无创产前基因检测与胎儿染色体结果不一致的临床分析

Clinical analysis on inconsistent results between non-invasive prenatal gene testing and fetal chromosomal examination

目的分析无创产前基因检测(NIPT)在目前临床实践中的表现,探讨NIPT与胎儿染色体结果不一致的原因,为基于无创产前基因检测的遗传咨询积累有价值的临床资料,为NIPT检测技术更加规范有序地开展提供临床依据。方法2016年1月-2018年12月,共有268例孕妇因NIPT检测结果异常(包括高风险和有非报告性提示结果),采用细胞染色体核型分析和/或染色体微阵列分析(CMA)检测进行验证。同时收集同期发现的NIPT结果呈假阴性的6例孕妇的临床资料和胎儿染色体结果进行分析。结果在所有异常NIPT结果中,高风险占49.25%,非报告性提示占50.75%;验证结果显示21-三体综合征的阳性预测值77.65%,18-三体综合征72.73%,13-三体综合征20.00%,性染色体62.42%,非常见染色体异常24.31%,染色体微缺失微重复50.23%。6例NIPT结果正常的孕妇因超声检查异常,经染色体核型分析和/或CMA检测,均证实胎儿染色体异常。结论当前临床实践中NIPT对常见非整倍体异常的检出率并不像之前文献发表的那么高;NIPT结果正常,当超声发现异常时,应考虑介入性产前诊断验证,有助于假阴性结果的发现;NIPT可以发现额外的细胞遗传学异常,应建议结果可疑的孕妇接受介入性产前诊断进行验证。

Objective To analyze the performance of non-invasive prenatal gene testing( NIPT) in current clinical practice,explore the causes of inconsistent results between NIPT and fetal chromosomal examination,accumulate valuable clinical data for genetic counseling based on NIPT,and provide clinical basis for more regularly conducting NIPT. Methods From January 2016 to December 2018,268 pregnant women with abnormal NIPT results( positive and non-reportable) were verified by chromosome karyotyping and/or chromosomal microarray analysis( CMA). The clinical data and fetal chromosome results of 6 pregnant women with false negative NIPT were collected and analyzed during the same period. Results Among all the abnormal NIPT results,positive results and non-reportable results accounted for49. 3% and 50. 7%,respectively. The verification results showed that the positive predictive values of trisomy 21 syndrome,trisomy 18 syndrome,trisomy 13 syndrome,sex chromosome aneuploidies,uncommon chromosome aneuploidies,chromosome microdeletion/duplication were 77. 65%,72. 73%,20. 00%,62. 42%,24. 31%,and 50. 23%,respectively. Six pregnant women with normal NIPT results were confirmed to have fetal chromosomal abnormalities by chromosome karyotyping and/or CMA because of ultrasound anomalies. Conclusion The detection rate of NIPT for common aneuploidies is lower than reported in clinical practice. The study demonstrates that normal NIPT results inconsistent with abnormal ultrasounds should be confirmed by karyotyping and/or CMA to find false negative results. NIPT can detect additional cytogenetic abnormalities,invasive prenatal diagnosis is recommended to confirm diagnosis among the pregnant women with suspected results.