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Infant Outcomes, Risk Factors, and Diagnostic Yield After a Brief Resolved Unexplained Event: A Systematic Review and

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Brief Resolved Unexplained Events (BRUE) in infants rarely lead to serious diagnoses or death. Most routine tests offer little value, suggesting a shift to risk-informed clinical approaches for better infant care.

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Area of Science:

  • Pediatric Emergency Medicine
  • Neonatology
  • Clinical Epidemiology

Background:

  • Clinical uncertainty persists regarding Brief Resolved Unexplained Events (BRUE) due to limited research.
  • Variations in clinical practice arise from conflicting data on adverse outcomes, risk factors, and diagnostic utility.

Purpose of the Study:

  • To determine the frequency of serious underlying diagnoses and 3-month mortality in infants following a BRUE.
  • To identify prognostic risk factors for adverse outcomes.
  • To quantify the diagnostic yield of common investigations for BRUE.

Main Methods:

  • Systematic review and meta-analysis of cohort studies, case-control studies, and clinical trials.
  • Searched PubMed, Embase, Cochrane, and gray literature (January 2016-July 2025).
  • Pooled prevalence, mortality, risk factors, and diagnostic yield using random-effects meta-analyses; assessed evidence certainty with GRADE.

Main Results:

  • 24 studies including 6603 infants were analyzed.
  • Serious underlying diagnosis prevalence was 6.0% (high certainty); 3-month mortality was rare (1 in 1851 infants, moderate certainty).
  • Multiple events history and prematurity increased risk for serious diagnosis; routine tests (metabolic panels, ECGs, chest X-rays) showed very low diagnostic yield.

Conclusions:

  • Infant mortality after BRUE is exceedingly rare, with serious underlying diagnoses in a small percentage.
  • Most routine diagnostic tests provide minimal value and can yield false positives.
  • Clinical practice should transition to targeted, risk-informed evaluations for BRUE, guiding guideline revisions.