NIHRDataInsights/HRCSData huggingface dataset:
Title: Impact of Wood Burning Air Pollution on Preeclampsia and other Pregnancy Outcomes in Temuco
Funder: Natural Environment Research Council

Abstract: Impact of Wood Burning Air Pollution on Preeclampsia and other Pregnancy Outcomes in Temuco Exposure to air pollutants has important acute and chronic health effects. An important effect that has been recently studied is pregnancy effects of pollutants. Scarce literature exists related to impacts of pollutants on preeclampsia and even less about the specific impact of residential wood burning emissions on pregnancy outcomes. Temuco is located in southern Chile and is known for its very high concentrations of air pollutants associated to residential wood burning. The main objective of this proposal is to determine whether exposure to air pollutants (specifically PM2.5 and wood burning tracer) have an impact on preeclampsia and other pregnancy outcomes (low birth weight, birth weight, small of gestational age, preterm birth). Reproductive data will be obtained from available databases at the Hospital Dr. Hernan Henriquez Aravena in Temuco and Padre Las Casas between 2009 and 2015. A total of approximately 18,000 pregnancies are expected. A year-long air pollution campaign will be performed in 3 10-week sessions, including a total of 20 fixed-site sampling points and mobile measurements. The studied pollutants will be PM2.5 and wood burning tracers within it (levoglucosan and others). Data will be fitted to produce spatial models and maps using the Land-Use Regression approach. This model will be used to estimate individual exposures by trimester to the subjects using residential geocoding and historical PM measurements. Finally, logistic and linear regression models will be fitted to estimate the impact of air pollutants exposure on the selected outcomes, adjusting for other individual and temporal variables. Expected results are i) an air pollution characterization of the campaigns with emphasis in wood burning tracers, ii) a Land-Use Regression model for air pollutants in Temuco including maps of air pollutants, iii) a pregnancy outcome descriptive characterization for the study period in Temuco, iv) results of the epidemiological study showing whether air pollutants (emphasizing wood burning emissions) have impacts on the studied pregnancy outcomes. To achieve these objective, we will assemble a capable team of both Chilean and UK researchers. Four ISI articles are expected as scientific production. Additionally, four master thesis, one doctoral thesis, and a two final workshops in Chile to disseminate the research findings.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Opportunity-Led Research Proposal: Infant Death and Co-Sleeping
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Proposed area of research need. This proposal has been developed to provide much needed evidence to understand the relationship between infant death and co-sleeping in Northern Ireland and to raise awareness and develop education strategies to decrease 'sudden infant death syndrome' (SIDS through the risks of suffocation and co-sleeping, and provide health professionals, parents and families with the best evidence that is knowm about safe sleep environments for their infants. Although many new parents say that they will never sleep with their baby, about 50% of UK babies have bed-shared with a parent during their first three months. The need to identify potentially preventable infant deaths secondary to unintentional asphyxis to sharing a bed or sleeping with a baby elsewhere e.g. sofa is a major safeguarding priority area (DoH, 2010). The death of a baby is a devastating oss to a family and strategies are needed to develop clear communication processes and new safer sleeping guidance for all health professionals and parents about the preventative measures that theu can take to reduce risk factors for SIDS. Evidence suggests three factors have accounted for 79% of all SIDS deaths: prone infant sleeping position, maternal smoking (during pregnancy and postpartum), and not breastfeeding (Mitchell, 2009). Future 'Back to Sleep' campaigns (1991) have focused on public health messages that promote modifiable risk factors back to sleep, face uncovered, avoidance of cigarette smoke in pregnancy and after birth, safe-sleeping environment, room sharing and sleeping baby in own cot (Clair et al., 1996; Oyen et al., 1997; Gessner et al., 2001; Gilbert et al., 2005; Carpenter et al., 2013).


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Opportunity-Led Research Proposal: Social Complexity in Pregnancy
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: The proposed research aims to explore the feasibility of delivering an intensive manualised antenatal programme to women with complex circumstances who do not fit the current Family Nurse Partnership criteria.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Women and Maternity Care Providers' Experiences and Perceptions of Home Birth Service Provision in Northern Ireland
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: The place where a woman gives birth impacts not only on the type of birth, but also on the number of interventions that the mother and baby are exposed to during their labour and birth (Davis et al. 2011). Women who plan to give birth in a midwife-led unit or at home experience lower numbers of interventions than in an obstetric unit, including: amniotomy, augmentation of labour, instrumental vaginal birth and opiate or regional analgesia (Hutton et al. 2016; Halfdensdottir et al. 2015; Brocklehurst et al. 2011). There is also evidence that the outcomes for both multiparous and nulliparous women and babies of multiparous women who have delivered at home are equal to, if not better than those in other birth settings (NICE 2014, BirthPlace in England Collaborative Group et al., 2011; Hollowell et al. 2011). The BirthPlace study also reported a higher incidence of adverse outcomes for the baby of nulliparous women who had a planned home births (Brocklehurst et al. 2011). The NICE Intrapartum guideline (CG190, 2014) following Brocklehurst et al. findings, recommend that low-risk nulliparous women should be advised if they plan birth at home that there is a 'small increase in the risk of an adverse outcome for the baby' (p.6). Results from other cohort home birth studies however have identified perinatal outcomes from home birth as low and not significantly different for infants of nulliparous women (Offerhaus et al. 2012, Van der Kooy et al. 2011). Taking all the current evidence together NICE (2014), supports a policy of offering all women with straightforward pregnancies a choice of four birth settings (home birth, alongside MLU, free standing MLU or obstetric unit). Regionally, there is a dearth of recent homebirth research, with one study in 2002 which examined women’s experiences of home birth and highlighted their belief that birth is a normal physiological event and for them ‘…being at home gave them more control of events in their environment’ (Ng and Sinclair, 2002, https://www.rcm.org.uk/news-views-and analysis/analysis/women%E2%80%


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Can 3D cranial ultrasound be used to successfully reconstruct a 2D image without compromising on image quality in a neonatal population? A proof of concept study
Funder: Royal College of Radiologists

Abstract: The aim of the study is to compare standard images of the brain produced by 2D and 2D cross-sectional reconstructions from a 3D data set.


Research activity codes: 1.4 METHODOLOGIES AND MEASUREMENTS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Sex chromosomes in development and disease
Funder: The Francis Crick Institute

Abstract: Males and females differ fundamentally in their sex chromosome make-up: females have two X chromosomes (XX), while males have one X chromosome and one Y chromosome (XY). The sex chromosomes are highly enriched in genes functioning in germ cell and neural development, and they influence male-female differences in growth, behaviour and susceptibility to a variety of diseases, e.g. hypertension and cancer. The imbalance in dosage for X genes between females and males also presents unique challenges for the developing embryo that are overcome by X chromosome inactivation - the silencing of one X chromosome in each female cell by the non-coding RNA Xist. Our lab studies the epigenetics, evolution and cell biology of the sex chromosomes from a variety of organisms, including mammals, in order to understand how these chromosomes influence human health and disease.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Harris Wellbeing Centre
Funder: Wellbeing of Women

Abstract: We will build an internationally recognised sustainable research centre that brings together synergistic, multidisciplinary research teams focussing on personalised approach to mechanisms, phenotyping and treatments of preterm birth. We have assembled a strong team with compelling track records. The Harris/WoW funding will enable us to exploit our excellent space and facilities, to undertake world class preterm birth research with strong leadership. Our research strategy is underpinned by our expertise in personalised medicine, uterine physiology, and research synthesis. We are convinced that progress in preterm birth research requires blending of multiple omics platforms with functional testing and research synthesis. Our personalised medicine approach will use biochemical information from pregnant women to precisely tailor their healthcare provision. Our interconnected research programmes are directed at gaining increased understanding of aetiology and mechanisms of preterm birth and aim to provide leading-edge research training for early career researchers committed to preterm birth research. i) Genetic and metabolomic approach to preterm birth phenotyping. Our goal is to enable sophisticated biomarker phenotyping leading to personalised risk assessment in early pregnancy and better and safer use of preventative therapies. We will use high-throughput technologies to examine simultaneously millions of genes, transcripts and metabolites in an unbiased “hypothesis generating, multi layering” approach in women who suffered spontaneous preterm birth. We will then validate predictive value of these preterm birth gene/multifactorial/systematic signatures in low risk women. ii) Developing more effective tocolytic regimens. We will elucidate the contribution of uterine environment and gestation on tocolytic efficacy by using a range of techniques, including imaging, metabolomics and transcriptomics, to determine key pathways and molecular events, allowing us to identify novel tocolytic targets. iii) Evaluating different preventative strategies by research synthesis – global approach. Liverpool is an acknowledged world leader in research synthesis. By pioneering methods such as network meta-analysis, along with national and international collaborations, including RCOG, NICE and WHO, the best insights into effective preventative strategies will arise. Our Harris/WoW Research Centre will become the international reference centre for research synthesis related to preterm birth.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Pluripotency in embryogenesis and regeneration
Funder: Medical Research Council

Abstract: Mammals develop from a small group of pluripotent stem cells that have the task to generate all the cell types and tissue shapes of the organism in an organised manner. How they achieve this is an important and unsolved problem in biology. Up to date, most studies have focused on identifying changes in gene expression that guide pluripotent cell fate decisions and tissue morphogenesis. However, recent evidence indicates that changes in tissue shape impinge on gene regulatory networks to affect cell fate. The link between tissue shape and cell fate is particularly relevant at implantation, a critical period in mammalian development associated with high rates of pregnancy loss, but very poorly understood due to the inaccessibility of the embryo. Our aim is to understand how the organisation of pluripotent stem cells into an epithelial tissue at implantation affects their identity and subsequent specification into distinct cell types. To address this question, we have recently established a human embryo culture method that permits embryo development beyond implantation and up to day 14, the internationally recognised limit for human embryo culture. In addition, we have established 3D cultures of mouse and human embryonic stem cells (ESCs) that faithfully recapitulate the development of the embryonic tissue at implantation. We will capitalise on these novel culture methodologies, and apply state-of-the-art transcriptomics, proteomics, imaging, and functional experiments to determine how cell and tissue organisation affect pluripotent stem cell identity by modulation of signalling. Functional experiments in human embryos cultured beyond implantation have not been performed. To gain a mechanistic understanding of human embryo development we plan to perform human ESC – human embryo chimeras. This will allow us to modify the genetic material of the ESCs and assess the effects in the context of the embryo. We have already obtained approval from the Human Fertilisation and Embryology Authority (HFEA) to perform these experiments. Our final goal is to unveil the molecular basis of human embryogenesis, and how the exquisite coordination between fate and shape is affected when development fails. This work will be done in close collaboration with in vitro fertilisation clinics in the UK, which will provide supernumerary in vitro fertilised embryos for research.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Biomarkers of materno-fetal health: role placental endocrine mediators in normal and obese pregnancies
Funder: Medical Research Council

Abstract: In the UK and around the globe, the prevalence of obesity during pregnancy is increasing relentlessly. This is worrying as obesity adversely affects maternal and infant health both during and after pregnancy. It increases the risk of pregnancy complications such as gestational diabetes (GDM) and leads to neonatal and later health conditions including type-2 diabetes in the offspring. In obese women, the metabolic responses to pregnancy are often exaggerated. Maternal metabolic alterations are signalled, in part, by changes in placental hormone production. However, to date, little is known about the role of placental endocrine function in determining pregnancy outcomes in obese mothers. Thus, this study aims to identify the role of placental hormone production for maternal metabolism, fetal growth and offspring metabolic health, in pregnancies where the mother is obese. It will use the latest sequencing techniques to identify the hormones secreted from the placenta that are dysregulated in mouse pregnancies associated with maternal obesity. It will then use a new model of genetically-induced placental endocrine malfunction in mice (achieved by cell-specific deletion of the imprinted growth gene, Igf2, which controls placental endocrine cell formation and function), to test the hypothesis that abnormal placental hormone production contributes to the metabolic maladjustments of the obese mother and the developmental programming of the offspring. Placental hormones important in the deregulation of maternal metabolism in mouse pregnancies will then be measured in the placenta and blood of lean and obese women with normal metabolism or GDM to establish whether they too predict pregnancy outcome in humans. The ultimate goal of this work is identify placental biomarkers that indicate materno-fetal health during gestation and can be used to diagnose, or as therapy targets to prevent, pregnancy complications and the associated programming impacts in obese women.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: OMWaNA Operationalising kangaroo Mother care before stabilisation among low birth Weight Neonates in Africa: RCT to examine mortality impact in Uganda
Funder: Medical Research Council

Abstract: Globally, there are 2.6 million neonatal deaths annually. Over 80% of these occur in neonates who are small at birth. Kangaroo Mother Care (KMC) involves placing a preterm/low birthweight neonate skin-to-skin with a caregiver. A Cochrane review reported 40% mortality reduction with KMC in stable neonates. The WHO recommends KMC for routine care of newborns 2000g or less, initiated when clinically stable; yet, estimates suggest at least 75% of neonatal deaths occur before stabilisation in settings without intensive care. The only RCT of KMC before stabilisation (Ethiopia, 123 neonates) reported major mortality impact (RR 0.57) but had design challenges. The Operationalising kangaroo Mother care before stabilisation among low birth Weight Neonates in Africa (OMWaNA) trial is a partnership of MRC/UVRI, LSHTM and Makerere University. The trial will be conducted in four Ugandan hospitals without intensive care (Jinja, Masaka, Iganga, Entebbe). We will undertake an individually randomised, controlled, superiority trial with two parallel groups to determine the effect of KMC initiated before stabilisation on mortality at 7 and 28 days relative to incubator care among 2188 neonates 2000g or less. Secondary outcomes include length of stay, weight gain, and underlying mechanisms by which KMC may influence mortality (e.g., temperature instability, apnoea, oxygen desaturation, intraventricular haemorrhage). The economic evaluation will estimate the incremental costs and cost-effectiveness of KMC relative to incubator care from the provider, household, and societal perspectives, and model the total cost of scaling up KMC nationally. We will also utilise a novel tool to assess women's well-being, qualitatively explore enablers and barriers to implementation, and conduct a process evaluation of KMC initiation before stabilisation. Key stakeholders engaged include the Ugandan Ministry of Health, Uganda Paediatric Association, UNICEF, WHO, and the International KMC Network.


Research activity codes: 6.7 PHYSICAL
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Prenatal influences on childhood health: what role for mums and dads?
Funder: Medical Research Council

Abstract: It is widely recognised that pregnant mothers can influence the health and characteristics of their children via non-genomic "maternal effects", but there are still gaps in our understanding regarding causality and the range and mechanism of effects. Consequently, current public health advice for women who are pregnant or looking to conceive can be inconsistent, misleading and often based on the precautionary principle rather than robust, empirical evidence of causation. Additionally, there is increasing evidence that fathers can also exert "paternal effects" on the health of their unborn children, but very little advice is currently offered to fathers-to-be. This research will address an urgent unmet need to better understand how both maternal and paternal health behaviours in the prenatal period influence offspring health outcomes. The four specific research questions are: 1) Which prenatal maternal and paternal health behaviours associate with offspring outcomes? 2) Which of these associations are causal? 3) How do maternal and paternal influences interact or mediate each other? 4) What are the underlying molecular mechanisms? The project uses existing questionnaire and 'omics data (therefore representing excellent value-for-money) from six major European birth cohorts, focusing on parental exposures that might be considered modifiable (smoking, alcohol, physical activity, diet) and offspring outcomes spanning three domains of child development (anthropometry/adiposity, neurodevelopmental/psychosocial, congenital anomalies) as well as potential molecular mediators (DNA methylation, metabolites). Evidence garnered using different state-of-the-art epidemiological approaches will be triangulated to help identify and refine causal pathways. Findings will identify the most appropriate prenatal targets (mothers, fathers or both parents) for public health advice to improve offspring outcomes.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES;3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: How does a multi-country, multilateral network focused on specific health care improvements evolve and what shapes its ability to achieve its goals?
Funder: Medical Research Council

Abstract: Our research seeks to evaluate, via three research questions (see objectives above) the emergence, legitimacy and effectiveness of a multi-lateral multi-country purposefully created implementation-focused network to improve the quality of care for maternal, newborn and child health (QCN). We will study the QCN global level, and national and local levels in three case study countries. We will examine the global-national and national-local level interfaces. We will develop theory relating to how QCN functions utilising and advancing underlying theories relating to the policy process, the interplay of structure, agency and power and its relation to policy capacity determinants including individual, organisational and systemic level capacities, and pertinent contextual and cultural factors. We will also explore network implementation in relation to the theory of change proposed by QCN and seek to develop this further in relation to the role of network actors and stakeholders. Here we will utilise framing theories related to diffusion of innovation, network organisation and effectiveness, knowledge management, and behaviour change. To answer our research questions we will collect a mixture of qualitative and quantitative data over five iterative prospective rounds. We will interview key QCN actors and stakeholders at global, national, and local levels, conduct observations at best and worst performing hospitals in our case study countries, review key QCN documents, and conduct surveys of QCN members, and triangulate across these data. We will also access, and critique, the monitoring and evaluation data of QCN (including retrospective data) to track key processes, outputs and outcomes and assess the plausibility of QCN effects on health outcomes. We will conduct within-case, cross-case and case synthesis analyses using process-tracing, stakeholder network analysis, and thematic analyses framed by the aforementioned theories.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH