NIPT提示胎儿性染色体非整倍体疾病高危孕妇的产前诊断及妊娠选择

doi:10.12280/gjfckx.20230703

摘要/Abstract

摘要：

目的：调研无创产前筛查（noninvasive prenatal testing，NIPT）胎儿性染色体非整倍体（sex chromosomal aneuploidy，SCA）疾病高危孕妇接受产前诊断的情况以及对于SCA胎儿的接受程度和妊娠选择。方法：选取2019年12月—2023年2月自愿来天津市妇女儿童保健中心进行NIPT的孕妇共23 804例，收集NIPT成功检测并提示胎儿SCA高危的孕妇情况，对其介入性产前诊断情况以及分娩情况等进行回顾性分析。结果：NIPT检测成功者中阳性率为0.30%（72/23 730）。72例中仅44例（61.11%）接受介入性产前诊断（均进行羊膜腔穿刺）并确诊SCA病例25例，阳性预测值为56.82%（25/44）。NIPT针对性染色体三体综合征的总体阳性预测值为95.45%（21/22），针对性染色体单体综合征的阳性预测值为13.64%（3/22），2组比较，差异有统计学意义（χ²=29.700，P<0.001）。确诊SCA者中13例孕妇选择继续妊娠，均足月活产。不同类型的SCA终止妊娠率不同（47,XXX 20%，47,XXY 100%，47,XYY 40%，45,X 100%）；28例拒绝进行介入性产前诊断的孕妇经追访，2例妊娠晚期失访；1例自然流产，未进行相关遗传学检测；1例因超声发现胎儿胸腔积液、脐膨出引产，引产胎儿未作相关检测；24例足月活产（其中1例分娩后半年追访：因生殖器问题行染色体核型分析，确诊47,XXY）。结论：NIPT提示胎儿SCA高危的遗传咨询应全面谨慎，针对胎儿确诊为SCA而选择继续妊娠以及拒绝产前诊断的孕妇，应提供完善的妊娠期产检监测，以及胎儿分娩后的生长发育监测和干预的健康管理。

关键词: 无创产前检测, 产前诊断, 性染色体, 非整倍体, 妊娠选择

Abstract:

Objective: To investigate the status of prenatal diagnosis of pregnant women at high risk of fetal sex chromosomal aneuploidy (SCA) by noninvasive prenatal testing (NIPT), and the acceptance of SCA fetuses and pregnancy decision among them. Methods: Assemble basic information of 23 804 pregnant women who voluntarily came to Tianjin Women's and Children's Health Center for NIPT testing from December 2019 to February 2023, and conducted retrospective analysis for the interventional prenatal diagnosis and delivery of pregnant women with high risk of fetal SCA suggested by NIPT. Results: The positive rate of NIPT was 0.30% (72/23 730). Among the 72 pregnant women with high risk of fetal SCA detected by NIPT, only 44 cases (61.11%) underwent interventional prenatal diagnosis (all of whom underwent amniocentesis), then 25 cases were confirmed of SCA, with the total positive predictive value (PPV) of 56.82% (25/44). The overall PPV of NIPT for sex chromosomal trisomy syndrome was 95.45% (21/22), and the PPV for sex chromosomal monosomy syndrome was 13.64% (3/22), and the difference between the two groups was statistically significant ( χ²=29.700, P<0.001). Among the patients diagnosed with SCA, 13 cases chose to continue their pregnancies, and all of them had live births at term. The pregnancy termination rates varied for SCA of different subtypes following prenatal diagnosis (47, XXX 20%, 47, XXY 100%, 47, XYY 40%, 45, X 100%). 28 pregnant women who refused to undergo interventional prenatal diagnosis were followed up. 2 cases were lost to follow-up in the third trimester; 1 case of spontaneous abortion did not undergo relevant genetic testing; 1 case was induced due to fetal pleural effusion and omphalocele detected by ultrasound, and the fetus was induced without relevant testing. 24 full-term live births (one of them was followed up half a year after delivery: chromosomal karyotype analysis was performed due to genital problems, and 47, XXY was confirmed). Conclusions: Genetic counseling for high risk of fetal SCA should be comprehensive and cautious. For pregnant women diagnosed with fetal SCA who choose to continue their pregnancy and pregnant women who refuse prenatal diagnosis, comprehensive prenatal monitoring during pregnancy, as well as health management of fetal growth and development monitoring and intervention after delivery, should be provided.

Key words: Non-invasive prenatal testing, Prenatal diagnosis, Sexual chromosomes, Aneuploidy, Pregnancy decision

姚静怡, 冯树人, 谢晓媛, 刘霞. NIPT提示胎儿性染色体非整倍体疾病高危孕妇的产前诊断及妊娠选择[J]. 国际妇产科学杂志, 2024, 51(1): 32-36.

YAO Jing-yi, FENG Shu-ren, XIE Xiao-yuan, LIU Xia. Prenatal Diagnosis and Pregnancy Selection in Pregnant Women at High Risk of Fetal Sex Chromosome Aneuploidy Disease with NIPT[J]. Journal of International Obstetrics and Gynecology, 2024, 51(1): 32-36.

图/表 2

参考文献 23

[1]	Berglund A, Stochholm K, Gravholt CH. The epidemiology of sex chromosome abnormalities[J]. Am J Med Genet C Semin Med Genet, 2020, 184(2):202-215. doi: 10.1002/ajmg.c.31805.
[2]	王燕, 陈雪美, 林敏, 等. 无创产前筛查技术筛查胎儿性染色体变异的效能评价[J]. 中华医学遗传学杂志, 2021, 38(4):325-328. doi: 10.3760/cma.j.cn511374-20200422-00295.
[3]	熊诗诣, 杨颖俊, 陈建平, 等. 35827例单胎无创产前检测性染色体非整倍体病例的产前诊断及妊娠选择[J]. 中华围产医学杂志, 2018, 21(1):18-23. doi: 10.3760/cma.j.issn.1007-9408.2018.01.005.
[4]	周元圆, 翟秀璋, 卢庆, 等. 无创产前筛查技术在胎儿性染色体非整倍体中的临床应用[J]. 中国计划生育和妇产科, 2023, 15(2):96-98,107. doi: 10.3969/j.issn.1674-4020.2023.02.22.
[5]	凌颖聪, 孙淑湘, 徐进美, 等. 152例无创产前检测性染色体异常高风险的遗传学分析[J]. 中国实用医药, 2022, 17(27):122-125. doi: 10.14163/j.cnki.11-5547/r.2022.27.033.
[6]	Zheng Y, Wan S, Dang Y, et al. Clinical experience regarding the accuracy of NIPT in the detection of sex chromosome abnormality[J]. J Gene Med, 2020, 22(8):e3199. doi: 10.1002/jgm.3199.
[7]	Shear MA, Swanson K, Garg R, et al. A systematic review and meta-analysis of cell-free DNA testing for detection of fetal sex chromosome aneuploidy[J]. Prenat Diagn, 2023, 43(2):133-143. doi: 10.1002/pd.6298.
[8]	Wang JC, Sahoo T, Schonberg S, et al. Discordant noninvasive prenatal testing and cytogenetic results: a study of 109 consecutive cases[J]. Genet Med, 2015, 17(3):234-236. doi: 10.1038/gim.2014.92.
[9]	Hartwig TS, Ambye L, Sørensen S, et al. Discordant non-invasive prenatal testing (NIPT) - a systematic review[J]. Prenat Diagn, 2017, 37(6):527-539. doi: 10.1002/pd.5049.
[10]	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, 28(4):802-811. doi: 10.1002/jgc4.1122. pmid: 30946507
[11]	石海娟, 张昊晴, 李彩云, 等. 无创产前检测技术在筛查胎儿性染色体非整倍体中的应用价值[J]. 湘南学院学报(医学版), 2019, 21(4):19-22. doi: 10.16500/j.cnki.1673-498x.2019.04.005.
[12]	Johnston M, Warton C, Pertile MD, et al. Ethical issues associated with prenatal screening using non-invasive prenatal testing for sex chromosome aneuploidy[J]. Prenat Diagn, 2023, 43(2):226-234. doi: 10.1002/pd.6217.
[13]	So PL, Cheng K, Cheuk KY, et al. Parental decisions following prenatal diagnosis of sex chromosome aneuploidy in Hong Kong[J]. J Obstet Gynaecol Res, 2017, 43(12):1821-1829. doi: 10.1111/jog.13451.
[14]	李莉, 刘丽, 阮祥燕, 等. 特纳综合征中国专家共识(2022年版)[J]. 中国实用妇科与产科杂志, 2022, 38(4):424-433.doi: 10.19538/j.fk2022040111.
[15]	石苇, 梁灼健, 纪媛君, 等. 胎儿Y染色体增多的产前诊断以及遗传咨询[J]. 中国产前诊断杂志(电子版), 2021, 13(3):17-23. doi: 10.13470/j.cnki.cjpd.2021.03.004.
[16]	张丽娜, 甄恩明, 乔志坤, 等. 性染色体异常的产前诊断指征及妊娠结局分析[J]. 中国妇幼健康研究, 2020, 31(6):774-777. doi: 10.3969/j.issn.1673-5293.2020.06.015.
[17]	Ramdaney A, Hoskovec J, Harkenrider J, et al. Clinical experience with sex chromosome aneuploidies detected by noninvasive prenatal testing (NIPT): Accuracy and patient decision-making[J]. Prenat Diagn, 2018, 38(11):841-848. doi: 10.1002/pd.5339.
[18]	刘兴章, 刘晃, 郑立新, 等. 896例Klinefelter综合征遗传学诊断与临床分析[J]. 中国优生与遗传杂志, 2021, 29(6):818-820.
[19]	杨席伟, 王佳, 佴震. Klinefelter综合征研究进展[J]. 中华男科学杂志, 2021, 27(3):269-273. doi: 10.13263/j.cnki.nja.2021.03.013.
[20]	田文艳, 罗营, 李小燕, 等. 45,X/47,XYY性发育异常一例并文献复习[J]. 国际生殖健康/计划生育杂志, 2024, 43(1):11-16. doi:10.12280/gjszjk.20230352.
[21]	张晓翠, 于丽菲, 杨跃伟, 等. 45,X/46,XY染色体嵌合型不育症一例[J]. 国际生殖健康/计划生育杂志, 2024, 43(1):20-23. doi:10.12280/gjszjk.20230265.
[22]	中华医学会医学遗传学分会临床遗传学组, 中国医师协会医学遗传医师分会遗传病产前诊断专业委员会, 中华预防医学会出生缺陷预防与控制专业委员会遗传病防控学组. 低深度全基因组测序技术在产前诊断中的应用专家共识[J]. 中华医学遗传学杂志, 2019, 36(4):293-296. doi: 10.3760/cma.j.issn.1003-9406.2019.04.001.
[23]	中华医学会内分泌学分会性腺学组. 特纳综合征诊治专家共识[J]. 中华内分泌代谢杂志, 2018, 34(3):181-186. doi: 10.3760/cma.j.issn.1000-6699.2018.03.001.

SCA高危类型	NIPT报告提示内容	NIPT 高危（例）	接受介入性产前诊断（例）	接受产前诊断率（%）	确诊 SCA （例）	阳性预测值（%）
47,XXX	性染色体偏多	13	10	76.92	10	100.00
47,XXY	性染色体偏多	15	6	40.00	6	100.00
47,XYY	性染色体偏多	6	6	100.00	5	83.33
45,X	性染色体偏少	38	22	57.89	3	13.64

SCA高危类型	NIPT报告提示内容	NIPT 高危（例）	接受介入性产前诊断（例）	接受产前诊断率（%）	确诊 SCA （例）	阳性预测值（%）
47,XXX	性染色体偏多	13	10	76.92	10	100.00
47,XXY	性染色体偏多	15	6	40.00	6	100.00
47,XYY	性染色体偏多	6	6	100.00	5	83.33
45,X	性染色体偏少	38	22	57.89	3	13.64

非整倍体类型	胎儿染色体核型	确诊例数	终止妊娠例数	终止妊娠率（%）
三体	47,XXX	10	2	20.00
	47,XXY	6	6	100.00
	47,XYY	5	2	40.00
单体	45,X	1	1	100.00
嵌合体	45,X(25%)/46,XX(75%)	1	0	33.33
	45,X(10%)/46,XX(90%)	1	1
	46,XX(67%)/47,XXX(33%)（非真阳性）	1	0
合计	-	25	12	48.00

非整倍体类型	胎儿染色体核型	确诊例数	终止妊娠例数	终止妊娠率（%）
三体	47,XXX	10	2	20.00
	47,XXY	6	6	100.00
	47,XYY	5	2	40.00
单体	45,X	1	1	100.00
嵌合体	45,X(25%)/46,XX(75%)	1	0	33.33
	45,X(10%)/46,XX(90%)	1	1
	46,XX(67%)/47,XXX(33%)（非真阳性）	1	0
合计	-	25	12	48.00