Diagnostic yield of copy number variation sequencing in fetuses with increased nuchal translucency: a retrospective study

Abstract Objective To assess the clinical application value of copy number variation sequencing (CNV-seq) combined with karyotype analysis in prenatal diagnosis of fetuses with increased nuchal translucency. Methods 205 fetuses who were diagnosed with increased nuchal translucency (NT ≥ 2.5 mm) by ultrasound between gestational ages of 11 and 13 + 6 weeks from June 2017 to December 2020 in Tongji Hospital were enrolled. Amniotic fluid samples were extracted for performing karyotype analysis and CNV-seq after patient’s written informed consent was obtained. Results Chromosome abnormalities were discovered in 40 fetuses (19.51%) with increased NT by karyotype and the trisomy 21 was the most common. 50 fetuses (24.39%) with chromosomal abnormalities were detected by CNV-seq, producing an incremental yield of 6.06% (10/165) in fetuses with increased NT and normal karyotype. The prevalence of chromosome abnormality increased by from 13.64% for those with NTs of 2.5–3.4 mm to 38.64% for NTs of 3.5–4.4 mm and 51.72% for NTs of over 4.5 mm. The difference had statistically significance (P < 0.05). Those with increased NT complicated with ultrasound soft markers or high risk of non-invasive prenatal testing showed higher rate of chromosome abnormality than those with isolated NT or low risk, and difference had statistically significance (P < 0.05). Conclusion As the thickness of NT increases, the odds of chromosome abnormalities also increase, which could be detected by karyotype or CNV-seq, and the combination application of two tests can greatly shorten the turnover time of prenatal diagnosis and the occurrence of missed diagnosis. Besides, we recommend that the NTs of 2.5-3.4mm should be considered as a critical risk range of chromosome abnormality and attention should be paid to those fetuses whether complicated with other ultrasound soft markers or not.