Risk Factors
The risk factors for ALTE are not as well defined as for SIDS, further complicating the diagnostic picture. One prospective study found increased risk of recurrent ALTE in infants presenting beyond 2 months of age, or with abnormal findings on physical examination.4 Another study identified prematurity, upper respiratory infection symptoms, and postconceptional age younger than 43 weeks to be associated with a higher likelihood of having a prolonged, significant bradycardic, apneic, or hypoxic event after presenting with ALTE.5 Premature infants who present with ALTEs are particularly concerning as they have unique and often dynamic pulmonary, cardiac, and central nervous system physiology which may require additional investigation.
Initial Evaluation
Many patients presenting with ALTE will have returned to their baseline healthy appearance by the time they arrive at the ED. If the physical examination reveals no clues to etiology of the event, the history may lead to the diagnosis—underscoring the need to take a thorough history.
The case history of an ALTE can be limited by a frightened and worried parent’s inability to accurately recall the event. It is important, therefore, to systematically review what was happening before, during, and after the event (eg, the temporal relationship to feeding, sleeping). Questions about color change, vomiting, limb and eye movements, breathing, and loss of consciousness can further help direct diagnostic efforts. It is therefore crucial to obtain a thorough prenatal, birth, and family history.6
Etiologies
Gastrointestinal
Gastroesophageal reflux disease (GERD) is the most commonly cited underlying cause of ALTE, and is diagnosed in 42% to 54% of cases.7,8 However, many diagnoses of GERD are made clinically, without the use of a pH probe or upper gastrointestinal series imaging. In fact, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition does not currently recommend invasive testing for GERD.9 Gastroesophageal reflux is a common condition, and even thought to be physiologic in infancy; moreover, some studies have failed to demonstrate a relation between apnea and reflux.10
Neurological
Two recent systematic reviews have found seizure to be the second most frequent diagnosis after ALTE, present in 11% to 30% of cases.7,8 In one study, 3.6% of ALTE patients were ultimately diagnosed with chronic epilepsy, with 47% of those diagnoses made within 1 week of the initial ALTE.11 Yet, electroencephalography (EEG) at the time of the ALTE presentation had only a 15% sensitivity for diagnosing chronic epilepsy.11 Despite this low sensitivity, EEG is a reasonable diagnostic tool in patients whose history is suggestive of seizure-like activity.
Respiratory
Problems of the respiratory tract may account for up to 20% of ALTEs.8 Obstructive sleep apnea has been described in infants, and may be idiopathic, the result of anatomic abnormalities, or associated with infections.8 Respiratory tract infections, including pertussis and respiratory syncytial virus (RSV), are diagnosed in 8% of ALTE cases.7 Respiratory syncytial virus causes apnea, particularly in premature infants, with a frequency of up to 20% in patients hospitalized due to this infection.7,12 The presence of upper respiratory infection (URI) symptoms, such as cough or rhinorrhea, in patients presenting with ALTE must be taken into consideration when deciding on further workup or disposition. One clinical prediction rule suggested the absence of URI as a predictor of ALTE patients requiring intervention and admission.13 However, a separate retrospective review found that infants presenting with symptoms of URI at the time of an ALTE were at an increased risk of a subsequent prolonged apneic, bradycardic, or significant desaturation event.5 These contradictory findings regarding URI symptoms highlight the importance of considering the entire clinical picture in determining the disposition of ALTE patients.
Infectious
Serious bacterial infection (SBI), such as meningitis, bacteremia or urinary tract infection (UTI), is a rare, but critical diagnosis in the infant with ALTE. One study of 182 well-appearing, afebrile infants younger than 61 days old who presented with ALTE found the rate of SBI to be 2.7% (5 patients).14 Of those five infants, three had positive bacterial blood cultures, one had a positive urine culture, and one had a positive pertussis polymerase chain reaction. There were no cases of meningitis or positive cerebrospinal fluid culture. Prematurity was a positive predictor of increased risk of SBI in these patients.14 A 2004 systematic review of 8 studies reported 1.1% of ALTE patients were diagnosed with UTI.7
Cardiac
Underlying cardiac disease is a less frequent cause of ALTE, with cardiac abnormalities detected in less than 5% of patients, and significant cardiac disease in less than 1%.15 Prematurity was associated with cardiac abnormalities and an electrocardiogram was 100% sensitive in detecting cardiac pathology.15