OVERVIEW: What every practitioner needs to know.
An apparent life-threatening event (ALTE) was defined at a NIH Consensus Development Conference on Infantile Apnea and Home Monitoring in 1986. An ALTE is an episode that is frightening to the observer and that is characterized by some combination of apnea (central or occasionally obstructive), color change (usually cyanotic or pallid but occasionally erythematous or plethoric), marked change in muscle tone (usually marked limpness), choking, or gagging.
The key signs of an ALTE are in its definition: apnea, color change, and change in muscle tone. The descriptors are vague, however the concept is that an ALTE is described by the parents or other caretakers who have been “frightened” by the event. An ALTE is more of a “chief complaint” as opposed to a “diagnosis.”
The diagnosis of ALTE is best reserved for those infants in whom the clinical evaluation does not reveal an apparent cause of the event.
One must take care during the clinical evaluation of patients with ALTE that an identified potential cause of the event is the actual cause of the event. For example, the work-up could reveal gastroesophageal reflux (GER), which is a common finding in the same age group of infants presenting with ALTE, but that does not mean that GER was the cause of the event. Identifying an accurate cause and effect in ALTE is a challenge. Patients presenting repeatedly with recurrent ALTEs are more likely to end up with a causative diagnosis than are those infants with a one-time event.
There is no difference between an “apnea spell” and ALTE. One way to think of an ALTE is how a lay person would describe a witnessed apnea episode.
The terms apnea of infancy, pathologic apnea, and apnea of prematurity add to the confusion because the definitions are similar. Pathologic apnea is a respiratory pause that is prolonged (>20 seconds) or briefer episodes associated with bradycardia, cyanosis, pallor, or hypotonia.
With this definition, the only difference between an ALTE and pathologic apnea is the “frightened observer” in the former. However, one can argue that any parent would be frightened if their infant stopped breathing, changed color, and became limp.
Apnea of infancy is a term used when these events are unexplained and are occurring in infants of a gestational age of 37 weeks or greater. Apnea spells that occur in infants less than 37 weeks gestation are referred to as apnea of prematurity.
Before the “Back-to-Sleep” campaign dramatically decreased the incidence of sudden infant death syndrome (SIDS) and researchers discovered decreased serotonin levels in the medulla oblongota of SIDS victims, much of the focus was on infantile apnea.
This was first described in 1972 by Alfred Steinschneider in Pediatrics. He concluded that “these data support the hypothesis that prolonged apnea, a physiologic component of sleep, is part of the final pathway resulting in sudden death. It is suggested also, that infants at risk might be identified prior to the final tragic event.” Thus, “at risk” infants were identified: those with ALTE, subsequent SIDS siblings, premature infants with apnea, and drug-affected infants. This resulted in “at risk” infants frequently being studied with polysomnography and home monitors to “prevent SIDS.”
However, a 1986 study by David Southall did not demonstrate any significant differences between a cohort of infants who died of SIDS and normal controls. Later, after these recordings were digitized and analyzed by computer, it was found that the SIDS infants had less heart rate beat to beat variability and fewer apnea pauses than did the control infants. Additionally, despite the widespread use of home monitors during this 20-year era, there was no change in the incidence of SIDS.
The back to sleep campaign was launched in 1994 and SIDS research headed in a new direction. The final end to the apnea hypothesis came in 2001 when the results of the CHIME (Collaborative Home Infant Monitoring Evaluation) study were published in JAMA. One of their conclusions was that extreme events (apnea >30 seconds and associated with significant bradycardia) were not likely to be immediate precursors to SIDS.
The diagnosis of ALTE was meant to replace the term near-miss SIDS. In 1986 it was not known if an ALTE was a precursor to SIDS; the intent was to create some separation between these events and SIDS. In the late 1980s and early 1990s, when an ALTE was thought to be a potential precursor to SIDS, it was a popular diagnosis. The focus then was on preventing SIDS more than on discovering the underlying cause of the event. Today the focus is on finding the underlying cause of the episode and directing the clinical management to the cause. Despite the NIH defining ALTE in 1986, it was not given an ICD-9 diagnosis code until 2010. The current ICD-10 code for an ALTE is R68.13. Generally this diagnostic code is reserved for episodes that remain idiopathic after a diagnostic work-up and evaluation.
There are many conditions that can have an ALTE as part of their symptom complex. These include but are not limited to:
Upper and lower respiratory infections (especially respiratory syncytial virus)
Sepsis (e.g., secondary to UTI)
Gastroesophageal Reflux (GER)
Cardiac causes: Breath holding spells
Congenital cardiac disease
Head or other bodily trauma
Munchausen syndrome by proxy
Metabolic syndromes (MCAD deficiency, etc.)
Apnea of infancy or prematurity
Breath holding spells
Because of this extensive differential, the work-up must be guided by the history and physical findings. Despite the long list of diagnostic possibilities, more than half of patients presenting with ALTE remain idiopathic after the history, physical examination, and diagnostic evaluation.
Often it is not clear if the ALTE was actually caused by the findings from the clinical evaluation. For example, GER is very common in the same age group of infants presenting with ALTEs. If the evaluation of the ALTE results in the finding of GER, one cannot be certain that the cause of the ALTE was the GER.
Studies of GER have shown no significant correlation between apnea and GER episodes. Other studies have shown apnea preceding the GER. In contrast, studies on the causes of ALTEs have reported that more than half of ALTEs are due to GER. These studies are retrospective with no control group. It could be possible that 50% of all infants presenting to the emergency department have GER.
Cause and effect is frequently in doubt when assessing an ALTE. Most infants are not going to have recurrent ALTEs. For the infant who receives a diagnosis and/or intervention, and then has no further spells, it is not clear if the diagnosis was accurate and treatment successful or if the infant was just not destined to have any further events.
Sometimes the episode can be explained as a variation of normal or as an expected response to an event. These are generally one-time events and do not recur. An example is what has been referred to as “car seat spells.” Young infants who are not fitted properly to their car seat can have airway instability leading to an obstructive apnea in the infant seat. Another expected response is when an infant regurgitates milk; they stop breathing until the airway clears.
Respiratory syncytial virus and ALTE:
Young infants (generally less than 1 month) and those who are born preterm are more likely to exhibit apnea when infected with respiratory syncytial virus (RSV). Some of these RSV-infected infants will present with apnea as their sole symptom. RSV is the most common infection presenting as an ALTE.
Other infections and ALTE:
Most other infectious causes of ALTE are obvious from the history and physical findings. They include bronchiolitis, croup, pertussis, pneumonia, sepsis, and meningitis. However, urinary tract infection (UTI) may not be obvious, and some have suggested that assessment for UTI is a useful diagnostic evaluation in ALTE. Others have suggested obtaining a chest radiograph, even with no signs or symptoms consistent with pneumonia. However, most cases (>80%) of pneumonia will be obvious on the history and physical examination, and there is a concern that those cases identified only by chest radiography may be an “over reading” of the study.
Gastroesophageal Reflux (GER) and ALTE:
GER has been reported to be the most frequent cause of ALTE. However, multiple studies have not demonstrated a correlation between GER episodes and ALTEs or apneas. Both occur in the same age group of infants and both are less likely to occur as the infant ages.
The relationship between GER and apnea is complex. Both acid and non-acid reflux have been implicated as a cause of apnea. Apnea may precede the GER, as opposed to ensuing after GER. Reflux into the distal esophagus may have different effects than reflux into the proximal esophagus.
GER is also difficult to diagnose, and it is not clear when it is pathologic and when it is a normal physiologic phenomenon. Diagnostic tests include pH probe studies, modified barium swallow studies, multiple intraluminal impedance, and others. Despite numerous studies, no causal link has been demonstrated. Thus, it is generally not recommended to obtain further reflux testing. In infants with frequent reflux with an ALTE observed immediately after feeding, then testing can be considered.
Child abuse and ALTE:
There are several ways in which child abuse can present as an ALTE. In non-accidental trauma, infants with an acute injury—that is, head trauma—can present symptomatically as an ALTE. Identification of child abuse in infants presenting with an ALTE can be difficult.
One study found that 4% of ALTEs were explained by child abuse, and all cases were suspected after the history and physical examination. Neuroimaging, ophthalmologic examination, and a skeletal survey were all helpful in confirming the diagnosis. In contrast, however, another study found that 54/471 (11%) patients with ALTE were ultimately diagnosed with child abuse, but only two of these cases were diagnosed during the first admission.
Parents and others inflicting repeated injury on an infant may also bring the infant to medical attention describing an ALTE. Roy Meadow, who described Munchausen syndrome by proxy, found that 24 of 27 infants who had been suffocated by their mothers were initially seen by physicians for ALTE. In none of the cases had a cause been identified for the attacks. David Southall also documented suffocation and other injuries occurring in the hospital, through the use of covert video surveillance, in infants admitted for ALTE.
The American Academy of Pediatrics (AAP) Committee on Child Abuse and Neglect, in their clinical report on distinguishing SIDS from child abuse fatalities, noted that a clue to intentional suffocation could be recurrent ALTEs occurring while the child was in the care of the same person.
When taking the history, recurrent ALTE, previous SIDS victims in the family or SIDS deaths occurring at a late age, delay in seeking care, suspicious injuries in other children, a confusing history that is not consistent over time or is inconsistent with the findings can point to non-accidental trauma as being the cause of an ALTE.
Physical findings such as fresh blood around the nose or mouth, bruising, an abnormal neurologic examination, and unusual pattern of injuries also indicate non-accidental trauma.
Seizures and ALTE:
Seizures as a cause of ALTE can be very difficult to diagnose. In young infants, seizures frequently present atypically and findings may be subtle. Infants with seizures presenting as ALTEs will generally present with recurrent ALTE. Prolonged electroencephalographic monitoring with video may be needed to confirm the diagnosis. A routine electroencephalogram (EEG) may be normal if the patient does not have a seizure during the study. Long-term studies have also shown that inpatient admission with EEG monitoring did not help to establish a diagnosis or change outcomes. Seizures not uncommonly present with apnea and desaturation without associated bradycardia (there may even be tachycardia).
The first step in the evaluation of an infant presenting with an ALTE is to take a thorough history. The important questions to ask are:
What was the baby doing? (sleeping, eating, crying)
Who witnessed the event? (try to get the history directly from that person)
When did the event happen?
How long did it last?
Any color changes? (blue, red, pale)
Other associated behaviors? (choking, stiffening, floppy, vomiting, eye deviation)
Did the baby seem to lose consciousness?
Did the baby experience any trauma?
Has it happened before?
How did it resolve? Did you have to do anything to get the episode to stop?
How quickly did the infant recover?
How was the infant acting in general on the day of the event?
How has the infant been acting after the event?
What medications has the infant received (including supplements and over the counter medications) in the last 24 hours?
What is the infant’s birth history and gestational age?
Is the infant healthy at baseline?
Has anyone else in the family ever had an episode like this?
Since the differential diagnosis is long, the physical examination needs to be very thorough and complete, including the monitoring of all vital signs and pulse oxygen saturation. The neurologic examination should focus on the infant’s level of alertness and activity. Look for any focal neurologic signs that could be an indicator of an intracranial bleed or subdural hemorrhage.
Look for signs of injury, for example, bruises and swelling. If child abuse is suspected, an ophthalmologic examination should be done under dilation to look for retinal hemorrhage.
Respiratory examination should evaluate for upper or lower respiratory infection, stridor, or other signs airway obstruction. Cardiac examination should assess pulses and listen for murmurs.
A detailed history can be the key to determining the cause of the ALTE and to assess its significance. Try to obtain information that is as accurate as possible. If the parents tell you the event lasted 2 minutes, say to them, “Let’s say the event started right now. Tell me when it was over.” During this time look at a clock. Frequently you will find the event lasted only 10-15 seconds using this technique.
If they say they had to do cardiopulmonary resuscitation (CPR) to resolve the event, ask specific questions to determine what they actually did. If the infant turned blue, ask specifically where they saw the blueness to determine if it was central cyanosis or acrocyanosis.
There are no laboratory studies to be done specifically for the diagnosis of ALTE. The laboratory studies should be guided by the history and physical findings. For example, if you suspect an infectious cause, order a complete blood count with differential, RSV nasal wash, blood culture, urine culture, and CSF analysis and culture. For a possible seizure, evaluating for meningitis along with an EEG and head imaging may be indicated.
Really, no specific studies to order for ALTE?
In one study, when there were no clues from the history and physical examination, diagnostic studies were rarely helpful (<5%) in identifying a cause.
There are no specific imaging studies to be done specifically for the diagnosis of ALTE. The studies obtained should be guided by the history and physical findings.
Some authors have suggested that a chest radiograph should be routinely obtained in these infants. However, the diagnostic yield is low, especially when no other symptoms are present.
If child abuse is suspected, neuroimaging and a skeletal survey may be helpful in the evaluation of the abused child.
There are no evidence-based clinical algorithms for the evaluation of infants with ALTE. Almost all studies on ALTE are retrospective reviews, which do not give us good evidence-based approaches to this condition.
Immediate treatment should be based on the patient’s condition on presentation. Most infants will appear normal by the time they are seen by a provider; however, based on the underlying cause the infant may not have fully recovered or may be having recurrent events at the time of presentation.
Emergency interventions should be performed as indicated. After the patient has been stabilized (if needed), there is no specific treatment for an infant with an ALTE, although if an underlying cause is discovered, treatment should be directed specifically at that condition.
A decision must be made about the need for hospitalization. This can be for a period of observation or to complete a diagnostic evaluation that cannot be completed in the ambulatory setting. Some authors recommend admission for all infants experiencing an ALTE; however in the current era with increased concern regarding use of resources, a judgment needs to be made about the value of hospitalization.
There is no clear evidence supporting the value of hospitalization and cardiorespiratory monitoring. If the infant is admitted and monitored, there is no consensus about how long the period of monitoring should be to look for recurrent events. General factors to consider regarding hospitalization include:
Severity of the event
Single or recurrent event
Age of the infant (<1 month of age should probably be admitted)
Anxiety level of the parents
Suspicion of an underlying event that could lead to further or worsening events (e.g., RSV infection)
Baseline health of infant
It is important to remain calm and reassure the family when appropriate. Many parents still view an ALTE as a “near-SIDS” event. Parents fear SIDS, and for good reason. There is no test that can be done to screen for SIDS, and there is no warning before its occurrence.
Counseling should be aimed at explaining to families that the approach to their infant is to determine an underlying cause of the event. ALTEs by themselves are rarely life-threatening, unless the underlying cause is life-threatening, for example, bacterial sepsis.
When is a home monitor indicated?
Home monitors alert parents to bradycardia and apneic events. No evidence exists to show that the use of a home monitor can prevent SIDS or ALTEs. However, home monitors may be useful if the infant is premature or if the infant has some form of lung disease or unstable airways. Premature infants are more likely to have recurrent ALTEs and home monitors may help to alert parents to an event.
Most infants will not have another ALTE. Infants with recurrent ALTEs are more likely to have an underlying diagnosis identified as a cause of the events. The reverse is also true: An infant with an underlying condition associated with apneic events is more likely to experience recurrent ALTEs.
The focus should be on finding the underlying cause of the ALTE and reassuring the parents that these events are not precursors to SIDS.
ALTE is not a single, specific disease entity. (See the diseases/conditions that share these symptoms above.) Frequently, however, despite a thorough investigation, no underlying cause will be identified. This group of infants rarely have recurrent events. There is no seasonal variability, other than the seasonality of some of the conditions that can present with apnea, for example, RSV infection. There is no genetic predisposition for ALTE. However, because by definition ALTEs are frightening to the observer, parents may be over vigilant and overreact to relatively minor events in subsequent infants.
The only complications that may occur from an ALTE are the expected outcomes for the underlying conditions that present as an ALTE.
ALTEs cannot be prevented.
“Infantile apnea and home monitoring. Natl Inst Health Consens Dev Conf Consens Statement”. vol. 6. 1986. pp. 1-10. (This publication is the result of a NIH-sponsored consensus development conference on infantile apnea and home monitoring. The main focus of this conference was to review neonatal and infant apnea and their relation to mortality, especially SIDS, and to review the efficacy, safety, and effectiveness of home monitors in detecting apnea and reducing mortality. It included definitions for ALTEs and apnea.)
Steinschneider, A. “Prolonged apnea and the sudden infant death syndrome: clinical and laboratory observations”. Pediatrics. vol. 50. 1972. pp. 646-54. (This publication was referred to by Jerold Lucey, MD (editor of Pediatrics) as the paper that started the "whole apnea home monitoring to prevent SIDS movement." Steinschneider concluded that prolonged apnea is part of the final pathway resulting in sudden death and that infants at risk might be identified before the event. However, 5 of the patients were from 1 family, and 20 years later their mother [Waneta Hoyt] admitted killing them.)
Ramanathan, R, Corwin, MJ, Hunt, CE. “Cardiorespiratory events recorded on home monitors: comparison of healthy infants with those at increased risk for SIDS”. JAMA. vol. 285. 2001. pp. 2199-207. (Also known as the CHIME [Collaborative Home Infant Monitoring Evaluation] study. This was the first real comparison between high-risk SIDS infants (ALTE, SIDS siblings, preterm infants) and healthy term infants being monitored on on home cardiorespiratory monitors. Extreme events were more common in the preterm group only, and the timing of their occurrence suggested that these events were not precursors to SIDS. Even the term control infants in this study had extreme events [>30 seconds of apnea associated with bradycardia.])
“Task Force on Sudden Infant Death Syndrome. American Academy of Pediatrics. SIDS and Other Sleep-Related Infant Deaths: Expansion of Recommendations for a Safe Infant Sleeping Environment”. Pediatrics. 2011. pp. 128(This is the AAP’s current policy statement on the topic. This statement was reaffirmed in April of 2015.)
Bruhn, FW, Mokrohisky, ST, McIntosh, K. “Apnea associated with respiratory syncytial virus infection in young infants”. J. vol. 90. Pediatr 1977. pp. 382-6. (A good retrospective review of 274 infants less than 6 months of age who were hospitalized with RSV infection looking at the incidence of apnea and predisposing factors for apnea.)
Brand, DA, Altman, RL, Purtill, K. “Yield of diagnostic testing in infants who have had an apparent life-threatening event”. Pediatrics. vol. 115. 2005. pp. 885-93. (This article is a retrospective review of the usefulness of various diagnostic tests in 243 infants presenting with ALTE. Seventy percent of infants were diagnosed by history and physical examination alone or with diagnostic tests that confirmed the findings on the history and physical examination. Fourteen percent were diagnosed by tests alone, and 82% (27/33) of infants in this category were given the diagnosis of GER from either pH probe or upper gastrointestinal series. Sixteen percent had no diagnosis after history and physical examination and testing. Overall, when the history and physical examination were noncontributory, diagnostic testing was contributory in only 3.3% of cases.)
Arad-Cohen, N, Cohen, A, Tirosh, E. “The relationship between gastroesophageal reflux and apnea in infants”. J Pediatr. vol. 137. 2000. pp. 321-6. (This article is an evaluation of 67 infants less than 6 months of age who had an ALTE. They specifically focused on the 21 infants who had apnea and reflux diagnosed by pH monitoring. There was no correlation with reflux in 81% of the apneic episodes. In those with a correlation, apnea preceded the reflux in 94%.)
Meadow, R. “Suffocation, recurrent apnea, and sudden infant death”. J Pediatr. vol. 117. 1990. pp. 351-7. (This article describes how difficult it is to recognize suffocation by a parent. Most of these infants had presented recurrently with an ALTE. Although direct injury to the child in Munchausen syndrome by proxy is not common, it can present in this fashion.)
Southall, DP, Plunkett, MC, Banks, MW. “Covert video recordings of life-threatening child abuse: lessons for child protection”. Pediatrics. vol. 100. 1997. pp. 735-60. (This is a classic article describing the documentation of life-threatening child abuse occurring during the hospitalization of infants. Thirty-six of 39 infants had been admitted for the evaluation of an ALTE.)
Hymel, KP. “Committee on Child Abuse and Neglect; National Association of Medical Examiners. Distinguishing sudden infant death syndrome from child abuse fatalities”. Pediatrics. vol. 118. 2006. pp. 421-7. (An excellent clinical report from the AAP on this subject. Recurrent ALTEs are noted to be a clue to suffocation by a parent or caretaker.)
Vellody, K, Freeto, JP, Gage, SL. “Clues that aid in the diagnosis of nonaccidental trauma presenting as an apparent life-threatening event”. Clin Pediatr. vol. 47. 2008. pp. 912-8. (Four of 108 cases of ALTE were diagnosed as nonaccidental trauma. All four cases had clues from the history and physical examination, and all had diagnostic testing that confirmed the diagnosis.)
Bonkowsky, JL, Guenther, E, Filloux, FM. “Death, child abuse, and adverse neurological outcome of infants after an apparent life-threatening event”. Pediatrics. vol. 122. 2008. pp. 125-31. (Another retrospective study of the outcome of ALTE admissions. Their study population excluded patients with preexisting conditions that could cause an ALTE and patients in whom a causative diagnosis was obvious. Thus their 471 cases were for the most part idiopathic ALTEs. Fifty-four of 471 [11%] patients were ultimately diagnosed with child abuse. There were no cases of SIDS in these 471 patients. Seventeen of 471 patients were ultimately diagnosed with epilepsy.)
Altman, RL, Brand, DA. “Infections and apparent life-threatening events”. Clin Pediatr. vol. 47. 2008. pp. 372-8. (Another retrospective review by Brand [see reference above] that looked at 95 patients presenting with ALTE who had infectious causes for their events.)
Goldberg, S, Schwartz, S, Picard, E. “Do all infants with apparent life-threatening events need to be admitted”. Pediatrics. vol. 119. 2007. pp. 679-83. (A good attempt to develop criteria for which patients with ALTE need to be admitted. They concluded that infants more than 30 days old, who have experienced a single ALTE, may be discharged from the emergency department.)
Al-Kindy, HA, Gelinas, JF, Hatzakis, G. “Risk factors for extreme events in infants hospitalized for apparent life-threatening events”. J Pediatr. vol. 154. 2009. pp. 332-7. (Another paper that helps sort through who should be admitted and who is at risk for recurrent extreme events. The highest risk groups were those with upper respiratory tract infection, those born preterm, and infants <43 weeks postconceptional age.)
Tieder, JS, Cowan, CA, Garrison, MM. “Variation in inpatient resource utilization and management of apparent life-threatening events”. J Pediatr. vol. 152. 2008. pp. 629-35. (This article reviews 12,067 cases of ALTE and shows the marked variation in length of stay, use of diagnostic tests, and medications in infants with ALTE across U.S. Children's Hospitals.)
MCGovern, MC, Smith, MB. “Causes of apparent life-threatening events in infants: a systematic review”. Arch Dis Child. vol. 89. 2004. pp. 1043-8. (A good review of 8 studies on ALTE. The authors attempt to develop an algorithm for the management of ALTE.)
Farrell, PA, Winer, GM, Lemons, JA. “SIDS, ALTE, apnea, and the use of home monitors”. Pediatr Rev. vol. 23. 2002. pp. 3-9. (A good review of this topic and an excellent preparation for any board questions on this subject.)
Spitzer, AR, Clark, RH. “Putting reflux to rest”. J Pediatr. vol. 165. 2014. pp. 225-6. (An editorial commenting on an article in the same issue that speaks against a role for gastroesophageal reflux in ALTEs.)
DeWolfe, CC. “Apparent life-threatening event: a review”. Pediatr Clin North Am. vol. 52. 2005. pp. 1127-46. (Another good review article on ALTE. This author also attempts to develop an algorithmic approach to infants with ALTE.)
Kahn, A. “Recommended clinical evaluation of infants with an apparent life-threatening event. Consensus document of the European Society for the Study and Prevention of Infant Death, 2003”. Eur J Pediatr. vol. 163. 2004. pp. 108-15. (Another good review and consensus statement regarding ALTE from the European pediatric community.)
Tieder, JS. “Management of Apparent Life-Threatening Events in Infants: A systematic Review”. The Journal of Pediatrics. vol. 163. 2013. pp. 94-99. (Another good review that details the existing evidence.)
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