title: Role of second-trimester genetic sonography after Down syndrome screening.
abstract: OBJECTIVE
  To estimate the effectiveness of second-trimester genetic sonography in modifying Down syndrome screening test results.
  
  
  METHODS
  The First and Second Trimester Evaluation of Risk (FASTER) aneuploidy screening trial participants were studied from 13 centers where a 15- to 23-week genetic sonogram was performed in the same center. Midtrimester Down syndrome risks were estimated for five screening test policies: first-trimester combined, second-trimester quadruple, and testing sequentially by integrated, stepwise, or contingent protocols. The maternal age-specific risk and the screening test risk were modified using likelihood ratios derived from the ultrasound findings. Separate likelihood ratios were obtained for the presence or absence of at least one major fetal structural malformation and for each "soft" sonographic marker statistically significant at the P<.005 level. Detection and false-positive rate were calculated for the genetic sonogram alone and for each test before and after risk modification.
  
  
  RESULTS
  A total of 7,842 pregnancies were studied, including 59 with Down syndrome. Major malformations and 8 of the 18 soft markers evaluated were highly significant. The detection rate for a 5% false-positive rate for the genetic sonogram alone was 69%; the detection rate increased from 81% to 90% with the combined test, from 81% to 90% with the quadruple test, from 93% to 98% with the integrated test, from 97% to 98% with the stepwise test, and from 95% to 97% with the contingent test. The stepwise and contingent use of the genetic sonogram after first-trimester screening both yielded a 90% detection rate.
  
  
  CONCLUSIONS
  Genetic sonography can increase detection rates substantially for combined and quadruple tests and more modestly for sequential protocols. Substituting sonography for quadruple markers in sequential screening was not useful.
  
  
  METHODS
  II.
authors.affiliation: From the University of Utah, Salt Lake City, Utah; Royal College of Surgeons in Ireland, Dublin, Ireland; Swedish Medical Center, Seattle, Washington; University of California, San Francisco, California; Columbia University, New York, New York; DM-STAT, Malden, Massachusetts; William Beaumont Hospital, Royal Oak, Michigan; University of Texas Medical Branch at Galveston, Texas; Mount Sinai Medical Center, New York, New York; Albert Einstein College of Medicine, Bronx, New York; University of Colorado Health Sciences Center, Denver, Colorado; Tufts University, Boston, Massachusetts; NYU Medical Center, New York, New York; Brown University, Providence, Rhode Island; and University of North Carolina at Chapel Hill, North Carolina.
authors.forename: Kjersti M
authors.initials: KM
authors.lastname: Aagaard-Tillery
authors.forename: Fergal D
authors.initials: FD
authors.lastname: Malone
authors.forename: David A
authors.initials: DA
authors.lastname: Nyberg
authors.forename: T Flint
authors.initials: TF
authors.lastname: Porter
authors.forename: Howard S
authors.initials: HS
authors.lastname: Cuckle
authors.forename: Karin
authors.initials: K
authors.lastname: Fuchs
authors.forename: Lisa
authors.initials: L
authors.lastname: Sullivan
authors.forename: Christine H
authors.initials: CH
authors.lastname: Comstock
authors.forename: George R
authors.initials: GR
authors.lastname: Saade
authors.forename: Keith
authors.initials: K
authors.lastname: Eddleman
authors.forename: Susan
authors.initials: S
authors.lastname: Gross
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-Tritsch
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Carr
authors.forename: Honor M
authors.initials: HM
authors.lastname: Wolfe
authors.forename: Diana W
authors.initials: DW
authors.lastname: Bianchi
authors.forename: Mary E
authors.initials: ME
authors.lastname: D'Alton
mesh_terms: D000328:Adult; D004314:Down Syndrome / Q000175:diagnosis / Q000000981:diagnostic imaging*; D005260:Female; D005820:Genetic Testing; D006801:Humans; D011247:Pregnancy; D011446:Prospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016216:Ultrasonography, Prenatal; D055815:Young Adult