VP29.06: Cell‐free DNA screening for fetal aneuploidy by targeted method based on microarray quantitation as primary test in the average risk population: results from a single European laboratory

Abstract

Evaluation of the clinical performance in a single clinical laboratory of a cell-free DNA (cfDNA) screening based on targeted cfDNA analysis with microarray quantitation for Trisomies 21,18, and 13, and sex chromosome aneuploidies (SCAs) applied in a population of women at average risk. Targeted cfDNA analysis using DANSR™ and FORTE™ with microarray quantitation were conducted following the protocol described by Juneau et al (2014). Test results, positive predictive values and performance characteristics were evaluated. A total 14,289 samples were analysed. The indication was maternal choice (<35y) or advanced maternal age (>35y) in 96% and increased risk after first trimester combined test in 1.8%. Mean gestational age at specimen collection and maternal BMI were 12.6 weeks and 22.6, respectively. 97.2% were singleton pregnancies. No result rate at first draw was 3.5% and at second blood draw was 0.68%. Of the 14,190 samples with a result, 116 (0.82%) had a positive result for T21, 18, 13. A confirmatory invasive procedure was undertaken in 88 (76%). PPV for T21, T18 and T13 was 97%, 86%, and 50%, respectively. Of the 10,444 and 944 pregnancies requesting the risk assessment for all SCAs or MX only, 1.01% (n = 106) and 0.95% (n = 9) were partially not-informative for these chromosome targets, respectively. Of the samples with a result for all SCAs (n = 10338) or MX only (n = 11273), 41 (0.4%) and 6 (0.05%) had a positive result, respectively. Among cases that underwent a diagnostic confirmation (26;55.3%), PPV for MX, XXX, XXY and XYY was 50%, 33.3%, 45.5% and 100%, respectively. This targeted cfDNA prenatal screening based on microarray quantitation used in a regional laboratory as primary test in a population of pregnant women at average risk for fetal genetic abnormalities provides highly accurate discrimination between affected and unaffected pregnancies and low false positive rate.