Abstract
<title>Abstract</title> <p>Background Brief Resolved Unexplained Event (BRUE) is a diagnosis of exclusion in infants younger than one year and remains a common reason for emergency department visits and hospitalization. Although extensive diagnostic investigations are frequently performed in infants classified as high risk, evidence regarding their diagnostic yield and prognostic value remains limited. This study aimed to evaluate the diagnostic yield of investigations, determine explanatory diagnoses, assess short-term clinical outcomes, and identify factors associated with adverse outcomes among hospitalized infants with high-risk BRUE. Methods This retrospective observational cohort study included infants younger than 12 months hospitalized with high-risk BRUE at a tertiary referral center between January 2018 and December 2024. Demographic characteristics, clinical presentation, diagnostic investigations, explanatory diagnoses, and short-term outcomes were extracted from electronic medical records. Diagnostic yield was defined according to the clinical impact of each investigation on patient management. Univariable logistic regression analysis was performed to identify factors associated with adverse clinical outcomes. Results Fifty-five infants were included. The mean gestational age was 38.1 ± 1.7 weeks, and the mean birth weight was 3116 ± 474 g. An explanatory diagnosis was established in 21 infants (38.2%), whereas 34 (61.8%) remained without an identifiable cause despite comprehensive evaluation. Echocardiography, electroencephalography, and urinalysis provided the highest diagnostic yield, whereas electrocardiography, blood cultures, cerebrospinal fluid cultures, and tandem mass spectrometry did not identify clinically meaningful abnormalities. During follow-up, emergency department revisits occurred in 12.7% of infants, hospital readmission in 14.5%, and overall mortality was 7.3%. Apnea or irregular breathing at presentation was associated with an increased risk of adverse outcomes (OR 4.22, 95% CI 0.88–20.19), although statistical significance was not achieved. All deaths occurred among infants without an explanatory diagnosis. Conclusions Most hospitalized infants with high-risk BRUE had no explanatory diagnosis despite extensive diagnostic evaluation. Diagnostic investigations demonstrated variable clinical utility, supporting a selective rather than routine testing strategy. The absence of an explanatory diagnosis did not exclude subsequent adverse outcomes, emphasizing the importance of individualized clinical risk assessment and appropriate follow-up in infants with high-risk BRUE.</p>