It is essential that a very thorough and detailed history is provided by a witness. We can assess the severity of the event and the underlying diagnosis by reviewing the patient's history. Caregivers may overestimate or underestimate the events because of their anxiousness after frightening events. The collected information should contain the following facts in Table 1^10,11).

Infants may have no signs or symptoms of significant illness after an ALTE. When infants with ALTE underwent physical examination by paramedics in the prehospital setting, 83% of the inants had no abnormal findings, 13.3% showed mild distress, and 3.3% showed moderate distress¹²⁾. Infants who had abnormal findings during the initial clinical examination after an ALTE were more likely to have either recurrent ALTE or a definitive diagnosis⁷⁾.

A physical examination should include the review of general appearance, vital signs, weight, height, and head circumference measurements. We need to be observant for neurological, respiratory, or cardiac abnormalities during the examination.

Further evaluation of the patient with an ALTE is determined on the basis of their initial history and physical examination. There is no standard workup protocol, and the clinician should decide on the appropriate investigations depending on the circumstances of each individual case. The diagnostic procedures for ALTE infants are summarized in Table 2^10,11), and it is only a guideline for clinicians to refer to.

Tieder et al.¹³⁾ demonstrated that tests for gastroesophageal reflux (GER), neurologic/hematologic/metabolic abnormalities, infections, ingestions of toxic materials, and cardiac dysrhythmias were the most frequently performed. In 2009, the Dutch Pediatric Association offered the first evidence-based consensus pathway for the diagnosis, management, and follow-up of children with an ALTE¹⁴⁾. They recommend initial diagnostic tests for ALTEs that include the following: complete blood cell count with differential count, C-reactive protein, serum glucose, arterial blood gas analysis, urine analysis, electrocardiography, and assessments for seasonal virus such as Bordetella pertussis and respiratory syncytial virus (RSV). These tests are relatively inexpensive, sensitive, specific, and easy to perform. However, there is large inter-hospital diversity for the care of ALTE, including the costs of care.

The most common diagnosis is GI disease, including GER. However, an important consideration is that half of all normal infants aged 0–3 months may have daily regurgitation, so caution should be exercised before concluding GER to be a final diagnosis of an ALTE^5,16). Upper GI series is neither sensitive nor specific¹⁷⁾. The gold standard used in the diagnosis of GER is the 24-hour esophageal pH test, because it can demonstrate an association between GER and ALTEs. In addition, the intraluminal impedance helps to identify nonacid gastric reflux. However, these tests for GER are uncomfortable for infants and relatively expensive. Therefore, routine GER testing is not recommended for all infants with an ALTE¹⁸⁾. GER tests should be considered for infants with: a history of frequent GER, an ALTE that occurs during or immediately after feeding, or gastric contents in their mouth of nose during an ALTE¹⁰⁾.

Seizure is the most common neurologic disorder associated with ALTEs. Although electroencephalography (EEG) is first choice investigation for seizure, the sensitivity of EEG for diagnosing epilepsy is only 15%. Only 3.6% of infants with an ALTE were diagnosed with chronic epilepsy and in 71% of ALTE cases, a recurrent ALTE occurred within 1 month¹⁹⁾. Thus, the use of EEG is considered for the evaluation of infants with recurrent ALTEs¹⁵⁾. If EEG recordings are nondiagnostic, repeated EEGs or analysis of clinical history is important for diagnosing seizure²⁰⁾. Neurologic imaging, including cranial computed tomography (CT), magnetic resonance imaging, diffusion weighted imaging, and ultrasonography can help to diagnose chronic epilepsy, but it has a low sensitivity⁴⁾.

One of notable cause of an ALTE is breath-holding spells, which typically have an emotional precipitant and usually occur while awake, and crying²¹⁾. A rare cause of ALTEs is congenital central hypoventilation syndrome which usually occurs during sleep.

Obstructive sleep apnea, in association with anatomical abnormalities, infections, allergies or medications can induce ALTEs. Obstructive sleep apnea frequently occurs in premature babies, and obstructions are usually developed at the laryngeal level²²⁾. One of the common respiratory causes of ALTEs is infection, especially bronchiolitis caused by RSV²³⁾. An recent study showed that the age-group at high risk for apnea is: <1 month for full-term babies, and <48 weeks after conception for preterm babies²⁴⁾. Pertussis has been also identified as a cause of ALTEs⁷⁾.

Cardiovascular problems are divided into 2 categories; structural heart disease and structurally normal hearts with arrhythmia, myocarditis, or cardiomyopathy. Electrocardiography is the important initial test for infants with an ALTE, and 24-hour continuous Holter monitoring can provide additional information for arrhythmias, such as long QT syndrome or paroxysmal tachycardia²⁵⁾.

ALTEs can be an initial presentation of metabolic disorders. Clinicians should suspect an inborn error of metabolism if a patient with an ALTE has: (1) an atypical age (>1 year), (2) a failure to thrive, developmental delay, or seizures, (3) a family history of ALTEs, seizure disorders or SIDS, (4) laboratory abnormalities such as hyperammonemia, hypoglycemia, metabolic acidosis, elevated liver enzymes, or abnormal hemostasispatient^10,15). Various metabolic abnormalities have been reported, including anomalies of mitochondrial fatty acid oxidation (medium chain acyl-CoA dehydrogenase deficiency), urea cycle defects (arginase deficiency), organic acidemias, and galactosemias^26,27). Serum chemistry tests, including tests for sodium, potassium, urea, calcium, magnesium, ammonia, lactate, and pyruvate are inexpensive and simple, or sole diagnostic tools in some cases. Hence, we recommend these tests for the initial evaluation of ALTE.

Among the several infectious causes of ALTE, the prevalence were reported to be about 9%–82% for bronchiolitis, 0%–10% for lower respiratory tract infection, 0%–7.6% for urinary tract infection, 0%–2.5% for bacteremia, and 0%–1.6% for meningitis^28,29,30,31).

One of most difficult and challenging diagnoses in infants with an ALTE is nonaccidental trauma. Although only less than 3% of ALTEs are related to child abuse²¹⁾, the mortality associated with child abuse is high³²⁾. A clinician should keep in view the possibility of child abuse such as shaken baby syndrome and Munchausen by proxy. Several factors that may suggest abuse are recurrent ALTEs: previous occurrences of SIDS, fresh blood in the nose or mouth, delay in seeking medical care, a confusing or changing history, and the need for vigorous resuscitation during events³³⁾. A funduscopic examination should be included in the initial examination for retinal hemorrhage, and covert video surveillance can be used in suspicious cases^34,35). Neurologic imaging, such as head CT can be used to identify head trauma, and should be considered for suspicious cases of abuse, to avoid unnecessary irradiation³⁴⁾.

A diagnosable cause cannot be found in 35%–50% of total ALTE cases, despite the availability of a medical history and complete evaluation^5,10,36). These cases are reported as idiopathic or unexplained ALTE.

One study found that 13.6% of ALTEs had a subsequent extreme event, 85% of which occurred within the first 24 hours of hospitalization³⁷⁾. In another prospective study, 12% of infants had recurrent episodes within 24 hours in hospital, 9% required moderate stimulation, and 3% required resuscitation³⁸⁾. In a Korean study, Choi and Kim³⁹⁾ found that repeated ALTEs occurred in 69% of in-hospital infants that have experienced an ALTE. Therefore, regardless of the cause of the ALTE, all infants with an ALTE should require hospitalization, continuous cardiorespiratory monitoring and evaluation within at least 24 hours. The admission rate for ALTEs is usually 75%–100%^33,36,37,40), which follows the recommendations of many centers. However, in some countries, the hospital charges cannot be ignored. Mittal et al.³⁶⁾ proposed a clinical decision rule and identified the risk factors for hospitalization: prematurity, cyanosis, abnormal findings at initial examination, and the absence of a history of choking and upper respiratory infection (URI) symptoms. Also, other studies suggested that the major indicators of admission and further evaluation were prematurity, an age <30 days or >60 days, history of combined underlying illnesses, multiple ALTEs occurring within 24 hours, and an abnormal result in the initial examination^7,33,40). In Korea, the economic burden of admission is relatively low, so we strongly recommend that all infants with an ALTE should be admitted within 24 hours.

Appropriate medical or surgical treatment should be conducted for a specific cause of an ALTE. If GER is diagnosed as cause of an ALTE, interventions for GER such as feeding management, antireflux drugs, and surgical intervention may resolve further events¹¹⁾.

It is also important to educate the families. All caregivers of infants with an ALTE should be informed about preventative and emergency management (such as standard cardiopulmonary resuscitation techniques) for further episodes¹⁰⁾. For prevention of an ALTE, safe sleep position (including the supine position, with the face free, in an adequately heated room) and avoiding exposure to tobacco smoke will be beneficial⁴¹⁾.

Cardiorespiratory monitors are the preferred devices for apnea monitoring. Although the effect of oxygen saturation monitoring alone is controversial, oxygen monitors have been used as an alternative to cardiorespiratory monitoring^42,43,44). Home cardiorespiratory monitors help to alert caregivers to apnea and bradycardia. However, there is no evidence that apnea monitoring can prevent SIDS after an ALTE. Routine monitoring of all infants with an ALTE is not generally recommended. Although there are no accepted criteria to determine which patient should be home monitored, some publications recommended home monitoring for infants with an idiopathic ALTE or those who needed vigorous resuscitation^42,45). Moreover, monitoring may be considered for infants with airway abnormalities (upper airway malformation or tracheostomy), idiopathic dysfunction of their respiratory center (CCHS), and chronic lung disease requiring oxygen supplementation and mechanical airway support^42,46).

During home monitoring, continuous medical, psychological, and technical support will be needed for infants with ALTE and their caregivers. Home monitoring is usually stopped after a 6-week event-free period. For a preterm infant, usually it may be discontinued after 46 weeks' postmenstrual age^42,46).

Recurrent ALTEs tend to occur during the first month after discharge^46,47). Kant et al.⁴⁸⁾ reported that the mortality rate after discharge was 1.1% (2 deaths/174 infants) during 34 months of follow-up, and 2 cases of death occurred within 15 days of discharge. The other study of ALTE recurrence showed that 71% of the infants with an initial ALTE revisited the hospital with a second event within 1 month. Therefore, infants with an ALTE should be followed up at least within a month after discharge.