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

doi:10.3877/cma.j.issn.1673-5250.2020.05.012

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
SCA核型	NIPT结果为SCA呈阳性孕妇例数	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
SCA核型	NIPT结果为SCA呈阳性孕妇例数	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)
NIPT提示SCA核型	例数	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	28^a	30^a	9	29(19～36)	29(24～40)
47，XXX	4	3	34(28～37)	36(29～37)	1	30^a	28^a
47，XXY	3	2	39(38～39)	39(38～39)	1	35^a	35^a
47，XYY	4	3	36(30～42)	40(31～42)	1	30^a	31^a
47，XNN	11	9	37(28～42)	37(29～42)	12	30(30～35)	30(28～35)

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)
NIPT提示SCA核型	例数	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	28^a	30^a	9	29(19～36)	29(24～40)
47，XXX	4	3	34(28～37)	36(29～37)	1	30^a	28^a
47，XXY	3	2	39(38～39)	39(38～39)	1	35^a	35^a
47，XYY	4	3	36(30～42)	40(31～42)	1	30^a	31^a
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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