ALTE: A Four-Letter Word?

Case

An emergency medical services (EMS) telemetry call notified the ED of an 8-week-old infant who had turned blue during a choking and coughing episode at home. While en route to the ED, the EMS technicians stated that the infant was currently appearing well, with the following vital signs: heart rate, 122 beats/minute; respiratory rate, 30 breaths/minute; and blood pressure, 90/54 mm Hg. They also noted that the infant’s oxygen saturation was 100% on room air. At the time of the call, the patient’s estimated time to arrival at the ED was 5 minutes.

When the patient arrived at the ED, followed by his tearful mother, the emergency physician (EP) noted that the infant was alert and in no acute distress. The patient was triaged and placed on a cardiorespiratory monitor while the EP spoke with his mother. The infant’s mother stated that the event occurred approximately 15 minutes after she had finished breastfeeding the patient and had placed him on his back in his crib. She said that she had heard her son making choking and gurgling sounds and had gone back to his room to check on him, whereupon she noticed that his face had turned purple. She further noted that when she picked her son up, he was limp and did not seem to be breathing. She immediately shouted for her husband to call EMS while she “blew air into his mouth.” After about 10 seconds, she said her infant responded and seemed to be back to his normal self by the time EMS arrived.

With respect to history, the mother reported her son was born via normal vaginal delivery at 39 weeks gestation and that there were no complications during pregnancy or delivery. After the standard 48-hour inpatient stay, both mother and patient were discharged home together and had been doing well up until the time of the incident.

The patient, who was up to date on his routine preventive pediatric-care visits, was in the 85^th percentile for height, weight, and head circumference. Regarding his feeding routine, the patient was exclusively breastfed and, according to his mother, he tolerated his feedings well and did not typically spit-up afterward. The patient was not taking any medications. He resided at home with both his mother and father and did not attend daycare.

The physical examination showed a well-appearing 8-week-old boy, who acted appropriately for his age and was breathing comfortably on room air. His temperature at presentation was 98.4˚F, and his mother reported no history of fever. The patient’s fontanel was soft and flat, his lungs were clear on auscultation, and he had no murmurs. The abdomen was soft and without mass or hepatosplenomegaly. There were no rashes, bruises, or birthmarks.

After the examination, the patient’s mother, who was understandably distressed, asked the EP if she could breastfeed her son. As the EP prepared to answer this question, several questions came to mind: (1) Is this an apparent life-threatening event (ALTE)? (2) Is there a way to stratify this child’s risk for coexistent serious illnesses? (3) Will this patient be cleared for discharge from the ED today? (4) What tests should be ordered during his stay in the ED?

Overview

Few pediatric diagnoses result in as much consternation and uncertainty as the nebulous ALTE. The term was established to describe a spectrum of symptoms with a great number of possible underlying etiologies, and its definition leaves much room for interpretation. According to the 1986 National Institutes of Health Consensus Development Conference on Infantile Apnea and Home Monitoring, an ALTE is “an episode that is frightening to the observer, that is characterized by some combination of apnea (centrally 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. In some cases, the observer feels that the infant has died.”¹

Parents, as well as some providers, may have misconceptions about the relation of ALTE to sudden infant death syndrome (SIDS). While ALTEs were previously considered to be “near-miss SIDS” or “aborted crib death,” fewer than 8% of SIDS patients have a history of ALTE prior to death.² Additionally, rates of ALTE peak before 2 months of age, whereas SIDS rates are highest between 2 and 4 months of life.³  

Apparent life-threatening events are less prevalent in preterm patients compared to their full-term counterparts—though most study cohorts are comprised of full-term infants. When ALTEs, however, do occur in preterm infants, EPs should have a higher index of suspicion for an undiagnosed medical etiology associated with the patient’s prematurity—one that may potentially place the patient at an increased risk for SIDS (eg, limited pulmonary functional residual capacitance, hypoxic ischemic encephalopathy leading to seizure disorder).

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

Metabolic

Although in-born errors of metabolism are uncommon diagnoses, they must be considered as a cause of ALTE in the appropriate clinical context as they are reported in 1.5% to 7.7% of ALTE patients.⁷ Clinical clues suggesting an inborn error of metabolism include poor weight gain, unusual body odors (eg, of urine or sweat), symptom onset with institution of formula or diet change (eg, protein introduction), metabolic acidosis, hypoglycemia, thrombocytopenia, and neutropenia. Any of these clinical clues can point the practitioner toward a metabolic workup.

Nontraumatic Injury

The EP must always be watchful for signs of nonaccidental trauma in pediatric patients, as abusive head injury is diagnosed in 1% to 3% of ALTE case presentations.^6,16 A retrospective review found vomiting, irritability, and a documented 911 call to be risk factors associated with increased likelihood of abusive head trauma.¹⁶ Again, a thorough history and physical examination is prudent in all ALTE patients, and close attention should be paid to inconsistent or poorly explained histories and findings such as bruising or burns. Fictitious illness has also been documented in cases of ALTE in less than 3% of all cases, and should be considered especially in cases of repeated ALTEs witnessed by the same caregiver.⁷

Hematologic and Idiopathic

Almost a quarter of patients presenting with ALTE are found to have low hemoglobin for their respective age, with higher rates of anemia in patients with repeat ALTEs.⁶ However, there is no clear causative effect between anemia and ALTE. Moreover, in 25% to 50% of ALTE cases, there is no clear diagnosis and therefore the cause is considered idiopathic in nature.^7,8

Workup

While there is no standardized workup for ALTE, a careful history and physical examination should help guide diagnostic testing ordered in the ED. A retrospective study of 243 patients found that in 49%, the history and physical examination suggested an etiology that was confirmed by diagnostic testing (eg, a patient presenting with wheezing and rhinorrhea, who has a positive RSV antigen).¹⁷ Another 21% of patients were diagnosed solely on history and physical examination findings. While these patients may have had diagnostic tests performed, the tests did not contribute to the final diagnosis. In this study cohort, a final diagnosis was made by positive diagnostic tests alone in only 14% of patients with both nonspecific histories and physical examination findings. As previously mentioned, these findings underscore  the critical role that history and physical examination play in the diagnosis of ALTE.

As no obvious pathology is found in up to half of all ALTE cases, the EP must decide which tests will most likely be of diagnostic utility. Diagnostic tests are ordered in a majority of patients¹⁸ and a chest X-ray is one of the most frequently positive tests.^4,19

A positive test, however, does not necessarily lead to a diagnosis for the etiology of the ALTE. Only approximately one-third of the positive tests in the previously cited study were determined to contribute to the final diagnosis.¹⁷ The list of possible diagnostic tests for ALTE patients is lengthy and, at times, invasive. For this reason, EPs should perform focused testing based on the concerning elements in the history and physical examination rather than order a set of specific screening labs for each infant.

Need for Admission

Disposition is often a difficult decision in treating ALTE patients (and their families). Infants often look well and are acting normally by the time they arrive in the ED and remain well-appearing throughout the ED stay. If a thorough history, physical examination, and focused diagnostic testing uncover no specific etiology, the EP must decide whether to admit the patient for observation or discharge him or her home with instructions for pediatric follow up.

The majority of patients presenting to the ED with ALTE are admitted to inpatient services, many for overnight observation.^13,20,21 Since 12% to 23% of patients with ALTE experience a repeat event or clinical condition requiring intervention,^13,20,21 multiple studies have attempted to design a clinical decision rule to determine high-risk infants requiring admission.^13,20,21 One small study had 100% sensitivity for infants requiring admission with two criteria: a history of multiple ALTEs and/or age younger than 1 month.²¹ Another study suggested high-risk criteria include prematurity and abnormal physical examination in the ED.¹³ To date, there are no well-validated clinical decision rules allowing for risk stratification of ALTE infants to home. As such, most infants with ALTE will be admitted for observation, but the appropriate disposition is best made in a collaborative decision-making process involving both the caregivers and the child’s pediatrician. 

Case Conclusion

The infant in this case was a full-term, healthy male, older than 1 month of age, with no significant findings on physical examination. He had never had a prior ALTE. Though this episode started with a choking sound following a feeding, the EP correctly recognized this presentation as an ALTE based on parental history of the event.

The EP appropriately ordered a chest X-ray to exclude foreign body aspiration or aspiration pneumonia. The X-ray was unremarkable and, based on the physical examination and history, there was no indication requiring additional workup of this patient. After a discussion with the patient’s mother, the EP admitted the infant to pediatric services for overnight evaluation. The patient had no further apneic episodes during admission, but did have reflux after most feeds. No further interventions were required during the hospital stay, and the infant was discharged home the following day after parental education on home management of infantile GERD.

Dr Clingenpeel is a fellowship director of pediatric emergency medicine, and an associate professor of pediatrics, Eastern Virginia Medical School, Norfolk. Dr Eason is a pediatric emergency medicine fellow at Eastern Virginia Medical School, Norfolk.

Case

An emergency medical services (EMS) telemetry call notified the ED of an 8-week-old infant who had turned blue during a choking and coughing episode at home. While en route to the ED, the EMS technicians stated that the infant was currently appearing well, with the following vital signs: heart rate, 122 beats/minute; respiratory rate, 30 breaths/minute; and blood pressure, 90/54 mm Hg. They also noted that the infant’s oxygen saturation was 100% on room air. At the time of the call, the patient’s estimated time to arrival at the ED was 5 minutes.

When the patient arrived at the ED, followed by his tearful mother, the emergency physician (EP) noted that the infant was alert and in no acute distress. The patient was triaged and placed on a cardiorespiratory monitor while the EP spoke with his mother. The infant’s mother stated that the event occurred approximately 15 minutes after she had finished breastfeeding the patient and had placed him on his back in his crib. She said that she had heard her son making choking and gurgling sounds and had gone back to his room to check on him, whereupon she noticed that his face had turned purple. She further noted that when she picked her son up, he was limp and did not seem to be breathing. She immediately shouted for her husband to call EMS while she “blew air into his mouth.” After about 10 seconds, she said her infant responded and seemed to be back to his normal self by the time EMS arrived.

With respect to history, the mother reported her son was born via normal vaginal delivery at 39 weeks gestation and that there were no complications during pregnancy or delivery. After the standard 48-hour inpatient stay, both mother and patient were discharged home together and had been doing well up until the time of the incident.

The patient, who was up to date on his routine preventive pediatric-care visits, was in the 85^th percentile for height, weight, and head circumference. Regarding his feeding routine, the patient was exclusively breastfed and, according to his mother, he tolerated his feedings well and did not typically spit-up afterward. The patient was not taking any medications. He resided at home with both his mother and father and did not attend daycare.

The physical examination showed a well-appearing 8-week-old boy, who acted appropriately for his age and was breathing comfortably on room air. His temperature at presentation was 98.4˚F, and his mother reported no history of fever. The patient’s fontanel was soft and flat, his lungs were clear on auscultation, and he had no murmurs. The abdomen was soft and without mass or hepatosplenomegaly. There were no rashes, bruises, or birthmarks.

After the examination, the patient’s mother, who was understandably distressed, asked the EP if she could breastfeed her son. As the EP prepared to answer this question, several questions came to mind: (1) Is this an apparent life-threatening event (ALTE)? (2) Is there a way to stratify this child’s risk for coexistent serious illnesses? (3) Will this patient be cleared for discharge from the ED today? (4) What tests should be ordered during his stay in the ED?

Overview

Few pediatric diagnoses result in as much consternation and uncertainty as the nebulous ALTE. The term was established to describe a spectrum of symptoms with a great number of possible underlying etiologies, and its definition leaves much room for interpretation. According to the 1986 National Institutes of Health Consensus Development Conference on Infantile Apnea and Home Monitoring, an ALTE is “an episode that is frightening to the observer, that is characterized by some combination of apnea (centrally 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. In some cases, the observer feels that the infant has died.”¹

Parents, as well as some providers, may have misconceptions about the relation of ALTE to sudden infant death syndrome (SIDS). While ALTEs were previously considered to be “near-miss SIDS” or “aborted crib death,” fewer than 8% of SIDS patients have a history of ALTE prior to death.² Additionally, rates of ALTE peak before 2 months of age, whereas SIDS rates are highest between 2 and 4 months of life.³  

Apparent life-threatening events are less prevalent in preterm patients compared to their full-term counterparts—though most study cohorts are comprised of full-term infants. When ALTEs, however, do occur in preterm infants, EPs should have a higher index of suspicion for an undiagnosed medical etiology associated with the patient’s prematurity—one that may potentially place the patient at an increased risk for SIDS (eg, limited pulmonary functional residual capacitance, hypoxic ischemic encephalopathy leading to seizure disorder).

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

Metabolic

Although in-born errors of metabolism are uncommon diagnoses, they must be considered as a cause of ALTE in the appropriate clinical context as they are reported in 1.5% to 7.7% of ALTE patients.⁷ Clinical clues suggesting an inborn error of metabolism include poor weight gain, unusual body odors (eg, of urine or sweat), symptom onset with institution of formula or diet change (eg, protein introduction), metabolic acidosis, hypoglycemia, thrombocytopenia, and neutropenia. Any of these clinical clues can point the practitioner toward a metabolic workup.

Nontraumatic Injury

The EP must always be watchful for signs of nonaccidental trauma in pediatric patients, as abusive head injury is diagnosed in 1% to 3% of ALTE case presentations.^6,16 A retrospective review found vomiting, irritability, and a documented 911 call to be risk factors associated with increased likelihood of abusive head trauma.¹⁶ Again, a thorough history and physical examination is prudent in all ALTE patients, and close attention should be paid to inconsistent or poorly explained histories and findings such as bruising or burns. Fictitious illness has also been documented in cases of ALTE in less than 3% of all cases, and should be considered especially in cases of repeated ALTEs witnessed by the same caregiver.⁷

Hematologic and Idiopathic

Almost a quarter of patients presenting with ALTE are found to have low hemoglobin for their respective age, with higher rates of anemia in patients with repeat ALTEs.⁶ However, there is no clear causative effect between anemia and ALTE. Moreover, in 25% to 50% of ALTE cases, there is no clear diagnosis and therefore the cause is considered idiopathic in nature.^7,8

Workup

While there is no standardized workup for ALTE, a careful history and physical examination should help guide diagnostic testing ordered in the ED. A retrospective study of 243 patients found that in 49%, the history and physical examination suggested an etiology that was confirmed by diagnostic testing (eg, a patient presenting with wheezing and rhinorrhea, who has a positive RSV antigen).¹⁷ Another 21% of patients were diagnosed solely on history and physical examination findings. While these patients may have had diagnostic tests performed, the tests did not contribute to the final diagnosis. In this study cohort, a final diagnosis was made by positive diagnostic tests alone in only 14% of patients with both nonspecific histories and physical examination findings. As previously mentioned, these findings underscore  the critical role that history and physical examination play in the diagnosis of ALTE.

As no obvious pathology is found in up to half of all ALTE cases, the EP must decide which tests will most likely be of diagnostic utility. Diagnostic tests are ordered in a majority of patients¹⁸ and a chest X-ray is one of the most frequently positive tests.^4,19

A positive test, however, does not necessarily lead to a diagnosis for the etiology of the ALTE. Only approximately one-third of the positive tests in the previously cited study were determined to contribute to the final diagnosis.¹⁷ The list of possible diagnostic tests for ALTE patients is lengthy and, at times, invasive. For this reason, EPs should perform focused testing based on the concerning elements in the history and physical examination rather than order a set of specific screening labs for each infant.

Need for Admission

Disposition is often a difficult decision in treating ALTE patients (and their families). Infants often look well and are acting normally by the time they arrive in the ED and remain well-appearing throughout the ED stay. If a thorough history, physical examination, and focused diagnostic testing uncover no specific etiology, the EP must decide whether to admit the patient for observation or discharge him or her home with instructions for pediatric follow up.

The majority of patients presenting to the ED with ALTE are admitted to inpatient services, many for overnight observation.^13,20,21 Since 12% to 23% of patients with ALTE experience a repeat event or clinical condition requiring intervention,^13,20,21 multiple studies have attempted to design a clinical decision rule to determine high-risk infants requiring admission.^13,20,21 One small study had 100% sensitivity for infants requiring admission with two criteria: a history of multiple ALTEs and/or age younger than 1 month.²¹ Another study suggested high-risk criteria include prematurity and abnormal physical examination in the ED.¹³ To date, there are no well-validated clinical decision rules allowing for risk stratification of ALTE infants to home. As such, most infants with ALTE will be admitted for observation, but the appropriate disposition is best made in a collaborative decision-making process involving both the caregivers and the child’s pediatrician. 

Case Conclusion

The infant in this case was a full-term, healthy male, older than 1 month of age, with no significant findings on physical examination. He had never had a prior ALTE. Though this episode started with a choking sound following a feeding, the EP correctly recognized this presentation as an ALTE based on parental history of the event.

The EP appropriately ordered a chest X-ray to exclude foreign body aspiration or aspiration pneumonia. The X-ray was unremarkable and, based on the physical examination and history, there was no indication requiring additional workup of this patient. After a discussion with the patient’s mother, the EP admitted the infant to pediatric services for overnight evaluation. The patient had no further apneic episodes during admission, but did have reflux after most feeds. No further interventions were required during the hospital stay, and the infant was discharged home the following day after parental education on home management of infantile GERD.

Dr Clingenpeel is a fellowship director of pediatric emergency medicine, and an associate professor of pediatrics, Eastern Virginia Medical School, Norfolk. Dr Eason is a pediatric emergency medicine fellow at Eastern Virginia Medical School, Norfolk.

Case

An emergency medical services (EMS) telemetry call notified the ED of an 8-week-old infant who had turned blue during a choking and coughing episode at home. While en route to the ED, the EMS technicians stated that the infant was currently appearing well, with the following vital signs: heart rate, 122 beats/minute; respiratory rate, 30 breaths/minute; and blood pressure, 90/54 mm Hg. They also noted that the infant’s oxygen saturation was 100% on room air. At the time of the call, the patient’s estimated time to arrival at the ED was 5 minutes.

When the patient arrived at the ED, followed by his tearful mother, the emergency physician (EP) noted that the infant was alert and in no acute distress. The patient was triaged and placed on a cardiorespiratory monitor while the EP spoke with his mother. The infant’s mother stated that the event occurred approximately 15 minutes after she had finished breastfeeding the patient and had placed him on his back in his crib. She said that she had heard her son making choking and gurgling sounds and had gone back to his room to check on him, whereupon she noticed that his face had turned purple. She further noted that when she picked her son up, he was limp and did not seem to be breathing. She immediately shouted for her husband to call EMS while she “blew air into his mouth.” After about 10 seconds, she said her infant responded and seemed to be back to his normal self by the time EMS arrived.

With respect to history, the mother reported her son was born via normal vaginal delivery at 39 weeks gestation and that there were no complications during pregnancy or delivery. After the standard 48-hour inpatient stay, both mother and patient were discharged home together and had been doing well up until the time of the incident.

The patient, who was up to date on his routine preventive pediatric-care visits, was in the 85^th percentile for height, weight, and head circumference. Regarding his feeding routine, the patient was exclusively breastfed and, according to his mother, he tolerated his feedings well and did not typically spit-up afterward. The patient was not taking any medications. He resided at home with both his mother and father and did not attend daycare.

The physical examination showed a well-appearing 8-week-old boy, who acted appropriately for his age and was breathing comfortably on room air. His temperature at presentation was 98.4˚F, and his mother reported no history of fever. The patient’s fontanel was soft and flat, his lungs were clear on auscultation, and he had no murmurs. The abdomen was soft and without mass or hepatosplenomegaly. There were no rashes, bruises, or birthmarks.

After the examination, the patient’s mother, who was understandably distressed, asked the EP if she could breastfeed her son. As the EP prepared to answer this question, several questions came to mind: (1) Is this an apparent life-threatening event (ALTE)? (2) Is there a way to stratify this child’s risk for coexistent serious illnesses? (3) Will this patient be cleared for discharge from the ED today? (4) What tests should be ordered during his stay in the ED?

Overview

Few pediatric diagnoses result in as much consternation and uncertainty as the nebulous ALTE. The term was established to describe a spectrum of symptoms with a great number of possible underlying etiologies, and its definition leaves much room for interpretation. According to the 1986 National Institutes of Health Consensus Development Conference on Infantile Apnea and Home Monitoring, an ALTE is “an episode that is frightening to the observer, that is characterized by some combination of apnea (centrally 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. In some cases, the observer feels that the infant has died.”¹

Parents, as well as some providers, may have misconceptions about the relation of ALTE to sudden infant death syndrome (SIDS). While ALTEs were previously considered to be “near-miss SIDS” or “aborted crib death,” fewer than 8% of SIDS patients have a history of ALTE prior to death.² Additionally, rates of ALTE peak before 2 months of age, whereas SIDS rates are highest between 2 and 4 months of life.³  

Apparent life-threatening events are less prevalent in preterm patients compared to their full-term counterparts—though most study cohorts are comprised of full-term infants. When ALTEs, however, do occur in preterm infants, EPs should have a higher index of suspicion for an undiagnosed medical etiology associated with the patient’s prematurity—one that may potentially place the patient at an increased risk for SIDS (eg, limited pulmonary functional residual capacitance, hypoxic ischemic encephalopathy leading to seizure disorder).

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

Metabolic

Although in-born errors of metabolism are uncommon diagnoses, they must be considered as a cause of ALTE in the appropriate clinical context as they are reported in 1.5% to 7.7% of ALTE patients.⁷ Clinical clues suggesting an inborn error of metabolism include poor weight gain, unusual body odors (eg, of urine or sweat), symptom onset with institution of formula or diet change (eg, protein introduction), metabolic acidosis, hypoglycemia, thrombocytopenia, and neutropenia. Any of these clinical clues can point the practitioner toward a metabolic workup.

Nontraumatic Injury

The EP must always be watchful for signs of nonaccidental trauma in pediatric patients, as abusive head injury is diagnosed in 1% to 3% of ALTE case presentations.^6,16 A retrospective review found vomiting, irritability, and a documented 911 call to be risk factors associated with increased likelihood of abusive head trauma.¹⁶ Again, a thorough history and physical examination is prudent in all ALTE patients, and close attention should be paid to inconsistent or poorly explained histories and findings such as bruising or burns. Fictitious illness has also been documented in cases of ALTE in less than 3% of all cases, and should be considered especially in cases of repeated ALTEs witnessed by the same caregiver.⁷

Hematologic and Idiopathic

Almost a quarter of patients presenting with ALTE are found to have low hemoglobin for their respective age, with higher rates of anemia in patients with repeat ALTEs.⁶ However, there is no clear causative effect between anemia and ALTE. Moreover, in 25% to 50% of ALTE cases, there is no clear diagnosis and therefore the cause is considered idiopathic in nature.^7,8

Workup

While there is no standardized workup for ALTE, a careful history and physical examination should help guide diagnostic testing ordered in the ED. A retrospective study of 243 patients found that in 49%, the history and physical examination suggested an etiology that was confirmed by diagnostic testing (eg, a patient presenting with wheezing and rhinorrhea, who has a positive RSV antigen).¹⁷ Another 21% of patients were diagnosed solely on history and physical examination findings. While these patients may have had diagnostic tests performed, the tests did not contribute to the final diagnosis. In this study cohort, a final diagnosis was made by positive diagnostic tests alone in only 14% of patients with both nonspecific histories and physical examination findings. As previously mentioned, these findings underscore  the critical role that history and physical examination play in the diagnosis of ALTE.

As no obvious pathology is found in up to half of all ALTE cases, the EP must decide which tests will most likely be of diagnostic utility. Diagnostic tests are ordered in a majority of patients¹⁸ and a chest X-ray is one of the most frequently positive tests.^4,19

A positive test, however, does not necessarily lead to a diagnosis for the etiology of the ALTE. Only approximately one-third of the positive tests in the previously cited study were determined to contribute to the final diagnosis.¹⁷ The list of possible diagnostic tests for ALTE patients is lengthy and, at times, invasive. For this reason, EPs should perform focused testing based on the concerning elements in the history and physical examination rather than order a set of specific screening labs for each infant.

Need for Admission

Disposition is often a difficult decision in treating ALTE patients (and their families). Infants often look well and are acting normally by the time they arrive in the ED and remain well-appearing throughout the ED stay. If a thorough history, physical examination, and focused diagnostic testing uncover no specific etiology, the EP must decide whether to admit the patient for observation or discharge him or her home with instructions for pediatric follow up.

The majority of patients presenting to the ED with ALTE are admitted to inpatient services, many for overnight observation.^13,20,21 Since 12% to 23% of patients with ALTE experience a repeat event or clinical condition requiring intervention,^13,20,21 multiple studies have attempted to design a clinical decision rule to determine high-risk infants requiring admission.^13,20,21 One small study had 100% sensitivity for infants requiring admission with two criteria: a history of multiple ALTEs and/or age younger than 1 month.²¹ Another study suggested high-risk criteria include prematurity and abnormal physical examination in the ED.¹³ To date, there are no well-validated clinical decision rules allowing for risk stratification of ALTE infants to home. As such, most infants with ALTE will be admitted for observation, but the appropriate disposition is best made in a collaborative decision-making process involving both the caregivers and the child’s pediatrician. 

Case Conclusion

The infant in this case was a full-term, healthy male, older than 1 month of age, with no significant findings on physical examination. He had never had a prior ALTE. Though this episode started with a choking sound following a feeding, the EP correctly recognized this presentation as an ALTE based on parental history of the event.

The EP appropriately ordered a chest X-ray to exclude foreign body aspiration or aspiration pneumonia. The X-ray was unremarkable and, based on the physical examination and history, there was no indication requiring additional workup of this patient. After a discussion with the patient’s mother, the EP admitted the infant to pediatric services for overnight evaluation. The patient had no further apneic episodes during admission, but did have reflux after most feeds. No further interventions were required during the hospital stay, and the infant was discharged home the following day after parental education on home management of infantile GERD.

Dr Clingenpeel is a fellowship director of pediatric emergency medicine, and an associate professor of pediatrics, Eastern Virginia Medical School, Norfolk. Dr Eason is a pediatric emergency medicine fellow at Eastern Virginia Medical School, Norfolk.