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

Abstract: Our VISION is to reduce mortality of children under 5 years (one of the targets of sustainable_x000D_ development goal [SDG] 3), by reducing preterm birth and stillbirth and to optimise outcomes for_x000D_ babies born preterm. Globally 15 million babies are born preterm each year and over 2.5 million are_x000D_ stillborn. Deaths from preterm birth complications are the main global cause of under-5 mortality,_x000D_ accounting for an estimated 1·055 million [95% uncertainty range (UR) 0·935–1·179] child deaths in_x000D_ 2015 [1]. Low and middle income countries (LMIC) bear the brunt of this burden. Malawi and Zambia_x000D_ are ranked respectively 147 and 185 (out of 197 countries) for rates of preterm birth, and 129 and 124_x000D_ for rates of stillbirth (high ranks equivalent to worse outcomes) . Annual deaths from stillbirth and_x000D_ preterm birth in Malawi and Zambia are over 36,500. Despite this heavy burden, known effective_x000D_ interventions for reducing preterm birth/stillbirth and their consequences are poorly implemented in_x000D_ LMICs leading to unnecessary deaths. Indeed, WHO estimates that the majority of stillbirths and_x000D_ deaths from prematurity are preventable._x000D_ Alongside colleagues in Malawi and Zambia we will establish an NIHR GLOBAL HEALTH GROUP_x000D_ ON PRETERM BIRTH AND STILLBIRTH in LMIC._x000D_ We will share existing knowledge on evidence based practices (EBP) used in high income countries_x000D_ (HIC). We will use new trial designs to test in LIC the EFFECTIVENESS of a collection of the best_x000D_ practices, and to evaluate how they are best IMPLEMENTED. We recognise the differences that_x000D_ cultures, traditions, gender roles, resources, workforce constraints, disease burdens and community_x000D_ understandings of pregnancy and birth bring, and have therefore designed this group to examine_x000D_ strategies to develop and to implement contextualized evidenced based local practices building on_x000D_ successes and challenges of current best practice in the UK and other high income countries._x000D_ Together with partners, and using a Delphi exercise for consensus, we will identify potential EBP from_x000D_ recommendations from WHO and others and from regional expertise: for example kangaroo care for_x000D_ preterm newborns, antibiotics for women with preterm premature membrane rupture, first trimester_x000D_ ultrasound scanning to accurately determine gestation, and (where gestation is known) steroids for_x000D_ women likely to deliver preterm._x000D_ Within three years, we will have:_x000D_ (i) Enhanced clinical care strategies for the prevention of stillbirth and preterm birth in Malawi_x000D_ and Zambia, reducing rates of preterm birth, stillbirth and under-5 deaths._x000D_ (ii) Generated new knowledge on the effectiveness of interventions and on how best to_x000D_ implement them._x000D_ (iii) Developed a clinical trials platform to test NOVEL INTERVENTIONS, initially for stillbirth and_x000D_ preterm birth, but longterm in an NIHR unit on maternal newborn global health_x000D_ (iv) Enhanced the collection of perinatal outcomes in vital statistics and hospital datasets._x000D_ (v) Increased the accuracy of prematurity estimates by using first trimester ultrasound scaning to_x000D_ optimise assessment of gestational age._x000D_ The multidisciplinary DIPLOMATIC collaboration (Using eviDence, Implementation science, and a_x000D_ clinical trial PLatform to Optimise MATernal and newborn health in LICs) of clinicians and researchers_x000D_ from Malawi, Zambia builds on a UK team (Norman, Stock, Norrie) with a strong track record in_x000D_ design and conduct of clinical trials in preterm birth and stillbirth (STOPPIT, OPPTIMUM, AFFIRM,_x000D_ QUIDs, STOPPIT 2), largely funded by NIHR.

Lay abstract: a. Strategic objectives of the host university._x000D_ This NIHR global health group is closely aligned with the strategic objectives of the host university,_x000D_ the University of Edinburgh (UoE), to benefit society as a whole, and to make a significant,_x000D_ sustainable and socially responsible contribution to the world, through partnerships, exchange and_x000D_ engagement [2]. The group will benefit from the Global Health Academy (GHA, Director Grant, coapplicant),_x000D_ the Centre for Global Health Research (CGHR, Director Campbell, co-applicant who has_x000D_ professional focus on child health in LMIC), and a community of staff, students, alumni and global_x000D_ partners who integrate global education, interdisciplinary research and health service development_x000D_ and delivery._x000D_ UoE’s translational global health research is world class. For example, UoE-led research pioneered_x000D_ the use of a novel genetic test to identify and treat livestock infected with the parasite that causes_x000D_ sleeping sickness, resulting in a 90% fall in transmission to humans, and the prevention of many_x000D_ human deaths in subSaharan Africa. The quality of current translational global health research at UoE_x000D_ has led to the recent award of two NIHR Global Health Units: one in respiratory health (RESPIRE)_x000D_ and another in infectious disease (TIBA)._x000D_ Hence our preterm birth and stillbirth global health group will benefit from expertise and connections_x000D_ in RESPIRE, TIBA, GHA and CGHR and by building on their links with international agencies on_x000D_ guidelines, policy makers and public engagement we will accelerate the translation of research into_x000D_ clinical practice and education. We will make use of existing UoE global health experience to focus on_x000D_ the needs of DAC countries (specifically Malawi and Zambia) and build respectful reciprocal_x000D_ partnerships in a manner that protects and promotes human rights, in line with the recommendations_x000D_ of the Research Fairness Initiative[3] and others [4]. DIPLOMATIC will provide evidence on how to_x000D_ strengthen maternal health programmes for women– objectives identified as key in the 2016 DFID_x000D_ research review. We will identify trial interventions based on evidence in other countries, evaluate_x000D_ effectiveness (and implementation strategies) in Malawi and Zambia, address the shortage of skills in_x000D_ ultrasound scanning and build capacity and sustainability, according to good practice_x000D_ recommendations[5]. We believe the work from DIPLOMATIC will provide a measurable benefit to_x000D_ patients and the public, in currently underfunded and under researched areas._x000D_ b. Underpinning facilities from host University._x000D_ UoE conducts world class health research. In the 2014 Research Excellence Framework, our medical_x000D_ research was ranked 5th in the UK. Edinburgh has the only MRC Centre for Reproductive Health_x000D_ (MRC-CRH) in the UK. Two research groups within the MRC-CRH, The Edinburgh Tommy’s Centre_x000D_ for Maternal and Fetal Health research[6] (funding of £4 million since 2008, 23 current members of_x000D_ staff, directed by principal applicant Norman) and the Jennifer Brown Research Laboratory[7] (funding_x000D_ of £3.4 million since 2003, 8 current members of staff, directed by co-applicant Boardman) focus on_x000D_ issues key to this application, namely improving the health of pregnant women and newborn babies,_x000D_ respectively. UoE has an excellent track record in conducting large intervention trials in pregnancy,_x000D_ including preterm birth diagnosis and prevention trials STOPPIT[8] OPPTIMUM[9] and STOPPIT 2 (in_x000D_ progress NCT02235181) QUIDS (in progress ISRCTN41598423); stillbirth prevention trials AFFIRM_x000D_ (in progress NCTT01777022) and others EMPOWaR[10] GRACES[11] all led by applicants Norman_x000D_ or Stock and supported by a world class clinical trial unit, whose Director (Norrie) is co-applicant._x000D_ Underpinning facitilities in learning and teaching in global health are provided by the GHA which has_x000D_ 16 global online MSc programmes tailored for low and middle income country contexts and learning_x000D_ requirements, and a vibrant Global PhD network: access will be facilitated for those from LIC working_x000D_ in our NIHR global health group. The GHA currently undertakes implementation research_x000D_ programmes through partnerships with Ministries of Health in Malawi (eg on cervical cancer_x000D_ screening), and national and international NGOs in Zambia and Malawi. GHA is also host to Global_x000D_ Alliances such as the Zambia UK Health Workforce Alliance and the World Federation of Academic_x000D_ Institutes in Global Health. DIPLOMATIC will benefit from a wide variety of other programmes which_x000D_ the GHA supports including EU funded projects Advocacy for Neglected Zoonoses (ADVANZ) (FP7,_x000D_ £500,000) Investigating Networks of Zoonosis Innovation (INZI) (FP7 3M) and Africa UK Partnerships_x000D_ for Technology Enhanced and Blended Learning, Strategic Partnerships for Higher Education_x000D_ Innovation and Reform (£2 million)._x000D_ c. This application builds on existing institutional partnerships between UoE and each of the Malawi_x000D_ Liverpool Wellcome Trust (MLW), (for example, Dean Everett, Group Head at MLW has a_x000D_ Professorial appointment at UoE); Apex Medical University (through ZUKWA); and the College of_x000D_ Medicine Malawi on undergraduate teaching._x000D_ We note that of the 33 NIHR units and groups so far funded two units are currently working in Malawi,_x000D_ and one group is working in Malawi and Zambia. We have identified only one other project on_x000D_ maternal / newborn health: 16/137/53, PI Lavender, focussed on low-tech midwifery interventions to_x000D_ prevent and optimally manage stillbirth. The interventions we plan in our NIHR global group are_x000D_ different but complementary. We will connect and share expertise where relevant._x000D_ DIPLOMATIC will complement existing investments in research capacity from the UoE (described in_x000D_ a) and from the College of Medicine Malawi, the Malawi Epidemiology and Intervention Research Unit_x000D_ (MEIRU), and Lusaka Apex Medical University, Zambia, in enhancing health research systems for the_x000D_ conduct of basic, operational and clinical research. Capacity and capability in LIC will be strengthened_x000D_ by (i) joint supervision of students (ii) sharing of guideline, clinical trial and implementation science_x000D_ methodology from Scotland)[12] and (iii) access to online CPD programmes through GHA at UoE,_x000D_ and in the UK will be strengthened by (iv) translating expertise in preterm birth and stillbirth into global_x000D_ health._x000D_ d. Local priorities in maternal and newborn health were discussed at a meeting between the_x000D_ collaborators in Malawi in January 2017, and in Zambia in July 2017: preterm birth and stillbirth_x000D_ emerged as priorities in both countries given persistently high neonatal mortality rate despite_x000D_ consistent declines in other child mortality indices. The specific research themes (the need for better_x000D_ data collection, and the need to agree and to implement known effective evidence based interventions_x000D_ including optimising gestational age assessment) have been widely identified in the literature_x000D_ emerging from researchers and policy makers within LMIC and these were validated during the_x000D_ partners meetings earlier this year. The specific interventions to be tested by this group will be_x000D_ discussed and agreed by clinicians from Malawi and Zambia within the first 6 months of funding using_x000D_ an adapted Delphi methodology. We will use the INVOLVE principles to engage users of the research_x000D_ (patients, practitioners and policy makers), with culturally appropriate adaption as necessary. We_x000D_ anticipate that brokers may also be helpful for this and we will formulate a public engagement strategy_x000D_ within the first six months of this project. Local policy makers will be engaged through our existing_x000D_ links in Malawi and Zambia. Dissemination to clinicians, policy makers, and other users in other LMIC_x000D_ will be facilitated by links initiated by the NIHR TIBA and RESPIRE Units based at UoE and and_x000D_ inclusion of appropriate public and patient involvement (PPI) strategies will benefit from TIBA and_x000D_ RESPIRE experience in setting these up in LMIC.

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