title: New gestational phase-specific cutoff values for the use of the soluble fms-like tyrosine kinase-1/placental growth factor ratio as a diagnostic test for preeclampsia.
abstract: To establish gestational phase adapted cutoffs for the use of the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio as a diagnostic tool for preeclampsia in the clinical setting, a multicenter case-control study including a total of 1149 patients was performed. We report normal values of sFlt-1, PlGF, and the sFlt-1/PlGF ratio based on the analysis of a total of 877 patients with uneventful pregnancy outcome. A total of 234 patients with preeclampsia and a matched cohort consisting of 468 patients with normal pregnancy outcome were compared, and sFlt-1 and PlGF were measured on an automated platform. Separate cutoffs for the sFlt-1/PlGF ratio were determined for the early (20+0-33+6 weeks) and the late gestational phase (34+0 weeks-delivery). For each of the 2 gestational phases, 2 independent cutoffs framing an equivocal zone were determined: the first cutoff with focus on high sensitivity, and the second focusing on high specificity. Between 20+0 and 33+6 weeks, the cutoffs at ≤33 and ≥85 resulted in a sensitivity/specificity of 95%/94% and 88%/99.5%, respectively. An sFlt-1/PlGF ratio of ≤33 had the lowest likelihood of a negative test (0.05; 95% confidence interval, 0.02-0.13), whereas values ≥85 had the highest likelihood of a positive test (176; 95% confidence interval, 24.88-1245). After 34+0 weeks, the cutoffs at ≤33 and ≥110 yielded a sensitivity/specificity of 89.6%/73.1% and 58.2%/95.5%, respectively. The approach to use multiple cutoffs for the early and late gestational phase enhances the diagnostic accuracy of the sFlt-1/PlGF ratio as a diagnostic tool for preeclampsia.
authors.affiliation: Department of Obstetrics, Charité University Medicine Berlin, Charitéplatz 1, D-10117 Berlin, Germany. stefan.verlohren@charite.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Verlohren
authors.forename: Ignacio
authors.initials: I
authors.lastname: Herraiz
authors.forename: Olav
authors.initials: O
authors.lastname: Lapaire
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schlembach
authors.forename: Harald
authors.initials: H
authors.lastname: Zeisler
authors.forename: Pavel
authors.initials: P
authors.lastname: Calda
authors.forename: Joan
authors.initials: J
authors.lastname: Sabria
authors.forename: Filiz
authors.initials: F
authors.lastname: Markfeld-Erol
authors.forename: Alberto
authors.initials: A
authors.lastname: Galindo
authors.forename: Katharina
authors.initials: K
authors.lastname: Schoofs
authors.forename: Barbara
authors.initials: B
authors.lastname: Denk
authors.forename: Holger
authors.initials: H
authors.lastname: Stepan
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002624:Chemistry, Clinical / Q000379:methods / Q000592:standards*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008565:Membrane Proteins / Q000097:blood*; D011225:Pre-Eclampsia / Q000097:blood* / Q000175:diagnosis*; D011247:Pregnancy; D011256:Pregnancy Outcome; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012995:Solubility; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; C098069:PIGF protein, human; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: angiogenesis; angiogenic factors; antiangiogenic factors; hypertension; preeclampsia; pregnancy; sFlt1-PlGF ratio