Non-Invasive Genetic Test for Down Syndrome and Edwards Syndrome Highly Accurate
New study published in American Journal of Obstetrics & Gynecology
Philadelphia, PA, June 5, 2012 – Current screening strategies for Down syndrome, caused by fetal trisomy 21 (T21), and Edwards syndrome, caused by fetal trisomy 18 (T18), have false positive rates of 2 to 3%, and false negative rates of 5% or higher. Positive screening results must be confirmed by amniocentesis or chorionic villus sampling, which carry a fetal loss rate of approximately 1 in 300 procedures. Now an international, multicenter cohort study finds that a genetic test to screen for trisomy 21 or 18 from a maternal blood sample is almost 100% accurate. The results of the study are published online in the American Journal of Obstetrics and Gynecology.
The trial evaluated a novel assay known as Digital Analysis of Selected Regions (DANSR) that analyzes fetal cell-free DNA, small DNA fragments which circulate in maternal blood. Unlike similar tests that analyze DNA from the entire genome, DANSR analyzes only the chromosomes under investigation for a more efficient and less expensive process. The results are evaluated with a novel analysis algorithm, the Fetal-fraction Optimized Risk of Trisomy Evaluation (FORTE), which considers age-related risks and the percentage of fetal DNA in the sample to provide an individualized risk score for trisomy detection.
A total of 4,002 pregnant women from the United States, the Netherlands, and Sweden were enrolled in the NICE (Non-Invasive Chromosomal Evaluation) study. The mean maternal age was 34.3 years and the cohort was racially and ethnically diverse. Blood samples were taken before the women underwent invasive testing for any indication, and 774 samples were excluded prior to analysis. Of the 3,228 samples that underwent analysis, 57 cases were excluded due to low fetal cfDNA in the sample and 91 samples were excluded due to failure of the assay. The classification of samples as High Risk or Low Risk using the DANSR and FORTE method was compared with the results from amniocentesis and CVS.
The DANSR and FORTE method identified 100% of the 81 T21 cases as High Risk, and there was one false positive among the 2,888 normal cases, for a false-positive rate of 0.03%. Of the 38 T18 cases, 37 were classified as High Risk and there were 2 false positives among the 2,888 normal cases, for a sensitivity of 97.4% and a false positive rate of 0.07%.
Prior studies of cfDNA have been case-control studies, comparing detection in subjects identified with T21 or T18, to a selected group of those with normal karyotypes. The current study included a large cohort of subjects undergoing invasive prenatal diagnosis. This allowed the researchers to assess the potential impact of other complex and unusual abnormalities on cfDNA test results. Overall, the presence of other chromosomal variants did not interfere with the detection of T21 or T18. While the study included primarily high-risk women, all women undergoing invasive prenatal diagnosis for any indication were eligible, so the cohort represents a broader population than reported in previous studies.
“The improvement in sequencing efficiency achieved by the DANSR platform provides a more affordable, scalable approach to cfDNA analysis with high throughput and potential for widespread clinical utility,” says lead investigator Mary E. Norton, MD, director of perinatal research, Lucile Packard Children’s Hospital at Stanford University. “Cell-free DNA offers high accuracy with a single blood test. It is potentially suitable as a replacement for current, relatively inefficient aneuploidy screening.”
# # #
Notes for editors
“Non-Invasive Chromosomal Evaluation (NICE) Study: Results of a Multicenter, Prospective Cohort Study for Detection of Fetal Trisomy 21 and Trisomy 18,” by M.E. Norton, H. Brar, J. Weiss, et al. (doi: 10.1016/j.ajog.2012.05.021). It is available online in advance of publication in American Journal of Obstetrics & Gynecology, published by Elsevier.
This study was financially supported by Ariosa Diagnostics.
Full text of the article is available to credentialed journalists upon request. Contact Francesca Costanzo at +1 215 239 3249or email@example.com to obtain a copy. Journalists wishing to schedule interviews with the authors should contact Traci Tournoux, HealthStar PR, at +1 646 722 8830 or firstname.lastname@example.org.
About the American Journal of Obstetrics & Gynecology
The American Journal of Obstetrics & Gynecology ( www.AJOG.org), known as “The Gray Journal,” presents coverage of the entire spectrum of the field, from the newest diagnostic procedures to leading-edge research. The Journal provides comprehensive coverage of the specialty, including maternal-fetal medicine, reproductive endocrinology/infertility, and gynecologic oncology. It also publishes the annual meeting papers of several of its 7 sponsoring societies, including the Society for Maternal-Fetal Medicine and the Society of Gynecologic Surgeons.
The American Journal of Obstetrics & Gynecology's 2010 Impact Factor is 3.313. It is ranked 8th out of 75 and continues to be ranked #1 in citations in the Obstetrics & Gynecology category, according to the latest Journal Citation Reports® 2011, published by Thomson Reuters. The Journal’s standard of excellence and continued success can be attributed to the strong leadership of Editors-in-Chief Thomas J. Garite, MD, and Moon H. Kim, MD, and their outstanding nationally and internationally recognized editorial board and reviewers. The journal has also been recognized as one of the 100 most influential journals in Biology & Medicine over the last 100 years, as determined by the BioMedical & Life Sciences Division of the Special Libraries Association (2009).
Elsevier is a world-leading provider of information solutions that enhance the performance of science, health, and technology professionals, empowering them to make better decisions, deliver better care, and sometimes make groundbreaking discoveries that advance the boundaries of knowledge and human progress. Elsevier provides web-based, digital solutions — among them ScienceDirect, Scopus, Elsevier Research Intelligence,and ClinicalKey—and publishes over 2,200 journals, including The Lancet and Cell, and over 25,000 book titles, including a number of iconic reference works.
The company is part of Reed Elsevier Group PLC, a world leading provider of professional information solutions in the Science, Medical, Legal and Risk and Business sectors, which is jointly owned by Reed Elsevier PLC and Reed Elsevier NV. The ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).
+1 215 239 3249