title: Comparison of combined, stepwise sequential, contingent, and integrated screening in 7292 high-risk pregnant women.
abstract: OBJECTIVE
  To compare the efficacy of combined, stepwise sequential, and contingent screening versus the integrated test in detecting fetal aneuploidies.
  
  
  METHODS
  First trimester combined test, sequential second trimester, and contingent risks were retrospectively calculated for 7292 unselected pregnant women with singleton pregnancies who had received integrated screening. The first trimester testing was based on nuchal translucency, pregnancy-associated plasma protein-A, and free-beta-human chorionic gonadotrophin (free β-hCG) and the second trimester tests were alpha-fetoprotein, hCG, and unconjugated estriol. A second trimester risk of 1:250 defined a positive result for all protocols with the contingent protocol based on additional second trimester testing for those with risks between 1:30 and 1:1200.
  
  
  RESULTS
  Among the population submitted for the integrated test, the detection rate was 19/21 (90%) for Down syndrome (DS) and 6/6 (100%) for Edwards syndrome (ES) and the DS false-positive rate (FPR) was 247/7271 (3.4%). Provision of the first trimester combined test alone would have resulted in a 17/21 (81%) detection rate for DS, that of 4/6 (67%) for ES and a DS FPR of 292/7271 (4.0%). The sequential and contingent approaches had the same final detection rates as the integrated test but potentially allowed a high proportion of the affected pregnancies to be detected in the first trimester. The lowest net DS FPR was seen with the contingent approach (2.6%) and using this protocol only 12.7% of women would have required second trimester testing.
  
  
  CONCLUSIONS
  Integrated, sequential, and contingent screenings are all more efficacious than the combined test. Overall, the contingent approach was the most efficient with a high-detection rate, the lowest FPR, and the least amount of testing.
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: Chiara
authors.initials: C
authors.lastname: Palka
authors.forename: Barbara
authors.initials: B
authors.lastname: Matarrelli
authors.forename: Elisena
authors.initials: E
authors.lastname: Morizio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Calabrese
authors.forename: Peter
authors.initials: P
authors.lastname: Benn
mesh_terms: D000293:Adolescent; D000328:Adult; D000649:Amniocentesis; D000782:Aneuploidy; D004314:Down Syndrome / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D048208:Nuchal Translucency Measurement; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D018566:Pregnancy, High-Risk / Q000097:blood*; D011296:Prenatal Diagnosis / Q000379:methods*; D012189:Retrospective Studies; D018570:Risk Assessment; D055815:Young Adult