Please wait a minute...
浙江大学学报（医学版）
浙江大学学报（医学版）  2017, Vol. 46 Issue (3): 256-261    DOI: 10.3785/j.issn.1008-9292.2017.06.05
出生缺陷预防专题     
高龄孕妇外周血胎儿游离DNA产前筛查胎儿常见非整倍体的临床意义
朱晖1,2, 苗正友2, 钱叶青1, 李红阁1, 金晶磊1, 贺晶1, 董旻岳1
1. 浙江大学医学院附属妇产科医院 生殖遗传教育部重点实验室, 浙江 杭州 310006;
2. 嘉兴市妇幼保健院妇产科, 浙江 嘉兴 314051
Detection of cell-free fetal DNA in maternal plasma for noninvasive prenatal screening of fetal chromosomal aneuploidies in women of advanced maternal age
ZHU Hui1,2, MIAO Zhengyou2, QIAN Yeqing1, LI Hongge1, JIN Jinglei1, HE Jing1, DONG Minyue1
1. Key Laboratory of Reproductive Genetics, Ministry of Education, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China;
2. Department of Gynaecology and Obstetrics, Jiaxing Maternal and Child Health Hospital, Jiaxing 314015, China
 全文: PDF(1000 KB)  
摘要：

目的：评估孕妇外周血胎儿游离DNA检测这一无创产前筛查（NIPS）技术在高龄孕妇产前筛查中的效率，并据此提出高龄孕妇产前筛查及诊断的优化策略。方法：以2015年2月至2016年9月在浙江大学医学院附属妇产科医院和嘉兴市妇幼保健院行NIPS并完成妊娠结局随访的10 584名高龄孕妇为研究对象，统计NIPS在高龄孕妇中检测胎儿常见染色体非整倍体的敏感度、特异度、阳性预测值和阴性预测值，并分析孕妇年龄与胎儿常见染色体非整倍体疾病的相关性。结果：NIPS检测高龄孕妇胎儿21三体的敏感度为100.00%、特异度为99.96%、阳性预测值为91.67%、阴性预测值为100.00%；检测18三体的敏感度为100.00%、特异度为99.93%、阳性预测值为68.18%、阴性预测值为100.00%；检测13三体的敏感度为100.00%、特异度为99.97%、阳性预测值为25.00%、阴性预测值为100.00%。胎儿21三体的高风险率和真阳性率随孕妇年龄的增长而升高（均P<0.01）。其中，35~37岁组与38~40岁组21三体的高风险率和真阳性率差异有统计学意义（均P<0.05）；38~40岁组与41岁以上年龄组21三体的高风险率差异有统计学意义（P<0.05），但真阳性率差异无统计学意义（P>0.05）。结论：NIPS用于高龄孕妇的产前筛查具有良好的检测效率。对于预产期年龄38岁以下的孕妇，NIPS可作为优先选项；对于预产期年龄超过41岁的孕妇，建议选择介入性产前诊断；而对于预产期年龄为38~<41岁的孕妇，则可充分告知后酌情选择。
关键词： 孕妇/血液;  DNA;  新生儿筛查;  母亲年龄;  非整倍性;  产前诊断;  染色体畸变    
Abstract:

Objective:To evaluate the efficiency of cell-free fetal DNA detection as a non-invasive prenatal screening (NIPS) method for women of advanced maternal age. Methods:A total of 10 584 women of advanced maternal age who received NIPS were recruited from the Women's Hospital, Zhejiang University School of Medicine and Jiaxing Maternal and Child Health Hospital during February 2015 and September 2016. The pregnancy outcome was followed-up. The sensitivity, specificity, positive and negative predictive value of fetal chromosomal aneuploidy detected in NIPS were analyzed. And the relationship between maternal age and fetal common chromosomal aneuploidy was analyzed. Results:The sensitivity, specificity, positive and negative predictive value of NIPS were 100.00%, 99.96%, 91.67%, 100.00% for trisomy 21, 100.00%, 99.93%, 68.18%, 100.00% for trisomy 18, and 100.00%, 99.97%, 25.00%, 100.00% for trisomy 13. High-risk rate and true positive rate of trisomy 21 were positively correlated with the maternal age (all P<0.01). There were significant differences in high-risk rate and true positive rate between 35-37 year old groups and 38-40 year old groups (all P<0.05). Such difference was also found in high-risk rate between 38-40 year old group and ≥ 41 year old group (P<0.05), but not in true positive rate between two groups (P>0.05). Conclusions:NIPS is effective for fetal chromosomal aneuploidy screening in women of advanced maternal age. For women under 38 years of age, NIPS is preferred; for women of 41 and above, invasive diagnostic methods are suggested; and for women between 38-41 years old, the option can be determined by themselves after risks and advantages were fully informed.
Key words: Pregnant women/blood    DNA    Neonatal screening    Maternal age    Aneuploidy    Prenatal diagnosis    Chromosome aberrations
收稿日期: 2017-02-15 出版日期: 2017-06-25
CLC:  R394.3  
基金资助:

国家重点研发计划（2016YFC1000703）；浙江省医药卫生科技计划（2018KY809）
通讯作者: 董旻岳(1964-),男,博士,主任医师,博士生导师,主要从事生殖医学及围产医学研究;E-mail:dongmy@zju.edu.cn     E-mail: dongmy@zju.edu.cn
作者简介: 朱晖(1981-),女,硕士研究生,副主任医师,主要从事妇产科学研究;E-mail:6842839@qq.com
服务　　
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章　　

引用本文:

朱晖 等. 高龄孕妇外周血胎儿游离DNA产前筛查胎儿常见非整倍体的临床意义[J]. 浙江大学学报（医学版）, 2017, 46(3): 256-261.

ZHU Hui, MIAO Zhengyou, QIAN Yeqing, LI Hongge, JIN Jinglei, HE Jing, DONG Minyue. Detection of cell-free fetal DNA in maternal plasma for noninvasive prenatal screening of fetal chromosomal aneuploidies in women of advanced maternal age. Journal of ZheJiang University(Medical Science), 2017, 46(3): 256-261.

链接本文:

http://www.zjujournals.com/xueshu/med/CN/10.3785/j.issn.1008-9292.2017.06.05    或    http://www.zjujournals.com/xueshu/med/CN/Y2017/V46/I3/256

[1] 陈铁峰,毛倩倩,鲁莉萍,等.羊水细胞染色体核型分析与高龄孕妇年龄因素的相关性[J].中华检验医学杂志,2016,39(6):423-426. CHEN Tiefeng, MAO Qianqian, LU Liping, et al. Relationship between fetal karyotype and age of pregnancy[J]. Chinese Journal of Laboratory Medicine,2016,39(6):423-426. (in Chinese)
[2] 林晓娟,孙庆梅,何晓春,等.胎儿染色体核型异常的临床分析[J].中华妇幼临床医学杂志:电子版,2016,12(2):173-178. LIN Xiaojuan, SUN Qingmei, HE Xiaochun, et al. Clinical analysis of fetal chromosomes karyotype abnormalities[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics (Electronic Edition),2016,12(2):173-178. (in Chinese)
[3] 陈英苹,郑芳秀,周琴,等.无创产前检测在高龄孕妇中检测胎儿非整倍体的临床应用[J].生殖与避孕,2016,36(9):708-711. CHEN Yingping, ZHENG Fangxiu, ZHOU Qin, et al. Application of high-throughput sequencing in the diagnosis of fetal aneuploidies in women with advanced maternal age[J]. Reproduction & Contraception,2016,36(9):708-711. (in Chinese)
[4] 朱宇宁.胎儿染色体异常适宜产前诊断技术研究[D].杭州:浙江大学,2015. ZHU Yuning. Study on fetal chromosome abnormality and appropriate prenatal diagnostic technique[D]. Hangzhou:Zhejiang University,2015. (in Chinese)
[5] 中华人民共和国卫生部.产前诊断技术管理办法[Z].2002-12-13. Ministry of Health of the People's Republic of China. Regulations on the management of prenatal diagnostic techniques[Z].2002-12-13. (in Chinese)
[6] IWARSSON E, JACOBSSON B, DAGERHAMN J, et al. Analysis of cell-free fetal DNA in maternal blood for detection of trisomy 21, 18 and 13 in a general pregnant population and in a high risk population-a systematic review and meta-analysis[J]. Acta Obstet Gynecol Scand,2017,96(1):7-18.
[7] GIL M M, QUEZADA M S, BREGANT B, et al. Implementation of maternal blood cell-free DNA testing in early screening for aneuploidies[J]. Ultrasound Obstet Gynecol,2013,42(1):34-40.
[8] MACKIE F L, HEMMING K, ALLEN S, et al. The accuracy of cell-free fetal DNA-based non-invasive prenatal testing in singleton pregnancies:a systematic review and bivariate meta-analysis[J]. BJOG,2017,124(1):32-46.
[9] 葛建民,孙波,赵卫华,等.无创产前基因检测胎儿染色体非整倍体的临床应用研究[J].中国妇幼保健,2014,29(12):1889-1892. GE Jianmin, SUN Bo, ZHAO Weihua, et al. Study on clinical application of non-invasive prenatal genetic testing for fetal chromosomal aneuploidy[J]. Maternal and Child Health Care of China,2014,29(12):1889-1892. (in Chinese)
[10] 中华人民共和国国家卫生和计划生育委员会.孕妇外周血胎儿游离DNA产前筛查与诊断技术规范[Z].2016-10-27. National Health and Family Planning Commission of the People's Republic of China. Technical specifications for noninvasive prenatal screening and diagnosis using cell-free fetal DNA[Z].2016-10-27. (in Chinese)
[11] JIANG F, REN J, CHEN F, et al. Noninvasive Fetal Trisomy (NIFTY) test:an advanced noninvasive prenatal diagnosis methodology for fetal autosomal and sex chromosomal aneuploidies[J]. BMC Med Genomics,2012,5:57.
[12] CHEN S, LAU T K, ZHANG C, et al. A method for noninvasive detection of fetal large deletions/duplications by low coverage massively parallel sequencing[J]. Prenat Diagn,2013,33(6):584-590.
[13] TABOR A, ALFIREVIC Z. Update on procedure-related risks for prenatal diagnosis techniques[J]. Fetal Diagn Ther,2010,27(1):1-7.
[14] LO Y M, CORBETTA N, CHAMBERLAIN P F, et al. Presence of fetal DNA in maternal plasma and serum[J]. Lancet,1997,350(9076):485-487.
[15] LO Y M, ZHANG J, LEUNG T N, et al. Rapid clearance of fetal DNA from maternal plasma[J]. Am J Hum Genet,1999,64(1):218-224.
[16] CHIU R W, AKOLEKAR R, ZHENG Y W, et al. Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing:large scale validity study[J]. BMJ,2011,342:c7401.
[17] VRACHNIS N, VLACHADIS N, CREATSAS G. DNA Sequencing versus standard prenatal aneuploidy screening[J]. N Engl J Med,2014,371(6):578.
[18] HSIEH T T, LIOU J D, HSU J J, et al. Advanced maternal age and adverse perinatal outcomes in an Asian population[J]. Eur J Obstet Gynecol Reprod Biol,2010,148(1):21-26.
[19] MA J, HONG P, FU J, et al. Prenatal diagnostic testing among women referred for advanced maternal age in Beijing, 2001-2012[J]. Int J Gynaecol Obstet,2014,125(3):232-236.
[20] 李东明,林飞,徐钰琪,等.南宁地区19165例孕妇唐氏综合征干预研究[J].中国优生与遗传杂志,2014,22(12):61-62. LI Dongming, LIN Fei, XU Yuqi, et al. Study on interference in Down's syndrome for 19165 pregnant women in Nanning[J]. Chinese Journal of Birth Health & Heredity,2014,22(12):61-62. (in Chinese)
[21] 贺江梅,郑梅玲,张桂林,等.山西地区1691例羊膜腔穿刺产前诊断临床研究[J].中国优生与遗传杂志,23(10):46-48. HE Jiangmei, ZHENG Meiling, ZHANG Guilin, et al. The clinical research of prenatal diagnosis for amniocentesis 1691 cases of Shanxi area[J]. Chinese Journal of Birth Health & Heredity,2015,23(10):46-48. (in Chinese)
[22] GRANDE M, STERGIOTOU I, BOROBIO V, et al. Heterotrisomy recurrence risk:a practical maternal age-dependent approach for excess trisomy 21 risk calculation after a previous autosomal trisomy[J]. J Matern Fetal Neonatal Med,2017,30(13):1613-1615.
[1] 温弘 等. 产前诊断Joubert综合征一例并文献复习[J]. 浙江大学学报（医学版）, 2017, 46(3): 274-278.
[2] 黄新文 等. 浙江省新生儿氨基酸代谢疾病筛查及随访分析[J]. 浙江大学学报（医学版）, 2017, 46(3): 233-239.
[3] 陈益明 等. 中孕期母血清甲胎蛋白和游离β-hCG筛查胎儿腹裂和脐膨出的效率[J]. 浙江大学学报（医学版）, 2017, 46(3): 268-273.
[4] 洪芳 等. 浙江省新生儿有机酸尿症筛查及随访分析[J]. 浙江大学学报（医学版）, 2017, 46(3): 240-247.
[5] 郑静 等. 浙江省新生儿脂肪酸氧化代谢疾病筛查及随访分析[J]. 浙江大学学报（医学版）, 2017, 46(3): 248-255.
[6] 李恩书 等. 不同氧浓度培养对体外受精-胚胎移植及子代出生缺陷的影响[J]. 浙江大学学报（医学版）, 2017, 46(3): 290-294.
[7] 严恺 等. 出生缺陷相关遗传病产前诊断技术新进展[J]. 浙江大学学报（医学版）, 2017, 46(3): 227-232.
[8] 孙义锡 等. 单核苷酸多态性微阵列芯片在早期自然流产绒毛组织遗传学分析中的应用[J]. 浙江大学学报（医学版）, 2017, 46(3): 262-267.
[9] 历雪莹 等. DNA甲基化及其靶向治疗在急性髓系白血病中的研究进展[J]. 浙江大学学报（医学版）, 2016, 45(4): 387-394.
[10] 沈亲亲, 张檀. 产前筛查血清学指标与不良妊娠结局关系的研究进展[J]. 浙江大学学报（医学版）, 2015, 44(3): 339-343.
[11] 卢佩颖, 谷卫, 庞晓虹, 单鹏飞. 成人Silver-Russell综合征1例并文献复习[J]. 浙江大学学报（医学版）, 2015, 44(3): 335-338.
[12] 席晓平, 曾令霞, 余方方, 刘华胜. DNMT3A基因突变对急性髓系白血病预后影响的meta分析[J]. 浙江大学学报（医学版）, 2015, 44(2): 197-203.
[13] 苗华，等. 联合应用基因表达谱和拷贝数变异信息探索结直肠癌分子亚型[J]. 浙江大学学报（医学版）, 2014, 43(4): 420-426.
[14] 卢晓辉，等. 人源性抗乳腺癌HER-2噬菌体单链抗体库的构建与筛选[J]. 浙江大学学报（医学版）, 2014, 43(4): 434-440.
[15] 张薇，等. 神经系统显著表达的丝氨酸/精氨酸富集蛋白1在小鼠大脑发育过程中的表达与分布[J]. 浙江大学学报（医学版）, 2014, 43(1): 51-57.