title: The comprehensive midtrimester test: high-sensitivity Down syndrome test.
abstract: OBJECTIVE
  The purpose of this study was to develop a highly sensitive algorithm for midtrimester Down syndrome detection.
  
  
  METHODS
  Urine (hyperglycosylated human chorionic gonadotropin, beta-core fragment of human chorionic gonadotropin), serum (alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol [uE(3)]), and ultrasound biometry (nuchal thickness, humerus length, the presence of gross ultrasonographic anomalies), and maternal age were measured at genetic amniocentesis. Stepwise logistic regression analysis was used to identify the most significant markers. A multivariate Gaussian algorithm plus age was used to derive patient-specific Down syndrome risk. Sensitivity and false-positive rates at different risk thresholds and the area under the receiver-operating characteristic curve were determined. A probability value of <.05 was significant.
  
  
  RESULTS
  There were 568 study cases with 17 Down syndrome cases (3.0%). The mean (+/-SD) maternal and gestational ages for the study group were 36.9 (+/-3.5) years and 16.2 (+/-1.4) weeks, respectively. The significant markers were nuchal thickness (P =.0001), hyperglycosylated human chorionic gonadotropin(P <.001), and beta-core fragment (P <.002). Neither maternal age nor gross sonographic anomaly contributed significantly to Down syndrome detection. The comprehensive midtrimester test was extremely efficient for Down syndrome detection in advanced maternal age only cases with a sensitivity of 92.3% at a 0.8% false-positive rate. In women <35 years old, all the Down syndrome cases were detected at 2.2% false positive rate. For the overall population, the sensitivity was 93.7% at 5% false-positive rate.
  
  
  CONCLUSIONS
  In a preliminary study, the comprehensive midtrimester test appeared highly sensitive in different age groups. Gross anomaly detection was not required for high performance, which makes the comprehensive midtrimester test potentially suitable for low-risk screening and as an alternative to amniocentesis in women who wish to avoid the procedure. This was a small study; thus, the clinical value of this test can only be established in large trials.
authors.affiliation: Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA. ray.bahado-singh@yale.edu
authors.forename: Ray
authors.initials: R
authors.lastname: Bahado-Singh
authors.forename: Shohreh
authors.initials: S
authors.lastname: Shahabi
authors.forename: Mehmet
authors.initials: M
authors.lastname: Karaca
authors.forename: Maurice J
authors.initials: MJ
authors.lastname: Mahoney
authors.forename: Laurence
authors.initials: L
authors.lastname: Cole
authors.forename: Utku A
authors.initials: UA
authors.lastname: Oz
mesh_terms: D000328:Adult; D000465:Algorithms; D000649:Amniocentesis; D006063:Chorionic Gonadotropin / Q000097:blood / Q000652:urine; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000652:urine; D004314:Down Syndrome / Q000175:diagnosis*; D004964:Estriol / Q000097:blood; D005189:False Positive Reactions; D005260:Female; D005865:Gestational Age; D006801:Humans; D009333:Neck / Q000000981:diagnostic imaging / Q000196:embryology; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis / Q000379:methods*; D012680:Sensitivity and Specificity; D016216:Ultrasonography, Prenatal; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D000509:alpha-Fetoproteins; C024889:glycosylated HCG; D004964:Estriol