Fetal Cells in Maternal Blood for Noninvasive Prenatal Testing—Is it Still a Distant Star?

ABSTRACT Accurate and safe prenatal diagnosis of severe genetic disorders remains challenging despite advances in genomic technologies and increased use of cell‐free noninvasive prenatal testing (cfNIPT). Currently, approximately half of pathogenic copy number variants (pCNVs) and most monogenic disorders are identified only postnatally. cfNIPT primarily detects aneuploidies. Some extended cfNIPTs perform genome‐wide screening for larger pCNVs as well as selected microdeletion syndromes. Traditional invasive techniques, such as chorionic villus sampling (CVS), detect both aneuploidies and pCNVs but involve a slight risk of miscarriage. Emerging cell‐based noninvasive prenatal testing (cbNIPT) represents a promising advancement, potentially increasing prenatal detection rates by enabling accurate, safe, and comprehensive genome‐wide analysis, including small but clinically significant microdeletions, and monogenic disorders such as cystic fibrosis and sickle cell disease. In this review, we make a case for cbNIPT and describe its positioning with respect to cfNIPT. We also present the development of a cell‐based technology from finding fetal cell specific biomarkers, streamlining the technology of isolating cells from maternal blood, generating clinical data, and launching a test in the market. This advancement could substantially enhance informed decision‐making, timely clinical interventions, and pregnancy outcomes as compared to cfNIPT.