Chromosomal microarray analysis in 1292 fetuses with ultrasound soft markers during mid-term pregnancy

Background Soft markers found during mid-term pregnancy ultrasounds can indicate potential chromosomal abnormalities in fetuses. This study evaluates the association between ultrasound soft markers and chromosomal abnormalities, providing insights into the predictive value of these markers in prenatal screening.Methods We retrospectively analyzed 1,292 fetuses that underwent invasive prenatal diagnosis because of the presence of ultrasound soft markers. The cases were categorized into three groups: those with one ultrasound soft marker (n = 1,039), two markers (n = 199), and three or more markers (n = 54). The chromosomal microarray analysis (CMA) results were analyzed and compared across the defined groups and different types of isolated soft markers.Results Among the 1,292 fetuses with ultrasound soft markers, the overall incidence of chromosomal abnormalities was 13.24% (171/1292), of which 66.67% were numerical chromosomal abnormalities, 29.24% were pathogenic copy number variants, and 4.09% were likely pathogenic copy number variants. Specifically, the incidence rates were 10.49% in fetuses with one soft marker, 17.09% with two, and 51.85% with three or more, with statistically significant differences (p < 0.01). The highest rates of chromosomal abnormalities were observed in cases of thickened nuchal fold (26.32%), mild tricuspid regurgitation (17.86%), and absent/hypoplastic nasal bone (16.94%). Multivariable analysis indicated significant associations between certain soft markers (thickened nuchal fold, absent/hypoplastic nasal bone, pyelectasis and mild tricuspid regurgitation) and an increased risk of chromosomal abnormalities. Multiple ultrasound soft markers or certain specific markers were strongly linked to an increased risk of chromosomal abnormalities, underscoring the need for thorough prenatal screening.Conclusions Fetuses with multiple soft markers exhibited a significantly higher incidence of chromosomal abnormalities compared to those with isolated soft markers. Soft markers such as thickened nuchal fold and absent/hypoplastic nasal bone were strongly correlated with chromosomal abnormalities. These findings highlight the importance of comprehensive prenatal assessment in fetuses with ultrasound soft markers to identify potential chromosomal abnormalities early in pregnancy.