GW4 BioMed2 MRC DTP PhD project: How safe are antiseizure medications in pregnancy for conditions other than epilepsy?

This project is one of a number that are in competition for funding from the GW4 BioMed2 MRC Doctoral Training Partnership which is offering up to 21 studentships for entry in September 2025.

The DTP brings together the Universities of Bath, Bristol, Cardiff and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities. More information may be found on the DTP’s website.

Supervisory Team:

Dr Anita McGrogan, University of Bath, Department of Life Sciences - am399@bath.ac.uk

Dr Helen McDonald, University of Bath, Department of Life Sciences

Dr Jan Vollert, University of Exeter, Department of Clinical and Biomedical Sciences

Dr Rebecca Bromley, University of Exeter, School of Biological Sciences

The Project:

Research question: What is the impact of antiseizure medications for non-epilepsy indications in pregnancy?

Outline objectives:

• A systematic literature review to determine the current evidence available about antiseizure medications used in pregnancy for non-epilepsy indications.

• Form a cohort of women with at least one pregnancy recorded in the Clinical Practice Research Datalink during the study period who receive at least one anti-seizure medication for a non-epilepsy indication during their pregnancy

• Determine the prevalence of pregnancy outcomes including loss, or outcomes in the offspring (major congenital malformations, neurodevelopmental disorders) in those prescribed an antiseizure medication compared to those who are not.

• Determine whether any exposures or indications lead to an increased risk of these outcomes compared to unexposed women

Why is this topic important:

Understanding which medications are safe to use in pregnancy is vital both to ensure that the mother’s medical condition is effectively managed during her pregnancy and that her offspring have the best start in life. We have found a high number of women who are prescribed antiseizure medications during pregnancy for non-epilepsy indications including migraine, neuropathic pain and bipolar disorder. Given that current understanding and evidence is mostly in relation to epilepsy indications where doses tend to be higher, understanding the effect of antiseizure medications in non-epilepsy pregnancies is important in helping to untangle medicine, dose and disease effects in order to ensure that women are not denied effective treatments or that more children than necessary are placed at higher risk of developmental impacts.

What is already known about this topic?

We know that in women with epilepsy, studies have demonstrated that in pregnancy a number of anti-seizure mediations, such as valproate, phenobarbital, carbamazepine, increase the risk of adverse physical and neurodevelopmental outcomes in the offspring. The major congenital anomaly risk can be as high as 25% at higher doses of valproate with approximately 40% demonstrating neurodevelopmental impacts which are lifelong. As a result, much consideration needs to be given regarding initiating or continuing these medications during pregnancy and for valproate and topiramate a pregnancy prevention plan has been put in place, restricting their use in women of childbearing potential. These antiseizure medications and others including gabapentin, pregabalin and lamotrigine can also be prescribed for non-epilepsy indications, including migraine, neuropathic pain and bipolar disorder. There are very few studies and little evidence as to the impact of antiseizure medicines when taken to treat non-epilepsy indications, which are often used at lower doses. Those that have been undertaken have a small sample size, results are combined with epilepsy and only consider birth outcomes. Regulatory decisions to restrict use is often based upon data from cohorts with epilepsy indications.

How does this fit with MRC and the DTP’s strategic priorities?

This project: is evaluating interventions for population health; uses data which features strongly in the MRC’s cross-cutting themes; contributes to training of new researchers in data skills for research and innovation.

Methods

Large numbers of pregnancies need to be included to enable rare adverse outcomes, such as major congenital malformations, to be evaluated. The Clinical Practice Research Datalink is a large electronic data source that contains primary care records from 16.5% of general practices in England. The PhD researcher will learn to use SQL to work with the database and identify the cohort of women to be included. Information about prescribing, diagnoses, comorbidities and other characteristics will be collated and outcomes determined. Clinical information, from a specialist clinic for children exposed to medications in utero, will be reviewed to determine the types of symptoms and outcomes seen in childhood. Further, a group with lived experience will be formed to provide additional learning and direction on the outcomes we should be investigating. The PhD researcher will develop the specific direction of the project according to their interests and background: it will be up to the researcher in conjunction with their supervisory team to determine which outcomes and analysis methods to focus on.

Requirements:

Applicants must have obtained, or be expected to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an area appropriate to the skills requirements of the project. Applicants with a lower second class will only be considered if they also have a Master’s degree. Academic qualifications are considered alongside significant relevant non-academic experience.

Non-UK applicants will also be required to have met the English language entry requirements of the University of Bath.

Enquiries and Applications:

Informal enquiries are welcomed and should be directed to Dr Anita McGrogan - am399@bath.ac.uk

Formal applications must be submitted direct to the GW4 BioMed2 DTP using their online application form: GW4 BioMed MRC DTP - GW4 BioMed MRC DTP

A list of all available projects and guidance on how to apply may be found on the DTP’s website. You may apply for up to 2 projects.

APPLICATIONS CLOSE AT 17:00 (GMT) ON 4 NOVEMBER 2025.

IMPORTANT: You do NOT need to apply to the University of Bath at this stage – only those applicants who are successful in obtaining an offer of funding from the DTP will be required to submit an application for an offer of study from Bath.