title: DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study.
abstract: OBJECTIVE
  To determine whether maternal plasma cell-free DNA sequencing can effectively identify trisomy 18 and 13.
  
  
  METHODS
  Sixty-two pregnancies with trisomy 18 and 12 with trisomy 13 were selected from a cohort of 4,664 pregnancies along with matched euploid controls (including 212 additional Down syndrome and matched controls already reported), and their samples tested using a laboratory-developed, next-generation sequencing test. Interpretation of the results for chromosome 18 and 13 included adjustment for CG content bias.
  
  
  RESULTS
  Among the 99.1% of samples interpreted (1,971/1,988), observed trisomy 18 and 13 detection rates were 100% (59/59) and 91.7% (11/12) at false-positive rates of 0.28% and 0.97%, respectively. Among the 17 samples without an interpretation, three were trisomy 18. If z-score cutoffs for trisomy 18 and 13 were raised slightly, the overall false-positive rates for the three aneuploidies could be as low as 0.1% (2/1,688) at an overall detection rate of 98.9% (280/283) for common aneuploidies. An independent academic laboratory confirmed performance in a subset.
  
  
  CONCLUSIONS
  Among high-risk pregnancies, sequencing circulating cell-free DNA detects nearly all cases of Down syndrome, trisomy 18, and trisomy 13, at a low false-positive rate. This can potentially reduce invasive diagnostic procedures and related fetal losses by 95%. Evidence supports clinical testing for these aneuploidies.
authors.affiliation: Division of Medical Screening and Special Testing, Department of Pathology and Laboratory Medicine, Women & Infants Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, USA.
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Palomaki
authors.forename: Cosmin
authors.initials: C
authors.lastname: Deciu
authors.forename: Edward M
authors.initials: EM
authors.lastname: Kloza
authors.forename: Geralyn M
authors.initials: GM
authors.lastname: Lambert-Messerlian
authors.forename: James E
authors.initials: JE
authors.lastname: Haddow
authors.forename: Louis M
authors.initials: LM
authors.lastname: Neveux
authors.forename: Mathias
authors.initials: M
authors.lastname: Ehrich
authors.forename: Dirk
authors.initials: D
authors.lastname: van den Boom
authors.forename: Allan T
authors.initials: AT
authors.lastname: Bombard
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Grody
authors.forename: Stanley F
authors.initials: SF
authors.lastname: Nelson
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Canick
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002882:Chromosomes, Human, Pair 13; D002887:Chromosomes, Human, Pair 18; D004247:DNA / Q000097:blood*; D004314:Down Syndrome / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011247:Pregnancy; D011296:Prenatal Diagnosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D014314:Trisomy / Q000175:diagnosis*; D014481:United States; D055815:Young Adult
chemical_list: D004247:DNA