Understanding phenotype and mechanisms of spontaneous preterm birth in sub-Saharan Africa (PRECISE-SPTB)

Preterm birth, birth before 37 weeks of pregnancy, is a major cause of infant death and illness in sub-Saharan Africa. Over 80% of preterm births globally have been estimated to occur in sub-Saharan African (sSA) and Asian countries, the majority being due to women going into preterm labour spontaneously or their membranes (waters) rupture early (classified together as spontaneous preterm birth, SPTB).

Despite knowledge of the global impact of SPTB, most of the research into this often devastating pregnancy outcome has focussed on pregnant women in high income countries such as the UK and USA. Much less in known about SPTB in women from low income countries. However, the underlying biological causes of SPTB are complex and heavily influenced by environment, nutrition, infection and other risk factors that pregnant women are exposed to. Region specific research is essential if we are to improve maternal and newborn healthcare in countries where the burden of preterm birth is highest.

Addressing this need, we plan to study to clinical and social risk factors (from 5000 women recruited to the PRECISE Network pregnancy cohort, https://precisenetwork.org/) combined with biological markers of SPTB in the female reproductive tract, blood and placental tissue in women from Kenya, The Gambia and Mozambique. We will integrate these data to enhance our biological understanding of SPTB as well as identifying novel biomarkers relevant to sub-Saharan African populations to predict risk of SPTB.

We will also create sustainable teams of SPTB researchers by training five new African scientists and supporting their supervisor as research leaders. We will, with colleagues in The Gambia, establish a bioinformatics training programme and a laboratory science network for our researchers in Sub Saharan Africa and the UK.

We anticipate that this work will impact future strategies for clinical risk management, prevention and treatment that specifically addresses the needs of women in sub-Saharan Africa, as well as having potential relevance to SPTB globally.

Preterm birth is a major contributor to neonatal mortality and morbidity in sub-Saharan Africa. Recent estimates indicate births in Asian and sub-Saharan countries accounted for approximately 80% of preterm births globally, a significant proportion of which will be caused by spontaneous onset of labour and/or preterm premature rupture of membranes (classified together as spontaneous preterm birth, SPTB). Despite knowledge of the global impact of SPTB, a skewed emphasis of SPTB research in high income countries means less is known of SPTB amongst women from low income countries. The aetiology of SPTB is complex and heavily influenced by environment, infection nutrition and other co-exposures; it follows that region-specific research into epidemiology and other major contextual and biological drivers of SPTB is an essential pre-requisite to improved maternal and newborn healthcare where the burden is greatest.

This project will utilize the PRECISE Network bio-repository and database (a UKRI Global Challenges Research Funded project) which is storing well curated samples from approximately 10,000 pregnant women recruited in rural and urban sites in Kenya, The Gambia and Mozambique.

Using a combination of clinical phenotyping (n=5000 women) and a multi-omics approach (n=600 women), we will integrate clinical factors with cervicovaginal, plasma and placental biomarkers to characterise SPTB sub-groups. Mechanistic insights into the drivers for SPTB in sub Saharan populations has potential to identify novel biomarkers for predicting risk of SPTB as well as enabling enable comparisons with our understanding of preterm birth in other countries. This work will impact future strategies for clinical risk management, prevention and treatment that specifically addresses the needs of women in sub-Saharan Africa.

The ultimate aim of this project is, though robust science, to define the clinical, biological and contextual factors that influence risk of spontaneous preterm birth (SPTB) in women from sub-Saharan Africa. In addition to the immediate research and training beneficiaries, and the national and global academic sector (as detailed in the 'Pathways to Impact' statement), the most important and wider group of beneficiaries will be women and children living in sub Saharan Africa and other low-middle income countries. They, through improved antenatal care and management, will lead healthier and more fulfilling lives.

Impact is likely to come initially from the epidemiological identification of region-specific risk factors of SPTB that are modifiable through education and healthcare intervention. This impact will be mediated through local and national policy makers and multilaterals and NGOs, who will also be beneficiaries. The greater PRECISE Network, within which this project is linked, is already actively engaged with these beneficiaries in the three countries participating in the PRECISE NETWORK pregnancy cohort (The Gambia, Kenya and Mozambique). The work themes in the PRECISE NETWORK are already liaising with local health care providers, and through the 'Access and Maternity health system delivery' theme with the women themselves. This is informing our understanding of the many practical issues of health care delivery and how education and how new biomarker tests could interdigitate with existing pathways of care.

This impact will be increased as the scientific discoveries become apparent from our integrative multiomics approach. We anticipate identifying biomarkers that have potential for translation into point of care tests; this could have impact both on health and socioeconomic rewards for the Institutions and commercial sector involved in developing the technology. Investment in a spin-out company (or through partnership with known ethical commercial entities in the diagnostic industry) would open doors for expansion into markets in sub Saharan Africa and improve maternity healthcare for those who need it the most.

PRECISE-SPTB project is ODA compliant (see ODA statement for details).