BRUE (brief, resolved, unexplained event) is not a specific disorder, it is a term to describe a sudden, brief, and now resolved episode of the appearance of altered hemodynamic status and responsiveness in an infant.
In the 2016 American Academy of Pediatrics guidelines, BRUE replaced the term ALTE (apparent life-threatening event), which was thought to be overly broad and alarming to caregivers (1 References BRUE (brief, resolved, unexplained event) is an episode of cyanosis or pallor, abnormal breathing, abnormal muscle tone, or altered responsiveness in infants. A previous term for similar events... read more ) and may have resulted in unnecessary medical testing. BRUE is defined slightly differently than previous terms; the diagnosis requires the child to be < 1 year old; the event to have no other likely explanation; and the diagnosis to be based on the clinician’s characterization of features of the event and not on a caregiver’s perception that the event was life-threatening.
Some infants have a transient event involving some combination of altered respiration, consciousness, muscle tone, and/or skin color. This is alarming for caregivers—some of whom may fear that they are observing a life-threatening event and may even begin doing cardiopulmonary resuscitation (CPR). Although a small minority of these infants are found to have a significant underlying disorder, among infants who appear well after this type of episode, a large number do not have recurrences or complications and go on to develop normally (2 References BRUE (brief, resolved, unexplained event) is an episode of cyanosis or pallor, abnormal breathing, abnormal muscle tone, or altered responsiveness in infants. A previous term for similar events... read more ).
BRUE refers to events lasting < 1 minute in an infant < 1 year of age that are associated with ≥ 1 of the following:
Absent, decreased, or irregular breathing
Cyanosis or pallor
Altered level of responsiveness
Marked change in muscle tone (hypertonia or hypotonia)
In addition, infants must otherwise appear well and be back at their baseline state of health after the event. Thus, infants who are febrile, coughing, or showing any signs of distress or other abnormalities are not considered to have had a BRUE.
The term BRUE applies only to events for which there is no underlying cause (hence "unexplained"), which can be determined only after a thorough history and physical examination and sometimes testing and a period of observation. For infants with a similar presentation in whom a cause was identified, clinicians should identify a diagnosis for the episode based on the underlying cause.
Differential diagnosis
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/or skin color. Thus, it is important to search for a cause.
The most common possible causes include
Digestive: Gastroesophageal reflux disease Gastroesophageal Reflux Disease (GERD) Incompetence of the lower esophageal sphincter allows reflux of gastric contents into the esophagus, causing burning pain. Prolonged reflux may lead to esophagitis, stricture, and rarely metaplasia... read more
or swallowing difficulty Dysphagia Dysphagia is difficulty swallowing. The condition results from impeded transport of liquids, solids, or both from the pharynx to the stomach. Dysphagia should not be confused with globus sensation... read more when associated with laryngospasm or aspirationNeurologic: Neurologic disorders (eg, seizures Seizure Disorders A seizure is an abnormal, unregulated electrical discharge that occurs within the brain’s cortical gray matter and transiently interrupts normal brain function. A seizure typically causes altered... read more , brain tumors Overview of Central Nervous System Tumors in Children Central nervous system tumors are the most common solid cancer in children < 15 years old and are the leading cause of childhood death due to cancer. Diagnosis is typically by imaging (usually... read more , breath holding Breath-Holding Spells A breath-holding spell is an episode in which the child stops breathing involuntarily and loses consciousness for a short period immediately after a frightening or emotionally upsetting event... read more or abnormal brain stem neuroregulation of cardiorespiratory control, hydrocephalus Hydrocephalus Hydrocephalus is accumulation of excessive amounts of CSF, causing cerebral ventricular enlargement and/or increased intracranial pressure. Manifestations can include enlarged head, bulging... read more
, brain malformations Malformed Cerebral Hemispheres Cerebral hemispheres may be large, small, or asymmetric; the gyri may be absent, unusually large, or multiple and small. In addition to the grossly visible malformations, microscopic sections... read more 
)Respiratory: Infections (eg, respiratory syncytial virus Respiratory Syncytial Virus (RSV) and Human Metapneumovirus Infections Respiratory syncytial virus and human metapneumovirus infections cause seasonal lower respiratory tract disease, particularly in infants and young children. Disease may be asymptomatic, mild... read more , influenza Influenza Influenza is a viral respiratory infection causing fever, coryza, cough, headache, and malaise. Mortality is possible during seasonal epidemics, particularly among high-risk patients (eg, those... read more , pertussis Pertussis Pertussis is a highly communicable disease occurring mostly in children and adolescents and caused by the gram-negative bacterium Bordetella pertussis. Symptoms are initially those of... read more )
Infectious: Sepsis Sepsis and Septic Shock Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection. In septic shock, there is critical reduction in tissue perfusion; acute failure... read more , meningitis Acute Bacterial Meningitis Acute bacterial meningitis is rapidly progressive bacterial infection of the meninges and subarachnoid space. Findings typically include headache, fever, and nuchal rigidity. Diagnosis is by... read more
Less common possible causes include
Cardiac disorders
Metabolic disorders
Causes 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.
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 137(5):e20160590, 2016. doi: 10.1542/peds.2016-0590. Clarification and additional information. Pediatrics 138(2):e20161487, 2016.
2. McGovern MC, Smith MB: Causes of apparent life threatening events in infants: A systematic review. Arch Dis Child 89(11):1043–1048, 2004. doi: 10.1136/adc.2003.031740
Evaluation of BRUE
Evaluation of infants with any other manifestations besides those defined as BRUE is described elsewhere (see, for example, cough Cough in Children Cough is a reflex that helps clear the airways of secretions, protects the airway from foreign body aspiration, and can be the manifesting symptom of a disease. Cough is one of the most common... read more , fever Fever in Infants and Children Normal body temperature varies from person to person and throughout the day. Normal body temperature is highest in children who are preschool aged. Several studies have documented that peak... read more , nausea and vomiting Nausea and Vomiting in Infants and Children Nausea is the sensation of impending emesis and is frequently accompanied by autonomic changes, such as increased heart rate and salivation. Nausea and vomiting typically occur in sequence;... read more , seizures Neonatal Seizure Disorders Neonatal seizures are abnormal electrical discharges in the central nervous system of neonates and usually manifest as stereotyped muscular activity or autonomic changes. Diagnosis is confirmed... read more , and Approach to the Patient With a Suspected Inherited Disorder of Metabolism Approach to the Patient With a Suspected Inherited Disorder of Metabolism Most inherited disorders of metabolism (inborn errors of metabolism) are rare, and therefore their diagnosis requires a high index of suspicion. Timely diagnosis leads to early treatment and... read more ).
History
Evaluation of an event initially involves 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 Physical Growth of Infants and Children Physical growth includes attainment of full height and appropriate weight and an increase in size of all organs (except lymphatic tissue, which decreases in size). Growth from birth to adolescence... read more and development Childhood Development Descriptions of development are often divided into specific domains, such as gross motor, fine motor, language, cognition, and social/emotional growth. These designations are useful, but substantial... read more history (eg, length and weight percentiles, developmental milestones)
Prior events, including recent illness or trauma
Recent exposure to infectious illness
Family history of similar events, early deaths, long QT syndrome Torsades de Pointes Ventricular Tachycardia Torsades de pointes ventricular tachycardia is a specific form of polymorphic ventricular tachycardia in patients with a long QT interval. It is characterized by rapid, irregular QRS complexes... read more or other arrhythmias, or possible causative disorders
Features in the history suggestive of child abuse Physical abuse Child maltreatment includes all types of abuse and neglect of a child under the age of 18 by a parent, caregiver, or another person in a custodial role (eg, clergy, coach, teacher) that results... read more 
should be sensitively assessed. Recurrent events that are concerning for abuse include those where the examination findings do not match the history and the event occurs only in the presence of a caretaker.
Because disposition depends in part on family capabilities and resources, it is also important to assess the 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 done to check for abnormal vital signs, respiratory signs, obvious malformations and deformities, neurologic abnormalities (eg, posturing, inappropriate head lag), signs of infection or trauma (particularly including retinal hemorrhage on funduscopy), and indicators of possible physical abuse Physical abuse Child maltreatment includes all types of abuse and neglect of a child under the age of 18 by a parent, caregiver, or another person in a custodial role (eg, clergy, coach, teacher) that results... read more .
Risk classification
Possible BRUEs are classified as low or high risk based on history and physical examination.
Low-risk infants are those who meet the following criteria:
Age > 60 days
Gestational age at birth ≥ 32 weeks and post-conceptual age ≥ 45 weeks
One event only, no prior BRUE and no cluster of BRUEs
No CPR required by trained medical provider
No features of concern in history (eg, concern for child abuse, family history of sudden death)
Normal physical examination (eg, afebrile, normotensive)
Low-risk infants are very unlikely to have a serious underlying disorder, and the 2016 guidelines recommend few or no interventions other than caregiver education.
High-risk infants include all those who do not meet low-risk criteria. The current guidelines do not contain recommendations for their evaluation and management, so evaluation and management should be based on the history and findings in the infant.
Testing
For low-risk infants, guidelines recommend minimal testing. It is reasonable to observe the infant (including monitoring pulse oximetry) in the emergency department or office for a brief period and do 12-lead ECG and testing nasopharyngeal swab for pertussis (culture or PCR). Other tests, including imaging studies and blood tests, are not necessary. Routine hospital admission also is not necessary; however, infants may be hospitalized for cardiorespiratory monitoring if caregivers are extremely anxious or are unable to bring the infant for follow-up in 24 hours.
For high-risk infants, laboratory and imaging tests are done to check for possible causes. Some tests are done routinely and others should be done based on clinical suspicion of a specific etiology of the episode (see table ), including whether the infant is still symptomatic or has required medical intervention. Infants are often hospitalized for cardiorespiratory monitoring, particularly if they required resuscitation or if evaluation detected any abnormalities.
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 CPR for infants 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.
Guidelines regarding the use of home monitors state that home cardiorespiratory monitors should not be used as a strategy to reduce the risk of SIDS; their use has not been documented to decrease the incidence of SIDS (1 Treatment reference BRUE (brief, resolved, unexplained event) is an episode of cyanosis or pallor, abnormal breathing, abnormal muscle tone, or altered responsiveness in infants. A previous term for similar events... read more ). Some parents or caregivers are insistent about using a home cardiorespiratory monitor, and use of these monitors may give them peace of mind. However, there is a concern that use of monitors may make parents or caregivers complacent about following safe sleep guidelines Prevention Sudden unexpected infant death (SUID) is a term used to describe any unexpected and sudden death in a child less than 1 year of age, which often occurs during sleep or in the infant's sleep... read more . Parents or caregivers who choose to use a home monitor should be counseled that this is not a substitute for following recommended safe sleep measures. Parents should also receive CPR training.
Exposure to tobacco smoke must be eliminated.
Infants who were not hospitalized should receive follow-up with their primary care physician within 24 hours.
Treatment reference
1. Moon RY, Carlin RF, Hand I, Task Force on Sudden Infant Death Syndrome: Evidence base for 2022 updated recommendations for a safe infant sleeping environment to reduce the risk of sleep-related infant deaths. Pediatrics 150(1):e2022057991, 2022. doi: 10.1542/peds.2022-057991
Prognosis for BRUE
Most often, BRUE is harmless and not a sign of more serious health problems or death. BRUE is unlikely to be a risk factor for sudden infant death syndrome (SIDS Sudden Unexpected Infant Death (SUID) and Sudden Infant Death Syndrome (SIDS) Sudden unexpected infant death (SUID) is a term used to describe any unexpected and sudden death in a child less than 1 year of age, which often occurs during sleep or in the infant's sleep... read more ) (1 Prognosis reference BRUE (brief, resolved, unexplained event) is an episode of cyanosis or pallor, abnormal breathing, abnormal muscle tone, or altered responsiveness in infants. A previous term for similar events... read more ). Most victims of SIDS do not have any types of events beforehand.
Prognosis for an event in a high-risk infant depends on the cause. For example, risk of death is higher if the cause is a serious neurologic disorder. When no cause is identified after evaluation and observation, the relationship of such events to SIDS is unclear. About 4 to 10% of infants who die of SIDS have a history of such events, and the risk of SIDS is higher if an infant has had 2 or more. Also, infants who have had an event share many of the same characteristics with infants who die of SIDS. However, incidence of BRUE, unlike that of SIDS, has not decreased in response to the Safe to Sleep® campaign.
Prognosis reference
1. McGovern MC, Smith MB: Causes of apparent life threatening events in infants: A systematic review. Arch Dis Child 89(11):1043–1048, 2004. 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 done based on clinical findings.
Infants with abnormal examination findings or laboratory results or who required intervention or had a worrisome history are hospitalized.
Treatment is directed at the cause; home monitoring may be done but has not been shown to decrease mortality.
Prognosis depends on cause; risk of death is increased in children with a neurologic disorder, who have had 2 or more events, who have experienced nonaccidental trauma, or who are > 6 months and have had an event of longer duration, especially if they have heart disease.
More Information
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
American Academy of Pediatrics: Guidelines for brief resolved unexplained events (formerly apparent life-threatening events) and evaluation of lower-risk infants (2016)
Safe to Sleep®: Information for parents and caregivers about safe sleep practices for infants from the U.S. Department of Health and Human Services
