Alexandra Benachi1, Alexandra Letourneau, Pascale Kleinfinger, Marie-Victoire Senat, Evelyne Gautier, Romain Favre, Laurent Bidat, Véronique Houfflin-Debarge, Jean Bouyer, Jean-Marc Costa. 1. 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.
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. CONCLUSION: 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. LEVEL OF EVIDENCE: III.
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. CONCLUSION: 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. LEVEL OF EVIDENCE: III.
Authors: Brittany Dyr; Theresa Boomer; Eyad A Almasri; Jenna L Wardrop; Jill Rafalko; Jason Chibuk; Ron M McCullough Journal: PLoS One Date: 2019-08-08 Impact factor: 3.240
Authors: Yohann Dabi; Sarah Guterman; Jacques C Jani; Alexandra Letourneau; Adèle Demain; Pascale Kleinfinger; Laurence Lohmann; Jean-Marc Costa; Alexandra Benachi Journal: J Transl Med Date: 2018-12-03 Impact factor: 5.531
Authors: Annisa Mak; Helena Lee; C F Poon; S L Kwok; Teresa Ma; K Y K Chan; Anita Kan; Mary Tang; K Y Leung Journal: BMC Pregnancy Childbirth Date: 2019-02-04 Impact factor: 3.007