The case of the baby blues…BRUE diagnosis and management

A “BRUE” is defined as “Brief, Resolved, Unexplained Event” occurring in an infant less than 1 year of age involving one or more of the following (1):

• Central cyanosis or pallor
• Absent, decreased, or irregular breathing
• Hyper or hypotonia
• Altered level of responsiveness

BRUE is diagnosed when there is no other explanation for the event based on history and physical exam. Exclusion criteria for BRUE include (1):

• Duration ≥ 1 minute
• The presence of any of the following at the time of evaluation: recent fever, tachypnea, ongoing apnea or irregular breathing, vital sign abnormalities or hemodynamic instability, mental status change, continued significant changes in tone, vomiting, signs of trauma, a repeat event, or abnormal weight/growth pattern/head circumference
• Cyanosis described as peri-oral, acrocyanosis, or rubor
• Event more consistent with another explanation (gastroesophageal reflux, swallowing dysfunction, tonic-clonic seizures, infantile spasms, etc.)

Remember that while cyanosis, irregular breathing, altered mental status, or changes in tone define an event characterized as a BRUE, if any of these are still present during the time of evaluation, it is by definition NOT a brief, resolved, unexplained event. Other diagnoses should be sought. Also remember that in infants less than 60 days of age with a BRUE-like event, sepsis should be strongly considered.

The original term ALTE was developed in 1986 at an NIH Consensus Conference on Infantile Apnea, and stands for “Apparent, life-threatening event”. It was was defined as an episode that is frightening to the observer, characterized by a combination of apnea, color change, change in tone, and choking/gagging”. While ALTE was eventually and entirely separated from sudden infant death syndrome (SIDS), the definition was based on observed, subjective criteria, and could theoretically represent a broad range of disorders. One 2004 systematic review reported an incidence of 0.6 per 1000 live born infants and that ALTE accounted for 0.6-0.8% of all ED visits in children less than 1 year (2).

Given the diagnostic and management challenge that ALTE posed, new guidelines were published by the American Academy of Pediatrics in 2016 that replaced ALTE with the term BRUE. The “life threatening” portion is taken out of the term entirely, and the definition and diagnostic criteria for BRUE attempt to create a more specific, clear-cut term that reflects its transient nature and lack of clear cause (1).

Differences between the previous term ALTE and BRUE should be understood. There is a strict age limit for BRUE of 1 year. While the term ALTE referred to an observed event and could encompass a variety of explanations or underlying disorders, the term BRUE is by definition a diagnosis of exclusion. Next, the description of symptoms is more specific in BRUE. Color change must be either pallor or central cyanosis to qualify, as episodes of rubor may be common in healthy infants.

Apnea must specifically encompass irregular, absent, or decreased breathing. Instead of marked change in tone, hypertonia or hypotonia should be specified. Finally, while choking and gagging were part of the ALTE definition, it is not in the BRUE diagnostic criteria, and an alteration of responsiveness is included instead. While ALTE relied on the caregiver’s experience and observation, BRUE requires a physician to determine which of these diagnostic criteria are present based on a thorough evaluation.

Most events that can be characterized as a BRUE are idiopathic and unexplained. However, a thorough history and physical should be done to exclude other possible conditions and diagnoses. Some of these include nasal congestion, vomiting or choking that has resolved, viral infection, gastroesophageal reflux, seizure, pertussis, non-accidental trauma/child abuse, poisoning, serious bacterial infection especially in febrile patients, hypoglycemia, dysrhythmia, anemia, and metabolic disease.

There are evidence-based guidelines for the management of low-risk infants with BRUE. In order to be characterized as low-risk, infants must meet the following criteria (1):

• Age > 60 days
• Gestational age ≥ 32 weeks
• First BRUE occurrence and not occurring in clusters
• Duration of event < 1 minute
• No CPR required by a trained medical professional (determination of need for CPR should be made by the medical professional)
• No concerning findings in history or physical exam

Concerning findings in history include the presence of an inborn error of metabolism, developmental delay, environmental issues, tobacco/drug exposure, social concerns or concern for child abuse/trauma, recent exposure or presence of an infectious or respiratory illness, and family concerns or inability to care for infant.

Concerning findings in physical exam include abnormal growth findings, craniofacial abnormalities, abnormal vital signs, signs of abuse or trauma, abnormal skin color, abnormal pupillary response or retinal hemorrhages, abnormal tone or poor responsiveness, and any other abnormal findings. A thorough exam from “head to toe” should be conducted.

By definition, any infant with BRUE that do not not meet the above criteria are characterized as high-risk.

For a quick tool to help guide your risk stratification and management while you are in the ED, check out the BRUE Criteria Calculator by MD-Calc: MD-Calc BRUE Calculator. It helps you quickly assess whether your patient’s event qualifies as a BRUE and if your infant is low risk. If so, it lists all the key action statements for management and corresponding levels of evidence as stated by the AAP.

The guidelines put forth evidence-based recommendations for the management of low-risk patients with BRUE (1). These recommendations are based on a literature review of studies of ALTE patients prior to the terminology change and have been extrapolated for patients with BRUE. Admission is no longer recommended for cardiopulmonary monitoring in low-risk infants. The length of observation is debated. Since normal vital signs and appearance at one moment in time is not as accurate as over a period of time, guidelines suggest observation for 1-4 hours with continuous pulse oximetry. It may also be helpful to observe post-feeding for re-occurrence of the event. It is important to remember that infants may experience self-resolving hypoxemia especially during sleep. Further testing such as chest x-rays, neuroimaging, echocardiograms, EEG, blood testing, blood/urine cultures, and respiratory viral cultures are not recommended.

Tests that may be considered in addition to a brief period of observation include a screening ECG. Previous studies showed high negative predictive value of a screening ECG in ALTE patients (3). Pertussis can cause choking, gagging, respiratory issues or color change and can manifest as a BRUE-like event even prior to fever or onset of respiratory symptoms. Pertussis testing should only be considered with regard to potential exposures, immunization history of the infant and mother, and environment. Only babies with a high index of suspicion should undergo testing.

All children with BRUE should undergo a social risk assessment. Parents should be educated on BRUE and offered CPR training resources. In addition, as always, shared decision-making should be practiced.

Clinical judgement and shared decision-making should guide your management of children that do not fall into the low-risk category. Children who are pre-term, ill appearing or require resuscitation, or have multiple desaturations on pulse oximetry, respiratory disease or pertussis, or any concerning past medical or family history should prompt further testing as needed, a longer period of observation, and hospitalization if needed (4).

According to the guidelines you review, your patient can safely be characterized as low-risk. After a thorough history and physical exam, you decide to observe your patient with continuous pulse oximetry for 2 hours and defer additional testing. You feed the child and observe post-feed. You use shared decision-making with the parents and ensure they are comfortable with taking the child home.  The child continues to be well-appearing and you can ensure follow-up, so you discharge her with appropriate parent education and return precautions. Good job! Now onto the next fever and runny nose…