Abstract：
The diagnostic accuracy of cell-free fetal DNA in screening for rare autosomal trisomies is uncertain. We conducted a systematic review and meta-analysis aiming to determine the predictive value of cell-free DNA in screening for rare autosomal trisomies.
PubMed, Embase, and Web of Science were searched from inception to January 2022.
All studies that reported on the diagnostic accuracy of cell-free DNA in the detection of rare autosomal trisomies were included. Case series were included if they contained at least 10 cases with diagnostic test results or postnatal genetic testing.
Study appraisal was completed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Statistical analysis was performed using random-effects meta-analysis of double-arcsine transformed proportions of confirmed results in the fetus out of the positive tests to obtain a pooled estimate of the positive predictive value.
The search identified 7553 studies, of which 1852 were duplicates. After screening 5701 titles and abstracts, 380 studies proceeded to the full-text screen; 206 articles were retrieved for data extraction, of which another 175 articles were excluded. A total of 31 studies, with a total of 1703 women were included for analysis. The pooled positive predictive value of cell-free DNA for the diagnosis of rare autosomal trisomies was 11.46% (95% confidence interval, 7.80-15.65). Statistical heterogeneity was high (I2=82%). Sensitivity analysis restricted to 5 studies at low risk of bias demonstrated a pooled positive predictive value of 9.13% (95% confidence interval, 2.49-18.76). There were insufficient data to provide accurate ascertainment of sensitivity and specificity because most studies only offered confirmatory tests to women with high-risk results.
The positive predictive value of cell-free DNA in diagnosing rare autosomal trisomies is approximately 11%. Clinicians should provide this information when offering cell-free DNA for screening of conditions outside of common autosomal trisomies.
PubMed, Embase, and Web of Science were searched from inception to January 2022.
All studies that reported on the diagnostic accuracy of cell-free DNA in the detection of rare autosomal trisomies were included. Case series were included if they contained at least 10 cases with diagnostic test results or postnatal genetic testing.
Study appraisal was completed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Statistical analysis was performed using random-effects meta-analysis of double-arcsine transformed proportions of confirmed results in the fetus out of the positive tests to obtain a pooled estimate of the positive predictive value.
The search identified 7553 studies, of which 1852 were duplicates. After screening 5701 titles and abstracts, 380 studies proceeded to the full-text screen; 206 articles were retrieved for data extraction, of which another 175 articles were excluded. A total of 31 studies, with a total of 1703 women were included for analysis. The pooled positive predictive value of cell-free DNA for the diagnosis of rare autosomal trisomies was 11.46% (95% confidence interval, 7.80-15.65). Statistical heterogeneity was high (I2=82%). Sensitivity analysis restricted to 5 studies at low risk of bias demonstrated a pooled positive predictive value of 9.13% (95% confidence interval, 2.49-18.76). There were insufficient data to provide accurate ascertainment of sensitivity and specificity because most studies only offered confirmatory tests to women with high-risk results.
The positive predictive value of cell-free DNA in diagnosing rare autosomal trisomies is approximately 11%. Clinicians should provide this information when offering cell-free DNA for screening of conditions outside of common autosomal trisomies.
摘要：
无细胞胎儿DNA在筛选罕见常染色体三体中的诊断准确性尚不确定。我们进行了系统评价和荟萃分析，旨在确定无细胞DNA在筛选罕见常染色体三体中的预测价值。
PubMed,Embase,和WebofScience从成立到2022年1月进行了搜索。
包括所有报道了在检测罕见的常染色体三体中无细胞DNA的诊断准确性的研究。如果病例系列包含至少10例具有诊断测试结果或出生后基因检测的病例，则将其包括在内。
使用诊断准确性研究质量评估2（QUADAS-2）工具完成研究评估。使用阳性测试中胎儿中确认结果的双反正弦转换比例的随机效应荟萃分析进行统计分析，以获得阳性预测值的汇总估计。
搜索确定了7553项研究，其中1852年是重复的。筛选5701标题和摘要后，380项研究进入全文屏幕；检索到206篇文章进行数据提取，另有175篇文章被排除在外。共31项研究，共有1703名女性被纳入分析.对于罕见的常染色体三体的诊断，无细胞DNA的合并阳性预测值为11.46％（95％置信区间，7.80-15.65）。统计异质性高(I2=82%)。敏感性分析限制在低偏倚风险的5项研究中显示了9.13%的合并阳性预测值（95%置信区间，2.49-18.76).没有足够的数据来提供准确的敏感性和特异性的确定，因为大多数研究仅对具有高风险结果的女性提供验证性测试。
无细胞DNA在诊断罕见常染色体三体中的阳性预测值约为11％。临床医生在提供无细胞DNA以筛选常见常染色体三体以外的疾病时应提供此信息。
PubMed,
包括所有报道了在检测罕见的常染色体三体中无细胞DNA的诊断准确性的研究。
使用诊断准确性研究质量评估2（QUADAS-2）工具完成研究评估。
搜索确定了7553项研究，
无细胞DNA在诊断罕见常染色体三体中的阳性预测值约为11％。
