Performance of prenatal cfDNA screening for sex chromosomes
Document Type
Journal Article
Publication Date
5-5-2023
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
DOI
10.1016/j.gim.2023.100879
Keywords
Cell-free DNA; Fetal sex; Monosomy X; Sex chromosome aneuploidies; Sex chromosome trisomies
Abstract
PURPOSE: To assess the performance of cell-free DNA (cfDNA) screening to detect sex chromosome aneuploidies (SCA) in an unselected obstetrical population with genetic confirmation. METHODS: This was a planned secondary analysis of the multicenter, prospective SMART study. Patients receiving cfDNA results for autosomal aneuploidies and who had confirmatory genetic results for the relevant sex chromosomal aneuploidies were included. Screening performance for SCAs, including monosomy X (MX) and the sex chromosome trisomies (SCTs; 47,XXX; 47,XXY; 47,XYY) was determined. Fetal sex concordance between cfDNA and genetic screening was also evaluated in euploid pregnancies. RESULTS: 17,538 cases met inclusion criteria. Performance of cfDNA for MX, SCTs and fetal sex was determined in 17,297, 10,333 and 14,486 pregnancies, respectively. Sensitivity, specificity, and PPV of cfDNA were 83.3%, 99.9%, and 22.7% for MX, and 70.4%, 99.9%, and 82.6% for the combined SCTs. The accuracy of fetal sex prediction by cfDNA was 100%. CONCLUSION: Screening performance of cfDNA for SCAs is comparable to that reported in other studies. The PPV for the SCTs was similar to the autosomal trisomies, while the PPV for MX was substantially lower. No discordance in fetal sex was observed between cfDNA and postnatal genetic screening in euploid pregnancies. These data will assist interpretation and counseling for cfDNA results for sex chromosomes.
APA Citation
Martin, Kimberly; Dar, Pe'er; MacPherson, Cora; Egbert, Melissa; Demko, Zachary; Parmar, Sheetal; Hashimoto, Katelyn; Haeri, Sina; Malone, Fergal; Wapner, Ronald J.; Roman, Ashley S.; Khalil, Asma; Faro, Revital; Madankumar, Rajeevi; Strong, Noel; Silver, Robert M.; Vohra, Nidhi; Hyett, Jon; Rabinowitz, Matt; Kao, Charlly; Hakonarson, Hakon; Jacobsson, Bo; and Norton, Mary E., "Performance of prenatal cfDNA screening for sex chromosomes" (2023). GW Authored Works. Paper 2938.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2938
Department
Epidemiology

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