236 Trends from over 85,000 genome-wide cell-free DNA tests

Abstract

Genome-wide cell-free DNA (cfDNA) screening has been clinically-available since 2015. Since that time, over 85,000 samples have been submitted for testing, spanning various versions of the laboratory assay. The current study analyzes testing trends from one assay version (AV) to the next. Maternal blood samples submitted for genome-wide cfDNA testing were subjected to DNA extraction, library preparation, and genome-wide massively parallel sequencing as previously described by Jensen et al. Sequencing data were analyzed using a novel algorithm to detect aneuploidies and other subchromosomal events as described by Lefkowitz et al. Retrospective analysis of 86,902 genome-wide cfDNA samples (47,981 samples from AV4 and 38,921 from AV5) was performed. The gestational age of samples stayed relatively consistent over time, with the majority (59%) of samples submitted during the first trimester, and only 4% during the third trimester. The indication for testing shifted from AV4 to AV5, with significantly fewer advanced maternal age (AMA) cases, and significantly more cases with “no known high risk indication”. The average maternal age decreased significantly between assay versions from 34.3 to 32.9 years. Turn-around time decreased significantly from 5.7 calendar days with AV4 to 3.4 calendar days with AV5. The overall positivity rate of the test was 4.8%, with a statistically significant decrease from AV4 to AV5 (4.9% to 4.6%). No significant difference in positive findings was seen over time, with 25% of abnormalities detected being unique to genome-wide screening, consistent from AV4 to AV5. Over 5 years of genome-wide cfDNA screening has seen a significant decrease in the average maternal age of patients tested, and an increase in testing of patients with no known high-risk indication. As the number of presumably average risk patients has increased, the positivity rate of testing has decreased, though the frequency of genome-specific findings has remained constant. Significant improvements in turnaround time have been seen from one assay version to the next.