外周血胎儿游离DNA无创产前检测诊断染色体异常及假阳性原因分析

The value of non-invasive prenatal testing of fetal free DNA in peripheral blood of pregnant women for diagnosing fetal chromosome abnormality and the analysis of the causes of false positive of fetal chromosome abnormality

目的:探究外周血胎儿游离DNA无创产前检测(NIPT)诊断染色体异常及假阳性原因。方法:2016年7月—2019年12月本院行NIPT单活胎孕妇10236例,对NIPT提示异常者行羊膜腔穿刺胎儿染色体核型分析,评价NIPT对染色体异常诊断价值。选取NIPT假阳性而羊水穿刺核型分析正常且孕妇选择继续妊娠分娩孕妇,于新生儿出生后同时取胎盘组织和母血样本进行DNA测序分析。结果:10236例孕妇NIPT检测染色体异常111例(1.1%)。其中21-三体异常34例(30.6%)、18-三体异常20例(18.0%)、13-三体异常17例(15.3%)、性染色体异常35例(31.5%),其他染色体异常5例(4.5%)。NIPT检测提示异常者行羊膜腔穿刺检测复核,其中确诊92例(92/111,82.9%),未见异常19例(19/111,17.1%),总假阳性率为0.2%(19/10236)。NIPT对21-三体、18-三体、13-三体、性染色体的检测符合率分别为94.1%、90.0%、76.5%、74.3%。19例NIPT假阳性中12例胎盘组织检测与NIPT结果一致,5例母血检测与NIPT结果一致,另有2例无法确定NIPT假阳性原因。结论:NIPT在产前胎儿染色体异常诊断中具有较高检出率,但不排除假阳性可能。胎盘中异常游离DNA进入母血、母血已有异常游离DNA及孕周不足是导致NIPT假阳性的主要原因。

Objective: To explore the value of non-invasive prenatal(NIPT) of fetal free DNA in peripheral blood of pregnant women for diagnosing fetal chromosome abnormality, and to analyze the causes of false positive of fetal chromosome abnormality. Methods: From January 2017 to June 2019, 10236 pregnant women with single live fetus who had undergone NIPT were selected in this study, and the chromosome karyotype of fetus with abnormal NIPT results was analyzed by amniocentesis to evaluate the diagnostic value of NIPT for chromosome abnormality. The samples of placental tissue and maternal blood of the women with NIPT false positive and normal amniocentesis karyotype analysis who chosen continually pregnancy until to delivery were collected for DNA sequencing analysis. Results: A total of 111 cases in 10236 pregnant women were detected chromosomal abnormalities by NIPT, which’s detection rate was 1.08%. Among them, there were 34(30.6%) cases with 21-trisomy, 20(18.0%) cases with 18-trisomy, 17(15.3%) cases with 13-trisomy, 35(31.5%) cases with sex chromosome, and 5(4.5%) cases with other abnormal chromosomes. In the fetus with NIPT abnormalities after amniocentesis performed, there were 92(92/111, 82.9%) cases with confirmed abnormal chromosomes and 19(19/111, 17.12%) cases with normal chromosomes, and the overall false positive rate was 0.19%(19/10236). The coincidence rates of NIPT for screening 21-trisomy, 18-trisomy, 13-trisomy, and sex chromosome were 94.1%, 90.0%, 76.5%, and 74.3%, respectively. Among the 19 cases with false positive of NIPT, the detective results of placenta tissue of 12 cases had the same results as their NIPT, the detective results of maternal blood of 5 cases had the same results as their NIPT,and 2 cases could not determine the false positive reason of NIPT.Conclusion:NIPT has high value for prenatal screening fetal chromosomal abnormalities with certain false positive rate.The abnormal free DNA of placenta tissue enters the maternal blood and the abnormal maternal free DNA are the main causes of NIPT false positive.