Performance of prenatal cfDNA screening for sex chromosomes

K. Martin; P. Dar; C. MacPherson; M. Egbert; Z. Demko; S. Parmar; K. Hashimoto; S. Haeri; F. Malone; R. J. Wapner; A. S. Roman; A. Khalil; R. Faro; R. Madankumar; N. Strong; R. M. Silver; N. Vohra; Jon Hyett; M. Rabinowitz; C. Kao; H. Hakonarson; B. Jacobsson; M. E. Norton

Performance of prenatal cfDNA screening for sex chromosomes

K. Martin, P. Dar, C. MacPherson, M. Egbert, Z. Demko, S. Parmar, K. Hashimoto, S. Haeri, F. Malone, R. J. Wapner, A. S. Roman, A. Khalil, R. Faro, R. Madankumar, N. Strong, R. M. Silver, N. Vohra, Jon Hyett, M. Rabinowitz, C. KaoH. Hakonarson, B. Jacobsson, M. E. Norton

Western Sydney University

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

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.

Original language	English
Article number	100879
Number of pages	9
Journal	Genetics in Medicine
Volume	25
Issue number	8
Publication status	Published - Aug 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Open Access - Access Right Statement

Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Keywords

Monosomy X
Cell-free DNA
Sex chromosome trisomies
Sex chromosome aneuploidies
Fetal sex

Cite this

Martin, K., Dar, P., MacPherson, C., Egbert, M., Demko, Z., Parmar, S., Hashimoto, K., Haeri, S., Malone, F., Wapner, R. J., Roman, A. S., Khalil, A., Faro, R., Madankumar, R., Strong, N., Silver, R. M., Vohra, N., Hyett, J., Rabinowitz, M., ... Norton, M. E. (2023). Performance of prenatal cfDNA screening for sex chromosomes. Genetics in Medicine, 25(8), Article 100879.

@article{8968b65b953c421284bc6dd0edb71770,

title = "Performance of prenatal cfDNA screening for sex chromosomes",

abstract = "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.",

keywords = "Monosomy X, Cell-free DNA, Sex chromosome trisomies, Sex chromosome aneuploidies, Fetal sex",

author = "K. Martin and P. Dar and C. MacPherson and M. Egbert and Z. Demko and S. Parmar and K. Hashimoto and S. Haeri and F. Malone and Wapner, {R. J.} and Roman, {A. S.} and A. Khalil and R. Faro and R. Madankumar and N. Strong and Silver, {R. M.} and N. Vohra and Jon Hyett and M. Rabinowitz and C. Kao and H. Hakonarson and B. Jacobsson and Norton, {M. E.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = aug,

language = "English",

volume = "25",

journal = "Genetics in Medicine",

issn = "1098-3600",

publisher = "Elsevier B.V.",

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Martin, K, Dar, P, MacPherson, C, Egbert, M, Demko, Z, Parmar, S, Hashimoto, K, Haeri, S, Malone, F, Wapner, RJ, Roman, AS, Khalil, A, Faro, R, Madankumar, R, Strong, N, Silver, RM, Vohra, N, Hyett, J, Rabinowitz, M, Kao, C, Hakonarson, H, Jacobsson, B & Norton, ME 2023, 'Performance of prenatal cfDNA screening for sex chromosomes', Genetics in Medicine, vol. 25, no. 8, 100879.

TY - JOUR

T1 - Performance of prenatal cfDNA screening for sex chromosomes

AU - Martin, K.

AU - Dar, P.

AU - MacPherson, C.

AU - Egbert, M.

AU - Demko, Z.

AU - Parmar, S.

AU - Hashimoto, K.

AU - Haeri, S.

AU - Malone, F.

AU - Wapner, R. J.

AU - Roman, A. S.

AU - Khalil, A.

AU - Faro, R.

AU - Madankumar, R.

AU - Strong, N.

AU - Silver, R. M.

AU - Vohra, N.

AU - Hyett, Jon

AU - Rabinowitz, M.

AU - Kao, C.

AU - Hakonarson, H.

AU - Jacobsson, B.

AU - Norton, M. E.

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 - Monosomy X

KW - Cell-free DNA

KW - Sex chromosome trisomies

KW - Sex chromosome aneuploidies

KW - Fetal sex

UR - https://hdl.handle.net/1959.7/uws:78188

UR - http://www.scopus.com/inward/record.url?scp=85162192896&partnerID=8YFLogxK

M3 - Article

SN - 1098-3600

VL - 25

JO - Genetics in Medicine

JF - Genetics in Medicine

IS - 8

M1 - 100879

ER -

Performance of prenatal cfDNA screening for sex chromosomes

Abstract

Bibliographical note

Open Access - Access Right Statement

Keywords

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