NIPT在拷贝数变异筛查中的阳性预测值分析

Analysis of the positive predictive value of NIPT in copy number variations screening

目的 分析单中心无创产前检测(NIPT)在拷贝数变异(CNVs)筛查中的阳性预测值(PPV)及其影响因素。方法 回顾性分析2020年1月至2022年4月间在福建省漳州市医院行NIPT检测且提示胎儿CNVs异常的样本。收集临床信息包括孕妇年龄、超声记录、产前诊断结果及妊娠结局。根据产前诊断结果判断NIPT筛查CNVs的准确性,并计算PPV,同时分析其与CNVs片段长度、测序数据量和染色体分布的相关性。结果 期间福建省漳州市医院NIPT筛查样本19876例,其中61例提示CNVs异常,发生率0.31%。剔除妊娠结局缺失样本2例,拒绝产前诊断样本17例,共入组42例样本,平均年龄29.67±5.34岁。NIPT筛查CNVs的整体PPV为30.95%(13/42),CNVs片段长度<10Mb和≥10 Mb的分组PPV分别为45.00%(9/20)和18.18%(4/22),不存在统计学差异(P=0.215)。NIPT筛查CNVs真阳性及假阳性样本平均测序读长数量分别为10.69±1.94 M和10.60±1.95 M,不存在统计学差异(P=0.896)。不同染色体上NIPT筛查CNVs的检出率和PPV值均存在差异,5号染色体检出率最高且与未检出CNVs的染色体存在显著差异(P=0.004),染色体3、8、9和X的PPV为100%,染色体1、4、11、17、18和20的PPV为0%。结论 NIPT筛查CNVs的阳性预测值及检出率与染色体分布相关。本研究结果可为后续NIPT筛查CNVs性能提升提供研究思路和临床数据支撑。

Objective To analyze the positive predictive value(PPV)and its influencing factors of noninvasive prenatal testing(NIPT)for copy number variations(CNVs)screening.Methods A retrospective analysis was performed.Samples that underwent NIPT and the results showed abnormal fetal chromosomal CNVs were collected in Zhangzhou Municipal Hospital of Fujian Province from January 2020 to April 2022.Clinical information was collected including maternal age,prenatal ultrasound diagnosis results,prenatal diagnosis results,and pregnancy outcome information.According to the results of prenatal diagnosis,the accuracy of NIPT screening for CNVs was determined,and its PPV was calculated.The correlations between the positive predictive value of CNVs with the length of CNVs,the amount of sequencing data,and the chromosomal distribution of CNVs were also investigated.Results During this period,a total of 19876 samples underwent NIPT in Zhangzhou Municipal Hospital of Fujian Province,of which 61 were at high risk of CNVs,with an incidence of 0.31%.A total of 42 samples were included,excluding 2 samples of failed pregnancy outcomes follow-up,and 17 samples of refusal to undergo prenatal diagnosis.The mean age of the enrolled samples was 29.67±5.34 years old.The overall PPV of CNVs screened by NIPT was 30.95%(13/42),and the PPV of CNVs with fragment length<10 Mb and≥10 Mb were 45.00%(9/20)and 18.18%(4/22),respectively.There was no statistical difference between these two groups(P=0.215).The average amount of sequencing reads of true positive samples and false positive samples were 10.69±1.94 M and 10.60±1.95 M,separately,with no statistical difference(P=0.984).The detection rate and PPVs of NIPT screening CNVs on different chromosomes were different.The detection rate of chromosome 5 was the highest and significantly different from that of chromosomes without CNVs(P=0.004).The PPV of chromosomes 3,8,9,and X was 100%while the PPV of chromosomes 1,4,11,17,18,and 20 was 0%.Conclusion The positive predictive value and detection rate of NIPT for CNVs are related to chromosome distribution.The results of this study can provide research ideas and clinical data support for the subsequent performance improvement of NIPT for CNVs.