NIHRDataInsights/HRCSData huggingface dataset:
Title: The International DSD Network (I-DSD)
Funder: Medical Research Council

Abstract: Disorders of sex development (DSD) include a range of rare diseases that pose a clinical challenge because of poor standardization and understanding of the value of diagnostic investigations, differences in clinical practice and a gap in knowledge about the links between aetiology, clinical practice and long-term clinical outcome. Recent advances in information, clinical and basic sciences coupled with a greater drive for multicentre collaboration have raised the prospects for managing patients with these conditions. However, there is a need to harness all these initiatives so that common goals can be defined and reached. For DSD, this has already started to occur through regional and national networks of clinical and research excellence and more, recently, through the EuroDSD programme of research (www.eurodsd.eu). The European DSD Register funded initially by the European Society of Paediatric Endocrinology (www.eurospe.org), and, subsequently by EUFP7, is a cornerstone of the EuroDSD programme. It allows clinicians and researchers to interact in a secure, virtual research environment (VRE) where the data are stored with parent, patient and clinician approval. Interest in the VRE is now extending beyond Europe and across a wider group of clinical and scientific disciplines. Currently, 23 centres in 16 countries from 4 continents have expressed an interest in using the Register and 12 centres in 9 countries from 2 continents are actively using the Register which contains over 700 cases. We wish to sustain this unique and successful resource for research and extend its use beyond the original partners of the EuroDSD programme. In undertaking this, we wish to maintain and extend the clinical and research network and translate its efforts into improving standards of clinical care. This will be achieved through maintenance and further development of the VRE and regular meetings of the DSD network aimed at closer involvement of clinicians and patients in the research that arises from the Register.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Kv7 channel activators -a novel treatment for preterm labour?
Funder: Medical Research Council

Abstract: Premature births (37/40 weeks of gestation) account for ~7% of the deliveries in the UK, yet 75% of neonatal deaths, and most admissions to intensive care occur in infants born before 32 weeks of gestation The cost of premature birth in the UK was recently estimated at #939 million/year and economic modelling suggests that delaying preterm birth by one week could save #260 million/year. The ultimate strategy for reducing the impact of preterm labour would be the development of a prediction tool with high sensitivity and specificity to enable early pregnancy stratification of women according to risk, and development of prophylactic therapy. However, in the absence of either, the development of effective tocolytics (drugs that inhibit uterine contractions) would be a major advance in management and prevention of preterm delivery. This application focuses on the unmet need to develop a safe and effective tocolytic therapy that can prolong gestation (when appropriate) for more than one or two days and improve neonatal outcomes for babies. The overarching goal of this project is to facilitate the translation of our recent novel animal and human in vitro data on Kv7 channels into a useful therapeutic tool for the treatment of preterm labour in women. Firstly, our aim is to provide ?proof of principle? data demonstrating that Kv7 activators can inhibit uterine contractions in vivo in pregnant mice (including preterm labour models) and that they are associated with limited side effects; an essential step in the translation pathway. Secondly, to enhance the potential for use of Kv7 channels modulators in pregnant women, the predominant Kv7 channel in myometrium from labouring women needs to be identified. Radio-telemetry will be utilised to measure uterine pressure and cardiovascular parameters and micro-ultrasound to assess uterine artery blood flow in vivo. Kv7 channel subunit composition and function will be explored, using combined electrophysiological/molecular approaches, in human myometrium from pregnant women (?labour). Together this programme of work will aid selection and development of specific Kv7 channel activators for translation to clinical studies.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Over 3 years to study computerised fetal heart rate analysis in labour to assist the timely diagnosis of fetal distress and prevent birth asphyxia
Funder: Action Medical Research

Abstract: Background During birth, the stress of contractions and descent through the birth canal can reduce a baby's oxygen supply. Most babies have the resilience to cope but two per cent suffer birth asphyxia (suffocation), of which, 250 babies in the UK die each year. Those who survive asphyxia may suffer convulsions and permanent brain damage. Therefore, babies at risk of birth asphyxia must be rescued by urgent delivery. To diagnose fetal distress and prevent birth asphyxia, the baby's heart beat is electronically recorded during labour on a paper strip called a Cardiotocogram or CTG. It is difficult to assess the complicated patterns by eye and even experts disagree when reviewing the same trace at different times. Such uncertainty causes 'fail-safe' decisions and many unneeded Caesarean sections. The research project This team will design a new diagnostic system, using objective computer analysis to assist interpretation of the labour CTGs. The researchers have saved the electronic CTGs of nearly 30,000 babies with relevant clinical details. They can now use this important database to perform statistical analysis. This analysis is complex, because CTGs change as labour advances or with events such as epidural use, but the unique size of their database makes the analysis very powerful. The labour experiences of nearly 30,000 women will be distilled into the memory of this computerised system. The aim is to identify the CTG patterns that matter most for the baby and develop a new system to aid recognition of impending asphyxia, at the bedside.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Over 3 years to study vitamin D insufficiency and pre-eclampsia: establishing a causal link through effects on placental development and function.
Funder: Action Medical Research

Abstract: Background Vitamin D deficiency is a global health problem. Pregnant women are one of the at risk groups and up to 95 per cent of pregnant women in the UK may have low vitamin D levels. During pregnancy, development of the placenta is important for a healthy mother and baby and failure of normal placental development can lead to an increased risk of high blood pressure (pre-eclampsia) in the mother during pregnancy. Pre-eclampsia affects up to eight per cent of all pregnancies and becomes severe in two per cent with potential life threatening consequences for mother and baby. There is new evidence that suggests pregnant women with lower levels of vitamin D are more likely to develop pre-eclampsia. The project These researchers aim to establish if there is a link between lower levels of vitamin D in mothers and pre-eclampsia, through both clinical and laboratory based research. Researchers will measure vitamin D levels in the blood and placenta of both women who have uncomplicated pregnancies and women who have pre-eclampsia. They will also study the roles of important biological compounds which are critical to placental development and which they suspect are affected by vitamin D levels. The researchers hope to understand how lower vitamin D levels could result in pre-eclampsia. Data generated by this study could lead to future clinical trials to assess the benefits of vitamin D supplementation in pregnancy, specifically in the reduction of pre-eclampsia risk.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Over two years for identifying placental dysfunction in pregnancies complicated by reduced fetal movement as a model of high risk pregnancy.
Funder: Action Medical Research

Abstract: Background_x000D_ Stillbirth is when a baby of 24 or more weeks' gestation is born with no signs of life. One in 200 babies in the UK dies before birth accounting for more than 4,000 deaths each year, several times more than neonatal and cot deaths. Yet, if problems in the pregnancy had been detected at an earlier stage, it is possible that three out of four stillborn babies could have been born alive. The most frequent reason for stillbirth is that the placenta is not working properly. Babies are also more likely to suffer long term ill health if their placenta was unhealthy. Current pregnancy screening and monitoring assessments do not identify placental disease. A reduction in how many baby movements a pregnant woman feels (reduced fetal movement - RFM) is reported in many pregnancies that end in stillbirth, poor growth of the baby or premature delivery. The placenta from some pregnancies with reduced fetal movement may look and work differently and could therefore be used as a way of identifying possible high risk pregnancies where further investigation and monitoring is warranted._x000D_ The research project_x000D_ Dr Higgins believes that placental disease, resulting in poor pregnancy outcome, could be detected before birth and before the baby develops serious problems Since RFM pregnancies have an above average risk of complications, she plans to test her idea in a group of 300 women reporting RFM. Dr Higgins will use ultrasound to measure the size and shape of the placenta and to assess how well it is working before birth. Once the babies are born, these measurements will be compared between women with normal and poor pregnancy outcomes to see if any of them could have helped to predict which babies were at highest risk of stillbirth and other complications. To make sure that placental screening by ultrasound is providing accurate information, the measurements taken before birth will also be compared to actual measurements taken after the placenta is delivered. This study aims to provide a way of identifying which babies are at highest risk of stillbirth and poor growth before birth. This would allow closer monitoring and, if appropriate, delivery in order to prevent stillbirth. It would also reassure and relieve the anxiety of many prospective parents.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Over three years: The Midlands and North of England Stillbirth Study
Funder: Action Medical Research

Abstract: Background _x000D_The UK has one of the highest rates of stillbirth in high-income countries, with more than 4,000 stillbirths every year. Unfortunately, the rate of stillbirth has decreased very little over the last 20 years. One way of tackling this unacceptable situation is to identify things people can do themselves to improve outcomes (modifiable factors). For example, using information from medical research, a public health campaign advising that babies be placed on their backs to sleep has led to a reduction in the number of cases of sudden infant death syndrome (cot death). A recent study in New Zealand investigating modifiable factors associated with stillbirth (the Auckland Stillbirth Study) confirmed links between stillbirth and modifiable factors such as cigarette smoking and a reduction in fetal activity. A new finding of this study was that mothers who went to sleep in some positions were more likely to have a late stillbirth (occurring after 28 weeks of pregnancy) than mothers who went to sleep in other positions. Further studies are needed to see if these findings can be confirmed in other groups of women. _x000D_The research project_x000D_ This study aims to confirm or disprove the findings of the Auckland Stillbirth Study with regard to behavioural factors including sleep practices in pregnant women and the risk of late stillbirth. The researchers will also investigate any potential interaction with other factors linked to stillbirth, such as reduced growth or reduced movements of the baby in the womb. Mothers will be recruited from maternity units in the Midlands and North of England. The team aim to interview 290 women who have experienced a late stillbirth about their pregnancy. This information will be compared to interviews from a control group of 580 women with ongoing pregnancies at the same stage to that at which stillbirths occurred. If a link between sleeping practices and stillbirth is confirmed, this could form the basis of a public health campaign where pregnant women are advised on the safest sleeping positions. The researchers estimate that, if a link is confirmed, up to 37 per cent of late stillbirths could be prevented by a change in sleeping practices.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Over two years to study the long term outcome of increased birth weight and attenuated brain sparing in pregnancies complicated by fetal growth restriction
Funder: Action Medical Research

Abstract: Background_x000D_ Fetal growth restriction is a pregnancy complication in which a baby fails to achieve its true growth potential in the womb. The condition affects up to eight per cent of all pregnancies in the UK and is severe in one out of every 500 cases. Severely affected babies are extremely small (less than 500g) and sadly many die before or soon after birth. Those who survive may have lifelong disabilities such as cerebral palsy or learning difficulties. Research has shown that babies with fetal growth restriction also have an increased risk of developing diseases as adults, including heart disease, diabetes and high blood pressure. At present there is no treatment available. _x000D_Fetal growth restriction often results from poor blood flow to the placenta meaning the baby cannot get enough oxygen and nutrients and stops growing properly. These researchers are developing gene therapy for mothers with fetal growth restricted pregnancies which delivers a substance called Vascular Endothelial Growth Factor (VEGF) to blood vessels supplying the uterus. In studies of fetal growth restriction in animals, this therapy increased blood flow to the uterus and placenta and resulted in an increase in the weight of the babies at birth. _x000D_The research project_x000D_ In this study, the team aim to find out whether the use of VEGF gene therapy to improve growth in the womb has long term health benefits for babies born from pregnancies complicated by fetal growth restriction. Using an animal model of fetal growth restriction, they will monitor brain development, physical growth, blood pressure and glucose metabolism in the offspring of mothers treated with VEGF gene therapy. This study will provide further understanding into the long term effects of improving fetal growth by giving mothers VEGF gene therapy during pregnancy. It will provide useful information for doctors designing a large clinical trial of VEGF gene therapy in women with pregnancies complicated by severe fetal growth restriction, which has recently received funding from the European Commission.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Over three years to investigate heat shock protein 20 (Hsp20) as a viable drug target for altering uterine function
Funder: Action Medical Research

Abstract: Background_x000D_ Each year, over 60,000 babies in the UK are born prematurely, and nearly 1,400 babies die in the UK each year after being born too soon. Worldwide, it is estimated that as many as 15 million babies are born prematurely each year. Children who survive being born too soon have an increased risk of cerebral palsy, visual impairment, hearing loss and learning difficulties. Therefore research into the causes and prevention of preterm birth is of paramount importance. One avenue of research is to investigate how contraction of muscles in the wall of the uterus is controlled. These muscles need to be relaxed during pregnancy and then to contract strongly during labour to help deliver the baby. _x000D_The research project_x000D_ These researchers have recently discovered that a small protein called heat shock protein 20 (Hsp20) is important in keeping the uterus in a relaxed state during pregnancy. Hsp20 is present in muscle cells of the uterus and is activated by chemical modification within the cell. The team wants to investigate the two main types of Hsp20 modification (phosphorylation and acetylation) and to determine the effect of each in regulating the balance between a relaxed uterus needed to maintain pregnancy and a contracting uterus needed for successful delivery of the baby at the end of pregnancy. In addition, they will establish whether new proteins that mimic the activity of modified Hsp20 are able to prevent premature contractions of the uterus and therefore have future potential as drugs for the prevention of some cases of preterm birth.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Over two years to investigate the role of microRNAs in parturition and as predictors of preterm labour
Funder: Action Medical Research

Abstract: Background Preterm labour occurs when a baby is born spontaneously before 37 weeks of pregnancy. Each year, over 60,000 babies in the UK are born prematurely and nearly 1,400 die as a result of being born too soon. Children who survive being born too early have an increased risk of cerebral palsy, visual impairment, hearing loss and learning difficulties. We do not fully understand what causes a woman to go into 'normal' term labour, so it is difficult to predict and stop preterm labour. Currently, there is only one laboratory test used to predict preterm delivery, but it cannot give an early or accurate prediction of which women are at risk. Another method of predicting preterm delivery is measuring the cervix using ultrasound, but this is time consuming and expensive and only offered to women already known to be at risk. The research project The aim of this research is to produce a test which can be used very early in pregnancy to predict which women are at risk of preterm labour. When a woman goes into labour many different genes are 'switched on.' Dr Cook plans to study small molecules called microRNAs which might control these genes. MicroRNAs are a newly discovered type of gene regulator and it has been estimated that they control over a third of all genes. Dr Cook will detect which microRNAs are altered in the muscle of the womb during labour to try and understand the process of labour better. She will also compare blood samples taken during early pregnancy to see if different microRNA molecules can be detected in those women who went on to have a preterm baby. If so, it may be possible to use these molecules to predict preterm labour in other women by means of a simple blood test in early pregnancy. If women at risk can be identified, interventions such as stitching the cervix and giving hormone tablets could be used to help prevent preterm birth.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Immediate Point of Care Molecular Diagnostics for Lung Inflammation/Infection in Critical Care.
Funder: Department of Health (England)

Abstract: At least 40% of all patients in ICU need a ventilator to support their lungs, with many associated complications. Currently the main indications of clinical deterioration are problems with oxygen and carbon dioxide exchange and the presence/spreading of shadowing on the chest x- ray which many different causes (all requiring different treatments). There is a pressing need for rapid bedside tests to provide definitive diagnostic information about what is happening in the lungs themselves. Many studies have used blood markers, but in patients with multi-system disease these are not specific for the lung and the results are too slow to be useful in the rapidly-changing ICU setting. We will employ cutting-edge technology to pass a tiny optical fibre deep into the lungs of ventilated patients and spray a microdose' of an imaging agent that will tell us the reasons for the lung deterioration. This approach has the potential to rapidly determine, at the bedside, if the lung shadowing is due to inflammation without infection or inflammation with infection due to bacteria such as MRSA. Such an approach could revolutionise the way we deal with the critically ill patient and provide rapid, point of care diagnostics that would help tailor the patient's management.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Development and validation of a screening test to predict the likelihood of fertilisation failure caused by sperm ion channel dysfunction (ICD)
Funder: Chief Scientist Office, Scotland

Abstract: 5-7% of In Vitro Fertilisation (IVF) treatment using apparently normal sperm is affected by no or low fertilisation. This causes significant patient distress and considerable financial loss. Up to 30% of these cases may be caused by sperm with unknown molecular defects. By assessing sperm used in IVF, and related treatment outcomes, we have previously shown that up to 10% of total failed fertilisations are caused by defective pores in the sperm cell membrane, or ‘ion channel dysfunction’ (ICD). This suggests that a routine standardised screening test for (ICD) could determine clinical decisions and reduce IVF treatment failure. The purpose of this study is to i) develop a screening test for sperm ICD, ii) prove it has predictive value for poor/failed IVF outcomes in a large patient group iii) work with (inter) national partner clinics to assess the feasibility of using the screen in clinical practice and iv) study the characteristics of sperm with ICD and use that knowledge to discover new drugs that could rescue defective sperm function. These novel tests offer the prospect of enhancing clinical decision making in order to reduce the number of failed assisted conception cycles.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Pravastatin for the treatment of preterm labour, a pilot study
Funder: Chief Scientist Office, Scotland

Abstract: Preterm birth (early delivery – before 37 weeks) affects 1 in 10 babies born in Scotland, and is a leading cause of death and ill health in early life. The aim of this study is to see if a trial to test whether drugs called statins can prevent preterm birth is possible. We have shown that statins prevent preterm birth in an animal model of pregnancy. The proposed pilot/feasibility study will show what proportion of women are willing to participate in a trial of statins, demonstrate any barriers to participation, and identify how many hospitals we will need to involve and for how long. The results of the study described here, will support a funding application for a larger trial to test whether statins, given to women with signs and symptoms of preterm labour, will reduce the risk of preterm birth and improve babies’ health, without major side effects.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH