[MI] Medicines and Pregnancy Registry - Antiepileptic use in females aged 0 to 54 in England: April 2018 to September 2023

This analysis has been undertaken as requested by the MHRA. 

The first stage of development of this registry was the ingestion into NHS England of prescribing data from the NHS Business Services Authority (BSA) and linkage of this to the Maternity Services Data Set (MSDS) and Hospital Episode Statistics (HES) data to form the core register on which the full registry will be based. The first report from this core register, restricted in the first instance to girls and women prescribed valproate, was published in February 2021. The publication series is available: https://digital.nhs.uk/data-and-information/publications/statistical/mi-medicines-and-pregnancy-registry

 This core register will be further developed with linkage to additional existing and new datasets, including clinical registries and data on developmental outcomes, and with new bespoke data collections to fully deliver on its key objectives and include all women prescribed antiepileptics. In July 2020, the Independent Medicines and Medical Devices Safety Review, tasked in part with examining how the healthcare system in England responded to reports about harmful side effects with valproate and how to respond to them more quickly and effectively in the future, recommended the establishment of a registry for all women on antiepileptic drugs who become pregnant, to include mandatory reporting of data relating to them and their child(ren) collated over lifetimes. This report represents the first findings for the core register for the antiepileptics registry, developed in line with this recommendation, while also providing a basis for the development of medicines in pregnancy registries in other clinical areas. This report is not solely an investigation into the prescribing of antiepileptics. It is foremost an analysis of existing administrative patient data as a proof of concept, to establish the use and value of these data sets in supporting robust and sustainable medicine registries. However, the data produced are designed to support the MHRA in monitoring the level of success of the valproate pregnancy prevention plan and to enable the wider health and care system to further understand outcomes for women prescribed antiepileptics during pregnancy and their children and consequently to improve patient care. In particular, in light of the data highlighted in the CHM report on emerging data on the potential risk of neurodevelopmental disorders, specific analyses describing the use of topiramate around and during pregnancy are presented.

Antiepileptics are important in controlling seizures and other epilepsy symptoms and untreated epilepsy in pregnancy can result in harm to the mother and child. However, use of some antiepileptic drugs during pregnancy has been associated with a range of harmful effects to the child. Valproate is a licensed treatment for epilepsy and bipolar disorder. It is associated with a significant risk of birth defects and developmental disorders in children born to women who take valproate during pregnancy. In 2018, following further evidence on the nature and magnitude of risks to the unborn child the MHRA advised that valproate must not be used in any woman or girl able to have children unless she is supported by a Pregnancy Prevention Programme (PPP). This is designed to make sure patients are fully aware of the risks and the need to avoid becoming pregnant. Further details from the MHRA on valproate and the PPP can be found on the Government's Valproate use by women and girls guidance page. 

In January 2021, the Commission on Human Medicine (CHM) published a review of the available safety data for antiepileptics during pregnancy. Their report concluded that data show that carbamazepine, phenobarbital, phenytoin, and topiramate are associated with an increased risk of major congenital malformations although data on the risk with some of these other antiepileptics are limited. They also highlighted data for topiramate, phenobarbital, and phenytoin that raises concerns that use of these products during pregnancy may be associated with poorer development outcomes in children, although available studies are limited for these as they are for other antiepileptics with regards to this risk. The report concluded that lamotrigine and levetiracetam are the safer antiepileptics to use during pregnancy. However, even for these medicines, data are not available to rule out a risk of neurodevelopmental disorders and delays. As of March 2023, cenobamate has been proactively included in the list of medicines monitored by the registry. This is due to the existing non-clinical data on the potential risks to the unborn child and their future development.

This report is to provide information on the prescribing of medicines in relation to pregnancies based upon data from the core register which has been developed to form the basis of the planned wider medicines registries and to identify limitations in the existing data sources.

It is important women do not stop taking their antiepileptic medicine without first discussing it with their doctor. Women receiving treatment who anticipate they may become pregnant at any point in the future are advised to discuss their treatment with a healthcare professional.

These statistics are classified as management information, further releases are planned as the time span of the data increases and more insights and detailed statistics are developed. These statistics are published to involve users and stakeholders in their development and to build in quality at an early stage. It is important that users understand that limitations may apply to the interpretation of this data. NHS England welcome feedback on the analysis included and suggestions for further analysis. Information on each data source is also provided in the report. A wealth of further information on each individual dataset is available through specific, more detailed publications referenced there.