TY - JOUR
T1 - Performance of prenatal cfDNA screening for sex chromosomes
AU - Martin, Kimberly
AU - Dar, Pe'er
AU - MacPherson, Cora
AU - Egbert, Melissa
AU - Demko, Zachary
AU - Parmar, Sheetal
AU - Hashimoto, Katelyn
AU - Haeri, Sina
AU - Malone, Fergal
AU - Wapner, Ronald J.
AU - Roman, Ashley S.
AU - Khalil, Asma
AU - Faro, Revital
AU - Madankumar, Rajeevi
AU - Strong, Noel
AU - Silver, Robert M.
AU - Vohra, Nidhi
AU - Hyett, Jon
AU - Rabinowitz, Matt
AU - Kao, Charlly
AU - Hakonarson, Hakon
AU - Jacobsson, Bo
AU - Norton, Mary E.
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/8
Y1 - 2023/8
N2 - Purpose: The aim of this study was to assess the performance of cell-free DNA (cfDNA) screening to detect sex chromosome aneuploidies (SCAs) in an unselected obstetrical population with genetic confirmation. Methods: This was a planned secondary analysis of the multicenter, prospective SNP-based Microdeletion and Aneuploidy RegisTry (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 (SCT: 47,XXX; 47,XXY; 47,XYY) was determined. Fetal sex concordance between cfDNA and genetic screening was also evaluated in euploid pregnancies. Results: A total of 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 positive predictive value (PPV) of cfDNA were 83.3%, 99.9%, and 22.7% for MX and 70.4%, 99.9%, and 82.6%, respectively, 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, whereas 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.
AB - Purpose: The aim of this study was to assess the performance of cell-free DNA (cfDNA) screening to detect sex chromosome aneuploidies (SCAs) in an unselected obstetrical population with genetic confirmation. Methods: This was a planned secondary analysis of the multicenter, prospective SNP-based Microdeletion and Aneuploidy RegisTry (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 (SCT: 47,XXX; 47,XXY; 47,XYY) was determined. Fetal sex concordance between cfDNA and genetic screening was also evaluated in euploid pregnancies. Results: A total of 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 positive predictive value (PPV) of cfDNA were 83.3%, 99.9%, and 22.7% for MX and 70.4%, 99.9%, and 82.6%, respectively, 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, whereas 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.
KW - Cell-free DNA
KW - Fetal sex
KW - Monosomy X
KW - Sex chromosome aneuploidies
KW - Sex chromosome trisomies
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U2 - 10.1016/j.gim.2023.100879
DO - 10.1016/j.gim.2023.100879
M3 - Article
C2 - 37154148
AN - SCOPUS:85162192896
SN - 1098-3600
VL - 25
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 8
M1 - 100879
ER -