title: Cell-free DNA analysis in maternal plasma in cases of fetal abnormalities detected on ultrasound examination.
abstract: OBJECTIVE
  To evaluate the utility of noninvasive prenatal testing using cell-free circulating fetal DNA for detection of the three main autosomal fetal trisomies in the setting of ultrasonographically identified fetal anomalies.
  
  
  METHODS
  Nine hundred patients at risk for fetal aneuploidy with or without ultrasonography anomalies and who underwent invasive procedures were included in the study. Cell-free DNA analysis was performed by massive parallel sequencing during a multicenter, noninterventional, prospective study and the results were compared with a fetal karyotype.
  
  
  RESULTS
  Among all 900 pregnancies, cell-free DNA identified 76 of 76 (100%) fetal Down syndrome, 22 of 25 (88%) trisomy 18, and 12 of 12 (100%) trisomy 13. In those with a normal ultrasonogram and normal cell-free DNA analysis, karyotype identified 2 of 483 (0.4%) additional aneuploidies other than trisomies 13, 18, and 21. In those with an abnormal ultrasonogram and a normal cell-free DNA analysis, there were 23 of 290 (7.9%) additional pathogenic karyotypes. These additional aneuploidies included sex chromosome abnormalities and triploidy. The rates of additional aneuploidies not identifiable by standard cell-free DNA screening in the two groups is significantly different at P<.01.
  
  
  CONCLUSIONS
  In women with fetal abnormalities by ultrasonography, the rate of pathogenic chromosome abnormalities missed by cell-free DNA was 8%. Noninvasive prenatal testing should not be offered to women with fetal abnormalities because a negative result is falsely reassuring.
  
  
  METHODS
  III.
authors.affiliation: Service de Gynécologie-Obstétrique et Médecine de la Reproduction, Hôpital Antoine Béclère, Clamart, France; Université Paris Sud, Paris, France; Laboratoire CERBA, Saint-Ouen l'Aumône, France; Gynécologie-Obstétrique, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; Centre de Diagnostic Prénatal, Hôpital Américain de Paris, Neuilly-sur-Seine, France; Gynécologie-Obstétrique, SIHCUS-CMCO, Schiltigheim, France; Gynécologie-Obstétrique, Centre Hospitalier René Dubos, Pontoise, France; Centre de Diagnostic Prénatal, Centre Hospitalier Régional Universitaire, Lille, France; and Inserm, Le Kremlin-Bicêtre, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Benachi
authors.forename: Alexandra
authors.initials: A
authors.lastname: Letourneau
authors.forename: Pascale
authors.initials: P
authors.lastname: Kleinfinger
authors.forename: Marie-Victoire
authors.initials: MV
authors.lastname: Senat
authors.forename: Evelyne
authors.initials: E
authors.lastname: Gautier
authors.forename: Romain
authors.initials: R
authors.lastname: Favre
authors.forename: Laurent
authors.initials: L
authors.lastname: Bidat
authors.forename: Véronique
authors.initials: V
authors.lastname: Houfflin-Debarge
authors.forename: Jean
authors.initials: J
authors.lastname: Bouyer
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Costa
mesh_terms: D000328:Adult; D025063:Chromosome Disorders / Q000000981:diagnostic imaging / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13 / Q000000981:diagnostic imaging / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000000981:diagnostic imaging / Q000235:genetics; D041321:Chromosomes, Human, X; D004247:DNA / Q000097:blood*; D004314:Down Syndrome / Q000000981:diagnostic imaging / Q000235:genetics*; D005188:False Negative Reactions; D005260:Female; D005820:Genetic Testing; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D059785:Karyotype; D011247:Pregnancy; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012729:Sex Chromosome Aberrations; D014314:Trisomy / Q000235:genetics*; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome; D016216:Ultrasonography, Prenatal
chemical_list: D004247:DNA