研究背景：唐氏综合症(Down's Syndrome)是一种因婴儿21号染色体异常而引起的疾病。目前如果需要明确诊断是否为妊娠唐氏综合症患儿，需要进行抽取胎儿血、羊水或胎盘绒毛进行检查，但是这些侵入性检查对胎儿和孕妇都有一定的危险。来自香港中文大学，英国伦敦国王学院医院（King's College Hospital），深圳华大基因的研究人员在前文（Maternal Plasma DNA Sequencing Reveals the Genome-Wide Genetic and Mutational Profile of the Fetus）的基础上，再次发文，提出可以通过给孕妇进行血液DNA检验筛查唐氏综合症风险，从而无需类似羊膜穿刺这样的侵入性检查。这一研究成果公布在2011年的《BMJ》杂志上。

研究成果：在最新的这篇文章中，这一研究团队仍然以双末端测序技术为基础，利用Illumina的GA升级版：Genome Analyzer II进行分析。

技术手段：血液DNA测序，生物信息学分析

研究意义：目前临床上使用的侵入性检查，对胎儿和孕妇都有一定的危险：胎儿流产、早产、宫内感染的风险约为1％-2%。目前采用血液检测的产检只是检测母体血清中甲型胎儿蛋白（AFP）和绒毛促进腺激素（HGG）的浓度，并不十分可靠。通过非侵入性的血液DNA检查，不仅避免了侵入性检查的风险，同时还提高了检查结果的准确性，研究人员相信这将最终成为临床使用的检验手段。

点评： 通过检测孕妇外周血中存在的“漂流”的胎儿DNA，进而实现产前诊断的低风险和高准确性。

参考文献： Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ 2011.342:c7401.

Abstract Objectives ：To validate the clinical efficacy and practical feasibility of massively parallel maternal plasma DNA sequencing to screen for fetal trisomy 21 among high risk pregnancies clinically indicated for amniocentesis or chorionic villus sampling.

Design ：Diagnostic accuracy validated against full karyotyping, using prospectively collected or archived maternal plasma samples. Setting：Prenatal diagnostic units in Hong Kong, United Kingdom, and the Netherlands. Participants ：753 pregnant women at high risk for fetal trisomy 21 who underwent definitive diagnosis by full karyotyping, of whom 86 had a fetus with trisomy 21. Intervention ：Multiplexed massively parallel sequencing of DNA molecules in maternal plasma according to two protocols with different levels of sample throughput: 2-plex and 8-plex sequencing.

Main outcome measures： Proportion of DNA molecules that originated from chromosome 21. A trisomy 21 fetus was diagnosed when the z score for the proportion of chromosome 21 DNA molecules was >3. Diagnostic sensitivity, specificity, positive predictive value, and negative predictive value were calculated for trisomy 21 detection. Results： Results were available from 753 pregnancies with the 8-plex sequencing protocol and from 314 pregnancies with the 2-plex protocol. The performance of the 2-plex protocol was superior to that of the 8-plex protocol. With the 2-plex protocol, trisomy 21 fetuses were detected at 100% sensitivity and 97.9% specificity, which resulted in a positive predictive value of 96.6% and negative predictive value of 100%. The 8-plex protocol detected 79.1% of the trisomy 21 fetuses and 98.9% specificity, giving a positive predictive value of 91.9% and negative predictive value of 96.9%.

Conclusion： Multiplexed maternal plasma DNA sequencing analysis could be used to rule out fetal trisomy 21 among high risk pregnancies. If referrals for amniocentesis or chorionic villus sampling were based on the sequencing test results, about 98% of the invasive diagnostic procedures could be avoided.