遵义市6903例无创产前检测(NIPT)分指征统计及阳性验证分析
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摘要
目的了解遵义地区无创产前检测(NIPT)各分类指征开展情况和阳性的验证,探讨其在产前筛查的应用价值。方法回顾分析2017年4月至2018年6月到我院接受NIPT产前筛查的6903例孕妇,按照高龄妊娠(≥35岁)、血清学筛查高风险/临界风险、NT增厚、B超软指标异常/结构异常、双胎/IVF-ET妊娠、错过其它筛查时机(≥22w)、自愿要求及其它(流产≥2次和有不良妊娠或生育史)检测进行分指征统计,同时统计各分类指征下的二胎例数。对NIPT筛查阳性孕妇进行遗传咨询,并建议做产前诊断。结果分指征统计中选择NIPT检测人数前三依次是自愿要求67.38%(4651/6903)、高龄妊娠19.79%(1366/6903)、血清学筛查高风险/临界风险7.17%(495/6903),其次为错过其它筛查时机(≥22w)2.62%(181/6903)、双胎/IVF-ET妊娠1.87%(129/6903),占比最少为NT增厚和B超异常合计仅为0.56%(39/6903)。生育二孩数占全部分类指征51%(3521/6903)。NIPT共筛查出77例阳性,检出率为1.11%(77/6903),15例未做产前诊断,最终确诊34例,符合率为54.84%(34/62),产前筛查阳性预测值最高的为47,XXY(5/5)和47,XXX(4/4)均为100%,21三体高风险的阳性预测值71.43%(15/21),18三体高风险的阳性预测值66.67%(4/6),13三体高风险的阳性预测值25%(1/4),Turner筛查阳性的阳性预测值为23.08%(3/13),其他常染色体数目异常阳性预测值最低为14.29%(1/7)。结论 NIPT技术有助于提升我市产前筛查技术水平,能有效减少需直接做产前诊断的人数,但NIPT并非诊断性检测方法,其阳性结果必须做进一步产前诊断才能确诊,本研究中47,XXY和47,XXX虽不在无创检测范围,但阳性预测值能达到100%,期望后续能有更多数据支撑将这两种性染色体类型纳入NIPT检测范围。
Objective:To understand the development and positive verification of the classification of noninvasive prenatal testing(NIPT)in Zunyi area,and to explore its application value in prenatal screening. Methods:From April 2017 to June2018,6903 pregnant women who received NIPT prenatal screening in our hospital were retrospectively analyzed. According to the age of pregnancy(>35 years),serological screening for high risk/critical risk,NT thickening,abnormal B-ultrasonographic soft index/structural abnormalities,twin/IVF-ET pregnancy,missed other screening opportunities(>22 weeks),voluntary requests and other(abortion(>2 times)and adverse pregnancy or birth history(tests were used for sub-index statistics,and the number of secondary births under each classification was also calculated. Genetic screening was performed for pregnant women with positive NIPT screening,and prenatal diagnosis was recommended. Results:The first three criteria for NIPT were 67.38%(4651/6903),19.79%(1366/6903),7.17%(495/6903),7.17%(495/6903),2.62%(181/6903)and 1.87%(129/6903)of twins/IVFET pregnancies. The proportion of NT thickening and B-ultrasound abnormality was only 0.56%(39/6903). The total number of two births accounted for 51%(3521/6903). NIPT screened 77 positive cases,the detection rate was 1.11%(77/6903),15 cases did not make prenatal diagnosis,34 cases were finally diagnosed,the coincidence rate was 54.84%(34/62). The highest positive predictive value of prenatal screening was 47,XXY(5/5)and 47,XXX(4/4)were 100%,trisomy 21 was 71.43%(15/21),trisomy 18 was 66.67%(4/6),trisomy 13 was 25%(1/4),and Turner was 23.08%(4/4). The lowest positive predictive value for other autosomal abnormalities was 14.29%(1/7). Conclusion:NIPT technology can help to improve the prenatal screening technology and reduce the number of people who need direct prenatal diagnosis,but NIPT is not a diagnostic test method,its positive results must be further prenatal. In this study 47,XXY and 47,XXX are not non-invasive detection,but the positive predictive value can reach 100%. It is hoped that more data will support the inclusion of these two sex chromosome types in the non-invasive detection.
Objective:To understand the development and positive verification of the classification of noninvasive prenatal testing(NIPT)in Zunyi area,and to explore its application value in prenatal screening. Methods:From April 2017 to June2018,6903 pregnant women who received NIPT prenatal screening in our hospital were retrospectively analyzed. According to the age of pregnancy(>35 years),serological screening for high risk/critical risk,NT thickening,abnormal B-ultrasonographic soft index/structural abnormalities,twin/IVF-ET pregnancy,missed other screening opportunities(>22 weeks),voluntary requests and other(abortion(>2 times)and adverse pregnancy or birth history(tests were used for sub-index statistics,and the number of secondary births under each classification was also calculated. Genetic screening was performed for pregnant women with positive NIPT screening,and prenatal diagnosis was recommended. Results:The first three criteria for NIPT were 67.38%(4651/6903),19.79%(1366/6903),7.17%(495/6903),7.17%(495/6903),2.62%(181/6903)and 1.87%(129/6903)of twins/IVFET pregnancies. The proportion of NT thickening and B-ultrasound abnormality was only 0.56%(39/6903). The total number of two births accounted for 51%(3521/6903). NIPT screened 77 positive cases,the detection rate was 1.11%(77/6903),15 cases did not make prenatal diagnosis,34 cases were finally diagnosed,the coincidence rate was 54.84%(34/62). The highest positive predictive value of prenatal screening was 47,XXY(5/5)and 47,XXX(4/4)were 100%,trisomy 21 was 71.43%(15/21),trisomy 18 was 66.67%(4/6),trisomy 13 was 25%(1/4),and Turner was 23.08%(4/4). The lowest positive predictive value for other autosomal abnormalities was 14.29%(1/7). Conclusion:NIPT technology can help to improve the prenatal screening technology and reduce the number of people who need direct prenatal diagnosis,but NIPT is not a diagnostic test method,its positive results must be further prenatal. In this study 47,XXY and 47,XXX are not non-invasive detection,but the positive predictive value can reach 100%. It is hoped that more data will support the inclusion of these two sex chromosome types in the non-invasive detection.
引文
[1]刘静,王华,席惠,等.新一代测序技术用于胎儿染色体非整倍体无创产前检测的研究[J].中华医学遗传学杂志,2015,32(4):533-537.DOt:10.3760/cma.j.issn.1003-9406.201 5.04.019.
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[4]李敏,王杜娟,周云,曹森杨,张庆娥,董晶晶.高通量测序在胎儿性染色体非整倍体异常检测中的临床应用[J].中国优生与遗传杂志,2018,26(08):37-38.
[5]杨洁霞,郭芳芳,彭海山,等.无创产前基因检测技术在胎儿染色体非整倍体筛查中的应用研究[J/CD].中国产前诊断杂志(电子版),2016,8(3):31-34.
[6]卢建,侯亚萍,黄伟伟,李怡,周伟宁,尹爱华. 471例NIPT阳性孕妇产前诊断结果分析[J].中国产前诊断杂志(电子版),2017,9(04):14-17.
[7]刘学军,刘慈,马良,刘芸兰,师园园.无创产前检测阳性患者的验证及临床意义[J].中国优生与遗传杂志,2018,26(04):45-47+54
[8]周舒香,刘妮,杨一琼,张小敏,陈玲,徐丽,李靓,罗浑金,谭赛男.5076例孕妇无创DNA产前检测结果的分析[J].中国优生与遗传杂志,2018,26(05):63-64.
[9]张卫华,周赤燕,朱晖.嘉兴地区11989例无创产前基因检测结果分析[J].中国优生与遗传杂志,2018,26(07):30-32.
[10]Gunther DF,Eugster E,Zagar AJ,et al. Ascertainment bias in Turner syndrome:new insights from girls who were diagnosed incidentally in prenatal life[J]. Pediatrics,2004,1 14(3):640-644. DOI:10.1542/peds.2003-1122-L.
[11]Lo YM,Corbetta N,Chamberlain PF,et al. Presence of fetal DNA in maternal plasma and serum[J]. Lancet 1997,350,485-487.
[12]马京梅,杨慧霞.基于母体外周血胎儿游离核酸的无创产前检查:来自国际两大学术组织的最新指南[J].中华围产医学杂志,2015,18(11):834-837. DOI:10.3760/cma.j.issn.1007-9408.2015.11.009.
[2]Evans MI.Wapner ILl.Invasive prenatal diagnostic procedures,2005[J]3.Semin Perinato1,2005,29(4):215-218.
[3]侯亚萍,杨洁霞,郭芳芳,齐一鸣,彭海山,王东梅,欧阳浩新,尹爱华.无创DNA产前检测在胎儿染色体非整倍体疾病筛查中的应用[J].检验医学与临床,2018,15(11):1542-1544+1548.
[4]李敏,王杜娟,周云,曹森杨,张庆娥,董晶晶.高通量测序在胎儿性染色体非整倍体异常检测中的临床应用[J].中国优生与遗传杂志,2018,26(08):37-38.
[5]杨洁霞,郭芳芳,彭海山,等.无创产前基因检测技术在胎儿染色体非整倍体筛查中的应用研究[J/CD].中国产前诊断杂志(电子版),2016,8(3):31-34.
[6]卢建,侯亚萍,黄伟伟,李怡,周伟宁,尹爱华. 471例NIPT阳性孕妇产前诊断结果分析[J].中国产前诊断杂志(电子版),2017,9(04):14-17.
[7]刘学军,刘慈,马良,刘芸兰,师园园.无创产前检测阳性患者的验证及临床意义[J].中国优生与遗传杂志,2018,26(04):45-47+54
[8]周舒香,刘妮,杨一琼,张小敏,陈玲,徐丽,李靓,罗浑金,谭赛男.5076例孕妇无创DNA产前检测结果的分析[J].中国优生与遗传杂志,2018,26(05):63-64.
[9]张卫华,周赤燕,朱晖.嘉兴地区11989例无创产前基因检测结果分析[J].中国优生与遗传杂志,2018,26(07):30-32.
[10]Gunther DF,Eugster E,Zagar AJ,et al. Ascertainment bias in Turner syndrome:new insights from girls who were diagnosed incidentally in prenatal life[J]. Pediatrics,2004,1 14(3):640-644. DOI:10.1542/peds.2003-1122-L.
[11]Lo YM,Corbetta N,Chamberlain PF,et al. Presence of fetal DNA in maternal plasma and serum[J]. Lancet 1997,350,485-487.
[12]马京梅,杨慧霞.基于母体外周血胎儿游离核酸的无创产前检查:来自国际两大学术组织的最新指南[J].中华围产医学杂志,2015,18(11):834-837. DOI:10.3760/cma.j.issn.1007-9408.2015.11.009.