Natera Inc., Austin, TX.
Department of Obstetrics and Gynecology and Women's Health, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Genet Med. 2023 Aug;25(8):100879. doi: 10.1016/j.gim.2023.100879. Epub 2023 May 5.
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.
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.
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%.
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.
本研究旨在评估游离胎儿 DNA（cfDNA）筛查在具有遗传确认的未选择产科人群中检测性染色体非整倍体（SCAs）的性能。
这是一项多中心、前瞻性基于 SNP 的微缺失和非整倍体登记研究（SMART）的计划二次分析。纳入了接受常染色体非整倍体 cfDNA 结果且相关性染色体非整倍体具有确认遗传结果的患者。确定了 SCAs（包括单体 X [MX] 和性染色体三体：47,XXX；47,XXY；47,XYY）的筛查性能。还评估了 cfDNA 和遗传筛查在整倍体妊娠中的胎儿性别一致性。
共有 17538 例符合纳入标准。在 17297、10333 和 14486 例妊娠中分别确定了 cfDNA 对 MX、SCT 和胎儿性别的性能。cfDNA 对 MX 的敏感性、特异性和阳性预测值（PPV）分别为 83.3%、99.9%和 22.7%，联合 SCTs 的敏感性、特异性和阳性预测值分别为 70.4%、99.9%和 82.6%。cfDNA 预测胎儿性别的准确性为 100%。
cfDNA 筛查 SCAs 的性能与其他研究报告的性能相当。SCTs 的 PPV 与常染色体三体相似，而 MX 的 PPV 则明显较低。在整倍体妊娠中，cfDNA 和产后遗传筛查之间未观察到胎儿性别不一致。这些数据将有助于解释和咨询 cfDNA 对性染色体的结果。
