Brief Resolved Unexplained Event

A brief resolved unexplained event (BRUE) is defined as a reported, sudden, brief (< 1 minute) event in a child < 1 year of age, which is resolved at the time of presentation. The definition includes ≥ 1 finding of either change in color (cyanosis or pallor), breathing pattern (absent, decreased, or irregular), muscle tone (hypertonia or hypotonia), or level of consciousness. The findings are based on a report given by a parent or caregiver. Adopted by the American Academy of Pediatrics in 2016, the new term was to replace the previously used terms “apparent life-threatening event” (ALTE) and “near sudden infant death syndrome”. The change in terminology was to better define an unexplained event after a thorough evaluation, stratify high- and low-risk groups, identify those needing further evaluation, and avoid unnecessary testing and admissions. Importantly, BRUE can be diagnosed only if there is no other explanation for the episode after a careful history and physical examination.

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Overview

Definition

A brief resolved unexplained event (BRUE) is defined as a sudden and unexplained change in an infant’s breathing, appearance, or behavior that was brief (< 1 minute, average 20–30 sec) and is fully resolved.

  • A thorough history and physical exam do not identify another cause to explain the event. 
  • Further criteria to meet the diagnosis include:
    • The child is < 1-year-old.
    • 1 or more of the following is described:
      • Cyanosis or pallor (but no redness or rubor, which can be normal)
      • Absent, decreased, or irregular breathing during the brief event
      • A marked change in tone (hyper- or hypotonia)
      • An altered level of responsiveness

Change in terminology

An “apparent life-threatening event” (ALTE) is no longer current but was defined as:

  • “An episode that is frightening to the observer and is characterized by some combination of apnea, color change, a marked change in muscle tone, and choking or gagging”
  • The term “life-threatening” was removed due to a lack of causal relationship between ALTE and SIDS:
    • The majority of SIDS deaths occur 12 AM-6 AM; the majority of ALTE episodes occur 8 AM-8 PM.
    • Peak incidence of SIDS is between 2–4 months of age; ALTE events are < 2 months of age.
    • “Back to sleep” initiatives for supine sleeping, which led to a dramatic decrease in the incidence of SIDS, have not changed the incidence of ALTE events.

BRUE specifies “there is no other explanation on a thorough history and physical examination” and it removes “choking or gagging.”

Epidemiology

  • Data is not yet fully known in part due to a change in the terms and definition.
  • Current estimates of occurrence: 0.5%–0.6% of healthy infants to term
  • 0.6%–0.8% of all emergency room visits for children under 1 year of age
  • May be reported more in infants with:
    • Feeding difficulties
    • Recent upper respiratory infection
    • < 2 months of age
    • History of prematurity
    • Low birth weight
    • Maternal tobacco use
    • Firstborn child

Etiology

By definition, there is no explanation or cause for BRUE, but common and important non-BRUE causes need to be identified.

Common conditions leading to an event and exclude BRUE:

  • Neonatal gastroesophageal reflux
  • Feeding or swallowing difficulty leading to laryngospasm or aspiration
  • Neurologic:
    • Brain tumor
    • Seizure
    • Breath-holding behavior
  • Conditions affecting brainstem respiratory regulation:
    • Hydrocephalus
    • Brain malformations
  • Respiratory infections:
    • Respiratory syncytial virus (RSV)
    • Influenza
    • Pertussis
  • Other infections:
    • Meningitis
    • Sepsis 

Less common conditions leading to an event and exclude BRUE:

  • Cardiac:
    • Critical cyanotic heart disease often screened for in the newborn nursery
    • Undiagnosed ductal-dependent lesion when patent ductus arteriosus (PDA) closes
    • Arrhythmia 
  • Metabolic disorders:
    • Diseases screened for via newborn metabolic screening (varies between states)
    • Can present with hypoglycemia, electrolyte disturbances, or toxic effect of metabolite build up
  • Upper airway obstruction:
    • Obstructive sleep apnea
    • Anatomic abnormalities of head or airways
  • Nonaccidental trauma (child abuse)
  • Other:
    • Toxins including unintentional ingestions and cold medications
    • Anaphylaxis

Pathophysiology

BRUE is “unexplained”, therefore the mechanism producing the event is unknown. Well-defined findings in infants, however, help to determine if an event has an underlying pathology.

Newborn checkup

Normal baby on examination:
Respiratory rate is 30–60/min; periodic breathing patterns noted in term and late-preterm babies. Skin is normally pink (indicating adequate oxygenation), both upper and lower extremities have a flexor tone, and the baby arouses on stimulation.

Image: “Newborn checkup” by Topato. License: CC BY 2.0

Breathing

Normal term infant breathing:

  • The respiratory rate is 30–60/min.
  • Healthy term and late-preterm (> 36 weeks) infants will sometimes exhibit “periodic breathing” patterns:
    • Brief pattern of rapid breathing and pauses (lasting 10–15 sec)
    • Not associated with color change or change in behavior
    • May show modest/brief desaturation and bradycardia if measured but requires no intervention
  • Educate parents on periodic breathing as a normal variant going away outside the newborn period.

Apnea (> 20 sec pause) can result from: 

  • Apnea of prematurity (resolves on its own)
  • Obstructive apnea with paradoxical movement of the diaphragm and upper airway due to:
    • Upper respiratory infection
    • Lower respiratory infection
    • Laryngospasm: often seen with reflux or vomiting
  • Central apnea

Tone

Normal infant tone:

  • Normal muscle tone: both upper and lower extremities are predominantly flexor tone (supine)
  • Compared to term infants, preterm infants exhibit decreased muscle tone.
  • Flexor tone decreases with decreased gestational age (preterm infants).

Hypotonia (decreased muscle tone): 

  • The infant is “frog-like” in the supine position.
  • The infant has abducted hips and abnormally extended lower limbs.
  • Reduced spontaneous activity

Hypertonia (increased muscle tone):

  • Spasticity: 
    • Muscles have abnormal shorten-lengthen reactions.
    • Clasp-knife resistance on passive muscle examination
  • Opisthotonus: continuous neck and trunk arching

Alertness/consciousness

Check for normal response to arousal maneuvers (tactile stimulation) and noxious stimuli (sternal rub).

Clinical Presentation

Reporting the event

  • At the time of presentation, a baby < 1 year of age will appear at a normal baseline with the parent/caregiver reporting the observed event.
  • The following details are needed to determine if the presentation is a BRUE and whether it is a low- or high-risk event:
    • Witness description of breathing, color, tone, appearance of the eyes, and/or sounds made
    • Duration 
    • Any preceding event/activity
    • Any intervention (e.g., CPR)
    • Age of gestation when the baby was born and current age (when the event occurred)

Distinguishing other events

Event and historical descriptions pointing to other explanations for the event:

  • Feeding issues:
    • Gastroesophageal reflux: common in infants, ranges from mild to severe
    • Overfeeding can increase the incidence of reflux.
    • Emesis or regurgitation suggests gastroesophageal reflux or laryngospasm.
  • Respiratory issues in the premature: Apnea of prematurity is typically found in infants < 37 weeks of age. 
  • Neurologic issues:
    • Seizure:
      • Often the baby will not be back to baseline.
      • Tonic-clonic movements or repeated spasms may be noted.
    • Brain tumor:
      • The baby may have developmental delays.
      • Poor feeding and vomiting may be observed.
    • Breath-holding behavior in some older infants: Often the event is observed when the infant is starting to cry.
    • Brainstem abnormalities or lesions causing central apnea: Cyanosis is noted during sleep.
  • Cardiac issues:
    • History of a murmur or known lesion
    • Poor feeding and growth
  • Infections:
    • Apnea may be more predominant than cough in RSV, pertussis, and influenza (especially if < 60 days of age).
    • Altered consciousness in sepsis, meningitis
  • Nonaccidental trauma (child abuse) findings:
    • Unexplained bruises or fractures
    • Subconjunctival or retinal hemorrhages
    • Torn frenulum in a young infant
    • Inconsistent history
    • Previous episodes
  • Toxins or medications at home:
    • An older, mobile infant may put a substance in their mouth while exploring.
    • Includes herbal or homeopathic medications and over-the-counter cold remedies
Image of a baby with pertussis

An infant with pertussis:
Presentation of the infection is atypical and can include eye-bulging, cyanosis, subcostal/intercostal retractions, gagging, and apnea.

Image: “6379” by CDC. License: Public Domain

Diagnosis

BRUE is diagnosed when there is no other explanation for the event. Therefore, a thorough history and physical is key.

History

  • Was the baby asleep, awake, or crying when the event occurred?
  • Were respirations absent, shallow, or increased?
  • Was the cyanosis or pallor affecting the entire body or localized?
  • Was the baby’s tone decreased (hypotonia), increased (hypertonia), or tonic-clonic (possible seizure)?
  • Were the baby’s eyes open? Did the eyes deviate?
  • Did the baby make choking sounds or exhibit stridor? Were objects nearby?
  • Did the baby spit-up or vomit? What was the relationship in time to a feeding?
  • Who witnessed the event? How long did it last? Were any interventions needed for the event to resolve?
  • Was there an intervention by a trained medical provider?
  • Also include:
    • Past medical history/birth history
    • Family history (including the unexpected death of a sibling)
    • Medications (including over-the-counter or herbal/homeopathic)
    • Known allergies
    • History of prior events

Physical exam

  • BRUE is ruled in with a normal exam of a term baby who is back to baseline.
  • Measurements of weight, height, and head circumference
  • Vital signs and pulse oximetry
  • Examination for signs of trauma
  • Anterior fontanel should be soft and flat
  • Normal alertness and tone for age
  • Evaluation of breathing and breath sounds
  • Cardiac auscultation with no murmur and normal pulses
  • Normal development for age without dysmorphic features

Management

Babies are stratified as low risk (little evaluation needed) or high risk (may need further evaluation, monitoring, and observation).

Low-risk BRUE

Criteria:

  • Asymptomatic
  • > 60 days old
  • If premature: born ≥ 32 weeks gestational age, now ≥ 45 weeks postconceptional age
  • No more than 1 BRUE 
  • BRUE lasted < 1 minute
  • The infant did not receive CPR from a trained medical provider.
  • No concerning history to suggest infection, child abuse, toxin, or a congenital/metabolic condition 
  • No family history of sudden and unexplained death of a sibling
  • No concerning findings on physical exam

Minimal management:

  • Briefly observe 1–4 hours on continuous pulse oximetry.
  • Follow-up with primary care provider within 24 hours.
  • Optional:
    • Serial checks
    • ECG to evaluate QT interval 
    • Viral test
    • Pertussis test
  • Further labs, imaging, and monitoring are NOT recommended.
  • Educate parents about BRUE: There is no association between BRUE and SIDS.
  • Offer resources for CPR.

High-risk BRUE

High-risk infants (do not meet low-risk criteria):

  • Pulse oximetry for at least 4 hours
  • Consider admission.
  • Tests may include the following to broaden evaluation for common or targeted conditions based on presentation and suspicion:
    • ECG
    • CBC
    • Electrolytes
    • Lactic acid (if considering possible metabolic condition)
    • Venous blood gas
    • Viral panel (RSV, pertussis, influenza)
    • Review newborn screen
    • Toxicology screen
    • EEG
    • MRI
    • Skeletal survey (if child abuse suspected)
    • Ophthalmology exam
  • Home monitoring:
    • Limited use
    • Not correlated to reduce SIDS
    • Determine on a case-by-case basis.

Clinical Relevance

  • Apnea of prematurity: an episode of apnea (and sometimes associated bradycardia) > 20 sec in infants < 37 weeks of age. Increased incidence occurs with the degree of prematurity and resolves by 43 weeks postconceptual age. Apnea of prematurity is due to respiratory control immaturity. 
  • Sudden infant death syndrome (SIDS): the sudden and unexpected death of an infant that is unexplained postmortem on autopsy. Peak occurrence is 1–4 months of age. Risk factors include maternal smoking, alcohol, and drug use, low socioeconomic status, boy gender, and prematurity. Sleep position was identified as a major risk factor. Since the implementation of supine sleeping (back to sleep), the rate has significantly and progressively declined. Co-sleeping is also associated with mortality. 
  • Neonatal gastroesophageal reflux: a common condition in newborns and younger infants. The range of neonatal gastroesophageal reflux may include mild spit-ups, severe vomiting, or silent reflux. Symptoms include fussiness with feeds, arching, coughing, or gagging. The mechanism of choking, gagging, and obstructive breath pattern is likely laryngospasm and not necessarily related to the severity of reflux. Management includes frequent burping, holding upright 15–20 minutes after feeding, and avoidance of overfeeding (usually bottle-fed babies). Sometimes nondairy milk, thickened feeds, or acid suppression therapy is indicated. Additional testing is usually not needed and the majority of babies will outgrow the condition.

References

  1. Alhaboob, Ali. “Clinical Characteristics and Outcomes of Patients Admitted with Brief Resolved Unexplained Events to a Tertiary Care Pediatric Intensive Care Unit”. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370642/#:~:text=According%20to%20a%20previous%20report,have%20experienced%20BRUE%20%5B5%5D
  2. Jilani, N., Hussain, A., et al. (2019). Gastro-oesophageal reflux is not a major cause of brief resolved unexplained events in infants. Breathe (Sheff) 15(2):e32-e39. doi: 10.1183/20734735.0174-2019.
  3. Kliegman, R., St. Geme, J. (2019). Nelson Textbook of Pediatrics. Ed. 21. Pages 2167–2179.
  4. Kondamudi, N., Virji, M. (2020). Brief resolved unexplained event. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK441897/
  5. Raab, Christopher MD.“ALTE and BRUE”. Merck Manuals Professional. Retrieved March 3, 2021, from https://www.merckmanuals.com/professional/pediatrics/miscellaneous-disorders-in-infants-and-children/alte-and-brue?query=brue.
  6. Tieder, Joel, et al. “Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower-Risk Infants”. Retrieved March 18, 2021, from https://pediatrics.aappublications.org/content/137/5/e20160590#sec-4

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