Association between increased nuchal translucency and copy number variations in fetuses during the first trimester at Hanoi Obstetrics and Gynecology Hospital

Abstract

Fetuses with increased nuchal translucency (NT) have traditionally been assessed primarily for the risk of aneuploidy. However, growing evidence suggests an association between increased NT and copy number variants (CNVs), including chromosomal microdeletions and microduplications. Advanced genomic techniques such as array Comparative Genomic Hybridisation (aCGH) and CNV sequencing (CNVseq) can identify additional genetic abnormalities not detected by conventional karyotyping. This study aimed to determine the prevalence of abnormal CNVs in pregnancies with NT ≥3 mm. A retrospective cross-sectional study was conducted on 235 fetuses with NT ≥3 mm who underwent amniocentesis followed by aCGH or CNVseq testing at Hanoi Obstetrics and Gynecology Hospital between January 2023 and December 2024. The results showed that aneuploidy was detected in 8.5% of cases. Among 215 cases with normal karyotype, 6% had pathogenic or likely pathogenic CNVs (P/LP-CNVs), and 8.9% had variants of uncertain significance (VUS), with 4.2% undetectable by standard karyotyping. The most frequently observed CNVs were microdeletion at 15q11.2 and duplication at 22q11. A significant association was found between P/LPCNVs and increased NT, either isolated or accompanied by other structural anomalies on prenatal ultrasound. In conclusion, aCGH and CNVseq enabled the detection of an additional 6% of P/LP-CNVs in fetuses with increased NT and normal karyotype, contributing to improved prenatal diagnostic accuracy.