无创产前检测失败相关因素与重复检测的可行性分析

Factors affecting the failure of non-invasive prenatal testing and the feasibility analysis of retesting

目的探讨无创产前检测(non-invasive prenatal testing,NIPT)失败的原因及重复检测的可行性。方法对2011年1月至2018年12月行NIPT检测的40311例孕妇的临床资料、诊断结果和妊娠结局进行回顾。结果在全部孕妇中,首次检测失败1116例,9例(0.81%)胎儿游离DNA浓度低于4%,663例(59.41%)因Z值灰区需要重新建库后再检测,其余444例(39.78%)因胎儿游离DNA浓度低于4%需重新采血后再检测。再检测后共有1069例(95.78%)获得有效的NIPT结果,结果提示53例高风险(6例21三体、6例18三体、13例13三体、16例性染色体异常、12例染色体拷贝数变异),48例选择介入性产前诊断,确诊2例47,XXY和2例CNV。最终共有47例(0.12%)因胎儿游离DNA浓度低于4%无法出结果,其中仅16例(34%)选择了介入性产前诊断。结论对Z值灰区的重复检测可以降低NIPT的假阳性率,减少介入性产前诊断,重复检测的可行性较高。对于胎儿游离DNA浓度低于4%者,重新采血再检测获得有效NIPT结果的成功率随孕周的增大而增加,但会延迟胎儿非整倍体的诊断时间,应根据孕周和临床指征进行个性化估计。再次检测仍失败者应建议孕妇选择介入性产前诊断。

Objective To explore the cause for the failure of non-invasive prenatal testing(NIPT)and feasibility of repeated testing.Methods Clinical data,test results and pregnancy outcomes of 40311 pregnant women who received NIPT test from January 2011 to December 2018 were reviewed.Results Among all the pregnant women,1116 cases failed in the first test,9 cases(0.81%)had fetal free DNA concentration lower than 4%,663 cases(59.41%)were retested after the establishment of Z value gray area,and the remainder 444 cases(39.78%)needed to be retested after the blood collection due to the fetal free DNA concentration lower than 4%.After retesting,1069 cases(95.78%)obtained effective NIPT results.The results showed that 53 cases were at high risk(6 cases for trisomy 21,6 cases for trisomy 18,13 cases for trisomy 13,16 cases for sex chromosomal abnormality,12 cases for chromosomal copy number variation).Forty eight cases were selected for invasive prenatal diagnosis,and 2 cases of 47,XXY and 2 CNV were confirmed.A total of 47 cases(0.12%)did not obtain results because the concentration of fetal free DNA was lower than 4%.Only 16 cases(34%)chose invasive prenatal diagnosis.Conclusion Repeated detection of the gray area of Z value can reduce the false positive rate of NIPT and invasive prenatal diagnosis,and the feasibility of repeated detection is high.In the case of fetal free DNA concentration lower than 4%,the success rate of obtaining effective NIPT results by re-sampling and re-detection increases with the increase of gestational age,but may delay the diagnosis for fetal aneuploidies.Therefore,personalized estimation should be made according to gestational age and clinical indications.It is suggested that pregnant women should choose invasive prenatal diagnosis when they have failed in the retest.