1、Med J Chin PLA,Vol.48,No.7,July 28,2023797北京市NIPT产前筛查的临床应用效果分析临床研究基金项目国家重点研发计划(2018YFC1002304)作者简介张彦春，医学博士，副主任医师，主要从事产前筛查与产前诊断方面的研究通信作者徐宏燕，E-mail：论著张彦春，刘凯波，张雯，徐宏燕*首都医科大学附属北京妇产医院/北京妇幼保健院，北京100026中图分类号R715.5文献标志码ADOI10.11855/j.issn.0577-7402.0095.2022.1209声明本文所有作者声明无利益冲突引用本文张彦春,刘凯波,张雯,等.北京市NIPT产前筛查的临床
2、应用效果分析J.解放军医学杂志,2023,48(7):797-801.收稿日期2022-01-12录用日期2022-01-23上线日期2022-12-09摘要目的分析北京市孕妇外周血胎儿游离DNA无创产前检测(NIPT)对胎儿染色体非整倍体筛查的效率，并评价NIPT在产前筛查中的临床效果。方法收集2019年1月2020年12月在北京市8家产前诊断机构行NIPT产前筛查的133 899例孕妇的临床资料进行回顾性分析，记录检测指征、检测结果和产前诊断结果。所有孕妇按照检测指征计算阳性率；按照检测结果分为21-三体综合征、18-三体综合征、13-三体综合征、性染色体异常、其他染色体异常，计算产前诊断
3、率、阳性率、阳性预测值、敏感度和特异度。结果NIPT筛查指征中高龄孕产妇检测占比最高，达34.0%(45 509/133 899)，其次为自愿要求，占32.7%(43 860/133 899)。NIPT高风险1647例，阳性率为1.2%(1647/133 899)，其中胎儿颈后透明层厚度(NT)增厚和超声结构异常孕妇的阳性率最高。NIPT高风险孕妇中1348例进行了产前诊断，18-三体综合征高风险的产前诊断率最高，为91.5%(130/142)，最低的是性染色体异常率，为76.4%(488/639)，总体产前诊断率为81.8%(1348/1647)。21-三体综合征、18-三体综合征、13-三
4、体综合征、性染色体异常和其他染色体异常的阳性率分别为0.2%(318/133 899)、0.1%(142/133 899)、0.1%(77/133 899)、0.5%(639/133 899)和0.4%(471/133 899)，阳性预测值分别为71.1%(226/318)、38.0%(54/142)、18.2%(14/77)、31.3%(200/639)和17.8%(84/471)。21-三体综合征、18-三体综合征及13-三体综合征的筛查敏感度分别为98.7%、96.4%和100.0%，特异度均为99.9%。结论NIPT的筛查敏感度和特异度较高，但仍存在假阳性和假阴性的可能。NIPT高风险
5、孕妇应行产前诊断，加强检测前后的遗传咨询至关重要。关键词无创产前检测；阳性预测值；产前诊断率Clinical effect analysis of NIPT prenatal screening in BeijingZhang Yan-Chun,Liu Kai-Bo,Zhang Wen,Xu Hong-Yan*Beijing Maternity Hospital Affiliated to Capital Medical University/Beijing Maternal and Child Health Care Hospital,Beijing 100026,China*Corresp
6、onding author,E-mail:This work was supported by the National Key Research and Development Program of China(2018YFC1002304)AbstractObjectiveTo evaluate the clinical effect of non-invasive prenatal testing(NIPT)by analyzing the efficiency of fetal chromosomal aneuploidy screening in Beijing.MethodsThe
7、 clinical data of 133 899 pregnant women,who underwent NIPT in eight prenatal diagnosis institutions of Beijing from January 2019 to December 2020,were collected and retrospectively analyzed.The test indications,results and prenatal diagnosis results were recorded.The positive rate of all pregnant w
8、omen was calculated according to the test indications;According to the test results,it can be divided into trisomy 21 syndrome,trisomy 18 syndrome,trisomy 13 syndrome,sex chromosome abnormality,and other chromosome abnormalities.The prenatal diagnosis rate,positive rate,positive predictive value(PPV
9、),sensitivity and specificity were calculated.ResultsAmong the NIPT screening indicators,the detection rate of elderly pregnant women was the highest,accounting for 34.0%(45 509/133 899),followed by voluntary requirements,accounting for 32.7%(43 860/133 899).There were 1647 cases with high risk of N
10、IPT,the positive rate was 1.2%(1647/133 899),and the positive rate of NT thickening and ultrasound structure abnormal were the highest in pregnant 解放军医学杂志2023年7月28日第48卷第7期798women.One thousand three hundred and forty-eight cases received prenatal diagnosis.The highest prenatal diagnostic rate was tr
11、isomy 18 reached to 91.5%(130/142),the lowest was the rate of sex chromosome abnormality reached to 76.4%(488/639).The overall prenatal diagnostic rate was 81.8%(1348/1647).The positive rates of trisomy 21,trisomy 18,trisomy 13,sex chromosome abnormality and other chromosomes abnormality were 0.2%(3
12、18/133 899),0.1%(142/133 899),0.1%(77/133 899),0.5%(639/133 899)and 0.4%(471/133 899),respectively.The positive predictive values were 71.1%(226/318),38.0%(54/142),18.2%(14/77),31.3%(200/639)and 17.8%(84/471),respectively.The sensitivity of trisomy 21,trisomy 18 and trisomy 13 was 98.7%,96.4%and 100
13、.0%,and all the specificity of was 99.9%.ConclusionsThe NIPT had high sensitivity and specificity but also still had the limitations of false positive and false negative.Therefore,prenatal diagnosis should be carried out for NIPT high-risk pregnant women,and it is important to strengthen the genetic
14、 counseling before and after testing.Key wordsnon-invasive prenatal testing;positive predictive value;prenatal diagnosis rate染色体非整倍体异常是最常见的出生缺陷，主要表现为新生儿智力落后、发育迟缓、多发畸形等，在活产新生儿中的发生率为6.251。对孕妇进行产前筛查及产前诊断是有效降低染色体异常的重要手段。目前应用最为广泛的产前筛查方法是母亲血清学筛查，该方法费用低，但检出率和阳性预测值(positive predictive value，PPV)也较低，且假阳性率较高2
15、。随着高通量测序技术的发展，无创产前检测(non-invasive prenatal testing，NIPT)已成为目前筛查准确性最高的非介入性产前筛查方法。NIPT对于21、18、13-三体综合征的敏感度分别为95.9%、86.5%及77.5%，特异度分别为99.9%、99.8%及99.9%3，但其PPV各研究报道并不一致4-5。PPV是反映筛查诊断效益的重要指标，PPV越高，筛查结果阳性者成为患者的可能性越高。本研究回顾性分析北京市NIPT产前筛查情况，从敏感度、特异度和PPV等三个方面探讨NIPT在胎儿染色体非整倍体产前筛查中的临床应用价值。1资料与方法1.1研究对象2019年1月20
16、20年12月在北京市8家产前诊断中心接受NIPT筛查的133 899例孕妇，筛查出染色体异常高风险1647例。收集胎儿染色体检测结果、妊娠结局等信息。所有孕妇均在采集标本前签署知情同意书。本研究由首都医科大学附属北京妇产医院/北京妇幼保健院牵头，且已获得首都医科大学附属北京妇产医院医学伦理委员会审核批准(2019-KY-025-01)。1.2方法由国家卫生健康委员会审批的8家北京市产前诊断机构开展孕妇外周血胎儿游离DNA检测，筛查高风险人群行染色体核型分析，NIPT高风险的定义为Z值3或36。通过电话及北京市出生缺陷监测信息系统完成相应的随访，随访内容包括产前诊断、妊娠及分娩结局等，随访时间至生后1年。同时按照北京市管理要求上报产前筛查与产前诊断报表及假阳性和假阴性个案。再将报表和个案根据NIPT检测指征计算阳性率、PPV、敏感度、特异度和产前诊断率。1.3统计学处理采用SPSS 18.0软件进行统计分析。所有数据均为计数资料，以频数、率或构成比表示，检测结果间的比较采用2检验。P0.05为差异有统计学意义。2结果2.1NIPT检测指征的构成及阳性率分析133 899例行NIPT检测的
