NIHRDataInsights/HRCSData huggingface dataset:
Title: Does promoting increased awareness of decreased fetal movements reduce stillbirth, a stepped wedge cluster randomised trial?
Funder: Chief Scientist Office (Scotland)

Abstract: Rates of stillbirth in Scotland are amongst the highest in resource rich countries. The majority of stillbirths occur in normally formed infants, with (retrospective) evidence of placental insufficiency being the commonest clinical finding. Maternal perception of decreased fetal movements appears to be an early biomarker both of placental insufficiency and subsequent stillbirth. The study proposed here will test the hypothesis that rates of stillbirth will be reduced by introduction of a package of care consisting of strategies for increasing pregnant women’s awareness of the need for prompt reporting of decreased fetal movements, followed by a management plan for identification of placental insufficiency with timely delivery in confirmed cases. The odds of stillbirth fell by 30% after the introduction of a similar package of care in Norway but the efficacy of this intervention (and possible adverse effects and implications for service delivery) have not been tested in a randomized trial. We plan a stepped wedge cluster design trial, in which hospitals in Scotland and Ireland will be randomized to the timing of introduction of the care package. Outcomes (including the primary outcome of stillbirth) will be derived from Scotland and Ireland’s detailed routinely collected maternity data, allowing us to robustly test our hypothesis. A nested qualitative study will examine the acceptability of the intervention to patients and health care providers and identify process issues (barriers to implementation).


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Improving intrapartum outcomes for mothers and babies in Scotland: a steppedwedge RCT of an intrapartum emergencies training package in 15 Scottish Maternity Units
Funder: Chief Scientist Office (Scotland)

Abstract: Intrapartum care is not as safe as it could and should be, with poor outcomes causing significant harm to women and their families, and financial burden to health services. An inexpensive intrapartum emergencies training programme has been developed and tested, and shown to improve critical outcome measures, but only in beforeafter studies of early adopters. What is needed now is robust evidence from implementation across a whole health sector: 15 Scottish maternity units who have not undertaken the training yet. The project is a stepped-wedge cluster RCT, where units are randomised in the orc^er they receive training, so in the end they are all trained. The perinatal outcome measure, low Apgar score at five minutes after birth, is Important for service users, clinicians, and insurers, as it is a marker strongly associated with a more than sixty-fold increase in one of the most litigated complications, cerebral palsy.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Integrating abortion within a specialist contraceptive service: a qualitative evaluation of the experiences of women and health professionals
Funder: Chief Scientist Office (Scotland)

Abstract: Over 12,000 women in Scotland each year have an abortion, 29% of whom have previously undergone an abortion. There is a need for the provision of high quality contraceptive advice with the intention of lowering the rate of abortions. The integration of abortion services into sexual and reproductive health (SRH) centres in Scotland is intended to improve contraceptive uptake and sexually transmitted infections identification following abortion and to enhance the quality of service and patient satisfaction. Using interviews this qualitative study will (1) Contribute to an evaluation of a new model for the provision of abortions within an integrated SRH service (2) Compare the experience and provision of medical abortion services at an SRH clinic and a hospital-based clinic from patient and health care providers' perspectives. (3) Demonstrate whether and in what ways receiving care in the two types of settings influences and informs (different) decisions about future contraceptive use.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Cochrane Review Update: Plastic barriers for the reduction of heat loss in preterm infants immediately after birth
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Preventing low body temperature at birth in premature and low birth weight infants may be important to survival and long-term outcome. Newborn babies rely on external help to maintain temperature particularly in the first 12 hours of life. For vulnerable preterm very small babies, abnormally low body temperature (hypothermia) is a world-wide issue and has been linked to a variety of problems and even death. Preventative action is taken by reducing heat loss and/or providing warmth using external sources. Routine steps include a warm delivery room; drying immediately, especially the head; wrapping in pre-warmed dry blankets; pre-warming surfaces and eliminating draughts. Twenty studies using additional preventative actions in the first 10 minutes of life to prevent hypothermia were reviewed. Results showed that plastic wraps or bags, plastic caps, heated mattresses and skin-to-skin contact keep babies warmer than routine care. However, combining these methods may have the unintended effect of making infants too warm which should be avoided by careful monitoring. Limitations included the small numbers of infants and studies in some of the comparison groups; variations in the methods, definitions of normal body temperature and routine care. Although this review confirmed that some of these measures are effective in preventing hypothermia, across all studies, there were no improvements in number of deaths or short-term illnesses. Therefore, the authors recommend that future research should focus on longer-term consequences.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;6.3 MEDICAL DEVICES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Development, usability testing and a pilot trial of decision support for breech presentation at term: development, usability testing and a pilot trial of a decision support tool and decision quality instrument
Funder: Department of Health (England)

Abstract: Background: Pregnant women with a breech baby need to decide whether to have an external cephalic version (turning the baby), an elective Caesarean section or vaginal breech birth. There is high quality evidence available to support the decision making process in the form of Cochrane systematic reviews. Aims and objectives: To review the available evidence regarding the management of breech presentation at term as well as the theory of decision support design; to develop understanding about what is required to support pregnant women engaging in decision making about breech presentation; to design and develop a decision support tool; to test the usability of the decision support tool with pregnant women and health professionals; to develop an instrument to assess decision quality to use as a primary outcome to evaluate the decision support tool; to conduct a pilot (exploratory) trial of the decision support tool; and to develop a protocol for a definitive randomised controlled trial. Method: This research will be completed in three stages: firstly decision support tool development and usability testing; secondly decision quality instrument development; and thirdly a pilot (exploratory) trial and development of a protocol for a definitive randomised controlled trial. A combination of qualitative and quantitative research methods will be used including: semi-structured interviews, focus groups, systematic review and a pilot (exploratory) trial comparing the decision support tool to usual care.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: How much is too much? Exploring clinical recognition of excessive maternal blood loss during childbirth.
Funder: Department of Health (England)

Abstract: Excessive bleeding following childbirth is the leading cause of maternal death worldwide. Assessing the amount of maternal blood loss is difficult and treatment can be delayed. This study will explore how midwives and doctors assess blood loss, decide if it is too much, and whether treatment is required. Women and birth partners will be asked about their experiences of blood loss and decisions made during their care. A better understanding of decision-making during blood loss will help develop new ways to assist midwives and doctors in that process, aiming to reduce delays in recognition and treatment of excessive bleeding.


Research activity codes: 1.4 METHODOLOGIES AND MEASUREMENTS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Understanding Change Management in Neonatal Intensive Care- An investigation into the factors affecting the successful integration into routine care of a complex intervention to improve the nutritional support of preterm infants
Funder: Department of Health (England)

Abstract: Premature babies do not grow well, despite good evidence regarding how they should be fed. However, they are complicated patients and their care is delivered in a complicated intensive care environment, so introducing findings from research into routine hospital care is challenging. This study will introduce a set of new working practices for feeding premature babies in the intensive care unit aimed at improving their nutrition and growth. It will also measure and study the process of changing working practices amongst staff, assessing the degree to which the new practices have become part of routine care.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Predictors and measures of success in a full course of IVF treatment: a modelling approach.
Funder: Department of Health (England)

Abstract: The recommended treatment for infertility is in vitro fertilisation (IVF). IVF treatment is a complex, multi-phase process, involving stimulation of the ovaries, retrieval and fertilisation of eggs, and transfer of some of these eggs back to the uterus. Some eggs may be frozen for later transfer and the process may be repeated. This results in a complex multilevel data structure, making it difficult to establish the contribution of interventions at each of these different phases to the end result. I will develop statistical models of the IVF process and apply these to large IVF datasets to answer important clinical questions.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES);2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Selection of sperm for Assisted Reproductive Treatment by prior hyaluronic acid binding: increasing live birth outcomes and reducing miscarriage rates (Hyaluronic Acid Binding Sperm Selection; HABSelect).
Funder: Department of Health (England)

Abstract: RESEARCH DESIGN: Patients randomized into two equally sized groups for sperm selection by either Hyaluronan binding (PICSI) or standard polyvinylpyrrolidone (PVP).POPULATION: Patients undergoing IntraCytoplasmic Sperm Injection (ICSI) procedures for male factor infertility at the IVF units in 10 UK centres (Leeds Sheffield Manchester Dundee Liverpool London Guys London Barts Birmingham Aberdeen and Southampton).PLANNED INTERVENTIONS: Men recruited into the study will be assessed for sperm hyaluronan binding using a proprietary assay kit (Hydak HBA slide). A single sperm will be injected directly into the egg following capture by PICSI or PVP. The clinical embryologist will monitor formation of pronuclei and cell division. High-gradeembryos will be transferred into recipient partners and the management of the patient will then return to the clinical consultant for follow-up.ASSESSMENT AND FOLLOW-UP: Efficacy determined by comparison of outcomes from PICSI and PVP-selected sperm as follows: Biochemical pregnancy (BP) at 7 days post embryo transfer (pET); Ultrasound detection of fetal sac and/or heartbeat at 6-8 weeks (CP); Live birth rate (LBR) at > or =37 weeks (reported per first cycle and per couple). Safety will be assessed at all times during follow up by recording miscarriage and preterm labour rates throughout. Patient (and fetal) safety will be closely monitored and clear trial stopping criteria will be in place. PROPOSED SAMPLE SIZE: With 90% power (p=0.05) a minimum of 3266 couples (1633 in each arm) is required to detect a 5% improvement in LBR (24% - 29% per cycle) falling to 852 couples (426 in each arm) at 10.0% improvement. We aim to recruit 3730 couples into the study over 24 months.STATISTICAL ANALYSIS: Descriptive statistics will be recorded for Biochemical (BPR) Clinical (CPR) Live Birth (LBR) rates and pregnancy loss. Statistical tests will look for significant differences between the control and interventional trial arms for each of these outcome measures in relation to rates of DNA fragmentation and chromatin compaction of sperm in (i) high v low Hyaluronan Binding Score (BPS); (ii) CPR LBR and pregnancy loss. Structural equation modelling will be used to probe these relationships for evaluation of mechanism. TIMETABLE: 6 months set up recruitment is estimated at 1864 PA (40% of total eligible ICSI patients over 10 centres) requiring 24 months. Mechanistic evaluation will take 24 months running concurrently. Follow up for 10 months to include capture of Live Birth Data. Study completed main outcomes analysed and final report available at 42 months.


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Productivity, Family Planning & Reproductive Health: an inter-disciplinary study in Burkina Faso
Funder: Economic and Social Research Council

Abstract: Our study focuses on the impact of reproductive health on women's economic empowerment at both the household and individual levels in Burkina Faso, a country in Sub-Saharan Africa with high fertility, high unmet need for family planning and high female labour participation. The ultimate aim of this research project is to conduct multi-disciplinary research on the impact of pregnancy on income-generating and non-income-generating production in Burkina Faso; and to investigate how investments in reproductive health might contribute to reducing poverty and fostering economic development and equity. The proposed project consists of three interlinked study components: Study A: will be a secondary analysis of existing data (collected by Immpact) on the productivity costs of pregnancy and childbearing. Study B: will collect primary quantitative data on reproductive health, family planning behaviour and productivity in a prospective cohort. Study C: will be a qualitative, ethnographic analysis of women's reproduction, productivity and empowerment. Study C will be nested within the prospective cohort of Study B, allowing us to link to the quantitive data. We will also interview the husband/partners of these women, to enable us to explore men's perspectives and roles. The three studies provide complementary information. Our mixed methods approach will allow us to triangulate data from different sources and explore the key issues from the perspectives of each key discipline represented in the team (demography, economics, anthropology and epidemiology). Analysis of the Immpact data (Study A) gives us access to a rich data source on the direct and productivity costs of delivery. However, Immpact did not collect information on a number of key variables (most importantly family planning); therefore we propose to collect primary prospective data (through Studies B and C) to supplement the findings of Study A. The main project outputs anticipated are: (i) increased knowledge and understanding of the relationship between reproduction and production in Burkina Faso (ii) policy & practice-relevant results published in at least three open-access peer-reviewed publications (iii) two archived datasets (1x quantitative, 1x qualitative) available to other researchers for future analysis (iv) increased capacity in Burkina Faso.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Understanding light in the late term human fetus: Proof of concept for social research techniques
Funder: Economic and Social Research Council

Abstract: Recently it has been determined that a human fetus lives in an environment which is not dark. This joint project between Lancaster and Durham Universities, seeks to understand how human fetuses respond to aspects of the world related to social information. The aim of this project is to send light to the fetus. Within that light, we will present shapes which are face-like in shape. A human fetus will have never seen a face before. When a baby is first born, she will look at faces more than any other form of visual stimulus. We are aiming to understand if this is something that is learned quickly after birth, or if human genes mean that we look at faces more than anything else. If there is a genetic basis for this behavior, we will find that fetuses will look at a face-like stimulus more when we present it in an upright orientation when compared to showing this to them upside down. Before we do this, we need to first understand how light moves through skin, muscle and fat. We want the light to be the same for all fetuses, which means we need to create a device that can take into account these factors for every individual mother and fetus. Investigating how human fetuses understand things before they are born will tell us about the relationship between early learning and the environment. This work may also tell us how the understanding of social information related to other people changes in early development. This project has potential impacts and benefits related to our understanding of early learning. This has implications for our understanding of the development of different forms of developmental disorders that have a social deficit, such as autism. This is because the ability to process aspects of social information is often impaired in those diagnosed with autism. Therefore, in order to map the parameters of autism, we first need to understand how these systems work in typically developing populations, including the role of the environment for early learning and what babies prefer to look at.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: The Role of Endogenous Vascular Protection Factors in Preeclampsia
Funder: Medical Research Council

Abstract: Preeclampsia (PE) is a systemic endothelial disease defined clinically as hypertension and proteinuria after 20 weeks gestation. PE involves oxidative stress, dysregulation of placental angiogenesis including the release of soluble anti-angiogenic factors that induce systemic endothelial dysfunction. Little attention has been focussed on endogenous vascular protective factors that may inhibit anti-angiogenic factors such as soluble Flt-1 (sFlt-1; a VEGF antagonist) and soluble endoglin (sEng) that are elevated in preeclampsia. This programme will address the central hypothesis that preeclampsia is the result of a perturbation(s) in the vascular protective factors such as the important cytoprotective and anti-inflammatory enzyme, heme oxygenase-1 (HO-1), Thioredoxin reductase-1 (TrxR) and glutathione peroxidase-1 (Gpx), which function to tightly regulate pro- (Vascular endothelial growth factor-A (VEGF) / endothelial nitric oxide (NO) synthase (eNOS) and anti-angiogenic (sFlt-1 / sEng) factors possibly under the control of the phosphoinositide 3-kinase (PI 3-kinase) / Akt pathway. We propose that the HO/TrxR/GpX via PI 3-kinase /Akt pathways are defective in preeclampsia resulting in increased oxidative stress and exacerbated inflammation leading to the aberrant expression of anti-angiogenic factors (sFlt-1 / sEng) in the placenta. This hypothesis will be examined using three experimental systems (i) primary trophoblast and endothelial cell cultures, (ii) a human placental villous explant model and (iii) two transgenic mouse models of preeclampsia. The mechanism by which HO-1 modulates sFlt-1 and sEng expression mediated by pro-inflammatory cytokines (TNF-alpha, IL-1beta, IFN-gamma) and growth factors (VEGF, Ang-II) will be determined by manipulating the PI 3-kinase/PDK-1/Akt, phospholipase C-gamma1 and protein kinase C signal transduction pathways in these systems This will be achieved by selective RNAi-mediated gene knockdown or over-expression of wild-type and dominant-negative / constitutively active mutants of the appropriate signalling proteins using adenoviral vectors. Understanding the mechanisms that reduce the prevalence of oxidative stress, inflammatory and anti-angiogenic mediators in preeclampsia may prolong pregnancy, prevent premature delivery, and protect the mother post-partum from persistent endothelial cell activation, which increases her predisposition to cardiovascular disease.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: A Proof of Principle Randomised Placebo-Controlled Trial for Use of Statins to Ameliorate Early Onset Preeclampsia
Funder: Medical Research Council

Abstract: Preeclampsia (PE) is a systemic endothelial disease characterised by hypertension, proteinuria, exacerbated inflammation, dysregulated angiogenesis and can lead to morbidity and mortality in both mother and baby. Currently the only effective treatment for PE is delivery of the baby. However, early delivery, especially before 32 weeks gestation, often has serious consequences for the health of the baby. A cheap and effective therapy for prevention of PE complications is urgently needed. Increasing evidence shows that excess circulating soluble Flt-1 (sFlt-1) plays a role in the pathogenesis of PE. We showed that statins (HMG-CoA reductase inhibitors), a class of lipid-lowering drugs, inhibit cytokine-mediated release of sFlt-1 in ex vivo human placental model. This IES platform will test the hypothesis that statin use during early onset PE would lead to a significant reduction of sFlt-1 and alleviate the severity of PE. We will undertake a proof of principle randomised placebo-controlled multi-centre RCT trial for use of statins to ameliorate early onset PE. A minimum of 128 pregnancies will be randomised from six maternity units in the UK. Minimum inclusion clinical criteria will be gestational age range of 24-32 weeks with new onset hypertension; systolic 140mmHg and diastolic 90mmHg; Protein/creatinine ratio 30mg/mmol or 300mg proteinuria/24 hours. Consenting mothers will be randomised to receive either 40mg pravastatin capsules once a day or identical placebo until delivery with conservative management of their PE. The primary outcome measures will be changes in plasma levels of biomarkers (sFlt-1/sEng/PlGF). Secondary outcomes measures will be severity of PE, prolongation of pregnancy post treatment, maternal and neonatal outcomes and adverse effects. We will also formally assess the feasibility of a definitive trial by examining recruitment rates, compliance and physcian and patient readiness for randomisaiton to statins. This study will identify a novel intervention based on strong scientific rationale, which will inform a future large-scale multi-centre randomised trial.


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