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中华妇幼临床医学杂志(电子版)

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2018, Vol. 14 ›› Issue (06): 718 -723. doi: 10.3877/cma.j.issn.1673-5250.2018.06.015

Special Issue: ；

Original Article

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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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
[1]
郑静，卓越，孙大康，等. 不同年龄段孕妇无创DNA产前检测结果对比分析[J]．中国妇幼保健，2015，30(36):6538-6540.
[2]
季修庆，蒋涛，林颖，等. 无创产前检测在高龄孕妇产前筛查唐氏综合征中的应用[J]．临床检验杂志，2015, 33(5):325-327.
[3]
国家卫生计生委办公厅. 国家卫生计生委办公厅关于规范有序开展孕妇外周血胎儿游离DNA产前筛查与诊断工作的通知(国卫办妇幼发[2016] 45号)[EB/OL]. (2016-10-27) [2018-08-10].

URL    
[4]
Kuliev A, Verlinsky Y. The role of preimplantation genetic diagnosis in women of advanced reproductive age[J]. Curr Opin Obstet Gynecol, 2003, 15(3): 233-238.
[5]
Kong CW, Leung TN, Lung TY, et al. Risk factors for procedure related fetal losses after midtrimester genetic amniocentesis[J]. Prenat Diagn, 2006, 26(10): 925-930.
[6]
Tesng JJ, Chou MM, Lo FC, et al. Detection of chromosome aberrations in the second trimester using genetic amniocentesis: experience during 1995-2004[J]. Taiwan J Obstet Gynecol, 2006, 45(1): 39-41.
[7]
石庆华，许波，杨庆岭，等. 非整倍体和人类生殖健康[J]. 中国科学技术大学学报，2008, 38(8): 883-889.
[8]
Liang X, Ma J, Schatten H, et al. Epigenetic changes associated with oocyte aging[J]. Sci China Life Sci, 2012, 55(8): 670-676.
[9]
Alexander E, Kelly S, Kerzin-Storrar L. Non-invasive prenatal testing: UK genetic counselors′ experiences and perspectives[J]．J Genet Couns, 2015, 24(2): 300-311.
[10]
Dan S, Wang W, Ren JH, et al. Clinical application of massively parallel sequencing-based prenatal noninvasive fetal trisomy test for trisomies 21 and 18 in 11 105 pregnancies with mixed risk factors[J]. Prenat Diagn, 2012, 32(13): 1225-1232.
[11]
Palomaki GE, Kloza EM, Lambert-Messerlian GM, et al. DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study[J]. Genet Med, 2011, 13(11): 913-920.
[12]
Chiu RW, Akolekar R, Zheng YW, et al. Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study[J]. BMJ, 2011, 342(7790): c7401.
[13]
Ehrich M, Deciu C, Zwiefelhofer T, et al. Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting[J]. Am J Obstet Gynecol, 2011, 204(3): 205.e1-205.e11.
[14]
Sehnert AJ, Rhees B, Comstock D, et al. Optimal detection of fetal chromosomal abnormalities by massively parallel DNA sequencing of cell-free fetal DNA from maternal blood[J]. Chin Chem, 2011, 57(7): 1042-1049.
[15]
Sparks AB, Struble CA, Wang ET, et al. Noninvasive prenatal detection and selective analysis of cell-free DNA obtained from maternal blood: evaluation for trisomy 21 and trisomy 18[J]. Am J Obstet Gynecol, 2012, 206(4): 319. e1-319. e9.
[16]
Norton ME, Brar H, Weiss J, et al. Non-invasive chromosomal evaluation (NICE) study: results of a multicenter prospective cohort study for detection of fetal trisomy 21 and trisomy 18[J]. Am J Obstet Gynecol, 2012, 207(2): 137. e1-137. e8.
[17]
Bianchi DW, Platt LD, Coldberg JD, et al. Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing[J]. Obstet Gynecol, 2012, 119(5): 890-901.
[18]
Ashoor G, Syngelaki A, Wagner M, et al. Chromosome-selective sequencing of maternal plasma cell–free DNA for first-trimester detection of trisomy 21 and trisomy 18[J]. Am J Obstet Gynecol, 2012, 206(4): 322. e1-322. e5.
[19]
Gregg AR, Gross SJ, Best RG, et al. ACMG statement on noninvasive prenatal screening for fetal aneuploidy[J]．Genet Med, 2013, 15(5): 395-398.
[20]
Canick JA, Palomaki GE, Kloza EM, et al. The impact of maternal plasma DNA fetal fraction on next generation sequencing tests for common fetal aneuploidies[J]. Prenat Diagn, 2013, 33(7): 667-674.
[21]
Vora NL, Johnson KL, Basu S, et al. A multifactorial relationship exists between total circulating cell-free DNA levels and maternal BMI[J]. Prenat Diagn, 2012, 32(9): 912-914.
[22]
Wang E, Batey A, Struble C, et al. Gestational age and maternal weight effects on fetal cell-free DNA in maternal plasma[J]. Prenat Diagn, 2013, 33(7): 662-666.
[23]
Ashoor G, Poon L, Syngelaki A, et al. Fetal fraction in maternal plasma cell-free DNA at 11-13 weeks′ gestation: effect of maternal and fetal factors[J]. Fetal Diagn Ther, 2012, 31(4): 237-243.
[24]
Bianchi DW, Prosen T, Platt LD, et al. Massively parallel sequencing of maternal plasma DNA in 113 cases of fetal nuchal cystic hygroma[J]. Obstet Gunecol, 2013, 121(5): 1057-1062.
[25]
Mazloom AR, Dzakula Z, Oeth P, et al. Noninvasive prenatal detection of sex chromosomal aneuploidies by sequencing circulating cell-free DNA from maternal plasma[J]. Prenat Diagn, 2013, 33(6): 591-597.
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