The term ALTE has been replaced by BRUE (Brief Resolved Unexplained Event) per the 2016 AAP Clinical Practice Guideline. [1] A BRUE is defined as a sudden, brief (<1 minute), and now resolved episode in an infant <1 year of age involving ≥1 of: cyanosis/pallor, absent/decreased/irregular breathing, marked change in tone, or altered responsiveness — with no identifiable explanation after appropriate history and physical examination. [1] BRUE is a diagnosis of exclusion. Serious underlying diagnoses are found in approximately 6% of cases, recurrence occurs in ~14%, and mortality is exceedingly rare (~1 per 1,851 infants). [2]
1. History
- Who witnessed the event? Reliability of historian; was the infant directly observed or found in the described state?
- State before event: Awake vs. asleep, position (supine/prone/upright), feeding, anything in the mouth, recent spitting up or vomiting
- During the event: Breathing present/absent/labored? Color change (cyanotic, pallid — not red/flushed)? Tone increased or decreased? Repetitive movements (seizure-like)? Conscious/responsive? Choking/gagging noise?
- Duration: Typically <20–30 seconds; events ≥1 minute are higher-risk [3]
- Termination: Spontaneous vs. required stimulation, repositioning, back blows, mouth-to-mouth, or CPR
- Post-event state: Immediate return to baseline vs. prolonged lethargy, irritability, or altered state
- Preceding illness: Fever, congestion, rhinorrhea, cough, vomiting, diarrhea, decreased intake in prior days
- Feeding history: Choking with feeds, difficulty latching, coughing/gagging during or after feeds (suggests GER or dysphagia, which precludes BRUE diagnosis) [1]
- Important negatives: No choking/gagging (these suggest GER or respiratory infection and are NOT BRUE), no fever, no respiratory symptoms [1]
2. Alarm Features
- Event requiring CPR by a trained medical provider [3]
- Multiple or clustered events — strongest predictor of serious underlying diagnosis (RD 3.7%) [2]
- Event duration ≥1 minute [3]
- Age ≤60 days (AAP higher-risk criterion, though recent meta-analysis challenges this as an independent predictor) [2-3]
- Prematurity (<32 weeks GA or corrected age <45 weeks) — associated with increased risk (RD 2.6%) [2]
- Inconsistent or changing history (raises concern for non-accidental trauma) [1]
- Unexplained bruising, torn frenulum, or injuries inconsistent with developmental stage [1]
- Infant appearing ill or symptomatic at presentation (fever, respiratory distress, lethargy) — this is NOT a BRUE and warrants a directed workup [1]
- Family history of sudden unexplained death in first-degree relatives (cardiac channelopathy concern) [1]
3. Medications
- No specific medications treat BRUE — management is observation and risk stratification
- Review any medications the infant is receiving (e.g., anti-reflux medications, sedating antihistamines, opioid-containing cough preparations given by caregivers)
- If GER is suspected as the cause, acid suppression therapy may be considered but the event would then not qualify as a BRUE
- Caffeine citrate may be relevant in premature infants with apnea of prematurity (a separate diagnosis)
- Avoid prescribing home apnea monitors as a substitute for appropriate evaluation [4]
4. Diet
- Assess feeding technique and positioning — improper feeding can cause choking/aspiration events
- Evaluate for overfeeding or rapid feeding contributing to GER-related events
- Breastfed vs. formula-fed: assess for dysphagia, aspiration risk
- Thickened feeds may be considered if GER is identified as the underlying cause (but this moves the diagnosis away from BRUE)
- Ensure adequate hydration and caloric intake, especially if the infant has had decreased oral intake surrounding the event
5. Review of Systems
- Respiratory: Noisy breathing, stridor, snoring, chronic cough, congestion (airway abnormality)
- GI: Frequent spitting up, vomiting, feeding difficulties, poor weight gain (GER, malrotation)
- Neurologic: Abnormal movements, staring spells, developmental regression, seizure-like activity
- Cardiac: Diaphoresis with feeds, poor feeding, tachypnea at rest
- Infectious: Fever, rhinorrhea, sick contacts, pertussis exposure
- Metabolic: Poor feeding, lethargy, unusual odor, failure to thrive
- Growth: Plotting growth parameters — failure to thrive raises concern for chronic disease or neglect
6. Collateral History and Family History
- Multiple caregivers present? Obtain history from the direct witness whenever possible
- Family history: Sudden unexplained death in young relatives (long QT, Brugada), seizure disorders, inborn errors of metabolism, congenital heart disease [1]
- Social history: Assess for child abuse risk factors — caregiver stress, domestic violence, substance use, prior CPS involvement, inconsistent histories [1]
- Siblings: History of SIDS or ALTE/BRUE in siblings (raises concern for both genetic conditions and non-accidental trauma)
- Newborn screening results: Confirm normal metabolic and cardiac screening [1]
7. Risk Factors
- Multiple prior events — strongest risk factor for serious underlying diagnosis [2][5]
- Prematurity (<32 weeks GA or corrected age <45 weeks) [2-3]
- Abnormal medical history (congenital anomalies, prior hospitalizations, known comorbidities) [5]
- Age ≤60 days (AAP criterion, though recent evidence suggests this alone may not independently predict serious outcomes) [2]
- Event duration ≥1 minute [3]
- Need for CPR by trained provider [3]
- Male sex (some data suggest male predominance) [6]
- Congenital heart disease [6]
8. Differential Diagnosis
The differential is broad. The most common identified etiologies in the ALTE literature include: [7]
- GI (up to 50%): Gastroesophageal reflux, malrotation with volvulus, intussusception
- Neurologic (~30%): Seizures (most common serious diagnosis at ~1.1%), CNS infections, intracranial hemorrhage, hydrocephalus [5]
- Respiratory (~20%): RSV/pertussis/viral URI, laryngomalacia, tracheomalacia, foreign body aspiration, obstructive sleep apnea
- Cardiac (~5%): Long QT syndrome, SVT, other arrhythmias, congenital heart disease [1]
- Metabolic/Endocrine (<5%): Inborn errors of metabolism, hypoglycemia, electrolyte abnormalities
- Infectious: Sepsis, meningitis, UTI, pertussis
- Non-accidental trauma: Must always be considered — intracranial hemorrhage, suffocation, Munchausen by proxy [1][8]
Cannot-miss diagnoses:
- Child abuse/non-accidental trauma
- Cardiac arrhythmia (long QT)
- Seizure
- Sepsis/meningitis (especially in neonates)
- Inborn error of metabolism
9. Past Medical History
- Gestational age and birth history — prematurity is a key risk factor [3]
- Newborn screening results — metabolic disorders, congenital heart disease [1]
- Previous BRUE/ALTE episodes — recurrence is a strong predictor of serious diagnosis [2]
- Known GER — obtain details of severity and management
- Breathing problems — chronic noisy breathing, snoring, stridor
- Growth trajectory — failure to thrive suggests chronic underlying disease
- Surgical history — prior airway or cardiac procedures
- Immunization history — temporal association (though vaccines are not a recognized cause)
10. Physical Exam
- Vital signs: HR, RR, SpO₂, temperature, BP (four-extremity if cardiac concern) — must be normal to classify as BRUE [1]
- General: Well-appearing vs. ill-appearing; Pediatric Assessment Triangle (appearance, work of breathing, circulation)
- HEENT: Anterior fontanelle (bulging = ICP), nasal patency, oropharynx (torn frenulum = abuse), palate integrity
- Respiratory: Stridor, wheezing, retractions, grunting, tracheal tug
- Cardiovascular: Murmur, gallop, irregular rhythm, capillary refill, femoral pulses
- Abdomen: Distension, tenderness, masses
- Neurologic: Tone (hyper/hypotonia), reflexes, fontanelle, pupil reactivity, abnormal movements, developmental milestones
- Skin: Bruising (especially in pre-mobile infants — highly suspicious for abuse), petechiae, rashes, cyanosis pattern
- Musculoskeletal: Tenderness, swelling (occult fractures in abuse)
11. Lab Studies
For lower-risk BRUE, the AAP recommends against routine blood testing. [1] Most routine labs have exceedingly low diagnostic yield: [2]
- Metabolic panels: 0% yield (NNT = 852) [2]
- Routine blood tests are generally not indicated in lower-risk BRUE
For higher-risk BRUE, consider targeted testing based on clinical suspicion: [8]
- CBC with differential — infection, anemia
- BMP — electrolytes, glucose, calcium (metabolic derangement)
- Blood gas/lactate — metabolic acidosis (IEM, sepsis)
- Blood culture, UA/Urine culture — if infection suspected
- Pertussis testing (PCR) — if respiratory symptoms or known exposure
- Ammonia, lactate, pyruvate, acylcarnitine profile, urine organic acids — if IEM suspected
- CSF studies — if meningitis/encephalitis suspected (especially neonates)
12. Imaging
For lower-risk BRUE, the AAP recommends against routine imaging. [1]
- Chest radiograph: 0.4% yield (NNT = 256) — not routinely indicated [2]
- Cranial ultrasound: Consider in neonates if concern for intracranial hemorrhage or abuse [9]
- CT head (non-contrast): If concern for non-accidental trauma or acute intracranial pathology
- Skeletal survey: If any concern for child abuse (mandatory)
- Upper GI series: If concern for malrotation (not for GER evaluation)
- MRI brain: Secondary evaluation if seizure or neurologic abnormality suspected [8]
- Airway fluoroscopy or bronchoscopy: If recurrent events with suspected airway abnormality
13. Special Tests
- AAP Risk Stratification — classify as lower-risk vs. higher-risk BRUE (see Risk Factors section) [1][3]
- Pertussis PCR — consider in any infant with apneic episodes, especially if <3 months or incompletely immunized
- Polysomnography — may be considered for recurrent events or suspected obstructive sleep apnea (secondary evaluation) [9]
- Swallow study/VFSS — if dysphagia or aspiration suspected [8]
- pH/impedance probe — if GER strongly suspected as cause (but then it is not a BRUE)
- EEG — if seizure suspected; has moderately higher yield than other tests when applied selectively [2]
The following figure from a 2026 meta-analysis summarizes the diagnostic yield of common tests in BRUE, demonstrating that most routine investigations have yields <1%:
14. ECG
- The AAP states clinicians may obtain an ECG in lower-risk BRUE (Grade D, weak recommendation) [1]
- ECG yield: 0.2% (NNT = 623) — low overall, but the consequence of missing a channelopathy is catastrophic [2]
- Key findings to assess:
- QTc prolongation (>460 ms in infants) — long QT syndrome
- Pre-excitation (delta wave) — Wolff-Parkinson-White
- Brugada pattern
- SVT or other arrhythmia
- Consider echocardiogram if murmur, abnormal ECG, or structural heart disease suspected
15. Assessment
- BRUE is a diagnosis of exclusion — only applied after thorough history and physical examination reveal no explanation [1]
- The critical first step is determining whether the event qualifies as a BRUE vs. an explained event (e.g., GER-related choking, febrile seizure, respiratory infection)
- If BRUE criteria are met, risk-stratify into lower-risk vs. higher-risk [1][3]
- Lower-risk BRUE (ALL criteria must be met): age >60 days, GA ≥32 weeks and corrected age ≥45 weeks, first event, duration <1 minute, no CPR by trained provider, normal history and exam [3]
- Serious underlying diagnoses are uncommon (~6%) but include seizures and airway abnormalities as the most common [2][5]
- Mortality is exceedingly rare (~1/1,851 infants over 3 months) [2]
- The AAP higher-risk criteria have excellent NPV (98%) but poor PPV (5%), overclassifying ~92% of patients as higher-risk [3]
16. Treatment Plan
Lower-risk BRUE: [1]
- No routine admission required solely for cardiorespiratory monitoring (Grade B)
- Brief observation (1–4 hours) with continuous pulse oximetry and serial examinations may be performed [1]
- May obtain ECG — reasonable given low cost and potential to detect channelopathy [1]
- Do not obtain: routine blood work, chest radiograph, echocardiogram, EEG, or neuroimaging [1]
- Do not initiate home cardiorespiratory monitoring [1]
- Educate caregivers on CPR, safe sleep practices, and when to return
- Arrange follow-up within 24 hours [1]
Higher-risk BRUE: [8]
- Tiered evaluation approach:
- Tier 1 (time-sensitive): Assess for child maltreatment, feeding problems, cardiac arrhythmia (ECG), infection (pertussis, UTI, sepsis in neonates), congenital abnormalities
- Tier 2 (less time-sensitive): Dysphagia evaluation, airway assessment, EEG for seizure
- Admission for cardiorespiratory monitoring and observation is generally appropriate
- Tailor workup to specific clinical concerns identified on history and exam
- Multidisciplinary approach as needed (pediatric cardiology, neurology, GI, child protection team)
17. Disposition
Discharge criteria (lower-risk BRUE)
- Meets all lower-risk criteria [3]
- Normal vital signs and physical exam throughout observation period
- No recurrent events during observation
- Caregivers educated and comfortable with CPR and return precautions
- Reliable follow-up within 24 hours arranged [1]
Admission criteria
- Any higher-risk feature present [3]
- Recurrent event during ED observation
- Concern for non-accidental trauma
- Ill-appearing infant or abnormal vital signs
- Caregiver unable to provide reliable observation or follow-up
- Clinician concern despite meeting lower-risk criteria (shared decision-making)
Specialist consultation triggers
- Abnormal ECG → Pediatric Cardiology
- Seizure-like features → Pediatric Neurology
- Suspected abuse → Child Protection Team / Social Work
- Recurrent events with suspected airway pathology → Pediatric Pulmonology/ENT
- Suspected IEM → Pediatric Genetics/Metabolism
18. Follow Up / Return Precautions
- Follow-up within 24 hours of discharge for repeat history and physical examination [1]
- PCP follow-up within 1 week for reassessment and growth monitoring
- Caregiver education:
- Infant CPR training (offer resources)
- Safe sleep practices (supine positioning, firm sleep surface, no co-sleeping, no loose bedding)
- BRUE is NOT the same as SIDS — these are distinct entities [1]
- Return immediately if:
- Another episode occurs
- Infant develops fever, difficulty breathing, poor feeding, or lethargy
- Color change (blue/pale) recurs
- Infant becomes less responsive or difficult to arouse
- Expected course: Most infants with lower-risk BRUE have a benign clinical course. Recurrence occurs in ~14% within 3 months, but serious outcomes remain rare [2]
- Parental anxiety is common and should be addressed directly — reassurance grounded in evidence that mortality is exceedingly rare and most events are benign [2]
References
1. Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower-Risk Infants. — Tieder JS, Bonkowsky JL, Etzel RA, et al. Pediatrics. 2016.
2. Infant Outcomes, Risk Factors, and Diagnostic Yield After a Brief Resolved Unexplained Event. — Nama N, Liebert S, Abaji M, et al. JAMA Pediatrics. 2026.
3. External Validation of Brief Resolved Unexplained Events Prediction Rules for Serious Underlying Diagnosis. — Nama N, Shen Y, Bone JN, et al. JAMA Pediatrics. 2025.
4. Impact of the BRUE (Brief Resolved Unexplained Event) Definition on Hospital Clinical Practice and Recurrence: A Quasi-Experimental Study in Infants. — Comino-Hidalgo I, Gonzalez-Sanchez MI, Gonzalez-Martinez F, et al. European Journal of Pediatrics. 2025.
5. Risk Factors and Outcomes After a Brief Resolved Unexplained Event: A Multicenter Study. — Tieder JS, Sullivan E, Stephans A, et al. Pediatrics. 2021.
6. Etiology and Outcome of Severe Apparent Life-Threatening Events in Infants. — Radovanovic T, Spasojevic S, Stojanovic V, Doronjski A. Pediatric Emergency Care. 2018.
7. Evaluation and Management of Apparent Life-Threatening Events in Children. — Hall KL, Zalman B. American Family Physician. 2005.
8. A Framework for Evaluation of the Higher-Risk Infant After a Brief Resolved Unexplained Event. — Merritt JL, Quinonez RA, Bonkowsky JL, et al. Pediatrics. 2019.
9. Apparent Life-Threatening Events and Brief Resolved Unexplained Events: Management of Children at a Swiss Tertiary Care Center. — Evers KS, Wellmann S, Donner BC, Ritz N. Swiss Medical Weekly. 2021.