Clinical validation of a novel automated cell-free DNA screening assay for trisomies 21, 13, and 18 in maternal plasma

Abstract

Objective: To evaluate clinical performance of a new automated cell-free (cf)DNA assay in maternal plasma screening for trisomies 21, 18, and 13, and to determine fetal sex.

Method: Maternal plasma samples from 1200 singleton pregnancies were analyzed with a new non-sequencing cfDNA method, which is based on imaging and counting specific chromosome targets. Reference outcomes were determined by either cytogenetic testing, of amniotic fluid or chorionic villi, or clinical examination of neonates.

Results: The samples examined included 158 fetal aneuploidies. Sensitivity was 100% (112/112) for trisomy 21, 89% (32/36) for trisomy 18, and 100% (10/10) for trisomy 13. The respective specificities were 100%, 99.5%, and 99.9%. There were five first pass failures (0.4%), all in unaffected pregnancies. Sex classification was performed on 979 of the samples and 99.6% (975/979) provided a concordant result.

Conclusion: The new automated cfDNA assay has high sensitivity and specificity for trisomies 21, 18, and 13 and accurate classification of fetal sex, while maintaining a low failure rate. The study demonstrated that cfDNA testing can be simplified and automated to reduce cost and thereby enabling wider population-based screening.

Figure 1

Top: Cumulative distribution of trisomy 21 z scores as modeled based on published fetal fraction distribution (black line) and from the 112 trisomy 21 cases analyzed in this study (green line). The study trisomy 21 data points are well described by the theoretical model. The model predicts that 99.8% of trisomy 21 cases will have z‐score values above the cutoff used for trisomy 21 classification (dashed black line). Bottom: Individual z scores of unaffected (circles) and trisomy 21 cases (triangles) analyzed in this study [Colour figure can be viewed at http://wileyonlinelibrary.com]