title: Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia.
abstract: BACKGROUND
  The ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is elevated in pregnant women before the clinical onset of preeclampsia, but its predictive value in women with suspected preeclampsia is unclear.
  
  
  METHODS
  We performed a prospective, multicenter, observational study to derive and validate a ratio of serum sFlt-1 to PlGF that would be predictive of the absence or presence of preeclampsia in the short term in women with singleton pregnancies in whom preeclampsia was suspected (24 weeks 0 days to 36 weeks 6 days of gestation). Primary objectives were to assess whether low sFlt-1:PlGF ratios (at or below a derived cutoff) predict the absence of preeclampsia within 1 week after the first visit and whether high ratios (above the cutoff) predict the presence of preeclampsia within 4 weeks.
  
  
  RESULTS
  In the development cohort (500 women), we identified an sFlt-1:PlGF ratio cutoff of 38 as having important predictive value. In a subsequent validation study among an additional 550 women, an sFlt-1:PlGF ratio of 38 or lower had a negative predictive value (i.e., no preeclampsia in the subsequent week) of 99.3% (95% confidence interval [CI], 97.9 to 99.9), with 80.0% sensitivity (95% CI, 51.9 to 95.7) and 78.3% specificity (95% CI, 74.6 to 81.7). The positive predictive value of an sFlt-1:PlGF ratio above 38 for a diagnosis of preeclampsia within 4 weeks was 36.7% (95% CI, 28.4 to 45.7), with 66.2% sensitivity (95% CI, 54.0 to 77.0) and 83.1% specificity (95% CI, 79.4 to 86.3).
  
  
  CONCLUSIONS
  An sFlt-1:PlGF ratio of 38 or lower can be used to predict the short-term absence of preeclampsia in women in whom the syndrome is suspected clinically. (Funded by Roche Diagnostics.).
authors.affiliation: From the Department of Obstetrics and Gynecology, Medical University Vienna, Vienna (H.Z.); the Department of Obstetrics, Maternal-Fetal Medicine Unit, Hospital Universitari Vall d'Hebron, Barcelona, and the Maternal and Child Health and Development Network, Instituto de Salud Carlos III, Madrid (E.L.); the Department of Obstetrics and Gynecology, University of Liege, Liege, Belgium (F.C.); Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, United Kingdom (M.V.); the Departments of Gynecology and Obstetrics, Oslo University Hospital, and University of Oslo, Oslo (A.C.S.); the Department of Women's and Children's Health, Karolinska University Hospital, and Karolinska Institute, Stockholm (M. Sennström), and the Department of Women's and Children's Health, Uppsala University, Uppsala (M.O.) - both in Sweden; Pregnancy Research Centre, Department of Perinatal Medicine, Royal Women's Hospital and Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, VIC, Australia (S.P.B.); the Department of Obstetrics, University of Leipzig, Leipzig (H.S.), Roche Diagnostics, Penzberg (P.D., M. Schoedl), and the Department of Obstetrics, Campus Virchow-Klinikum Charité, Berlin (S.V.) - all in Germany; and Roche Diagnostics International, Rotkreuz, Switzerland (D.A., M.H.).
authors.forename: Harald
authors.initials: H
authors.lastname: Zeisler
authors.forename: Elisa
authors.initials: E
authors.lastname: Llurba
authors.forename: Frederic
authors.initials: F
authors.lastname: Chantraine
authors.forename: Manu
authors.initials: M
authors.lastname: Vatish
authors.forename: Anne Cathrine
authors.initials: AC
authors.lastname: Staff
authors.forename: Maria
authors.initials: M
authors.lastname: Sennström
authors.forename: Matts
authors.initials: M
authors.lastname: Olovsson
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Brennecke
authors.forename: Holger
authors.initials: H
authors.lastname: Stepan
authors.forename: Deirdre
authors.initials: D
authors.lastname: Allegranza
authors.forename: Peter
authors.initials: P
authors.lastname: Dilba
authors.forename: Maria
authors.initials: M
authors.lastname: Schoedl
authors.forename: Martin
authors.initials: M
authors.lastname: Hund
authors.forename: Stefan
authors.initials: S
authors.lastname: Verlohren
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1