PreOS (Preeclampsia Open Study), a Multicenter, Prospective, Non-Interventional Study Evaluating the Influence of the sFlt-1/PlGF Ratio on Physician Decision-Making in Pregnant Women with Suspicion of Preeclampsia

Problem statement:

Preeclampsia is a major cause of maternal, fetal and neonatal morbidity/mortality. Levels of serum sFlt-1 (soluble fms-like tyrosine kinase-1) are increased and levels of serum PlGF (placental growth factor) are decreased in pregnant women developing or having diagnosed preeclampsia/eclampsia/HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. Measurement of the sFlt-1/PlGF ratio is used as additional tool in preeclampsia diagnosis. However, the utility of the sFlt-1/PlGF ratio in guiding physicians' surveillance and treatment decisions for patients with suspicion of preeclampsia has not yet been evaluated in routine clinical practice. PreOS assessed the influence of the sFlt-1/PlGF test result on physicians' clinical decision-making regarding hospitalization, treatment and monitoring of patients who were considered likely to develop preeclampsia.

Methods:

PreOS is a multicenter, prospective, non-interventional study, including pregnant women (≥24+0 weeks) with suspicion of preeclampsia for whom the physician considered that the sFlt-1/PlGF ratio should be determined. The Elecsys® sFlt-1 and PlGF assays (Roche Professional Diagnostics) were used. Before the test result was known, physicians documented their intended clinical procedures using an iPad® application (questions included the need for: hospitalization; induction of delivery; induction of fetal lung maturation; additional laboratory measurements; cardiotocography; Doppler sonography; change of intensity of patient monitoring within one week; drug treatment). Decisions were data locked, time stamped and transferred to an online data center. After the sFlt-1/PlGF ratio results were available, decisions for further clinical procedures were confirmed/revised on the iPad®. Investigators were free to manage patients according to their own decisions. Maternal and neonatal outcomes were documented at delivery and postpartum. An independent adjudication committee evaluated the adequacy of the clinical decisions (based on outcome). The primary endpoint was the proportion of appropriate decisions to hospitalize/not to hospitalize patients with suspicion of preeclampsia before and after knowledge of the sFlt-1/PlGF result.

Results:

A total of 118 of 209 enrolled patients were included in the per-protocol population. For 11.0% of patients (per-protocol population), the sFlt-1/PlGF ratio influenced investigators to change their initial decision to hospitalize the patient into a decision not to hospitalize the patient. For 5.9% of patients (per-protocol population), the sFlt-1/PlGF result influenced investigators to hospitalize a patient after initially deciding not to hospitalize them. Changed hospitalization and other clinical decisions were in concurrence with important outcomes in mothers and neonates.

Conclusions:

PreOS is the first study to demonstrate the influence of sFlt-1/PlGF testing on physicians' clinical decision making for pregnant women with suspicion of preeclampsia in routine clinical practice. The test may be used to guide appropriate intensity of patient management with respect to hospitalization and diagnostic and therapeutic decisions in a clinically relevant proportion of pregnant women with signs and symptoms of preeclampsia/eclampsia/HELLP syndrome.