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,