title: Optimal cut-offs for Down syndrome contingent screening in a population of 10,156 pregnant women.
abstract: METHODS
  A population of 10,156 pregnant women with singleton pregnancies were screened by the integrated test. Risks were retrospectively recalculated for contingent test strategies with first step intermediate risk groups defined by first trimester upper cut-offs of 1 : 10, 1 : 30, 1 : 50, and 1 : 70 and lower cut-offs 1 : 1500, 1 : 1200, 1 : 1100, and 1 : 900. The second trimester high risk group was based on a single cut-off of 1 : 250.
  
  
  RESULTS
  In the first trimester, the detection rate (DR) ranged from 21% (6/29) to 52% (15/29) as the high risk first trimester cut-off was changed from 1 : 10 to 1 : 70. The corresponding first trimester false positive rate (FPR) increased from 0.2% to 1.4%. In the second trimester, an additional 21/29 (72%) to 12/29 (41%) affected pregnancies could be detected with an additional 1.6% to 2.7% false positives when lower first trimester cut-offs of 1 : 900 to 1 : 1500 were used. The best results were obtained with the upper first trimester cut-off of 1 : 30 and lower first trimester cut-off of 1 : 900, which yielded a rate of women requiring a second trimester test of only 12%, with overall DR and FPR of 93% and 2.8%, respectively.
  
  
  CONCLUSIONS
  Although the study population was relatively small, the results confirm the advantage of using contingent screening and suggest optimal first trimester cut-offs of 1 : 30 (lower cut-off) and 1 : 900 (upper cut-off).
authors.affiliation: Department of Medical Genetics, Spirito Santo Hospital, Pescara, Italy. paolo.guanciali@tin.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Guanciali-Franchi
authors.forename: Irene
authors.initials: I
authors.lastname: Iezzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Soranno
authors.forename: Chiara Palka-Bayard
authors.initials: CP
authors.lastname: de Volo
authors.forename: Melissa
authors.initials: M
authors.lastname: Alfonsi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Calabrese
authors.forename: Peter
authors.initials: P
authors.lastname: Benn
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D004314:Down Syndrome / Q000175:diagnosis* / Q000000981:diagnostic imaging; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008403:Mass Screening / Q000379:methods / Q000592:standards; D011153:Population; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000502:physiology; D011296:Prenatal Diagnosis / Q000379:methods / Q000592:standards*; D012016:Reference Values; D012189:Retrospective Studies; D014463:Ultrasonography; D055815:Young Adult