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中华妇幼临床医学杂志(电子版) ›› 2020, Vol. 16 ›› Issue (05) : 584 -589. doi: 10.3877/cma.j.issn.1673-5250.2020.05.012

所属专题： 文献；

论著

无创产前检测技术筛查胎儿性染色体非整倍体的临床价值
索峰1, 张燕1, 王亿1, 王鹏1, 方媛1, 张嫚2, 王娜3, 王传霞1, 顾茂胜1,†(), 缑灵山1   
  1. 1. 徐州市妇幼保健院遗传医学中心　221009
    2. 浙江博圣生物技术股份有限公司，杭州　310012
    3. 苏州贝康医疗器械有限公司　215123
  • 收稿日期:2020-01-09 修回日期:2020-07-07 出版日期:2020-10-01
  • 通信作者: 顾茂胜

Application value of non-invasive prenatal testing for fetal sex chromosome aneuploidy

Feng Suo1, Yan Zhang1, Yi Wang1, Peng Wang1, Yuan Fang1, Man Zhang2, Na Wang3, Chuanxia Wang1, Maosheng Gu1,†(), Lingshan Gou1   

  1. 1. Center for Genetic Medicine, Xuzhou Maternity and Child Health Care Hospital, Xuzhou 221009, Jiangsu Province, China
    2. Zhejiang Biosan Biochemical Technologies Co., Ltd., Hangzhou 310012, Zhejiang Province, China
    3. Suzhou Basecare Medical Corporation Limited, Suzhou 215123, Jiangsu Province, China
  • Received:2020-01-09 Revised:2020-07-07 Published:2020-10-01
  • Corresponding author: Maosheng Gu
  • Supported by:
    Maternity and Child Health Care Science Foundation of Jiangsu Province(F201819); Medical Scientific Research Foundation of Jiangsu Commission of Health(H2019007); Science and Technology Planning Project of Xuzhou(KC18027, KC18175)
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引用本文：

索峰, 张燕, 王亿, 王鹏, 方媛, 张嫚, 王娜, 王传霞, 顾茂胜, 缑灵山. 无创产前检测技术筛查胎儿性染色体非整倍体的临床价值[J]. 中华妇幼临床医学杂志(电子版), 2020, 16(05): 584-589.

Feng Suo, Yan Zhang, Yi Wang, Peng Wang, Yuan Fang, Man Zhang, Na Wang, Chuanxia Wang, Maosheng Gu, Lingshan Gou. Application value of non-invasive prenatal testing for fetal sex chromosome aneuploidy[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2020, 16(05): 584-589.

目的

探讨无创产前检测(NIPT)在胎儿性染色体非整倍体(SCA)筛查中的临床价值。

方法

选择2018年4月至2019年9月，在徐州市妇幼保健院进行NIPT筛查的7 144例单胎妊娠孕妇为研究对象。采集孕妇外周血5 mL进行全基因组大规模平行测序，预测发生胎儿SCA的风险值。再对NIPT提示胎儿SCA孕妇，进一步进行羊水穿刺术产前诊断。本研究遵循的程序符合徐州市妇幼保健院伦理委员会所制定的伦理学标准，并得到批准[审批文号：〔2019〕伦审第(05号)]。本研究与受试对象均签署知情同意书。

结果

①7 144例孕妇中，NIPT提示胎儿SCA为27例(0.4%，27/7 144)。胎儿SCA的27例胎儿中，13例(48.1%，13/27)胎儿染色体核型为45，X；6例(22.2%，6/27)为47，XXX；5例(18.5%，5/27)为47，XYY；3例(11.1%，3/27)为47，XXY。②对NIPT提示胎儿SCA的27例孕妇中，21例进一步进行羊水穿刺术胎儿染色体核型分析发现，12例无异常，其余9例的结果与NIPT结果相符，SCA阳性预测值为42.8%(9/21)。胎儿染色体核型异常的9例胎儿中，3例胎儿染色体核型为47，XXX；3例为47，XYY；2例为47，XXY；1例为45，X。③由于NIPT结果异常进一步进行羊水穿刺术结果亦异常的9例胎儿45，X，47，XXX，47，XXY和47，XYY阳性预测值分别为10.0%(1/10)，75.0%(3/4)，67.0%(2/3)和75.0%(3/4)，假阳性率分别为90.0%(9/10)，25.0%(1/4)，33.0%(1/3)和25.0%(1/4)。④NIPT结果显示胎儿染色体核型为47，XNN者进一步行羊水穿刺术后提示真阳性者父母中位年龄均为37岁，高于假阳性者父母(30岁)。

结论

NIPT在筛查胎儿SCA方面具有较好的应用价值，但是假阳性率较高，仍需进一步进行产前诊断以确诊。

关键词: 性染色体畸变, 无创产前检测, 性染色体非整倍体, 产前诊断, 羊膜腔穿刺术, 母亲年龄, 父亲年龄, 孕妇
Objective

To investigate the application value of non-invasive prenatal testing (NIPT) for fetal sex chromosome aneuploidy (SCA).

Methods

A total of 7 144 pregnant women who underwent NIPT in Xuzhou Maternal and Child Health Care Hospital from April 2018 to September 2019 were selected into this study. The maternal peripheral blood (5 mL) were collected for genome-wide parallel sequencing to predict the risk value of fetal SCA. Then, amniocentesis was further performed on those who showed fetal SCA by NIPT. This study was approved by the Ethics Committee of Xuzhou Maternal and Child Health Care Hospital[Approval No. 2019 (05)], and clinical research informed consent was signed with each patient.

Results

① Among 7 144 pregnant women, 27 cases (0.4%) showed fetal SCA by NIPT, of which 13 cases (48.1%) had fetal karyotype of 45, X, 6 cases (22.2%) were 47, XXX, 5 cases (18.5%) were 47, XYY, 3 cases (11.1%) were 47, XXY. ② Among 27 pregnant women with SCA, 21 underwent amniocentesis for fetal karyotype analysis. Among them, 12 cases showed no abnormality, and the other 9 cases were consistent with NIPT results. The incidence of SCA was 0.16%, and the positive predictive value of SCA was 42.8% (9/21). Among them, 3 cases were 47, XXX, and 3 cases were 47, XYY, 2 cases were 47, XXY, and 1 case was 45, X. ③ Twenty-one patients underwent amniocentesis because of abnormal NIPT results. The positive predictive values of 45, X, 47, XXX, 47, XXY and 47, XYY were 10.0%(1/10), 75.0%(3/4), 67.0%(2/3) and 75.0%(3/4), respectively; the false positive rates were 90.0%(9/10), 25.0%(1/4), 33.0%(1/3) and 25.0%(1/4), respectively. ④ After further amniocentesis, pregnant women with fetal karyotype 47, XNN showed that the median age of parents with true positive was 37 years old, which was higher than that of parents with false positive (30 years old).

Conclusion

NIPT could be a potential method for SCA screening, while this technique needed to be further investigated.

Key words: Sex chromosome aberrations, Non-invasive prenatal testing, Sex chromosomal aneuploidy, Prenatal diagnosis, Amniocentesis, Maternal age, Paternal age, Pregnant women
表1 21例NIPT结果提示胎儿SCA孕妇进一步接受羊水穿刺术检查结果(例)
SCA核型 NIPT结果为SCA呈阳性孕妇例数 羊水穿刺术检查结果
接受羊水穿刺术孕妇例数 和NIPT结果一致 正常
45，X 13 10 1(45，X) 9(46，XN)
47，XXX 6 4 3(47，XXX) 1(46，XN)
47，XXY 3 3 2(47，XXY) 1(46，XN)
47，XYY 5 4 3(47，XYY) 1(46，XN)
表2 NIPT提示胎儿SCA后接受羊水穿刺术孕妇及其丈夫年龄比较
NIPT提示SCA核型 例数 羊水穿刺术提示胎儿SCA为阳性者(n＝9) 羊水穿刺术提示胎儿SCA为假阳性者(n＝12)
例数 孕妇年龄[岁，M(最小值～最大值)] 丈夫年龄[岁，M(最小值～最大值)] 例数 孕妇年龄[岁，M(最小值～最大值)] 丈夫年龄[岁，M(最小值～最大值)]
45，X 10 1 28a 30a 9 29(19～36) 29(24～40)
47，XXX 4 3 34(28～37) 36(29～37) 1 30a 28a
47，XXY 3 2 39(38～39) 39(38～39) 1 35a 35a
47，XYY 4 3 36(30～42) 40(31～42) 1 30a 31a
47，XNN 11 9 37(28～42) 37(29～42) 12 30(30～35) 30(28～35)
[1]
雷雨，董旻岳. 孕妇年龄影响胎儿性染色体非整倍体风险[J]. 浙江大学学报(医学版), 2019, 48(4): 409-413. DOI: 10.3785/j.issn.1008-9292.2019.08.10.
[2]
Fleddermann L, Hashmi SS, Stevens B, et al. Current genetic counseling practice in the United States following positive non-invasive prenatal testing for sex chromosome abnormalities[J]. J Genet Couns, 2019: 1-10. DOI: 10.1002/jgc4.1122.
[3]
陈鑫苹，朱娟，胡俊杰，等. 无创产前基因检测技术的研究进展[J]. 中华检验医学杂志，2019, 42(6): 484-488. DOI: 10.3760/j.issn.1009-9158.2019.06.016.
[4]
Deng C, Zhu Q, Liu S, et al. Clinical application of noninvasive prenatal screening for sex chromosome aneuploidies in 50，301 pregnancies: initial experience in a Chinese hospital[J]. Sci Rep, 2019, 9(1): 7767. DOI: 10.1038/s41598-019-44018-4.
[5]
Margiotti K, Cesta A, Dello Russo C, et al. Cell-free DNA screening for sex chromosomal aneuploidies in 9 985 pregnancies: Italian single experience[J]. BMC Res Notes, 2020, 13(1): 167. DOI: 10.1186/s13104-020-05009-1.
[6]
Zheng Y, Wan S, Dang Y, et al. Non-invasive prenatal testing for detection of trisomy 13, 18, 21 and sex chromosome aneuploidies in 8 594 cases[J]. Ginekol Pol, 2019, 90(5): 270-273. DOI: 10.5603/GP.2019.0050.
[7]
周赤燕，宋勤浩，王路明，等. 无创产前筛查在胎儿性染色体异常诊断中的应用价值[J]. 中国卫生检验杂志，2019, 29(14): 1718-1720.
[8]
张月萍，伍俊萍，李笑天，等. 孕中期羊水细胞染色体核型分析及其异常核型发生率的比较[J]. 中华妇产科杂志，2011, 46(9): 644-648. DOI: 10.3760/cma.j.issn.0529-567x.2011.09.002.
[9]
Cheung SW, Patel A, Leung TY. Accurate description of DNA-based noninvasive prenatal screening[J]. N Engl J Med, 2015, 372(17): 1675-1677. DOI: 10.1056/NEJMc1412222.
[10]
赵晓曦，武艾宁，于荣鑫，等. 内蒙古自治区无创产前基因检测高危孕妇的染色体异常状况分析[J/CD]. 中华妇幼临床医学杂志(电子版)，2018，14 (2): 224-229. DOI: 10.3877/cma.j.issn.1673-5250.2018.02.016.
[11]
Hu H, Wang L, Wu J, et al. Noninvasive prenatal testing for chromosome aneuploidies and subchromosomal microdeletions/microduplications in a cohort of 8 141 single pregnancies[J]. Hum Genomics, 2019, 13(1): 14. DOI: 10.1186/s40246-019-0198-2.
[12]
Zhang B, Lu BY, Yu B, et al. Noninvasive prenatal screening for fetal common sex chromosome aneuploidies from maternal blood[J]. J Int Med Res, 2017, 45(2): 621-630. DOI: 10.1177/0300060517695008.
[13]
赵旭亮，田瑞霞，王伦善，等. 早孕期胎儿颈项透明层超声检测联合胎儿DNA无创产前检测对高龄孕妇胎儿性别发育异常的诊断价值 [J/CD] . 中华妇幼临床医学杂志(电子版)，2020，16 (4): 478-482. DOI: 10.3877/cma.j.issn.1673-5250.2020.04.016.
[14]
Gil MM, Quezada MS, Revello R, et al. Analysis of cell-free DNA in maternal blood in screening for fetal aneuploidies: updated Meta-analysis[J]. Ultrasound Obstet Gynecol, 2015, 45(3): 249-266. DOI: 10.1002/uog.14791.
[15]
Petersen AK, Cheung SW, Smith JL, et al. Positive predictive value estimates for cell-free noninvasive prenatal screening from data of a large referral genetic diagnostic laboratory[J]. Am J Obstet Gynecol, 2017, 217(6): 691. e1-691. e6. DOI: 10.1016/j.ajog.2017.10.005.
[16]
Suo F, Wang C, Liu T, et al. Non-invasive prenatal testing in detecting sex chromosome aneuploidy: a large-scale study in Xuzhou area of China[J]. Clin Chim Acta, 2018, 481: 139-141. DOI: 10.1016/j.cca.2018.03.007.
[17]
Xu Y, Chen L, Liu Y, et al. Screening, prenatal diagnosis, and prenatal decision for sex chromosome aneuploidy[J]. Expert Rev Mol Diagn, 2019, 19(6): 537-542. DOI: 10.1080/14737159.2019.1613154.
[18]
姚润斯，马容，揭深秋，等. 无创产前基因检测在胎儿性染色体疾病筛查中的应用[J/CD]. 中国产前诊断杂志(电子版), 2020, 12(1): 14-19. DOI: 10.13470/j.cnki.cjpd.2020.01.004.
[19]
Jacobs P, Dalton P, James R, et al. Turner syndrome: a cytogenetic and molecular study[J]. Ann Hum Genet, 1997, 61(Pt 6): 471-483. DOI: 10.1046/j.1469-1809.1997.6160471.x.
[20]
MacDonald M, Hassold T, Harvey J, et al. The origin of 47, XXY and 47, XXX aneuploidy: heterogeneous mechanisms and role of aberrant recombination[J]. Hum Mol Genet, 1994, 3(8): 1365-1371. DOI: 10.1093/hmg/3.8.1365.
[21]
De Souza E, Morris JK; EUROCAT Working Group. Case-control analysis of paternal age and trisomic anomalies[J]. Arch Dis Child, 2010, 95(11): 893-897. DOI: 10.1136/adc.2009.176438.
[22]
Ferguson-Smith MA, Yates JR. Maternal age specific rates for chromosome aberrations and factors influencing them: report of a collaborative european study on 52 965 amniocenteses[J]. Prenat Diagn, 1984, 4(Spec): 5-44. DOI: 10.1002/pd.1970040704.
[23]
Sloter E, Nath J, Eskenazi B, et al. Effects of male age on the frequencies of germinal and heritable chromosomal abnormalities in humans and rodents[J]. Fertil Steril, 2004, 81(4): 925-943. DOI: 10.1016/j.fertnstert.2003.07.043.
[24]
Ye M, Yeh J, Kosteria I, et al. Progress in fertility preservation strategies in Turner syndrome[J]. Front Med (Lausanne), 2020, 7: 3. DOI: 10.3389/fmed.2020.00003.
[25]
马刚，许超. 克氏综合征的生育相关研究进展[J]. 山东大学学报(医学版), 2019, 57(10): 67-73. DOI: 10.6040/j.issn.1671-7554.0.2019.765.
[26]
苏杭，刘之英，赖怡，等. 高龄孕妇产前诊断结果及其首选无创产前筛查局限性的大样本分析[J/CD]. 中华妇幼临床医学杂志(电子版)，2018，14(6): 718-723. DOI: 10.3877/cma.j.issn.1673-5250.2018.06.015.
[27]
李雅红，林颖，孙云，等. 性染色体异常无创产前筛查回顾性研究[J]. 检验医学与临床，2016, 13(4): 505-507. DOI: 10.3969/j.issn.1672-9455.2016.04.028.
[28]
Gil MM, Quezada MS, Revello R, et al. Analysis of cell-free DNA in maternal blood in screening for fetal aneuploidies: updated meta-analysis[J]. Ultrasound Obstet Gynecol, 2015, 45(3): 249-266. DOI: 10.1002/uog.14791.
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