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三体无创检查的无细胞DNA分析
Cell-free DNA Analysis for Noninvasive Examination of Trisomy


Mary E. Norton ... 围产医学和儿科 • 2015.04.23

摘要


背景

无细胞DNA(cfDNA)检测胎儿三体性在高风险妇女中非常有效。然而,对于常规产前人群孕期初3个月,却很少有对cfDNA检测与标准筛查进行比较的直接而且效能充足的研究。

 

方法

本项前瞻性多中心盲法研究在35个国际中心进行,我们选派妊娠10~14周时进行非整倍体筛查的孕妇进行标准筛查(测量颈后透明带和生化分析物)和cfDNA检测。参与者收到了标准筛查的结果,而cfDNA检测结果则盲化了。基于诊断性基因检测或新生儿检查确定出生结局。主要结局为用cfDNA检测vs.标准筛查21三体综合征(唐氏综合征)的受试者工作特征曲线 (ROC)的曲线下面积 (AUC)。我们还用cfDNA检测和标准筛查对18三体和13三体风险评估方面进行了评价。

 

结果

在纳入的18,955例女性中,15,841例的结果可供分析。孕产妇平均年龄为30.7岁,试验时平均孕龄为12.5周。cfDNA和标准筛查对21三体的AUC分别为0.999和0.958(P=0.001)。cfDNA检测组中,38例存在21三体妊娠的女性中,38例全部检出(100%;95%置信区间[CI],90.7~100),标准筛查组中,38例21三体妊娠女性中检出30例(78.9%;95% CI,62.7~90.4)(P=0.008)。cfDNA组假阳性率为0.06%(95% CI,0.03~0.11),标准筛查组假阳性率为5.4%(95% CI,5.1~5.8)(P<0.001)。cfDNA测试的阳性预测值为80.9%(95% CI,66.7~90.9),而标准筛查组的阳性预测值为3.4%(95% CI,2.3~4.8)(P<0.001)。

 

结论

大规模常规产前筛查人群中,与标准筛查(测量颈后透明带和生化分析物)相比,采用cfDNA检测21三体的敏感性较高,假阳性率较低,且阳性预测值较高(由Ariosa Diagnostics和Perinatal Quality Foundation提供金资助;NEXT ClinicalTrials.gov编号:NCT01511458)。





作者信息

Mary E. Norton, M.D., Bo Jacobsson, M.D., Ph.D., Geeta K. Swamy, M.D., Louise C. Laurent, M.D., Ph.D., Angela C. Ranzini, M.D., Herb Brar, M.D., Mark W. Tomlinson, M.D., Leonardo Pereira, M.D., M.C.R., Jean L. Spitz, M.P.H., Desiree Hollemon, M.S.N., M.P.H., Howard Cuckle, D.Phil., M.B.A., Thomas J. Musci, M.D., and Ronald J. Wapner, M.D.
From the University of California, San Francisco, San Francisco (M.E.N.), University of California, San Diego, San Diego (L.C.L.), Perinatal Diagnostic Center, Riverside (H.B.), and Ariosa Diagnostics, San Jose (D.H., T.J.M.) — all in California; Sahlgrenska University Hospital, Gothenburg, Sweden (B.J.); Duke University, Durham, NC (G.K.S.); Saint Peter's University Hospital, New Brunswick, NJ (A.C.R.); Northwest Perinatal Center (M.W.T.) and Oregon Health and Science University (L.P.) — both in Portland; Perinatal Quality Foundation, Oklahoma City (J.L.S.); and Columbia University, New York (H.C., R.J.W.). Address reprint requests to Dr. Norton at the Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, 550 16th St., 7th Fl., San Francisco, CA 94143, or at mary.norton@ucsf.edu.

 

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