Some infants have transient events involving some combination of altered respiration, consciousness, muscle tone, and/or skin color that are alarming for caregivers—some of whom even begin doing cardiopulmonary resuscitation (CPR). Because of their concerning manifestations, these events have been referred to as an "apparent life-threatening event" (ALTE). However, although a small minority of these infants are found to have a significant underlying disorder, a large number have neither recurrences nor complications and go on to develop normally. Thus, the current clinical practice guidelines from the American Academy of Pediatrics recommends eliminating the term "life-threatening" so that parents are not unnecessarily alarmed and clinicians do not feel compelled to do extensive testing, which is unnecessary in many cases. The new term is "brief, resolved, unexplained event" (BRUE).
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 at the time of presentation. Thus, infants who are febrile, coughing, or showing any signs of distress or other abnormalities are not considered to have a possible BRUE.
It must be noted that 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. Also, BRUE does not apply to infants with a similar presentation in whom a cause was identified; for these infants, some clinicians still consider the term ALTE useful.
Etiology of ALTE and BRUE
Although by definition 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 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 Brain Tumors in Children Brain tumors are the most common solid cancer in children 15 years of age and are the 2nd leading cause of childhood death due to cancer. Diagnosis is typically by imaging (usually MRI) and... 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 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.
Evaluation of ALTE and 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 taken (eg, gentle stimulation, mouth-to-mouth breathing, CPR)
Prenatal (maternal) and current family use of drugs, tobacco, and alcohol
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 Development is often divided into specific domains, such as gross motor, fine motor, language, cognition, and social/emotional growth. These designations are useful, but substantial overlap... 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 Long QT Syndrome and Torsades de Pointes Ventricular Tachycardia Torsades de pointes is a specific form of polymorphic ventricular tachycardia in patients with a long QT interval. It is characterized by rapid, irregular QRS complexes, which appear to be twisting... read more or other arrhythmias, or possible causative disorders
Features in the history suggestive of child abuse Physical abuse Child maltreatment is behavior toward a child that is outside the norms of conduct and entails substantial risk of causing physical or emotional harm. Four types of maltreatment are generally... read more 
should be sensitively assessed. Recurrent events that are concerning for abuse include those that begin only in the presence of a parent or 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 is behavior toward a child that is outside the norms of conduct and entails substantial risk of causing physical or emotional harm. Four types of maltreatment are generally... 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 > 32 weeks and post-conceptual age > 45 weeks
One event only, no prior BRUE, 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 guidelines recommend few or no interventions other than caregiver education.
High-risk infants include all those who do not meet low-risk criteria. The new guidelines do not contain recommendations for their evaluation and management.
Testing
For low-risk infants, current 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 ( see Table: Diagnostic Tests for High-Risk Infants Diagnostic Tests for High-Risk Infants 
), 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.
Prognosis for ALTE and 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 Infant Death Syndrome (SIDS) Sudden infant death syndrome is the sudden and unexpected death of an infant or young child between 2 weeks and 1 year of age in which an examination of the death scene, thorough postmortem... read more ). Most victims of SIDS do not have any types of events beforehand.
Prognosis of a high-risk event 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 ALTE, unlike that of SIDS, has not decreased in response to the Safe to Sleep® campaign.
There seem to be no long-term effects on development from the ALTE itself, but the causative disorder (eg, cardiac or neurologic) may have such effects.
Treatment of ALTE and BRUE
Treatment of cause
Sometimes home monitoring devices
Close follow-up
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.
If parents and caregivers are interested and seem capable of using them, they may be prescribed apnea monitoring devices to use at home for a specified period of time. Monitors should be equipped with event recorders. Parents should be taught how to use the monitor and be advised that false alarms are common and that home monitoring has not been shown to reduce the mortality rate. Also, exposure to tobacco smoke must be eliminated.
Infants who were not hospitalized should receive follow-up with their primary care physician within 24 hours.
Key Points
Some infants have transient, alarming events involving alterations of respiration, consciousness, muscle tone, and/or skin color.
Events can be divided into low-risk and high-risk based on history and physical examination.
Events meeting low-risk criteria are unlikely to have a dangerous cause and require minimal assessment.
BRUE (brief, resolved, unexplained event) is present only when there is no explanation for the event after a thorough history and examination.
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.
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.
Children 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.
More Information
The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources
Safe to Sleep®: Information for parents and caregivers about safe sleep practices for infants from the U.S. Department of Health and Human Services
