NIHRDataInsights/HRCSData huggingface dataset:
Title: Over three years to study PDE4 inhibitors: a treatment for mothers and babies at risk of preterm delivery?
Funder: Action Medical Research

Abstract: Worldwide, preterm birth has increased in the last 20 years and more than 50,000 babies are born prematurely each year in the UK. The rate of permanent disability, such as lung disease, cerebral palsy or blindness, rises when babies are born very early. The most important cause of premature delivery is preterm labour, but despite the introduction of novel treatments to reduce the risk of preterm labour, our interventions are yet to show any improvement in the outcome for babies. Maternal infection is thought to play a major role in the onset of preterm labour and, by causing an inflammatory response in the baby, lead to brain damage in the unborn child. Recently the emphasis has shifted from the treatment of established preterm labour to its prevention in high-risk women identified by a combination of history and the detection of a short cervix on ultrasound screening. The ability to identify a high-risk population gives doctors more opportunity to intervene with treatments not only to reduce the risk of preterm labour but also to protect the baby and the baby’s brain from the complications of premature delivery. Preliminary data from this team show that a molecule called cAMP reduces the activity of a key component that leads to uterine muscle contractions. Research by other teams has also shown that cAMP can reduce inflammation-induced preterm labour. This research will investigate cAMP in more detail. The aim is to inhibit muscle contractions to reduce the rates of preterm labour and also to see if they can protect the unborn baby’s brain from the effects of maternal inflammation as this can lead to brain damage. Drugs that affect cAMP are commercially available and have been used widely and safely during pregnancy in the management of asthma.


Research activity codes: 5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Over three years to study aberrant trophoblast functions in pregnancies at higher risk of developing pre-eclampsia
Funder: Action Medical Research

Abstract: Pre-eclampsia is a condition that only occurs during pregnancy or immediately after the delivery of a baby. Several hundred babies and around six women die each year in the UK following complications from severe pre-eclampsia. Symptoms in the mother include headache, pain in the area above the stomach and oedema (abnormal accumulation of fluid). A diagnosis is made with the development of new onset high blood pressure (hypertension) and protein in the urine (proteinuria) in the second half of the pregnancy. The cause of the condition is not fully understood and the only way to prevent pre-eclampsia is to deliver the baby early. Complications for the baby include intrauterine growth restriction, premature birth and stillbirth. In early pregnancy, the placenta starts to develop and fetal cells called trophoblasts invade and alter the blood vessels in the uterus to increase the blood supply to the growing baby. In some pregnancies trophoblasts don’t invade enough and the changes in the blood vessels fail to take place which can lead to serious problems such as pre-eclampsia. The reasons why this process fails is not understood but an important aspect may be whether the trophoblast cells survive in the uterus. Although it is not possible to definitively predict whether a mother will develop pre-eclampsia, using ultrasound scanning it is possible to determine whether there is an increased risk. This team has shown that trophoblast cells from women at a higher risk of pre-eclampsia are less likely to survive and they now aim to work out why. In the future, this knowledge could improve how we diagnose and treat pre-eclampsia.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Over three years to study the purinergic P2X7 receptor: regulation of uterine function in labour and preterm labour.
Funder: Action Medical Research

Abstract: Around 50,000 babies are born preterm in the UK each year and preterm labour is a major cause of infant death and disability. Many babies that are born very early are at risk of possible long term disability and conditions such as cerebral palsy, hearing and visual impairment. Inflammation is the body's natural way of fighting disease but certain situations arise where inflammation may make things worse. In some cases, preterm labour is thought to be caused by inflammation. Infection leads to inflammation and this may cause the uterus to contract too early. This research is aimed at studying the role of an important receptor (P2X7) in the membrane of white blood cells that sets up an inflammatory process. Overactivity of this receptor may lead to premature contractions. The team will measure the proteins produced by this process in the mother and unborn baby to examine whether harmful proteins are produced in preterm labour compared with women who deliver normally. They will also study whether the receptor has a role in normal pregnancy in the absence of labour. If there is a clear effect, it may be possible to block inflammation early in women who are at risk of preterm labour.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Over three years to study novel mechanisms of oxytocin function in human myometrial cells
Funder: Action Medical Research

Abstract: Background Preterm birth is a major cause of death or long term disability in newborn babies and affects 7-10 per cent of all pregnancies worldwide. Surprisingly we still know very little about the process that controls contractions during labour, and therefore it is very difficult to stop contractions when they start prematurely (before 37 weeks' gestation). In contrast, some women require an induction of labour for the benefit of the mother or the baby, but the process for starting labour artificially is fraught with potential failures and risks of emergency caesarean sections and other severe surgical complications. The research project The researchers aim to investigate how the hormone oxytocin, which is involved in the onset of labour, prepares the uterus (womb) for contractions. They are studying a previously unknown mechanism in uterus cells which involves specific proteins called transcription factors and the activation of certain genes. The researchers will try to understand how the uterus can change from being in a relaxed state, able to carry the baby safely for many weeks, to a state of contraction and delivery. This knowledge could help us manage preterm labour more successfully and may also indicate how to induce the onset of labour in a more safe and effective manner.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Over three years to study the effect of paraoxonase 3 on oxidative stress in fetal and neonatal lungs
Funder: Action Medical Research

Abstract: Background Premature birth in the UK causes approximately 1,000-1,500 deaths per year accounting for around 30 per cent all infant death. One of the causes of complications following premature birth is that the baby is exposed to a sudden increase in oxygen levels. While oxygen is clearly essential for life, sudden increases in oxygen levels can damage tissues. Normally, babies prepare for this challenge by increasing levels of protective proteins (antioxidants) in the weeks leading up to birth. However, premature babies are exposed to the sudden increase in oxygen levels following birth but lack these protective mechanisms The research project The researchers have previously identified a protein called PON3 which increases prior to birth in babies. They believe that PON3 levels increase before birth in order to protect the baby from the sudden increase in oxygen. In this study, the researchers will use a laboratory model to determine whether low levels of PON3 result in oxygen related damage to tissues and whether giving synthetic PON3 can reverse this effect. If both findings are positive, this could lead ultimately to studies with premature babies.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Over thirty months to study whether 1H MRS and MRI at 3 tesla detect intrauterine hypoxia in pregnancies with uteroplacental insufficiency
Funder: Action Medical Research

Abstract: Background In the UK, more than 3,500 babies are stillborn every year. Many more babies fail to grow properly within the womb. To prevent stillbirth, babies that are not growing well are often delivered preterm. Unfortunately, being born early can be damaging for babies. The leading cause of pregnancy omplications such as stillbirth and poor fetal growth is poor placental function, when the placenta stops working properly. Failure of the placenta often leads to low oxygen levels within the womb, which is harmful to the baby. Unfortunately, doctors currently do not have a test that can accurately detect low oxygen levels and poor placental function and predict complications. The research project The researchers aim to find out whether new imaging techniques can detect differences in oxygen levels and placental function between normal and at risk pregnancies. The long-term goals of this research are to assess whether information gained from novel imaging techniques can help with timing of delivery and improve the outcome in pregnancies complicated by poor placental function.


Research activity codes: 6.3 MEDICAL DEVICES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: The acceptability and feasibility of aerobic exercise as a treatment for vasomotor and other menopausal symptoms
Funder: Department of Health (England)

Abstract: Objectives Many women no longer want to take HRT for menopausal symptoms so it is important to identify alternatives. This study aims to examine the feasibility and acceptability of exercise as a potential treatment.DesignSystematic review, questionnaires/interviews and feasibility RCT.Expected outcomesEvidence on whether exercise is an acceptable and feasible treatment for menopausal symptoms The study will provide the information required to appropriately power and deliver a robust definitive RCT.Anticipated benefitsIf exercise is shown to be feasible and subsequently effective, it may be possible for clinicians to advise exercise as an evidence-based treatment for symptoms


Research activity codes: 6.7 PHYSICAL
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Novel gonadal and extragonadal functions and mechanisms of action of luteinising hormone .
Funder: Wellcome Trust

Abstract: The two gonadotrophic hormones secreted by the pituitary gland, luteinising hormone (LH) and follicle-stimulating hormone (FSH), play a key role in the regulation of gonadal hormone production and human fertility. On one hand, disturbances in gonadotrophin function are a common cause for male and female infertility, on the other hand many contraceptive methods are based on manipulation of their synthesis, secretion and actions. Pharmacological preparation of gonadotrophins are also widely used i n the treatment of infertility. Recent studies have shown that the functions of gonadotrohins may not be confined to the ovary and testis, but there is a possibility that also several other tissues of the body respond to gonadotrophins, and also a connection of high gonadotrophin levels to abnormal functions, such as adrenal hyperfunction and tumours has been demonstrated. Therefore, all new information about the functions at all levels, from basic molecular mechanisms to clinical applications, is necessary for the improvement human wellbeing. The purpose of these studies is, by using LH function in normal and genetically modified mice as the experimental model, to address the more basic aspects of gonadotrophin action, with special reference to the molecular mechanisms involved in the multitude of these actions.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Can Restoration of Adequate Selenium Status in Selenium-Deficient Pregnant Women Reduce Markers of Risk for Pre-eclampsia?
Funder: Wellcome Trust

Abstract: One in ten pregnant women will develop pre-eclampsia, a serious condition that affects around 25,000 UK expectant mothers every year. Babies born to these mothers are often premature and underweight with an increased risk of handicap. There is no cure for pre-eclampsia other than premature delivery. Some research shows that the trace mineral, selenium, which we get from food, can reduce the risk of pre-eclampsia. Given this information, it is of some concern that the amounts of selenium i n our diet have fallen recently and are now only half Government-recommended levels. We want to see whether a small increase in selenium intake in pregnancy is likely to reduce the risk of getting pre-eclampsia. Women with low blood selenium will be recruited in early pregnancy and given either a daily, low-dose selenium tablet or a dummy tablet. Blood samples taken in later pregnancy will be analysed for markers that are linked to the condition. If the risk has reduced in the selenium-tr eated group, we will then run a much larger study that could show conclusively if selenium reduces the risk of pre-eclampsia itself. If it did, then expectant mothers could be advised to increase their intake of selenium-rich foods or supplements.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: The impact of oxidative and endoplasmic reticulum stress on placental protein synthesis and maternal and fetal wellbeing.
Funder: Wellcome Trust

Abstract: If the baby fails to grow properly during pregnancy the risk of stillbirth and neonatal death is considerably increased. Childhood obesity, which is currently of epidemic proportions, Type 2 diabetes and cardiovascular disease in adult life are also associated with low birthweight. These present major challenges to public health, and so improving pregnancy outcome should be a priority. There are many potential causes of low birthweight, but poor development of the maternal blood supply to the pl acenta is thought to be the basis in the vast majority of cases. In a proportion of these the mother develops high blood pressure and preeclampsia, which can necessitate emergency preterm delivery. Our current research, funded by the Trust, has identified novel effects of malperfusion on stress-activated molecular pathways in human placentas from pregnancies associated with low birthweight and preeclampsia. These findings provide new insights into the fundamental cellular processes regulating pl acental, and hence fetal growth. We aim to extend these observations and explore the complex interplay between inhibitory and stimulatory signals. We also need to test their importance experimentally before we can translate them into clinical practice by improving diagnostic techniques, and potentially designing novel therapeutic interventions.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Population Science of Maternal and Child Survival.
Funder: Wellcome Trust

Abstract: Every year there are nearly 10 million deaths of children under five, and over 500 000 deaths of mothers during pregnancy, delivery or the newborn period. In sub-Saharan Africa, and many parts of south Asia, death rates have not fallen as expected. We are working with partner organizations in Bangladesh, India, Nepal and Malawi to evaluate low cost interventions in populations where death rates are high. Our studies are looking at ways to change care practices in the home, to speed up care-seeki ng when a problem occurs, and to improve the quality and effectiveness of care provided at health facilities. A Wellcome strategic award will help our network to do some of the largest combined population studies in the world, to compare results in different settings, to look at other benefits from our interventions as children grow and develop, and to understand the links between health and poverty. It is vital that research findings change policy and practice. We shall help partners to influ ence country policy quickly by sharing experiences, communicating in the media and with policymakers, as well as through scientific journals, and by giving vital information back to the communities in which we work.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Redefining families: Bioethics, assisted reproduction and emerging family forms
Funder: Wellcome Trust

Abstract: Social scientists at the Centre for Family Research have pioneered research that addresses ethical issues raised by the creation of families through assisted reproductive technologies. The findings have informed bioethical analysis in the field of assisted reproduction and have made a significant contribution to policy formation and legislation on assisted reproductive technologies around the world. Instead of working in parallel, we are keen to engage with biomedical ethics from the outset to ensure that our research is addressing the key issues at a time when the combination of technological advances and changes in regulation are resulting in new and controversial family forms. The current review of the HFE Act makes these issues particularly topical. An Enhancement Award would facilitate this process by allowing us to bring in biomedical ethicists with particular expertise in the field of assisted reproduction, thus increasing capacity and training in biomedical ethics in the Centre for Family Research and at the University of Cambridge generally. The aim would be to integrate bioethical and empirical approaches in our new studies of the next generation of assisted reproduction families - gay fathers, single mothers by choice and donor siblings - thus enhancing both the ethical analysis and the empirical research


Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Switchable Nanostructured Surfaces as a Sophisticated Tool for Cell Biologists .
Funder: Wellcome Trust

Abstract: Failure or severe difficulty in conceiving a child is a common, worldwide problem. The incidence of sub-fertility seems to be increasing, with defects in sperm (1 in 15 men) being the single most common cause. Therefore, understanding how sperm work and how to efficiently detect sperm fertilising ability are a matter both of interest and great importance. In comparison to other cells in our body, sperm are tiny with a much simplified structure. Nevertheless, in order to fertilise, the sperm must perform a series of activities which must be correctly timed, each one being induced by discrete stimuli encountered in the female reproductive tract. However, nobody yet fully understands the events that occur in response to different stimuli and how these events result in an appropriate response. This project focuses on tackling this issue by creating a novel technology where a silicon chip type device is coated with biological molecules that can be dynamically revealed and hidden. We w ill use this technology to understand how sperm can respond to signals in the female tract, and importantly try to assess how they relate to cell quality to allow us to pick the best cells for infertility diagnosis and treatment procedures.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.4 METHODOLOGIES AND MEASUREMENTS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: The role of decidual natural killer cells in pregnancies at high risk of pre-eclampsia.
Funder: Wellcome Trust

Abstract: In pregnancy, fetal cells called trophoblasts invade and alter the uterine blood vessels to increase the blood supply to the growing baby. Special maternal immune cells called decidual natural killer cells may play a role in this important process. These cells release factors that can attract trophoblasts and they may directly change the maternal blood vessels. Immune cells have to be controlled since they can recognise that trophoblasts carry markers of the fetus s father. In some pregnancies t rophoblasts don t invade enough and the changes in the blood vessel fail to take place leading to serious problems such as pre-eclampsia. Pre-eclampsia is a common pregnancy disorder that can result in the death of mother and baby. Although it is not possible to definitively predict whether a mother will develop pre-eclampsia, using ultrasound scanning it is possible to determine whether there is an increased risk. We have preliminary data that decidual natural killer cells from pregnancies most and least likely to develop pre-eclampsia are different. The aim of this project is to investigate whether these differences are important in the regulation of how trophoblasts behave and how the mother s blood vessels are remodelled.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Identification of trophoblast differentiation pathways regulated by Glial Cells Missing 1 using comparative studies of horse and human pregnancy.
Funder: Wellcome Trust

Abstract: Normal mammalian placental development is essential for survival of the fetus. Horse and human placentae are distinct from other species as both produce the hormone chorionic gonadotrophin (CG). This proposal combines veterinary and medical expertise using a comparative approach to study growth and function of specialised placental trophoblast cells that secrete CG. Our recent studies identified a protein called Glial Cells Missing 1 (GCM1) that appears essential for the normal development a nd function of CG-producing trophoblast cells. Firstly, we will determine the role of GCM1, and identify pathways it regulates during equine trophoblast growth. Due to restricted availability of human placental tissue during important windows of development, the horses provide a unique alternative for investigations of molecular pathways relevant to human pregnancy. Second, we will investigate the role of GCM1-regulated genes in the development of pre-eclampsia in human patients. Our propos al will lead to methods of producing CG in the laboratory that would represent a significant advance in horse welfare. Identification of mechanisms that control growth of CG-secreting trophoblast cells also has important applications for reducing pregnancy losses that occur in approximately 20% of mares and women, and for treatment of pre-eclampsia, the leading cause of maternal and fetal mortality.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH