545例NIPT筛查高风险孕妇的产前诊断结果分析

Analysis the prenatal diagnosis results of 545 pregnant woman with abnormal non-invasive prenatal genetic testing results

目的探讨无创产前基因检测(NIPT)技术在产前诊断中的分析效能和临床应用价值。方法回顾性分析2013年9月至2018年12月于北京大学深圳医院就诊的545例NIPT筛查高风险并接受羊水穿刺孕妇(不包括双胎孕妇)的产前诊断结果。结果545例NIPT高风险的孕妇中,21-三体165例、18-三体67例、13-三体41例、性染色体数目异常202例、常染色体数目异常49例、缺失或重复序列超过10Mb的结构异常病例21例,结合羊水细胞染色体核型分析发现21、18、13及性染色体NIPT假阳性率分别为11.5%、35.8%、78.0%和43.1%,而常染色体数目异常及染色体结构异常的假阳性率为91.8%和76.2%;另外,22例NIPT阳性病例的羊水核型分析结果提示为嵌合型,其中有13例性染色体嵌合体,占比最高;此外,还包括3例表现为+mar及+mar的嵌合型,2例为18-三体和1例性染色体数目异常,利用染色体微阵列分析(CMA)检测分析,确证了+mar为相应染色体的部分片段。结论无创产前基因检测具有较高的检测敏感性和特异性,但对产前筛查中常见的21、18、13-三体及性染色体异常仍存在一定程度的假阳性率,NIPT提示高风险的孕妇仍须进一步行有创产前诊断来确诊。

Objective To investigate the accuracy and applicability of noninvasive prenatal genetic testing for chromosome abnormalities in prenatal screening.Methods Retrospectively analyze 545 cases with abnormal NIPT results tested in our hospital between 2013.9-2018.12.Twin pregnancy cases were excluded from the study.Amniocentesis or cordocentesis were suggested to pregnant women with abnormal NIPT results.Results Among the 545 cases of pregnant women,NIPT results indicate 67 cases with Trisomy 18,41 cases with Trisomy 13,202 cases with sex chromosomal abnormalities,49 cases with autosomal abnormalities and 21 cases with chromosomal structural abnormalities(>10 Mb).The false positive rates of NIPT for trisomy 21/18/13 sex chromosomal abnormalities,autosomal abnormalities and chromosomal structural abnormalities were 11.5%,35.8%,78.0%,43.1%,91.8%and 76.2%,respectively.Additionally,karyotype analysis showed chromosome mosaicism in 22 cases including 13 cases of sex chromosome mosaicism.Moreover,+mar and+mar mosaic type in 3 cases of Trisomy 18 and sex chromosomal abnormalities were confirmed by chromosome microarray analysis(CMA).Conclusion NIPT has high sensitivity and specificity for screening fetal chromosome abnormalities.However,false positive results could also be detected in T21,T18,T13 and sex chromosomal abnormalities.Karyotype analysis for confirmation is still recommended for the patients with abnormal NIPT results.