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.

This study introduced whole-exome sequencing (WES) in prenatal diagnosis of fetal bowel dilatation to improve the detection outcome when karyotype analysis and copy number variation sequencing (CNV-seq) were uninformative in detecting pathogenic variants. The work reviewed 28 cases diagnosed with fetal bowel dilatation and analyzed the results of karyotype analysis, CNV-seq, and WES. Among the 28 cases, the detection rate in cases with low risk of aneuploidy was 11.54% (3/26), which is lower than 100% (2/2) in cases with high risk of aneuploidy. Ten low-risk aneuploidy cases with isolated fetal bowel dilatation had normal genetic testing results, while the remaining 16 cases with other ultrasound abnormalities were detected for genetic variants at a rate of 18.75% (3/16). The detection rate of gene variation was 3.85% (1/26) by CNV-seq and 7.69% (2/26) by WES. This study suggested that WES could reveal more genetic risk in prenatal diagnosis of fetal bowel dilatation and has value in prenatal diagnosis to reduce birth defects.

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.