Predictive value of cell-free fetal DNA for prenatal screening of sex chromosome aneuploidies and autosomal trisomies (21, 18 and 13) in singleton pregnancies: a systematic review.

Background: Non-invasive prenatal testing (NIPT) analyses the cell-free fetal DNA (cffDNA) present in maternal plasma. It is used for the screening of autosomal trisomies and sex chromosome aneuploidies (SCAs). Objectives: Compare the positive predictive value (PPV) of a high-risk cffDNA test result for SCAs (Monosomy X, 47,XXX, 47,XXY and 47,XYY) and autosomal trisomies (T21, T18 and T13) with confirmatory diagnostic tests in singleton pregnancies. Identify the main reason for discordant and inconclusive results. Search strategy . PubMed, Web of Science and Scopus from 2017. Selection criteria . Primary research articles on cffDNA testing of autosomal trisomies and SCAs in singleton pregnancies. Data collection and analysis . The methodological characteristics of the studies and the statistical results of each aneuploidy were collected. The risk of bias was assessed using the CASP tool. Main results. A total of 14 studies were included. Amongst the autosomal trisomies, T21 had the highest PPVs, whereas T13 showed the lowest PPVs. As for the SCAs, the lowest PPVs were found with Monosomy X. Although discordant and inconclusive results were not rigorously reported, mosaicism was the main cause of false positives and an insufficient cffDNA fraction was the main reason for inconclusive results. Conclusions: . CffDNA is a reliable screening tool for the common autosomal trisomies, and it is also useful for prenatal screening of SCAs, although the PPVs are lower. A positive NIPT result should be followed with a confirmatory test. Funding . The review was carried out with no funding. Keywords: . Cell-free fetal DNA, non-invasive prenatal testing, aneuploidy, trisomy.