title: Accuracy of circulating placental growth factor, vascular endothelial growth factor, soluble fms-like tyrosine kinase 1 and soluble endoglin in the prediction of pre-eclampsia: a systematic review and meta-analysis.
abstract: BACKGROUND
  Biomarkers have been proposed for identification of women at increased risk of developing pre-eclampsia.
  
  
  OBJECTIVE
  To investigate the capacity of circulating placental growth factor (PlGF), vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin (sENG) to predict pre-eclampsia.
  
  
  METHODS
  Medline and Embase through October 2010 and reference lists of reviews, without constraints.
  
  
  METHODS
  We included original publications on testing of PlGF, VEGF, sFLT1 and sENG in serum or plasma of pregnant women at <30 weeks of gestation and before clinical onset of pre-eclampsia.
  
  
  METHODS
  Two reviewers independently identified eligible studies, extracted descriptive and test accuracy data and assessed methodological quality. Summary estimates of discriminatory performance were obtained.
  
  
  RESULTS
  We included 34 studies. Concentrations of PlGF (27 studies) and VEGF (three studies) were lower in women who developed pre-eclampsia: standardised mean differences (SMD) -0.56 (95% CI -0.77 to -0.35) and -1.25 (95% CI -2.73 to 0.23). Concentrations of sFLT1 (19 studies) and sENG (ten studies) were higher: SMD 0.48 (95% CI 0.21-0.75) and SMD 0.54 (95% CI 0.24-0.84). The summary diagnostic odds ratios were: PlGF 9.0 (95% CI 5.6-14.5), sFLT1 6.6 (95% CI 3.1-13.7), sENG 4.2 (95% CI 2.4-7.2), which correspond to sensitivities of 32%, 26% and 18%, respectively, for a 5% false-positive rate.
  
  
  CONCLUSIONS
  PlGF, sFLT1 and sENG showed modest but significantly different concentrations before 30 weeks of gestation in women who developed pre-eclampsia. Test accuracies of all four markers, however, are too poor for accurate prediction of pre-eclampsia in clinical practice.
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, the Netherlands. c.e.kleinrouweler@amc.uva.nl
authors.forename: C E
authors.initials: CE
authors.lastname: Kleinrouweler
authors.forename: M M J
authors.initials: MM
authors.lastname: Wiegerinck
authors.forename: C
authors.initials: C
authors.lastname: Ris-Stalpers
authors.forename: P M M
authors.initials: PM
authors.lastname: Bossuyt
authors.forename: J A M
authors.initials: JA
authors.lastname: van der Post
authors.forename: P
authors.initials: P
authors.lastname: von Dadelszen
authors.forename: B W J
authors.initials: BW
authors.lastname: Mol
authors.forename: E
authors.initials: E
authors.lastname: Pajkrt
mesh_terms: D015703:Antigens, CD / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D000071063:Endoglin; D005260:Female; D006801:Humans; D016017:Odds Ratio; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011956:Receptors, Cell Surface / Q000097:blood*; D012680:Sensitivity and Specificity; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D042442:Vascular Endothelial Growth Factors / Q000097:blood*
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C064206:ENG protein, human; D000071063:Endoglin; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011956:Receptors, Cell Surface; D042442:Vascular Endothelial Growth Factors; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1