Test performance and clinical utility of expanded non-invasive prenatal test: Experience on 71,883 unselected routine cases from one single center

Objective: The balance between benefits and risks of discordant outcomes makes the Genome-Wide Non-Invasive Prenatal Test (GW-NIPT) controversial. This study aims to evaluate performance and clinical utility in a wide cohort of unselected clinical cases from a single center when a standardized protocol is applied and integrated with a secondary algorithm for data interpretation. Method: In 2 years, over 70,000 pregnant patients underwent GW-NIPT for fetal common trisomies, sex chromosome aneuploidies, rare autosomal aneuploidies, segmental abnormalities (CNVs >= 7 Mb) and microdeletions (CNVs < 7 Mb). All samples were uniformly processed with Veriseq NIPT Solution v2 and analyzed using all data metrics along with a home-made algorithm for sequencing data analysis. Results were retrospectively reviewed for clinical outcomes. Results: Among 71,883 eligible cases including twin pregnancies, 1011 (1.4%) received a positive result and 781 were confirmed by invasive prenatal diagnosis. Clinical sensitivity ranged from 99.65% for common trisomy (T21, T18, T13) to 83.33% for microdeletions, while specificity remained high (99.98%) for each class of fetal abnormalities detected. Conclusions: Integrating a standardized protocol with an internal algorithm allowed discordant results to be reduced, yielding high accuracy. Observed reliability in detecting genome-wide chromosomal conditions reinforced the expanded NIPT utility in clinical practice. What is already known about this topic? center dot Both accuracy and scope of GW-NIPT are detailed in several publications, often based on multisite assessment, selected study cohorts, or data clustered from different protocols, introducing bias in estimating test performance, and making expanded Non-Invasive Prenatal Testing (NIPT) still a matter of debate. What does this study add? center dot Clinical experience on a wide cohort of unselected cases from a single center proved that accurate data metrics evaluation, combined with a dedicated home-made algorithm for secondary data analysis, could reduce discordant results and allow to reconsider the clinical utility of genome-wide NIPT, even when widened to microdeletions.