Oneda B, Sirleto P, Baldinger R, et al. - Given the potential of non-invasive prenatal testing by targeted or genome-wide copy number profiling (cnNIPT) to outperform standard NIPT targeting the common trisomies 13, 18, and 21, only, researchers examined the performance of cnNIPT in 3,053 prospective and 116 retrospective cases. Special consideration was provided to maternal copy number variants (CNVs) in singleton and multiple gestational pregnancies at any risk, as well as comprehensive follow-up was performed. Among total prospective cases, 2,998 (98.2%) achieved result (89.2% analyzed genome-wide). Forty-five (1.5%) cases were detected to have confirmed fetal chromosomal abnormalities, of which five (11%) would have remained undetected in standard NIPTs. Findings suggest a very high sensitivity, specificity and PPV of cnNIPT for common trisomies in single and multiple pregnancies at any risk and very good values genome-wide when maternal CNVs are recognized as such. The resolution for segmental aberrations is generally similar to standard karyotyping; it exceeds the latter if the fetal fraction is above 10%, which enables detection of the 2.5 Mb 22q11.2 microdeletion linked with the velocardiofacial syndrome, even if the mother is not a carrier.