The BONDING Study
Research type
Research Study
Full title
Biomarkers of Neurological Disease in Utero (The BONDING study)
IRAS ID
253497
Contact name
Tayyib T A Hayat
Contact email
Sponsor organisation
Nottingham University Hospitals NHS Trust
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
There are approximately 50 million people with epilepsy worldwide [1], with approximately 3-5 births per thousand to women with epilepsy [2]; in the UK there are 2500 births/year to women with epilepsy [3]. The teratogenic effects of anti-epileptic drugs (AEDs) on the fetus is a major public health concern[4]. In 2016 UK national prescribing data showed around 18,000 women of child-bearing age were taking Valproate[5], for which current evidence suggests has the most potent teratogenic effects of all AEDs. The Medicines and Healthcare Products Regulatory Agency (MHRA) has formulated a prevention programme aimed at reducing the rates of valproate-associated teratogenicity. Longitudinal studies of fetal AED exposure show increased rates of congenital malformations, abnormal motor development, lower IQ, and poorer educational attainment[6-8]. Early exposure to neuromodulatory drugs likely induces abnormalities in structural brain development, neuromotor behaviour, and functional networks. Fetal MRI presents a novel multimodal approach for interrogating the effects of pathological exposures, identify biomarkers, define onset of abnormalities, and the dose response. This may aiding risk stratification, identify candidates for earlier intervention, and improve neurodevelopmental outcomes.
This study will undertake fetal MRI on 20 subjects to further characterise in utero brain development. This is a pilot study which will include 2 cohorts: women with epilepsy (WWE) (N=10), and age-matched controls healthy pregnant controls (HC) with no known neurological disorder (N=10). All fetal subjects will be scanned from 18 weeks gestation to term. Once characterised, the aim is to undertake a larger study, to disentangle the effects of AEDs from the effects of the Epilepsy syndrome.
References
[1] de Boer et al. Epilepsy Behav (2008)
[2] Harden et al. Epilepsia (2009)
[3] Thanagaratinam et al. RCOG Guideline No. 68 (2016)
[4] Tomson et al. Epilepsia (2004)
[5] Sodium Valproate Prescribing. NHS England (2017)
[6] Bromley et al.JAMA (2017)
[7] Baker et al. Neurology (2015)
[8] Meador et al. Lancet Neurology (2013)REC name
East Midlands - Derby Research Ethics Committee
REC reference
19/EM/0074
Date of REC Opinion
9 Apr 2019
REC opinion
Further Information Favourable Opinion