Introduction
Congenital anomalies comprise a wide range of abnormalities that are present at birth and are of prenatal origin. Chromosomal anomalies are a subtype of congenital anomalies and may be classified as numerical (aneuploidies: trisomy, monosomy) or structural (translocation, deletion and duplication). In turn, numerical chromosomal anomalies, which are the object of this systematic review, comprise autosomal aneuploidies and SCAs. The most common autosomal aneuploidy is Trisomy 21 (T21, Down syndrome), followed by Trisomy 18 (T18, Edwards syndrome) and Trisomy 13 (T13, Patau syndrome). SCAs include monosomies and trisomies: Turner syndrome (monosomy X, 45,X0), Klinefelter syndrome (47,XXY), triple X syndrome (47,XXX) and Jacobs syndrome (47,XYY). Prenatal screening protocols include analysis of autosomal trisomies and SCAs.
Cell-free fetal DNA (cffDNA) was first discovered by Lo et al. in 1997, described as the percentage of cell-free DNA in the mother’s peripheral blood of fetal origin (cffDNA is eliminated rapidly after delivery). It is used as a test for aneuploidies in non-invasive prenatal testing (NIPT). In addition to prenatal screening, cffDNA is also used for fetal sex determination, fetal Rhesus D genotyping, early identification of pre-eclampsia, fetal growth restriction prediction and diagnosis of diseases such as cystic fibrosis and achondroplasia.
CffDNA testing has the advantage of being a non-invasive procedure, avoiding the risk of miscarriage associated with invasive prenatal testing. It has recently generated interest, as it has the potential of reducing the rate of invasive prenatal testing of chromosomal anomalies and, as a consequence, a large number of studies have been published on this topic in recent years. Despite the existence of a number of systematic reviews, none have compared the accuracy of cffDNA testing for autosomal trisomies 21, 13 and 18 and for SCAs, since 2017. The objective of this review is to investigate the predictive performance of cffDNA testing for prenatal screening of SCAs and of the common autosomal trisomies, compared with gold-standard confirmatory methods. The study aims to be of value to clinicians by constructing an up-to-date review of the available evidence on the topic.