摘要
目的探讨无创DNA产前检测(NIPT)技术在胎儿染色体非整倍体检测中的应用价值及高风险Z值分类的意义。方法选择2015年6月至2023年1月于乌海市妇幼保健院遗传咨询门诊接受NIPT的7478例孕妇为研究对象。对孕妇外周血胎儿游离DNA(cffDNA)进行NIPT检测,通过生物信息分析,得到Z值,把高风险例数的Z值按大小分为四组:A组(3≤Z≤5)、B组(5<Z≤8)、C组(8<Z≤12)和D组(Z>12),进行假阳性率比较;并对高风险的孕妇,进行羊膜腔穿刺液荧光原位杂交(FISH)检测和胎儿染色体核型分析。结果7478例NIPT样本检测到62例染色体异常,阳性率为0.83%,包括21-三体高风险44例、18-三体高风险12例、13-三体高风险5例、性染色体异常1例;其中54例孕妇自愿接受羊水穿刺产前诊断,50例在我院经荧光原位杂交(FISH)技术及染色体核型分析,其中40例得到确诊(21-三体29例、18-三体9例、13-三体1例、X-三体1例);4例在外院进行了羊穿检测,其中21三体3例,正常1例。后期追踪随访得知,未进行羊穿的8例中,5例直接引产,胎盘验证4例为21-三体,1例为13-三体;1例个人原因产下21-三体患儿;1例双胎,其中一个胎死宫内,诊断为21-三体,另一个34周时行剖腹产,为正常婴儿;1例18-三体高风险最终产下正常婴儿。经计算,NIPT对21-三体、18-三体和13-三体阳性预测值(PPV)分别为86.4%(38/44)、75.0%(9/12)和40.0%(2/5)。排除掉1例性染色体异常,将其余61例高风险按Z值大小分为四组进行分析,结果显示,3≤Z≤5时,假阳性率为69.2%;5<Z≤8时,假阳性率为14.3%;8<Z≤12时,假阳性率为5.3%;Z>12时,假阳性率为0。结论NIPT对21-三体和18-三体的筛查准确性高;NIPT在产前诊断胎儿染色体非整倍体疾病中敏感性、特异性、阳性预测值和阴性预测值等诊断指标更为理想,具有很好的临床应用价值;假阳性主要集中在3≤Z≤5的范围,Z值与假阳性率呈负相关。对NIPT高风险的Z值进行适当分类及划分能进一步提高21-三体、1-8三体、13-三体在不同区间内的阳性预测值,同时更利于指导临床医师对高风险孕妇进行遗传咨询。
Objective:To explore the application of non-invasive prenatal testing(NIPT)in detecting fetal chromosomal aneuploidy and the significance of high-risk Z-value classification.Methods:A total of 7478 pregnant women who experienced NIPT at the Genetic Consultation Clinic of Wuhai Maternal and Child Health Hospital from June 2015 to January 2023 were recruited.The NIPT of fetal free DNA from maternal peripheral blood was conducted.The Z value was developed by a bioinformatics analysis and those of high-risk women were divided into four groups:Group A(3≤Z≤5),Group B(5<Z≤8),Group C(8<Z≤12)and Group D(Z>12).The false positive rates were compared among four groups.Fluorescence in situ hybridization(FISH)detection of amniocentesis fluid and analysis of fetal chromosome karyotype were conducted among high-risk pregnant women.Results:A total of 62 chromosomal abnormalities were detected in 7478 NIPT samples,with a positive rate of 0.83%,including 44 cases with high-risk for trisomy 21,12 cases with high-risk for trisomy 18 and 5 cases with high-risk for trisomy 13,and 1 chromosomal abnormality.Among them,54 pregnant women voluntarily underwent amniocentesis for prenatal diagnosis,and 50 of them underwent FISH technology and chromosomal karyotype analysis.Forty cases were confirmed in Wuhai Maternal and Child Health Hospital,in which 29 cases of trisomy 21,9 cases of trisomy 18,1 case of trisomy 13,and 1 case of trisomy X.Four cases underwent amniocentesis in other hospitals.Among them,3 cases of trisomy 21 and 1 normal case were found.Subsequent follow-up revealed that among 8 women without amniocentesis,5 women underwent induction of labor.Four cases were confirmed as trisomy 21 and 1 case as trisomy 13.A child suffered from trisomy 21 was born due to personal reasons.Intrauterine fetal death and a normal infant delivered by cesarean section at 34 gestational week were found in a case of twins.A women with high-risk of trisomy 18 ultimately delivered a normal baby.The positive predictive values(PPV)of NIPT for trisomy 21,trisomy 18,and trisomy 13 were 86.4%(38/44),75.0%(9/12),and 40.0%(2/5),respectively.Excluding one case of sex chromosome abnormality,the evaluation results of Z values of the remaining 61 high-risk cases showed that the false positive rates were 69.2%,14.3%,5.3%and 0 when the Z values were between 3 and 5,greater than 5 but not more than 8,greater than 8 and not more than 12,and greater than 12,respectively.Conclusions:There is a high screening accuracy for trisomy 21 and trisomy 18 by NIPT.Some diagnostic indicators such as sensitivity,specificity,positive predictive value,and negative predictive value should be used in NIPT for prenatal diagnosis of fetal chromosomal aneuploidy diseases.False positives appear mainly when the Z values are between 3 and 5,and the Z-value is negatively correlated with the false positive rate.Proper classification of high-risk Z values for NIPT can further improve the positive predictive results of trisomy 21,trisomy 1-8,and trisomy 13,and are beneficial to guiding clinical physicians in genetic counseling for high-risk pregnant women.
作者
郑海燕
武燕红
张欣
吴雪溶
吕伟
张海平
王震
沈静
高敏
ZHENG Hai-yan;WU Yan-hong;ZHANG Xin;WU Xue-rong;Lü Wei;ZHANG Hai-ping;WANG Zhen;SHEN Jing;GAO Min(Wuhai Maternal and Child Health Hospital Central Laboratory,Wuhai 016000)
出处
《生殖医学杂志》
CAS
2023年第12期1843-1848,共6页
Journal of Reproductive Medicine
基金
内蒙古自治区科技创新引导奖励资金(2022765)。
关键词
无创产前检测
荧光原位杂交
羊水细胞培养
产前诊断
Z值
Non-invasive prenatal testing
Fluorescence in situ hybridization
Amniotic fluid cell culture
Prenatal testing
Z value
