Illumina无创产前诊断Verifi可减少唐氏假阳性率10倍以上

莺歌燕舞

胎儿游离DNA：cell-free fetal DNA（cffDNA）

通过在多个监测中心进行的盲样测试，对1914名怀孕妇女做了检测，1909个样本中的21号染色体三体，Verifi只有6个假阳性，而传统方法是69例假阳性；18号染色体三体，Verifi只有3例假阳性，而传统方法是11例假阳性。

在此次对比试验中，Verifi方法和传统方法都分别找出了所有的21三体和18三体病例，也就是没有假阴性。

在同样假阴性率的前提下，更低的假阳性率可以让怀孕妇女少的接受有创的羊水才穿刺等手术，从而减少孕妇的痛苦，也减少不必的流产风险。

无创产前诊断背景资料

唐氏综合症是一种染色体疾病（21号染色三体综合症），养一个唐氏儿一辈子，生活消费至少要花1-2百万人民币。高通量测序无创检测胎儿是否患有唐氏综合症是先进手段，能够极大地减轻唐氏婴儿出生所造成的家庭痛基和社会负担。

检测原理

多出的21号染色体片段胎儿的DNA会部分释放到母体新的血液中，在3月龄的孕妇血液中约有5——10%的有力DNA是来自于胎儿， 如果胎儿是唐氏婴儿，那么母亲血液中的游离DNA中就会比怀正常胎儿的多约2.5~5%的21号染色体DNA片段。

高通量测序可以一次测几千万条、甚至几亿条DNA片段，所测得DNA片段的序列，经过与已知人类 基因组序列的比对，可以确定每条DNA片段来自于哪一条染色体。

数据统计、结果判断

正常情况下，人的21号染色体占全部染色体总长度的1.5%，孕妇血液中的21号染色体，正常情况下也是占全部染色体总长度的1.5%，如果孕妇怀的是唐氏婴儿，因为婴儿多出的一条21号染色体，那么孕妇血中的21号染色体DNA片段就会增加到1.5375%，比怀正常胎儿的，多了约0.0375%的21号染色体片段。如果用高通量测序测2500万条DNA片段，就可以让医生判断婴儿油99.9%以上的可能是唐氏婴儿。

优点

相对于羊水穿刺

羊水穿刺的判断准确性为100%，但羊水穿刺需做进入羊水包膜内的手术，有1%的流产可能性；

相对于测母血中的甲胎蛋白

甲胎蛋白方法是对婴儿无创的，但是甲胎蛋白的方法有1/3 的假阴性率。

[size=1em]Illumina’s Non-Invasive verifi® Prenatal Test Using cfDNA Significantly Reduces False Positive Rate of Fetal Aneuploidy Detection Compared to Current Standard Pregnancy Screening Practices

[size=1em] Study Results Published in New England Journal of Medicine Show the verifi&#174; Prenatal Test Achieves Positive Predictive Value Tenfold Higher Than Current Standard of Care SAN DIEGO--(BUSINESS WIRE)--Feb. 26, 2014-- Illumina, Inc. (NASDAQ: ILMN) today announced that in a direct comparison of non-invasive prenatal testing (NIPT) using cell free DNA (cfDNA) to standard prenatal aneuploidy screening in a general obstetrical population, the verifi&#174; prenatal test1 significantly reduced the rate of false positive results for the detection of fetal trisomies 21 and 18. In addition, the study demonstrated that the verifi&#174; prenatal test performs consistently well in all pregnant women, regardless of their risk level for fetal aneuploidy. The results of the study, entitled “DNA Sequencing versus Standard Prenatal Aneuploidy Screening,” are available online today in The New England Journal of Medicine and the full article can be accessed at www.verifitest.com/news-events. The paper will be included in the February 27, 2014 print edition. “The study reflects the diverse clinical screening practices and ethnic variation present throughout the United States, and effectively answers questions from the medical and scientific communities regarding the positive predictive value (PPV) of the verifi&#174; prenatal test in the general obstetric population,” said  Diana W. Bianchi, M.D., Executive Director of the Mother Infant Research Institute at Tufts Medical Center, and lead author of the publication. “In addition to the significant increase in PPV, the study shows similar fetal fraction distributions in both high- and low-risk pregnant women. Thus, from both a biological and technical perspective, the verifi&#174; prenatal test performs well in pregnant women of all risk levels.” The prospective, multi-center, blinded study analyzed samples from 1,914 pregnant women (mean age 29.6 years) at all risk levels for fetal chromosome abnormalities. The false positive rate for detection of trisomy 21 with the verifi&#174; prenatal test was significantly lower than conventional standard screening (6/1909, 0.3% vs. 69/1909, 3.6%, p<0.0001). For trisomy 18, the verifi&#174; prenatal test also demonstrated a lower false positive rate when compared to standard testing (3/1905, 0.2% vs. 11/1905, 0.6%, p=0.0325). Importantly, the study showed a tenfold improvement in the PPV for the verifi&#174; prenatal test (45.4%) when compared to standard screening for trisomy 21 (4.2%) and a fivefold improvement in PPV for trisomy 18 (40% vs. 8.3%). Both the verifi&#174; prenatal test and standard screening correctly detected all cases of trisomies 21 and 18. For all of the women enrolled in the study, pregnancy outcome and neonatal follow-up data were obtained, including physical examinations and karyotypes, if performed. “The results of this study demonstrate that the verifi&#174; prenatal test could significantly improve clinical practice by reducing the number of invasive procedures needed to clarify false positive results obtained with standard screening,” said  Richard Rava, Ph.D., Vice President, Research and Development for Reproductive and Genetic Health at Illumina. “In this study using the verifi&#174; prenatal test, we have shown a tenfold improvement in the PPV for trisomy 21 over conventional screening methods. Importantly, the performance of NIPT using cfDNA in a general obstetric population, representative of contemporary clinical practice in the US, is equivalent to previously demonstrated performance in high-risk pregnant women.” Illumina’s Reproductive and Genetic Health solutions use next-generation sequencing (NGS) technology and advanced microarrays to generate comprehensive, accurate genomic information to assist healthcare providers and patients in making informed decisions for their reproductive health and well-being. Illumina offers the non-invasive verifi&#174; prenatal test (formerly offered by Verinata Health, Inc.) in their CLIA-certified, CAP-accredited clinical services laboratory, to detect chromosome abnormalities and aberrations with improved resolution for consistent and dependable results. About Illumina Illumina (www.illumina.com) is a leading developer, manufacturer, and marketer of life science tools and integrated systems for the analysis of genetic variation and function. We provide innovative sequencing and array-based solutions for genotyping, copy number variation analysis, methylation studies, gene expression profiling, and low-multiplex analysis of DNA, RNA, and protein. We also provide tools and services that are fueling advances in consumer genomics and diagnostics. Our technology and products accelerate genetic analysis research and its application, paving the way for molecular medicine and ultimately transforming healthcare. Forward-Looking Statements This release may contain forward looking statements that involve risks and uncertainties. Important factors that could cause actual results to differ materially from those in any forward-looking statements are detailed in our filings with the Securities and Exchange Commission, including our most recent filings on Forms 10-K and 10-Q, or in information disclosed in public conference calls, the date and time of which are released beforehand. We do not intend to update any forward-looking statements after the date of this release. 1 The verifi&#174; prenatal test is a non-invasive blood test that analyzes DNA found in a pregnant woman’s blood to detect the most common fetal chromosome abnormalities, including Down syndrome (trisomy 21 or T21), Edwards syndrome (trisomy 18 or T18), Patau syndrome (trisomy 13 or T13) and sex chromosome abnormalities.