Noninvasive Genetic Test Screens for Fetal Trisomies

A noninvasive genetic test has been introduced that accurately screens for trisomy 21 or 18 from a maternal blood sample.

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.

Scientists at Lucile Packard Children's Hospital (Palo Alto, CA, USA) have carried out an international, multicenter cohort study to evaluate the genetic test. Pregnant women from the USA, the Netherlands, and Sweden were enrolled in the 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 cell-free DNA (cfDNA) in the sample and 91 samples were excluded due to failure of the assay. The method was compared with the results from amniocentesis and chorionic villus sampling (CVS).

The trial evaluated a novel assay known as Digital Analysis of Selected Regions (DANSR; Ariosa Diagnostics Inc., San Jose, CA, USA) that analyzes fetal cfDNA, which are small DNA fragments that 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.

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 two false positives among the 2,888 normal cases, for a sensitivity of 97.4% and a false positive rate of 0.07%. Overall, the presence of other chromosomal variants did not interfere with the detection of T21 or T18.

Mary E. Norton, MD, the senior author said, "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. Cell-free DNA offers high accuracy with a single blood test. It is potentially suitable as a replacement for current, relatively inefficient aneuploidy screening." The study was published on June 4, 2012, in the American Journal of Obstetrics and Gynecology.

Related Links:
Lucile Packard Children's Hospital
Ariosa Diagnostics Inc.