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

Importance

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 (&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.

Objective

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.

Exposures

The BRUE prediction rules.

Main Outcome and Measure

The primary outcome was a serious underlying diagnosis, defined as conditions where a delay in diagnosis could lead to increased morbidity or mortality.

Results

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 &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 Relevance

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.