The PAPAGAIO Project is a multi-country research initiative designed to evaluate innovative approaches for improving the diagnosis and management of pre-eclampsia in low- and middle-income countries (LMICs).

In many resource-limited settings, treatments for pre-eclampsia such as antihypertensives, anticonvulsants, and expedited delivery are available. However, delays in detecting women at high risk and initiating timely interventions remain major drivers of maternal and newborn deaths.

• We recognize that there is urgent need for robust studies to assess whether placental growth factor (PlGF) testing and other biomarkers can:
  Improve early detection of pre-eclampsia
• Enable timely referral and safe delivery
  Reduce maternal and perinatal deaths in settings where fetal ultrasound and monitoring are limited.

The objectives of PAPAGAIO are to :

• Determine whether PlGF testing reduces adverse maternal and newborn outcomes in women with suspected preterm pre-eclampsia in LMICs.
• Assess health resource use and cost-effectiveness of PlGF testing versus usual care.
• Evaluate how accurately PlGF-based tests predict adverse maternal and newborn outcomes.

The challenge of balancing maternal survival with newborn health is especially acute in low-resource settings. By tailoring solutions to local contexts in Sierra Leone, Zambia, India, and Brazil, the PAPAGAIO Project aims to generate the evidence needed to bring life-saving innovation to where it is needed most.

PAPAGAIO Workstreams

The PAPAGAIO Project is structured around five core interlinked workstreams, each addressing a critical piece of the puzzle:

1. Prepare for PAPAGAIO: An observational study of existing care pathways and management strategies for pre-eclampsia, including cost implications.
2. PAPAGAIO-Diagnosis: A randomized controlled trial investigating the impact of PlGF testing on clinical outcomes, including diagnosis, timing of birth, and complications.
3. PAPAGAIO-Delivery: A randomized controlled trial comparing planned early birth to watchful waiting in women with pre-eclampsia between 34 and 37 weeks of pregnancy, with diagnosis informed by PlGF. The primary outcome: stillbirth or early neonatal death.
4. PAPAGAIO-Biobank: An international, multi-centre biobank of samples from women with suspected or confirmed pre-eclampsia.
5. PAPAGAIO-Validation Study: A prospective study evaluating novel point-of-care biomarkers for pre-eclampsia, compared to gold-standard validated biomarker tests.

Complementary Workstream: Pregnancy Hypertension Priority Setting Partnership
Alongside the five core PAPAGAIO workstreams, we are undertaking a James Lind Alliance (JLA) Priority Setting Partnership (PSP) focused on pregnancy hypertension in low- and lower-middle-income countries (LMICs).

This partnership brings together women, families, clinicians, academics, and government stakeholders in Sierra Leone and Zambia to identify and prioritize the most pressing unanswered questions about hypertensive disorders in pregnancy including pre-eclampsia, gestational hypertension, and chronic hypertension.

By amplifying the voices of communities and frontline health workers, the PSP ensures that future research reflects the real-world needs and lived experiences of those most affected.

The PSP aims to:

• Identify uncertainties about pregnancy hypertension in LMICs.
• Prioritize research questions that matter most to women, families, and clinicians.
• Inform global funders and research commissioning bodies to direct funding towards locally relevant solutions.

This work complements the PAPAGAIO trials by ensuring future interventions and policies are shaped by the communities they aim to serve.

Further information about the Pregnancy Hypertension Priority Setting Partnership, including the survey and details of the James Lind Alliance process, is available on the official James Lind Alliance PSP webpage here.