Differential diagnosis of a brief resolved unexplained event (BRUE) in an infant

Cause	Comments	Evaluation for low-risk infants*	Further evaluation in selected infants
Normal (misinterpreted as abnormal behavior)
Transient choke, gag, or cough during feeding or during an episode of regurgitation	Suggests laryngospasm. Does not necessarily mean abnormal degree of GER or that treatment of GER will prevent similar events in the future.	History is sufficient in low-risk infants*.	Swallowing evaluation if recurrent events. Possible evaluation for pathologic GER, but results are rarely conclusive.
Periodic breathing or respiratory pauses	Pauses of 5 to 15 seconds are normal, with longer pauses after a sigh.	History, PE with spot pulse oximetry.	Observation, possible polysomnography.
Infectious disease
Respiratory infections (pertussis, RSV, bronchiolitis)	Somewhat common cause of apneic episodes in infants who are premature or <2 months.	History, PE. Optional testing for pertussis or RSV in infants with respiratory symptoms.	Respiratory virus testing panel (including RSV). Pertussis testing – If suggestive symptoms, incomplete immunization, or outbreak.
Sepsis, meningitis, encephalitis, pneumonia, UTI	Usually have other symptoms and/or multiple BRUE. Isolated UTI causes <3% of BRUE.	History, PE.	Evaluation as indicated by clinical symptoms; may include cultures of urine, blood, and cerebrospinal fluid, and chest radiography.
Child abuse
Intentional suffocation, abusive head trauma, intentional poisoning, or medical child abuse	Reported in 0.5 to 11% of infants with BRUE.	Focused history for social risk factors; PE for any signs of abuse.	Neuroimaging, skeletal series, toxicology screen, dilated eye examination for retinal hemorrhage.
Gastrointestinal
GER or swallowing dysfunction	Physiologic GER can cause laryngospasm and BRUE in healthy infants and is usually benign.	History, PE, observe feeding.	Evaluation by a feeding specialist; may include VFSS. Rarely indicated – Esophageal pH or impedance monitoring.
Anatomic and functional abnormalities	Many causes; refer to UpToDate content on aspiration due to swallowing dysfunction.	History, PE, observe feeding.	As above.
Neurologic disease
Epilepsy Structural brain abnormalities Neuromuscular disorders	Clues to consider epilepsy include recurrent events with loss of muscle tone and unresponsiveness, sustained or stereotyped events. Epilepsy is ultimately diagnosed in approximately 10% of infants with BRUE, but testing has low sensitivity.	Routine testing not warranted.	Observation, neuroimaging, EEG, and/or polysomnography with expanded EEG montage.
Cardiopulmonary
Central or obstructive apnea	Uncommon in infants who are not premature and who are >60 days old. More common in infants with syndromic features or neuromuscular disorders. Causes of central apnea include brain injury (eg, from abusive head trauma or infection), brain malformations, or a disorder of ventilatory control (very rare).	PE with spot pulse oximetry.	Observation, continuous pulse oximetry; possible polysomnography.
Airway obstruction or abnormality	Eg, due to choanal atresia, vocal cord dysfunction, laryngotracheomalacia, TEF, or vascular ring.	History, PE.	Evaluation as indicated by respiratory symptoms (refer to UpToDate topics on stridor and congenital abnormalities of the intrathoracic airways).
Arrhythmias or congenital heart disease	Clues include cyanotic episodes; family history of sudden unexplained death <35 years or BRUE in a sibling.	PE with spot pulse oximetry. ECG optional.	ECG, cardiology evaluation.
Metabolic disease
Inborn error of metabolism	Rare; diverse manifestations including apnea, vomiting, lethargy, and altered sensorium, often in recurrent or cyclic patterns. These episodes may be triggered by fasting or an intercurrent illness. Metabolic acidosis or hypoglycemia warrants a detailed evaluation.	History, PE, family history for metabolic disease or unexplained death; review newborn screening results.	Laboratory testing including glucose, electrolytes, BUN, creatinine, lactic acid, and ammonia. Further testing for metabolic disorders may include liver enzymes, urine organic acids, plasma amino acids, and acylcarnitines (refer to UpToDate topic reviews on inborn errors of metabolism and hypoglycemia in infants).
Other
Acute gastrointestinal obstruction (intussusception, volvulus)	Suggested by vomiting, abdominal distention, bloody stools, and/or lethargy.	History, PE.	Abdominal ultrasound and/or plain radiographs.
Toxic ingestion (eg, medications such as hypoglycemic agents or sedatives) or ethanol; carbon monoxide poisoning	Often associated with altered sensorium, respiratory depression, or vomiting.	History, PE.	Toxicology screen and/or specific testing.
Disorder of central respiratory control (eg, CCHS)	Very rare; typically present with cyanosis at rest or during sleep, with no respiratory distress.	History, PE.	Pulse oximetry during sleep; blood gas (refer to UpToDate topic on CCHS).

BRUE: brief resolved unexplained event; GER: gastroesophageal reflux; PE: physical examination; RSV: respiratory syncytial virus; UTI: urinary tract infection; VFSS: videofluoroscopic swallow; CNS: central nervous system; EEG: electroencephalogram; TEF: tracheoesophageal fistula; ECG: electrocardiogram; BUN: blood urea nitrogen; CCHS: congenital central hypoventilation syndrome.
* Low-risk infants are those who are >60 days old and not premature; have experienced only one BRUE (no prior BRUE and no clusters), which lasted <1 minute; no cardiopulmonary resuscitation by a trained provider was performed; and no concerning features on history or PE.

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Differential diagnosis of a brief resolved unexplained event (BRUE) in an infant