Abstract
Background Previously, fetuses with increased nuchal translucency (NT) were mainly tested for aneuploidy. Recent evidence has shown an incidence of other genetic disorders in euploidy fetuses with thickened NT. Chromosomal microarray analysis (CMA) and next-generation sequencing (NGS) can detect the incremental yield of microdeletions and microduplications (copy number variants (CNVs)) and provide useful information for prenatal counseling. This study aims to determine the frequency of pathogenic CNV (pCNV) and its associated factors in euploidy fetuses with increased NT. Methods This was a retrospective study of 491 fetuses with NT ≥ 3 mm that underwent chorionic villus sampling or amniocentesis and was tested either by CMA or CNV-seq at Tu Du Hospital between August 2020 and January 2022. Results A total of 491 cases with NT ≥ 3 mm were indicated for genetic testing. Among 397 euploidy fetuses, 36 (9.1%) were pCNV, 24 (6.0%) were submicroscopic pCNV (not visible by karyotyping), and 25 (6.3%) were variants of unknown significance (VUS). The most common pCNV were 22q11 duplication and 16p11.2-p12.2 deletion. The incidence of pCNV in fetuses with increased NT and other structural abnormalities was significantly higher than in fetuses with isolated increased NT in the first trimester (OR 3.75, 95% CI 1.79-7.86, p < 0.001). Maternal age and the thickness of NT were not associated with an increased risk of harboring pCNV. Conclusion CMA or CNV-seq can detect the incremental yield of pCNV in euploidy fetuses with increased NT to assist in more accurate prenatal counselling.
Keywords:
increased nuchal translucency (nt); live fetus; microarray; opy number of variants (cnv); pregnancy counseling.