title: Screening for pre-eclampsia using serum placental growth factor and endoglin with Down's syndrome Quadruple test markers.
abstract: OBJECTIVE
  To estimate the pre-eclampsia screening performance of placental growth factor (PlGF) and endoglin with second-trimester Quadruple test markers used for antenatal Down's syndrome screening.
  
  
  METHODS
  A nested case-control study of 88 pregnant women with known early second-trimester Down's syndrome Quadruple test marker levels who subsequently developed pre-eclampsia and 275 unaffected controls. Frozen maternal serum samples were thawed and assayed for PlGF and endoglin. Monte Carlo simulation was used to estimate the pre-eclampsia screening performance of a pre-eclampsia detection algorithm using the Quadruple test markers with or without the addition of PlGF and/or endoglin.
  
  
  RESULTS
  Median PlGF was 33% lower (95% confidence interval 24-41%) and endoglin 31% (20-43%) higher in pre-eclampsia than in unaffected pregnancies. Adding PlGF to the Quadruple test markers increased the pre-eclampsia detection rate from 34% to 45% at a 5% false-positive rate - it increased it to 43% with endoglin and to 50% with both. The corresponding estimates for early pre-eclampsia (before 36 weeks' gestation) were a few percentage points higher (48%, 48% and 55% respectively). Including information on parity, pre-eclampsia in a previous pregnancy, family history (woman's mother) and assuming a pre-eclampsia prevalence of 2%, the detection rates for a 5% false-positive rate were 39% with the Quadruple test markers, 48% with addition of endoglin, 49% with addition of PlGF, and 54% with addition of both.
  
  
  CONCLUSIONS
  Adding PlGF to the Quadruple test Down's syndrome screening markers improves pre-eclampsia screening performance. There is a modest extra benefit in also adding the measurement of endoglin.
authors.affiliation: Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK. n.j.wald@qmul.ac.uk
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wald
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Bestwick
authors.forename: Lynne M
authors.initials: LM
authors.lastname: George
authors.forename: Tiesheng
authors.initials: T
authors.lastname: Wu
authors.forename: Joan K
authors.initials: JK
authors.lastname: Morris
mesh_terms: D015703:Antigens, CD / Q000097:blood*; D016022:Case-Control Studies; D004314:Down Syndrome / Q000097:blood*; D000071063:Endoglin; D005260:Female; D006801:Humans; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000175:diagnosis*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011264:Pregnancy Trimesters; D011956:Receptors, Cell Surface / Q000097:blood*
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011956:Receptors, Cell Surface; D000072483:Placenta Growth Factor