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Article|Articles in Press, 100879

Performance of prenatal cfDNA screening for sex chromosomes

Open AccessPublished:May 05, 2023DOI:https://doi.org/10.1016/j.gim.2023.100879
Performance of prenatal cfDNA screening for sex chromosomes
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      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.

      Keywords

      Article info

      Publication history

      Accepted: April 30, 2023
      Received in revised form: April 29, 2023
      Received: January 4, 2023

      Publication stage

      In Press Accepted Manuscript

      Footnotes

      Conflict of Interest

      All site principal investigators (P.D., B.J., F.M., R.W., A.R., A.K., R.F., R.M., S.H., R.S., N.V., J.H., C.M., and M.N.) received institutional research support from the funding sponsor (Natera). M.E., Z.D. and M.R. are employed by the study’s funding sponsor (Natera) and hold stock or options to hold stock. K.M. is a consultant to the funding sponsor (Natera) and holds stock and options to hold stock. J.H. has an ongoing research collaboration that includes financial support for biochemical analytes from Perkin Elmer, has earned honoraria and/or given talks that were not compensated from Natera, Roche and Canon, and has participated in Asian/Australasian expert consultancies for Natera and Roche. B.J. reports research clinical diagnostic trials with Ariosa (completed), Vanadis (completed), Natera (ongoing) and Hologic (completed) with expenditures institutional reimbursed per patient and no personal reimbursements; clinical probiotic studies with product provided by FukoPharma (ongoing, no funding) and BioGaia (ongoing; also provided a research grant for the specific study); coordination of scientific conferences and meetings with commercial partners as such as ESPBC 2016 and a Nordic educational meeting about NIPT and preeclampsia screening. B.J. collaborated in the IMPACT study where Roche, Perkin Elmer and Thermo Fisher provides reagents to PLGF analyses. R.J.W. receive research funding from NICHD and receive support from Illumina for research reagents. M.N. is a consultant to Invitae. All other authors report no conflicts of interest.

      Identification

      DOI: https://doi.org/10.1016/j.gim.2023.100879

      Copyright

      © 2023 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics.

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