Nama Nassr, Shen Ye, Bone Jeffrey N, Lee Zerlyn, Picco Kara, Jin Falla, Foulds Jessica L, Gagnon Josée Anne, Novak Chris, Parisien Brigitte, Donlan Matthew, Goldman Ran D, Sehgal Anupam, Holland Joanna, Mahant Sanjay, Tieder Joel S, Gill Peter J
Division of Hospital Medicine, Department of Pediatrics, University of Washington, Seattle Children's Hospital, Seattle.
BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
JAMA Pediatr. 2025 Feb 1;179(2):188-196. doi: 10.1001/jamapediatrics.2024.4399.
The American Academy of Pediatrics (AAP) higher-risk criteria for brief resolved unexplained events (BRUE) have a low positive predictive value (4.8%) and misclassify most infants as higher risk (>90%). New BRUE prediction rules from a US cohort of 3283 infants showed improved discrimination; however, these rules have not been validated in an external cohort.
To externally validate new BRUE prediction rules and compare them with the AAP higher-risk criteria.
DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective multicenter cohort study conducted from 2017 to 2021 and monitored for 90 days after index presentation. The setting included infants younger than 1 year with a BRUE identified through retrospective chart review from 11 Canadian hospitals. Study data were analyzed from March 2022 to March 2024.
The BRUE prediction rules.
The primary outcome was a serious underlying diagnosis, defined as conditions where a delay in diagnosis could lead to increased morbidity or mortality.
Of 1042 patients (median [IQR] age, 41 [13-84] days; 529 female [50.8%]), 977 (93.8%) were classified as higher risk by the AAP criteria. A total of 79 patients (7.6%) had a serious underlying diagnosis. For this outcome, the AAP criteria demonstrated a sensitivity of 100.0% (95% CI, 95.4%-100.0%), a specificity of 6.7% (95% CI, 5.2%-8.5%), a positive likelihood ratio (LR+) of 1.07 (95% CI, 1.05-1.09), and an AUC of 0.53 (95% CI, 0.53-0.54). The BRUE prediction rule for discerning serious diagnoses displayed an AUC of 0.60 (95% CI, 0.54-0.67; calibration intercept: 0.60), which improved to an AUC of 0.71 (95% CI, 0.65-0.76; P < .001; calibration intercept: 0.00) after model revision. Event recurrence was noted in 163 patients (15.6%). For this outcome, the AAP criteria yielded a sensitivity of 99.4% (95% CI, 96.6%-100.0%), a specificity of 7.3% (95% CI, 5.7%-9.2%), an LR+ of 1.07 (95% CI, 1.05-1.10), and an AUC of 0.58 (95% CI, 0.56-0.58). The AUC of the prediction rule stood at 0.67 (95% CI, 0.62-0.72; calibration intercept: 0.15).
Results of this multicenter cohort study show that the BRUE prediction rules outperformed the AAP higher-risk criteria on external geographical validation, and performance improved after recalibration. These rules provide clinicians and families with a more precise tool to support decision-making, grounded in individual risk tolerance.
美国儿科学会（AAP）针对短暂性不明原因事件（BRUE）的高风险标准具有较低的阳性预测值（4.8%），并且将大多数婴儿错误分类为高风险（>90%）。来自美国一个3283名婴儿队列的新BRUE预测规则显示出更好的辨别能力；然而，这些规则尚未在外部队列中得到验证。
对外验证新的BRUE预测规则，并将其与AAP高风险标准进行比较。
设计、背景和参与者：这是一项回顾性多中心队列研究，于2017年至2021年进行，并在首次就诊后监测90天。研究对象包括通过对11家加拿大医院的回顾性病历审查确定患有BRUE的1岁以下婴儿。研究数据于2022年3月至2024年3月进行分析。
BRUE预测规则。
主要结局是严重的潜在诊断，定义为诊断延迟可能导致发病率或死亡率增加的情况。
在1042例患者中（中位年龄[四分位间距]，41[13 - 84]天；529例为女性[50.8%]），根据AAP标准，977例（93.8%）被分类为高风险。共有79例患者（7.6%）有严重的潜在诊断。对于这一结局，AAP标准显示敏感性为100.0%（95%置信区间，95.4% - 100.0%），特异性为6.7%（95%置信区间，5.2% - 8.5%），阳性似然比（LR+）为1.07（95%置信区间，1.05 - 1.09），曲线下面积（AUC）为0.53（95%置信区间，0.53 - 0.54）。用于辨别严重诊断的BRUE预测规则的AUC为0.60（95%置信区间，0.54 - 0.67；校准截距：0.60），在模型修订后提高到0.71（95%置信区间，0.65 - 0.76；P <.001；校准截距：0.00）。163例患者（15.6%）出现事件复发。对于这一结局，AAP标准的敏感性为99.4%（95%置信区间，96.6% - 100.0%），特异性为7.3%（95%置信区间，5.7% - 9.2%），LR+为1.07（95%置信区间，1.05 - 1.10），AUC为0.58（95%置信区间，0.56 - 0.58）。预测规则的AUC为0.67（95%置信区间，0.62 - 0.72；校准截距：0.15）。
这项多中心队列研究的结果表明，在外部地理验证中，BRUE预测规则优于AAP高风险标准，并且重新校准后性能有所改善。这些规则为临床医生和家庭提供了一个更精确的工具，以支持基于个体风险承受能力的决策。
