DISCUSSION
prematurity, eclampsia, preeclampsia
PRETERM BIRTH, ECLAMPSIA, HYPERTENSIVE DISORDER, ELEVATED BLOOD PRESSURE, PREECLAMPSIA
The trial aimed to evaluate whether a combination of the sFlt-1/PlGF ratio and the fullPIERS algorithm, by classifying patients with suspected or diagnosed preeclampsia as low risk for adverse outcomes and therefore suitable for expectant management, would safely lead to a reduction in preterm deliveries.The main findings showed that the introduction of a new methodology for evaluating patients with elevated blood pressure, characterized by a biomarker test incorporating angiogenic and antiangiogenic factors, did not lead to a reduction in preterm birth. Regarding risk assessment, there was a large discrepancy between the 2 models combined (fullPIERS and sFlt-1/PlGF). The vast majority of patients admitted to the proposed intervention were classified as low risk for adverse maternal outcomes according to the fullPIERS criterion alone. However, 59.6% of these patients had sFlt-1/PlGF ratio >38, indicating a nonreassuring situation in the initial risk assessment. The implementation of the new management protocol, by increasing diagnosis and general awareness of preeclampsia among participating clinicians, may have led to earlier consideration of delivery. Regarding the safety, sensitivity analyses showed that this treatment protocol was able to identify patients at risk for preterm birth and maternal mortality or severe morbidity and, therefore, it did not put patients at risk of adverse outcomes. Overall, no differences were observed about the additional maternal and perinatal outcomes evaluated, except for a reduction in cases of eclampsia in the intervention group.To our knowledge, this is the first study to combine clinical and laboratory information from the fullPIERS algorithm in the care of patients with suspected or confirmed preeclampsia with the sFlt-1/PlGF ratio. The study evaluated management based on biomarkers in public hospitals that serve a low-income population in Brazil. It was a multicenter study that allowed the inclusion of a large number of patients.The study evaluated an important perinatal outcome, preterm birth, based on the use of biomarkers that were not in regular use by participating clinicians. We determined that management was different among the participating centers, especially in one of the centers (Finding a balance between reducing maternal adverse outcomes and the impact of prematurity is a difficult task and there is minimal evidence available to adequately guide this practice. The HYPTAT-II study (2016) compared delivery within 24 hours versus expectant management in patients with hypertensive disorders diagnosed between 34 and 37 weeks.Although the absolute occurrence of the primary outcome decreased after intervention, statistical analysis with appropriate adjustment demonstrated that the adjusted risk ratio was higher in the intervention group. There are several possible explanations for this finding: (1) the risk stratification tests are not adequate to determine timing of delivery in patients with suspected or diagnosed preeclampsia (as suggested by other authors)In conclusion, this trial demonstrate that implementation of the intervention did not decrease preterm birth for preeclampsia in this setting. The majority of patients enrolled in the trial did not meet the criteria for expectant management due to nonreassuring risk stratification. The threshold used (sFlt-1/PlGF <38) may be too low to lead to an impact in prematurity reduction as most patients entered the trial with higher sFlt-1/PlGF ratios. Future research may need to evaluate the impact of using different test thresholds for maternal and perinatal outcomes, mainly preterm deliveries. We encourage development of new trials in low- and middle-income settings, as these areas have the poorest outcomes for patients with preeclampsia and even small improvements in management may lead to great impact. Additionally, we emphasize the necessity of developing a continuous knowledge transfer program to help care providers to gain confidence and trust in reassuring results.