Title: Pre-eclampsia and long-term cardio-metabolic outcomes
Funder: Department of Health and Social Care

Abstract: BACKGROUND The proposed training and development plan is framed around a 3-stage research project, which forms the basis of an MPhil.Pre-eclampsia has been associated with future risks of cardiovascular disease and diabetes (cardio-metabolic' diseases). However, it remains unclear whether pre-eclampsia is an independent risk factor for future cardio-metabolic diseases or an early marker of women with high-risk profiles for these diseases in the future. As the incidence of pre-eclampsia continues to increase, this population will require more healthcare resources.AIMS 1. To acquire research skills to transition from a basic scientist into a clinical epidemiologist in Women's Health 2. To determine the relationship between pre-eclampsia and long-term cardio-metabolic complicationsPLAN Stage 1: Systematic review (months 1-6) Training Systematic review and evidence synthesis skills will be acquired through conducting a systematic review and attending a Cochrane evidence-based decision-making course (Oxford).Project The review will establish the validity and performance of cardio-metabolic disease risk scores which could be applied to pregnancy or high-risk pregnancy and identify studies which investigate these cardio-metabolic risk scores with regards to long-term outcomes. The identification of current evidence base and gaps in knowledge will inform the following stages.Stage 2: Local database study (months 6-18) Training I will further my skills by attending the advanced course in epidemiological analysis (London School of Hygiene and Tropical Medicine) and an analysis of repeated measures course (Bristol). A cross-sectional study will provide practical experience in statistical methods. Research governance understanding will be achieved through an ethics course (online), establishing the Pre-eclampsia registry, the collaborative visit to Sweden, and setting-up a PPIE stakeholder group. I will identify a potential collaborative project using the Swedish Medical Birth Register during my visit to Sweden.Project As part of quality of care audits, I have curated a database on women with pre-eclampsia and matched healthy pregnancies. A local primary care database, Consultations in Primary Care Archive, also contains similar data. I will conduct a cross-sectional study in women with and without pre-eclampsia, using appropriate composite cardio-metabolic risk scores identified in stage 1, in both databases. I will compare female characteristics, cardio-metabolic risk factors and the likelihood of being high risk' having adjusted for potential confounders, in women with and without pre-eclampsia. I will also analyse the risk scores against cardio-metabolic markers such as glucose level.These results will inform the design for a formal Pre-eclampsia registry to collect prospective antenatal, intrapartum and postpartum data for future research programmes. Furthermore, a Patient and Public Involvement and Engagement (PPIE) stakeholder group will be established to guide the set-up of the registry and to improve dissemination of research findings. Stage 3: National database study (months 12-24) Training Knowledge in epidemiological and statistical methods will be supported through the training courses in stage 2, courses on linked health data (Swansea) and Clinical Practice Research Datalink (CPRD) (online), and practical experience of the CPRD.Project This stage will include the use of a pilot sample to learn cleaning and organisation of data in CPRD. I will characterise women with and without pre-eclampsia, similar to the analyses in the stage 2 study. Furthermore, I will design a fuller scale cohort study to investigate outcomes, e.g. incident cardio-metabolic diseases, over 10 years using data linkage. This detailed protocol will support my application for an NIHR Clinician Scientist Award following this fellowship. POTENTIAL BENEFITS Improved long-term health of women with pre-eclampsia can lead to profound long-term benefits for them and their children. Women will be empowered with knowledge of their future cardiovascular risk, which improves their experience. Furthermore, we will gain more understanding of the interface between primary and secondary care.

Lay abstract: AIMS This Transitional Research Fellowship will enable me to develop the skills to become a leading researcher in the care of pregnant women. I am an NHS Consultant and want to change from my current expertise in basic sciences' about genes and molecules to focus on clinical research that directly relates to patient care and outcomes. Through a research based Master's degree (MPhil), advanced training courses in statistics and collaborations, this fellowship will help me to become a specialist in the risk factors affecting Women's Health and plan a programme of research, using routinely collected healthcare data, on how complications in pregnancies influence long-term outcomes.TRAINING AND PROJECT Summary I have planned a 3-stage project with Patient and Public Involvement and Engagement (PPIE) input to build evidence around questions about pregnancy-related complications, whether they have long-term effects on Women's Health, and the nature of these effects. This project will provide me with advanced training in risk factor and statistical analyses.Pre-eclampsia (high blood pressure with protein in the urine during pregnancy) has been linked with increased chances of developing heart disease and diabetes in later life (called cardio-metabolic diseases'). However, we do not yet know whether this link is real, why there is a link, and there are no clear recommendations on how to follow-up women who had pre-eclampsia during pregnancy.Methods Stage 1: Systematic review (months 1-6) Training: I will attend the national Cochrane evidence-based decision-making course in Oxford. This stage will provide me with training in conducting systematic reviews of research which forms the foundation for evidence-based clinical practice.Project: My systematic review of risk scores that predict longer-term outcomes after pregnancy will help to determine women's chance of future adverse outcomes. This practical application of my training will improve my knowledge of risk scoring and support the database studies in the following stages. Stage 2: Local database study (months 6-18) Training: I will attend statistics courses at the London School of Hygiene and Tropical Medicine and University of Bristol to help with conducting and analysing a hospital database study. My international collaboration with Sweden will enable me to learn from Swedish registries and apply similar approaches to the Pre-eclampsia registry I develop at my hospital. An online ethics training course will also help with registry set-up as well as creating a PPIE stakeholder group.Project: As part of quality of care audits, I started collecting data on women with pregnancies affected by pre-eclampsia and women with healthy pregnancies (around 3,000 women). This has resulted in an idea to create a long-term registry using routinely collected data. I will use this database and an existing local general practice database, to compare the risk factor profiles for cardio-metabolic diseases in women with and without pre-eclampsia, and practice the statistics skills I have learnt. The Swedish collaboration will improve the pregnant women registry I plan to develop to follow women with pre-eclampsia over time. I intend to identify a potential collaborative project using the Swedish Medical Birth Register during my visit to Sweden. I have already had PPIE and will establish a stakeholder group that informs the development of a more complete future registry. Stage 3: National database study (months 12-24) Training: Using Clinical Practice Research Datalink (CPRD), a national anonymised database of routinely collected healthcare records from general practice patients, this stage will enable me to understand big complex data', such as age, deprivation, smoking, and outcomes for cardio-metabolic diseases. I will undergo practical training with a statistician at the Keele NIHR School for Primary Care Research on how to clean, organise and link clinical data, supported by courses on linking data (Swansea) and using CPRD (online).Project: I will submit a scientific proposal to CPRD Scientific Committee for approval for a project which links information for pregnant women with pre-eclampsia to routinely collected data and study the factors that predict future cardio-metabolic diseases in pre-eclampsia. Within this stage, I will characterise the population of women with pre-eclampsia in terms of their ethnicity, deprivation and clinical features. My intention is to develop statistics and risk factor research skills to support a full project after the pilot training. The project will contribute to a part-time MPhil degree in Clinical Research at Keele University. In addition, with the proposed training and development programme, this fellowship will provide the foundation for me to become a clinical researcher and seek further NIHR funding to meet my goal of developing into an independent researcher in Women's Health.

Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH;CARDIOVASCULAR;METABOLIC AND ENDOCRINE