Abstract：
OBJECTIVE: We sought to analyze the genetic outcomes of fetuses with nuchal translucency (NT) > 95th centile, and determine whether prenatal genetic counseling, chromosomal microarray analysis (CMA) or non-invasive prenatal testing (NIPT) are truly beneficial for the outcomes of fetuses with increased NT > 95th centile and below 99th centile.
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.
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.
摘要：
目的：我们试图分析颈部透明（NT）>95百分位的胎儿的遗传结局，并确定产前遗传咨询，染色体微阵列分析(CMA)或非侵入性产前检测(NIPT)对于NT>95百分位数增加且低于99百分位数的胎儿的结局确实有益.
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。
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。
