游离胎儿DNA检测流产女性染色体异常的准确性：系统评价与荟萃分析

Accuracy of cell-free fetal DNA in detecting chromosomal anomalies in women experiencing miscarriage: systematic review and meta-analysis.

作者信息

Della Valle L, Piergianni M, Khalil A, Rizzo G, Mappa I, Matarrelli B, Lucidi A, Manzoli L, Flacco M E, Stuppia L, D'Antonio F

机构信息

Center for Fetal Care and High-Risk Pregnancy, University of Chieti, Chieti, Italy.

Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust, University of London, London, UK.

出版信息

Ultrasound Obstet Gynecol. 2025 Jan;65(1):13-19. doi: 10.1002/uog.29131. Epub 2024 Dec 7.

DOI:10.1002/uog.29131

PMID:39644510

Abstract

OBJECTIVE

To report the diagnostic accuracy of cell-free fetal DNA (cfDNA) in detecting fetal chromosomal anomalies in women experiencing miscarriage.

METHODS

PubMed, MEDLINE, EMBASE and Cochrane databases were searched from inception to June 2024. The inclusion criteria were women experiencing miscarriage (defined as pregnancy loss before 20 weeks of gestation) who underwent cfDNA screening for trisomies 21, 18 and 13, other autosomal aneuploidies, sex-chromosome aneuploidies and/or copy-number variants (CNVs). The index test was cfDNA screening for each of the chromosomal anomalies listed. The reference standard was cytogenetic analysis of pregnancy tissue. The quality of the studies was assessed using the revised tool for the quality assessment of diagnostic accuracy studies. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were computed using the hierarchical summary receiver-operating-characteristics model.

RESULTS

Seven studies (887 women) were included in the systematic review and meta-analysis. cfDNA had a sensitivity and specificity of 100% (95% CI, 81.5-100%) and 100% (95% CI, 99.1-100%), respectively, for trisomy 21, 100% (95% CI, 54.1-100%) and 100% (95% CI, 99.0-100%), respectively, for trisomy 18, and 88.9% (95% CI, 51.8-99.7%) and 100% (95% CI, 99.1-100%), respectively, for trisomy 13. The respective values for other autosomal trisomies were 75.8% (95% CI, 65.7-84.2%) and 99.4% (95% CI, 97.9-99.9%), while those for CNVs were 60.0% (95% CI, 14.7-94.7%) and 100% (95% CI, 97.4-100%). Failure of cfDNA testing was reported in 7.3% (95% CI, 5.7-9.2%) of cases.

CONCLUSION

cfDNA has high diagnostic accuracy in detecting fetal trisomies 21, 18 and 13 in women experiencing miscarriage, while its accuracy for other autosomal aneuploidies and CNVs is only moderate. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

摘要

目的

报告游离胎儿DNA（cfDNA）检测流产女性胎儿染色体异常的诊断准确性。

方法

检索PubMed、MEDLINE、EMBASE和Cochrane数据库，检索时间从建库至2024年6月。纳入标准为经历流产（定义为妊娠20周前妊娠丢失）且接受cfDNA筛查21-三体、18-三体和13-三体、其他常染色体非整倍体、性染色体非整倍体和/或拷贝数变异（CNV）的女性。索引检测为对所列每种染色体异常进行cfDNA筛查。参考标准为妊娠组织的细胞遗传学分析。使用修订后的诊断准确性研究质量评估工具评估研究质量。使用分层汇总接受者操作特征模型计算敏感性、特异性、阳性和阴性似然比以及诊断比值比的汇总估计值。

结果

7项研究（887名女性）纳入系统评价和荟萃分析。cfDNA检测21-三体的敏感性和特异性分别为100%（95%CI，81.5%-100%）和100%（95%CI，99.1%-100%）；检测18-三体的敏感性和特异性分别为100%（95%CI，54.1%-100%）和100%（95%CI，99.0%-100%）；检测13-三体的敏感性和特异性分别为88.9%（95%CI，51.8%-99.7%）和100%（95%CI，99.1%-100%）。其他常染色体三体的相应值分别为75.8%（95%CI，65.7%-84.2%）和99.4%（95%CI，97.9%-99.9%），而CNV的相应值分别为60.0%（95%CI，14.7%-94.7%）和100%（95%CI，97.4%-100%）。7.3%（95%CI，5.7%-9.2%）的病例报告cfDNA检测失败。