Down Syndrome and Edwards Syndrome Noninvasive Genetic Tests Highly Accurate
An international study finds that a genetic test of mom's blood is almost 100% accurate to screen for trisomy 21 or 18
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. But, a new international trial has conducted assays of maternal blood and able to accurately screen for both syndromes with 100% accuracy.
The results of the study are published online in the American Journal of Obstetrics and Gynecology.
The trial evaluated a new assay known as Digital Analysis of Selected Regions (DANSR) that analyzes small DNA fragments circulating in maternal blood.
Unlike similar tests that analyze DNA from the entire genome, DANSR analyzes only targeted chromosomes. A more efficient and less expensive process. The results were analyzed with a new algorithm, the Fetal-fraction Optimized Risk of Trisomy Evaluation (FORTE), comparing age-related risk with the percentage of fetal DNA in the sample, and provided an individual risk score for either syndrome.
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 women underwent invasive testing.
The DANSR and FORTE method identified 100% of the 81 T21 cases as High Risk, with 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 false positive rate of 0.07%.
Prior studies of cell-free DNA or cfDNA, have compared subjects identified with T21 or T18, to a selected group of subjects with normal karyotypes. The current study included a large cohort of subjects undergoing invasive prenatal diagnosis, which allowed researchers to assess the potential impact of other complex and unusual abnormalities on cfDNA test results.
Overall, the presence of other chromosomal variations 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."
Original article: http://www.eurekalert.org/pub_releases/2012-06/ehs-ngt060512.php