METHODS: A total of 535 pregnant women were included in this study, with a fetal NT > 95th centile at 11-13+6 weeks of gestation from January 2017 to December 2020. 324 pregnant women with fetal NT > 95th centile and below 99th centile combined with other risk factors and NT > 99th centile received prenatal diagnostic karyotype analysis and CMA, and 211 pregnant women with fetal isolated increased NT > 95th centile and below 99th centile were selected to carry out NIPT.
RESULTS: A total of 211 pregnant women who underwent NIPT were included in the study, NIPT results showed that 8 high-risk cases were confirmed by prenatal diagnosis. Overall, the detection rate of NIPT was 3.79%. A total of 324 pregnant women with fetal NT > 95th centile and below 99th centile, along with other risk factors, and those with fetal NT > 99th centile, received karyotype analysis and CMA for prenatal diagnosis. Among them, a total of 73 genetic abnormalities were detected, including 45 cases of chromosomal aneuploidy, 7 cases of structural abnormalities, and 21 cases of copy number variations (CNVs) with a size of less than 10 Mb. In addition, the 73 women with genetic abnormalities are divided into three groups based on the NT measurement (Group 1: Fetuses with NT > 95th centile and below 99th centile, Group 2: Fetuses with NT > 99th centile, and Group 3: Fetuses with NT > 99th centile). 13.11% (8/61) of pathogenic genetic abnormalities (6 chromosomal aneuploidy, 1 structural abnormality, and 1 likely pathogenic CNV) will be missed if genetic counseling and prenatal genetic testing were not conducted in fetuses with increased NT > 95th centile and below 99th centile combined with other risks. Pathogenic CNVs were the most common abnormalities in group 3, and one likely pathogenic CNV was detected in group 1 and group 3, respectively, and a total of 14 CNVs of unknown clinical significance (VOUS) were detected.
CONCLUSIONS: Through this study, we demonstrated that the critical value of NT > 95th centile for invasive detection or NIPT. Invasive testing combined with CMA may be recommended for fetuses with NT > 95th centile and below 99th centile and with other risks. But when isolated NT > 95th centile and below 99th centile, NIPT would be appropriate.
方法:本研究共纳入535名孕妇,在2017年1月至2020年12月妊娠11-13+6周时,胎儿NT>95百分位数。324例胎儿NT>95百分位和99百分位以下合并其他危险因素且NT>99百分位的孕妇接受产前诊断核型分析和CMA,选择胎儿孤立NT>95百分位和99百分位以下的211例孕妇进行NIPT。
结果:总共211名接受NIPT的孕妇被纳入研究,NIPT结果显示有8例高危病例经产前诊断确诊。总的来说,NIPT检出率为3.79%。共有324名孕妇,胎儿NT>95百分位和99百分位以下,以及其他风险因素,那些胎儿NT>99个百分位数的人,接受染色体核型分析和CMA进行产前诊断。其中,共检测到73个基因异常,包括45例染色体非整倍体,7例结构异常,和21例拷贝数变异(CNVs),大小小于10Mb。此外,根据NT测量,将73名遗传异常的妇女分为三组(第1组:NT>95百分位和低于99百分位的胎儿,第2组:NT>99百分位的胎儿,和第3组:NT>99百分位的胎儿)。13.11%(8/61)的致病性遗传异常(6染色体非整倍体,1结构异常,如果未在NT>95百分位和99百分位以下并伴有其他风险的胎儿中进行遗传咨询和产前遗传检测,则会错过1种可能的致病性CNV)。致病性CNV是3组中最常见的异常,1组和3组分别检测到1种可能的致病性CNV,共检测到14个临床意义未知的CNVs(VOUS)。
结论:通过这项研究,我们证明了NT>95百分位数的临界值对于侵入性检测或NIPT。对于NT>95百分位和低于99百分位和其他风险的胎儿,建议进行侵入性测试结合CMA。但是当孤立的NT>95百分位和低于99百分位时,NIPT是合适的。