Background:The ability to diagnose preeclampsia clinically is suboptimal. Our objective was to validate a novel multianalyte assay and characterize its performance, when intended for use as an aid to rule-out preeclampsia.Methods:Prospective, multicenter cohort study of pregnant individuals presenting between 28^0/7 and 36^6/7 weeks’ with preeclampsia-associated signs and symptoms. Individuals not diagnosed with preeclampsia after baseline evaluation were enrolled in the study cohort, with those who later developed preeclampsia, classified as cases and compared with a negative control group who did not develop preeclampsia. Individuals with assay values at time of enrollment ≥0.0325, determined using a previously developed algorithm, considered at risk. The primary analysis was the time to develop preeclampsia assessed using a multivariate Cox regression model.Results:One thousand thirty-six pregnant individuals were enrolled in the study cohort with an incidence of preeclampsia of 30.3% (27.6%–33.2%). The time to develop preeclampsia was shorter for those with an at-risk compared with negative assay result (log-rank P<0.0001; adjusted hazard ratio of 4.81 [3.69–6.27, P<0.0001]). The performance metrics for the assay to rule-out preeclampsia within 7 days of enrollment showed a sensitivity 76.4% (67.5%–83.5%), negative predictive value 95.0% (92.8%–96.6%), and negative likelihood ratio 0.46 (0.32–0.65). Assay performance improved if delivery occurred <37 weeks and for individuals enrolled between 28 and 35 weeks.Conclusions:We confirmed that a novel multianalyte assay was associated with the time to develop preeclampsia and has a moderate sensitivity and negative likelihood ratio but high negative predictive value when assessed as an aid to rule out preeclampsia within 7 days of enrollment.Registration:The study was registered on Clinicaltrials.gov (Identifier NCT02780414).

中文翻译：

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对疑似先兆子痫的孕妇进行多分析物“排除”测定

背景：临床诊断先兆子痫的能力并不理想。我们的目的是验证一种新型多分析物检测方法并表征其性能，用于辅助排除先兆子痫。方法：对妊娠 28 0/7 至 36 6/7 周之间的孕妇进行前瞻性、^多中心^队列研究患有先兆子痫相关的体征和症状。基线评估后未诊断为先兆子痫的个体被纳入研究队列，其中后来发展为先兆子痫的个体被分类为病例，并与未发展为先兆子痫的阴性对照组进行比较。使用先前开发的算法确定的入组时测定值≥0.0325的个体被视为有风险。主要分析是使用多变量 Cox 回归模型评估发生先兆子痫的时间。 结果：研究队列中纳入了 1,036 名孕妇，先兆子痫的发生率为 30.3% (27.6%–33.2%)。与阴性检测结果相比，高危人群发生先兆子痫的时间较短（对数秩P <0.0001；调整后的风险比为 4.81 [3.69–6.27，P <0.0001]）。入组后 7 天内排除先兆子痫的检测性能指标显示，敏感性为 76.4%（67.5%–83.5%），阴性预测值为 95.0%（92.8%–96.6%），阴性似然比为 0.46（0.32– 0.65）。如果分娩发生在 37 周以内且入组时间在 28 至 35 周之间，则检测性能会有所改善。结论：我们证实，一种新型多分析物检测与发生先兆子痫的时间相关，并且具有中等灵敏度和阴性似然比，但阴性预测值较高在入组后 7 天内进行评估，以排除先兆子痫。 注册：该研究已在 ClinicalTrials.gov 上注册（标识符 NCT02780414）。