Retrospective study of non-invasive prenatal screening using high-throughput sequencing technology in a single centre
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摘要:
目的 探讨无创产前检测(non-invasive prenatal testing, NIPT)在胎儿非整倍体筛查中临床应用价值和有效性。 方法 选择2017—2018年于中国科学技术大学附属第一医院自愿行NIPT检测的单胎孕妇8 246例，采集外周血样，抽提胎儿游离DNA，采用高通量测序平台检测，对孕妇外周血游离DNA进行分析，提示染色体异常高危者行侵入性产前诊断。期间记录其临床资料、检测结果及妊娠结局, 对特殊病例进行进一步分析, 对所有病例进行汇总分析, 探讨无创产前检测在胎儿染色体非整倍体筛查中的实际临床检测效力以及在染色体微缺失/微重复中临床应用价值。 结果 本研究检出68例NIPT高风险，其中25例21-三体、8例18-三体、5例13-三体、18例性染色体非整倍体、5例其他染色体数目异常、7例染色体微缺失/微重复。行遗传咨询后，有58例进行侵入性产前诊断，经羊水染色体核型分析确诊38例阳性病例。21-三体、18-三体、13-三体、性染色体非整倍体、其他染色体数目异常、染色体微缺失/微重复阳性预测值分别为87.50%、85.70%、25.00%、50.00%、25.00%、40.00%。 结论 NIPT是一项较好的筛查方法，对21-三体、18-三体检出效力与胎儿染色体核型分析有较好的一致性。对性染色体非整倍体、染色体微缺失/微重复和染色体嵌合体也有一定的检出效力。 -
关键词:
- 无创产前检测 /
- 性染色体非整倍体 /
- 染色体微缺失/微重复 /
- 染色体嵌合体
Abstract:Objective To explore the clinical application value and effectiveness of non-invasive prenatal testing (NIPT) for the identification of foetal chromosomal aneuploidies. Methods A total of 8 246 singleton pregnant women who were voluntarily undergoing NIPT testing at the First Affiliated Hospital of the University of Science and Technology of China from 2017 to 2018 were selected. Blood samples were collected from the subjects, and free foetal DNA was extracted. High-throughput sequencing was used to analyse the cell-free foetal DNA from the plasma of pregnant women. Those at high risk for chromosomal abnormalities underwent invasive prenatal diagnosis. The clinical data, test results and pregnancy outcomes were recorded during the period, and special cases were further analysed. All cases were analysed collectively to explore the actual clinical testing efficacy of NIPT. Results This study detected 68 cases at high risk using NIPT, including 25 cases of Trisomy 21, 8 cases of Trisomy 18, 5 cases of Trisomy 13, 18 cases of sexual chromosome aneuploid, 5 cases of other chromosomal abnormalities and 7 cases of microdeletion/microduplication. After genetic counselling, 58 patients underwent invasive prenatal diagnosis, and 38 positive cases were confirmed by chromosomal karyotyping analysis. The positive predictive values of the aforementioned detected cases were 87.50%, 85.70%, 25.00%, 50.00%, 25.00% and 40.00%, respectively. Conclusion NIPT is an effective screening method. Apart from being effective for the detection of trisomy 21 and 18, NIPT is effective in detecting sex chromosome aneuploidy, microdeletion/microduplication and chromosomal mosaicism. -
表 1 NIPT筛查高风险结果和介入性产前诊断结果比较分析(例)
染色体异常类型(例) NIPT
高风险介入性产
前诊断介入性产前诊断结果 敏感度(%) 特异度(%) PPV(%) TP FP T21 25 24 21 3 100.00 99.96 87.50 T18 8 7 6 1 100.00 99.99 85.70 T13 5 4 1 3 100.00 99.96 25.00 性染色体异常 18 14 7 7 50.00 其他染色体异常 5 4 1 3 25.00 微缺失/微重复 7 5 2 3 40.00 总计 68 58 38 20 注：TP为真阳性；FP为假阳性；PPV为阳性预测值。 
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表 2 染色微缺失微重复检测阳性结果
NIPT结果 羊水核型结果 CNVseq结果 del(13q31.3q34)(92439831-113576636) 46, XN, -13, +mar 46, XN, del(13q31.3q34)(92, 506, 151-115, 054, 392)×1 del(18q21.31q23)(55486475-78013426) 46, XN, del(18)(q21) 46, XN, del(18q21.2q23)(53, 392, 657-77, 958, 754)×1
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