External Validation of Brief Resolved Unexplained Events Prediction Rules for Serious Underlying Diagnosis
Authors: 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. ,   Canadian BRUE Collaboration (C-BRUE-C) and the Canadian Paediatric Inpatient Research Network (PIRN), Kyrychenko Polina , Kirolos Nardin , Opotchanova Ioulia , Harnois Émilie , Frizon-Peresa Elisa , Rajasegaran Praveen , Hosseini Parnian , Wyslobicky Melody , Akbaroghli Susan , Nalan Prathiksha , Goupil Marie-Pier , Lee Shawn , Philibert Emy , Dufrense Juliette , Chawla Raman , Ogwuru Martin 
Published: December 2024

ImportanceThe 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 (&amp;gt;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.ObjectiveTo externally validate new BRUE prediction rules and compare them with the AAP higher-risk criteria.Design, Setting, and ParticipantsThis 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.ExposuresThe BRUE prediction rules.Main Outcome and MeasureThe primary outcome was a serious underlying diagnosis, defined as conditions where a delay in diagnosis could lead to increased morbidity or mortality.ResultsOf 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 &amp;lt; .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).Conclusions and RelevanceResults 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.