Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Centre, Guangzhou Medical University, Guangzhou, P.R. China.
Department of Ultrasound, Guangzhou Women and Children's Medical Centre, Guangzhou Medical University, Guangzhou, P.R. China.
Prenat Diagn. 2021 May;41(6):690-696. doi: 10.1002/pd.5908. Epub 2021 Feb 11.
To assess the correlation between Z-scores of positive noninvasive prenatal testing (NIPT) results and the positive predictive value (PPV) of NIPT.
Pregnancies with positive NIPT results at Guangzhou Women and Children's Medical Centre between July 2017 and May 2020 were included in this study. Fetal karyotyping or microarray analysis was provided to patients with abnormal NIPT results for confirmatory testing. Logistic regression analyses was applied to study the relationship between the Z scores and the PPV performance. The optimal cutoff values for indicating fetal common trisomies were obtained based on receiver operating characteristic (ROC) curve analysis, and then the PPV were calculated in pregnancies with positive NIPT results at Z-score greater than or equal to cutoff value and in patients with a Z-score between 3 and cutoff value respectively.
A total of 214 pregnancies with positive NIPT results for fetal common trisomies were validated by invasive prenatal diagnosis and follow up in this study. Of these, NIPT indicated trisomy 13 in 25 cases, trisomy 18 in 54 cases and trisomy 21 in 135 patients. Logistic regression analyses showed a significant association (p < 0.05) between the Z-scores and true positive results for T21 and T18. For T13, the significant association was not observed (p > 0.05). The ROC curve analysis showed that the optimal cutoff Z-score for indicating fetal trisomies 13, 18, and 21 were 6.889, 7.574 and 6.612 respectively, and the corresponding area under curve were 0.706, 0.916, and 0.954. In this cohort with abnormal NIPT results, the cutoff values revealed a sensitivity of 96.8% and a specificity of 90% for indicating trisomies 21, and a sensitivity of 88.9% and a specificity of 92.6% for trisomies 18. However, probably due to the sample size, the sensitivity and specificity for indicating trisomy 13 were lower (85.7% and 61.1%) than that for trisomies 21 and 18. The PPVs in pregnancies with positive NIPT results at Z-score greater than or equal to cutoff value were 99.18% (121/122) for trisomy 21, 92.31% (24/26) for trisomy 18 and 46.15% (6/13) for trisomy 13. In patients with a Z-score between 3 and cutoff Z-score, the PPV of NIPT for trisomies 21, 18, and 13 were 30.77% (4/13), 10.71% (3/28), and 8.33% (1/12) respectively. Moreover, by classifying Z scores as 3 ≤ Z < 5, 5 ≤ Z < 10, and Z ≥ 10, the majority of Z scores were above 10 with a PPV of 99% for T21 and just 5.2% were between 3 and 5 with a PPV of 14.3%. In contrast for T18, over a third of tests had Z scores between 3 and 5. The PPV in this group is just over 5%.
The present results show that the PPV performance of NIPT for fetal trisomies 13, 18, and 21 are closely associated with Z-score. The higher the Z-score, the greater the likelihood that the aneuploidy result is correct. Our experience in evaluating the Z-score accuracy of NIPT in this study could be of use in similar work.
评估阳性无创产前检测（NIPT）结果的 Z 分数与 NIPT 的阳性预测值（PPV）之间的相关性。
纳入 2017 年 7 月至 2020 年 5 月期间在广州妇女儿童医疗中心进行阳性 NIPT 结果的妊娠病例。对 NIPT 结果异常的患者进行胎儿核型分析或微阵列分析以进行确认性检测。应用逻辑回归分析研究 Z 分数与 PPV 性能之间的关系。根据接收者操作特征（ROC）曲线分析获得用于指示常见三体胎儿的最佳截断值，然后计算 Z 分数大于或等于截断值的阳性 NIPT 结果的妊娠和 Z 分数在 3 与截断值之间的妊娠的 PPV。
在这项研究中，通过侵袭性产前诊断和随访验证了 214 例阳性胎儿常见三体 NIPT 结果。其中，NIPT 提示 25 例 13 三体、54 例 18 三体和 135 例 21 三体。逻辑回归分析显示 Z 分数与 T21 和 T18 的真阳性结果之间存在显著相关性（p<0.05）。对于 T13，未观察到显著相关性（p>0.05）。ROC 曲线分析表明，用于指示胎儿三体 13、18 和 21 的最佳截断 Z 分数分别为 6.889、7.574 和 6.612，相应的曲线下面积分别为 0.706、0.916 和 0.954。在本队列中，截断值对于指示 21 三体的敏感性为 96.8%，特异性为 90%，对于指示 18 三体的敏感性为 88.9%，特异性为 92.6%。然而，可能由于样本量较小，对于指示 13 三体的敏感性和特异性（85.7%和 61.1%）低于 21 三体和 18 三体。在 Z 分数大于或等于截断值的阳性 NIPT 结果的妊娠中，21 三体的 PPV 为 99.18%（121/122），18 三体为 92.31%（24/26），13 三体为 46.15%（6/13）。在 Z 分数在 3 与截断 Z 分数之间的患者中，21 三体、18 三体和 13 三体的 NIPT 的 PPV 分别为 30.77%（4/13）、10.71%（3/28）和 8.33%（1/12）。此外，将 Z 分数分类为 3≤Z<5、5≤Z<10 和 Z≥10，大多数 Z 分数大于 10，T21 的 PPV 为 99%，只有 5.2%在 3 到 5 之间，PPV 为 14.3%。相比之下，T18 中超过三分之一的检测 Z 分数在 3 到 5 之间。该组的 PPV 略高于 5%。
本研究结果表明，NIPT 对胎儿三体 13、18 和 21 的 PPV 性能与 Z 分数密切相关。Z 分数越高，染色体非整倍体结果正确的可能性越大。本研究评估 NIPT Z 分数准确性的经验可能对类似工作有用。
