Reported PPV in studies performed on mixed high- and low-risk populations, as well as the current study, far exceed current screening methodologies. Consistent with this, recent guidelines published by the American College of Medical Genetics and Genomics (ACMG) do not distinguish between high and low risk. Therefore, the transition of NIPT into a universal, first-line, aneuploidy screen should depend on the availability and affordability of NIPT, and not concerns about performance. In this cohort of women who were thought to have singleton

pregnancies at the time of NIPT, 127 cases were identified as having >2 fetal haplotypes suggesting either triploidy or a previously undetected multifetal pregnancy or vanishing twin. The SNP-based NIPT methodology provided the opportunity Cell Cycle inhibitor to identify these cases, pursue further diagnostic avenues, and avoid FPs that can arise using alternative methodologies.22 The main limitation of this study is the incomplete follow-up data, particularly on low-risk patients, precluding precise calculation of sensitivity and specificity. While follow-up was not conducted on low-risk patients, given the clinical significance of a FN report, and based on our laboratory

experience, it is likely that FNs would be voluntarily reported; there were 2 voluntarily reported FNs. However, the lack of comprehensive follow-up on all low-risk patients precluded determination of the negative predictive value. Oxymatrine Nevertheless, it is important to note that strong performance characteristics were in keeping with GSK2118436 prior validation studies,2, 3 and 24 even with the inclusion

of mosaic samples. Follow-up of normal results remains an issue for all laboratories that wish to track results for quality assurance, and we support the ACMG recommendation for a national registry.16 In conclusion, this is a large-scale report of clinical utilization of NIPT. Analysis of >31,000 samples from both low- and high-risk women supported that test performance of this NIPT method in a clinical setting mirrors the robust performance reported in validation studies. Clinical performance of SNP-based NIPT in a mixed high- and low-risk population is consistent with performance in validation studies. Similar PPVs were found in women aged <35 years and aged ≥35 years. The strength of the study is the robust information it provides on clinical application of NIPT. The primary limitation is the incomplete follow-up data, particularly on low-risk patients, precluding precise calculation of sensitivity and specificity. This study supports the use of NIPT as a first-line screening test for aneuploidy in all patients. Furthermore, it highlights the importance of, as well as provides data that can improve, counseling of patients.