无创产前检测在高龄孕妇产前筛查唐氏综合征中的应用  

Application of Noninvasive prenatal testing for Down syndrome in advanced maternal age pregnant women

作　　者：季修庆[1] 蒋涛[1] 林颖[1] 胡平[1] 李璃[1] 刘安[1] 周静[1] 许争峰[1] 

机构地区：[1]南京医科大学附属南京妇幼保健院产前诊断研究室,南京210004

出　　处：《临床检验杂志》2015年第5期325-327,共3页Chinese Journal of Clinical Laboratory Science

基　　金：国家自然科学基金(81300495);江苏省医学领军人才与创新团队(LJ201109);江苏省临床医学重点项目(BL2012039);江苏省卫生厅科学项目(H201343)

摘　　要：目的探讨无创产前检测(non-invasive prenatal testing,NIPT)在高龄孕妇产前筛查唐氏综合征(Down syndrome,DS)中的应用价值。方法采用高通量测序技术检测高龄孕妇血浆中胎儿游离DNA(cell-free Fetal DNA,cff DNA),结合生物信息分析,得出胎儿患染色体病的风险率;DS高危的高龄孕妇再用羊膜腔穿刺术进行胎儿染色体核型分析。结果 2 789例高龄孕妇中检测失败2例(0.07%,2/2 789)。余2 787例中共检测出25例DS高风险胎儿,阳性率0.9%(25/2 787),经羊水染色体核型分析证实24例为DS,1例核型正常。NIPT用于高龄孕妇检测DS胎儿的敏感性为100%(24/24),特异性为99.96%(2 762/2 763),假阳性率为0.04%(1/2 763)。NIPT还检测出16例其他染色体非整倍体高风险,均进行羊水穿刺术,其中确诊12例胎儿染色体核型异常。NIPT应用于2 789例高龄孕妇产前检测,其中共有43例进行有创性产前诊断,穿刺率为1.54%。结论 NIPT用于高龄孕妇检测DS胎儿具有高敏感性和特异性、无创取样的优点,但目前NIPT检测仍存在假阳性。对染色体结构异常无法准确检测。NIPT检测高风险者仍需有创性产前诊断。Objective To investigate the feasibility of non-invasive prenatal testing（ NIPT） for Down syndrome prenatal diagnosis in advanced maternal age. Methods 2 789 advanced maternal age pregnant women were chosen to analyze their cell-free fetal DNA copy numbers from maternal plasma by high-throughput sequencing. Fetal karyotyping was also carried out on amniocentesis if the women were judged as high risk by high-throughput sequencing. Results 2 cases（ 0. 07%,2 /2 789） final detection of NIPT failed. 25 cases（ 0. 9%,25 /2 787） were high Down syndrome risk by NIPT,among which 24 were confirmed by karyotyping to be Down syndrome. The sensitivity and specificity of NIPT were 100. 00%（ 24 /24） and 99. 96%（ 2 762 /2 763）,respectively. The false positive rate is 0. 04%（ 1 /2 763）. We also detected 16 cases of other chromosomal aneuploidies in high risk（ including trisomy 18,trisomy13,sex chromosome aneuploidies） by NIPT,all of them also were carried out the amniotic fluid puncture,and 12 cases of fetal chromosomal abnormalities were confirmed. NIPT was applied to 2 789 cases of pregnant women in advanced maternal age,and a total of43 cases were carried out invasive prenatal diagnosis,so the puncture rate was 1. 54%. Conclusion NIPT can be popularized for detection of Down syndrome fetal in advanced maternal age,which has the advantages of high sensitivity and specificity,and noninvasive sampling. However,there are still false positive cases in NIPT detection,so the high risk cases still need to prenatal diagnosis,in addition the chromosome structure abnormalities can＇t be accurately detected by the method at present.

关 键 词：无创产前检测 高龄孕妇 唐氏综合征 胎儿游离DNA 高通量测序技术 

分 类 号：R394[医药卫生—医学遗传学]