title: Discordant noninvasive prenatal testing and cytogenetic results: a study of 109 consecutive cases.
abstract: OBJECTIVE
  Recent published studies have demonstrated the incremental value of the use of cell-free DNA for noninvasive prenatal testing with 100% sensitivity for trisomies 21 and 18 and a specificity of ≥99.7% for both. Data presented by two independent groups suggesting positive results by noninvasive prenatal testing were not confirmed by cytogenetic studies.
  
  
  METHODS
  Concordance of results among cases with noninvasive prenatal testing referred for cytogenetic prenatal and/or postnatal studies by karyotyping, fluorescence in situ hybridization, and/or oligo-single-nucleotide polymorphism microarray was evaluated for 109 consecutive specimens.
  
  
  RESULTS
  Cytogenetic results were positive for trisomy 21 in 38 of the 41 noninvasive prenatal testing-positive cases (true-positive rate: 93%) and for trisomy 18 in 16 of the 25 noninvasive prenatal testing-positive cases (true-positive rate: 64%). The true-positive rate was only 44% (7/16 cases) for trisomy 13 and 38% (6/16 cases) for sex chromosome aneuploidy.
  
  
  CONCLUSIONS
  These findings raise concerns about the limitations of noninvasive prenatal testing and the need for analysis of a larger number of false-positive cases to provide true positive predictive values for noninvasive testing and to search for potential biological or technical causes. Our data suggest the need for a careful interpretation of noninvasive prenatal testing results and cautious transmission of the same to providers and patients.
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, California, USA.
authors.forename: Jia-Chi
authors.identifier: 0000000210951091
authors.initials: JC
authors.lastname: Wang
authors.affiliation: 1] Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, California, USA [2] Current affiliation: CombiMatrix, Irvine, California, USA.
authors.forename: Trilochan
authors.initials: T
authors.lastname: Sahoo
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, Chantilly, Virginia, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Schonberg
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, California, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Kopita
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, California, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Ross
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, Chantilly, Virginia, USA.
authors.forename: Kyla
authors.initials: K
authors.lastname: Patek
authors.affiliation: Cytogenetics Laboratory, Quest Diagnostics Nichols Institute, San Juan Capistrano, California, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Strom
mesh_terms: D002474:Cell-Free System; D002887:Chromosomes, Human, Pair 18; D020732:Cytogenetic Analysis / Q000379:methods*; D004314:Down Syndrome / Q000175:diagnosis*; D005260:Female; D006801:Humans; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D012680:Sensitivity and Specificity; D014314:Trisomy / Q000175:diagnosis*; D000073842:Trisomy 18 Syndrome
references.citation: Genet Med. 2014 Apr;16(4):281-5
references.pmid: 24009001
references.citation: N Engl J Med. 2014 Feb 27;370(9):799-808
references.pmid: 24571752