Discussion
In this large Canadian cohort of over 1000 patients with BRUE, the vast majority of which were classified as ‘higher-risk’, we found that most infants did not have an explanatory diagnosis and only 8% had serious underlying conditions, where delayed treatment could have increased morbidity or mortality. Serious diagnoses primarily included seizures/infantile spasms and apnoea. Gastrointestinal diagnoses were predominant among non-serious aetiologies. Our findings support the growing body of evidence indicating a low likelihood of serious diagnoses presenting as BRUE,7 11 14 and provide clinicians and caregivers with metrics to guide management.
Infants with BRUE are commonly admitted and undergo diagnostic testing to identify serious underlying diagnoses.14 25–29 While these practices are intended to be reassuring, they can inadvertently increase caregiver anxiety, risk for harm due to testing cascades as well as elevate costs.2–5 30 The low prevalence and heterogeneity of serious underlying diagnoses contribute to a low diagnostic yield. Routine tests frequently unveil incidental or clinically insignificant findings (eg, haemolysed samples requiring multiple repeats), rather than explaining the index event.14 The AAP recommends consideration of pertussis testing and an ECG for lower risk patients.1 However, combining data from our cohort with the BRUE Quality Improvement and Research Collaborative from 15 US children’s hospitals,7 a total of 4325 patients, revealed that only six had pertussis, and four had a serious underlying cardiac diagnosis. This calls into question the value of routine ECG and pertussis testing unless specific clinical concerns exist. While some may perceive ECG as a simple non-invasive test to provide reassurance, research has shown that this often leads to a diagnostic cascade where non-specific ECG findings lead to prolonged hospital stay for further testing or cardiology consultation, inadvertently increasing parental anxiety.14 Epilepsy was the most common serious underlying diagnosis. Patients exhibiting red flags for neurological conditions or experiencing recurrent events—identified as a significant risk factor for serious illness in both our study and others8 12—might benefit from a close outpatient neurological evaluation to assess the need for an electroencephalogram.31–33
Apart from serious diagnoses, non-serious underlying conditions are prevalent, and identifying them could offer an explanation and potentially bring reassurance.4 The majority of these diagnoses relate to feeding and gastrointestinal issues.7 Having a specialist provider or service observe feeding can help identify issues like reflux or oropharyngeal dysphagia. However, providers should exercise caution when prescribing reflux medications, given the mounting evidence of their limited benefits and potential side effects.34–37 Despite the lack of worrisome signs in most infants with reflux (eg, no failure to thrive), we noted a high number of patients being discharged on reflux medications, presenting an area for quality improvement and provider and caregiver education.
Healthcare providers commonly express concern regarding the risk for an underlying diagnosis, while caregivers are similarly anxious about event recurrence.5 10 Notably, our results show a strong association between the two outcomes, with the odds of a serious underlying diagnosis being more than three times higher in patients with multiple events prior to presentation. Hospital monitoring for event recurrence has been suggested as a potential advantage of admission.5 23 However, it is important to note that such recurrences are infrequent, and rarely do they contribute to reaching a diagnosis, given that the majority of BRUE events remain unexplained without an underlying aetiology. In our study, a mere 5% of hospitalised patients experienced a recurrent event while in the hospital, which then led to an explanatory diagnosis. This observation aligns with findings from Bochner et al, where only 7% of cases noted a similar outcome.9 Conveying these findings may allow caregivers to assess whether hospital admission aligns with their individual values. Some caregivers might value the observation period, while others may question the benefits of hospitalisation.2–5 This highlights the need for personalised BRUE management centred on shared decision-making (SDM). The successful application of SDM in paediatric conditions like traumatic brain injury has reduced low-yield investigations and improved parental satisfaction.38 SDM benefits in the context of BRUE have been acknowledged by caregivers,4 5 clinicians10 and researchers.1 7 13 A critical piece in SDM is the discussion of risk. Our study results can guide these discussions, helping providers and caregivers understand potential BRUE outcomes on a population level. Other strategies that focus on individual risk factors and estimate specific patient’s risk have been explored but remain to be validated.7 These approaches may offer more precise risk estimates than the current AAP higher risk stratification, which categorises most patients as higher risk,7 17 39 40 and has been increasingly questioned for its effectiveness and utility.7 8 41 Despite the overall low risk of serious underlying diagnoses and event recurrence during hospitalisation, we observed a relatively high rate of ICU admissions, predominantly for observation, consistent with trends reported in single-centre studies in the USA.27 42 Additionally, there was variability between hospital practices. ICU care should be reserved for patients requiring high-acuity interventions, such as respiratory support, vasoactive medications or continuous close monitoring. Patients presenting with BRUE who are asymptomatic on admission generally do not warrant ICU-level care, representing another area for targeted quality improvement efforts.
The study strengths include its large sample size, and multisite involvement across a vast geographical area (spanning different Canadian regions) and including diverse hospital settings. A limitation is the potential for missing patients who might have had a serious diagnosis but lack specific BRUE-related International Classification of Diseases codes. However, our selection approach has been validated with 99% sensitivity, and it is unlikely that patients meeting the BRUE criteria will have a clear explanatory diagnosis coded at the time of admission.22 Given the retrospective nature of our study, there is also a possibility that patients may have subsequently sought care at a different hospital or healthcare system, which our review might have missed. However, our study covered major paediatric centres, where critically ill patients are likely to receive both inpatient and outpatient care. Moreover, several provinces in our study have a shared data system within the province, ensuring comprehensive data capture. Finally, in three hospitals where the number of patients approached 200, our sampling approach may have reduced our power, with potential differences between the cases sampled and those not sampled. However, the randomisation process implemented is anticipated to significantly mitigate this potential bias.
In conclusion, our study, describing a large BRUE cohort, demonstrates a low risk for a serious underlying diagnosis, where the majority of patients remain without a clear explanation. This provides evidence-based risk for adverse outcomes, critical information to be used when engaging in SDM with caregivers, to convey the pros and cons of different management approaches, understand the family’s values and risk tolerance and offer reassurance. Future research should focus on operationalising how to share these data with caregivers and how to engage in SDM, along with evaluating its benefits.