title: Contingent screening for Down syndrome--results from the FaSTER trial.
abstract: OBJECTIVE
  Comparison of contingent, step-wise and integrated screening policies.
  
  
  METHODS
  Mid-trimester Down syndrome risks were retrospectively calculated from FaSTER trial data. For contingent screening, initial risk was calculated from ultrasound measurement of nuchal translucency (NT), maternal serum pregnancy-associated plasma protein (PAPP)-A and free beta-human chorionic gonadotrophin (hCG) at 11-13 weeks, and classified positive (>1 in 30), borderline (1 in 30-1500) or negative. Borderline risks were recalculated using alpha-fetoprotein, hCG, unconjugated estriol (uE3) and inhibin at 15-18 weeks, and reclassified as positive (>1 in 270) or negative. For step-wise screening, initial negative risks were also recalculated. For integrated screening, a single risk was calculated from NT, PAPP-A and the second trimester markers.
  
  
  RESULTS
  There were 86 Down syndrome and 32,269 unaffected pregancies. The detection rate for contingent screening was 91% and false-positive rate was 4.5%; initial detection rate was 60%, initial false-positive rate was 1.2% and borderline risk was 23%. Step-wise screening had 92% detection rate and 5.1% false-positive rate; integrated screening had 88% and 4.9% respectively.
  
  
  CONCLUSIONS
  As predicted by modelling, the contingent screening detection rate for a fixed false-positive rate is comparable with step-wise and integrated screening, but substantially reduces the number needing to return for second trimester testing.
authors.affiliation: Columbia University, New York, USA. hc2340@columbia.edu
authors.forename: Howard S
authors.initials: HS
authors.lastname: Cuckle
authors.forename: Fergal D
authors.initials: FD
authors.lastname: Malone
authors.forename: David
authors.initials: D
authors.lastname: Wright
authors.forename: T Flint
authors.initials: TF
authors.lastname: Porter
authors.forename: David A
authors.initials: DA
authors.lastname: Nyberg
authors.forename: Christine H
authors.initials: CH
authors.lastname: Comstock
authors.forename: George R
authors.initials: GR
authors.lastname: Saade
authors.forename: Richard L
authors.initials: RL
authors.lastname: Berkowitz
authors.forename: Jose C
authors.initials: JC
authors.lastname: Ferreira
authors.forename: Lorraine
authors.initials: L
authors.lastname: Dugoff
authors.forename: Sabrina D
authors.initials: SD
authors.lastname: Craigo
authors.forename: Ilan E
authors.initials: IE
authors.lastname: Timor
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Carr
authors.forename: Honor M
authors.initials: HM
authors.lastname: Wolfe
authors.forename: Mary E
authors.initials: ME
authors.lastname: D'Alton
mesh_terms: D015415:Biomarkers / Q000097:blood; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D004314:Down Syndrome / Q000175:diagnosis*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008403:Mass Screening; D048208:Nuchal Translucency Measurement; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000097:blood*; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A