母血游离DNA大规模并行测序技术在唐氏综合征产前诊断中应用价值的Meta分析

The application of maternal serum free DNA by massively parallel sequencing technology in prenatal diagnosis of Down syndrome:a meta-analysis

目的 应用荟萃（Meta）分析的方法系统评价母血游离DNA大规模并行测序技术（massively parallel sequencing,MPS）在唐氏综合征（Down Syndrome,DS）产前诊断中的应用价值。方法 查找Pub Med、Cochrane Library、Web of knowledge（Medline、BIOSIS Previews、SCI）、EMBASE、中国生物医学文献数据库（CBM）、中国知网、万方、重庆维普等数据库。检索2000年至2013年12月,研究应用MPS技术检测母血游离DNA在唐氏综合征产前诊断中的应用类文章,运用Stata SE12.0和Meta-Disc1.4软件对文献进行定量综合评价。结果 共纳入文献15篇（其中英文12篇,中文3篇）,经异质性检验（I2=0.0%）,提示不存在异质性,采用固定效应模型合并检验统计量。灵敏度（sensitivity,SEN）合并=0.99（95%CI 0.98-1.00）;特异度（specificity,SPE）合并=1.00（95%CI 1.00-1.00）;阳性似然比（positive likelihood ratio,PLR）合并=267.52（95%CI 177.74-402.64）;阴性似然比（negative likelihood ratio,NLR）合并=0.01（95%CI 0.01-0.03）;SROC曲线下面积为0.9990。结论 利用MPS技术检测母血游离DNA对DS的产前诊断具有无创、高敏感性、高特异性等特点,具有重要的临床应用价值。

Objective： To evaluate the diagnostic value of maternal serum free DNA by massively parallel sequencing technology in prenatal diagnosis of Down syndrome by meta- analysis systematicly. Methods： The database of Pub Med, Cochrane Library, Web of knowledge （Medline, BIOSIS Previews, SCI） , EMBASE, Chinese Biomedical Literature Database （CBM） , CNKI （China National Knowledge Infrastructure） , Wang fang, VIP （VIP Database for Chinese Technical Periodicals） , Chongqing VIP were searched. To collect the articles that study the detection of maternal serum free DNA by MPS technology in the prenatal diagnosis of Down syndrome from 2000 to December 2013. The StataSE12.0 and Meta- Discl.4 software were used for the evaluation of the literatures quantitatively. Results： 15 articles were collected （ 12 Chinese and 5 English articles） . After the test of the Heterogeneity （I2=0.0%） , Prompts there was no heterogeneity, so the fixed-effect model was used to combine the test statistics. And the pooled sensitivity was 0.99 （95%CI 0.98- 1.00） , the pooled specificity was 1.00 （95%CI 1.00- 1.00） , the pooled positive likelihood ratio was 267.52 （95%CI 177.74-402.64） , the pooled negative likelihood ratio was 0.01 （95%CI 0.01-0.03） , and the area under the SROC curve （AUC） was 0.9990. Conclusions： The detection of maternal serum free DNA by MPS technology in the prenatal diagnosis of Down syndrome has characteristics of non- invasive, high sensitivity and high specificity, so it has a important value in the clinical application.