目的:尽管无细胞DNA(cfDNA)筛查性染色体异常(SCAs)越来越多地用于临床实践,其诊断准确性和临床实用性尚不清楚.本系统综述和荟萃分析的目的是确定cfDNA在SCA检测中的性能。
方法:Medline/Pubmed,EMBASE,和WebofScience从开始到2022年1月进行了搜索,以查找与针对SCA的cfDNA筛选相关的文章。
方法:原创文章,随机对照试验,会议摘要,队列和病例对照研究,并考虑纳入超过10例确诊病例的病例系列。
方法:使用QUADAS-2工具对每个纳入的出版物进行质量评估。阳性预测值(PPV)计算为测试阳性并接受诊断测试的人中真实阳性病例的比例。合并敏感性和特异性,使用双变量模型,包括对高危和低危女性进行诊断确认的研究,生成了受试者-工作特征(ROC)总结曲线.
结果:搜索确定了7,553个结果。其中,380进行了全文筛选,其中94篇文章被纳入荟萃分析,共有1,531,240名女性进行了测试。所有研究都报告了确证基因测试。合并的PPV为49.4%(95%CI45.8-53.1)。X单体的合并PPV为32.0%(95%CI27-37.3%),XXY为67.6%(95%CI62.5-72.5%),XXX的57.5%(95%CI51.7-63.1%),XYY为70.9%(95%CI63.9-77.1%)。cfDNA对SCAs的合并敏感性和特异性分别为94.1%(95%CI90.8-96.3%)和99.5%(95%CI99.0-99.7%),分别,汇总ROC曲线下面积为0.934(95%CI0.907-0.989)。
结论:虽然cfDNA对SCAs的敏感性和特异性很高,PPV约为50%。对于具有多余Y染色体的SCA,PPV更高,和较低的单体X。临床医生应告知夫妇这些发现时,为SCA提供cfDNA。
Although cell-free DNA screening for sex chromosome abnormalities is increasingly used in clinical practice, its diagnostic accuracy and clinical utility remain unclear. This systematic
review and meta-analysis aimed to determine the performance of cell-free DNA in the detection of sex chromosome abnormalities.
Medline and PubMed, Embase, and Web of Science were searched from inception to January 2022 for articles relating to cell-free DNA screening for sex chromosome abnormalities.
Original articles, randomized control trials, conference abstracts, cohort and case-control studies, and case series with more than 10 cases with diagnostic confirmation were considered for inclusion.
Quality assessment of each included publication was performed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. The positive predictive value was calculated as the proportion of true positive cases among those who tested positive and underwent diagnostic testing. Sensitivity and specificity were pooled, and a summary receiver operating characteristic curve was produced using bivariate models that included studies that had diagnostic confirmation for high- and low-risk women.
The search identified 7553 results. Of these, 380 proceeded to the full-text screening, of which 94 articles were included in the meta-analysis with a total of 1,531,240 women tested. All studies reported a confirmatory genetic test. The pooled positive predictive value was 49.4% (95% confidence interval, 45.8-53.1). The pooled positive predictive value was 32.0% (95% confidence interval, 27.0%-37.3%) for monosomy X, 67.6% (95% confidence interval, 62.5%-72.5%) for XXY, 57.5% (95% confidence interval, 51.7%-63.1%) for XXX, and 70.9% (95% confidence interval, 63.9%-77.1%) for XYY. The pooled sensitivity and specificity of cell-free DNA for sex chromosome abnormalities were 94.1% (95% confidence interval, 90.8%-96.3%) and 99.5% (95% confidence interval, 99.0%-99.7%), respectively, with an area under the summary receiver operating characteristic curve of 0.934 (95% confidence interval, 0.907-0.989).
Although the sensitivity and specificity of cell-free DNA for sex chromosome abnormalities are high, the positive predictive value was approximately 50%. The positive predictive value was higher for sex chromosome abnormalities with a supernumerary Y chromosome and lower for monosomy X. Clinicians should inform couples about these findings when offering cell-free DNA for sex chromosome abnormalities.