无创DNA检测在诊断高龄孕妇胎儿非整倍体中的应用

目的:探讨高龄妊娠胎儿染色体异常的风险以及无创DNA产前检测(NIPT)在诊断高龄孕妇胎儿非整倍体染色体病中的应用价值。方法:选择≥35岁的高龄孕妇2714例,按年龄分为35~39岁,≥40岁两组,采用NIPT高通量测序检测孕妇血浆游离DNA,并对检测结果提示21-三体、18-三体、13-三体及性染色体高风险者行羊膜腔穿刺术及胎儿染色体核型分析,对检测结果阴性者通过电话随访进行验证。计算NIPT检测的敏感度、特异度、阳性预测值、阴性预测值及Youden指数。结果:2714例高龄孕妇NIPT检测结果提示胎儿非整倍体染色体异常高风险47例,6例高风险孕妇拒绝侵入性产前诊断,余41例高风险孕妇行羊膜腔穿刺术及羊水细胞染色体核型分析,结果显示21-三体19例,18-三体1例,13-三体2例,性染色体异常7例。与现有的金标准羊膜腔穿刺术核型分析相比较,NIPT对高龄孕妇除外性染色体异常的胎儿非整倍体染色体异常检出敏感度为100.00%,特异度为99.93%,阳性预测值为90.91%,阴性预测值为100.00%,Youden指数为0.99。进一步通过年龄分组发现,40岁及以上年龄组异常率显著高于35~39岁年龄组(P=0.011)。结论:高龄孕妇可通过NIPT快速、安全地筛查出胎儿非整倍体染色体异常,减少侵入性产前检测比例,降低胎儿出生缺陷率。

Application of Non-invasive Prenatal Testing for Fetal Chromosomal Aneuploidy in Advanced Age Pregnant Women

Objective:To investigate the risk of fetal chromosomal abnormalities and explore the diagnostic application value of using noninvasive prenatal testing (NIPT)to detect fetal chromosomal aneuploidy in advanced age pregnancy.Methods:2714 pregnant women(≥35 years old)were divided into two groups:35-39y and ≥40y.free plasma DNA were detected by NIPT.Pregnant women with positive result gin trisomy 21,trisomy 18,trisomy 13 or high-risk sex chromosomal abnormalities underwent cell culture and chromosomal karyotyping;and negative ones were validated by telephone follow-up.Figure out sensitivity,specificity,positive predictive value,negative predictive value,and the Youden's index.Results:47 of 2714 cases were in high-risk fetal abnormal chromosome aneuploidy,6 cases of high risk pregnant women refused to invasive prenatal diagnosis;41 cases got amniotic cavity puncture and amniotic fluid cells karyotype analysis,and the result showed that 19 cases with trisomy 21,1 cases with trisomy 18,2 cases with trisomy 13,7 cases of sex chromosome abnormality.Compared with amniotic cavity puncture karyotype analysis,which was designed as the final criteria for definite diagnosis of fetal chromosomal aneuploidy,the sensitivity of NIPT in advanced age pregnant for fetal aneuploidy abnormality detection was 100％,specificity analysis was 99.93％.positive predictive value was 90.91％,negative predictive value was 100％ and the Youden's index was 0.99.Furthermore,the abnormal rate was significantly higher in the group (≥40y) than the group(35-39y) (P =0.011).Conclusions:NIPT can screen for fetal chromosome aneuploidy quickly and safely,decrease the invasive prenatal detection ratio and reduce birth defects.