无创产前检测胎儿染色体非整倍体阳性预测值的影响因素分析

Analysis of the factors influencing positive predictive value of noninvasive prenatal testing for chromosome aneuploidies

目的探讨Z值以及不同风险因素对无创产前检测(NIPT)胎儿染色体非整倍体阳性预测值(PPV)的影响。方法回顾性分析2016年1月1日至2021年5月31日于郑州大学第一附属医院行NIPT检测的样本,共81838份。NIPT提示为高风险的样本,后续行侵入性产前诊断,计算对应的PPV。比较不同Z值区间样本的PPV的差异;将进行NIPT检测的人群分为高风险组和非高风险组:高风险组(n=39114):包括超声软指标异常、血清学筛查高风险和高龄妊娠;非高风险组(n=42724):包括血清学筛查临界风险和低风险。对比不同风险人群进行NIPT检测后PPV的差异;分析不同Z值和不同风险组间PPV的差异。结果NIPT共检出471份胎儿染色体非整倍体高风险样本,包括362份21-三体高风险、77份18-三体高风险和32份13-三体高风险。经侵入性产前诊断,最终确诊的样本分别为226份、46份和6份,对应的PPV分别为79.3%(226/285)、82.1%(46/56)和27.3%(6/22)。21-三体和18-三体的PPV与Z值大小皆呈正相关(r=0.92、0.62,均P<0.05),13-三体因确诊病例偏少,无法分析。高风险组的复合PPV为85.2%(207/243),高于非高风险组的59.2%(71/120)(χ^(2)=30.30,P<0.01)。在Z值区间分别为3~<4、4~<5时,高风险人群的PPV分别为46.2%(12/26)和62.5%(15/24),均高于非高风险人群的16.0%(4/25)和14.3%(3/21)(χ^(2)=4.10、8.90,均P<0.05);随着Z值的升高,两组间PPV差异均无统计学意义(均P>0.05)。结论21-三体和18-三体的PPV和Z值呈正相关;高风险组的PPV大于非高风险组;结合Z值和不同风险因素可对NIPT检测高风险人群提供更准确的遗传咨询。

Objective To investigate the influence of Z-score and different risk factors on positive predictive value(PPV)of noninvasive prenatal testing(NIPT)for chromosome aneuploidies.Methods A total of 81838 NIPT samples from January 1,2016 to May 31,2021 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed.Invasive prenatal diagnosis was applied to verify the diagnosis of NIPT-positive results and the corresponding PPV was calculated.The PPV of the samples with different Z-score were compared.The women were divided into high-risk group and non-high-risk group:high-risk group(n=39114)included those with ultrasound soft index abnormalities,advanced maternal age or high risk for maternal serum screening,while non-high-risk group(n=42724)included those with intermediate risk for maternal serum screening or no indications.The differences of the PPV between these two groups were compared.Finally,the comprehensive influence of Z-score and different risk factors on PPV were analyzed.Results A total of 471 high-risk cases were detected by NIPT results,including 362 cases of trisomy 21,77 cases of trisomy 18 and 32 cases of trisomy 13.For trisomy 21,trisomy 18 and trisomy 13,there were 226 cases,46 cases and 6 cases which were confirmed via invasive prenatal diagnosis respectively.The corresponding PPV were 79.3%(226/285),82.1%(46/56)and 27.3%(6/22),respectively.PPV of trisomy 21 and trisomy 18 were positively correlated with the corresponding Z-score(r=0.92,0.62,all P<0.05),while trisomy 13 could not be analyzed due to the small sample size.The PPV of high-risk group was 85.2%(207/243),which was higher than that of the non-high-risk group with PPV of 59.2%(71/120,χ^(2)=30.30,P<0.01).When the Z-score was between 3-<4 and 4-<5,the PPV of the high-risk group were 46.2%(12/26)and 62.5%(15/24)respectively,which were higher than those of the non-high-risk group[16.0%(4/25)and 14.3%(3/21),χ^(2)=4.10,8.90,all P<0.05].With the increase of Z-score,there was no significant difference in PPV between the two groups(all P>0.05).Conclusions The PPV of trisomy 21 and trisomy 18 are positively correlated with Z-score.The PPV of high-risk group is higher than that of non-high-risk group.The combination of Z-score and other risk factors may provide more accurate genetic counseling for those with NIPT positive results.