AbstractAfter decades of research, non-invasive prenatal testing (NIPT) using maternal blood to determine fetal chromosome status has found its way from the research laboratory into clinical practice, triggering a long-awaited paradigm shift in prenatal care. A variety of methods using sequencing of maternal cell-free DNA (cfDNA) have now been studied, primarily demonstrating their ability to detect the most common fetal aneuploidy, trisomy 21 (T21). The focus of this article is on massively parallel sequencing (MPS) with optimized sequence tag mapping and chromosome quantification, which accurately detects T21 as well as multiple other aneuploidies across the genome. The power of this technique resides in its high precision and reduction of variation within and between sequencing runs. Using MPS, classification of aneuploidy status for a given sample can be reliably assigned from the genetic information alone without the need to factor in other maternal pre-test risk or other clinical variables. Performance of this method has been prospectively demonstrated in a rigorous, blinded, multi-center study in the United States. The findings suggest that MPS can be incorporated into existing prenatal screening algorithms to reduce unnecessary invasive procedures. This technology and key considerations for clinical implementation are discussed.
Fetal aneuploidy screening by non-invasive prenatal testing of maternal plasma DNA sequencing with “false negative” result due to confined placental mosaicism