SIDS, BRUE, and Safe Sleep Guidelines

In 2016, the American Academy of Pediatrics (AAP) published a clinical practice guideline in which they recommended redefining apparent life-threatening event with the more specific term brief resolved unexplained event (BRUE). The purpose of this review is to detail how to apply the BRUE classification guidelines in practice. The recently updated AAP guidelines for sudden infant death syndrome prevention and safe infant sleeping environment are also discussed.After completing this article the reader should be able to:In April 2016, the American Academy of Pediatrics (AAP) published a new clinical practice guideline for brief resolved unexplained events (BRUEs). This new term, risk classification, and management recommendations replaced what was formerly known as an apparent life-threatening event (ALTE). BRUE describes transient events without a clear etiology after a thorough medical evaluation by a clinician, in contrast to ALTE, in which the definition refers to the subjective experience of a frightening event by a caregiver is detailed. In addition, the new guideline recommendations differentiate a BRUE from episodes that might warrant further investigation secondary to an increased risk of a serious underlying condition.The purpose of this review is to clarify the differences between these 2 definitions, as well as to distinguish them from sudden infant death syndrome (SIDS) and sudden unexpected infant death (SUID). Historically, ALTE was thought to be linked to SIDS; however, evidence reveals striking differences between these 2 conditions, which continues to reaffirm that they are not interconnected. Current known risk factors and preventive strategies for SIDS and SUID are also discussed.Also known as sudden unexpected death in infancy, SUID is an inclusive term used to characterize any sudden and unexpected death, whether explained or unexplained, occurring during the first year of life and does not have an obvious cause before further investigation. (1)SIDS is defined as a sudden, unexpected death before 12 months of age that occurs in a previously healthy infant, in which the cause of death remains unknown despite a thorough case investigation, including a complete autopsy, death scene investigation, and analysis of the clinical history. (1) SIDS is a subcategory of SUID and composes approximately half of these cases; other common causes of SUID events are strangulation and accidental suffocation. This is illustrated in Fig 1.ALTE is a term coined by the National Institutes of Health Consensus Development Conference on Infantile Apnea and Home Monitoring in 1986 and is defined as “an event that is frightening to the observer and that is characterized by some combination of apnea (central or occasionally obstructive), color change (usually cyanotic or pallid but occasionally erythematous or plethoric), marked change in muscle tone (usually limpness), and choking or gagging.” (2) This was created to discard the old definition that would categorize these episodes as “near missed SIDS,” enabling clinicians and researchers to separate ALTE from SIDS as 2 different entities. However, due to its broad description, ALTE introduced ambiguity as well as difficulties in application to patient care and further research. One of the challenges is basing the definition on a subjective description by an inexperienced or medically naive caregiver, who is often distraught and unable to recall the event accurately. Although concerning to the caregiver, these episodes are not often life threatening, and frequently may be either a self-limited condition or a benign phenomenon of normal infancy (eg, periodic breathing). The ALTE concept is also very broad and imprecise and includes an extensive differential diagnosis. In a minority of patients, the event may be an undiagnosed severe disease process that may result in significant illness and mortality. This small possibility can drive clinicians to do extensive, unnecessary evaluation in all infants presenting with ALTE, as well as recommend admission to the hospital for monitoring. This, in turn with inpatient evaluation, can result in escalated parental anxiety and increased risks for the infant inherent to a hospitalization, which will frequently not lead to a final diagnosis or a management plan to help prevent recurrent events. (1)A BRUE is defined as “an event occurring in infants younger than 12 months of age that is described by the observer as brief (lasting less than 1 minute, but typically <20-30 seconds), resolved (meaning the patient returned to baseline state of health after the event), and with a reassuring history, physical examination, and vital signs at the time of clinical evaluation by trained medical providers.” During a BRUE, “the observer reports ≥1 of the following: cyanosis or pallor; absent, decreased or irregular breathing; marked change in tone (hypertonia or hypotonia) and altered level of responsiveness.” (3) The authors reinforce the idea that to diagnose a BRUE there cannot be any other explanation for the event. For example, events in which the history and physical examination findings are compatible with a choking episode, seizures, or gastroesophageal reflux are by definition not considered BRUEs. Differences between BRUEs and ALTEs are further depicted in Table 1.In the United States, approximately 2,300 infants die of SIDS each year. Although its incidence has declined since the 1994 “Back to Sleep” campaign, SIDS continues to be the second leading cause of postneonatal death and the fourth most common cause of death in infancy. (6) In the past 20 years, there have been increases in other causes of SUIDs. This is thought to be primarily due to advances and augmented training in death scene investigation, and as a result, deaths once classified as SIDS are now often more accurately diagnosed (eg, child abuse and sleep-related asphyxia). Consequently, the percentage of SUID events due to accidental/mechanical suffocation and strangulation in bed has increased significantly over time, from 2.1% in the neonatal population and 3.4% in the postneonatal population in 1999 to 22.7% and 24.9%, respectively, in 2014. (7)Accurate ALTE epidemiology is difficult to obtain based on the imprecise nature of the definition, the lack of an International Classification of Diseases code for ALTE until 2012, and the possibility of an ALTE eventually having an etiologic explanation. In the latter case, the diagnosis of ALTE might then be substituted with a separate final diagnosis. The estimated incidence varies between 0.6 and 5.0 per 1,000 live births and accounts for 0.6% to 1.7% of all emergency hospital visits in patients younger than 1 year. (8)A recent meta-analysis was published regarding the risk of death in patients with BRUE. Owing to the lack of studies using this terminology, most of the studies included were related to ALTE. The mortality estimate was 1.8 postevent deaths per 10,000 patient-months of follow-up, which can be translated into a risk of death of approximately 1 in 800. For comparison, the overall risk of death of an infant in the general population over a similar period is estimated to be 1 in 500. Because this is extracted from the ALTE population, without distinction of a lower or higher risk of BRUE, it can be presumed that the mortality risk for patients with lower risk of BRUE is probably even less. (9)To date, there are no reports of the incidence of BRUE because this terminology has been recently introduced, but further study of this condition might improve our understanding of this phenomenon.There is no evidence that having an ALTE is a predisposing factor for SIDS. The 2 entities have some distinct epidemiologic differences, as outlined in Table 2. There are more differences than similarities between the 2 conditions. (11) The only risk factor that has been shown to influence both entities is maternal smoking, which is known to be implicated in many other health conditions, yet there is not enough evidence to link maternal smoking to the etiology of ALTE and SIDS. Research into the relationship between ALTE and SIDS has determined that only 4% to 13% of patients with SIDS had a history of apnea, a number only mildly increased compared with controls. (4)As detailed previously, BRUE describes a witnessed episode occurring in a child younger than 1 year, lasting less than 1 minute, after which the patient returns to his or her baseline health status, including normal appearance and vital signs. In addition, qualifying BRUE criteria must be met, including a distinct color change of cyanosis or pallor, an abnormal or absent breathing period, a change in muscle tone, and/or a change in alertness of the patient. The episode must have at least 1 of these event criteria present. If, after a thorough history and examination, the event cannot be explained by a specific medical diagnosis, it then meets the BRUE diagnosis. (3) If a diagnosis is made after this evaluation, such as suspected reflux, seizure, or feeding difficulties, the event is not categorized as a BRUE, and should be subsequently managed according to the presumed diagnosis. Figure 2 shows the BRUE algorithm. The most common diagnoses that have been associated with ALTE, and that should be ruled out before making a BRUE diagnosis, include gastroesophageal reflux in 20% to 54% of patients, respiratory tract infections in close to 8%, seizures in approximately 4% to 7%, serious bacterial infections have in 2% to 8% of infants, and implicated child abuse in 1% to 11%. (12)The subject of child abuse as an underlying cause of an ALTE episode has been the topic of further research due to the difficulty in making the diagnosis and the risk of death associated with missing nonaccidental trauma. One study in particular reported mortality of 33% of all abused children who presented with an ALTE; in contrast, overall mortality with ALTE is reported to be approximately 1.3%. (13) These data should drive clinicians to maintain a high index of suspicion for nonaccidental trauma when evaluating infants. Examples of findings that should trigger further investigation into nonaccidental trauma include a developmentally inconsistent history, a witness who changes the event history, delays in seeking medical care for the patient, patient history of recurrent ALTEs/BRUEs, a family history of ALTE/BRUE, and previous calls to emergency medical services. On physical examination, signs such as bruising, oropharynx or frenulum damage, retinal hemorrhages, and subconjunctival hemorrhages should raise concern for child abuse. A recent study introduced the possibility of screening patients with ALTEs for abuse with dilated fundoscopic examination. In this study, 1 of 73 infants (1.4%) exhibited retinal hemorrhages. (11) It is important to mention that this patient was otherwise asymptomatic on presentation and was later found to have several fractures. (13) Although retinal hemorrhages may be helpful in identifying patients who have experienced abusive head trauma, it may not aid in the diagnosis of a factitious illness or imposed suffocation. In these instances, the recurrence of events is what will usually guide the clinician to suspect these diagnoses. Studies have reported that the occurrence of child abuse in recurrent ALTEs has varied between 10.6% and 16.7%. (11)Once a BRUE diagnosis is made, the clinician needs to determine whether the infant qualifies in either the lower-risk or higher-risk classification group (Fig 3). This risk category should guide the decisions for appropriate evaluation and management based on specific concerns elicited. Previous studies in patients with ALTEs have shown that extensive, wide-ranging laboratory or radiologic tests that are not guided by clinical suspicion are of low yield, and the probability of a contributory result is very unlikely. The BRUE guidelines, as well as previous ALTE recommendations, state that the most important diagnostic investigation is to perform a thorough history and physical examination. A detailed description of the episode should be obtained from any caretaker or medical professional witness. A comprehensive interview includes obtaining a history of preceding illness and an extensive medical, family, social, and environmental history, as well as always screening for child abuse. The clinician should document the state of the patient before, during, at the conclusion of, and after the event. (3) A thorough initial evaluation may increase the index of suspicion for a specific diagnosis and, therefore, exclude a patient from the BRUE risk classification. These diagnoses include, but are not limited to, vital sign instability; growth curve abnormalities; altered infant alertness and responsiveness to the environment, craniofacial anomalies, nasal congestion; abnormal auscultation findings; palpation of masses; tenderness or organomegaly; genital abnormalities; gross motor movement, reflex, and tone irregularities; and any signs of trauma, bruising, injury, or pain. (3) If any findings lead to concern, the event does not qualify as a lower-risk BRUE but rather as a higher-risk BRUE. A list of possible differential diagnoses to consider by systems in lower- and higher-risk BRUE are detailed in Table 3.A lower-risk BRUE is an event that after a thorough history and comprehensive examination yields no concerning findings in a patient who is older than 60 days and was born at 32 to 45 weeks' gestational age. The event must also be the first episode of its kind, must not have required cardiopulmonary resuscitation (CPR) by a medical professional, and have lasted for less than 1 minute (Fig 3). All of these parameters must be met to be considered a lower-risk BRUE. Patients who qualify for the lower-risk category are less likely to have an undiagnosed life-threatening condition or a recurrence of an episode. As such they have a decreased risk of adverse outcomes and do not warrant hospitalization or a broad clinical evaluation. (3) This category assumes that clinicians have screened for social risk factors, and in particular for child abuse. The new guidelines offer recommendations for this specific population of patients based on current available evidence.All families of lower-risk patients should participate in shared medical decision making to guide evaluation and ensure follow-up. This entails the clinician, after taking a careful history and conducting a thorough physical examination, discussing his or her findings with caregivers and educating them about a lower-risk BRUE. There are handouts available for parents and caregivers at the AAP Pediatric Patient Education website. (14) Appropriate and timely follow-up with a clinician should be established for a safe transition of care, ideally before discharge. Families should also be offered CPR training resources.The guidelines state that lower-risk patients do not need admission for observation solely for cardiorespiratory monitoring. This is probably the most considerable change from previous ALTE guidelines. The authors suggest that infants with a lower-risk BRUE may be briefly monitored with continuous pulse oximetry and serial observations that can be performed in an outpatient setting from 1 to 4 hours. Furthermore, based on available evidence, it is optional to obtain a 12-lead electrocardiogram (ECG) on lower-risk patients. This recommendation is based on ALTE studies that looked at the of screening The review authors found that there was a high of screening for disease in ALTE These with the of and the outcomes of or to the of in the lower-risk BRUE (3) recommendation is to consider for because it can cause events such as apnea, irregular breathing and cyanosis or in infants who may not yet signs of a respiratory However, it is that clinicians consider infant and maternal of this history, and of timely Because a of would change should be considered in the appropriate patient also recommend obtaining a complete with a differential and analysis or complete respiratory by or and and It is also that these patients do not need hospitalization for vital or reflux or any for seizures or Patients should not be from the hospital with an apnea The AAP also that and for life for all CPR training does not increase parental anxiety and, on the can result in caregivers by them with the of they may during emergency once the child is higher-risk patient is who was diagnosed as having a BRUE but does not all of the lower-risk If an event meets any of the it is considered a higher-risk BRUE. This includes patients after a thorough history and examination, it is determined that there is a concerning that should be further but the does not lead to an diagnosis. If the child is younger than 60 days or was born at less than 32 and has a gestational age of less than 45 the patient in the higher-risk If the event occurs more than or for more than 1 minute, or CPR was performed by a trained the child is also considered higher this time, data are available to help guide clinicians in the management of this and hospital admission are not for all patients in this case should be managed and a clinical process based on the suspicion until further guidelines are The management and evaluation of a higher-risk BRUE should be based on patient history and clinical findings and should be performed in the of shared decision making with the In when presented with a higher-risk patient, it is helpful to differential diagnoses that would the event more accurately. 2016, the AAP updated recommendations for SIDS and sleep-related infant such as and As previously when the “Back to Sleep” was in the there was a of approximately in infant sleep-related but since then the mortality has about the It is important to that safe recommendations have not shown a in ALTE which further evidence that ALTE and SIDS have no The updated guidelines are for the general population and children to 1 year of age. 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(1) to be that these have not been to prevent SIDS and may lead to and that lead to unnecessary and increased caregiver Furthermore, when an infant is is recommended to help with the of motor and of but should otherwise not be used for is a of evidence to suggest that SIDS (1) studies that mortality may increase the or is into a other than there should be research into the etiology of the of training for all on risk and of as well as for These by many will help to the of all SIDS events. the that this the at authors would to for his and into the topic of BRUE as well as his and which the