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ALTE and BRUE

(Brief, Resolved, Unexplained Event)

By Christopher P. Raab, MD, Associate Professor of Pediatrics;Attending Physician, Diagnostic Referral Division, Sidney Kimmel Medical College at Thomas Jefferson University;Nemours/Alfred I. duPont Hospital for Children

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ALTE (apparent life-threatening event) and BRUE (brief, resolved, unexplained event) are not specific disorders but terms for a group of alarming symptoms that can occur in infants. They involve the sudden appearance of respiratory symptoms (eg, apnea), change in color or muscle tone, and/or altered responsiveness. The caregiver may fear that the child is dead or that his or her life is in jeopardy. Events typically occur in children < 1 yr with peak incidence at 10 to 12 wk. Some of these events are unexplained (and designated BRUEs), but others result from numerous possible causes including digestive, neurologic, respiratory, infectious, cardiac, metabolic, or traumatic (eg, resulting from abuse) disorders. Treatment is aimed at specific causes when identified.

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, a recent clinical practice guideline from the American Academy of Pediatrics recommended 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 min in an infant < 1 yr 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 wasidentified; for these infants, some clinicians still consider the term ALTE useful.

Etiology

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

Less common causes include

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

Evaluation of infants with any other manifestations (eg, cough, fever, nausea and vomiting, seizures) besides those defined as BRUE is described elsewhere.

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 and development 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 or other arrhythmias, or possible causative disorders

Features in the history suggestive of child abuse 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.

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 wk and post-conceptual age > 45 wk

  • 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 new 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 h.

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), 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.

Diagnostic Tests for High-Risk Infants

Tests

Possible Causes

Typical initial testing

Blood tests, typically including

  • CBC and differential

  • Electrolytes (magnesium, calcium, sodium, potassium), bicarbonate, and glucose

  • Liver function tests

  • Lactate

Acidosis

Anemia

Dehydration

Infection

Liver disorders

Metabolic disorders

Chest x-ray

Cardiomegaly, pneumonia

Cultures (blood, stool, urine, CSF)

Infection

ECG

Cardiac monitoring in hospital

Arrhythmias

QT abnormalities

Echocardiography

Cardiomegaly

Lumbar puncture

Pertussis testing

Skeletal survey

Toxicology screen

Drugs or toxins

Urinalysis

Infection

Additional tests based on clinical suspicion

ABGs

Acidosis

Brain imaging (head CT, MRI)

Trauma, hemorrhage, tumor

EEG

Esophageal pH monitoring*

Genetic testing

Possible genetic/metabolic disorder

Nasal swab

Sleep study

Breathing or other problems during sleep

Upper GI with radioisotope milk scanning*

Gastroesophageal reflux disease

*In infants with a history of spitting up, gagging, vomiting, coughing, or difficulty feeding.

Prognosis

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). 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, 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

  • 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 h.

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 h.

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 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 GI 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 mo 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.

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