Cell-free DNA screening for trisomies 21, 18, and 13 in pregnancies at low and high risk for aneuploidy with genetic confirmation

• DOI: 10.1016/j.ajog.2022.01.019
• Publication Date: 2022-01-25T01:44:54Z
• Authors: Pe’er Dar; Bo Jacobsson; Cora MacPherson; Melissa Egbert; Fergal Malone; Ronald J. Wapner; Ashley S. Roman; Asma Khalil; Revital Faro; Rajeevi Madankumar; Lance Edwards; Sina Haeri; Robert Silver; Nidhi Vohra; Jon Hyett; Garfield Clunie; Zachary Demko; Kimberly Martin; Matthew Rabinowitz; Karen Flood; Ylva Carlsson; Georgios Doulaveris; Ciara Malone; Maria Hallingstrom; Susan Klugman; Rebecca Clifton; Charlly Kao; Hakon Hakonarson; Mary E. Norton
• Keywords: Cell-free fetal DNA; Trisomy; Interquartile range

Cell-free DNA noninvasive prenatal screening for trisomies 21, 18, and 13 has been rapidly adopted into clinical practice. However, previous studies are limited by a lack of follow-up genetic testing to confirm the outcomes accurately assess test performance, particularly in women at low risk aneuploidy.To measure compare performance cell-free between high aneuploidy large, prospective cohort with confirmation results STUDY DESIGN: This was multicenter observational study 21 centers 6 countries. Women who had single-nucleotide-polymorphism-based were enrolled. Genetic obtained from or newborn samples. The failure (no-call) rates assessed cohort, risks compared. An updated algorithm blinded pregnancy outcome also assessed.A total 20,194 enrolled median gestational age 12.6 weeks (interquartile range, 11.6-13.9). confirmed 17,851 cases (88.4%): 13,043 (73.1%) low-risk 4808 (26.9%) high-risk aneuploidy. Overall, 133 diagnosed (100 trisomy 21; 18 18; 15 13). screen positive rate lower vs group (0.27% 2.2%; P<.0001). sensitivity specificity similar groups. predictive value low- groups 85.7% 97.5%; P=.058 50.0% 81.3%; P=.283 62.5% 83.3; P=.58 13, respectively. 602 (3.4%) patients no-call result after first draw 287 (1.61%) including second draw. higher than on (2.8% 0.7%; P=.001). showed rate.In aneuploidy, specificity, 74.3% 3 common trisomies. Patients receive an increased require additional investigation.