Non-Invasive Prenatal Diagnosis: A Comparison of Cell Free Fetal DNA (cffDNA) Based Screening and Fetal Nucleated Red Blood Cell (fnRBC) Initiated Testing

Current prenatal diagnosis uses non-invasive procedures of maternal serum screening and ultrasound exam to evaluate the risk of chromosomal abnormalities and invasive procedures of chorionic villus sampling and amniocentesis for the diagnosis of cytogenomic abnormalities and gene mutations. The discovery of cell free fetal DNA (cffDNA) in maternal blood prompted the application of massive parallel sequencing to screen fetal aneuploidies. The multi-center large-scale validation of cffDNA based prenatal screening has resulted in rapid integration of this close-to-diagnostic non-invasive procedure into clinical application. Further improvement of this approach could lead to the screening of pathogenic copy number variants and known disease-causing gene mutations. The success from cffDNA fuels efforts in isolating circulating fetal nucleated red blood cells (fnRBCs) for direct non-invasive prenatal testing of fetal genetic disorders. Various isolation and enrichment methods based on the physical and biologic features of the fnRBCs have been developed but the analytic and clinical validities have not yet been established. The cffDNA based prenatal screening has significantly reduced unnecessary invasive procedures. Future breakthrough on fnRBC initiated prenatal testing will further shift the paradigm toward non-invasive prenatal diagnosis. [N A J Med Sci. 2013;6(4):194-199. DOI: 10.7156/najms.2013.0604194]