GCRF: The PRECISE (PREgnancy Care Integrating translational Science, Everywhere) Network: a sub-Saharan network for placental disorders

The PRECISE Network is a new and broadly-based group of research scientists and health advocates mainly based in the UK and Africa, but also including the World Health Organization. We will establish this network through a shared project that will investigate three important complications of pregnancy, namely high blood pressure (hypertension), babies who are smaller than they should be before birth (fetal growth restriction) and babies who die before birth (stillbirth). We think that about 46,000 women and two-and-a-half million babies (both before and after birth) die due to these problems every year, and half of them die in Africa. In addition, about 50 million women and babies will have their short and long term health altered because of these complications. These numbers represent one of the great global inequalities of our time.
In developed countries like the UK, we know that these three pregnancy complications are caused by problems with the afterbirth (placenta), and we know quite a lot about how they develop and complicate pregnancies.
In contrast, in sub-Saharan Africa, we know very little about how and why these placental conditions occur. This is especially complex as women in Africa often have many other challenges: limited diets that change with the seasons, chronic infections such as HIV or malaria, acute infections like Ebola, limited power to make decisions for themselves, life in communities that are prone to either flooding or drought and are remote from health facilities. Therefore, the way that pregnancy complications arise are probably very different for these women in sub-Saharan Africa, compared with women living in the UK. Yet, these women and their babies bear most of the burden of death and illness related to pregnancy complications. We need to address this area of neglected global health research.
In PRECISE, we will train and mentor junior investigators in how to do pregnancy research, and we will establish new databases related to pregnant and some non-pregnant women, the context of their lives, their pregnancy complications and what happens at the end of their pregnancies. We will save samples of blood, urine and placental tissue, and test them to increase our knowledge about how women's bodies cope with both normal and complicated pregnancies. All the samples and the data will remain in Africa for use primarily by Africans in collaboration with UK-based and other scientists.
To have a sample of pregnancies that are typical of women in sub-Saharan Africa, we will invite about 12,000 women in The Gambia and Senegal (West Africa), Kenya (East Africa) and Mozambique (Southern Africa) to share their stories, the data related to their pregnancy and babies, and their blood, urine and placental samples with their regional team and the wider global research community, especially the PRECISE scientists. This large number of women will allow us to gain new and important insights into how and why women in sub-Saharan Africa develop these pregnancy complications, and how and why may of them and their babies die from these complications.
Through these activities, we hope to improve the health and well-being of women and their families in Africa, to build resilience to environmental events such as flooding or infectious disease outbreaks, to advise about where infrastructure such as roads will improve pregnancy outcomes, and to reduce the inequality of maternal and child deaths that is visited on families in sub-Saharan Africa.

Through our work in West Africa (the Gambia & Senegal; both ODA 'least-developed' countries), East Africa (Kenya; ODA 'Other' low income country) and Southern Africa (Mozambique; ODA 'least developed' country), we have set ourselves the task of fulfilling the following objectives, each of which relates to at least one GCRF thematic area:
Objective 1: To increase and disseminate knowledge related to the origins and consequences of the placental disorders of pregnancy in sub-Saharan Africa.
This addresses the thematic areas: (i) sustainable health and well-being; (ii) reducing gender and childhood inequalities, as the placental disorders are leading causes of maternal, fetal and infant death and disability; (iii) resilience to short-term environmental shocks (which will advise creating strong infrastructure for sustainable and inclusive development).
This requires an understanding of the complex interplay between an individual woman's biology, her burden of acute and chronic infectious disease, her nutritional and societal status, and her existence in place and time throughout a 2-year period. In addition, it requires an understanding of the biology of non-pregnant and physiologically-pregnant reproductive age women in these settings as these foundational data do not exist. Our targets for knowledge dissemination will be women, their communities, local and national decision makers, NGOs and multilaterals. Many of the key relationships already exist and will be strengthened through this shared set of activities.

Objective 2: To develop a collaborative team focussed on women's and reproductive health
This addresses the thematic areas of: (i) sustainable health and well-being; (ii) strengthening foundations and research infrastructure for inclusive innovation; (iii) reducing inequality within science; and (iv) creating inclusive and equitable education and training for all team members and their trainees.
While some members of the proposed PRECISE team have worked together previously, this initiative will create a team through activity in LMICs. We will grow capacity in both LMICs and the UK by developing and strengthening skills around pregnancy research, especially, but not exclusively, focussed on placental disorders. This is especially pertinent for the MRC Gambia unit, which does have a track record of research around the prevention of mother-to-child transmission of HIV, but is otherwise limited in its pregnancy research portfolio. Through the Gates Foundation-funded PRE-EMPT (PRE-eclampsia - Eclampsia Monitoring, Prevention & Treatment) initiative lead by the PRECISE CI, Peter von Dadelszen, the Mozambique team has recently become engaged in pregnancy research related to pregnancy hypertension.
Twenty-two (55%) of the 40 named investigators and staff scientists are women, and some are gay.

Objective 3: To create an African-controlled resource of a regional biobank that is linked to replete clinical, epidemiological, nutritional, social context, and geographical data.
This will address the thematic areas of: (i) reducing inequality through ownership of research resources in Africa by Africans; (ii) inclusive and equitable quality research education and training; and (iii) sustainable health and well-being.
This model of local control of data and biological samples in central to our model of global health research and is essential for the development of research strength in Africa. These resources would underpin future hypothesis-driven and -generating projects in these areas and would contribute to the Global Pregnancy Collaboration established by PRE-EMPT. In addition, we believe that the PRECISE project will create a pregnancy cohort that could be followed-up in terms of both maternal and child outcomes related to the origins and consequences of non-communicable diseases

The key groups with which we shall engage to ensure maximal impact include:
Pregnant women, non-pregnant women of reproductive age (WRA), and their communities in Sub-Saharan Africa (sSA). We have developed a highly interactive programme of formative qualitative research and community engagement with pregnant women, non-pregnant WRA, adolescent girls and boys, mothers-in-law, matrons, husbands, men's groups, faith leaders, and local chiefs and kings to advise what they perceive to be the status of women in their communities and the facilitators and barriers to healthy pregnancy. This will complement existing research activity that has been largely infectious disease-oriented. Also, we will learn about the burden of morbidity borne by women during and following pregnancy. The stories that women tell will inform the design of follow-on activities (e.g., clinical trials). With the increasing impact of urban drift across sSA, comparing and contrasting these stories between rural and urban poor will be important as we design precision medicine for all women, everywhere.
Health care providers including midwives, nurses, medical officers, and obstetricians in sSA. We are already engaged with local providers in many of these communities. Health care providers request accurate pregnancy dating and risk stratification tools to identify and manage those at greatest risk of, and at time-of-disease with, placental complications. We will invite these and other key health care providers to national launches of the network and engage with facility staff throughout. We have strong links with national societies of obstetrics and gynaecology and the relevant nursing and midwifery councils.
Heath Care Policy Makers. Early engagement with health care funders and policy makers is essential. During the course of this project, UK-based and local leads will continue to meet with staff of the district, provincial and national Departments and Ministries of Health. We will host an all-country roundtable where regional implications will be discussed.
Existing research, knowledge translation and advocacy networks. PRECISE will strengthen the PRE-EMPT-initiated Global Pregnancy Collaboration. The WHO Department of Reproductive Research has strong and effective links with WHO Maternal, Child and Adolescent Health, UNFPA, and UNICEF, their implementing partners. The AKU Nairbobi is linked with the Aga Khan Development Network of health facilites through South and Central Asia and East Africa.
National mapping agencies and ministries of public works. We will expand our existing relationships with the Mozambique and Zimbabwe mapping agencies to include the relevant agencies in the Gambia, Senegal, and Kenya. These maps and related app will enable ministries of public works to model the impact of proposed infrastructure spending (e.g., roads, bridges) on health-related outcomes.
UK and Africa clinicians and scientists in training. We will create opportunities for bi-directional knowledge transfer between UK and African researchers and students involved in the study to build capacity and research experience.
The commercial sector The St George's Joint Research and Enterprise Office, and equivalent offices at KCL, LSHTM and Oxford, will be engaged from the outset to strengthen exsting relationships with industry. Such relationships include those around devices (oximetry, BP), mobile health (ultrasound, clinical and demographic data collection), and point-of-care devices.
Researchers in the fields of pregnancy hypertension, fetal growth restriction, stillbirth, adolescent and pregnancy nutrition, and infectious diseases. Pathways to impact are well-established in the clinical and scientific community, but dissemination amongst sSA scientists and clinicians requires overcoming some, barriers including their inability to attend conferences due to financial constraints. We will disseminate our research outputs at local and regional meetings in Africa.