无创DNA产前检测在早孕期高龄人群中的筛查价值

发布时间：2018-03-08 21:25

本文选题：早孕期　切入点：无创产前检测　出处：《北京协和医学院》2014年硕士论文　论文类型：学位论文

【摘要】：目的采用前瞻性双盲研究方法评估早孕期无创产前检测(noninvasive prenatal t esting, NIPT)对胎儿性染色体非整倍体、21三体(trisomy21, T21)、18三体(trisomy18, T18)、13三体(trisomy13, T13)的筛查效率,及其临床可行性。方法采用前瞻性双盲研究方法,于2012年5月15日-2013年8月31日在北京协和医院收集孕8-13周高龄单胎妊娠孕妇的外周血,以12-plex高通量Hiseq2000平台进行检测；同时建议行侵入性产前诊断,首选绒毛活检(chorionic villus sampl ing, CVS)。胎儿染色体核型分析结果为诊断金标准。通过病历记录或电话随访拒绝产期诊断孕妇的妊娠结局。结果 1.共收集215份样本,其中34例拒绝侵入性产前诊断(15.8%),1例因溶血NIPT检测失败(0.5%),有效样本数180份,失访率为6%(13/215)。 2.孕妇外周血采样孕周分布于8-13周,平均9.67±1.214周；高龄孕妇预产期年龄35-45岁,平均37.33±2.19岁。 3.180例有效样本中染色体核型分析结果阳性7例,包括2例T21,1例T18,1例T13,其他染色体异常3例,阳性率7/180(3.9%)；NIPT检测结果阳性5例,包括4例与染色体核型分析结果一致的T21、T18、T13,及1例45,XO,阳性率5/180(2.8%)。 4. NIPT检测的假阳性率1/180(0.6%)。对T21、T18、T13的检测灵敏度、特异度、阳性预测值、阴性预测值均为100%。其他染色体异常情况较复杂,NIPT结果均阴性。 5.103份男性样本的cffDNA含量个体差异大。其中2例绒毛穿刺后当日采样病例的cffDNA含量为27.13%、20.61%明显升高,余101JcffDNA含量分布于2.69%-19.57%,中位数为8.58%,平均含量为9.18%±3.85%。cffDNA含量与体重负相关,与孕周无显著性相关。结论早孕期NIPT检测对T21、T18、T13的筛查效率高,具有临床可行性。孕早期情况复杂样本NIPT无法检出,如：胚胎停育,染色体嵌合体。
[Abstract]:Purpose. A prospective double-blind study was used to evaluate the screening efficiency and clinical feasibility of noninvasive prenatal testing in early pregnancy for trisomy21 trisomy21, trisomy18 trisomy18, T18 trisomy13. Method. A prospective double-blind study was used to collect the peripheral blood of 8-13-week-old single pregnancy pregnant women from May 15th 2012 to August 31st 2013 in Beijing Union Hospital. The peripheral blood samples were detected by 12-plex high-throughput Hiseq2000 platform, and invasive prenatal diagnosis was recommended. The first choice was chorionic villus sampl. Fetal chromosome karyotype analysis was the diagnostic gold standard. The pregnancy outcome of pregnant women was refused to be diagnosed by medical records or telephone follow-up. Results. 1. A total of 215 samples were collected, including 34 cases of non-invasive prenatal diagnosis (15.8%) and 1 case of hemolytic NIPT failure (0.5%). The effective sample number was 180, and the missing rate was 613% (215%). 2.Peripheral blood samples were collected from 8 to 13 weeks in pregnant women with an average of 9.67 卤1.214 weeks, and the mean gestational age of aged pregnant women was 37.33 卤2.19 years old (35-45 years). 3. Among the 180 effective samples, 7 were positive in karyotype analysis, including 2 cases with T21, 1 with T18N, 1 with T13, 3 with other chromosomal abnormalities. The positive rate was 7 / 180 / 3.9. the positive results of NIPT were positive in 5 cases. The positive rate was 5 / 180 / 2. 8%, including 4 cases of T21, T18, T13, and 1 of 45, XO, which were consistent with the results of karyotype analysis. 4. The false positive rate of NIPT was 1 / 180 / 0.60.The sensitivity, specificity, positive predictive value and negative predictive value of T21T _ (18) T _ (13) were 100. All the other chromosomal abnormalities were negative. 5.103 male samples showed significant individual differences in cffDNA content. The cffDNA content of 2 samples on the same day after choriocentesis was 27.13% and 20.61%. The remaining 101 Jcff DNA content was distributed between 2.69 and 19.57 and the median was 8.58. The average content of cffDNA was 9.18% 卤3.85 and negatively correlated with body weight. There was no significant correlation with gestational age. Conclusion. The screening efficiency of T21T _ (18) T _ (13) by NIPT in early pregnancy is high, and the clinical feasibility. The complex samples of early pregnancy can not be detected by NIPT, such as: embryo suspension, chromosome chimera.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R714.5

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