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CHAPTER 117: Brief Resolved Unexplained Events and Apparent Life-Threatening Events 739 life. Although cessation of breastfeeding will result in a rapid decline of bilirubin over 2 to 3 days, it is not routinely recommended. Breast milk jaundice is unlikely to cause kernicterus and usually can be treated with phototherapy, when necessary. This should be distinguished from breastfeeding jaundice, or starvation jaundice , which can occur when a newborn is exclusively breastfed and the mother’s milk supply is still inadequate. Poor oral intake resulting in reduced bowel movement and bilirubin excretion through the GI tract, coupled with relative dehydration, may accentuate physiologic jaundice. Optimizing the neonate’s feeding pattern with controlled supplementation, whether with expressed breast milk, donated breast milk, or formula, usually resolves the problem, but severe hyperbilirubinemia may require treatment. The treatment of hyperbilirubinemia depends on the cause, but for most cases of unconjugated hyperbilirubinemia, phototherapy is suf ficient. Phototherapy causes a configurational change in the bilirubin structure that allows it to be excreted in the urine. There is no additional benefit to IV fluids coupled with phototherapy, so enteral feeding should always be encouraged, although the dehydrated infant may require fluid resuscitation. Extreme levels of hyperbilirubinemia are treated emer gently with exchange transfusion and require admission to hospital. Risk factors include hemolysis risks (e.g., isoimmune hemolytic dis ease, glucose-6-phosphate dehydrogenase deficiency, ABO incompat ibility), sepsis (lethargy, temperature instability, irritability), asphyxia, hypoalbuminemia, and acidosis. In the first 24 hours of life, response to phototherapy is less predictable, and specific exchange transfusion indications are less certain during this period.  EYE COMPLAINTS Watery Eyes Clear eye discharge, and occasionally crusting over of the eyelashes without associated conjunctival redness or irritation, is commonly seen in neonates and infants and results from narrow or obstructed nasolacrimal ducts. This condition usually resolves sponta neously and requires antibiotics only when complicated by conjunctival erythema and inflammation (conjunctivitis or dacryocystitis). Ophthalmologic consultation for nasolacrimal duct probing is appropriate if this problem persists past 12 months of age or earlier if complicated by recurrent infection. Red Eye and Irritation Corneal irritation or abrasion can result from an eyelash or scratch from a fingernail. Perform fluorescein staining and evaluate with a Wood’s lamp or a hand-held slit lamp to identify corneal abrasions. Acute glaucoma, although rare, also presents as a red, teary eye. The cornea is cloudy, the anterior chamber is shallow, and the intraocular pressure may be increased. Promptly consult pediatric ophthalmology for all suspected cases of glaucoma. Red Eye and Discharge Conjunctivitis is described in detail in Chapter 122, “Eye Emergencies in Infants and Children. ” The most common causes of neonatal conjunctivitis are chemical irritation, bacterial or chlamydial infection, and herpes simplex infection. Chemical conjunctivitis due to ocular prophylaxis usually occurs on the first day of life and requires no treatment. Gonococcal conjunctivitis generally has its peak time of onset between 3 and 5 days after birth.

l conjunctivitis are chemical irritation, bacterial or chlamydial infection, and herpes simplex infection. Chemical conjunctivitis due to ocular prophylaxis usually occurs on the first day of life and requires no treatment. Gonococcal conjunctivitis generally has its peak time of onset between 3 and 5 days after birth. Despite antibiotic prophylaxis at delivery, the failure rate of prophylaxis is about 1%. Neisseria gonorrhoeae invades superficial layers of the conjunctiva and, if untreated, causes corneal ulceration and can result in permanent loss of vision. For diagnosis, obtain a Gram stain and culture for N. gonorrhoeae. Treat gonococcal conjunctivitis with cefotaxime (50 milligrams/kg IV or IM). Cefotaxime is recommended for neonates, as ceftriaxone can displace bound bilirubin and precipitate kernicterus. Perform septic workup includ ing lumbar puncture. Disseminated disease should be suspected until cerebrospinal fluid cultures are negative. Supportive care includes ocular irrigation with normal saline as soon as diagnosis is suspected, with frequent irrigation until the discharge is eliminated. Admit the neonate and obtain ophthalmology consultation. Topical antibiotic treatment alone is inadequate and unnecessary when systemic antibiotic treatment is given. Chlamydial conjunctivitis becomes evident by the end of the first week throughout the first month after birth. The disorder varies in severity, from mild to severe hyperemia with a thick, profuse mucopu rulent discharge and pseudomembrane formation. There often is severe edema of both lids. Because isolation of Chlamydia trachomatis requires specialized tissue cultures, ensure proper technique in collecting culture specimens (e.g., Dacron swabs) and specimens for antigen detection. Treat chlamydial conjunctivitis and pneumonia in neonates with oral erythromycin (50 milligrams/kg PO per day in four divided doses, for 14 days). Oral sulfonamides may be used after the immediate neonatal period for infants who do not tolerate erythromycin. Topical treatment is unnecessary. Because the efficacy of erythromycin therapy is approximately 80%, a second course is sometimes required. A specific diagnosis of C. trachomatis infection in an infant should prompt the treatment of the mother and her sexual partners. The finding of vesicles anywhere on the skin or mucous membranes in association with neonatal conjunctivitis suggests herpes simplex infection and warrants a full sepsis evaluation with cerebrospinal fluid evaluation for herpes simplex virus and treatment with acyclovir, 20 milligrams/ kg/dose three times a day.  ABNORMAL MOVEMENTS AND SEIZURES Seizures are covered in detail in Chapter 138, “Seizures in Infants and Children. ” It is important to distinguish benign sleep myoclonus in infancy and the normal startle reflex from actual seizures. Sleep myoclonus consists of rhythmic myoclonic jerks observed when the infant is drowsy or in quiet sleep and can be suppressed upon touching and/or waking the infant; the startle reflex is a single myoclonic jerk with extension of the arms and legs triggered by noise or tactile stimulation. Tetany due to hypocalcemia is associated with congenital syndromes, such as DiGeorge’s syndrome, and must also be distinguished from seizure activity. Recognition of seizures in the newborn period is important, because seizure management and outcome are different than at any other age. Neonatal seizures are likely to present with subtle manifestations, such as eye deviation, tongue thrusting, eyelid fluttering, apnea, pedaling movements, or arching, rather than generalized activity. Neonatal seizures usually indicate a severe underlying structural or metabolic problem and are rarely idiopathic.

age. Neonatal seizures are likely to present with subtle manifestations, such as eye deviation, tongue thrusting, eyelid fluttering, apnea, pedaling movements, or arching, rather than generalized activity. Neonatal seizures usually indicate a severe underlying structural or metabolic problem and are rarely idiopathic. Common causes include hypoxic ischemic encephalopathy, neonatal stroke, electrolyte disturbances, and underly ing metabolic and genetic conditions. Nonaccidental injury must be considered. If seizures occur in the first 6 hours of life, consult neonatology and/or neurology, and consider therapeutic hypothermia to improve neurodevelopmental outcomes in hypoxic ischemic encephalopathy. 12,13 Acknowledgment: The authors gratefully acknowledge the contribu tions of Tonia J. Brousseau, the lead author of this chapter in the previ ous edition. REFERENCES The complete reference list is available online at www.TintinalliEM.com. Brief Resolved Unexplained Events and Apparent Life-Threatening Events Ilene Claudius Joel Tieder DEFINITIONS It is quite common for infants to have events that are brief, self-resolved, and difficult to characterize. Sometimes these events appear respiratory, cardiovascular, or neurologic in origin, and caregivers may seek medical attention for reassurance that the event is not a sign of a serious underlying condition. Through a comprehensive history and physical, clinicians CHAPTER Tintinalli_Sec12_p0669-0996.indd 739 8/2/19 7:50 PM

metimes these events appear respiratory, cardiovascular, or neurologic in origin, and caregivers may seek medical attention for reassurance that the event is not a sign of a serious underlying condition. Through a comprehensive history and physical, clinicians CHAPTER Tintinalli_Sec12_p0669-0996.indd 739 8/2/19 7:50 PM 740 SECTION 12: Pediatrics after the event as well as the relationship of the event to feeding, sleeping, and upper and lower respiratory problems. Many newborns experience physiologic patterns of breathing that can be frightening to a layperson but are normal. Healthy infants often have cyclic periods of rapid breathing interposed with respiratory pauses, termed periodic breathing. Periodic breathing is observed in nearly all preterm and most term infants, and lasts until about 2 months of age in term infants. In addition, irregular respirations are the hallmark of active sleep (later referred to as rapid eye movement sleep or dream sleep) at all ages. Irregular breathing during rapid eye movement sleep continues into adulthood and is normal. Apnea is typically characterized as central, obstructive, or mixed. Apneic pauses of >20 seconds or those associated with changes in color, tone, or heart rate are considered pathologic. Apnea is difficult to char acterize subjectively, so the new American Academy of Pediatrics BRUE guideline includes any brief and resolved irregularity in respiration as a component of BRUE, unlike the ALTE definition, which specified apnea. Central apnea implies a disruption in the central respiratory centers resulting in a cessation of respiratory effort; there is no attempt to breathe. This can be a manifestation of a number of disorders, including traumatic brain injury and infectious disorders (including both serious bacterial infections and respiratory diseases such as bronchiolitis and pertussis). Infants with obstructive apnea appear to be attempting to breathe through an occluded airway, with paradoxical movements of the chest and abdomen. 12 This is commonly described in upper and lower respiratory tract infections. In cases of oral dysphagia or gastroesopha geal reflux disease, infants may exhibit obstructive apnea in relationship to feeds. There can be, at least subjectively, components of both central and obstructive apnea, indicating a mixed picture. Apnea of prematurity is a disorder in the control of breathing in premature infants, occurring in up to 25% of this group. 13 Its frequency decreases with increasing maturity, and it is usually outgrown by 37 weeks of postconceptual age. Episodic changes in infant skin color are often difficult for observers to characterize, particularly in infants with darker skin tones. The color change may be a manifestation of normal infant physiology (e.g., acrocyanosis) or may indicate more serious problems with perfusion or oxygenation (e.g., central cyanosis). Cyanosis becomes apparent when at least 5 grams/100 mL of blood is deoxygenated. Because young infants are often polycythemic, this threshold is more easily met in this age group, and cyanosis may be observed in normal newborns, typically seen in the dense perioral veins. In the distal extremities, vasomotor instability can cause acrocyanosis without underlying pathology. Both of these entities are benign. Normal infant polycythemia can also lead to a ruddy appearance (plethoric), which, in the crying infant, may be misinterpreted by lay caregivers as cyanosis or “purple” coloring. For this reason, plethora was not included in the definition of BRUE. Pallor is characteristic of the vasovagal response and can be seen in association with gastroesophageal reflux, choking on feeds, or a vagal event.

which, in the crying infant, may be misinterpreted by lay caregivers as cyanosis or “purple” coloring. For this reason, plethora was not included in the definition of BRUE. Pallor is characteristic of the vasovagal response and can be seen in association with gastroesophageal reflux, choking on feeds, or a vagal event. In neonates, changes in muscle tone are difficult to classify because baseline neurologic status varies due to immaturity. Seizures in infants uncommonly present as stereotypical tonic-clonic activity and are more likely to present with altered consciousness or intermittent high and low tone (e.g., infantile spasms). In addition, infants may exhibit changes in tone (either decreased or increased) in the postictal state. Changes in tone may also be secondary to hypoxia resulting from apnea. Stiffening and arching behavior have been well described in infants with gastroesophageal reflux events (Sandifer’s syndrome). An altered level of responsiveness is part of the definition of BRUE because it can be an important component of the event associated with a serious underlying disorder. It was not part of the ALTE definition. Infants may lose consciousness or become unresponsive from a seizure, hypoglycemia, or hypoxemia. However, reports of altered consciousness often represent normal physiology or benign events as well. Because of an immature nervous system, infants may normally appear somnolent, appear unresponsive briefly, or lose consciousness after a breath-holding spell. DIFFERENTIAL DIAGNOSIS There are many potential causes of a BRUE or ALTE. The vast major ity of conditions attributable to events previously referred to as ALTEs are self-limiting and not life threatening. For example, most patients can explain many of these events as a benign or normal process such as choking or gagging from feeding or gastroesophageal reflux. Sometimes, however, the event remains poorly understood or unexplainable, and this uncertainty poses a diagnostic and management challenge.  APPARENT LIFE-THREATENING EVENT In 1986, before the risk factors for sudden infant death syndrome were well understood, an expert consensus group from the National Institutes of Health coined the term apparent life-threatening event (ALTE). ALTE was defined as an episode that is frightening to a caregiver and involves some combination of apnea, color change (cyanosis, pallor, or plethora), change in muscle tone (limp or stiff), choking, or gagging. 1 Unfortunately, the term ALTE described a constellation of presenting symptoms rather than a diagnosis and relied heavily on the subjective impression of nonmedical caregivers. No differentiation was made between the ~80% of ALTE patients who are well-appearing at the time of presentation 2-5 and patients with ongoing symptoms such as respiratory difficulty or an ill appearance. To address these concerns, in 2016, the American Acad emy of Pediatrics more precisely defined these events as brief resolved unexplained events (BRUEs).  BRIEF RESOLVED UNEXPLAINED EVENTS A BRUE specifically includes infants <1 year of age who have expe rienced a brief (<1 minute), unexplained event consisting of one or more of the following features: cyanosis or pallor; absent, decreased, or irregular breathing; marked change in tone (hyper- or hypotonia); and/or altered level of responsiveness. The infant must return to his or her baseline state of health after the brief event and have a reassuring history and physical exam after medical evaluation, including vital signs. 6 The BRUE guideline provides risk stratification criteria and management recommendations for lower-risk patients (Figure 117-1).

siveness. The infant must return to his or her baseline state of health after the brief event and have a reassuring history and physical exam after medical evaluation, including vital signs. 6 The BRUE guideline provides risk stratification criteria and management recommendations for lower-risk patients (Figure 117-1). BRUE patients considered lower risk for subsequent events or serious underlying diagnosis include those >60 days old, with gestational age ≥32 weeks and postconceptional age ≥45 weeks, only one event (no prior BRUE ever and not occurring in clusters), event duration <1 minute, no CPR required by trained medical provider, no concerning historical features, and no concerning physical examination findings (see “Risk Stratification”). This chapter does not address patients with ongoing symptoms (e.g., fever [Chapter 119], failure to thrive, respiratory distress [Chapters 123 to 125], recurrent seizures [Chapter 138]) because these patients should be evaluated based on their symptoms. Because BRUE is a newer classification that has not yet been specifically studied, most of the studies cited in this chapter were performed using the previous definition of ALTE. EPIDEMIOLOGY It can be normal for infants to choke, gag, demonstrate skin discol oration, change tone, or exhibit periodic and irregular breathing. In healthy infants, 43% are reported to have a 20-second respiratory pause and up to 5% of parents recall seeing an apnea event. The incidence of ALTE ranges from 0.05% to 6.0%, depending on the population studied. 7-9 In Europe, 1 out of 250 to 400 children are hospitalized for an ALTE. The peak incidence is between 1 week and 2 months of age, with the major ity of ALTEs occurring before 10 weeks of age. 10 The male-to-female ratio is 2:1.11 Known risk factors for ALTE include respiratory syncytial virus infection, prematurity, recent anesthesia, gastroesophageal reflux, and airway/maxillofacial anomalies. The epidemiology using the more specific term BRUE has not yet been described. PATHOPHYSIOLOGY AND EVENT CLASSIFICATION It is important to characterize the event with a comprehensive history, paying particular attention to changes in breathing, skin color, muscle tone, and level of consciousness. To differentiate normal from poten tially pathologic events, determine what occurred before, during, and Tintinalli_Sec12_p0669-0996.indd 740 8/2/19 7:50 PM

t to characterize the event with a comprehensive history, paying particular attention to changes in breathing, skin color, muscle tone, and level of consciousness. To differentiate normal from poten tially pathologic events, determine what occurred before, during, and Tintinalli_Sec12_p0669-0996.indd 740 8/2/19 7:50 PM CHAPTER 117: Brief Resolved Unexplained Events and Apparent Life-Threatening Events 741 FIGURE 117-1. Diagnosis, risk classification, and recommended management of a brief resolved unexplained event (BRUE). *See Tables 3 and 4 of the original article for the determination of an appropriate and negative family history (FH) and physical examination (PE). **See Figure 2 of the original article for the American Academy of Pediatrics method for rating of evidence and recommendations. ALTE = apparent life-threatening event; CSF = cerebrospinal fluid; EEG = electroencephalogram; GER = gastroesophageal reflux. [Reproduced with permission from Tieder JS, Bonkowsky JL, Etzel RA, et al: Brief resolved unexplained events (formerly apparent life-threatening events) and evaluation of lower-risk infants, Pediatrics. 2016;137(5): pii: e20160590.] Patient presents for initial medical assessment after a brief, resolved event that was observed by caregiver in a child <1 year of age Perform appropriate history and PE* Higher risk patient Lower risk patient Apply risk stratification • Age >60 days • Born ≥32 wks gestation and corrected gestational age ≥45 wks • No CPR by trained medical provider • Event lasted <1 minute • First event • Educate caregivers about BRUEs and engage in shared decision-making to guide evaluation, disposition, and follow-up • Offer resources for CPR training to caregiver • Obtain WBC count, blood culture, or CSF analysis or culture, serum sodium, potassium, chlo ride, blood urea nitrogen, creatinine, calcium, ammonia, bl ood gases, urine organic acids, plasma amino acids or acylcamitine s, chest radiograph, echocar diogram, EEG, studies for GER • Initiate home cardio-respiratory monitoring • Prescribe acid suppression therapy or anti-epileptic medications Should not • Obtain viral respiratory test, urinalysis, blood glucose, serum bicarbonat e, serum lactic acid, laboratory evaluation for anemia, or neuroimaging • Admit the patient to the hospital solely for cardiorespiratory monitoring Need not • Obtain pertussis testing and 12-lead ECG • Briefly monitor patients with continuous pulse oximetry and serial observations May Should Use event characteristics rather than the term “ALTE,” to describe the event Event criteria absent Out of guideline scope; manage accordingly Diagnosis of Brief Resolved Unexplained Event is made Not a BRUE Patient is well-appearing Patient has additional symptoms or abnormal vital signs (eg, cough, respiratory difficulties, or fever) Explanation for event identified (eg, GER, feeding difficulties, or airway abnormality) Clinician characterizes the event as a sudden, brief, and now resolved episode of one or more of the following: • Cyanosis or pallor • Absent, decreased, or irregular breathing • Marked change in tone (hyper- or hypotonia) • Altered responsiveness No explanation for event identified No concerns identified from history and PE* Concerns identified from history or PE (eg, FH of sudden cardiac death or subtle, non-diagnostic social, feeding or respiratory problems) Yes Management recommendations for lower risk patients** BRUE risk classification BRUE diagnosis Event criteria present Tintinalli_Sec12_p0669-0996.indd 741 8/2/19 7:50 PM

ry and PE* Concerns identified from history or PE (eg, FH of sudden cardiac death or subtle, non-diagnostic social, feeding or respiratory problems) Yes Management recommendations for lower risk patients** BRUE risk classification BRUE diagnosis Event criteria present Tintinalli_Sec12_p0669-0996.indd 741 8/2/19 7:50 PM 742 SECTION 12: Pediatrics TABLE 117-1 Explanations for Events Previously Referred to as ALTEs Common, Benign Explanation Common Serious Pathology Less Common Serious Pathology Gastroesophageal reflux/ vomiting episode Seizure/infantile spasm/ febrile seizure Maxillofacial obstruction or tracheoesophageal fistula Upper respiratory tract infection Lower respiratory infections Arrhythmia/cardiac Coughing or choking episode Laryngotracheomalacia Pertussis Periodic breathing Inflicted injury Serious bacterial infection Oral dysphagia   Metabolic disease Breath-holding spell

ure Maxillofacial obstruction or tracheoesophageal fistula Upper respiratory tract infection Lower respiratory infections Arrhythmia/cardiac Coughing or choking episode Laryngotracheomalacia Pertussis Periodic breathing Inflicted injury Serious bacterial infection Oral dysphagia   Metabolic disease Breath-holding spell Electrolyte/glucose Poisoning presenting with an ALTE are diagnosed as having an idiopathic cause or gastroesophageal reflux. 14,15 However, some patients may have a serious underlying disorder or risk for recurrence. The risk of a serious underlying disorder or recurrence in BRUE patients is unknown . Table 117-1 lists common, uncommon, and rare diagnoses assigned to patients presenting with a concerning event previously termed an ALTE. Select processes are discussed independently below.  GASTROESOPHAGEAL REFLUX Gastroesophageal reflux is among the most common explanations for these events. Gastroesophageal reflux is the involuntary passage of gastric contents into the esophagus and occurs daily in infants during the first year of life. This form of reflux, or frequent “spitting up, ” is entirely normal and should be considered physiologic. As a result of the temporal correlation between peak age for these events and that of gastroesophageal reflux and the fact that reflux of gastric contents into the hypopharynx can trigger laryngospasm, a diagnosis of gas troesophageal reflux disease provides an easy explanation for events. Pathologic gastroesophageal reflux disease is defined as regurgitation of gastric contents into the esophagus with accompanying symptoms and complications such as failure to thrive. If events are recurrent and appear to be associated with gastroesophageal reflux events or symp toms, then initiating “reflux precautions” may be helpful, including small frequent feedings, upright positioning after feedings, frequent burping, and avoidance of tobacco smoke. Routine use of medications to reduce the acidity of the gastric contents (proton pump inhibitors, histamine-2 blockers) is not recommended . 16 If events persist despite conservative empiric treatment, then further evaluation for GI and other causes (see “ Anatomic Causes” below) may be indi cated. Unfortunately, testing has limitations, and causation is difficult to prove. Even when invasive testing has linked apnea to gastroesopha geal reflux, a difference between acid and nonacid reflux has not been demonstrated. 17,18  ORAL DYSPHAGIA Problems with feeding coordination commonly cause these events, particularly in newborn infants. If the events appear to be related primarily to feeding, evaluation by speech or occupational therapy to evaluate and manage feeding and swallowing is recommended. 8,19  UPPER AND LOWER RESPIRATORY TRACT INFECTIONS AND PERTUSSIS Respiratory infections such as respiratory syncytial virus and pertussis can cause central, obstructive, or mixed apnea in infants by directly affecting the brain or by causing laryngospasm, coughing, choking, or oral dysphagia. In younger infants, the events can be difficult to characterize particularly because they can precede the typical viral prodrome (Chapter 128, “Pneumonia in Infants and Children”). Obstructive apnea commonly occurs when infants choke on respiratory secretions. Dysregulation of mucosal immune responses and sensorineural stimu lation have been postulated as the cause of central apnea. 20-22 Wilwerth and colleagues reported a 2.7% rate of apnea among infants admitted with bronchiolitis, and apnea at presentation is a risk factor for subse quent apneic episodes.

tory secretions. Dysregulation of mucosal immune responses and sensorineural stimu lation have been postulated as the cause of central apnea. 20-22 Wilwerth and colleagues reported a 2.7% rate of apnea among infants admitted with bronchiolitis, and apnea at presentation is a risk factor for subse quent apneic episodes. 23 Most studies have been performed on clinical or respiratory syncytial virus–proven bronchiolitis, but recently, the same association was found with metapneumovirus-associated bron chiolitis and a spectrum of respiratory pathogens. Bordetella pertussis, or “whooping cough, ” causes a respiratory infection that persists despite vaccination due to waning immunity in older individuals, vaccine failures, and vaccine refusal. Infants <6 months old are particularly susceptible because the initial immunization series begins at 2 months of age. Classically, the infection begins with upper respiratory infection symptoms (catarrhal phase) and progresses to paroxysmal coughing (paroxysmal phase) over 3 to 6 weeks. However, it is important to understand that infants may present with isolated apnea. Diagnosis can be difficult because apnea may be the first present ing symptom of bronchiolitis or pertussis in younger infants. While routine testing of bronchiolitis patients for viral pathogens is not rec ommended, testing for subclinical viral causes and pertussis in unclear cases presenting with apnea may be beneficial if exposure is of concern and test results are readily available. Infants presenting with apnea associated with proven or probable bronchiolitis or pertussis should be admitted for observation.  SEIZURES Seizures have been identified in 4% to 7% of infants with ALTEs. Most often, they are the initial presentation of epilepsy in this age group but can rarely be secondary to underlying causes such as congenital brain malformation, metabolic disorders, electrolyte abnormalities, prena tally acquired brain injury, or intracranial bleeding (including abusive head injury). In well-appearing patients, an electroencephalogram seldom leads to a diagnosis of epilepsy and performing it often requires a hospital stay. The American Academy of Pediatrics BRUE guideline recommends against routine testing for seizures, including elec troencephalogram and head imaging for lower-risk patients. For patients with recurring events and no explanation, particularly those concerning for seizures, neuroimaging and electroencephalogram may be indicated (Chapter 138, “Seizures in Infants and Children”).  CHILD ABUSE/POISONING Child abuse, including suffocation, abusive head injury, and poison ing, are potential serious causes of these events and are reported in 1.4% to 2.5% of all infants presenting with ALTEs (Chapter 150, “Child Abuse and Neglect”). 26-28 Clinicians should have a high index of suspi cion for these diagnoses since they can be difficult to recognize early on. A careful history and physical examination can determine risk most of the time. Patients meeting the criteria for a lower-risk BRUE and with a negative history and physical exam have an incidence <0.3% of abusive head trauma and likely do not warrant additional investigation for child abuse. 6 However, higher-risk BRUEs and those with social concerns or recurrent unexplained events may warrant additional investigation. Truman and Ayoub 29 reported an increased risk of future death or recurrent ALTEs among ALTE patients presenting with fresh blood from the nose/mouth and higher potential for nonaccidental trauma in infants >6 months of age.

hose with social concerns or recurrent unexplained events may warrant additional investigation. Truman and Ayoub 29 reported an increased risk of future death or recurrent ALTEs among ALTE patients presenting with fresh blood from the nose/mouth and higher potential for nonaccidental trauma in infants >6 months of age. Vomiting, irritability, bruising, subcon junctival hemorrhage, rapid head enlargement or head circumference >95% for age, a prior ALTE, a recent emergency services call, and a discrepant history have also been found to be associated with abusive head injury. 30-35 Southall et al 31 performed covert video surveillance in a highly selective population of recurrent ALTE patients considered suspicious for abuse and found an association between intentional suffocation and bleeding from the nose and mouth, marital dissatisfac tion and parental personality disorders, and unexplained sibling death. One small study found subsequent abuse-related death to occur in 9% of patients followed for 12 months after an ALTE, 36 and another study Tintinalli_Sec12_p0669-0996.indd 742 8/2/19 7:50 PM

and bleeding from the nose and mouth, marital dissatisfac tion and parental personality disorders, and unexplained sibling death. One small study found subsequent abuse-related death to occur in 9% of patients followed for 12 months after an ALTE, 36 and another study Tintinalli_Sec12_p0669-0996.indd 742 8/2/19 7:50 PM CHAPTER 117: Brief Resolved Unexplained Events and Apparent Life-Threatening Events 743 found that 11% of hospitalized ALTE patients became victims of child abuse over a 5-year follow-up period.37 This would seem to indicate that, while a small percentage of ALTE patients are found to be victims of nonaccidental trauma during their index visit, they are at long-term risk of abuse. It is extremely difficult to discern from the currently available data whether that indicates that the index visit represented subtle abuse or whether presentation with an ALTE may be associated with psycho social issues that lead later to abuse. Poisoning as a cause of an ALTE is also a concern and may be intentional or unintentional. Intentional poisonings frequently involve narcotics, benzodiazepines, or phenothiazines in an attempt to quiet or sedate a fussy infant. 38,39 Unintentional poisonings may involve inappropriate dosing of medications or mixing of over-the-counter cough and cold preparations containing ingredients with similar activity. Homeo pathic medications, such as colic preparations, have also been associated with ALTEs.  SERIOUS BACTERIAL INFECTIONS Serious bacterial infections are an extremely rare cause of lower-risk BRUEs, and testing for bacterial infection, including cultures of blood, urine, and cerebrospinal fluid, chest radiographs, and WBC counts, is not recommended. In some situations, higher-risk infants, particularly those under 2 months, may warrant screening tests such as urinalysis. How ever, infants with fever, hypothermia, localizing symptoms and signs of infection, persistently ill appearance, or concerning comorbidities should receive appropriate testing for serious bacterial infections (see Chapter 119, “Fever and Serious Bacterial Illness in Infants and Children”). Even for infants below 2 months of age with events previously referred to as ALTE, unless one of the above risk factors is present, a full “ruleout sepsis” will rarely identify an occult infection. A study of 112 infants <60 days old with ALTE who underwent testing for serious bacterial infection identified three cases of bacteremia and one urinary tract infection, as well as one case of pertussis. This constituted 2.7% of the sample, and four of the five affected patients had a history of prematurity. Chest radiograph is rarely indicated in absence of any respiratory findings. The rare exception to this includes patients under 2 months of age who may present without classic findings for pneumonia. 42,43 Additionally, respiratory symptoms and/or radiograph-proven pneumonia can develop after the initial presentation for ALTE, 4 and a paper documenting two deaths after discharge of 176 infants found both to have succumbed to pneumonia. 44 However, neither had a radiograph deemed to be positive in the ED. Careful outpatient follow-up is preferable to identify these patients, not routine radiographs.  BREATH-HOLDING SPELLS Breath-holding spells occur in 4% to 5% of children <8 years of age and entail a cessation of respiration at the end of expiration, usually in response to pain, anger, or fear. Spells typically last <1 minute and may be accompanied by cyanosis, pallor, syncope, and seizures. Breathholding spells have not been associated with any underlying medical condition, although there is some literature supporting the finding that pallid spells are associated with pronounced QT dispersion and may have a cardiac etiology.

last <1 minute and may be accompanied by cyanosis, pallor, syncope, and seizures. Breathholding spells have not been associated with any underlying medical condition, although there is some literature supporting the finding that pallid spells are associated with pronounced QT dispersion and may have a cardiac etiology. Breath-holding spells are generally easily recognized in older children, but they may be diagnosed in infants as young as 6 months of age: one study found that in 15% of children with breathholding spells, the age of onset was <6 months.  ANATOMIC CAUSES Anatomic anomalies of the airway such as laryngomalacia, tracheomalacia, tracheoesophageal fistulas, vascular rings, and clefts may cause obstructive apnea, oral dysphagia, gastroesophageal reflux, sleep-disordered breathing, and obstructive sleep apnea. Subtle dysmorphisms may lead to abnormal breathing and obstruction during sleep, presenting with snoring, apnea, and mouth breathing. 46 An ear, nose, and throat evalu ation is indicated for infants experiencing repeat and serious events, particularly those that indicate an unstable airway.  METABOLIC CAUSES Inborn errors of metabolism rarely present as a BRUE in the face of negative newborn screens and a noncontributory history and physical examination. Therefore, routine testing is not indicated. 42 Inborn errors of metabolism might be suspected in patients who experience an event after their first period of prolonged fasting (e.g., an infant who just began sleeping through the night) or a history of poor feeding and somnolence throughout the neonatal period (see Chapter 146, “Metabolic Emergencies in Infants and Children”). Importantly, these infants are often symptomatic upon presentation and would not qualify as having a BRUE.  CARDIAC CAUSES Cardiac arrhythmias, channelopathies, Wolfe-Parkinson-White syn drome, cardiomyopathy, and myocarditis can present as a BRUE but are rare causes when there is a noncontributory history and physical examination. 42,48 An ECG, when available, is an accurate and inexpen sive test that can be helpful in diagnosing this life-threatening disorder (see Chapter 130, “Syncope, Dysrhythmias, and ECG Interpretation in Children”). ED APPROACH When a caregiver seeks medical attention for an event, the first step for the provider is to characterize the event as objectively as possible by taking a careful history. Ask targeted questions to understand the event including what happened before, during, and after the event and include any relationship to feeding, color change, central versus obstructive apnea, event duration, loss of consciousness, stereotypical seizure activity, and so on. If patients are currently exhibiting symptoms such as fever or respiratory illness and/or if there is a clear explanation for the event such as gastroesophageal reflux or upper respiratory infection, then manage the patient accordingly. These events should not be called ALTEs or BRUEs. For children with an upper respiratory infection, cough and cold preparations are contraindicated in infancy, even when it appears that an infant has choked on mucus. Infants with a concern for an airway abnormality should be evaluated by an otolaryngologist. Infants presenting with a potential seizure in the first year of life will certainly need neurologic consultation; an immediate electroencepha logram need not be ordered and antiepileptic medications should not be empirically initiated for a lower-risk BRUE patient (see Chapter 138, “Seizures in Infants and Children”). These consultations can be arranged on an urgent, outpatient basis rather than requiring admission for inpatient consultation in a stable infant. Home monitoring is not indicated following discharge.

should not be empirically initiated for a lower-risk BRUE patient (see Chapter 138, “Seizures in Infants and Children”). These consultations can be arranged on an urgent, outpatient basis rather than requiring admission for inpatient consultation in a stable infant. Home monitoring is not indicated following discharge. Infants for whom the diagnosis is not immediately clear but who appear unstable should be resuscitated aggressively, and the aforemen tioned causes should be considered. The well-appearing infants without an explanation who fall under the guidelines for a BRUE should be riskstratified and managed in accordance with their risk category.  RISK STRATIFICATION Once a child has met criteria for a BRUE, implying no current symptoms and no explanation for the event, the next step is to assess the infant for risk of recurrence or a serious underlying disorder in the same manner that a patient with chest pain or young infant with fever might be riskstratified. Patients who meet all the criteria in Table 117-2 are presumed to be lower risk. 6 Infants not meeting all of these criteria are considered as having higher-risk BRUE. It is important to recognize that these cri teria define a very low-risk group. Infants not meeting lower-risk BRUE criteria are a pleomorphic group to be assessed on an individual basis. Not every infant assigned to this “higher-risk group” is at substantial risk of future events.  DIAGNOSTIC TESTING AND DISPOSITION IN LOWER-RISK BRUE It has been common to admit infants presenting with ALTE to the hospital for workup and monitoring. However, this is not without cost: the mean adjusted charge for children’s hospitals in the United States is Tintinalli_Sec12_p0669-0996.indd 743 8/2/19 7:50 PM

ts.  DIAGNOSTIC TESTING AND DISPOSITION IN LOWER-RISK BRUE It has been common to admit infants presenting with ALTE to the hospital for workup and monitoring. However, this is not without cost: the mean adjusted charge for children’s hospitals in the United States is Tintinalli_Sec12_p0669-0996.indd 743 8/2/19 7:50 PM 744 SECTION 12: Pediatrics $15,567 per admission (average length of stay, 4.4 days).49 The financial burden is compounded by the frequency of iatrogenic complications, including medical errors and nosocomial infections, and the social implications from unnecessary admission and added anxiety. The American Academy of Pediatrics BRUE guideline recommends against routine admission of these infants . This is based on literature indicating which patients are at risk of a serious underlying pathology or recurrent event. 50-53 Instead, a period of observation on pulse oxim etry with serial exams lasting 1 to 4 hours can be offered. The duration of this period of observation is a good opportunity for shared decision making with caregivers. A follow-up exam in 24 hours is recommended. Reassurance that BRUE is not considered a precursor to sudden infant death syndrome and CPR instruction resources may provide additional reassurance to caregivers. Recommended laboratory and radiographic evaluation of the lower-risk BRUE patient is minimal ( Table 117-3). In a child without referable symptoms, WBC count, cultures, electrolytes, chest radiograph, echocardiogram, and evaluation for metabolic disease are not indicated. Similarly, viral respiratory testing, blood glucose, bicarbonate, hemoglobin, and neuroimaging are not necessary. Provid ers are given the option of testing for pertussis and obtaining an ECG in appropriate situations. These recommendations are based on a wealth of literature indicating a negligible yield of routine testing in ALTE patients, particularly those that the new guidelines would place in a lower-risk category. 3,42,54  DIAGNOSTIC TESTING AND DISPOSITION OF HIGHER-RISK BRUES Testing and hospitalization are useful in higher-risk BRUE patients, compared to lower-risk infants. 55 The risk of recurrence or an underlying condition is not well understood in this population, and there are no formal guidelines published for the management of the higher-risk BRUE patient. While no evidence exists to support a wide battery of screening labs, testing and observation periods may be warranted for certain populations. In this group, obtain a careful history and physical to uncover potential diagnoses that should be pursued, with emphasis on excluding oral dysphagia, abuse, arrhythmia, and CNS and anatomic problems. Laboratory and radiographic evaluation should be pursued for reasonable differential diagnoses after the history and physical exam. While admission is not mandatory in these patients, have a low threshold for admission and monitoring.

phasis on excluding oral dysphagia, abuse, arrhythmia, and CNS and anatomic problems. Laboratory and radiographic evaluation should be pursued for reasonable differential diagnoses after the history and physical exam. While admission is not mandatory in these patients, have a low threshold for admission and monitoring. For patients experiencing TABLE 117-2 Criteria for Brief Resolved Unexplained Events (BRUE) and Lower-Risk BRUE Criteria for BRUE Age <1 y Sudden, brief episode Patient at baseline state of heath after event Event unexplained by history and physical exam ≥1 of the following •  Cyanosis  or pallor •  Absent,  decreased, or irregular breathing •  Marked  change in tone •  Altered  level of responsiveness Criteria for lower-risk BRUE >60 d old Born at a gestational age of ≥32 wk and currently at a postcon ceptual age ≥45 wk First and single event Event lasting <1 min No CPR required by trained medical provider No concerning historical features No concerning physical exam features TABLE 117-3 Recommendations for the Lower-Risk Patient With a Brief Resolved Unexplained Event (BRUE) Clinician should: Educate caregivers about BRUE Use shared decision making when possible Offer CPR resources Clinician may: Monitor for 1–4 h with pulse oximetry and serial exams Perform pertussis testing Perform ECG Clinician need not: Admit patient solely for monitoring Obtain respiratory viral testing Obtain urinalysis Obtain blood glucose, bicarbonate, or lactate Obtain neuroimaging Screen for anemia Clinician should not: Obtain WBC Obtain blood culture Obtain cerebrospinal fluid studies Obtain electrolytes Obtain metabolic workup Obtain chest radiograph Obtain echocardiogram Obtain electroencephalogram Obtain studies for gastroesophageal reflux Initiate home monitoring Prescribe acid suppression therapy Prescribe antiepileptics events formerly referred to as ALTE, between 12% and 14% have a subsequent event or are diagnosed with a condition that requires hospitalization. This rate is probably much lower under the BRUE definition. Premature infants, infants 2 months old, infants with cyanosis, and those with chronic medical conditions seem to be at highest risk of recurrence. 51,56 If events recur during hospitalization, events can be better explained. For example, oral dysphagia, sleep apnea, breathholding spells, and seizures may be easily recognized by a medical provider during careful observation, and arrhythmias can be identified by monitoring.  POSTDISCHARGE OUTCOMES ED physicians and caregivers may worry about subsequent sudden infant death syndrome or occult illness in infants who have experienced BRUE or ALTE. However, such patients are not at increased risk of sudden infant death syndrome. 48,57 That said, an event may be an initial sign of an underlying serious condition, such as nonaccidental trauma, that would place the infant at increased risk of recurrence or death. Overall postdischarge mortality in ALTE studies is 0% to 0.4%. 5,8,37 The likeli hood of a subsequent ALTE after discharge ranges from 7.1% to 15.4%.58 In lower-risk BRUE patients, recurrent events or an underlying disorder are very unlikely. For all BRUE patients, it is important to impart reas surance without offering false guarantees that another event will not occur. Currently, home monitors are not recommended for lower-risk BRUE patients. REFERENCES The complete reference list is available online at www.TintinalliEM.com. Tintinalli_Sec12_p0669-0996.indd 744 8/2/19 7:50 PM