河北省无创产前基因检测假阴性率评估与原因分析

Evaluation of false negative rate and reasons analysis of non-invasive prenatal testing in Hebei Province

目的评估河北省无创产前基因检测(NIPT)假阴性率,并对假阴性的原因进行分析。方法基于河北省开展的NIPT民生项目,收集2019年7月—2022年6月项目实施期间发现的标准型21-三体综合征、18-三体综合征、13-三体综合征假阴性案例及其相关临床和实验室检测结果,进行NIPT假阴性率评估和假阴性原因分析,并对假阴性案例进行追踪随访,探讨进一步避免或减少假阴性出现的可能方案。结果在1187464例孕妇中共发现6例假阴性,其中4例为21-三体综合征,2例为18-三体综合征,总体假阴性率为0.51/10万,21-三体综合征为0.34/10万,18-三体综合征为0.17/10万。6例案例加测25M NIPT后结果依然为低风险。送检胎盘样本1例,存在低比例胎盘嵌合,嵌合比例平均为26%。初步明确了2例假阴性的可能原因,分别为双胎妊娠和胎盘嵌合。追踪随访结果显示6例案例中有4例发现超声异常。结论NIPT对常见染色体非整倍体筛查的漏检率(假阴性率)极低,可以作为一线普筛技术推广应用。造成假阴性的主要原因可能是限制性胎盘嵌合。NIPT联合超声筛查可以进一步减少假阴性的出现。

Objective To evaluate the false negative rate of non-invasive prenatal testing(NIPT)in Hebei Province,and analyze the reasons of false negative cases.Methods Based on the NIPT livelihood project carried out in Hebei Province,the study involved the false negative cases of standard types of trisomy 21,trisomy 18 and trisomy 13 from July 2019 to June 2022.The clinical and laboratory test results were collected to evaluate the false negative rate,and reasons of the cases were also analyzed.The false negative cases were followed up to explore the possible schemes to further avoid or reduce the occurrence of false negative.Results A total of 6 false negative cases were found in 1187464 pregnant women,of which 4 were trisomy 21 and 2 were trisomy 18.The overall false negative rate was 0.51/100000,and the rate of trisomy 21 and trisomy 18 were 0.34/100000 and 0.17/100000,respectively.The results of 25M NIPT in 6 cases were still low risk.A low proportion of placental mosaicism was found in 1 placental sample,the average mosaicism was 26%.The possible causes of false negative in 2 cases were identified,which were twin pregnancy and placental mosaicism.Follow-up results showed ultrasound abnormalities were found in 4 of the 6 cases.Conclusion The missing rate(false negative rate)for common chromosome aneuploidy screened by NIPT was very low,which indicates that NIPT can be popularized as a first-line screening technology.The main cause of false negative may be confined placental mosaicism(CPM).NIPT combined with ultrasound screening can further reduce the occurrence of false negatives.