speculate on hypothetical rare situations in which potential benefits of valproate may outweigh potential harms in such women. We also review the literature on shared decision-making – on which there is now a NICE guideline and numerous evidence-based decision tools. Drawing on previous work by experts in shared decision-making, we offer a list of ‘frequently asked questions’ and a matrix of options to support conversations with women about continuing or discontinuing the drug in (or in anticipation of) pregnancy. We also consider whether shared decision-making is an appropriate paradigm when considering whether to continue a teratogenic drug.ConclusionWe conclude that because valproate in pregnancy remains the subject of such debate, there is scope for further research – not only into the relative efficacy and safety of alternatives to it – but also into the dynamics of communication and shared decision-making in this situation.

Patterns and determinants of prescribed drug use among pregnant women in Adigrat general hospital, northern Ethiopia: a cross-sectional study

“…The use of such drugs in pregnant women should be avoided unless the potential benefit outweighs their risk. Valproate sodium can cause neural tube defects [38] and maternal use of diclofenac sodium can cause premature closure and constriction of ductus arteriosus with subsequent severe pulmonary hypertension and transient right-sided hypertrophic cardiomyopathies [39]. The use of diazepam may lead to neonatal withdrawal syndrome and cardiorespiratory instability when maternal use occurred shortly before delivery [1,12].…”

Laboratory screening and diagnosis of open neural tube defects, 2019 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

“…Syndromic NTDs are those associated with other birth defects, and these may occur as part of specific single-gene disorders or chromosome disorders. Environmental factors that have been associated with an increased likelihood that a fetus will be affected with an NTD include inadequate maternal folate intake, 13,14 exposure to anticonvulsant medications (e.g., valproate) [15][16][17] (or other folate antimetabolites), early maternal hyperthermia, and increased maternal body mass index (BMI). 18,19 Preconception supplementation with folic acid reduces the incidence of ONTD by up to 80%, dependent on adherence, dose, and NTD prevalence.…”

Challenges of Valproate Treatment During Pregnancy: Pros and Cons

“…It has been documented that changing VPA with other antiepileptic drugsshortly before or during pregnancy in women with good seizure control under VPA treatment may result in status epilepticus. Thus, the decision to treat a woman with VPA should be balanced between the benefit to risk associated with intrauterine exposure [24].…”