title: First-trimester screening for trisomies 21 and 18.
abstract: BACKGROUND
  Screening for aneuploid pregnancies is routinely performed after 15 weeks of gestation and has a sensitivity of approximately 65 percent, with a false positive rate of 5 percent. First-trimester markers of aneuploidy have been developed, but their use in combination has not been adequately evaluated in clinical practice.
  
  
  METHODS
  We conducted a multicenter study of screening for trisomies 21 and 18 among patients with pregnancies between 74 and 97 days of gestation, based on maternal age, maternal levels of free beta human chorionic gonadotropin and pregnancy-associated plasma protein A, and ultrasonographic measurement of fetal nuchal translucency. A screening result was considered to be positive for trisomy 21 if the calculated risk was at least 1 in 270 pregnancies and positive for trisomy 18 if the risk was at least 1 in 150.
  
  
  RESULTS
  Screening was completed in 8514 patients with singleton pregnancies. This approach to screening identified 85.2 percent of the 61 cases of Down's syndrome (95 percent confidence interval, 73.8 to 93.0), with a false positive rate of 9.4 percent (95 percent confidence interval, 8.8 to 10.1). At a false positive rate of 5 percent, the detection rate was 78.7 percent (95 percent confidence interval, 66.3 to 88.1). Screening identified 90.9 percent of the 11 cases of trisomy 18 (95 percent confidence interval, 58.7 to 99.8), with a 2 percent false positive rate. Among women 35 years of age or older, screening identified 89.8 percent of fetuses with trisomy 21, with a false positive rate of 15.2 percent, and 100 percent of fetuses with trisomy 18.
  
  
  CONCLUSIONS
  First-trimester screening for trisomies 21 and 18 on the basis of maternal age, maternal levels of free beta human chorionic gonadotropin and pregnancy-associated plasma protein A, and measurement of fetal nuchal translucency has good sensitivity at an acceptable false positive rate.
authors.affiliation: Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Wapner
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Thom
authors.forename: Joe Leigh
authors.initials: JL
authors.lastname: Simpson
authors.forename: Eugene
authors.initials: E
authors.lastname: Pergament
authors.forename: Richard
authors.initials: R
authors.lastname: Silver
authors.forename: Karen
authors.initials: K
authors.lastname: Filkins
authors.forename: Lawrence
authors.initials: L
authors.lastname: Platt
authors.forename: Maurice
authors.initials: M
authors.lastname: Mahoney
authors.forename: Anthony
authors.initials: A
authors.lastname: Johnson
authors.forename: W Allen
authors.initials: WA
authors.lastname: Hogge
authors.forename: R Douglas
authors.initials: RD
authors.lastname: Wilson
authors.forename: Patrick
authors.initials: P
authors.lastname: Mohide
authors.forename: Douglas
authors.initials: D
authors.lastname: Hershey
authors.forename: David
authors.initials: D
authors.lastname: Krantz
authors.forename: Julia
authors.initials: J
authors.lastname: Zachary
authors.forename: Rosalinde
authors.initials: R
authors.lastname: Snijders
authors.forename: Naomi
authors.initials: N
authors.lastname: Greene
authors.forename: Rudy
authors.initials: R
authors.lastname: Sabbagha
authors.forename: Scott
authors.initials: S
authors.lastname: MacGregor
authors.forename: Lyndon
authors.initials: L
authors.lastname: Hill
authors.forename: Alain
authors.initials: A
authors.lastname: Gagnon
authors.forename: Terrence
authors.initials: T
authors.lastname: Hallahan
authors.forename: Laird
authors.initials: L
authors.lastname: Jackson
mesh_terms: D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D002887:Chromosomes, Human, Pair 18; D004314:Down Syndrome / Q000175:diagnosis*; D005189:False Positive Reactions; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000000981:diagnostic imaging; D006801:Humans; D008423:Maternal Age; D009333:Neck / Q000000981:diagnostic imaging* / Q000196:embryology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D011296:Prenatal Diagnosis / Q000379:methods*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014314:Trisomy / Q000175:diagnosis*; D016216:Ultrasonography, Prenatal
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A