NIHRDataInsights/HRCSData huggingface dataset:
Title: Investigating a novel molecular diagnostic tool for identification and stratification of pregnancy complications
Funder: Medical Research Council

Abstract: Small for gestational age infants (SGA) are at considerably increased risk of fetal and maternal mortality. Moreover, low birth weight at term is correlated not only with health problems in early life, but also predisposes to metabolic and cognitive dysfunction later. Despite the enormous cost to public health, little is known about the causes of SGA and few diagnostic tools are available to predict compromised fetal growth. This is important because there is evidence that perinatal outcome can be improved by increasing maternal surveillance and optimising the timing of delivery. The 2008 NICE Guideline on Antenatal Care identified improving detection of SGA infants as one of 5 major research priorities. Therefore early prediction of the onset and etiology of SGA would considerably improve perinatal wellbeing and survival. Failures of placentation are thought to be a common cause of pregnancy complications leading to early termination and/or growth restriction. The placenta forms the critical interface between the maternal and fetal circulations, facilitating the exchange of gases and metabolites. We have recently produced exciting data that links the expression dosage of an imprinted gene, Delta-like homologue 1 (DLK1), to fetal growth and placental function. Importantly, conceptus-derived DLK1 enters the maternal circulation and can be measured during pregnancy. Our first small study in a human cohort indicated that low DLK1 levels are predictive of SGA secondary to a specific type of placental failure. These data are supported by our preliminary studies in mice lacking Dlk1 which have small placentas with reduced nutrient exchange surface area. We believe that further study of DLK1 signalling in pregnancy will help to define critical molecular pathways for healthy placentation, and provide a candidate for prenatal, non-invasive diagnostic testing for the complications of pregnancy.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Engaging Users for Quality Enhancement and Rights (EU QUERO):Strengthening the maternal and child healthcare system over the first 1000 days in Brazil
Funder: Medical Research Council

Abstract: Maternal and child health care in Brazil is highly variable in quality and reach, both within and between states. Brazil as a nation, including the two states of Goiás and Maranhão, both failed to achieve the MDG on maternal health. Community engagement in the health system, as well as greater knowledge of rights to healthcare, are both known, with varying levels of evidence, to improve quality of care. A small number of studies have demonstrated this for maternal and child healthcare in South Asia and sub-Saharan Africa, while evidence in Latin America is scarce. Little knowledge exists concerning whether interventions targeting engagement and rights are feasible within the Brazilian context. EU QUERO is a feasibility study for an intervention to improve the quality of health care received by mothers and children in the first 1000 days of life in two states of Brazil. The research has three main steps: (1) the development of facility level scorecards and a mapping of quality of care for mothers and children within the two states using existing data. This will be of use in itself, while also being used in the following intervention. (2) the implementation of an intervention, facilitated by community health agents within Basic Health Units (BHU), to improve knowledge of rights amongst women and the wider community. The intervention will also disseminate scorecards in order that the women are fully knowledgeable about the service quality. The intervention will also target the health workers within the BHU itself. (3) an investigation into the pathways through which increased knowledge about quality and rights actually feeds through into improved service quality. These pathways are not currently understood. Results of EU QUERO will indicate whether and how to roll out at scale and also enhance our understanding of community accountability as a tool to improve the quality of services offered by health systems at local level.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Infection, inflammation and hepcidin-mediated iron deficiency anaemia in African children
Funder: Medical Research Council

Abstract: The 2016 Global Burden of Disease analysis estimates that 1.225 billion people suffer from iron deficiency anaemia (IDA) and it is the fourth largest contributor to years lived with disability (YLD) globally. The burden is concentrated in sub-Saharan Africa and South Asia. Iron is crucial for neural development and early deficiencies during fetal and infant growth cause irreparable damage to brain development. Until now IDA has been largely attributed to diets low in iron and to infections such as malaria and intestinal helminths. However carefully controlled trials of iron supplements (often with deworming and malaria control) have very poor efficacy in Africa. The discovery of hepcidin - the master regulator of iron - throws a new light on the causes of IDA and may guide future therapeutic pathways. We have recently shown that even low-grade inflammation is a major contributor to ID in rural African children due to hepcidin/ferroportin-mediated blockade of intestinal absorption of iron. IDA is likely further exacerbated by EPO resistance. This project seeks to identify the sources of persistent low-grade inflammation in well and sick Gambian children. It will additionally try to understand the complex interacting mechanisms linking iron absorption, distribution and erythropoiesis to the effects of inflammation mediated through hepcidin, erythropoietin (EPO) and the newly discovered hormone erythroferrone (ERFE) which signals to the liver that the bone marrow requires iron. Finally we will conduct a randomised controlled trial to test whether it is possible to circumvent the hepcidin-induced blockade of iron absorption by administering iron in the form of haem. Another arm of this trial will be a proof-of-principle trial to assess the impact of reducing inflammation by co-administering azithromycin and galacto-oligosaccharides with iron. These studies, if successful, would suggest the need for a radical revision of current policies to combat IDA


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Cell atlas of the human female reproductive system across the lifespan
Funder: Medical Research Council

Abstract: Sexual reproduction depends on the fusion of haploid gametes during fertilisation to form a diploid embryo, and on the endocrine regulation of the endometrium by the ovary to provide conditions for successful implantation. Despite their intimate cellular interactions and functional interdependence, holistic approaches to studying the female germline, the ovary, and the endometrium have been lacking. Indeed, in the context of human development, there is a dearth of systematic studies involving any of the tissues to be investigated here. Gametes halve their genome in preparation for fertilisation during a specialized cell division known as meiosis. However, the process by which meiosis is co-ordinated with gamete formation in females is poorly understood, principally because it commences in utero and is not completed until decades later when the mature egg is ovulated and fertilised. In the present work, we will study the cell types and states, their spatial location and cellular interactions during the development of the fetal ovaries and the adult monthly remodelling of the ovaries and endometrium. We will combine single-cell and spatial transcriptomics methods to create a molecular spatial atlas of the female reproductive tissue in the fetal and adult life. In addition, by combining spatial transcriptomics methods with high-resolution microscopy we will be able to map the female germ cell proliferation and differentiation. Finally, we will use our cell-cell communication pipeline (www.cellphonedb.org) to map the cell-cell communication events in the female reproductive tissue across the menstrual cycle. Because our experimental approach enables us to give biological context to gene expression data, the work proposed here will hugely advance our understanding of the basic biology of human female reproduction. It will also give foundation to a better understanding of the causes of female infertility.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: The PartoSure Test to aid diagnosis of preterm labour in women with intact membranes.
Funder: Department of Health and Social Care

Abstract: To evaluate the effectiveness and cost-effectiveness of PartoSure, Actim Partus and Rapid fFN 10Q Cassette Kit (quantitative test) for the diagnosis of preterm labour (=36+6 weeks of gestation) in symptomatic women with intact amniotic membranes and for whom transvaginal ultrasound is not available or acceptable.

Lay abstract: Preterm (premature) birth, or the delivery of a baby before 37 weeks, is the main cause of death or illness in newborns. In England and Wales in 2013, the infant mortality rate for babies born preterm was 21.1 deaths per 1,000 live preterm births, which is significantly lower than for babies born at term or posterm (1.4 infant deaths per 1,000 live births).1 Preterm labour may be caused by a combination of different things including infection, overstretching of the uterus, cervical weakness and placental problems. Other causes include diabetes, high blood pressure, drug use and smoking. 2, 3 Long-term physical and neuro-developmental issues are not uncommon for babies that survive being born early. Being able to identify women who are likely to have a preterm birth allows doctors to start interventions that may help improve the survival of the baby and mother. Interventions that may delay or stop labour include tocolytics (anti-contraction medicine), cervical stitch, progesterone therapy (hormones) and the insertion of an Arabin pessary (cone-shaped device that supports the cervix). Whilst interventions that may help the survival of the baby include a transfer to a specialist hospital whilst the baby is still in the womb and corticosteroids and magnesium sulphate (medicine given to the mother to help the baby). Current tests used in clinical practice to predict whether a woman showing signs of labour is likely to deliver preterm include transvaginal ultrasound measurement of cervical length, fetal fibronectin, Actim Partus and clinical assessment. PartoSure is a new test which also claims to be able to predict preterm birth. This work will look at the evidence for how accurate the biomarker tests (PartoSure, Actim Partus and fetal fibronectin) are for predicting preterm birth and how effective and cost-effective these tests would be if used in the NHS.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Babies born at the limits of viability: understanding variation in birth and death certification to reduce the impact on parents and the NHS.
Funder: Department of Health and Social Care

Abstract: Objective: To reduce variation in the way the deaths of babies born at 22-24 weeks gestation are certified as a late miscarriage or infant death. Anticipated benefits Improved data quality to ensure standardised comparisons of maternity services; Reduced inequalities in parents' access to benefits and improved parents' experiences. Design Mixed-methods approach combining: statistical analyses of national and international births and deaths; and qualitative studies of health professionals' practice and parents' experiences. Expected outcomes Web-based education package for health professionals; Web-based support for parents; Recommendations for best practice in comparing mortality rates; Peer-reviewed publications in key perinatal health journals

Lay abstract: Objective: To reduce variation in the way the deaths of babies born at 22-24 weeks gestation are certified as a late miscarriage or infant death. Anticipated benefits Improved data quality to ensure standardised comparisons of maternity services; Reduced inequalities in parents' access to benefits and improved parents' experiences. Design Mixed-methods approach combining: statistical analyses of national and international births and deaths; and qualitative studies of health professionals' practice and parents' experiences. Expected outcomes Web-based education package for health professionals; Web-based support for parents; Recommendations for best practice in comparing mortality rates; Peer-reviewed publications in key perinatal health journals

Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Threatened preterm labour: a prospective cohort study of a clinical risk assessment tool and a qualitative exploration of women's experiences of risk assessment and management.
Funder: Health Education England

Abstract: Some women have symptoms of labour (contractions) too early in their pregnancy. Most are not in true labour, but are admitted to hospital and treated unnecessarily, just in case. This is very expensive for the NHS and may increase women's anxiety. This study will test a risk assessment tool that combines several factors including clinical history and test results to generate a risk score to aid diagnosis of preterm labour. An accurate risk assessment tool should reduce unnecessary interventions. Additional exploration of women's experiences and views will provide valuable insight into care priorities from a patient perspective.

Lay abstract: Some women have symptoms of labour (contractions) too early in their pregnancy. Most are not in true labour, but are admitted to hospital and treated unnecessarily, just in case. This is very expensive for the NHS and may increase women's anxiety. This study will test a risk assessment tool that combines several factors including clinical history and test results to generate a risk score to aid diagnosis of preterm labour. An accurate risk assessment tool should reduce unnecessary interventions. Additional exploration of women's experiences and views will provide valuable insight into care priorities from a patient perspective.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;7.3 MANAGEMENT AND DECISION MAKING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Modelling care pathways in neonatal care: costs and consequences for the future.
Funder: Department of Health and Social Care

Abstract: Three levels of care exist for the babies admitted to hospital: intensive, high dependency and standard. Each level has costs and consequences associated with it. The overall aim of this project is to predict the length of time spent in hospital in total and at each level of care. Firstly the time spent at each level of care will be investigated. Secondly, neonatal networks will be compared to identify inequalities in care, and differences examined to aid investigation of the fair allocation of resources. Finally, economic costs will be used to compare the allocation of money between neonatal networks.

Lay abstract: Three levels of care exist for the babies admitted to hospital: intensive, high dependency and standard. Each level has costs and consequences associated with it. The overall aim of this project is to predict the length of time spent in hospital in total and at each level of care. Firstly the time spent at each level of care will be investigated. Secondly, neonatal networks will be compared to identify inequalities in care, and differences examined to aid investigation of the fair allocation of resources. Finally, economic costs will be used to compare the allocation of money between neonatal networks.

Research activity codes: 8.2 HEALTH AND WELFARE ECONOMICS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Biomarkers for the prediction and management of threatened spontaneous preterm birth
Funder: Department of Health and Social Care

Abstract: Spontaneous preterm birth (sPTB) is a consequence of premature shortening of the neck of uterus (cervix) and uterine contractions. This study addresses two major challenges: 1) accurate identification of women at risk of sPTB, and 2) the use of this information to direct optimal management. Known substances (biomarkers) in saliva and vaginal fluid of women at risk of sPTB will be measured in order to develop a combined clinical sPTB prediction tool. The usefulness of the biomarkers to identify how women respond to treatment (vaginal progesterone versus cervical stitch) will also be assessed in a pilot randomised clinical trial.

Lay abstract: Spontaneous preterm birth (sPTB) is a consequence of premature shortening of the neck of uterus (cervix) and uterine contractions. This study addresses two major challenges: 1) accurate identification of women at risk of sPTB, and 2) the use of this information to direct optimal management. Known substances (biomarkers) in saliva and vaginal fluid of women at risk of sPTB will be measured in order to develop a combined clinical sPTB prediction tool. The usefulness of the biomarkers to identify how women respond to treatment (vaginal progesterone versus cervical stitch) will also be assessed in a pilot randomised clinical trial.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Reproductive and Perinatal Health
Funder: Department of Health and Social Care

Abstract: Our aim is to conduct translational research, covering women’s reproductive life from fertility through pregnancy to the menopause, that supports appropriate precision prevention and stratified medicine to improve women’s and their children’s health. Short-term S1. Determine optimal In Vitro Fertilisation (IVF) treatment strategies to increase livebirth rate and maximise short- to long-term health of mothers and infants (workstream 1 (WS1)). S2. Determine the potential of a novel biomarker to identify risk of adverse gestational diabetes (GDM) outcomes early in pregnancy (WS2). S3. Test the feasibility of using automated delivery of Xenon to protect neonates requiring surgery from anaesthetic neurotoxicity (WS3). Medium-term M1. Identify modifiable mechanisms of IVF success (WS1). M2. Develop accurate tools to identify risk of stillbirth, hypoxia, hypertensive disorder of pregnancy (HDP), preterm birth and delivering a small for gestational age (SGA) infant (WS2). M3. Evaluate the acceptability and optimal time of intervening to prevent morbidity and mortality in term infants (WS2). M4. Identify biomarkers for cooling therapy response (WS3). M5. Determine the impact of menopausal transition on health and wellbeing (WS4). Long-term L1. Test the feasibility and acceptability of stratified medicine approaches to IVF treatment (WS1). L2. Test the feasibility of replacing oral glucose tolerance tests (OGTT) with an early non-fasting biomarker for GDM (WS2). L3. Conduct phase I evaluations of the efficacy of Xenon to protect neonates undergoing surgery from neurotoxicity (WS3). L4. Explore methods at work and home for promoting women’s health as they go through the menopausal transition (WS4).


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Position in the second stage of labour for women with epidural anaesthesia
Funder: Department of Health and Social Care

Abstract: This review has been commissioned to potentially feed into relevant NICE guidance. Relevant NICE guidance: CG190 – intrapartum care for healthy women and babies Recommendation 1.13.9 in this guideline states “Discourage the woman from lying supine or semi supine in the second stage of labour and encourage her to adopt any other position that she finds most comfortable” The BUMPES trial was published in November 2017 https://www.journalslibrary.nihr.ac.uk/programmes/hta/082202#/ and while this trial was in the subgroup of women who have had an epidural, it found a higher rate of spontaneous vaginal birth in women randomised to a supine position. This seems to contradict the recommendation above. A systematic review would be helpful to understand the overall body of evidence before deciding if an update is needed. Relevant Cochrane reviews There is a relevant Cochrane review that was last updated in 2017, before the BUMPES trial was published. Kibuka M, Thornton JG. Position in the second stage of labour for women with epidural anaesthesia. Cochrane Database of Systematic Reviews 2017, Issue 2. http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD008070.pub3/full This review failed to find a difference between different positions, so the BUMPES trial result seems to be qualitatively different. An updated review could usefully explore possible reasons for these results. Alignment of questions The NICE guideline does not have a clear question for this subgroup of women who have had an epidural, but the following points are relevant. Population It appears the Cochrane review definitions would match the guideline population. Interventions and comparison Again, the Cochrane review interventions and comparisons appear to match what was considered in the guideline. Outcomes The choice of outcomes in the Cochrane review seem similar to those discussed in the guideline.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH