Cell-­‐free DNA analysis in maternal blood, new accurate approach for non-­‐invasive/nprenatal screening of chromosomal aneuploidies: review

Abstract

Prenatal screening and diagnostic tests for the detection of fetal chromosomal/nabnormalities are routine standard of care in pregnancy management. Traditional/nmethods consist of a non-invasive combined test, which gives an individual risk,/nfollowed by an invasive procedure if necessary. Recently, non-invasive prenatal testing/n(NIPT) through the analysis of cell-free DNA (cfDNA) in maternal blood, has been/nshown to accurately detect common fetal autosomal trisomies during the first trimester/nof pregnancy. About 6-20% of cell free DNA circulating in maternal plasma are small/nDNA molecules coming from apoptotic trophoblastic cells. This approach, whose/nefficacy exceeds by far that of conventional screening, is based on sequencing and/ncounting the cfDNA sequences originating from different maternal and fetal genomic/nregions. In pregnancies with aneuploid fetuses, the extra or missing copy of the/naffected chromosome would alter the proportional representation of this specific/nchromosome in the maternal plasma. This innovative approach is more sensitive and/nspecific, offering a greater detection rate (DR) and a significantly lower false-positive/nrate (FPR), which would result in a reduction of invasive diagnostic procedures that/ncarry a risk of miscarriage. CfDNA testing is gaining widespread acceptability./nHowever, its high cost is actually still limiting its application to high- and intermediaterisk/npatients, identified as such by the conventional first-line method of screening. This/nproject is based on a detailed bibliographic search of recent and relevant studies to/nreview the current state of the art regarding the cfDNA screening test and its future/nperspectives and applicability in clinical practice.