40628例无创产前胎儿21、18、13号染色体筛查结果的分析  

Analysis of the results of chromosomal trisomies 21,18 and 13 screening among 40628 women by non-invasive prenatal testing

作　　者：王东梅[1] 杨洁霞[1] 彭海山[1] 侯亚萍[1] 王奕霞[1] Wang Dongmei;Yang Jiexia;Peng Haishan;Hou Yaping;Wang Yixia(Medical Genetics Centre,Maternal and Child Health Care Hospital of Guangdong Province,Guangzhou,Guangdong 511442,China)

机构地区：[1]广东省妇幼保健院医学遗传中心,广州511442

出　　处：《中华医学遗传学杂志》2021年第11期1045-1050,共6页Chinese Journal of Medical Genetics

基　　金：广东省医学科研基金(A2020062)。

摘　　要：目的探讨无创产前检测(non-invasive prenatal testing,NIPT)对于筛查胎儿21、18、13号染色体三体及基因组拷贝数变异(copy number variation,CNV)的价值。方法选取40628例单胎孕妇作为研究对象,利用高通量测序以及生物信息学分析对母体血浆中的胎儿游离DNA进行检测,为高风险孕妇提供介入性产前诊断,对低风险孕妇进行电话随访。结果最常见的检测指征依次为血清学筛查临界风险、血清学筛查高风险以及高龄。共检出21、18、13号三体高风险257例(分别为170、49、38例),其中227例接受了介入性产前诊断,分别确诊122例、28例、10例,阳性预测值(positive predictive value,PPV)分别为81.33%(122/150)、65.12%(28/43)、29.41%(10/34)。低风险人群随访发现2例18-三体假阴性。同时NIPT检出21、18、13号染色体CNV共46例(分别为15、16、15例),其中37例接受了介入性产前诊断,分别确诊5、3、5例,PPV分别为41.67%(5/12)、25%(3/12)、33.33%(5/15)。在假阳性样本中意外发现2例其他染色体CNV。结论NIPT检测指征中血清学筛查高风险组染色体异常率较其他组高,达52.02%。NIPT对于筛查胎儿21、18、13三体具有极高的敏感度和特异度,对于筛查胎儿CNV的准确性尚有待提高。作为一项筛查手段,NIPT具有较高的临床应用价值,但存在假阳性与假阴性结果,须做好检测前后的遗传咨询工作。Objective To assess the clinical value of non-invasive prenatal testing(NIPT)for the screening of trisomy and copy number variations(CNVs)of chromosomes 21,18 and 13.Methods From January 2015 to December 2019,40628 pregnant women underwent NIPT testing using high-throughput sequencing and bioinformatics analysis to test the cell-free fetal DNA in maternal plasma.High-risk pregnant women underwent invasive prenatal diagnosis,while low-risk ones were followed up by telephone.Results The three most common indications included intermediate risk of serological screening,high risk of serological screening and advanced maternal age.Among all pregnant women,257 cases were detected as trisomy 21,18 and 13(170,49 and 38 cases,respectively).227 cases chose invasive prenatal diagnosis,with respectively 122,28 and 10 cases confirmed.The positive predictive value(PPV)was 81.33%(122/150),65.12%(28/43),29.41%(10/34),respectively.Two false negative cases of trisomy 18 were found during follow-up.Meanwhile,NIPT has detected 46 cases(15,16 and 15 cases,respectively)CNVs on chromosomes 21,18 and 13,among which 37 cases underwent invasive prenatal diagnosis.There were 5,3 and 5 positive cases,which yielded a PPV of 41.67%(5/12),25%(3/12)and 33.33%(5/15),respectively.Two other chromosome CNVs were accidentally discovered among the false positive samples.Conclusion The incidence of chromosomal abnormalities in the serological screening high-risk group was 52.02%,which was significantly higher than other groups.NIPT has a high sensitivity and specificity for the screening of trisomies 21,18 and 13,while its accuracy for detecting CNVs of chromosomes 21,18 and 13 needs to be improved.As a screening method,NIPT has a great clinical value,though there are still limitations of false positive and false negative results.Comprehensive pre-and post-test genetic counseling should be provided to the patients.

关 键 词：无创产前检测 染色体三体 拷贝数变异 阳性预测值 血清学筛查 

分 类 号：R714.5[医药卫生—妇产科学]