The Role of Thickened Nuchal Translucency on Copy Number Variations and Pregnancy Outcomes in Northeast Coast of Fujian Province, China: A Comparison Between Traditional Karyotyping and Single Nucleotide Polymorphism Array Analysis

Abstract

AbstractBackground Thickened nuchal translucency (NT; ≥2.5 mm) is closely associated with various chromosomal abnormalities, structural abnormalities, and genetic diseases. However, the cutoff value of thickened NT for invasive prenatal diagnosis remains inconsistent, and little research has been conducted on pathogenic copy number variations (CNVs) affecting the outcomes in foetuses with thickened NT. This study aimed to assess the cutoff value for thickened NT to predict aneuploid foetuses and CNVs associated with thickened NT in prenatal diagnosis to determine the characteristics of pathogenic CNVs, which would assist the genetic counselling of women with thickened NT. Methods Ninety pregnant women with thickened NT who underwent invasive prenatal diagnosis using traditional karyotyping and single nucleotide polymorphism (SNP) array analysis in diagnostic institutions between January 2021 and March 2023 were included. The accuracy of the thickened NT cutoff value for diagnosing aneuploid abnormalities was assessed using receiver operating characteristic (ROC) curve analysis. Results Karyotype analysis identified 15 chromosomal abnormalities. In addition to the 10 chromosomal abnormalities corresponding to routine karyotyping, SNP array analysis identified six patients with CNVs but normal karyotypes. ROC curves demonstrate that the NT measured between 11 and 13+ 6weeks was associated with 0.729 area under the curve (AUC; 95% CI: 0.56–0.898, P = 0.019) with the foetal aneuploidy. The ROC curve revealed that the cutoff value of NT was 4.15 mm, which showed 50% sensitivity and 90% specificity for detecting aneuploidies. With increasing NT thickness, the probability of aneuploidy increases in the first trimester. Conclusion Aneuploid abnormalities and CNVs are closely related to a thickened NT, which affects pregnancy outcomes. Thickened NT and abnormal CNVs are closely related and are not only associated with chromosome aneuploidy in the first trimester. We recommend that karyotyping and SNP array analysis should be performed for prenatal diagnosis in all foetus with NT thickness > 2.5 mm, regardless of NT thickness > 3.0 or 3.5 mm to avoid the occurrence of child birth with genetic defects due to missing prenatal diagnosis.