Title: Prevention of epilepsy by reducing neonatal encephalopathy (PREVENT) study
Funder: Department of Health and Social Care

Abstract: The aim of our program is to examine if a pragmatic, evidenced based and generalisable intrapartum care bundle involving birth companions and empowering mothers will reduce birth injury related epilepsy at 18 months of age in India. Twelve million people with epilepsy live in India accounting for one sixth of the global burden. Every year, 500,000 new cases of epilepsy occur in India, of which birth related brain injury is estimated to account for 87,000 (17.4%). Hypoxic ischemic encephalopathy (HIE) is the commonest birth related brain injury and occurs in 14 per 1000 live births; 10 times more than in the UK. Many of these are preventable by better intrapartum care. Approximately 20% of the babies with birth related brain injury will develop epilepsy during early childhood, with an onset before the first birthday in 69%. Our care bundle will have four key elements (interventions): (1) birth companion providing constant 1:1 care during labour and early perinatal period; (2) fetal surveillance during active labour by a nurse or midwife using a graphic display Doppler; (3) labour management by an electronic partogram with an alert and nag feature based on the current WHO guidelines; (4) brain oriented early newborn care with resuscitation where indicated. The care bundle will be evaluated using a prospective interrupted time series design, recruiting 80,000 women delivering in one of the three participating centres in south India, over two years. Accurate baseline data will be collected during the first year and the optimised care bundle will be introduced during the second year. All full term newborn infants admitted to the neonatal unit with perinatal brain injury during both periods, will have detailed assessments including video electroencephalography, and magnetic resonance imaging, and will be followed up until 18 months of age. Primary outcome is the number of infants with epilepsy (categorised per current ILAE guidelines) at 18 months of age expressed as per 1000 term livebirths. We will use a segmented logistic regression to divide the time series into pre- and post-intervention segments, with the intervention date as the intersection between segments. The difference in the two segments will be quantified using the level (step change) and slope (trend change). The total duration of the study is four years including 24 months of recruitment and 18 months of follow-up. We have partnered with the Government of India who were involved in drafting the key elements of our care bundle. If effective, our care bundle can be readily incorporated into the Labour Room Quality Improvement (LaQshya) programme, for national implementation, thus averting approximately 50,000 epilepsy cases every year in India. Our programme will provide opportunities for academic and clinical capacity building in India in midwifery, neonatal/paediatric neurology and epilepsy, and public health. The work program and results will be disseminated through a carefully designed communication programme involving parent groups, Vidyasagar foundation and the Epilepsy association of India, in addition to effective use of social media, short documentaries, scientific presentations and publications.

Lay abstract: Approximately 12 million people with epilepsy live in India, costing at least $1.7 billion USD per annum to the Indian economy. Although epilepsy is not curable in most cases, by reducing birth related brain injury a substantial number of these cases could be prevented. Birth related brain injury occurs in 14 per 1000 livebirths in India, as opposed to 1 to 3 per 1000 livebirths in the UK, and a substantial proportion are preventable by better labour (intrapartum) care. Our program will examine if a simple, pragmatic, evidenced based and generalisable intrapartum care bundle for labour involving birth companions and empowering mothers, will reduce perinatal brain injury and thus prevent epilepsy in India. A multi-disciplinary team of world leading experts in neonatal brain injury and neuroimaging, obstetrics, midwifery, neurology and epilepsy, qualitative research and public health from the UK and India, along with parent representatives and community leaders, will undertake this work. Our care bundle will be evaluated using a prospective interrupted time series study over four years in three public sector hospitals in south India recruiting at-least 80,000 women. During the first year of the study, we will collect accurate base line data on birth related brain injury, optimise and pilot the care bundle. The care bundle will be implemented during the 2nd year, with outcomes evaluated during years 3 and 4. All term babies with birth related brain injury admitted to the neonatal unit during the first two years will be followed up until 18 months of age. The primary outcome is the number of term infants developing epilepsy at 18 months following the implementation of the care bundle. In parallel we will examine the views of stakeholders and the cost-effectiveness of the care bundle to inform national health policy in India. An international expert scientific advisory committee including the Deputy Commissioner of Maternal Health, Govt of India, will advise on the development and evaluation of the care bundle. Wider engagement of the public and community, will be promoted through an extensive and carefully planned communications program. This work will provide opportunities for academic and clinical capacity in India in midwifery, neonatal/paediatric neurology, and public health. As our work builds on the existing strong collaboration between Imperial College London and premier Indian institutions as a part of the HELIX (Hypothermia for Encephalopathy in Low and Middle-income countries) trial, the start-up time and additional risks are minimal. Our program is complementary and well aligned with the ongoing major health programs of the Govt of India, including the Alliance for Saving Mothers and Newborn (ASMAN) and Labour Room Quality Improvement (LaQshya) program, and hence can be readily adopted into the national health policy.

Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: NEUROLOGICAL;REPRODUCTIVE HEALTH AND CHILDBIRTH