By Rachel Arkell.
On 2nd May 2023, the World Health Organization (WHO) published a statement on “the risks associated with valproic acid in women and girls of childbearing potential”, alerting stakeholders to its revised guidance. It states valproic acid should not be prescribed to this cohort of patients due to associated risks of “birth defects and developmental disorders” in children exposed in utero. It continues that valproic acid should not be used as a first-line treatment in this group only, and highlights the need for “effective contraception, without interruption, during the entire duration of treatment.”
Valproic acid, more commonly known as sodium valproate, is a high effective anti-seizure medication used primarily in the treatment of epilepsy. It is widely considered the most effective medication for Idiopathic Generalized Epilepsies (IGEs) (SANAD I, SANAD II), which account for around 25% of all cases of epilepsy. However, since it was first licenced for use in the early 1970s, a growing body of evidence has pointed to its teratogenic risks and, currently, the Medicines and Healthcare products Regulatory Agency (MHRA) estimates a 10% risk of major foetal malformation and around a 40% risk of development disorders if sodium valproate is taken during pregnancy.
Despite these risks, valproate remains a lifesaving drug for many people. It remains on the WHO’s “Model List of Essential Medicines” and, for some with epilepsy, it is the only medicine which provides adequate seizure control. While some countries, including the U.K., have chosen to regulate the prescription of valproate through the use of a Pregnancy Prevention Programme (PPP), it is striking that the WHO would make such a statement. In thus prioritising the prevention of foetal exposure, valproate is considered an “essential medication” unless you could conceive, then the interests of the foetus prevail.
The aim of this blog is twofold. First, I explore the U.K.’s highly restrictive PPP programme, outlining some ethical and legal concerns. Second, I contextualize the WHO’s statement in light of its previous statements concerning alcohol exposure during pregnancy. I argue the WHO should avoid treating all women and girls of childbearing potential as “pre-pregnant”, as such an approach, while aimed at preventing risks of foetal harm, comes at an enormous risk to women and girls.
The Problems of Pregnancy Prevention Programmes
Following a large Public Hearing held by the European Medicines Agency in 2017, a message was communicated to Member States that the efficacy of previous safety measures were insufficient, and more needed to be done to prevent the risks associated with valproate exposed pregnancies. In response, the MHRA introduced its PPP the following year.
The PPP has a number of conditions: first, it removes valproate as first-line treatment for girls and women of childbearing potential. Second, it endorses mandatory contraception for those wishing to remain on valproate. Third, it requires an annual risk acknowledgement form, confirming that patients have received adequate counselling surrounding the risks which valproate may cause in pregnancy. The PPP endorses a blanket approach for all in receipt of valproate. In its place, the PPP imposes a decision on both clinicians and patients, ignoring individual goals and priorities and displacing the usual standards of medical decision making and consent, as endorsed in professional guidance.
Importantly, it conflates capacity for pregnancy, with intention. Embedded within a PPP is the assumption that just because you could conceive, preventing foetal exposure to a (potential) foetus must be the most important priority in choosing medication. Such an approach is inherently sexist, and unfortunately, this is not the first time that the WHO has chosen to treat “women and girls of childbearing potential” in this way.
In June 2021, the WHO faced considerable criticism for prioritising foetal interests over women’s autonomy within their draft global alcohol action plan for 2022-2030. This recommended that “Appropriate attention should be given to… prevention of drinking among pregnant women and women of childbearing age” with the aim of preventing fetal alcohol spectrum disorders (FASD), a range of conditions associated with prenatal alcohol exposure.
This phrasing garnered a huge amount of media attention. In a letter to the Times, Professor Marian Knight argued that this draft was “another example of a systemic bias that affects women simply because they are or may become pregnant.” Highlighting that women receive a lower quality of care, Knight noted:
The default appears to be always to consider (often theoretical) risks of medication in pregnancy to a foetus or infant without considering the benefits of treatment to the woman herself.
She further notes that since the introduction of the PPP, “deaths of pregnant and postnatal women owing to sudden unexpected death in epilepsy (SUDEP) have doubled.” My doctoral research has found that many clinicians struggle with an awareness that they are denying women the best treatment available to them, sometimes with catastrophic consequences. As one clinician summarised:
I think there’s a lot of women out there who have suffered horrible seizures, humiliating seizures, injurious seizures and SUDEP. People who’ve maybe died of epilepsy who didn’t need to because they could have been on a drug that really, really worked. And I don’t know how you weigh those various things up, but I’m sure that is the case because that’s my experience, in that I have struggled. [emphasis included]
Not only is the “prioritisation of foetal interests” used to justify treating women as “permanently pre-pregnant”, undermining their legal right to medical decision-making, it results in huge inequities which, in some cases, will cost lives.
However well-intentioned, policies and regulations which undermine autonomy and remove fundamental rights should be cautiously deployed. PPPs, as currently formulated, raise a number of difficult ethical questions: what does it mean to restrict the reproductive autonomy of those with chronic conditions when their long-term medication poses risks to (potential) foetuses? Should patients be forced to try less-effective medication, which carries a smaller risk to (potential) foetuses, regardless of their pregnancy intentions? And for how long? What degree of risk is acceptable for a patient to take on, just to avoid potential foetal exposure? And finally, who is best placed to make these decisions, the MHRA or women in consultation with their doctors?
Many of these questions remain unanswered, but as such policies grow in popularity, the need to answer them is not just warranted, but necessary.
Author names: Rachel Arkell
Affiliations: University of Kent
Competing interests: None declared
Social media accounts: @R_Arkell