title: Fetoplacental mosaicism: potential implications for false-positive and false-negative noninvasive prenatal screening results.
abstract: OBJECTIVE
  Noninvasive prenatal screening for fetal aneuploidy analyzes cell-free fetal DNA circulating in the maternal plasma. Because cell-free fetal DNA is mainly of placental trophoblast origin, false-positive and false-negative findings may result from placental mosaicism. The aim of this study was to calculate the potential contribution of placental mosaicism in discordant results of noninvasive prenatal screening.
  
  
  METHODS
  We performed a retrospective audit of 52,673 chorionic villus samples in which cytogenetic analysis of the cytotrophoblast (direct) and villus mesenchyme (culture) was performed, which was followed by confirmatory amniocentesis in chorionic villi mosaic cases. Using cases in which cytogenetic discordance between cytotrophoblast and amniotic fluid samples was identified, we calculated the potential contribution of cell line-specific mosaicism to false-positive and false-negative results of noninvasive prenatal screening.
  
  
  RESULTS
  The false-positive rate, secondary to the presence of abnormal cell line with common trisomies in cytotrophoblast and normal amniotic fluid, ranged from 1/1,065 to 1/3,931 at 10% and 100% mosaicism, respectively; the false-negative rate was calculated from cases of true fetal mosaicism, in which a mosaic cell line was absent in cytotrophoblast and present in the fetus; this occurred in 1/107 cases.
  
  
  CONCLUSIONS
  Despite exciting advances, underlying biologic mechanisms will never allow 100% sensitivity or specificity.
authors: Research & Development, Cytogenetics, Molecular Cytogenetics and Molecular Biology, TOMA Advanced Biomedical Assays, S.p.A., Busto Arsizio (VA), Italy.
authors: Francesca R
authors: FR
authors: Grati
authors: Research & Development, Cytogenetics, Molecular Cytogenetics and Molecular Biology, TOMA Advanced Biomedical Assays, S.p.A., Busto Arsizio (VA), Italy.
authors: Francesca
authors: F
authors: Malvestiti
authors: Department of Obstetrics and Women's Health, Albert Einstein College of Medicine, Bronx, New York, USA.
authors: Jose C P B
authors: JC
authors: Ferreira
authors: Department of Obstetrics and Women's Health, Albert Einstein College of Medicine, Bronx, New York, USA.
authors: Komal
authors: K
authors: Bajaj
authors: Research & Development, Cytogenetics, Molecular Cytogenetics and Molecular Biology, TOMA Advanced Biomedical Assays, S.p.A., Busto Arsizio (VA), Italy.
authors: Elisa
authors: E
authors: Gaetani
authors: Research & Development, Cytogenetics, Molecular Cytogenetics and Molecular Biology, TOMA Advanced Biomedical Assays, S.p.A., Busto Arsizio (VA), Italy.
authors: Cristina
authors: C
authors: Agrati
authors: Research & Development, Cytogenetics, Molecular Cytogenetics and Molecular Biology, TOMA Advanced Biomedical Assays, S.p.A., Busto Arsizio (VA), Italy.
authors: Beatrice
authors: B
authors: Grimi
authors: Research & Development, Cytogenetics, Molecular Cytogenetics and Molecular Biology, TOMA Advanced Biomedical Assays, S.p.A., Busto Arsizio (VA), Italy.
authors: Francesca
authors: F
authors: Dulcetti
authors: Research & Development, Cytogenetics, Molecular Cytogenetics and Molecular Biology, TOMA Advanced Biomedical Assays, S.p.A., Busto Arsizio (VA), Italy.
authors: Anna M
authors: AM
authors: Ruggeri
authors: Research & Development, Cytogenetics, Molecular Cytogenetics and Molecular Biology, TOMA Advanced Biomedical Assays, S.p.A., Busto Arsizio (VA), Italy.
authors: Simona
authors: S
authors: De Toffol
authors: Research & Development, Cytogenetics, Molecular Cytogenetics and Molecular Biology, TOMA Advanced Biomedical Assays, S.p.A., Busto Arsizio (VA), Italy.
authors: Federico
authors: F
authors: Maggi
authors: Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, New York, USA.
authors: Ronald
authors: R
authors: Wapner
authors: Department of Obstetrics and Women's Health, Albert Einstein College of Medicine, Bronx, New York, USA.
authors: Susan
authors: S
authors: Gross
authors: Research & Development, Cytogenetics, Molecular Cytogenetics and Molecular Biology, TOMA Advanced Biomedical Assays, S.p.A., Busto Arsizio (VA), Italy.
authors: Giuseppe
authors: G
authors: Simoni
mesh_terms: D015193:Chorionic Villi Sampling; D004247:DNA / Q000032:analysis; D005260:Female; D006801:Humans; D059785:Karyotype; D007621:Karyotyping; D009030:Mosaicism / Q000196:embryology*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D012189:Retrospective Studies; D014314:Trisomy / Q000175:diagnosis*; D014327:Trophoblasts / Q000166:cytology*
chemical_list: D004247:DNA