Joel S. Tieder
Infants commonly experience acute, self-resolving changes in their breathing, tone, mental status, and skin color. Usually these events are normal manifestations of developmental immaturity. Nonetheless, caregivers may worry that the acute event could have been life-threatening or is a sign of an undiagnosed medical problem and seek medical attention. In most cases, after a comprehensive history and physical examination, a clinician will determine the event to have been a benign or normal process, such as gastroesophageal reflux (GER) or periodic breathing of the newborn. At times, however, the event defies a simple explanation and drives uncertainty about risk from a serious underlying cause or a future event. This situation poses a diagnostic and management challenge for both the family and the clinician.
Historically, these events were feared as precursors to sudden infant death syndrome (SIDS) and were referred to as near-miss SIDS , aborted crib deaths , or apparent life-threatening events (ALTEs) . These terms have been replaced because we now know that these events are not associated with SIDS and are rarely life-threatening. Clinical use of ALTE as a diagnostic term is additionally problematic because it relies on the subjective interpretation of the caregiver and includes a nonspecific constellation of symptoms. It also does not distinguish well-appearing patients from those with symptoms.
Most of these acute events in infants are best described as brief resolved unexplained events (BRUEs). A BRUE is a diagnosis of exclusion and should be used only when the event is transient and remains unexplained after an appropriate medical evaluation.
A BRUE (pronounced brew ) is an event that occurs in an infant younger than 1 yr that typically lasts less than 30 sec and is described by the observer as a sudden, brief, and now-resolved episode that involved at least one of the following:
The diagnosis of BRUE applies only to infants who were asymptomatic prior to the event and during evaluation, and when no explanation for the event is found through appropriate history and physical examination.
Infants who experience a BRUE are categorized as either lower or higher risk for a subsequent event or a serious underlying disorder based on patient factors, characterization of the event, additional historical factors, and the physical examination.
A lower-risk infant is defined as
The incidence of BRUEs is unknown. However, studies of ALTE patients provide some insight because BRUEs are a subset of what had been considered ALTEs. Hospitalization for an ALTE was common; 1 out of every 2.5-9.4/1,000 infants was hospitalized for an ALTE. Acute events that do not lead to hospitalization are even more common according to large epidemiologic studies of healthy infants. Of normal infants followed longitudinally with home monitoring, up to 43% had a 20-sec apnea episode over a 3-mo period. Of parents asked when their infant was 1 yr of age, 5% recalled an apneic event.
BRUEs are not precursors to SIDS . The incidence of mortality after a BRUE from an underlying cause is unknown but is also likely to be extremely uncommon. The few reports of mortality in studies of ALTE are limited to patients who would not qualify as a BRUE because of the presence of other symptoms or an explanatory diagnosis.
However, for patients presenting with a BRUE, numerous risks must be considered. First is the risk of an underlying serious diagnosis. Although each is rare, clinicians must consider a wide variety of illnesses, such as cardiac arrhythmias, metabolic disorders, and brain injury (Table 403.1 ). The risk for an underlying serious diagnosis in patients with a BRUE is much lower than the rate reported in ALTE research, where many of the patients had underlying conditions or ongoing symptoms (e.g., lower respiratory tract infection). In infants meeting lower-risk criteria, the likelihood of an underlying serious cause is extremely low. In higher-risk infants, the likelihood is unknown but probably much lower than suggested by research on ALTEs. Second is the risk of a recurrent event, which is currently unknown. These events can be stressful for caregivers, particularly when the cause is unknown. Third is the risk that the caregivers become unnecessarily concerned about their healthy child. Clinicians should be aware the challenges caregivers face when perceiving a threat of losing their child, there is medical uncertainty, or when their child is hospitalized. Fourth are the risks associated with medical care, such as nosocomial infections and inaccurate testing.
Table 403.1
Symptom-Based Approach to BRUEs: Possible and Other Conditions That Might Be Confused With BRUE
| DIAGNOSTIC CATEGORIES | COMMON AND/OR CONCERNING CAUSES TO CONSIDER | SUGGESTIVE HISTORICAL FINDINGS | SUGGESTIVE PHYSICAL EXAMINATION FINDINGS | TESTING TO CONSIDER |
|---|---|---|---|---|
| Gastrointestinal |
GER Intussusception Volvulus Oropharyngeal dysphagia |
Coughing, vomiting, choking, gasping temporally related to feeds or regurgitation of gastric contents Feeding difficulties Recent preceding feed Irritability following feeds Milk in mouth/nose Bilious emesis Pulling legs to chest Bloody/mucousy stool Lethargy following event |
Gastric contents in the nose and mouth Choking, gagging, or oxygen desaturation temporally related to feeding or regurgitation of gastric contents |
Upper GI to assess for anatomic anomalies Clinical swallow evaluation Abdominal ultrasound pH probe |
| Infectious |
Upper and lower respiratory tract infection (RSV, pertussis, pneumonia) Bacteremia Meningitis Urinary tract infection |
Preceding URI symptoms Multiple events on the day of presentation Sick exposures Foul-smelling urine |
Fever/hypothermia Lethargy Ill appearance Coryza Cough Wheeze Tachypnea |
NP swab for RSV, pertussis Chest radiograph CBC and blood culture Cerebrospinal fluid analysis and culture Urinalysis and culture |
| Neurologic |
Seizures Breath holding spells Congenital central hypoventilation syndrome Neuromuscular disorders Congenital malformations of the brain and brainstem Malignancy Intracranial hemorrhage |
Multiple events Loss of consciousness Change in tone Abnormal muscular movements Eye deviation Preceding triggers |
Papilledema Abnormal muscular movements Hypertonicity or flaccidity Abnormal reflexes Micro- or macrocephaly Dysmorphic features Signs of trauma or poisoning (see “Child maltreatment” below) |
EEG Neuroimaging |
| Respiratory/ENT |
Apnea of prematurity Apnea of infancy Periodic breathing Airway anomaly Aspiration Foreign body Obstructive sleep apnea |
Prematurity Foreign body Aspiration Noisy breathing |
Wheezing Stridor Crackles Rhonchi Tachypnea |
Chest radiograph Neck radiograph Laryngoscopy Bronchoscopy Esophagoscopy Polysomnography |
| Child maltreatment |
Nonaccidental head trauma Smothering Poisoning Factitious syndrome (formerly Munchausen syndrome) by proxy |
Multiple events Unexplained vomiting or irritability Recurrent BRUEs Historical discrepancies Family history of unexplained death, SIDS, or BRUEs Single witness of event Delay in seeking care |
Bruising (especially in a nonmobile child) Ear trauma, hemotympanum Acute abdomen Painful extremities Oral bleeding/trauma Frenulum tears Unexplained irritability Retinal hemorrhages Depressed mental status |
Skeletal survey Computed tomography/MRI of the head Dilated funduscopic examination if head imaging concerning for trauma Toxicology screen Social work evaluation |
| Cardiac |
Dysrhythmia (prolonged QT syndrome, Wolff-Parkinson-White syndrome) Cardiomyopathy Congenital heart disease Myocarditis |
Feeding difficulties Growth difficulties Diaphoresis Prematurity |
Abnormal heart rate/rhythm Murmur Decreased femoral pulses |
Four-extremity blood pressure Pre- and postductal oxygen saturation measurements ECG Echocardiogram Serum electrolytes, calcium, magnesium |
| Metabolic/genetic |
Hypoglycemia Inborn errors of metabolism Electrolyte abnormalities Genetic syndromes including those with craniofacial malformations |
Severe initial event Multiple events Event associated with period of stress or fasting Developmental delay Associated anomalies Growth difficulties Severe/frequent illnesses Family history of BRUE, consanguinity, seizure disorder, or SIDS |
Dysmorphic features Microcephaly Hepatomegaly |
Serum electrolytes; glucose, calcium, and magnesium levels Lactate Ammonia Pyruvate Urine organic and serum amino acids Newborn screen |
BRUE , Brief resolved unexplained event; ECG , electrocardiogram; EEG , electroencephalogram; ENT , ear, nose, and throat; GER , gastroesophageal reflux; GI , gastrointestinal; NP , nasopharyngeal; RSV , respiratory syncytial virus; SIDS , sudden infant death syndrome; URI , upper respiratory infection.
From Kliegman RK, Lye PS, Bordini BJ, et al: Nelson pediatric symptom-based diagnosis , Philadelphia, 2018, Elsevier. Table 5.3.
An appropriate history and physical examination are key to evaluating an infant who has experienced an acute event (Table 403.2 ). Attention should be given to characterizing the event and interpreting the subjective experience of the caregiver to provide an objective description. The following questions can guide this process:
Table 403.2
Important Historical Features of a BRUE
| PREEVENT | |
| Condition of child | Awake vs. asleep |
| Location of child | Prone vs. supine, flat or upright, in crib/car seat, with pillows, blankets |
| Activity | Feeding, crying, sleeping |
| EVENT | |
| Respiratory effort |
None, shallow, gasping, increased Duration of respiratory pauses |
| Color |
Pallor, red, cyanotic Peripheral, whole body, circumoral, lighting of room |
| Tone/movement |
Rigid, tonic-clonic, decreased, floppy Focal vs. diffuse Ability to suppress movements |
| Level of consciousness | Alert, interactive, sleepy, nonresponsive |
| Duration |
Time until normal breathing, normal tone, normal behavior Detailed history of caregiver actions during event to aid in defining time course |
| Associated symptoms | Vomiting, sputum production, blood in mouth/nose, eye rolling |
| POSTEVENT | |
| Condition |
Back to baseline, sleepy, postictal, crying If altered after event, duration of time until back to baseline |
| INTERVENTIONS | |
| What was performed | Gentle stimulation, blowing in face, mouth-to-mouth, cardiopulmonary resuscitation |
| Who performed intervention | Medical professional vs. caregiver |
| Response to intervention | Resolution of event vs. self-resolving |
| Duration of intervention | How long was intervention performed |
| MEDICAL HISTORY | |
| History of present illness | Preceding illnesses, fever, rash, irritability, sick contacts |
| Past medical history |
Prematurity, prenatal exposures, gestational age, birth trauma Noisy breathing since birth Any medical problems, prior medical conditions, prior hospitalizations Developmental delay Medications |
| Feeding history | Gagging, coughing with feeds, poor weight gain |
| Family history |
Neurologic problems Cardiac arrhythmias Sudden death, childhood deaths, BRUEs Neonatal problems Consanguinity |
| Social history |
Home situation Caregivers Smoke exposure Medications in the home |
BRUE , Brief resolved unexplained event.
From Kliegman RK, Lye PS, Bordini BJ, et al: Nelson pediatric symptom-based diagnosis , Philadelphia, 2018, Elsevier. Table 5.4.
What was the infant doing before, during, and after the event? An event occurring during or after feeding will likely have a different explanation than one occurring during sleep or after crying. The sequence of events can also be diagnostic. A breath holding spell begins with crying, followed by a period of apnea, perioral cyanosis, change of consciousness, and return to baseline.
Did the infant change color? It is often normal for infants to have blueish discoloration (perioral cyanosis or acrocyanosis ) around the lips or hands because of circulatory immaturity. Turning red or purple is also common when infants cry or become upset. The clinician's goal is to distinguish less concerning color change from central cyanosis , which is blue discoloration of the face, trunk, gums, or tongue that can indicate hypoxemia.
Did the infant experience central or obstructive apnea, or just choking or gagging? It is normal for infants to exhibit respiratory pauses of up to 20 sec while awake and asleep. These can reflect periodic breathing of the newborn or normal REM sleep. Much more concerning are periods of no air movement that last longer than 20 sec. Obstructive apnea results in paradoxical movement of the diaphragm and upper airway. In infants, this is most commonly caused by upper and lower respiratory tract infections (e.g., bronchiolitis) and may precede the recognition of symptoms typically seen in viral respiratory infections. Infants also commonly gag or choke briefly during or shortly after feeds or with GER or vomiting. The resulting reflexive pause in respiration to protect the airway is sometimes referred to as laryngospasm . Central apnea is always concerning and occurs when the brainstem does not properly control the respiratory muscles. This may be seen in brain trauma from non-accidental trauma and in rare disorders such as congenital central hypoventilation syndrome .
Was there a concerning change in muscle tone? Seizures in infants are concerning and difficult to diagnose, and they rarely present as typical seizure activity. They can present as staring spells, periods of episodic increased or decreased tone, or infantile spasms . It is normal for infants to have rapid jerking movements because of neurological immaturity and infant reflexes (e.g., Moro, startle, and fencing reflex), and sometimes these can appear similar to seizures. One of the most serious and time-sensitive causes of seizures or central apnea is undiagnosed brain trauma from non-accidental trauma, which may result in no other symptoms or physical examination findings upon presentation.
Was there an altered level of responsiveness? Episodic changes in consciousness and mental status can be difficult to assess in infants because of neurological immaturity and variability in sleep-wake cycles. However, abrupt changes where the infant appears to lose consciousness after episodes of apnea or color change can be concerning for hypoxemia, hypoglycemia, or seizures.
Did the event self-resolve, or was an intervention required? Infants with choking from GER, vomit, or feeding difficulties generally improve spontaneously or with help clearing the airway. A serious underlying cause is more likely if CPR was indicated and then provided, though this may be difficult to assess if no medically trained individuals witnessed the event.
A careful, detailed history can lead to an explanation; the key elements are summarized in Tables 403.1 and 403.2 . A clinician should inquire about other symptoms (e.g., fever, upper respiratory infection [URI] symptoms, spitting up). A history of breathing problems, prenatal or perinatal concerns, prematurity, and growth and developmental problems is important. Premature infants, particularly those still under 43 wk after correcting for gestational age, are at higher risk for underlying causes, such as apnea of prematurity. A careful feeding history can detect oropharyngeal dysphagia or GER-related problems (i.e., laryngospasm).
A targeted family history can reveal risk for sudden death, cardiac arrhythmias, and metabolic, genetic, and neurologic disease.
A social history, particularly by someone trained to detect non-accidental trauma, can reveal recent trauma, prior child welfare involvement, substance abuse, poisoning or misuse of medications, and environmental exposures (e.g., second-hand smoke and mold). It is important to understand who observed the event, who normally takes care of the infant, and if there are any discrepancies in the explanation of the event.
Consider infectious exposures. Infants exposed to underimmunized family members are at risk for pertussis. Respiratory syncytial virus (RSV) and other respiratory viruses, as well as pertussis, and can present with apnea prior to the onset of URI symptoms.
A careful physical examination may reveal a causative or underlying diagnosis. Abnormal growth and head circumference may reflect feeding, developmental, and neurological problems. Abnormal vital signs and pulse oximetry can suggest infectious, cardiac, and neurological abnormalities. A careful skin and mouth examination can reveal subtle signs. For example, child abuse should be suspected in infants with bruises, petechiae, or a torn frenulum. Signs of airway abnormalities, such as inspiratory or expiratory stridor or stertor, can lead to diagnosis of respiratory infections, vascular rings, hemangioma, laryngomalacia, tracheomalacia, or facial dysmorphism.
In the past, it was common for clinicians to routinely test infants presenting with such events using complete blood counts (CBC), appropriate cultures, and GER testing. However, it is known that these tests are unlikely to reveal a cause and even more likely to lead to a false positive result. False positives can, in turn, contribute to missed diagnoses, additional unnecessary testing, patient harm, greater parental concern, and increased costs.
In lower-risk infants, routine laboratory testing and diagnostic imaging (CBC, bacterial cultures, blood gas and glucose, metabolic panels, urinalysis, GER testing, chest radiograph, neuroimaging, electroencephalogram [EEG], sleep study) is not recommended. The few situations where testing may be considered in the lower-risk population include:
In higher-risk infants, routine screening tests may not be needed. Testing should be done due to concerns from the history and physical, or to further characterize repeat BRUEs.
Although the value of hospital admission is debatable, lower-risk infants are much less likely to benefit from admission compared to higher-risk infants. For all BRUEs, it is uncommon for a hospital admission to lead to a diagnosis of a serious underlying disorder. Sometimes, however, a longer period of observation than is practical in a clinic or emergency department can help characterize repeat events, should they recur, and reduce the uncertainty of a recurrent event for parents. Additional benefits of hospitalization include serial assessments of feeding, breathing, sleep, and social patterns. The decision for hospital admission should incorporate the needs and preferences of the family and patient, and the ability to follow-up closely with a primary care physician . In weighing the risks and benefits of this decision, it is important to recognize that hospitalization can unnecessarily increase stress for the family and patient through false alarms and iatrogenic complications. CPR education should be considered for all families. Home apnea monitoring should not be done. Close outpatient follow-up with a primary care physician is important to monitor for repeat events and caregiver support.