In April 2018, strengthened regulatory measures for valproate were introduced following a European-wide review of the latest evidence on harms from valproate exposure during pregnancy, including congenital anomalies and neurodevelopmental disorders including autism in children. These measures include the valproate Pregnancy Prevention Programme, the goal of which is to rapidly reduce and eventually eliminate pregnancies exposed to valproate.
The Medicines and Healthcare products Regulatory Agency (MHRA) is monitoring the impact of, and adherence to, the strengthened regulatory recommendations for valproate including the Pregnancy Prevention Programme, using research studies and routinely collected healthcare data. These include data from the Clinical Practice Research Datalink, national databases in England (NHS Business Services Authority and NHS Digital), Scotland (Information Services Division), and Northern Ireland (Health and Social Care Northern Ireland) linking community drug dispensing and maternity services data where these are available. The MHRA is also accessing data on valproate from clinical audits run by healthcare professional organisations, and information on patients’ experience of introduction of the strengthened regulatory measures via surveys conducted by charitable organisations and patient groups.
Monitoring of prescribing of valproate has shown a slow, continued decline in women of childbearing age. Data show variability in levels of prescribing of valproate to women of childbearing age across different clinical commissioning groups in England. The current monitoring methods used by the MHRA do not enable comprehensive monitoring of compliance at the prescriber or patient level. It is therefore not possible to estimate the number of healthcare professionals who are not complying with all aspects of the Pregnancy Prevention Programme. Surveys of patient experiences have shown some evidence of non-compliance amongst healthcare professionals with the valproate Pregnancy Prevention Programme. Actions are being taken by the relevant professional regulators to follow up and address this.
The recent European review of valproate in pregnancy considered a possible association between birth defects and persistent developmental disorders associated with paternal valproate treatment at the time of conception. The review concluded that there was insufficient evidence at present to establish such a link. A retrospective observational study is to be undertaken to further investigate this issue for which a study protocol is currently being agreed by the European Medicines Agency.