In our major prospective, blinded clinical study involving more than 60 leading U.S. medical research and teaching institutions, the verifi® test demonstrated high sensitivity and specificity for the detection of trisomies 21, 18, 13 test suggesting that it can be incorporated into existing aneuploidy screening algorithms to reduce unnecessary invasive procedures. The verifi® test results were compared to fetal karyotype by clinical cytogenetic analysis.
Optimal Detection of Fetal Chromosomal Abnormalities by Massively Parallel DNA Sequencing of Cell-Free Fetal DNA form Maternal Blood
Sehnert A et al. Clinical Chemistry. 2011 Jul; 57(7):1042-9.
Key Study Findings
- “Existing algorithms can detect T21, but have trouble detecting T18 and T13.
In this study, blood samples were collected from 1014 patients, DNA from 119 patients underwent massively parallel sequencing.”
- “Sequencing led to 100% correct classification of T21 and T18, and other chromosomal abnormalities.”
- “In conclusion, we have shown that massively parallel sequencing is capable of detecting multiple fetal chromosomal abnormalities from the plasma of pregnant women when the optimized algorithm for normalizing the chromosome counting is optimized.”
- “Our Verinata algorithms for quantification not only minimize random and systematic variation between sequencing runs but also allow for effective classification of aneuploidies across the entire genome, most notably T21 and T18.”
Genome-wide Fetal Aneuploidy Detection by Maternal Plasma DNA Sequencing
Bianchi D et al. Obstet Gynecol. 2012 May; 119(5.) Level of Evidence: II
Key Study Findings
- “This prospective study demonstrates the efficacy of massively parallel sequencing of maternal plasma DNA to detect fetal aneuploidy for multiple chromosomes across the genome. The high sensitivity and specificity for the detection of trisomies 21, 18, 13 and monosomy X suggest that massively parallel sequencing can be incorporated into existing aneuploidy screening algorithms to reduce unnecessary invasive procedures.”
- “In the early stages of clinical implementation, massively parallel sequencing for chromosomes 21, 18, and 13 should be used after a positive first trimester or second-trimester screening result.”
- “This will reduce unnecessary invasive procedures caused by the false-positive screening results, with a concomitant reduction in procedure related adverse events. Invasive procedures could be limited to confirmation of a positive result from sequencing. We acknowledge, however, that there are certain clinical scenarios (e.g., advanced maternal age and infertility) in which pregnant women will want to avoid an invasive procedure; they may request this test as an alternative to the primary screen or invasive procedure or both.”
In a theoretical population of 100,000 pregnant women, use of the verifi® test versus serum testing followed by amniocentesis results in an estimated 6,600 fewer false positives.
|Screen -||Screen +||True
|85% / 93%||~93,000||~7,000||~400||~6,600|
|100% / 100%||~99,600||~400||~0|
- Buckley F et al. Wrongful deaths and rightful lives — screening for Down Syndrome. Down Syndrome Research and Practice. 2008; 12(2):79:86.
- Theoretical scenario; sensitivity & specificity based on findings from Bianchi D et al. Genome-wide Fetal Aneuploidy Detection by Maternal Plasma DNA Sequencing. Obstet Gynecol. 2012 May; 119(5). Published ahead of print: