title: DNA sequencing of maternal plasma to identify Down syndrome and other trisomies in multiple gestations.
abstract: OBJECTIVE
  Studies on prenatal testing for Down syndrome (trisomy 21), trisomy 18, and trisomy 13 by massively parallel shotgun sequencing (MPSS) of circulating cell free DNA have been, for the most part, limited to singleton pregnancies. If MPSS testing is offered clinically, it is important to know if these trisomies will also be identified in multiple pregnancies.
  
  
  METHODS
  Among a cohort of 4664 high-risk pregnancies, maternal plasma samples were tested from 25 twin pregnancies (17 euploid, five discordant and two concordant for Down syndrome; one discordant for trisomy 13) and two euploid triplet pregnancies [Correction made here after initial online publication.]. Results were corrected for GC content bias. For each target chromosome (21, 18, and 13), z-scores of 3 or higher were considered consistent with trisomy.
  
  
  RESULTS
  Seven twin pregnancies with Down syndrome, one with trisomy 13, and all 17 twin euploid pregnancies were correctly classified [detection rate 100%, 95% confidence interval (CI) 59%-100%, false positive rate 0%, 95% CI 0%-19.5%], as were the two triplet euploid pregnancies.
  
  
  CONCLUSIONS
  Although study size is limited, the underlying biology combined with the present data provide evidence that MPSS testing can be reliably used as a secondary screening test for Down syndrome in women with high-risk twin gestations.
authors.affiliation: Division of Medical Screening and Special Testing, Department of Pathology and Laboratory Medicine, Women and Infants Hospital, Alpert Medical School of Brown University, Providence, RI, USA. jcanick@wihri.org
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Canick
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: 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: Cosmin
authors.initials: C
authors.lastname: Deciu
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Palomaki
mesh_terms: D004314:Down Syndrome / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008297:Male; D011247:Pregnancy; D059286:Pregnancy, Triplet / Q000097:blood; D059285:Pregnancy, Twin / Q000097:blood*; D017422:Sequence Analysis, DNA; D014314:Trisomy / Q000175:diagnosis*