目的:评估无细胞DNA(cfDNA)筛查的性能,以检测未经选择的产科人群中的性染色体非整倍体(SCA)。
方法:这是对多中心的计划二次分析,前瞻性SMART研究。包括接受常染色体非整倍体的cfDNA结果以及相关性染色体非整倍体的确证遗传结果的患者。SCA的筛选性能,确定了包括X(MX)和性染色体三体(SCT;47,XXX;47,XXY;47,XYY)。在整倍体妊娠中还评估了cfDNA与遗传筛查之间的胎儿性别一致性。
结果:17,538例符合纳入标准。MX的cfDNA性能,在17,297、10,333和14,486例怀孕中确定了SCT和胎儿性别,分别。灵敏度,特异性,cfDNA的PPV为83.3%,99.9%,MX为22.7%,70.4%,99.9%,合并的SCT为82.6%。cfDNA预测胎儿性别的准确率为100%。
结论:用于SCA的cfDNA的筛选性能与其他研究中报道的性能相当。SCT的PPV与常染色体三体相似,而MX的PPV则大大降低。在整倍体妊娠中,cfDNA与出生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性染色体的cfDNA结果。
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.