相关研究结果发表在四月一日的《新英格兰医学杂志》（New
England Journal of Medicine）。当相同的孕妇接受标准筛查时，38个胎儿当中有30个被标记为患有唐氏综合征。筛查包括抽血、对染色体缺陷相关激素和蛋白质进行鉴定、连同在颈部后面颈褶液的超声波，如果其中一项超标则暗示有唐氏综合征。
Cell-free DNA Analysis for Noninvasive Examination of Trisomy
Background Cell-free DNA (cfDNA) testing
for fetal trisomy is highly effective among high-risk women. However, there
have been few direct, well-powered studies comparing cfDNA testing with
standard screening during the first trimester in routine prenatal populations.
Methods In this prospective, multicenter, blinded study conducted at 35
international centers, we assigned pregnant women presenting for aneuploidy
screening at 10 to 14 weeks of gestation to undergo both standard screening
(with measurement of nuchal translucency and biochemical analytes) and cfDNA
testing. Participants received the results of standard screening; the results
of cfDNA testing were blinded. Determination of the birth outcome was based on
diagnostic genetic testing or newborn examination. The primary outcome was the
area under the receiver-operating-characteristic curve (AUC) for trisomy 21
(Down's syndrome) with cfDNA testing versus standard screening. We also
evaluated cfDNA testing and standard screening to assess the risk of trisomies
18 and 13. Results Of 18,955 women who were enrolled, results from 15,841 were
available for analysis. The mean maternal age was 30.7 years, and the mean
gestational age at testing was 12.5 weeks. The AUC for trisomy 21 was 0.999 for
cfDNA testing and 0.958 for standard screening (P=0.001). Trisomy 21 was
detected in 38 of 38 women (100%; 95% confidence interval [CI], 90.7 to 100) in
the cfDNA-testing group, as compared with 30 of 38 women (78.9%; 95% CI, 62.7
to 90.4) in the standard-screening group (P=0.008). False positive rates were
0.06% (95% CI, 0.03 to 0.11) in the cfDNA group and 5.4% (95% CI, 5.1 to 5.8)
in the standard-screening group (P<0.001). The positive predictive value for
cfDNA testing was 80.9% (95% CI, 66.7 to 90.9), as compared with 3.4% (95% CI,
2.3 to 4.8) for standard screening (P<0.001). Conclusions In this large,
routine prenatal-screening population, cfDNA testing for trisomy 21 had higher
sensitivity, a lower false positive rate, and higher positive predictive value
than did standard screening with the measurement of nuchal translucency and
biochemical analytes.
NEJM发布更精确的唐氏筛查法
发布时间：2015-04-09 00:00 文章来源： 作者：
最近，加州大学旧金山分校（UCSF）研究人员提出了一种新方法，在妊娠10到14周之间进行血液测试，可比标准非侵入式筛查技术更加有效地诊断唐氏综合征和其他两种不常见的染色体异常。
这项研究随访了近16,000名孕妇的妊娠结局，用无细胞DNA血液测试，正确识别出所有患有唐氏综合征的胎儿（38名），唐氏综合症是一种与认知障碍相关的疾病，可增加几种疾病风险。研究人员通过新生儿检查、产前或产后遗传分析，证实了这些诊断结果。
本研究重点在于漂浮在孕妇血液中的小部分胎儿DNA。用一种分子“复印”技术（称为聚合酶链反应）扩增DNA并进行测序，这样可以比较每个染色体的DNA之间的相对量。更大数量的DNA是一些染色体疾病的标示，包括唐氏综合症，是由染色体异常（多了一条21号染色体）而导致的疾病。
相关研究结果发表在四月一日的《新英格兰医学杂志》（New England Journal of Medicine）。当相同的孕妇接受标准筛查时，38个胎儿当中有30个被标记为患有唐氏综合征。筛查包括抽血、对染色体缺陷相关激素和蛋白质进行鉴定、连同在颈部后面颈褶液的超声波，如果其中一项超标则暗示有唐氏综合征。
孕女的平均年龄为30岁，约四分之一超过35岁，这些女性在传统上被认为具有高风险，并为他们提供产前侵入性检测，如羊膜穿刺术。
本文第一作者、UCSF临床妇产科学教授Mary Norton介绍，无细胞DNA分析第二个引人注目的优势是，唐氏综合征的误诊发生率相对较低。而标准筛查法被公认可导致大量假阳性，利用无细胞DNA工具，假阳性则少很多。用这种新方法只有有九次误报，而用标准筛查法则有854次误报。
同时，研究人员在受试人群中发现了其他两种不常见的染色体异常病例，无DNA筛查的准确性仍然超过了其他标准筛查方法。在10例18三体综合征（也被称为爱德华兹综合征）中，无细胞DNA技术确定了九例，有一次假阳性。采用标准筛查方法，共鉴定出八例，有49次假阳性。对于13三体综合征（又称为三体综合征），无细胞DNA检验鉴定了两例，并标记一次假阳性，而标准筛查法只鉴定了一例，标记28次假阳性。
虽然这些研究结果表明，无细胞DNA筛查优于标准程序，但该研究强调了需要注意的地方。“标准筛选”可以确定一系列广泛的异常，用无细胞DNA筛查检测不到。唐氏综合征的病例包括超过50%的非整倍体（由染色体数目异常所致）。
此外，在488名孕妇中存在异常高数量的非整倍体，她们的血浆样品不合格，因为所含胎儿DNA的数量不足或无法估量，或检测失败或高测序方差，这会导致结果难以解释。这些胎儿中约有2.7%的胎儿染色体异常，包括那些用无细胞DNA技术没有被发现的异常。这明显高于总体组的0.4患病率。因为研究包括了这一不合格队列，无细胞DNA筛查工具的检出率都较低。
Norton博士说，使用无细胞DNA测试将比目前的筛查方法有更少的假阳性，从而减少侵入性检查和所致流产的次数。然而，她补充说，患者应该意识到这种技术的局限性。
“提供商需要适应病人的喜好，告诉他们产前筛查和诊断测试选择的差异。选择无细胞DNA测试的这些女性都应该被告知，这种技术对唐氏综合征是非常准确的，但它集中在一小部分的染色体异常，并不能不提供其他方法所提供的综合评价。”
“咨询还应包括关于测试失败相关风险的信息，如果没得到结果，采用侵入式检测的优点和缺点。”
原文摘要：
Cell-free DNA Analysis for Noninvasive Examination of Trisomy
Background Cell-free DNA (cfDNA) testing for fetal trisomy is highly effective among high-risk women. However, there have been few direct, well-powered studies comparing cfDNA testing with standard screening during the first trimester in routine prenatal populations. Methods In this prospective, multicenter, blinded study conducted at 35 international centers, we assigned pregnant women presenting for aneuploidy screening at 10 to 14 weeks of gestation to undergo both standard screening (with measurement of nuchal translucency and biochemical analytes) and cfDNA testing. Participants received the results of standard screening; the results of cfDNA testing were blinded. Determination of the birth outcome was based on diagnostic genetic testing or newborn examination. The primary outcome was the area under the receiver-operating-characteristic curve (AUC) for trisomy 21 (Down's syndrome) with cfDNA testing versus standard screening. We also evaluated cfDNA testing and standard screening to assess the risk of trisomies 18 and 13. Results Of 18,955 women who were enrolled, results from 15,841 were available for analysis. The mean maternal age was 30.7 years, and the mean gestational age at testing was 12.5 weeks. The AUC for trisomy 21 was 0.999 for cfDNA testing and 0.958 for standard screening (P=0.001). Trisomy 21 was detected in 38 of 38 women (100%; 95% confidence interval [CI], 90.7 to 100) in the cfDNA-testing group, as compared with 30 of 38 women (78.9%; 95% CI, 62.7 to 90.4) in the standard-screening group (P=0.008). False positive rates were 0.06% (95% CI, 0.03 to 0.11) in the cfDNA group and 5.4% (95% CI, 5.1 to 5.8) in the standard-screening group (P<0.001). The positive predictive value for cfDNA testing was 80.9% (95% CI, 66.7 to 90.9), as compared with 3.4% (95% CI, 2.3 to 4.8) for standard screening (P<0.001). Conclusions In this large, routine prenatal-screening population, cfDNA testing for trisomy 21 had higher sensitivity, a lower false positive rate, and higher positive predictive value than did standard screening with the measurement of nuchal translucency and biochemical analytes.
（来源：Medical Research）
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