Non-invasive prenatal testing that uses cell-free fetal DNA (cfDNA) from the plasma of pregnant women offers tremendous potential as a screening tool for fetal aneuploidy. Recently, a number of groups have validated a technology known as massively parallel genomic sequencing, which uses a highly sensitive assay to quantify millions of DNA fragments in biological samples in a span of days and has been reported to accurately detect trisomy 13, trisomy 18 and trisomy 21 as early as the 10th week of pregnancy with results available approximately 1 week after maternal sampling. cfDNA has a very high detection rate for trisomy 21: 99% or 100%. It does not replace the precision obtained with diagnostic tests, such as chorionic villus sampling (CVS) or amniocentesis, and currently does not offer other genetic information. Given that the fetus is the source of perhaps 5% of cfDNA in maternal plasma, blood from a mother carrying a trisomy 21 pregnancy should have 2.5% more chromosome 21 sequences than if her fetus were not trisomic. cfDNA analysis will remain a screen, not a test requiring no additional assays before a management decision. Expert patient counseling may be important before and after testing. Metabolomic analysis could lead to the development of additional biochemical markers to improve Down syndrome screening. Metabolomics provide insights into the cellular dysfunction in Down syndrome. Clinical management guidelines and education are essential. As with all new screening tests and technologies, the expanded panel should be appropriately studied before it replaces current standard of care and changes clinical practice.Read More