What are the causes and management of brief resolved unexplained events (BRUE)?

Brief Resolved Unexplained Events (BRUE): Causes and Management

Brief resolved unexplained events (BRUE) are characterized by sudden, brief episodes of cyanosis/pallor, breathing irregularities, tone changes, or altered responsiveness in infants under 1 year of age that remain unexplained after a thorough history and physical examination. 1 These events represent a diagnosis of exclusion that replaced the older term "apparent life-threatening event" (ALTE) in 2016.

Definition and Diagnostic Criteria

A BRUE is diagnosed when an infant under 1 year presents with a sudden, brief (typically <1 minute), and resolved episode involving one or more of:

• Cyanosis or pallor
• Absent, decreased, or irregular breathing
• Marked change in tone (hyper- or hypotonia)
• Altered level of responsiveness

Importantly, the diagnosis is made only when there is no explanation for the event after conducting an appropriate history and physical examination 1.

Risk Stratification

The American Academy of Pediatrics (AAP) classifies BRUE into two categories:

Lower-Risk BRUE

Infants who meet all of the following criteria:

• Age >60 days
• Gestational age ≥32 weeks and postconceptional age ≥45 weeks
• First BRUE episode (no previous BRUE events)
• Duration of event <1 minute
• No CPR required by trained medical provider
• No concerning historical features or physical examination findings

Higher-Risk BRUE

Infants who have any of the following:

• Age ≤60 days
• Premature birth (<32 weeks) or postconceptional age <45 weeks
• Multiple BRUE episodes
• Event duration ≥1 minute
• CPR required by trained medical provider
• Concerning historical or physical examination findings

Potential Causes of BRUE

While by definition a BRUE has no immediately identifiable cause, several underlying conditions may be associated with these events:

1. Neurological disorders:

   • Seizures
   • Central nervous system abnormalities

2. Respiratory issues:

   • Obstructive sleep apnea
   • Central apnea
   • Upper airway anomalies

3. Cardiovascular problems:

   • Arrhythmias
   • Congenital heart disease

4. Gastrointestinal disorders:

   • Gastroesophageal reflux (though not typically a cause of true BRUE)
   • Swallowing dysfunction

5. Metabolic/endocrine disorders:

   • Inborn errors of metabolism
   • Hypoglycemia

6. Infectious causes:

   • Respiratory infections
   • Sepsis (rare in lower-risk BRUE)

7. Child abuse/trauma:

   • Non-accidental head trauma
   • Intentional suffocation

8. Other:

   • Breath-holding spells
   • Toxin exposure

Management Approach

For Lower-Risk BRUE

The AAP provides specific recommendations for lower-risk patients 1:

1. Education and reassurance:

   • Explain the diagnosis and its benign nature
   • Provide education about BRUE
   • Engage in shared decision-making with caregivers

2. Recommended evaluations:

   • Consider brief period of observation (1-4 hours)
   • Consider obtaining 12-lead ECG to identify cardiac causes

3. NOT recommended for lower-risk BRUE:

   • Hospital admission
   • Home cardiorespiratory monitoring
   • Neuroimaging (CT, MRI, or ultrasound)
   • EEG
   • Blood tests (CBC, blood culture)
   • Cerebrospinal fluid analysis
   • Chest radiograph
   • Polysomnography
   • Gastroesophageal reflux studies
   • Pertussis or respiratory viral testing

4. Follow-up:

   • Arrange timely outpatient follow-up
   • Provide anticipatory guidance

For Higher-Risk BRUE

For higher-risk patients, management should be more comprehensive 1:

1. Consider hospitalization for observation and monitoring

2. Targeted evaluation based on history and physical findings:

   • Cardiorespiratory monitoring
   • Neurological evaluation (consider EEG if seizure suspected)
   • Infectious workup if indicated
   • Metabolic screening if indicated
   • Evaluation for child abuse if suspicious findings

3. Specialist consultation as appropriate:

   • Neurology
   • Cardiology
   • Pulmonology
   • Gastroenterology

Clinical Pearls and Pitfalls

1. Distinguish BRUE from normal infant physiology:

   • Periodic breathing of newborns
   • Breath-holding spells
   • Normal color changes during feeding

2. Avoid common pitfalls:

   • Labeling all concerning events as BRUE
   • Missing signs of child abuse
   • Overdiagnosis of gastroesophageal reflux as a cause
   • Unnecessary testing in lower-risk infants

3. Red flags requiring further evaluation:

   • Multiple or changing versions of the history
   • History inconsistent with child's developmental stage
   • Unexplained bruising
   • Incongruence between caregiver expectations and child's development

Outcomes

Recent data suggests that only about 4% of BRUE cases are caused by a serious underlying illness 2. The most common serious diagnoses include seizures and airway abnormalities 3. Prior BRUE events are associated with higher risk of serious diagnoses and episode recurrence 3.

The AAP guidelines for lower-risk infants can be safely implemented, reducing unnecessary hospitalizations and testing while maintaining patient safety 3, 4.