923: Avoiding trade-offs: Clinical experience for noninvasive prenatal screen with low no-call rate and high accuracy

Noninvasive Prenatal Screening (NIPS) via cell-free DNA analysis (cfDNA) has been rapidly incorporated into prenatal care since 2011. The Counsyl Prelude Prenatal Screen utilizes a widely reported whole genome sequencing (WGS) approach to NIPS. Here we describe the clinical experience of offering Prelude in our laboratory. We retrospectively analyzed results from 58,028 patients who underwent NIPS over a nine month period to assess clinical performance for identifying Trisomy 21, Trisomy 18, and Trisomy 13 in singleton pregnancies. We sought pregnancy outcomes for all positive results and 10% of negative results. Voluntarily reported false negatives were also included. The patient cohort included average-risk (41%, n=23,735) and high-risk patients (59%, n=34,293). Median maternal age was 34 years (interquartile range (IQR): 29-37 years). Median gestational age was 12.4 weeks (IQR: 11.3-13.7 weeks). Unlike several NIPS offerings that do not provide a result when fetal fraction (FF) is below a specified threshold, Prelude does not fail samples solely based on fetal fraction. As such, the screen yielded a result for 99.9% of patients; no result was issued for 0.1% of cases (n=59) due to technical reasons. Median turnaround time was three days (IQR: 2-4 days). 572 cases (1%) screened positive (“aneuploidy detected” or “aneuploidy suspected”) with 362 positive for Trisomy 21, 142 positive for Trisomy 18, and 68 positive for Trisomy 13. “Aneuploidy suspected” reports accounted for 6.5% of positive results (n=37), 0.06% of the total cohort. Informative clinical outcomes were received for 244 (42.7%) positive results and 1,510 negative results (23% of those requested). Based on cytogenetically confirmed cases and adjusting cohort size for ascertainment bias, observed sensitivities for Trisomy 21, Trisomy 18, and Trisomy 13 were 99.3%, 95.9%, and 94.4%, respectively. Twenty-nine false positives were identified (seven Trisomy 21, seven Trisomy 18, and fifteen Trisomy 13). Prelude clinical performance is consistent with the NIPS literature, and is achieved without a FF failure threshold. Our results demonstrate that Prelude achieves high accuracy and a low test-failure rate in a large general obstetric population.