Title: Improving maternal and perinatal outcomes in high-risk pregnancies
Funder: Department of Health and Social Care

Abstract: Background 800,000 women give birth every year in the UK. Medical co-morbidities now affect 45% of all pregnancies and greatly increase the risk of maternal and perinatal mortality and morbidity. This research programme focuses on high-risk pregnant women, aiming to reduce adverse outcomes for the mother and baby. The programme, funded principally by existing NIHR grants, comprises six work streams (WS) based at King's College London (KCL) and Guy's and St Thomas' NHS Foundation Trust (GSTT), and working within the national collaborative NIHR Clinical Research Networks. Hypertensive disorders of pregnancy (including pre-eclampsia and pre-existing chronic hypertension) and intrahepatic cholestasis of pregnancy (ICP) are associated with increased maternal and fetal morbidity and mortality in the UK and worldwide but uncertainties remain over management and treatment options. Aims To improve maternal and perinatal outcomes in high-risk pregnancies within five years this programme has the following aim: Aim 1 is to reduce maternal and perinatal mortality and morbidity through evidence-based interventions The following uncertainties have been identified as contributing to adverse maternal and perinatal outcomes and will be addressed (each through use of a multi-centre randomised controlled trial): In women with pre-eclampsia between 34+0 and 36+6 weeks' gestation, does delivery with minimal delay reduce maternal complications without short or long-term (neurodevelopmental) detriment to the infant, compared to expectant management? In pregnant women with chronic hypertension, which antihypertensive agent provides optimal blood pressure control and does ethnicity affect the efficacy of each drug class? In women with intrahepatic cholestasis of pregnancy, does ursodeoxycholic acid treatment reduce perinatal death, preterm delivery and neonatal unit admission? Aim 2 is to improve diagnostic and prognostic tests to enable increased stratified surveillance and improved management As current diagnostic tests perform poorly in women with suspected pre-eclampsia, and particularly in women with chronic hypertension and kidney disease, contributing to inadequate surveillance in those at highest risk of complication, the following studies will be undertaken to address these research questions: In women presenting with suspected pre-eclampsia before 37 weeks' gestation, does assessment incorporating PlGF measurement improve time to diagnosis, maternal and fetal outcomes and health resource use? (through a multi-centre stepped wedge design randomised controlled trial)In women with chronic hypertension and chronic kidney disease, is it possible to distinguish the phenotypes of super-imposed pre-eclampsia and pregnancy associated kidney injury in order to improve clinical decision-making and reduce iatrogenic preterm delivery? (through a prospective longitudinal cohort study) Aim 3 is to evaluate the implementation of evidence into clinical practice through new service delivery models Implementation of a new service delivery model and care pathway for women with hypertension in pregnancy will be evaluated through investigation of barriers and facilitators with robust measurement of clinically relevant processes and outcomes in order to inform dissemination of best practice for implementation of such a service on a wider level, regionally and nationally. Aim 4 is to build research capacity, inspiring and nurturing the next generation of multidisciplinary researchers in this field Potential benefits to patients and the NHS The personal, family, societal and economic costs of adverse outcomes in high-risk pregnancies are immense. This programme seeks to undertake rigorous high-quality research within the NHS designed to address the uncertainties identified, and evaluate implementation of a new service delivery model for these women, in order to have a direct, measurable impact on improving health of pregnant women and babies within a five-year timescale. The benefits will be to the women (through reduction of multi-organ complications), to their babies (through lower short- and long-term morbidity), to the health service (by safe, cost-effective management) and to society through improved health and wealth of this important population.

Lay abstract: The nine months of a pregnancy have a lasting impact on the health and wellbeing of the baby and the mother. When all goes well, pregnancy is an exciting time for a woman and her family. But when complications occur, the consequences can be far-reaching for her, the baby, and the wider society. Just under half of all women in the UK now have a medical problem when they are pregnant, such as high blood pressure or liver and kidney complications. Sometimes these medical conditions are present before pregnancy, such as long-standing high blood pressure, and at other times, they start for the first time during the pregnancy, such as pre-eclampsia. Pre-eclampsia only occurs in pregnancy. It is thought to be caused by the way the placenta sticks to the wall of the womb. Mothers with pre-eclampsia can suffer from high blood pressure, problems with their kidneys, liver and blood clotting. The baby's growth is often affected and in some cases the baby can be stillborn. In the UK around 800,000 babies are born every year. Between 80,000 and 120,000 women have high blood pressure at some point in their pregnancy, and around 35,000 will develop pre-eclampsia, the more complicated form of high blood pressure. Other women can have liver complications in pregnancy. Intrahepatic cholestasis of pregnancy is the commonest liver disease in pregnancy. Affected women itch and have abnormal liver blood tests. It is important to diagnose this disease because it is associated with risks for the unborn baby, including being born too early, being sick and needing to go to the neonatal unit, or in severe cases, being stillborn. At present, babies in the UK are still dying or being born too early and too small from these conditions, and mothers are still developing complications from them. Our research group is dedicated to finding out why these conditions occur, the best way to diagnose them, and how to prevent them (or the complications) through new treatments. We use a variety of different ways to find out the answers through doing trials (where participants are usually chosen at random to receive one or other of two treatments) or by following women through the pregnancy and doing extra tests to find out why they develop the complications. We use these answers to change how we look after pregnant women and helping women to make informed decisions about the best care. We do this so that we can improve the health of women and their babies. In this research programme, we are bringing together a number of different ways of working with the single aim of preventing complications for the baby and the mother. Our planned work includes the following: Doing a trial in women with pre-eclampsia between 34 and 37 weeks of pregnancy to see whether delivery (by bringing on labour within 48 hours or by caesarean section if necessary) or waiting and watching the pregnant woman leads to fewer complications in the mother, and fewer babies needing to be admitted to the neonatal unit Testing two types of blood pressure tablets for women with long-standing high blood pressure (that started before pregnancy) to find out which tablets are best at keeping the blood pressure down, without any harmful effects on the health of the mother or baby Using a new simple blood test (for a protein called placental growth factor) to diagnose pre-eclampsia to find out which women are likely to have pre-eclampsia and need to be watched in hospital and which women (with normal levels on the blood test) are at low risk of complications and can return to normal antenatal care Developing a new and better urine test for women in pregnancy so that they, or their midwife, can pick up the disease earlier at home, or in the antenatal clinic, without needing to have a blood test and wait for the result. This may help prevent some of the complications that occur when women do not realise that they are ill with pre-eclampsia Doing a trial of a drug (called ursodeoxycholic acid) to treat a liver complication in pregnancy to see if it can protect the unborn baby from being born too early or being sick and needing to go to the neonatal unit Looking after women with high blood pressure in pregnancy in a joined-up way, using all the information that we know, to make sure that they receive the best care, so that they and their babies have the best start in life

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH