Preterm pre-eclampsiA: PlAcental Growth factor testing for reduction of Adverse Outcomes

The PAPAGAIO Global Health Research Group is focused on reducing maternal and perinatal mortality and morbidity from pre-eclampsia, across low- and middle-income countries (LMICs) through the use of placental growth factor testing.

Globally, pre-eclampsia causes 30,000 maternal and 500,000 perinatal deaths annually, with the majority in LMICs. Many of these are preventable, with early diagnosis and appropriately timed delivery; however, pre-eclampsia diagnosis can be challenging in high-burden, low-resource settings. Placental growth factor (PlGF), an angiogenic biomarker, is abnormally low in pre-eclampsia.

In high income settings, PlGF outperforms all other pre-eclampsia diagnostics, reducing adverse maternal outcomes and time to diagnosis. It is recommended in the UK but has not been evaluated in low resource settings, where the greatest health burden lies.

The only definitive treatment for pre-eclampsia is delivery. Recent evidence has demonstrated planned early delivery is safe in late preterm pre-eclampsia (34-37 weeks’ gestation). Early delivery in LMICs in the absence of pre-eclampsia, would increase neonatal morbidity. Angiogenic markers, such as PlGF, should enhance diagnostic precision and enable rule-in and rule-out of women for whom early delivery is beneficial.

Objectives: • Describe care pathways for preterm pre-eclampsia, identify barriers to, and facilitators of PlGF testing in LMICs • Assess clinical and cost effectiveness of PlGF testing in suspected preterm pre-eclampsia

• Evaluate clinical and cost effectiveness of planned early delivery in late preterm pre-eclampsia with diagnosis incorporating PlGF testing • Sustainably build local research capacity at individual and institutional levels Methods:

Workstream 1 (Prepare for PAPAGAIO): a six-month mixed-methods observational feasibility study to describe current pre-eclampsia care, optimise PlGF testing and conduct community engagement

Workstream 2 (PAPAGAIO-Diagnosis): a randomised controlled trial comparing revealed PlGF to usual care, in women with suspected pre-eclampsia from 20 – 36+6 weeks gestation.

Workstream 3 (PAPAGAIO-Delivery): a randomised controlled trial comparing planned early delivery with usual care of expectant management, in women with late preterm pre-eclampsia (diagnosis confirmed by PlGF testing) at 34-36+6 weeks gestation.

A strong element of this programme is our community engagement and involvement strategy. Building on our existing partnerships with communities and stakeholders, we will reach the most vulnerable women by embedding research in rural communities with limited access to healthcare. The project will be planned, designed, and implemented by the people who will benefit from it and decisions will align with local priorities that are relevant beyond the timeline of the research group.

Anticipated impact and dissemination:

We anticipate improved maternal and neonatal outcomes through demonstrating the clinical and economic benefit of PlGF testing in low-income settings and establishing how it can be used to optimally time delivery. Our partnerships will enable rapid translation into policy and nationwide scaleup. The evidence accrued will offer generalisability and we will share our findings to encourage widespread adoption and achieve large-scale impact.

We envision increased community awareness of preeclampsia, long-term improvements in management, sustainable strengthening of the LMIC research capacity and, ultimately, safer pregnancies for women and their babies.