title: Noninvasive prenatal detection and selective analysis of cell-free DNA obtained from maternal blood: evaluation for trisomy 21 and trisomy 18.
abstract: OBJECTIVE
  We sought to develop a novel biochemical assay and algorithm for the prenatal evaluation of risk for fetal trisomy 21 (T21) and trisomy 18 (T18) using cell-free DNA obtained from maternal blood.
  
  
  METHODS
  We assayed cell-free DNA from a training set and a blinded validation set of pregnant women, comprising 250 disomy, 72 T21, and 16 T18 pregnancies. We used digital analysis of selected regions in combination with a novel algorithm, fetal-fraction optimized risk of trisomy evaluation (FORTE), to determine trisomy risk for each subject.
  
  
  RESULTS
  In all, 163/171 subjects in the training set passed quality control criteria. Using a Z statistic, 35/35 T21 cases and 7/7 T18 cases had Z statistic >3 and 120/121 disomic cases had Z statistic <3. FORTE produced an individualized trisomy risk score for each subject, and correctly discriminated all T21 and T18 cases from disomic cases. All 167 subjects in the blinded validation set passed quality control and FORTE performance matched that observed in the training set correctly discriminating 36/36 T21 cases and 8/8 T18 cases from 123/123 disomic cases.
  
  
  CONCLUSIONS
  Digital analysis of selected regions and FORTE enable accurate, scalable noninvasive fetal aneuploidy detection.
authors.affiliation: Aria Diagnostics, San Jose, CA 95138, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Sparks
authors.forename: Craig A
authors.initials: CA
authors.lastname: Struble
authors.forename: Eric T
authors.initials: ET
authors.lastname: Wang
authors.forename: Ken
authors.initials: K
authors.lastname: Song
authors.forename: Arnold
authors.initials: A
authors.lastname: Oliphant
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics*; D004314:Down Syndrome / Q000175:diagnosis*; D005260:Female; D005333:Fetus; D006801:Humans; D008297:Male; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011296:Prenatal Diagnosis / Q000379:methods*; D012306:Risk; D012680:Sensitivity and Specificity; D014314:Trisomy / Q000175:diagnosis*
chemical_list: D004247:DNA