Performance of prenatal cfDNA screening for sex chromosomes

• DOI: 10.1016/j.gim.2023.100879
• Publication Date: 2023-05-05T20:52:04Z
• Authors: Kimberly Martin; Pe’er Dar; Cora MacPherson; Melissa Egbert; Zachary Demko; Sheetal Parmar; Katelyn Hashimoto; Sina Haeri; Fergal Malone; Ronald J. Wapner; Ashley S. Roman; Asma Khalil; Revital Faro; Rajeevi Madankumar; Noel Strong; Robert M. Silver; Nidhi Vohra; Jon Hyett; Matt Rabinowitz; Charlly Kao; Hakon Hakonarson; Bo Jacobsson; Mary E. Norton
• Keywords: Concordance; Cell-free fetal DNA; Monosomy; Klinefelter syndrome; Trisomy

PurposeThe aim of this study was to assess the performance cell-free DNA (cfDNA) screening detect sex chromosome aneuploidies (SCAs) in an unselected obstetrical population with genetic confirmation.MethodsThis a planned secondary analysis multicenter, prospective SNP-based Microdeletion and Aneuploidy RegisTry (SMART) study. Patients receiving cfDNA results for autosomal who had confirmatory relevant chromosomal were included. Screening SCAs, including monosomy X (MX) trisomies (SCT: 47,XXX; 47,XXY; 47,XYY) determined. Fetal concordance between also evaluated euploid pregnancies.ResultsA total 17,538 cases met inclusion criteria. Performance MX, SCTs, fetal determined 17,297, 10,333, 14,486 pregnancies, respectively. Sensitivity, specificity, positive predictive value (PPV) 83.3%, 99.9%, 22.7% MX 70.4%, 82.6%, respectively, combined SCTs. The accuracy prediction by 100%.ConclusionScreening SCAs is comparable that reported other studies. PPV SCTs similar trisomies, whereas substantially lower. No discordance observed postnatal pregnancies. These data will assist interpretation counseling chromosomes.