BRUE (brief, resolved, unexplained events) denotes an episode of cyanosis or pallor, abnormal breathing, abnormal muscle tone, or altered responsiveness in an infant. BRUE is not a specific disorder and is diagnosed only when no other cause is identified for the qualifying event. Expert consensus holds that BRUE is a distinct entity from SIDS (sudden infant death sydrome) and SUID (sudden unexpected infant death).
BRUE is formally defined as an event occurring in an infant < 1 year of age that is reported by an observer as a sudden, brief, and then resolved episode and includes ≥ 1 of the following (1):
Cyanosis or pallor
Absent, decreased, or irregular breathing
Marked change in tone (hyper- or hypotonia)
Altered level of responsiveness
Defining elements of a BRUE include: duration of < 1 minute (brief); return to baseline health with normal vital signs and appearance after the episode (resolved); and lack of detection of an explanatory underlying medical condition on initial assessment (unexplained). BRUE can be diagnosed only when there is no explanation for the qualifying event after an appropriate history and physical examination have been conducted. Symptomatic infants, for example, those with fever or respiratory distress, are excluded from this diagnosis as is any infant whose history or physical assessment suggests a cause.
Similar events were previously termed apparent life-threatening events (ALTEs), which described frightening, short-lived events in infants that caregivers feared were life threatening (2). Although the definition of ALTE overlaps with BRUE, the two are separate entities. Ultimately, research has shown that most ALTEs are not life threatening, and clinicians have grown to recognize that the diagnostic criterion of “frightening to the observer” is less clinically useful than physiologic descriptions of the infant during the event (while in no way minimizing the importance of caregivers acting responsibly by seeking medical attention). Study of the physiologic elements, moreover, has allowed clinicians to differentiate between high-risk events requiring definitive diagnosis and low-risk events where further assessment is unlikely to prove useful.
Relationship to SIDS
Terminology regarding these types of events has evolved over time. The diagnostic construct of BRUE evolved from the study of medical events that were once called “near-miss SIDS.” Frequently, infants who have such an event are brought to medical attention by a caregiver who interrupted the event and is worried it would have been otherwise fatal to the infant.
Beyond questions about whether infants who have SIDS can be resuscitated or can survive, SIDS and BRUE have distinct risk profiles, and current consensus among medical experts is that they are unrelated. The distinction is based on several factors:
Different ages of peak incidence (SIDS: 1 to 4 months with peak in third month of life; BRUE: < 2 months) (3–5)
Substantially higher risk of SIDS/SUID associated with prematurity and low birth weight than BRUE (7, 8)
Strong association of SIDS but not BRUE with sleep and elements of the sleep environment (prone sleeping, sleeping on sofas, most events occurring during sleep hours and many after midnight) (4, 9)
Differential response of event rates after the increased adoption of supine sleep (SIDS rate decreased, BRUE/ALTE rate did not) (10)
Additional differences in risk factor profiles have also been described (8, 11). Although apnea is included in the differential diagnosis of BRUE, its association with SIDS is weak, and numerous studies over the years have failed to confirm a causal relationship between preexisting apnea and SIDS (4). Breastfeeding and consumption of human milk are protective against SIDS; whereas factors such as overfeeding and feeding coordination are related to BRUE (1, 12, 13).
Maternal smoking is a risk factor for both SIDS and BRUE.
General references
1. Tieder JS, Bonkowsky JL, Etzel RA, et al. Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower-Risk Infants. Pediatrics. 2016;137(5):e20160590. doi:10.1542/peds.2016-0590
2. National Institutes of Health Consensus Development Conference on Infantile Apnea and Home Monitoring, Sept 29 to Oct 1, 1986. Pediatrics. 1987;79(2):292-299.
3. Nama N, Shen Y, Bone JN, et al. External Validation of Brief Resolved Unexplained Events Prediction Rules for Serious Underlying Diagnosis. JAMA Pediatr. 2025;179(2):188-196. doi:10.1001/jamapediatrics.2024.4399
4. Moon RY, Carlin RF, Hand I; TASK FORCE ON SUDDEN INFANT DEATH SYNDROME and THE COMMITTEE ON FETUS AND NEWBORN. Evidence Base for 2022 Updated Recommendations for a Safe Infant Sleeping Environment to Reduce the Risk of Sleep-Related Infant Deaths. Pediatrics. 2022;150(1):e2022057991. doi:10.1542/peds.2022-057991
5. Habich M, Zielenkiewicz P, Paczek L, Szczesny P. Correlation of gestational age and age at death in sudden infant death syndrome: another pointer to the role of critical developmental period?. BMC Pediatr. 2024;24(1):259. Published 2024 Apr 19. doi:10.1186/s12887-024-04712-3
6. Oltman SP, Rogers EE, Baer RJ, et al. Early Newborn Metabolic Patterning and Sudden Infant Death Syndrome. JAMA Pediatr. 2024;178(11):1183-1191. doi:10.1001/jamapediatrics.2024.3033
7. Carlin RF, Moon RY. Risk Factors, Protective Factors, and Current Recommendations to Reduce Sudden Infant Death Syndrome: A Review. JAMA Pediatr. 2017;171(2):175-180. doi:10.1001/jamapediatrics.2016.3345
8. Esani N, Hodgman JE, Ehsani N, Hoppenbrouwers T. Apparent life-threatening events and sudden infant death syndrome: comparison of risk factors. J Pediatr. 2008;152(3):365-370. doi:10.1016/j.jpeds.2007.07.054
9. Blair PS, Platt MW, Smith IJ, Fleming PJ; SESDI SUDI Research Group. Sudden Infant Death Syndrome and the time of death: factors associated with night-time and day-time deaths. Int J Epidemiol. 2006;35(6):1563-1569. doi:10.1093/ije/dyl212
10. Kiechl-Kohlendorfer U, Hof D, Peglow UP, Traweger-Ravanelli B, Kiechl S. Epidemiology of apparent life threatening events. Arch Dis Child. 2005;90(3):297-300. doi:10.1136/adc.2004.049452
11. Hoppenbrouwers T, Hodgman JE, Ramanathan A, Dorey F. Extreme and conventional cardiorespiratory events and epidemiologic risk factors for SIDS. J Pediatr. 2008;152(5):636-641. doi:10.1016/j.jpeds.2007.10.003
12. Meek JY, Noble L. Technical Report: Breastfeeding and the Use of Human Milk. Pediatrics. 2022;150(1):e2022057989. doi:10.1542/peds.2022-057989
13. Quitadamo P, Mosca C, Verde A, et al. Infants' Feeding Habits and Brief Resolved Unexplained Events (BRUEs): A Prospective Observational Study. J Clin Med. 2025;14(6):1910. Published 2025 Mar 12. doi:10.3390/jcm14061910
Etiology of BRUE
Etiologies of BRUE may be genetic or acquired. If an infant is under the care of one person and has repeated episodes with no clear etiology, child abuse should be considered.
The most common possible underlying causes include:
Digestive: Gastroesophageal reflux disease or swallowing difficulty when associated with laryngospasm or aspiration
Neurologic: Neurologic disorders (eg, seizures, brain tumors, breath holding or abnormal brain stem neuroregulation of cardiorespiratory control, hydrocephalus, brain malformations)
Respiratory: Infections (eg, respiratory syncytial virus, influenza, pertussis)
Infectious: Sepsis, meningitis
Less common possible underlying causes include:
Metabolic disorders
Upper airway obstruction (eg, obstructive sleep apnea)
Other (eg, drug- or toxin-related [eg, ethanol, nonprescription antihistamine and/or decongestant preparations] [1, 2], anaphylaxis, abuse)
In cohort studies of patients presenting with BRUE, an explanatory diagnosis was reached in 45 to 47% of patients, and a serious underlying diagnosis was reached in between 4% and 17% of patients, sometimes after recurrence of the initial BRUE (3–6). In one study, diagnoses requiring prompt recognition because delays could cause morbidity and mortality, including seizures, were identified in 4.6% of patients (5). In a single center cohort study of 124 infants hospitalized with BRUE, the most common diagnoses included gastroesophageal reflux (42%), oropharyngeal dysphagia (7%), laryngomalacia (6%), and feeding difficulties (4%) (7). Many of these infants had recurrent symptoms after discharge.
Etiology references
1. Pitetti RD, Whitman E, Zaylor A. Accidental and nonaccidental poisonings as a cause of apparent life-threatening events in infants. Pediatrics. 2008;122(2):e359-e362. doi:10.1542/peds.2007-3729
2. Tieder JS, Bonkowsky JL, Etzel RA, et al. Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower-Risk Infants. Pediatrics. 2016;137(5):e20160590. doi:10.1542/peds.2016-0590
3. Tieder JS, Sullivan E, Stephans A, et al. Risk Factors and Outcomes After a Brief Resolved Unexplained Event: A Multicenter Study. Pediatrics. 2021;148(1):e2020036095. doi:10.1542/peds.2020-036095
4. Nama N, Lee Z, Picco K, et al. Identifying serious underlying diagnoses among patients with brief resolved unexplained events (BRUEs): a Canadian cohort study. BMJ Paediatr Open. 2024;8(1):e002525. Published 2024 Sep 24. doi:10.1136/bmjpo-2024-002525
5. Nama N, Hall M, Neuman M, et al. Risk Prediction After a Brief Resolved Unexplained Event. Hosp Pediatr. 2022;12(9):772-785. doi:10.1542/hpeds.2022-006637
6. Mittal MK, Tieder JS, Westphal K, et al. Diagnostic testing for evaluation of brief resolved unexplained events. Acad Emerg Med. 2023;30(6):662-670. doi:10.1111/acem.14666
7. Duncan DR, Liu E, Growdon AS, Larson K, Rosen RL. A Prospective Study of Brief Resolved Unexplained Events: Risk Factors for Persistent Symptoms. Hosp Pediatr. 2022;12(12):1030-1043. doi:10.1542/hpeds.2022-006550
Epidemiology of BRUE
BRUE is a relatively new term, and the incidence of BRUE is unclear. Studies of the previous term, ALTE, estimate the incidence of ALTEs was 2.5 to 4.1 per 1000 live births (1, 2). However, one study of patients diagnosed with ALTE found that less than half met diagnostic criteria for BRUE (3).
Prognostic estimates for BRUE also remain provisional. In data regarding ALTE, one-year mortality after an event is below 1% (4).
Epidemiology references
1. Kiechl-Kohlendorfer U, Hof D, Peglow UP, Traweger-Ravanelli B, Kiechl S. Epidemiology of apparent life threatening events. Arch Dis Child. 2005;90(3):297-300. doi:10.1136/adc.2004.049452
2. Monti MC, Borrelli P, Nosetti L, et al. Incidence of apparent life-threatening events and post-neonatal risk factors. Acta Paediatr. 2017;106(2):204-210. doi:10.1111/apa.13391
3. Ramgopal S, Soung J, Pitetti RD. Brief Resolved Unexplained Events: Analysis of an Apparent Life Threatening Event Database. Acad Pediatr. 2019;19(8):963-968. doi:10.1016/j.acap.2019.08.001
4. Parker K, Pitetti R. Mortality and child abuse in children presenting with apparent life-threatening events. Pediatr Emerg Care. 2011;27(7):591-595. doi:10.1097/PEC.0b013e3182225563
Risk Stratification for BRUE
Infants with BRUE are stratified as low or high risk of having a serious underlying disorder and/or an adverse outcome based on certain criteria.
Criteria for low-risk infants include the following (1, 2):
Age > 60 days
Gestational age at birth ≥ 32 weeks and corrected gestational age ≥ 45 weeks
Presentation to medical attention after a single, unrepeated event (no prior BRUE and no cluster of BRUEs)
No CPR administered by a trained medical provider
No concerning features identified in history (eg, concern for child abuse, family history of sudden death) or during physical examination (eg, afebrile, normotensive)
Low-risk infants are very unlikely to have a serious underlying disorder, and the guidelines recommend few or no interventions other than limited observation and caregiver education (1).
High-risk infants include all those who do not meet low-risk criteria (2). Patients in the high-risk group are more likely to have a serious underlying disorder, and clinicians should pursue an explanatory diagnosis. In studies, the majority (87 to 94%) of BRUEs are categorized as high risk (3, 4).
Risk stratification references
1. Tieder JS, Bonkowsky JL, Etzel RA, et al. Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower-Risk Infants. Pediatrics. 2016;137(5):e20160590. doi:10.1542/peds.2016-0590
2. Merritt JL 2nd, Quinonez RA, Bonkowsky JL, et al. A Framework for Evaluation of the Higher-Risk Infant After a Brief Resolved Unexplained Event. Pediatrics. 2019;144(2):e20184101. doi:10.1542/peds.2018-4101
3. Nama N, Hall M, Neuman M, et al. Risk Prediction After a Brief Resolved Unexplained Event. Hosp Pediatr. 2022;12(9):772-785. doi:10.1542/hpeds.2022-006637
4. Nama N, Lee Z, Picco K, et al. Identifying serious underlying diagnoses among patients with brief resolved unexplained events (BRUEs): a Canadian cohort study. BMJ Paediatr Open. 2024;8(1):e002525. Published 2024 Sep 24. doi:10.1136/bmjpo-2024-002525
Diagnosis of BRUE
History and physical examination
For low-risk infants: Observation with continuous pulse oximetry monitoring, electrocardiogram, pertussis testing
For high-risk infants: Additional testing guided by clinical scenario
BRUE is diagnosed only when there is no explanation for the event. A number of disorders can manifest with similar abnormalities of breathing, responsiveness, tone, and skin color, and the differential diagnosis and testing possibilities are broad. Any infant who does not meet low-risk criteria is, by definition, high-risk. Clinicians who are evaluating and managing infants with a high risk of BRUE should pursue an explanatory diagnosis.
Evaluation of infants with symptoms or signs precluding the diagnosis of BRUE is described elsewhere (see, for example, cough, fever, nausea and vomiting, seizures, and Approach to the Patient With a Suspected Inherited Disorder of Metabolism).
Infants diagnosed with infection, arrhythmia, seizures, or child abuse during their initial assessment do not have an unexplained event, and thus BRUE is not an appropriate diagnosis.
History
Evaluation of a BRUE event initially involves taking a thorough history, including:
Observations by the caregiver who witnessed the event, particularly a description of changes in breathing, color, muscle tone, and eyes; noises made; length of episode; and any preceding signs such as respiratory distress or hypotonia
Interventions performed (eg, gentle stimulation, mouth-to-mouth breathing, CPR)
Prenatal (maternal) or current caregiver use of medications, tobacco, alcohol, or illicit substances
Information about the infant’s birth (eg, gestational age, perinatal complications)
Feeding habits (whether gagging, coughing, vomiting, or poor weight gain has occurred)
Growth and development history (eg, length and weight percentiles, developmental milestones)
Prior events, including recent illness or trauma
Recent exposure to infectious diseases
Family history of similar events, early deaths, long QT syndrome or other arrhythmias, or possible causative disorders
Features in the history suggestive of child abuse should be carefully assessed. Recurrent events that are concerning for abuse include those for which the examination findings do not match the history and the event occurs only in the presence of the same caretaker while alone with the infant.
Because disposition depends in part on family capabilities and resources, it is also important for clinicians to assess the infant's housing and family situation, the level of caregiver anxiety, and whether the infant has ready access to follow-up medical care.
Physical examination
Physical examination is performed to check for abnormal vital signs, respiratory abnormalities, obvious malformations and deformities, neurologic abnormalities (eg, posturing, inappropriate head lag), signs of infection or trauma (particularly including retinal hemorrhage on funduscopy) and other indicators of possible physical abuse.
Testing
For low-risk infants, guidelines recommend minimal testing (1). If there are any findings or exceptions to low-risk criteria, the infant is considered high risk, and a thorough assessment is warranted.
For low-risk infants, it is reasonable to briefly monitor them with continuous pulse oximetry and observation for 1 to 4 hours (1). A 12-lead electrocardiogram and pertussis testing may be considered; however, additional testing, including imaging studies, echocardiography, electroencephalography, and blood tests are not recommended. Admission to the hospital solely for cardiorespiratory monitoring is discouraged.
Discharge planning for the low-risk infant should include education about BRUE and shared decision making with the parent or caregiver about further evaluation and follow-up. Caregiver CPR training should be encouraged.
For high-risk infants, laboratory and imaging tests are performed to evaluate for potential etiologies. Some tests are performed routinely, whereas others should be performed based on clinical suspicion of a specific etiology as suggested by specific characteristics of the episode (see table Evaluation of High-Risk Infants With BRUE). Infants are often hospitalized for cardiorespiratory monitoring, particularly if they required resuscitation or have any abnormalities.
The yield of diagnostic testing is relatively low, even in high-risk infants. In studies, a laboratory, imaging, or other test contributed to an explanatory diagnosis in approximately 3% of patients with a high-risk BRUE and in 7% of infants hospitalized with BRUE (2, 3).
Evaluation of High-Risk Infants With BRUE
Evaluation | Possible Etiologies |
|---|---|
Potential initial testing | |
Electrocardiogram | Inherited arrhythmia syndromes, other conduction abnormalities |
Pertussis testing | |
Cardiac and pulse oximetry monitoring in hospital | Arrhythmia, apnea/hypopnea, hypoxia |
Complete blood count and differential | Infection, anemia |
Cultures (blood, stool, urine, cerebrospinal fluid), urinalysis, lumbar puncture | Infection |
Nasal swab | Respiratory syncytial virus and other respiratory pathogens |
Electrolytes (magnesium, calcium, sodium, potassium), bicarbonate, and glucose | Dehydration, electrolyte derangement, acidosis, metabolic disorders |
Liver tests | Hepatobiliary disorders |
Toxicology screen | Medications, illicit drugs or other substances, or toxins |
Chest radiograph | Pneumonia, cardiomegaly |
Skeletal survey radiograph | |
Echocardiogram | Congenital heart disease, cardiomyopathy |
Additional tests based on clinical suspicion | |
Arterial blood gases, blood lactate, ammonia | Acidosis, metabolic disorders |
Genetic testing | Genetic/metabolic disorder |
Brain imaging (head CT, MRI) | Trauma, hemorrhage, tumor |
Electroencephalogram | |
Esophageal pH monitoring* | |
Upper gastrointestinal study with radioisotope milk scanning* | Gastroesophageal reflux disease |
Polysomnography or nocturnal oximetry | Sleep apnea/hypopnea (central or obstructive), nocturnal hypoxemia |
* In infants with a history of spitting up, gagging, vomiting, coughing, or difficulty feeding. | |
BRUE = brief, resolved, unexplained event. | |
Diagnosis references
1. Tieder JS, Bonkowsky JL, Etzel RA, et al. Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower-Risk Infants. Pediatrics. 2016;137(5):e20160590. doi:10.1542/peds.2016-0590
2. Bochner R, Tieder JS, Sullivan E, et al. Explanatory Diagnoses Following Hospitalization for a Brief Resolved Unexplained Event. Pediatrics. 2021;148(5):e2021052673. doi:10.1542/peds.2021-052673
3. Mittal MK, Tieder JS, Westphal K, et al. Diagnostic testing for evaluation of brief resolved unexplained events. Acad Emerg Med. 2023;30(6):662-670. doi:10.1111/acem.14666
Treatment of BRUE
Caregiver education
Close follow-up
Treatment of cause if identified
Low-risk infants
Parents and caregivers should be educated about BRUEs and offered training in infant CPR and in safe infant care. Home cardiorespiratory monitoring is not necessary.
Infants should be reevaluated within 24 hours.
High-risk infants
The cause, if identified, is treated.
Parents should receive training in infant CPR and in safe infant care. To date, no study has shown that home monitors provide information that can be used to intervene during events or to successfully prevent unexplained sudden death. Consideration of home monitor use should follow a specific diagnosis (1, 2).
Exposure to tobacco smoke must be eliminated.
Infants who were not hospitalized should receive follow-up care with their primary care physician within 24 hours.
Treatment references
1. Moon RY, Carlin RF, Hand I; TASK FORCE ON SUDDEN INFANT DEATH SYNDROME and THE COMMITTEE ON FETUS AND NEWBORN. Evidence Base for 2022 Updated Recommendations for a Safe Infant Sleeping Environment to Reduce the Risk of Sleep-Related Infant Deaths. Pediatrics. 2022;150(1):e2022057991. doi:10.1542/peds.2022-057991
2. Ramanathan R, Corwin MJ, Hunt CE, et al. Cardiorespiratory events recorded on home monitors: Comparison of healthy infants with those at increased risk for SIDS. JAMA. 2001;285(17):2199-2207. doi:10.1001/jama.285.17.2199
Prognosis for BRUE
Recurrence risk of BRUE is approximately 10%.
Among infants hospitalized after BRUE, 15% had additional emergency department visits or hospitalizations, 65% had subsequent choking spells, and 10% had subsequent BRUE (1).
In a large comparative study of ALTE, all deaths occurred in infants with underlying medical conditions (2).
Prognosis references
1. Duncan DR, Liu E, Growdon AS, Larson K, Rosen RL. A Prospective Study of Brief Resolved Unexplained Events: Risk Factors for Persistent Symptoms. Hosp Pediatr. 2022;12(12):1030-1043. doi:10.1542/hpeds.2022-006550
2. McGovern MC, Smith MB. Causes of apparent life threatening events in infants: A systematic review. Arch Dis Child. 2004;89(11):1043–1048. doi:10.1136/adc.2003.031740
Key Points
BRUE (brief, resolved, unexplained event) is defined as an episode of cyanosis or pallor, abnormal breathing, abnormal muscle tone, or altered responsiveness in an infant < 1 year old, with no identifiable cause, and based on the clinician’s characterization of the event and not on a caregiver’s perception that the event was life-threatening.
Infants who experience a BRUE can be classified as low-risk or high-risk based on history and physical examination.
Events in low-risk infants are unlikely to be due to a serious medical condition and require minimal assessment.
High-risk events have many possible causes, but often no etiology is found.
Respiratory, neurologic, infectious, cardiac, metabolic, and gastrointestinal disorders as well as abuse should be considered, with testing performed based on clinical findings.
Infants with abnormal examination findings or laboratory results, who required intervention, or who have worrisome history are hospitalized.
Treatment is directed at the cause; home monitoring has not been shown to decrease mortality.
Prognosis depends on cause.
