Objective: To evaluate the test performance of a novel sequencing technology using molecular inversion probes applied to cell-free DNA screening for fetal aneuploidy.
Methods: Two cohorts were included in the evaluation; a risk-based cohort of women receiving diagnostic testing in the first and second trimesters was combined with stored samples from pregnancies with fetuses known to be aneuploid or euploid. All samples were blinded to testing personnel before being analyzed, and validation occurred after the study closed and results were merged.
Results: Using the new sequencing technology, 1414 samples were analyzed. The findings showed sensitivities and specificities for the common trisomies and the sex chromosome aneuploidies at >99% (Trisomy 21 sensitivity 99.2 CI 95.6–99.2; specificity 99.9 CI 99.6–99.9). Positive predictive values among the trisomies varied from 85.2% (Trisomy 18) to 99.0% (Trisomy 21), reflecting their prevalence rates in the study. Comparisons with a meta-analysis of recent cell-free DNA screening publications demonstrated equivalent test performance.
Conclusion: This new technology demonstrates equivalent test performance compared with alternative sequencing approaches, and demonstrates that each chromosome can be successfully interrogated using a single probe.
Trial registration: ClinicalTrials.gov NCT02317965.
Keywords: Fetal aneuploidy; cell-free DNA; molecular inversion probes; sequencing technology.