Cell-free DNA Analysis for Noninvasive Examination of Trisomy

To the Editor: Norton et al. (April 23 issue) 1 report near-perfect accuracy of detection for trisomy 21 (Down’s syndrome) with the use of cell-free DNA (cfDNA) (sensitivity, 100% [38 of 38 cases of trisomy 21]; false positive rate, 0.06% [9 false positives among 15,841 women]) in the Noninvasive Examination of Trisomy (NEXT) study. These seemingly promising results may be misleading because they excluded 488 patients (3% of their sample) with indeterminate cfDNA results. The prevalence of aneuploidy was higher among these patients than in the overall cohort (2.7% vs. 0.4%); thus, their exclusion may introduce bias. 2 Estimates of accuracy should . . .