高龄孕妇无创产前DNA筛查效能分析
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摘要
目的探讨无创产前DNA筛查在高龄孕妇中的应用价值。方法在知情同意原则下3 585例高龄孕妇(高龄孕妇组)与1 517例非高龄低风险孕妇(对照组)选择无创产前筛查(NIPT),结果异常的孕妇再行羊膜腔穿刺,羊水细胞培养后染色体G320显带核型分析。结果高龄孕妇组中NIPT共检出T21高风险16例,T18高风险3例;对照组中检出T21高风险1例,T18高风险1例;经羊水产前诊断对T21、T18的阳性预测值均达100. 0%。高龄孕妇组中NIPT检出19例性染色体非整倍体高风险,经知情同意10例行羊水产前诊断,其中确诊符合4例,对性染色体的阳性预测值为40. 0%;与对照组孕妇相比,NIPT对高龄孕妇性染色体异常筛查效能差异无统计学意义(P>0. 05)。但>38岁的高龄孕妇性染色体的阳性预测值(61. 5%)显著高于<38岁的人群(28. 6%)。高龄孕妇组应用NIPT后介入性产前诊断率仅为0. 6%。结论 NIPT对于T21和T18有较高的准确性和敏感性,对性染色体的准确性随年龄增加而提高。NIPT的临床应用可明显减少不必要的介入性产前诊断,提高产前筛查的效能。
Objective To explore the application value of noninvasive prenatal DNA screening in pregnant women of advanced maternal age. Methods Noninvasive prenatal screening was performed among 3 585 pregnant women of advanced maternal age( advanced maternal age group) and 1 517 low-risk pregnant women of childbearing age( control group) under the principle of informed consent,then the pregnant women with abnormal results underwent amniocentesis,chromosomal G320 banding karyotyping was carried out after amniotic cell culture. Results In advanced maternal age group,16 T21 high-risk pregnant women and 3 T18 high-risk pregnant women were detected by NIPT. In control group,1 T21 high-risk pregnant woman and 1 T18 high-risk pregnant woman were detected by NIPT. The positive predictive values of amniocentesis for T21 and T18 were both 100. 0%. In advanced maternal age group,19 high-risk sex chromosome aneuploidy were detected by NIPT. Under the principle of informed consent,10 pregnant women underwent amniocentesis during prenatal examination,then 4 pregnant women were diagnosed definitely,the positive predictive value for sex chromosome was 40. 0%. There was no statistically significant difference in screening efficiency of NIPT for sex chromosome between advanced maternal age group and control group( P>0. 05).The positive predictive value of sex chromosome in pregnant women more than 38 years old was 61. 5%,which was statistically significantly higher than that in pregnant women under 38 years old( 28. 6%). The invasive prenatal diagnostic rate was only 0. 6% after NIPT in advanced maternal age group. Conclusion NIPT has high accuracy and sensitivity for T21 and T18. The accuracy of sex chromosome increases with age. NIPT can significantly reduce unnecessary invasive prenatal diagnosis and improve efficiency of prenatal screening.
Objective To explore the application value of noninvasive prenatal DNA screening in pregnant women of advanced maternal age. Methods Noninvasive prenatal screening was performed among 3 585 pregnant women of advanced maternal age( advanced maternal age group) and 1 517 low-risk pregnant women of childbearing age( control group) under the principle of informed consent,then the pregnant women with abnormal results underwent amniocentesis,chromosomal G320 banding karyotyping was carried out after amniotic cell culture. Results In advanced maternal age group,16 T21 high-risk pregnant women and 3 T18 high-risk pregnant women were detected by NIPT. In control group,1 T21 high-risk pregnant woman and 1 T18 high-risk pregnant woman were detected by NIPT. The positive predictive values of amniocentesis for T21 and T18 were both 100. 0%. In advanced maternal age group,19 high-risk sex chromosome aneuploidy were detected by NIPT. Under the principle of informed consent,10 pregnant women underwent amniocentesis during prenatal examination,then 4 pregnant women were diagnosed definitely,the positive predictive value for sex chromosome was 40. 0%. There was no statistically significant difference in screening efficiency of NIPT for sex chromosome between advanced maternal age group and control group( P>0. 05).The positive predictive value of sex chromosome in pregnant women more than 38 years old was 61. 5%,which was statistically significantly higher than that in pregnant women under 38 years old( 28. 6%). The invasive prenatal diagnostic rate was only 0. 6% after NIPT in advanced maternal age group. Conclusion NIPT has high accuracy and sensitivity for T21 and T18. The accuracy of sex chromosome increases with age. NIPT can significantly reduce unnecessary invasive prenatal diagnosis and improve efficiency of prenatal screening.
引文
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[11]马京梅,潘虹,付杰,等.高危孕妇外周血胎儿游离核酸无创性产前检测的前瞻性研究[J].中华医学杂志,2015,95(11):849-852.
[12]Chiu RW,Akolelar R,Zheng YW,et al.Noninvasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing:arge scale validity study[J].BMJ,2011,172(342):c7401.
[13]Yaegashi N,Senoo M,Uehara S,et al.Age-specific incidencesof chromosome abnormalities at the second trimester amniocentesis for Japanese mothers aged 35 and older:collaborative study of 5484 cases[J].J Hum Genet,1998,43(2):85-90.
[14]ACOG Committee on Practice Bulletins.ACOG Practice Bulletin No77 screening for fetal chromosomal abnormalities[J].Obstet Gynecol,2007,109(1):217-227.
[15]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.
[2]张晓青,韩小亚,孙达成,等.常州地区2005~2009年孕中期产前筛查结果分析.中国现代医学杂志,2011,21(10):1258-1260.
[3]Heffner LJ.Advanced maternal age-how old is too old?[J].N Engl J Med,2004,351:1927-1929.
[4]Zhu Y,Lu S,Bian X,et al.A multicenter study of fetal chromosomal abnormalitiesin Chinese women of advanced maternal age[J].Taiwan J Obstet Gynecol,2016,55(3):379-384.
[5]戚庆炜,蒋宇林,刘俊涛,等.对高龄孕妇于孕中期行血清学二联指标筛查唐氏综合性的中心前瞻性研究[J].中华妇产科杂志,2008,43(10):737-741.
[6]郭晓莉,赵悦淑.高龄孕妇拒绝羊水穿刺的原因分析及对策.中国妇幼保健,2013,28(23):3875-3876.
[7]Lau TK,Chen F,Pan X,et al.Noninvasive prenatal diagnosis of common fetal chromosomal aneuploidies by maternal plasma DNA sequencing[J].J Matern Fetal Neonatal Med,2012,25(8):1370-1374.
[8]Bianchi DW,Platt LD,Goldberg JD,et al.Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing[J].ObstetGynecol,2012,119(5):890-901.
[9]Benn P,Cuckle H,Pergament E.Non-invasive prenatal testing for aneuploidy:current status and future prospects[J].Ultrasound Obstet Gynecol,2013,42(1):15-33.
[10]向萍霞,刘翎,冷培,等.游离胎儿DNA高通量基因测序技术在产前筛查的临床应用[J].实用妇产科杂志,2013,29(10):777-780.
[11]马京梅,潘虹,付杰,等.高危孕妇外周血胎儿游离核酸无创性产前检测的前瞻性研究[J].中华医学杂志,2015,95(11):849-852.
[12]Chiu RW,Akolelar R,Zheng YW,et al.Noninvasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing:arge scale validity study[J].BMJ,2011,172(342):c7401.
[13]Yaegashi N,Senoo M,Uehara S,et al.Age-specific incidencesof chromosome abnormalities at the second trimester amniocentesis for Japanese mothers aged 35 and older:collaborative study of 5484 cases[J].J Hum Genet,1998,43(2):85-90.
[14]ACOG Committee on Practice Bulletins.ACOG Practice Bulletin No77 screening for fetal chromosomal abnormalities[J].Obstet Gynecol,2007,109(1):217-227.
[15]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.