孕妇外周血胎儿游离DNA产前检测假阳性结果影响因素分析

Study on the influence factors of false-positive results on maternal cell-free DNA prenatal testing

目的探讨孕妇外周血胎儿游离DNA产前检测假阳性结果的影响因素。方法回顾分析2015年1月—2021年6月,在南京鼓楼医院产前诊断中心因孕妇外周血胎儿游离DNA产前检测(简称NIPT)阳性的651例孕妇进行产前诊断的结果,选择其中10例NIPT结果假阳性的病例采集孕妇外周血和胎盘样本行进一步测序分析。结果651例行羊膜腔穿刺产前诊断的病例中,357例为真阳性,其中204例是21-三体高风险、49例是18-三体高风险、7例是13-三体高风险、97例是性染色体高风险;294例为假阳性,包括21-三体高风险41例、18-三体高风险33例、13-三体高风险40例、性染色体高风险180例。选择4例21-三体高风险假阳性、2例18-三体高风险假阳性、4例性染色体高风险假阳性,共10例病例进行追踪检查,病例1(P1)在21号染色体上存在重复区域;病例2(P2)患有系统性红斑狼疮,而且在X染色体上存在重复区域;病例9(P9)在妊娠31周时提示可能存在胎儿生长受限;病例3(P3)、病例4(P4)、病例5(P5)、病例6(P6)和病例7(P7)的胎盘样本中发现限制性胎盘嵌合。病例8(P8)和病例10(P10)胎盘样本及外周血结果均无异常。结论限制性胎盘嵌合和母体因素是可能造成NIPT假阳性的主要因素。因此NIPT仍然是一种筛查试验,不能作为侵入性产前诊断的替代方法。

Objective To explore the influence factors of false positive results on fetal free DNA prenatal testing in peripheral blood of pregnant women.MethodsThe results on prenatal diagnosis of 651 pregnant women with positive fetal free DNA(NIPT)in prenatal diagnosis center of Nanjing Drum Tower Hospital from January 2015 to June 2021 were retrospectively analyzed.Among them,10 cases with false positive NIPT results were selected to collect maternal peripheral blood and placental samples for further sequencing analysis.ResultsAmong the 651 cases of prenatal diagnosis by amniocentesis,357 cases were true positive,including 204 cases with high risk of trisomy 21,49 cases with high risk of trisomy 18,7 cases with high risk of trisomy 13,and 97 cases with high risk of sex chromosome.There were 294 false positives,including 41 at high risk of trisomy 21,33 at high risk of Trisomy 18,40 at high risk of trisomy 13,and 180 at high risk of sex chromosome.A total of 10 cases were selected for follow-up examination,including 4 high-risk false positives of trisomy 21,2 highrisk false positives of trisomy 18,and 4 high-risk false positives of sex chromosome.Case 1(P1)had a duplicated region on chromosome 21.Case 2(P2)had systemic lupus erythematosus and had duplicated regions on the X chromosome.Case 9(P9)suggested possible fetal growth restriction at 31 weeks of gestation;Restrictive placental chimerism was found in the placental samples from cases 3(P3),4(P4),5(P5),6(P6),and 7(P7).The results of placental samples and peripheral blood were normal in case 8(P8)and case 10(P10).Conclusion Confined placental mosaicism and maternal factors are the main factors on false positive NIPT.Therefore,NIPT is still a screening test and cannot be used as an alternative to invasive prenatal diagnosis.