Prenatal cell‐free DNA screening for fetal aneuploidy in pregnant women at average or high risk: Results from a large US clinical laboratory

Abstract

BackgroundWe evaluated the performance of a cell‐free DNA (cfDNA) prenatal screening assay for trisomies 21, 18, and 13, and sex chromosome aneuploidies (SCAs) among a population of pregnant women that included both those at average and high risk.MethodsSpecimen collection, cfDNA extraction, massively parallel sequencing, and bioinformatics analysis were conducted per laboratory protocol. Assay results, concordance with pregnancy outcomes, and performance characteristics were evaluated.ResultsA total 75,658 specimens from 72,176 individual pregnant women were received. Technical reasons accounted for 288 (0.4% of all received samples) tests not performed. In the final analysis cohort (N = 69,794), 13% of pregnancies were considered at average risk and 87% at high risk. Mean gestational age at specimen collection was 15.1 weeks. Of the 69,794 unique pregnancies, 1,359 (1.9%) had positive test results. Among the results with confirmed outcomes, PPV for trisomies 21, 18, and 13 was 98.1%, 88.2%, and 59.3%, respectively; the PPV was 69.0% for SCAs and 75.0% for microdeletions. Overall, PPV was 87.2%, sensitivity was 97.9%, and specificity was 99.9%.ConclusionThis cfDNA prenatal screening assay provides highly accurate discrimination between affected and unaffected pregnancies among a population of pregnant women at average and high risk for fetal genetic abnormalities.