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中华妇幼临床医学杂志(电子版) ›› 2018, Vol. 14 ›› Issue (06) : 718 -723. doi: 10.3877/cma.j.issn.1673-5250.2018.06.015

所属专题： 文献；

论著

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
苏杭1, 刘之英1, 赖怡1, 秦利1, 刘红倩1, 张雪梅1, 祝倩1, 胡婷1, 张迅1, 赵小文1, 刘珊玲1, 王和1,†()   
  1. 1. 610041　成都，四川大学华西第二医院妇产科产前诊断中心、出生缺陷与相关妇儿疾病教育部重点实验室
  • 收稿日期:2018-04-28 修回日期:2018-09-22 出版日期:2018-12-01
  • 通信作者: 王和

Prenatal diagnosis results of advanced maternal age women and limitations of preferred non-invasive prenatal screening to them: a large sample analysis

Hang Su1, Zhiying Liu1, Yi Lai1, Li Qin1, Hongqian Liu1, Xuemei Zhang1, Qian Zhu1, Ting Hu1, Xun Zhang1, Xiaowen Zhao1, Shanling Liu1, He Wang1,†()   

  1. 1. Department of Prenatal Diagnosis of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2018-04-28 Revised:2018-09-22 Published:2018-12-01
  • Corresponding author: He Wang
  • About author:
    Corresponding author: Wang He, Email:
  • Supported by:
    National Science and Technology Infrastructure Program(2014BAI06B03)
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引用本文：

苏杭, 刘之英, 赖怡, 秦利, 刘红倩, 张雪梅, 祝倩, 胡婷, 张迅, 赵小文, 刘珊玲, 王和. 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/OL]. 中华妇幼临床医学杂志(电子版), 2018, 14(06): 718-723.

Hang Su, Zhiying Liu, Yi Lai, Li Qin, Hongqian Liu, Xuemei Zhang, Qian Zhu, Ting Hu, Xun Zhang, Xiaowen Zhao, Shanling Liu, He Wang. Prenatal diagnosis results of advanced maternal age women and limitations of preferred non-invasive prenatal screening to them: a large sample analysis[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2018, 14(06): 718-723.

目的

探讨高龄(预产期年龄≥35岁)孕妇产前诊断应用无创产前筛查(NIPS)的价值，以及首选NIPS的局限性。

方法

选择2009年1月至2013年12月，于四川大学华西第二医院接受产前诊断的20 751例高龄孕妇为研究对象。采用回顾性分析方法，对其羊水穿刺胎儿细胞遗传学产前诊断结果进行分析，对胎儿染色体异常进行分类，计算各类染色体异常所占比例。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。

结果

这20 751例高龄孕妇产前诊断结果显示：①胎儿的细胞遗传学产前诊断，检出染色体异常为380例，检出率为1.83%(380/20 751)。其中，21-、18-及13-三体综合征胎儿分别为173例(45.53%，173/380)，51例(13.42%，51/380)及9例(2.37%，9/380)，总计为233例(61.32%)；性染色体异常胎儿为78例(20.53%，78/380)，染色体异常携带者为49例(12.89%，49/380)，其他染色体异常胎儿为20例(5.26%，20/380)，总计为147例(38.68%)。如果首先采取NIPS进行产前诊断，则检测胎儿的目标疾病为21-、18-、13-三体综合征，可检出的胎儿染色体异常仅占全部有临床表型的染色体异常胎儿总数的70.39%(233/331)。②2009—2013年，胎儿染色体异常检出率依次为1.49%(38/2 543)、1.44%(51/3 548)、1.87%(87/4 651)、1.85%(99/5 345)、2.25%(105/4 664)，胎儿染色体异常检出率整体呈逐年上升趋势。

结论

NIPS作为产前诊断的一线检测手段，首选该技术筛查胎儿染色体异常，尤其是对于高龄孕妇具有局限性，应该慎重。

关键词: 染色体畸变, 母亲年龄, 产前诊断, 染色体, 无创产前筛查, 胎儿
Objective

Based on the analysis of the cytogenetic prenatal diagnosis results, the values of non-invasive prenatal screening (NIPS) were analyzed in the detection of the advanced maternal age women (≥35 years old) and limitations of preferred to NIPS according to the fetal chromosomal abnormalities.

Methods

From January 2009 to December 2013, a total of 20 751 advanced maternal age women who received prenatal diagnosis in West China Second University Hospital, Sichuan University were selected as research subjects. The results of the fetal cytogenetic prenatal diagnosis by amniocentesis of those 20 751 advanced maternal age women were analyzed retrospectively. The chromosome abnormalities of the fetus were classified and the proportions of all kinds of chromosome abnormalities were calculated. This research was in line with the requirements of World Medical Association Declaration of Helsinki revised in 2013.

Results

① A total of 380 chromosome abnormalities were detected among those 20 751 advanced maternal age women according to the results of the cytogenetic prenatal diagnosis. The total detection rate of chromosome abnormalities in advanced maternal age women was 1.83% (380/20 751), including 173 cases of trisomy 21 (45.53%, 173/380), 51 cases of trisomy 18 (13.42%, 51/380), 9 cases of trisomy 13 (2.37%, 9/380), 78 cases of sex chromosome abnormalities (20.53%, 78/380), 49 carriers of chromosomal abnormality (12.89%, 49/380), 20 cases of other chromosome abnormalities (5.26%, 20/380). If NIPS was used as the preferred prenatal diagnosis method, then the aimed diseases of NIPT detecting were trisomy 21, trisomy 18 and trisomy 13, so the chromosome abnormalities which could be detected out would probably account for 70.39% (233/331) of all chromosomal abnormalities with clinical phenotypes. ②From 2009 to 2013, the detection rates of fetal chromosomal abnormalities were 1.49% (38/2 543), 1.44% (51/3 548), 1.87% (87/4 651), 1.85% (99/5 345), and 2.25% (105/4 664), respectively, and the detection rate of fetal chromosomal abnormalities was increasing year by year.

Conclusion

NIPS as the preferred detection method for screening of fetal chromosomal abnormalities in advanced maternal age women should be cautiously used.

Key words: Chromosome aberrations, Maternal age, Prenatal diagnosis, Chromosome, Non-invasive prenatal screening, Fetus
表1 380例胎儿染色体异常分类、检出率及其构成比分析结果[%(n/n′)]
胎儿染色体异常分类 例数 胎儿染色体异常检出率 胎儿染色体异常构成比
21-三体综合征 173 0.83(173/20 751) 45.53(173/380)
18-三体综合征 51 0.25(51/20 751) 13.42(51/380)
13-三体综合征 9 0.04(9/20 751) 2.37(9/380)
性染色体异常 78 0.38(78/20 751) 20.53(78/380)
染色体异携带者 49 0.23(49/20 751) 12.89(49/380)
其他染色体异常 20 0.10(20/20 751) 5.26(20/380)
合计 380 1.83(380/20 751) 100.00(380/380)
表2 380例染色体异常胎儿的染色体核型及其构成比[例数(%)]
染色体核型 构成比 染色体核型 构成比
21-三体综合征 173(45.53) ? 46，X，inv(X) 1(0.26)
? 47，XX(XY)，＋21 173(45.53) ? 46，XX，t(1；16)(q10；p10)mat 1(0.26)
18-三体综合征 51(13.42) ? 46，XX，t(1；9)(p35；p11)pat 1(0.26)
? 47，XX(XY)，＋18 51(13.42) ? 46，XX，t(11；22)(q24；q13) 1(0.26)
13-三体综合征 9(2.37) ? 46，xx，t(12；18)(q21；q12) 1(0.26)
? 47，XX(XY)，＋13 9(2.37) ? 46，XX，t(2；12)(q11；q11)mat 1(0.26)
性染色体异常 78(20.53) ? 46，XX，t(2；15)(q22；q24)，9qh＋ 1(0.26)
? 45，X 6(1.58) ? 46，XX，t(4；5)(q28；q23) 1(0.26)
? 45，X，[9]/47，XXX[5]/46，XX[6] 1(0.26) ? 46，XX，t(4；8)(q21；p11) 1(0.26)
? 45，X，inv9 1(0.26) ? 46，XX，t(5；15)(q23；q25) 1(0.26)
? 45，X[4]/46，XX[97] 1(0.26) ? 46，XX，t(6；19)(p11；q11)mat 1(0.26)
? 45，X[1]/46，XXY[1]/46，XY[34] 1(0.26) ? 46，XX，t(8；10)(q23；p25)pat 1(0.26)
? 45，X[3]/46，X，i(X)(q10)[21] 1(0.26) ? 46，XX，t(8；22)(q24.2；q12)mat 1(0.26)
? 45，X[3]/46，XX[17] 1(0.26) ? 46，XX，t(9；10)(q21；p12) 1(0.26)
? 45，X[3]/46，XY[27] 1(0.26) ? 46，XX，t(9；14)(q32；q31)mat 1(0.26)
? 45，X[4]/46，XX[32] 1(0.26) ? 46，XY，der(10)(q？) 1(0.26)
? 45，X[4]/46，XY[28] 1(0.26) ? 46，XY，t(1；2)(p31；q21) 1(0.26)
? 45，X[5]/46，XX[30] 1(0.26) ? 46，XY，t(1；4)(q31；p12) 1(0.26)
? 45，X[7]/46，X，i(X)(q10)[13] 1(0.26) ? 46，XY，t(10；13)(q11；q33) 1(0.26)
? 45，X[7]/46，XX[27] 1(0.26) ? 46，XY，t(12；16)(p12；p12)pat 1(0.26)
? 45，X[7]/46，XY[31] 1(0.26) ? 46，XY，t(19；20)(p13；q22)pat 1(0.26)
? 45，X[9]/46，XX[11] 1(0.26) ? 46，XY，t(2；11)[5]/46，XY[27] 1(0.26)
? 46，X，del(X)(p21→ter) 1(0.26) ? 46，XY，t(2；15)(p14；q24) mat 1(0.26)
? 46，X，i(X) 1(0.26) ? 46，XY，t(2；18)(q34；p11) 1(0.26)
? 46，X，i(Xq) 1(0.26) ? 46，XY，t(4：18)(q21；q23)mat 1(0.26)
? 46，XX[5]/46，XY，[25] 1(0.26) ? 46，XY，t(5；7)(q22；p22) 1(0.26)
? 46，XY[27]/46，XX[14] 1(0.26) ? 46，XY，t(6；13)(q14；q33) 1(0.26)
? 47，XXX[5]/46，XX[15] 1(0.26) ? 46，XY，t(8；12)(q23；q13)[11]/46，XY[19] 1(0.26)
? 47，XXX 12(3.16) ? 46，XY，t(8；15)(p23；q22) 1(0.26)
? 47，XXX[12]/45，X[5] 1(0.26) ? 46，XY，t(3；15)(q22；q22) 1(0.26)
? 47，XXX[5]/46，XX[18] 1(0.26) ? 46，XX，t(2；4)(q21；q32) 1(0.26)
? 47，XXY 25(6.58) ? 46，XX，t(6；9)(p10′p10) 1(0.26)
? 47，XXY[10]/46，XY[29] 1(0.26) ? 46，XY，t(X；3)(q21；q21)mat 1(0.26)
? 47，XXY[19]/46，XY[14] 1(0.26) 其他染色体异常 20(5.26)
? 47，XYY 6(1.58) ? 46，XX，del(18)(q21) 1(0.26)
? 47，XYY，inv9 1(0.26) ? 46，XX，der(17) 1(0.26)
? 47，XYY[6]/46，XY[14] 1(0.26) ? 46，XX，der(18)(p？) 1(0.26)
? 47，XYY[14]/46，XY[13] 1(0.26) ? 46，XX，der(4)(p？) 1(0.26)
? 47，XYY[3]/46，XY[35] 1(0.26) ? 46，XY，del(11)(q？) 1(0.26)
? 47，XYY[4]/46，XY[35] 1(0.26) ? 46，XY，del(21)(qter→p10) 2(0.53)
染色体异常携带者 49(12.89) ? 47，XY，＋22[3]/46，XY[83] 1(0.26)
? 45，XX，rob(13；14)(q10；q10) 3(0.79) ? 47，XX，＋16[6]/46，XX[20] 1(0.26)
? 45，XX，rob(13；14)(q10；q10)pat 1(0.26) ? 47，XX，＋4[2]/46，XX[28] 1(0.26)
? 45，XX，rob(13；21)(q10；q10) 1(0.26) ? 47，XX，＋7[3]/46，XY[3] 1(0.26)
? 45，XX，rob(14；22)(q10；q10) 2(0.53) ? 47，XX，＋9 1(0.26)
? 45，XX，rob(15；22)(q10；q10)[23]/46，XX[7] 1(0.26) ? 47，XY，＋2[2]/46，XY[33] 1(0.26)
? 45，XX，rob(15；22)(q10；q10)pat 1(0.26) ? 47，XY，＋2[2]/46，XY[36] 1(0.26)
? 45，XY，rob(13；14)(q10；q10)mat 2(0.53) ? 47，XY，＋20[13]/46，XY[17] 1(0.26)
? 45，XY，rob(13；14)(q10；q10) 1(0.26) ? 47，XY，＋20[5]/46，XY[46] 1(0.26)
? 45，XY，rob(14；21)(q10；q10)pat 1(0.26) ? 47，XY，＋4[3]/46，XY[32] 1(0.26)
? 45，XY，rob(14；21)(q10；q10) 1(0.26) ? 47，XY，＋M[8]/46，XY[2] 1(0.26)
? 45，XY，rob(14；22)(q10；q10) 1(0.26) ? 47，XY，＋mar 1(0.26)
? 45，XY，rob(13；14)(q10；q10) 1(0.26) ? 47，XY，＋mar[4]/46，XY[10] 1(0.26)
图1 2009-2013年20 751例高龄孕妇中，不同年份胎儿染色体异常检出率折线图
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