title: Second and first trimester estimation of risk for Down syndrome: implementation and performance in the SAFER study.
abstract: OBJECTIVE
  Document patient choices and screening performance (false positive and detection rates) when three improved Down syndrome screening protocols were introduced coincidentally.
  
  
  METHODS
  Second-trimester 'triple marker' screening was expanded by adding second-trimester dimeric inhibin-A (four-marker), with or without first-trimester pregnancy-associated plasma protein-A (five-marker). Nuchal translucency (NT) measurements were included when available from accredited sonographers (six-marker). For assigning risk, two sets of marker distribution parameters were evaluated.
  
  
  RESULTS
  Over 3.5 years, 8571 women enrolled (median age 30.6 years). Uptake of the four-, five- and six-marker protocols was 18%, 46% and 36%, respectively. Of those selecting an integrated test (five or six markers), 9.7% did not provide the second trimester serum sample. False positive rates decreased with added markers (5.2%, 5.1% and 2.5%, respectively) and varied between the two parameter sets, while detection remained high. Overall, 21 of 23 cases were detected (91%, 95% CI 73-98%) at a 4.2% false positive rate (95% CI 3.3-5.1%).
  
  
  CONCLUSIONS
  Integrated screening protocols were chosen 4.6 times more often than four-marker screening (82% vs. 18% uptake). Overall detection was higher and false positives lower, consistent with recent guidelines. Important performance factors include gestational dating method, risk cut-off, and the parameter set used to assign risk.
authors.affiliation: Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada. macrae@cc.umanitoba.ca
authors.forename: Andrew R
authors.initials: AR
authors.lastname: MacRae
authors.forename: Bernie N
authors.initials: BN
authors.lastname: Chodirker
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Davies
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Palomaki
authors.forename: George J
authors.initials: GJ
authors.lastname: Knight
authors.forename: Jane
authors.initials: J
authors.lastname: Minett
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kavsak
authors.forename: Ants
authors.initials: A
authors.lastname: Toi
authors.forename: David
authors.initials: D
authors.lastname: Chitayat
authors.forename: Paul G
authors.initials: PG
authors.lastname: Van Caeseele
mesh_terms: D000328:Adult; D000465:Algorithms; D015415:Biomarkers / Q000097:blood*; D004314:Down Syndrome / Q000097:blood* / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D048208:Nuchal Translucency Measurement; D057240:Patient Preference; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D018570:Risk Assessment
chemical_list: D015415:Biomarkers