Can non-invasive prenatal screening based on cell-free fetal DNA be utilized to assess chromosome abnormalities in fetuses with increased Nuchal Translucency?

Objective: The study compared the incidence of aneuploidy and copy number variations (CNVs) in fetuses with increased nuchal translucency (NT) to those with clear indications for non-invasive prenatal screening (NIPS), aiming to evaluate the risk of routine aneuploidy (RA) and pathogenic submicroscopic abnormalities and the potential use of NIPS for fetuses with increased NT. Methods: The study retrospectively analyzed 716 pregnant women with isolated increased NT in Group IiNT and 2960 pregnant women in the control group. The control group was divided into sub-Group A (1531 patients underwent invasive prenatal diagnosis for advanced maternal age (AMA)), sub-Group B (1331 for high-risk maternal serum screening (hMSS)), and sub-Group C (98 for both hMSS and AMA). All cases underwent karyotyping and chromosomal microarray analysis. Results: In Group IiNT and each sub-group, there were cases of RA (17, 28, 24, and 1) and clinically significant CNVs (22, 19, 39, and 5), respectively. There was no significant difference in RA incidence between Group IiNT and the control group/subgroups. Similarly, there was no statistical difference in clinically significant CNVs and CNVs <10 Mb between Group IiNT and sub-Group B/C or the control group. Only Group IiNT and sub-Group A showed a significant difference. Conclusion: Using NIPS with broader and deeper sequencing could theoretically potentially serve as a screening tool for identifying global chromosomal and submicroscopic abnormalities in fetuses with isolated increased NT. However, further research is required to determine the clinical application and to assess the efficacy of NIPS in detecting abnormalities. Traditional karyotyping and SNP array was performed on all 3676 pregnancies. SNP array was performed on various pregnancy types. *** Submitter declares that some chp and CEL files have been lost. ***