Supplementary Material for: Observed and Modeled Positive Predictive Values Using Cell-free DNA Testing for Fetal Trisomy in a Clinical Laboratory Population

<b><i>Introduction:</i></b> The objective of this study was to explore different approaches to communicating the positive predictive value (PPV) of cell-free DNA screening for fetal trisomy. <b><i>Methods:</i></b> PPV was established for 4 maternal age-groups (&lt;30, 30–34, 35–39, and &gt;39 years) from clinical laboratory data and compared to the modeled PPV from an online calculator. In women under 35, PPV was compared between 2 subsets, high risk and low risk, classified based on the diagnosis codes that were provided to the laboratory. <b><i>Results:</i></b> In 503 high-probability trisomy 21 results, the observed PPVs in the 4 age-groups were 97.0% (&lt;30), 98.9% (30–34), 99.5% (35–39), and 96.3% (&gt;39), all higher than those from the calculator, which ranged from 53 to 95%. Likewise, PPVs were 77.4–97.0% observed versus 16–78% modeled in 131 trisomy 18 cases and 30.4–80.0% observed versus 6–61% modeled in 80 trisomy 13 cases. In women under 35, PPV for the trisomies combined was 90.4% in the higher-risk group compared to 79.7% in the lower-risk group. <b><i>Conclusion:</i></b> Modeling PPV based on maternal age will provide an underestimate in a clinical population. Although the PPV is higher for the samples with higher-risk diagnosis codes, the information that accompanies clinical samples is too general to model PPV for a specific patient.

<b><i>引言：</i></b> 本研究旨在探索不同的沟通方案，用于传递针对胎儿三体综合征的细胞游离DNA（cell-free DNA）筛查的阳性预测值（positive predictive value, PPV）。<b><i>方法：</i></b> 研究基于临床实验室数据，针对4个产妇年龄组（＜30岁、30~34岁、35~39岁及＞39岁）分别计算得到PPV，并与在线计算器生成的模型预测PPV进行对比。针对35岁以下的产妇，根据送检实验室提供的诊断编码将其划分为高风险、低风险两个亚组，对比两组的PPV差异。<b><i>结果：</i></b> 在503例高概率21三体综合征（trisomy 21）检测结果中，4个年龄组的实测PPV分别为97.0%（＜30岁）、98.9%（30~34岁）、99.5%（35~39岁）及96.3%（＞39岁），均高于在线计算器生成的53%~95%的模型预测值。同样，在131例18三体综合征（trisomy 18）病例中，实测PPV为77.4%~97.0%，模型预测值为16%~78%；在80例13三体综合征（trisomy 13）病例中，实测PPV为30.4%~80.0%，模型预测值为6%~61%。在35岁以下的产妇中，合并三体综合征的高风险亚组PPV为90.4%，高于低风险亚组的79.7%。<b><i>结论：</i></b> 仅基于产妇年龄构建的PPV模型会低估临床队列中的实际PPV水平。尽管携带高风险诊断编码的样本对应的PPV更高，但临床样本附带的信息过于宽泛，无法针对特定患者实现PPV的精准建模。