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."
Francesca Costanzo | EurekAlert!
During HIV infection, antibody can block B cells from fighting pathogens
14.08.2018 | NIH/National Institute of Allergy and Infectious Diseases
First study on physical properties of giant cancer cells may inform new treatments
14.08.2018 | Brown University
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur
What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...
The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.
Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...
08.08.2018 | Event News
27.07.2018 | Event News
25.07.2018 | Event News
14.08.2018 | Information Technology
14.08.2018 | Life Sciences
14.08.2018 | Life Sciences