Molecular genetic and pregnancy outcomes of fetuses with increased Nuchal Translucency.

Abstract

Increased nuchal translucency (NT; ≥ 2.5 mm) is closely associated with various chromosomal abnormalities, structural abnormalities, and genetic diseases. However, research on pathogenic copy number variations (CNVs) affecting pregnancy outcomes in fetuses with increased NT remains limited. This study aimed to summarize the clinical features, chromosomal abnormalities and obstetric outcomes of increased NT to provide a clinical reference for prenatal diagnosis. A retrospective analysis was conducted on 180 pregnant women with increased NT who underwent invasive prenatal testing via conventional karyotyping and single nucleotide polymorphism (SNP) array analysis between January 2021 and December 2025. These cases were selected from a cohort of 1,678 pregnant women. Chromosomal karyotyping revealed a total of 24 chromosomal abnormalities. Chromosomal polymorphisms were also observed in four cases, including two cases with pericentric inversion of chromosome 9 [inv(9)(p12q13)], one case with 1qh+, and one case with 21pss (double satellites on the short arm of chromosome 21). In addition, SNP-array analysis detected CNVs in 13 fetuses with normal karyotypes. Among the 24 fetuses harboring pathogenic variants, 21 (87.5%) exhibited aneuploidy. These aneuploid cases included 16 fetuses with trisomy 21 syndrome and 5 fetuses with either trisomy 18 syndrome or Klinefelter syndrome, with trisomy 21 accounting for 76.2% (16/21) of the aneuploid cohort. Among the CNVs detected by SNP-array, one was classified as pathogenic, one as likely pathogenic, and the remaining as variants of uncertain significance (VUS). Postnatal follow-up of 10 infants with VUS revealed growth and speech developmental delays in two cases, while no obvious abnormalities were observed in the remaining eight. Aneuploidy was found to be the predominant type of abnormality in fetuses with increased NT. This study suggests that high-resolution SNP-array exhibit greater sensitivity in detecting chromosomal microstructural abnormalities and can serve as an effective complement to conventional karyotyping.