title: Multicenter prospective clinical study to evaluate the prediction of short-term outcome in pregnant women with suspected preeclampsia (PROGNOSIS): study protocol.
abstract: BACKGROUND
  Preeclampsia is defined as new onset of hypertension and proteinuria at gestational week 20 or after. However, use of these measures to predict preeclampsia before its clinical onset is unreliable, and evidence suggests that preeclampsia, eclampsia, or hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome may develop without hypertension or proteinuria being evident. Because of its unpredictability, varying clinical presentation and potential adverse outcomes, pregnant women with suspected preeclampsia require intensive monitoring or hospitalization. Beyond preeclampsia diagnosis, there is a high unmet medical need for more reliable predictive markers for preeclampsia to improve maternal and fetal outcomes and reduce unnecessary hospital admissions. An imbalance of circulating angiogenic and antiangiogenic factors, including raised soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased placental growth factor (PlGF), has been found in women diagnosed with preeclampsia and before clinical onset of the disease. The PRediction of short-term Outcome in preGNant wOmen with Suspected preeclampsIa Study (PROGNOSIS) was designed to investigate the use of the sFlt-1/PlGF ratio in the short-term prediction of preeclampsia.
  
  
  METHODS
  This global, multicenter, prospective, double-blind, non-interventional study aims to derive and validate cutoffs for the sFlt-1/PlGF ratio, to rule out (for 1 week) or rule in (within 4 weeks) the occurrence of preeclampsia/eclampsia/HELLP syndrome. Eligible participants are women presenting at 24 to <37 weeks' gestation with clinical suspicion of, but not manifest preeclampsia/eclampsia/HELLP syndrome. Clinical assessments, maternal serum sFlt-1/PlGF sampling and documentation of maternal/neonatal outcomes are performed at regular intervals, using strict diagnostic criteria for preeclampsia-related conditions and outcomes. Serum sFlt-1 and PlGF analysis will be performed using fully automated Elecsys® immunoassays. Investigators and participants will remain blinded to the results. Target recruitment is 1000 participants. Health economic analysis is also planned.
  
  
  CONCLUSIONS
  The results of PROGNOSIS will provide the most comprehensive evidence to date on the accuracy of the sFlt-1/PlGF ratio for short-term prediction of preeclampsia/eclampsia/HELLP syndrome. Adoption of the sFlt-1/PlGF test in clinical practice has the potential to reduce the frequency of adverse pregnancy outcomes for both mother and fetus, and decrease healthcare costs associated with unnecessary hospitalization of women with suspected preeclampsia.
authors.affiliation: Roche Diagnostics International Ltd, Forrenstrasse 2, CH-6343 Rotkreuz, Switzerland. martin.hund@roche.com.
authors.forename: Martin
authors.initials: M
authors.lastname: Hund
authors.forename: Deirdre
authors.initials: D
authors.lastname: Allegranza
authors.forename: Maria
authors.initials: M
authors.lastname: Schoedl
authors.forename: Peter
authors.initials: P
authors.lastname: Dilba
authors.forename: Wilma
authors.initials: W
authors.lastname: Verhagen-Kamerbeek
authors.forename: Holger
authors.initials: H
authors.lastname: Stepan
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D004461:Eclampsia / Q000097:blood / Q000175:diagnosis*; D005260:Female; D005865:Gestational Age; D017359:HELLP Syndrome / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D008565:Membrane Proteins / Q000097:blood*; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011446:Prospective Studies; D012107:Research Design; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; C098069:PIGF protein, human; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1