PREPARE: protocol for a stepped wedge trial to evaluate whether a risk stratification model can reduce preterm deliveries among women with suspected or confirmed preterm pre-eclampsia.

BACKGROUND: Preeclampsia (PE) is a major cause of short and long-term morbidity for affected infants, including consequences of fetal growth restriction and iatrogenic prematurity. In Brazil, this is a special problem as PE accounts for 18% of preterm births (PTB). In the PREPARE (Prematurity REduction by Pre-eclampsia cARE) study, we will test a novel system of integrated care based on risk stratification and knowledge transfer, to safely reduce PTB. METHODS: This is a stepped wedge cluster randomised trial that will include women with suspected or confirmed PE between 20 + 0 and 36 + 6 gestational weeks. All pregnant women presenting with these findings at seven tertiary centres in geographically dispersed sites, throughout Brazil, will be considered eligible and evaluated in terms of risk stratification at admission. At randomly allocated time points, sites will transition to risk stratification performed according to sFlt-1/PlGF (Roche Diagnostics) measurement and fullPIERS score with both results will be revealed to care providers. The healthcare providers of women stratified as low risk for adverse outcomes (sFlt-1/PlGF ≤38 AND fullPIERS< 10% risk) will receive the recommendation to defer delivery. sFlt-1/PlGF will be repeated once and fullPIERS score twice a week. Rates of prematurity due to preeclampsia before and after the intervention will be compared. Additionally, providers will receive an active program of knowledge transfer about WHO recommendations for preeclampsia, including recommendations regarding antenatal corticosteroids for foetal benefits, antihypertensive therapy and magnesium sulphate for seizure prophylaxis. This study will have 90% power to detect a reduction in PTB associated with PE from a population estimate of 1.5 to 1.0%, representing a 33% risk reduction, and 80% power to detect a reduction from 2.0 to 1.5% (25% risk reduction). The necessary number of patients recruited to achieve these results is 750. Adverse events, serious adverse events, both anticipated and unanticipated will be recorded. DISCUSSION: The PREPARE intervention expects to reduce PTB and improve care of women with PE without significant adverse side effects. If successful, this novel pathway of care is designed for rapid translation to healthcare throughout Brazil and may be transferrable to other low and middle income countries. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03073317.

Creating biobanks in low and middle-income countries to improve knowledge - The PREPARE initiative.

The Millennium Development Goal 5, a project signed in 2000, intended to improve maternal health and reduce maternal mortality by 75% by 2015. Despite all efforts, little progress has been achieved in low and middle-income countries (LMIC) and 99% of all maternal deaths related to pre-eclampsia (PE) still occur in these settings. It is important to determine whether women in LMIC, where PE carries a greater risk than in high-income countries (HIC), have unique risk factors. Some variances may alter the risk, severity and pertinent pathophysiology of PE. We posit based upon this, that women from LMIC may have biomarkers specific to this population. Discovering such specific biomarkers and testing the relevance of biomarkers developed in high-income populations could increase the clinical usefulness of these analyses without increasing cost-effective approaches for prediction of PE. Here we briefly describe our platform to develop the PREPARE - Biobank in tertiary hospitals or basic units for antenatal care from 6 different cities in Brazil. The PREPARE - Biobank has been developed with two arms. The first arm is a cross-sectional study that will collect clinical information and biosamples from more than 1000 women who developed preterm PE. The second arm is a cohort study of 7000 women. It will collect clinical information and longitudinal biosamples from women at three times during pregnancy, <16 weeks, between 28 and 32 weeks and at delivery or diagnosis of adverse outcomes. The biobank will be supported and complemented by a Brazilian database using the CoLab COLLECT Database.