Optimising outcomes in pregnant women with epilepsy and their babies: Reducing maternal seizure risks and assessing long-term safety of antiepileptic drugs

RESEARCH QUESTIONS In pregnant women with epilepsy, can implementation of an evidence-based intervention with structured risk assessment (Epi-Safe) improve care than currently provided, reduce seizures, optimise anti-epileptic drug (AED) use, reduce complications to mother and baby, and be cost-effective?

BACKGROUND Seizures in pregnancy can result in maternal death and complications. In-utero exposure to AEDs may cause congenital malformations and/or affect the neurodevelopment of the baby.

The two main factors contributing to poor outcomes in pregnant women with epilepsy and their babies are high-risk women either not accessing specialist epilepsy care or accessing it late, as their underlying risk of seizures or suboptimal AED use are not recognised. women s non-adherence to AEDs in pregnancy because of concerns about the effect of AEDs on their babies.

But stopping AEDs predisposes them to seizures. There is a lack of evidence on the long-term safety of the commonly used newer AEDs.

AIMS AND OBJECTIVES Our aim is to improve maternal and offspring outcomes in pregnant women with epilepsy through early identification of women and their babies at risk of complications, and ensuring timely specialist epilepsy input with evidence-based information on the risks-benefits of their treatment.

We will Co-design and evaluate an intervention (Epi-Safe) incorporating structured risk assessment with robust implementation strategies to primarily facilitate early specialist epilepsy care for high-risk women, and secondarily, reduce seizures and complications.

Assess the long-term impact of the newer AEDs on child neurodevelopment (7-11-years, Epi-Follow) Determine the acceptability, implementability and cost-effectiveness of Epi-Safe and its long-term impact. METHODS Our Programme has six interlinked work packages (WP).

WP1(12m): Map evidence and gather stakeholder views to design the intervention (Epi-Safe) by (a) reviewing existing recommendations on seizure risk assessment (systematic review) (b) quantifying the adverse effects of AEDs on mothers and babies (systematic review); association between maternal AED non-adherence, AED levels and seizures (secondary analysis of primary study) (c) mapping care and baseline data in participating sites (observational study); identifying the barriers to women from diverse groups to access care, and for healthcare professionals to deliver care (qualitative research).

WP2(12m): Co-design and field-test the Epi-Safe bundle (mixed methods study).

WP3(39m): Evaluate whether Epi-Safe increases the proportion of high-risk women accessing specialist epilepsy care in the first trimester, and reduces seizures and complications in women with epilepsy (cluster randomised trial, 30 sites), and its acceptability to stakeholders (qualitative research).

WP4(28m): Study the longer-term development of children (7-11-years) exposed in-utero to newer AEDs in two NIHR-funded cohorts (Epi-Follow, observational study). WP5(41m): Investigate the cost and long-term impact of Epi-Safe (economic evaluation).

WP6(60m): Promote involvement and engagement of women and their support networks TIMELINES 60 months ANTICIPATED IMPACT AND DISSEMINATION We expect a reduction in maternal mortality and morbidity for women with epilepsy, and improved offspring outcomes, through timely access to specialist care, thereby reducing seizure risks and optimising AED use.

We will disseminate the work widely to patients and public, healthcare professionals, and policymakers through academic, and social media channels to achieve impact.