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Multicenter Study
. 2025 Feb 1;179(2):188-196.
doi: 10.1001/jamapediatrics.2024.4399.

External Validation of Brief Resolved Unexplained Events Prediction Rules for Serious Underlying Diagnosis

Nassr Nama  1 , Ye Shen  2 , Jeffrey N Bone  2 , Zerlyn Lee  3 , Kara Picco  4 , Falla Jin  2 , Jessica L Foulds  5 , Josée Anne Gagnon  6 , Chris Novak  7 , Brigitte Parisien  8 , Matthew Donlan  9 , Ran D Goldman  2 , Anupam Sehgal  10 , Joanna Holland  11 , Sanjay Mahant  4 , Joel S Tieder  12 , Peter J Gill  4 ; Canadian BRUE Collaboration (C-BRUE-C) and the Canadian Paediatric Inpatient Research Network (PIRN)
Collaborators, Affiliations
Multicenter Study

External Validation of Brief Resolved Unexplained Events Prediction Rules for Serious Underlying Diagnosis

Nassr Nama et al. JAMA Pediatr. .

Abstract

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 (>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 < .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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Nama reported receiving grants from the American Academy of Pediatrics and Canadian Paediatric Society during the conduct of the study and being a prior shareholder of insightScope outside the submitted work. Dr Lee reported receiving grants from the Canadian Pediatric Society during the conduct of the study. Dr Tieder reported receiving personal fees from Children’s Hospital Association outside the submitted work. Dr Gill reported receiving grants from the Canadian Institutes of Health Research and the PSI Foundation outside the submitted work. No other disclosures were reported.

References

    1. Nama N, DeLaroche AM, Neuman MI, et al. . Epidemiology of brief resolved unexplained events and impact of clinical practice guidelines in general and pediatric emergency departments. Acad Emerg Med. 2024;31(7):667-674. doi:10.1111/acem.14881 - DOI - PubMed
    1. Tieder JS, Bonkowsky JL, Etzel RA, et al. ; Subcommittee on Apparent Life-Threatening Events . Brief resolved unexplained events (formerly apparent life-threatening events) and evaluation of lower-risk infants. Pediatrics. 2016;137(5):e20160590. doi:10.1542/peds.2016-0590 - DOI - PubMed
    1. Khan A, Wallace SS, Sampayo EM, Falco C. Caregivers’ perceptions and hospital experience after a brief resolved unexplained event: a qualitative study. Hosp Pediatr. 2019;9(7):508-515. doi:10.1542/hpeds.2018-0220 - DOI - PubMed
    1. Maksimowski K, Haddad R, DeLaroche AM. Pediatrician perspectives on brief resolved unexplained events. Hosp Pediatr. 2021;11(9):996-1003. doi:10.1542/hpeds.2021-005805 - DOI - PubMed
    1. Nama N, DeLaroche AM, Gremse DA. Brief resolved unexplained event (BRUE): is reassurance enough for caregivers? Hosp Pediatr. 2022;12(12):e440-e442. doi:10.1542/hpeds.2022-006939 - DOI - PubMed

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