NIHRDataInsights/HRCSData huggingface dataset:
Title: A pharmacoepidemiological study of maternal prescriptive drug use: the risks and benefits to mothers and neonates
Funder: Wellcome Trust

Abstract: Pregnant women are heavily underrepresented in clinical trials as it would be unethical to conduct a human trial with a potential outcome of neonatal birth defects. Thus, prescribing medication to pregnant patients provides a challenge for physicians as the beneficial effect of the drug must be balanced against possible maternal and neonatal adverse effects. This presents a significant problem as there are a range of chronic conditions requiring ongoing treatment that precede or develop during pregnancy. I aim to evaluate the potential risks and benefits currently associated with continuing medications through triangulation of evidence from pharmacoepidemiological and genetic studies to inform clinicians and patients. I will use electronic healthcare record data to investigate the beneficial and detrimental effects of maternal prescriptive drug use for diabetes, hypertension, and thyroid disorders for both mother and neonate. I will also proxy maternal prescriptive drug use through analysis of genetic drug exposures on neonatal outcomes to determine whether genetic proxies can indicate adverse neonatal drug reactions. This PhD will establish reliable evidence for the intrauterine exposure of prescription drugs on the mother and neonate to provide evidence to guide clinical decisions under circumstances where we are unable to perform a randomised controlled trial.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Defining optimal interventions for Perinatal Anxiety (PNA) in a general practice population: a mixed methods study.
Funder: Wellcome Trust

Abstract: Background to the research problem Perinatal anxiety (PNA) is anxiety that occurs during pregnancy or up to twelve months postpartum. The global prevalence of PNA is estimated to be over 15% and at least as common as perinatal depression (PND). PNA can adversely impact both mother and child. Whereas a significant amount of research has been conducted into PND; i in comparison there is very little work published that reviews PNA. The National Institute for Health and Clinical Excellence has recommended that further research is needed in order to develop psychological interventions to identify and treat moderate to severe anxiety disorders in pregnancy which is where my research intends to fill a vital gap. My approach My PhD aims to define optimal interventions for PNA. The PhD comprises of several parts including a systematic review of published literature, interviews with PNA stakeholders such as patients and professionals who deliver perinatal care with the final aim to co-develop an intervention for PNA with stakeholders. Expected impact of my work After development of an intervention I hope to secure funding after my PhD to test it. I hope that it may be recognised and recommended in clinical practice.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Defining the impact of androgens on macrophage function during endometrial tissue repair
Funder: Wellcome Trust

Abstract: Macrophages are essential mediators of tissue repair but we lack fundamental knowledge about how they are regulated in the endometrium. Androgens regulate macrophage function in other tissue repair contexts but their role in endometrial repair has not been defined. This project will determine how macrophages are regulated in endometrial repair by assessing their turnover and phenotype and how this is affected by androgens by using a highly reproducible mouse model of endometrial repair that we have developed. The key goals of this project are; 1. to determine whether monocytes contribute to the endometrial macrophage function in repair, 2. to define how androgens mediate intrinsic and extrinsic effects on endometrial macrophage function and 3. to investigate how androgen excess alter macrophage function in aberrant repair. This will be achieved by using fate-mapping techniques, transcriptomics analysis, multiparameter flow cytometry and immunohistochemistry combined with pharmacological and genetic approaches to modulate androgen action. These studies will establish that macrophages are critical mediators of endometrial repair and modulation of their phenotype by androgens determines the balance between healthy and disordered tissue repair. These important insights will provide a platform for assessing macrophage AR as a potential therapeutic target in reproductive health.

Lay abstract: The endometrium must repair following menstruation in order to maintain healthy function. Specialised immune cells called macrophages control repair but the specific subtypes and how they function in the endometrium are not known. Androgens are important for controlling endometrial function, but excess androgens are detrimental to repair. In other tissues androgens regulate macrophage function during repair but it is not known if this occurs in the endometrium. I aim to understand how androgens affect macrophages in endometrial repair. I will use a mouse model combined with detailed cell profiling to characterise different macrophage types and their function in endometrial repair. I will test how macrophage function can be changed by androgens and determine if blocking this can prevent poor repair associated with androgen excess. These studies will help to explain how macrophages are regulated during endometrial repair and provide a platform for developing new therapies for women’s health disorders.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: PRECISE-DYAD: linking maternal and infant health trajectories in sub-Saharan Africa
Funder: Wellcome Trust

Abstract: PRECISE-DYAD will extend the ongoing PRECISE network study [PRECISEnetwork.org] of 6,000 pregnant women and their infants (dyads); it will provide a greater epidemiological and mechanistic understanding of health and disease pathways in the sub-Saharan African context (The Gambia and Kenya), following uncomplicated pregnancies and those complicated by pregnancy hypertension, fetal growth restriction, stillbirth, and/or preterm birth. For women, we aim to determine if, and how, these pregnancy events identify those more likely to avoid complications in subsequent pregnancies, mental ill-health, or early onset of cardiometabolic diseases. For their children, we will assess the impact of these pregnancy disorders on their physical, mental, and neurodevelopmental health to 2-3 years of age. We will explore the consequences for maternal health trajectories of caring for children with moderate-to-severe neurodevelopmental delay resulting from complicated pregnancies, and will interrogate interactions with social determinants of health, including environmental exposures on maternal and infant health. We will develop a rich database and a large sample biorepository for future studies. Thereby, PRECISE-DYAD aims to achieve an overarching understanding of the factors that contribute to optimal maternal and child health within these contexts. Ultimately, the goal is to design interventions to optimise health of mothers and their children.

Lay abstract: PRECISE-DYAD extends the ongoing PRECISE study of pregnant women and their infants (dyads) in two sub-Saharan African countries, The Gambia and Kenya, especially after pregnancies complicated by high blood pressure, birth of a smaller-than-expected baby, stillbirth, or premature birth. For women, we want to know if these pregnancy events, or caring for children with delayed brain development due to these events, can cause similar complications in future pregnancies, influence mental health, or increase the risk of heart or breathing disease or diabetes. For their children, do these pregnancy complications change physical and mental health and brain development at two years of age? We will ask if these links are altered by social and environmental adversity, including environmental pollution. Our database and bank of biological samples will help us understand the processes behind whether women and their babies do well or poorly to help us design future preventative and treatment strategies.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: The natural history and NHS service use of women with depression and impact on children in a multi-ethnic inner-city population
Funder: Medical Research Council

Abstract: We aim to describe the natural history of depression and its consequences for women pre- and post-pregnancy in a multi-ethnic and economically deprived community in England. We plan to build an enhanced dataset composed of a suite of baseline measures taken at ~28 weeks gestation from the 13,000 women enrolled in the Born in Bradford Cohort; uniquely linked to the local GP database, SystmOne. To extract the NHS data we will devise and test an algorithm of previously validated Read codes for depression diagnoses, screening, symptoms, and treatment referrals along with anti-depressant prescribing and counts of consultations for any reason. NHS data will be drawn 15 months prior to the index birth and for 3 years post-natally. Further measures of mental health (GHQ-28 and Kessler Scale for Psychological Distress) and parenting practices are available for 5 time points up to 3 years post-partum for a subsample of ~1300 women along with child behavioural outcomes (SDQ) at 3 years. After data cleaning and validation, we will use rates and ratios to describe the data and population in terms of demographic characteristics, mental health and presentation to primary care. Receiver operator characteristic (ROC) curves will be used to calibrate the relative accuracy of cohort mental health measures against each other and NHS diagnoses. We will use structural equation modelling to explore the following; latent class analysis for characteristics related to presentation/non-presentation to primary care and latent transition for fluctuations over time, path analysis to explore moderators and mediators of child outcomes and confirmatory factor analysis to examine fit of latent measures. The results will describe social inequality in service use and quantify impacts of health seeking behaviour on children. Findings will be disseminated through academic routes, exploitation of local public involvement and engagement with NHS and other agencies via dissemination specialists.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Treatment for mothers with postnatal depression to improve child outcome: a randomised controlled trial.
Funder: Wellcome Trust

Abstract: Maternal postnatal depression (PND) is a major public health issue: it affects around 13% of mothers, and compared to children of non-depressed mothers, the children of mothers with PND are more likely to have intellectual, behavioural and attachment problems Treating maternal depression alone does not improve child outcome. An intervention focusing on mother-child interactions is needed to promote these children s development. We aim to examine whether, in the context of PND, a treatment to enhance mother-child interactions leads to improved child outcome. Furthermore, since treatment can be targeted at critical aspects of functioning, a treatment trial provides an opportunity to examine potential causal factors in determining child outcome. Thus, we will focus treatment on improving three key parenting capacities that are known to be compromised in PND, and examine whether this improves children s outcomes. Mothers with PND will receive home-based treatment from six months po stpartum. They will be randomised to one of two treatments: either video-feedback treatment (index) to improve mother-child interactions or relaxation training (control). Both groups will also receive cognitive behaviour therapy for depression. The two groups will be compared post-treatment (child age one year) and at follow-up (child age two years).


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Foetal testosterone effects on brain development.
Funder: Wellcome Trust

Abstract: We aim to test if levels of testosterone before birth (which are produced at significantly higher levels in males) influence brain development in humans. Whilst prenatal testosterone has been demonstrated to have an effect on brain development in animals, this has never been tested in humans. We have conducted a unique study where we measured prenatal testosterone in amniotic fluid and followed the children from birth to predict behavioural development longitudinally. Our research thus far had s hown that prenatal testosterone is a key predictor of social development and may mediate sex differences in behaviour. We now have a valuable opportunity to employ neuroimaging with this sample, to test for the first time if fT is associated with sex differences in the brain. We will also take measures of current testosterone, since the prediction is that only prenatal testosterone will exert permanent effect on long-term social development, brain structure and function.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Functional and structural thalamocortical connectivity after preterm birth and its relation to later cognitive abilities.
Funder: Wellcome Trust

Abstract: Preterm birth is increasingly common, and although most infants now survive many suffer some degree of brain damage and develop problems with learning as they grow up. It is not known exactly what causes this, but many areas of the brain seem to be affected, including the cerebral cortex where much high-level processing occurs, the white matter that connects brain regions together, and the nerve cells at the centre of the brain which have a major controlling effect on many functions. The se abnormalities develop very early, while the infants are still preterm, and are present by the time they should be born. This is the period when the connections between the cortex and the brain's central structures are developing, and this has led to the theory that the problems faced by preterm infants may be caused by failure of these connections to develop normally. Using new MRI techniques it is possible to study the development of these connections in detail, and this project aims t o discover if abnormal connections account for problems the children may have at 2 years of age.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: What are the relationships between the degree of pregnancy intention and key neonatal and maternal outcomes in the Mchinji district of Malawi?.
Funder: Wellcome Trust

Abstract: Every year there are approximately 75 million unintended pregnancies globally because so many women do not have access to family planning. It is possible that these unintended pregnancies are more likely to result in death or illness in the mother and/or their baby than intended pregnancies. This may be because of the additional stress and anxiety an unintended pregnancy may cause or because women whose pregnancy is unintended may be less likely to use services such as antenatal care. This pro ject, which will be carried out in Malawi, will investigate the relationships between how intended the pregnancy is, women's behaviour during pregnancy and the health of the woman and baby after birth. If we find that unintended pregnancies do carry greater risks for mother and baby we will be able to strengthen the arguments for providing family planning to women who would like to use it. At the same time we will explore the attitudes of men, women and communities to family planning and exami ne the provision of family planning in Malawi to provide information on how to improve women's access to family planning and reduce the burden of unintended pregnancies.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Wellcome Trust Joint Basic and Clinical PhD Programme at the University of Birmingham: Unravelling the link between insulin resistance and androgen in excess
Funder: Wellcome Trust

Abstract: Polycystic ovary syndrome (PCOS) is a disorder of the female reproductive system associated with infertility and high levels of male sex hormones calledandrogens in the bloodstream and tissues. Patients with PCOS have an impaired response to the hormone insulin ('insulin resistance'), putting them at risk of future diabetes and heart disease. It is unclear whether insulin resistancein PCOS causes androgen excess and infertility or if androgen excess drives insulin resistance. We know that patients with genetic causes of insulin resistance have high androgens; conversely patients with genetic causes of androgen excess are insulin resistant. This study examining the link between insulin resistance and androgen excess in PCOS will be conducted at the Wellcome Clinical Research Facility, Queen Elizabeth Hospital Birmingham and the Institute of Biomedical Research, University of Birmingham. It will involve patients with PCOS and genetic insulin resistance, as well as healthy controls. Each patient will undergo blood and urine testing, a fat biopsy and adipose microdialysis, which measures hormones in fatty tissues. We believe that these investigations, backed up by laboratory experiments, will give us key insights into how insulin affects androgen production and vice versa.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Does daily antenatal multiple micronutrient supplementation, compared to iron and folic acid, lead to a difference in IQ at 10 years of age among children in Nepal?
Funder: Wellcome Trust

Abstract: Little is known about the impact of antenatal multiple micronutrient supplementation on childrens mental development, especially in low and middle-income settings. My research has two objectives: 1. To review the pathways through which antenatal multiple micronutrient supplementation could affect children's mental development, and the evidence for each of these. 2. To follow up children born during a randomized controlled trial testing the effect of daily antenatal multiple micronutrient s upplementation on birth weight in Nepal in order to determine whether children exposed to supplementation have improved IQ at 10 years of age. Specifically, as part of my MSc dissertation, I hope to carry out a desk-based review of studies examining the associations between individual and multiple micronutrient supplementation in pregnancy, and children's mental development. Then, during a subsequent 18 months research project, I wish to follow up children born during the randomized controlle d trial carried out by Osrin et al. (2005) in order to measure their IQ at 10 years.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Understanding the relationship between apnoeas and brain function in premature infants
Funder: Wellcome Trust

Abstract: Apnoea of prematurity is a common problem in neonatal care, affecting all preterm infants born before 29 weeks’ gestation. These potentially life-threatening events are associated with pronounced physiological instability, reduced cerebral oxygenation, and long-term consequences including reduced cognitive ability in childhood. However, it is unclear how these frequent intermittent episodes of hypoxia affect brain activity, and whether this alters brain development. The aim of this Fellowship is to understand the complex interplay between brain function and apnoeas in preterm infants. I will establish the effects of apnoeas on brain activity, considering how this is altered by the degree of physiological instability. I will identify biomarkers of apnoea to create a probabilistic model of the risk of apnoea so that early interventions can be provided. By conducting detailed longitudinal recordings of physiology from birth, and neurophysiological recordings weekly, I will investigate whether episodes of apnoea can alter the trajectory of brain development and whether this affects cognitive ability at 2 years of age. Gaining a better mechanistic understanding of the pathophysiology of apnoea is essential to improve treatment options, and could ultimately lead to better neurological outcome in prematurely-born children.

Lay abstract: 1 in every 10 babies are born prematurely, which can have a long-term impact on brain function and cognitive ability. However, what drives these long-term effects is poorly understood. Premature infants often experience apnoeas – cessation of breathing – which can result in decreased oxygen supply to the brain. Yet how this impacts brain function is unclear. The aim of this Fellowship is to gain a better mechanistic understanding of the interaction between brain activity and apnoeas in premature infants. I will examine whether brain activity is altered during apnoeas, and identify physiological markers predictive of apnoeas, allowing for early interventions. Studying infants longitudinally, I will investigate whether frequent apnoeas alter the trajectory of brain development, and determine how this relates to cognitive ability at 2 years of age. This research will enhance our understanding of apnoeas and the long-term effects of premature birth, ultimately improving outcomes for prematurely-born children.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH;NEUROLOGICAL
Title: A randomised controlled trial to identify if cognitive behavioural therapy delivered by respiratory nurses reduces anxiety and depression in patients with chronic obstructive pulmonary disease.
Funder: Department of Health (England)

Abstract: Background - Up to 40% patients with COPD (chronic bronchitis and emphysema) have anxiety and/or depression. Patients report a reduction in quality of life. Disease progression leads to increased hospital admission, many patients die early. Aim - to identify if cognitive behavioural therapy (a psychological talk therapy), delivered by respiratory nurses (RN) reduces anxiety and depression, improves the patients quality of life and results in reduced hospital admissions. Design - a randomised controlled trial involving 300 patients who will be randomised into one of 3 groups a) CBT delivered by RN who have advanced (post graduate diploma) CBT training, b) RN with basic (3 day short course) CBT training and c) control group receiving standard care. Patients attending clinic are currently screened for anxiety and depression. Patients with probable anxiety and providing consent will be randomised as above. Data will be collected using patient completed questionnaires pre CBT and 3, 6 and 12 months.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH;RESPIRATORY