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

Abstract

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 uid samples were extracted for performing karyotype analysis and CNV-seq after patient's written informed consent was obtained. ResultsChromosome 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 signi cance (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 signi cance (P < 0.05). ConclusionAs 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.

Chromosome abnormalities and copy number variations in fetuses with ultrasound soft markers: a retrospective study

“…Previous research revealed that NT thickness was positively associated with the detection rates of genetic aberrations [13]. Meanwhile, although the cut-off value of NT thickness was 3.0mm or above the 99 th percentile of crown-rump length according to the American College of Obstetricians and Gynecologists (ACMG) and Society for Maternal Fetal Medicine, previously reports indicated that NT thickness larger than 2.5mm was associated with an increased risk of genetic aberrations [13,14]. So, chromosomal aberrations in fetuses with different NT thicknesses were investigated in our study.…”

“…In fetuses with choroid plexus cysts, nasal bone hypoplasia and ventriculomegaly, the detection rates of chromosome abnormalities were 7.5% [7], 5.9%-17.8% [8-10] and 6.8% [11], respectively. In fetuses with increased NT thickness, the detection rates of chromosome abnormalities ranged from 19.4-23.7% [12][13][14]. In addition to abnormal karyotypes, pathogenic/likely pathogenic copy number variations (P/LP CNVs) were found to be associated with ultrasound soft markers via chromosomal microarray analysis (CMA) and copy number variation sequencing (CNV-seq) [15].…”