Title: NIHR global health research group on preterm birth and stillbirth at the University of Edinburgh (the DIPLOMATIC collaboration) at the University of Edinburgh
Funder: Department of Health and Social Care

Abstract: a. Strategic objectives of the host university. This NIHR global health group is closely aligned with the strategic objectives of the host university, the University of Edinburgh (UoE), to benefit society as a whole, and to make a significant, sustainable and socially responsible contribution to the world, through partnerships, exchange and engagement [2]. The group will benefit from the Global Health Academy (GHA, Director Grant, coapplicant), the Centre for Global Health Research (CGHR, Director Campbell, co-applicant who has professional focus on child health in LMIC), and a community of staff, students, alumni and global partners who integrate global education, interdisciplinary research and health service development and delivery. UoE’s translational global health research is world class. For example, UoE-led research pioneered the use of a novel genetic test to identify and treat livestock infected with the parasite that causes sleeping sickness, resulting in a 90% fall in transmission to humans, and the prevention of many human deaths in subSaharan Africa. The quality of current translational global health research at UoE has led to the recent award of two NIHR Global Health Units: one in respiratory health (RESPIRE) and another in infectious disease (TIBA). Hence our preterm birth and stillbirth global health group will benefit from expertise and connections in RESPIRE, TIBA, GHA and CGHR and by building on their links with international agencies on guidelines, policy makers and public engagement we will accelerate the translation of research into clinical practice and education. We will make use of existing UoE global health experience to focus on the needs of DAC countries (specifically Malawi and Zambia) and build respectful reciprocal partnerships in a manner that protects and promotes human rights, in line with the recommendations of the Research Fairness Initiative[3] and others [4]. DIPLOMATIC will provide evidence on how to strengthen maternal health programmes for women– objectives identified as key in the 2016 DFID research review. We will identify trial interventions based on evidence in other countries, evaluate effectiveness (and implementation strategies) in Malawi and Zambia, address the shortage of skills in ultrasound scanning and build capacity and sustainability, according to good practice recommendations[5]. We believe the work from DIPLOMATIC will provide a measurable benefit to patients and the public, in currently underfunded and under researched areas. b. Underpinning facilities from host University. UoE conducts world class health research. In the 2014 Research Excellence Framework, our medical research was ranked 5th in the UK. Edinburgh has the only MRC Centre for Reproductive Health (MRC-CRH) in the UK. Two research groups within the MRC-CRH, The Edinburgh Tommy’s Centre for Maternal and Fetal Health research[6] (funding of £4 million since 2008, 23 current members of staff, directed by principal applicant Norman) and the Jennifer Brown Research Laboratory[7] (funding of £3.4 million since 2003, 8 current members of staff, directed by co-applicant Boardman) focus on issues key to this application, namely improving the health of pregnant women and newborn babies, respectively. UoE has an excellent track record in conducting large intervention trials in pregnancy, including preterm birth diagnosis and prevention trials STOPPIT[8] OPPTIMUM[9] and STOPPIT 2 (in progress NCT02235181) QUIDS (in progress ISRCTN41598423); stillbirth prevention trials AFFIRM (in progress NCTT01777022) and others EMPOWaR[10] GRACES[11] all led by applicants Norman or Stock and supported by a world class clinical trial unit, whose Director (Norrie) is co-applicant. Underpinning facitilities in learning and teaching in global health are provided by the GHA which has 16 global online MSc programmes tailored for low and middle income country contexts and learning requirements, and a vibrant Global PhD network: access will be facilitated for those from LIC working in our NIHR global health group. The GHA currently undertakes implementation research programmes through partnerships with Ministries of Health in Malawi (eg on cervical cancer screening), and national and international NGOs in Zambia and Malawi. GHA is also host to Global Alliances such as the Zambia UK Health Workforce Alliance and the World Federation of Academic Institutes in Global Health. DIPLOMATIC will benefit from a wide variety of other programmes which the GHA supports including EU funded projects Advocacy for Neglected Zoonoses (ADVANZ) (FP7, £500,000) Investigating Networks of Zoonosis Innovation (INZI) (FP7 3M) and Africa UK Partnerships for Technology Enhanced and Blended Learning, Strategic Partnerships for Higher Education Innovation and Reform (£2 million). c. This application builds on existing institutional partnerships between UoE and each of the Malawi Liverpool Wellcome Trust (MLW), (for example, Dean Everett, Group Head at MLW has a Professorial appointment at UoE); Apex Medical University (through ZUKWA); and the College of Medicine Malawi on undergraduate teaching. We note that of the 33 NIHR units and groups so far funded two units are currently working in Malawi, and one group is working in Malawi and Zambia. We have identified only one other project on maternal / newborn health: 16/137/53, PI Lavender, focussed on low-tech midwifery interventions to prevent and optimally manage stillbirth. The interventions we plan in our NIHR global group are different but complementary. We will connect and share expertise where relevant. DIPLOMATIC will complement existing investments in research capacity from the UoE (described in a) and from the College of Medicine Malawi, the Malawi Epidemiology and Intervention Research Unit (MEIRU), and Lusaka Apex Medical University, Zambia, in enhancing health research systems for the conduct of basic, operational and clinical research. Capacity and capability in LIC will be strengthened by (i) joint supervision of students (ii) sharing of guideline, clinical trial and implementation science methodology from Scotland)[12] and (iii) access to online CPD programmes through GHA at UoE, and in the UK will be strengthened by (iv) translating expertise in preterm birth and stillbirth into global health. d. Local priorities in maternal and newborn health were discussed at a meeting between the collaborators in Malawi in January 2017, and in Zambia in July 2017: preterm birth and stillbirth emerged as priorities in both countries given persistently high neonatal mortality rate despite consistent declines in other child mortality indices. The specific research themes (the need for better data collection, and the need to agree and to implement known effective evidence based interventions including optimising gestational age assessment) have been widely identified in the literature emerging from researchers and policy makers within LMIC and these were validated during the partners meetings earlier this year. The specific interventions to be tested by this group will be discussed and agreed by clinicians from Malawi and Zambia within the first 6 months of funding using an adapted Delphi methodology. We will use the INVOLVE principles to engage users of the research (patients, practitioners and policy makers), with culturally appropriate adaption as necessary. We anticipate that brokers may also be helpful for this and we will formulate a public engagement strategy within the first six months of this project. Local policy makers will be engaged through our existing links in Malawi and Zambia. Dissemination to clinicians, policy makers, and other users in other LMIC will be facilitated by links initiated by the NIHR TIBA and RESPIRE Units based at UoE and and inclusion of appropriate public and patient involvement (PPI) strategies will benefit from TIBA and RESPIRE experience in setting these up in LMIC.

Lay abstract: Our VISION is to reduce mortality of children under 5 years (one of the targets of sustainable development goal [SDG] 3), by reducing preterm birth and stillbirth and to optimise outcomes for babies born preterm. Globally 15 million babies are born preterm each year and over 2.5 million are stillborn. Deaths from preterm birth complications are the main global cause of under-5 mortality, accounting for an estimated 1·055 million [95% uncertainty range (UR) 0·935–1·179] child deaths in 2015 [1]. Low and middle income countries (LMIC) bear the brunt of this burden. Malawi and Zambia are ranked respectively 147 and 185 (out of 197 countries) for rates of preterm birth, and 129 and 124 for rates of stillbirth (high ranks equivalent to worse outcomes) . Annual deaths from stillbirth and preterm birth in Malawi and Zambia are over 36,500. Despite this heavy burden, known effective interventions for reducing preterm birth/stillbirth and their consequences are poorly implemented in LMICs leading to unnecessary deaths. Indeed, WHO estimates that the majority of stillbirths and deaths from prematurity are preventable. Alongside colleagues in Malawi and Zambia we will establish an NIHR GLOBAL HEALTH GROUP ON PRETERM BIRTH AND STILLBIRTH in LMIC. We will share existing knowledge on evidence based practices (EBP) used in high income countries (HIC). We will use new trial designs to test in LIC the EFFECTIVENESS of a collection of the best practices, and to evaluate how they are best IMPLEMENTED. We recognise the differences that cultures, traditions, gender roles, resources, workforce constraints, disease burdens and community understandings of pregnancy and birth bring, and have therefore designed this group to examine strategies to develop and to implement contextualized evidenced based local practices building on successes and challenges of current best practice in the UK and other high income countries. Together with partners, and using a Delphi exercise for consensus, we will identify potential EBP from recommendations from WHO and others and from regional expertise: for example kangaroo care for preterm newborns, antibiotics for women with preterm premature membrane rupture, first trimester ultrasound scanning to accurately determine gestation, and (where gestation is known) steroids for women likely to deliver preterm. Within three years, we will have: (i) Enhanced clinical care strategies for the prevention of stillbirth and preterm birth in Malawi and Zambia, reducing rates of preterm birth, stillbirth and under-5 deaths. (ii) Generated new knowledge on the effectiveness of interventions and on how best to implement them. (iii) Developed a clinical trials platform to test NOVEL INTERVENTIONS, initially for stillbirth and preterm birth, but longterm in an NIHR unit on maternal newborn global health (iv) Enhanced the collection of perinatal outcomes in vital statistics and hospital datasets. (v) Increased the accuracy of prematurity estimates by using first trimester ultrasound scaning to optimise assessment of gestational age. The multidisciplinary DIPLOMATIC collaboration (Using eviDence, Implementation science, and a clinical trial PLatform to Optimise MATernal and newborn health in LICs) of clinicians and researchers from Malawi, Zambia builds on a UK team (Norman, Stock, Norrie) with a strong track record in design and conduct of clinical trials in preterm birth and stillbirth (STOPPIT, OPPTIMUM, AFFIRM, QUIDs, STOPPIT 2), largely funded by NIHR.

Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH