Emergency (****); * (*): *-* This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Copyright © 2015 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com 8 Emergency (2015); 3 (1): 8-15 REVIEW ARTICLE Infantile Apparent Life-Threatening Events, an Educational Review Hamed Aminiahidashti Emergency Medicine Department, Mazandaran University of Medical Sciences, Sari, Iran *Corresponding Author: Hamed Aminiahidashti, Emergency Department, Imam Khomeini Hospital, Amir Mazandarani Bololivar, Sari, Iran. Tel: +89113540546; Email: hamedaminiahidashti@yahoo.com Received: October 2014; Accepted: December 2014 Abstract Many physicians have received a frantic call from anxious parents stating that their child had stopped breathing, become limp, or turned blue but then had recovered quickly. An apparent life-threatening event (ALTE) is defined as “an episode that is frightening to the observer, and is characterized by some combination of apnea, color change, marked change in muscle tone, choking, gagging, or coughing”. The incidence of ALTE is reported to be 0.05% to 6%. The knowledge about the most common causes and factors associated with higher risk of ALTE could be resulted in a more purposeful approach, improving the decision making process, and benefiting both children and parents. The aim of this review article was to report the epidemiology, etiology, evaluation, man- agement, and disposition of ALTE. Infants with an ALTE might present no signs of acute illness and are commonly managed in the emergency settings that often require significant medical attention; hence, the emergency medi- cine personnel should be aware of the its clinical importance. There is no specific treatment for ALTE; th erefore, the clinical evaluations should be focused on the detection of the underlying causes, which will define the out- comes and prognosis. ALTE is a confusing entity, representing a constellation of descriptive symptoms and signs; in other words, it is not a diagnosis. There are multiple possible etiologies and difficulties in evaluating and man- aging infants with these events, which are challenges to primary care physicians, emergency medicine specialists, and subspecialty pediatricians. The evaluation of these events in infants includes a detailed history, appropriate physical examination, diagnostic tests guided by obtained clues from the history and physical examination, and observation in the emergency department. Key words: Infantile apparent life-threatening event; death, sudden; pediatrics; emergency medicine Cite this article as: Aminiahidashti H. Apparent life-threatening events, an educational review. Emergency. 2015;3(1):8-15. Introduction: n apparent life-threatening event (ALTE) was defined as “an episode that is frightening to the observer and is characterized by some combina- tion of apnea (central or occasionally obstructive), color change (usually cyanotic or pallid but occasionally ery- thematous or plethoric), marked change in muscle tone (usually marked limpness), choking, gagging, or cough- ing” (1, 2). This definition replaced the term “near-miss sudden infant death syndrome” that implied a close association with sudden infant death syndrome (SIDS) but was subsequently dismissed based on scarce evi- dence of the overlap between ALTE and SIDS. Whether SIDS and ALTE are strictly correlated is still a major argument among neonatologists (3, 4). Although a number of ALTE risk factors are similar to those of SIDS, the differences warrant a separate focus on ALTE beyond that on SIDS (5). ALTEs presenting to the emer- gency department (ED) might remain as a single, unex- plained event or be attributable to numerous causes, ranging from minor to serious ones (6). Knowledge about the most common causes and factors associated with higher risk of ALTE could result in a more pur- poseful approach, improving the decision-making pro- cess, and benefiting both the infants and their parents (6). Infants with ALTE usually present with an acute and unexpected change in behavior that has alarmed the caregivers (5). They might present with signs of acute illness that usually mandates management in the emergency medicine settings. These patients often re- quire significant medical attention as well as interven- tion; hence, the emergency medical service (EMS) per- sonnel should be aware of the clinical importance of these events to provide timely and thorough medical evaluation and treatment for infants meeting the crite- ria for an ALTE (7). Demographic data of cases with ALTE are obtained from children admitted to hospitals or EDs and because not all the children are brought for evaluation, the precise incidence of ALTE is not clear. The reported incidence ranges from 0.05% to 6% or is A This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Copyright © 2015 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com 9 Aminiahidashti Emergency (2014); 2 (3): ***-*** estimated at 2.4 in every 1000 live births (5, 8, 9). The incidence of ALTE among neonates is reported to range from 1.57 to 2.46 in every 1000 live births (4, 10). Most of the ALTEs occur in children younger than one year old (11, 12). In most published studies, a substantial portion of reported patients with ALTE were in neonate or at least younger than three months old with 50% to 80% being younger than two to three months old (9, 13-15). The median age was two months and 50% of infants showed normal findings on clinical examina- tions (16, 17). It has been reported that 2.27% of hospi- talized children are the Infants with ALTE (18). Based on above-mentioned, the aim of this review was to pre- sent the epidemiology, etiology, evaluation, manage- ment, and disposition of ALTE. Etiology The underlying etiology of ALTE varies and an episode of ALTE should be considered the manifestation of oth- er conditions rather than a diagnosis. An etiology would be found in one-half of patients, implying a potential for an intervention that could eliminate further events. The most frequent problems associated with ALTE are gas- trointestinal (50%), neurologic (30%), respiratory (20%), cardiovascular (5%), metabolic and endocrine (< 5%), or other problems such as child abuse. Despite through evaluations, no specific diagnosis would be made for the remaining patients, i.e. idiopathic cases (2, 19). The approach to investigate and manage an ALTE during admission is unstructured. A large number of patients are discharged from the ED and inpatient ser- vice with different diagnoses, mostly with convulsion, febrile convulsion, gastroesophageal reflux disease (GERD), and lower respiratory tract infection. The diag- nosis changes in those attending more than once for ALTE (16). ALTE might occur in the first 24 hours of birth, particularly within the first two hours. Events are often related to a potentially asphyxiating position. Parents might be too fatigued or unable to assess their infant's condition correctly (20). Of the infants with ALTE, 83.3% appeared to be in no distress, 13.3% mild, and 3.3% moderate distress. In most patients, findings of the general appearance and vital signs were not clini- cally abnormal (7). Differential Diagnosis The ALTE might be associated with a variety of underly- ing diseases (21). Epidemiologic studies found that the most frequent causes of ALTE were consecutively GERD, respiratory infections, and seizures (22, 23). Ta- ble1 lists the common, uncommon, and rare diagnoses assigned to patients with ALTE. Common causes are discussed independently (19, 21-23)(table 1). Gastroesophageal reflux disease GERD was the most common diagnosis among patients with ALTE (24). GERD induces significant histopatho- logic changes in larynx mucosa (25). Given the temporal correlation between peak age of ALTE and that of GERD, and the fact that reflux of gastric contents into the hypopharynx can trigger laryngospasm, a diagnosis of GERD provides an easy explanation for an ALTE. However, researchers have been unable to demonstrate a temporal association between episodes of GERD on pH probe and ALTEs or apneic events (26, 27). Respiratory Disorders Respiratory disorders are another common diagnosis in patients with ALTE; however, the frequency of diagnosis is widely varied (28). This might be due to epidemic bronchiolitis, pertussis, or lower respiratory tract infec- tions (29). Up to 20% of infants younger than six months old, who were hospitalized due to infection with respira- tory syncytial virus (RSV) had apnea and this association was strongest during the first month of life and in pre- term neonates (30). Apnea occurred in 0.5% to 12.0% of children younger than two years of age with pertussis (31, 32). In infants with ALTE, prolonged respiratory events are associated with ineffective esophageal motili- ties, characterized by frequent primary peristalsis and significant propagation failure, which is suggestive of dysfunctional regulation of swallow-respiratory junction interactions. Hence, treatment should target the proxi- mal aerodigestive tract rather than GERD (33). Seizures Seizures are diagnosed in 4% to 7% of infants with AL- TE (34). ALTE might be the first sign of an epileptic sei- zure. Diagnosis is often difficult because the interictal electroencephalogram (EEG) findings are usually nor- mal or show nonspecific changes; moreover, GERD Table 1: Reported final diagnoses for patients with apparent life-threatening events Common Less Common Rare Reported Gastroesophageal reflux disease Seizure/febrile seizure Upper/lower respiratory tract infection Misinterpretation of benign process such as periodic breathing Vomiting/choking episode Pertussis Inflicted injury Poisoning Serious bacterial infection Electrolyte abnormality Arrhythmia or other cardiovascular diseases Anemia Breath-holding spell Metabolic diseases Anatomic maxillofacial obstruction This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Copyright © 2015 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com Emergency (2015); 3 (1): 8-15 10 might mimic these events (35). During the etiologic in- vestigation of ALTE, first seizures and epilepsy should be included in the differential diagnosis and ictal re- cordings would be important tools to confirm these diagnoses (36-38). Seizures are secondary to underly- ing causes such as congenital brain malformation, met- abolic disorders, electrolyte abnormalities, prenatally acquired brain injury, or intracranial bleeding (includ- ing nonaccidental head trauma); therefore, these possi- bilities must be considered during assessments (39). Trauma The diagnosis of child abuse should be considered in pa- tients with ALTE. The evaluation of ALTEs should include funduscopic examination as ALTEs and retinal hemor- rhages are associated with child abuse. Retinal hemor- rhage was detected in 1.4% of infants with ALTEs (40). The diagnosis of inflicted traumatic head injury cannot rely on the finding of retinal hemorrhage alone, but the finding of severe bilateral retinal hemorrhage particular- ly with retinal folds or detachments is suggestive of the diagnosis (41). Child abuse was detected in 2.3% of pa- tients with ALTE (40). Infant with inflicted head injury might appear well on presentation with no external signs of abuse (42, 43); hence, inflicted head injury must be considered in a patient who has an ALTE unless an alter- native cause is readily apparent (14). Poisoning A large number of children referred to the ED with ALTE had positive toxicology screening results. In par- ticular, a number of these children were found to be given an over-the-counter cold medicine. The most frequently detected medications were acetaminophen, amphetamine, benzodiazepines, cocaine, codeine, me- peridine, methadone, phenobarbital, and phenothia- zine (44, 45). Thus, toxicological screening tests should be included in routine evaluation of children with ALTE (44) and poisoning by a caregiver (Munchhausen by proxy) should be added to the dif- ferential diagnosis of these infants. Moreover, urine drug screening tests should be considered in the eval- uation (45). Induced illness is a severe form of abuse that might cause death or permanent neurologic im- pairment. It might be accompanied by other severe abuse forms, which results in behavioral disorders. Detection of this abuse requires a closed and focused collaboration of hospitals and community’s child health professionals, child psychiatrists, social work- ers, and police officers (46). Bacterial Infection Serious bacterial infections (SBIs) must be considered in all febrile infants with ALTE. The reported rates range from 0% to 8.2% and the possibility of bactere- mia, meningitis, or urinary tract infection should be considered in infant presenting with an afebrile ALTE. The concern is greatest for infants younger than 60 days of age who might show few other symptoms to indicate the possibility of SBIs (47). In patients with ALTE who appear well without suggestive signs of SBI, it might be possible to forego routine sepsis evaluation beyond a chest radiograph and urine culture without risking a serious missed diagnosis (42). Routinely, chil- dren who present to the ED with ALTE do not need to undergo a full evaluation of SBI, while infants with such situation require infectious evaluation for SBI (48, 49). Breath holding spells Breath holding spells (BHS) are among the common benign paroxysmal nonepileptic disorders occurring in otherwise healthy children (50). The pathogenesis of BHS is not understood well, but some studies suggested that imbalance between the sympathetic and parasym- pathetic activity could play role in developing such a manifestation (51). The reported prevalence ranges from 0.1% to 4.6% in the general population (52). The diagnosis is usually made through description or obser- vation of typical attacks characterized by a sequence of clinical events, beginning with a provoking event such as minor trauma or emotional upset, followed by a noiseless state of expiration accompanied by skin color change (paleness or cyanosis), and finally, loss of con- sciousness and postural tone (51). Based on the skin color change during the attacks, BHS has two types: pallid and cyanotic; however, some children might ex- perience mixed-type attacks (53). Overall, the cyanotic type is more common and the ratio of cyanotic to pallid type is 3:1. Although these attacks were previously con- sidered as benign and self-limited in children between six and eight years of age, recent studies have shown that many of these patients would develop syncope at- tacks in the future (54). Rarely, these spells might be an initial symptom of long QT syndromes or paroxysmal cardiac rhythm abnormalities (53). Therefore obtaining an electrocardiogram to evaluate prolonged QT syn- drome is strongly recommended. Although BHS should be a diagnosis of exclusion in younger patients, some ALTEs might present by early manifestations of BHS (54). Management Specific information that should be obtained in the his- tory and physical examination is outlined in Table 2 (54, 55). Table 3 reviews the medications type and doses that might be required for the treatment of these patients, depending on their clinical picture (55-57). Patients with ALTE can be easily categorized into one of the following three groups. The first group consists of those with clear diagnosis of ALTE obtained from the history or physical examinations. The second group included the infants without immediately clear diagnosis but appearing unstable. The third group, which is the largest, consists of well -appearing This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Copyright © 2015 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com 11 Aminiahidashti Emergency (2014); 2 (3): ***-*** infants with a concerning history, but their physical examinations show normal or noncontributory re- sults. Patients with a Clear Diagnosis ALTEs are heterogeneous disorders that might frighten infants' caregivers (57). ALTEs are not a diagnosis and therefore, the attention must be turn to find the under- lying diseases (2). With a careful history review, physi- cal examination, and some basic laboratory investiga- tions, the main causes of ALTE might be discovered. Invasive investigations like lumbar puncture (LP) should be reserved for ill patients or for those with la- boratory or clinical impressions suggestive of central nervous system infections. Clinicians should alarm the parents about recurrence of these episodes and train them on the primary life support activities as well as on avoiding any harmful reactions (58). After an ALTE work-up, hospitalization would be required if the etiol- ogy was life-threatening (57). Unstable patients without a clear diagnosis For unstable patients without a clear diagnosis, the prior- ity is stabilization, which requires assisted ventilation for infants with persistent compromised ventilation or those with frequent apnea requiring monitoring and stimula- tion in the ED. In such a situation, head injury, sepsis, metabolic or electrolyte disorder, poisoning, complicated Table 2: Important information of patient with apparent life-threatening event Past Medical History Prematurity (birth before 37 weeks) Prior hospitalization, surgery, or ED visits History of apnea Prior respiratory difficulties (snoring or stridor) Prior feeding difficulties (choking, gagging, or coughing with feeds) Immunization status (pertussis) history of urinary tract infection Family History History of SIDS or sudden death Cardiac arrhythmias or congenital heart disease Seizure disorder Metabolic diseases Event History Duration of event (< 1 min, 1-5 min, or > 5 min) Required Resuscitation (e.g., stimulation, mouth-to-mouth breath, chest compressions) Temporal relationship of feeding, sleeping, crying, vomiting, choking, or gagging Skin color (cyanosis, pallor, or flushing) Change in tone (including seizure activity, flaccid, or spastic) Central vs. obstructive pattern of apnea (i.e., apparent respiratory effort) Number of ALTEs experienced within 24 h of presentation Episodic vs. sustained change in mental status (syncope, postictal phase, irritability, or ob- tundation) Correlation with feeding (at feeding time, few minute after feeding, or not related feeding) Seasonal distribution (spring, summer, autumn, or winter) Asleep or awake (awake, asleep, or both) Position of the neonate (supine or prone) Place of attack occurrence (parent's lap or cradle) Review of Sys- tems Respiratory symptoms or other intercurrent illness Period of fasting (e.g. recent onset of sleeping through night) Medication use, medications in the home or used by breastfeeding parent Possible trauma Social History Possibility of follow-up Comfort level of parents Parental concern for abuse Parental psychiatric issues or marital stress (e.g. absentee parent) exposure to the infectious agents (pertussis, RSV, upper respiratory infection, lower respira- tory tract infection) ALTE, apparent life-threatening event; ED, emergency department; SIDS, sudden infant death syndrome; and RSV, respiratory syncytial virus. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Copyright © 2015 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com Emergency (2015); 3 (1): 8-15 12 No  Careful history and physical examination  Is this the first, short, self-correcting episode with feeding? Ye s  Examination is normal  Parentral anxiety is addressed  Ensure availability for follow-up Yes Are there any features that could be consistent with shaken baby? No  Discharge  Discuss the option of a home monitor with the family  Review stimulation technique, CPR tech- nique and SIDS risk factors  Ensure follow-up No  Admit  Observation and cardiopulmonary monitoring for a minimum duration of 24 hours  Is this history or examination point to a likely cause? Yes Initiate focused work-up and treatment plan based on the presumptive diagnosis  Perform baseline investigations and check child protection register  Full blood count and differential count, C- reactive protein, sodium, potassium, urea, calcium, magnesium, glucose, blood gas anal- ysis, ammonia, lactate, pyruvate, and blood culture  Urinalysis and culture  Toxicology screen  Freeze for metabolic studies if no other diag- nosis was made  Investigations for respiratory tract infection  ECG with measurement of QTc interval  Investigation of gastroesophageal reflux  EEG  Ultrasonography of brain Yes Is there any positive findings in head CT and skeletal survey study? Yes No  Treat underlying disease  Involve child protective ser- vices No clear diagnosis Severe or recurrent episode  Observation  Refer for invasive investiga- tions No Yes Figure 1: Investigation plan for an apparent life-threatening event This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Copyright © 2015 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com 13 Aminiahidashti Emergency (2014); 2 (3): ***-*** pertussis, and bronchiolitis (in the neonate or ex- preemie) are the most likely causes (59). Infants with ALTE should be investigated for the presence of respira- tory pathogens, particularly Bordetella pertussis and RSV. These infections might be accompanied by clinically undetected baseline and episodic hypoxemia (60, 61). Stable patients without precise diagnosis In the clinical situation, when the patients with ALTE are considered to be idiopathic, some clinicians advo- cate a minimal evaluation with unexpansive tests for early detection of a rare, yet potentially devastating disease (e.g. infection or metabolic disease), to prevent long-term complications (62). This evaluation would include a complete blood count, C-reactive protein, basic metabolic panel, ammonia, lactate, pyruvate, blood gas measurement, urinalysis, toxicology screen, electrocardiogram, and microbiologic assessment for B. pertussis and RSV infections (62, 63). Laboratory and paraclinical tests When the history includes an awake, supine infant fed in the last hour, GERD would be the most convincing diagnosis (64). In this case, a pH probe study is the best test although the nonacid reflux cannot be captured. Although temporal association might be seen between acid reflux and symptoms, this test does not establish causality (65). A chest radiograph can be obtained, as indicated by history and physical examinations. While bacterial meningitis, sepsis, and urinary tract infections account for approximately 9% of the diagnoses, they should be considered in an ill-appearing infant (39). EEG had a 15% sensitivity for diagnosing epilepsy (66). Some authors suggested that EEG should be taken from those with recurrent ALTE (63). Some studies have reported the very high rates of cardiac arrhythmia including pro- longed corrected QT interval, premature ventricular or atrial beats, or sinus node irregularity in full-term and otherwise healthy infants with previous ALTEs who were undergone a 24-hour continuous holter monitoring (64). Many metabolic conditions are triggered by fasting and might be accompanied by symptoms of hypotonia, leth- argy, or vomiting. In these cases, laboratory evaluation including blood glucose, pH, ammonia, lactate, and pyru- vic acid levels might help to find the underlying cause (2). It seems that performing LP is not necessary for all neonates with an episode of ALTE, especially those with normal findings on their physical exams. However, rec- ommendation of LP might be reserved cases with high index of suspicion (13). If there is a suspicion of abuse or trauma, the evaluation should include ophthalmologic exam for retinal hemorrhage, head computed tomogra- phy (CT), and skeletal survey (67). Disposition Multiple possible etiologies and difficulties in evaluat- ing and managing infants with ALTE pose a challenge for primary care physicians, emergency medicine spe- cialists, and subspecialty pediatricians. The evaluation of these infants should include a detailed history, thor- ough physical examinations, and appropriate diagnostic tests based on the clues obtained from the patient's his- tory and physical examinations (62). Only 12% of in- fants referred to the ED with ALTE need a significant intervention warranting hospital admission (57). Re- garding infants with ALTE and no acutely ill appear- ance, there is no consensus on the minimal diagnostic evaluations and on the part of history and risk factors that should lead a practitioner toward admission to or discharge from the ED. Clinical judgment remains a very important part of the decision-making process (68). A practical algorithm listed in Figure1 (55, 57, 68). The ALTE term is nonspecific and describes a cluster of symptoms with many possible causes. In the clinical situation when the etiology of the ALTE is not estab- lished after a detailed history and comprehensive phys- ical examination, which might be considered as idio- Table 3: Common intervention for ill patient with apparent life-threatening event Indication Medication/Intervention Dose/Size Hypoglycemia Glucose 5-10 mL/kg of 10% dextrose in water, IV Hyponatremia 3% Normal Saline 3-5 mL/kg bolus, IV Hypocalcemia Calcium 50-100 mg/kg calcium gluconate or 20 mg/kg calcium chloride, IV Infection Cefotaxime 50 mg/kg, IV Ampicillin 50 mg/kg, IV Anemia Packed red blood cells 10 mL/kg, IV Hypotension Normal Saline 20 mL/kg, IV Metabolic disease 10% dextrose in one-fourth normal saline 1.5 maintenance (6 mL/kg/h for the first 10 kg) Hypoventilation or frequent apnea Endotracheal intubation 3.0 mm3 for preterm; 3.5 mm3 for term neonate; and 4.0 mm3 for older infant IV: Intravenous; kg: Kilogeram; mL: Mililiter; h: houre; mm3: Cubic millimeter This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Copyright © 2015 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com Emergency (2015); 3 (1): 8-15 14 pathic, some clinicians advocate a minimal diagnostic evaluation. The three following variables could identify most but not all of the infants with ALTE and necessi- tate admission: the obvious need for admission, signifi- cant medical history, and more than one ALTE episode during 24 hours. These variables require external vali- dation and reliability assessment before clinical imple- mentation (67). Conclusion: Children with ALTE referred to ED with anxious par- ents. Several factors such as the number and type of ALTE manifestations, underlying diseases, and parents’ situation would affect the patient's management. The evaluation of these infants including detailed history, appropriate physical examination, and close observa- tion in ED. Further studies are recommended to identify the etiologic factors and appropriate management of children with ALTE. Conflict of interest: None. Funding support: None. References: 1. Patricia King J. National Institutes of Health Consensus Development Conference on Infantile Apnea and Home Monitoring, Sept 29 to Oct 1, 1986. Pediatrics. 1987;79(2). 2. Kahn A, European Society for the S, Prevention of Infant D. 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. 2004;163(2):108-15. 3. Edner A, Wennborg M, Alm B, Lagercrantz H. Why do ALTE infants not die in SIDS? Acta Paediatr. 2007;96(2):191-4. 4. Kiechl-Kohlendorfer U, Hof D, Peglow UP, Traweger- Ravanelli B, Kiechl S. Epidemiology of apparent life threatening events. Arch Dis Child. 2005;90(3):297-300. 5. Esani N, Hodgman JE, Ehsani N, Hoppenbrouwers T. Apparent life-threatening events and sudden infant death syndrome: comparison of risk factors. J Pediatr. 2008;152(3):365-70. 6. Davies F, Gupta R. Apparent life threatening events in infants presenting to an emergency department. Emerg Med J. 2002;19(1):11-6. 7. Stratton SJ, Taves A, Lewis RJ, Clements H, Henderson D, McCollough M. Apparent life-threatening events in infants: high risk in the out-of-hospital environment. Ann Emerg Med. 2004;43(6):711-7. 8. Carroll JL. Apparent Life Threatening Event (ALTE) assessment. Pediatr Pulmonol Suppl. 2004;26:108-9. 9. Santiago-Burruchaga M, Sanchez-Etxaniz J, Benito- Fernandez J, et al. Assessment and management of infants with apparent life-threatening events in the paediatric emergency department. Eur J Emerg Med. 2008;15(4):203-8. 10. Semmekrot BA, Van Sleuwen BE, Engelberts AC, et al. Surveillance study of apparent life-threatening events (ALTE) in the Netherlands. Eur J Pediatr. 2010;169(2):229-36. 11. Brooks JG. Apparent life-threatening events and apnea of infancy. Clin Perinatol. 1992;19(4):809-38. 12. MD Elias, VR Iyer, Cohen MS. Prevalence of Electrocardiogram Use in Infants With Apparent Life- Threatening Events: A Multicenter Database Study. Pediatr Emerg Care. 2014;30(4):236–9. 13. Brand DA, Altman RL, Purtill K, Edwards KS. Yield of diagnostic testing in infants who have had an apparent life- threatening event. Pediatrics. 2005;115(4):885-93. 14. Altman RL, Brand DA, Forman S, et al. Abusive head injury as a cause of apparent life-threatening events in infancy. Arch Pediatr Adolesc Med. 2003;157(10):1011-5. 15. Doshi A, Bernard-Stover L, Kuelbs C, Castillo E, Stucky E. Apparent life-threatening event admissions and gastroesophageal reflux disease: the value of hospitalization. Pediatr Emerg Care. 2012;28(1):17-21. 16. Gray C, Davies F, Molyneux E. Apparent life-threatening events presenting to a pediatric emergency department. Pediatr Emerg Care. 1999;15(3):195-9. 17. Romaneli MT, Fraga AM, Morcillo AM, Tresoldi AT, Baracat EC. Factors associated with infant death after apparent life- threatening event (ALTE). J Pediatr (Rio J). 2010;86(6):515-9. 18. Laisne C, Rimet Y, Poujol A, et al. A propos de cent malaises du nourrisson. Ann de pédiatrie. 1989;36(7):451-4. 19. Hall KL, Zalman B. Evaluation and management of apparent life-threatening events in children. Am Fam Physician. 2005;71(12):2301-8. 20. Poets A, Steinfeldt R, Poets CF. Sudden deaths and severe apparent life-threatening events in term infants within 24 hours of birth. Pediatrics. 2011;127(4):e869-e73. 21. Sarnat HB. Myasthenia gravis. Disorders of Neuromuscular transmission and motor Neurons. In: Klieg man RM, Behrman RE, Jenson HB, Stanton BF, editors. Nelson textbook of pediatrics. 18 ed. Philadelphia: Saunders; 2007. p. 253-80. 22. Frysinger RC, Harper RM. Cardiac and respiratory correlations with unit discharge in epileptic human temporal lobe. Epilepsia. 1990;31(2):162-71. 23. Galimberti CA, Marchioni E, Barzizza F, Manni R, Sartori I, Tartara A. Partial epileptic seizures of different origin variably affect cardiac rhythm. Epilepsia. 1996;37(8):742-7. 24. Zhang T, Jiang M. Advances in research on extra esophageal symptoms of pediatric gasteroesophageal reflux. Zhongguo Dang Dai Er Ke Za Zhi. 2012;14(5):391-5. [Chinese]. 25. Habesoglu M, Habesoglu TE, Gunes P, et al. How does reflux affect laryngeal tissue quality? An experimental and histopathologic animal study. Otolaryngol Head Neck Surg. 2010;143(6):760-4. 26. Arad-Cohen N, Cohen A, Tirosh E. The relationship between gastroesophageal reflux and apnea in infants. J Pediatr. 2000;137(3):321-6. 27. Peter CS, Sprodowski N, Bohnhorst B, Silny J, Poets CF. Gastroesophageal reflux and apnea of prematurity: no temporal relationship. Pediatrics. 2002;109(1):8-11. 28. Romaneli MTdN, Castro CCTdS, Fraga AdMA, Lomazi EA, Nucci A, Tresoldi AT. Recurrent apparent life-threatening event as the first manifestation of congenital myasthenia. Revista Paulista de Pediatria. 2013;31(1):121-3. 29. Fuger M, Merdariu D, Maurey H, Kaminska A, Chéron G. Pertinence de la prescription au service d’accueil des urgences d’un électroencéphalogramme après un malaise du nourrisson. Arch Pediatr. 2014;21(11):1206-12. 30. Dunne K, Matthews T. Near-miss sudden infant death syndrome: clinical findings and management. Pediatrics. 1987;79(6):889-93. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Copyright © 2015 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com 15 Aminiahidashti Emergency (2014); 2 (3): ***-*** 31. Jenkinson D. Natural course of 500 consecutive cases of whooping cough: a general practice population study. BMJ. 1995;310(6975):299-302. 32. Stojanov S, Liese J, Belohradsky B. Hospitalization and complications in children under 2 years of age with Bordetella pertussis infection. Infection. 2000;28(2):106-10. 33. Hasenstab KA, Jadcherla SR. Respiratory Events in Infants Presenting with Apparent Life Threatening Events: Is There an Explanation from Esophageal Motility? J Pediatr. 2014;165(2):250-5. 34. Hosain S, La Vega-Talbott M, Solomon G, Green N. Apneic seizures in infants: role of continuous EEG monitoring. Clinical EEG (electroencephalography). 2003;34(4):197-200. 35. Engel J. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia. 2001;42(6):796-803. 36. Nunes ML, Appel CC, da Costa JC. Apparent life-threatening episodes as the first manifestation of epilepsy. Clin Pediatr (Phila). 2003;42(1):19-22. 37. Heissessen L, Dusser A, Nouirygat V, et al. Epilepsy presenting as life-threatening events in infants. Arch de pediatrie. 2000;7(9):955-60. [French]. 38. Anjos AMd, Nunes ML. Prevalence of epilepsy and seizure disorders as causes of apparent life-threatening event (ALTE) in children admitted to a tertiary hospital. Arq Neuropsiquiatr. 2009;67(3A):616-20. 39. Bonkowsky JL, Guenther E, Filloux FM, Srivastava R. Death, child abuse, and adverse neurological outcome of infants after an apparent life-threatening event. Pediatrics. 2008;122(1):125-31. 40. Pitetti RD, Maffei F, Chang K, Hickey R, Berger R, Pierce MC. Prevalence of retinal hemorrhages and child abuse in children who present with an apparent life-threatening event. Pediatrics. 2002;110(3):557-62. 41. Duhaime A-C, Christian CW, Rorke LB, Zimmerman RA. Nonaccidental head injury in infants—the “shaken-baby syndrome”. N Engl J Med. 1998;338(25):1822-9. 42. Altman RL, Kutscher ML, Brand DA. Shaken-baby syndrome. N Engl J Med. 1998;339:1329- 30. 43. Morris MW, Smith S, Cressman J, Ancheta J. Evaluation of infants with subdural hematoma who lack external evidence of abuse. Pediatrics. 2000;105(3):549-53. 44. Pitetti RD, Whitman E, Zaylor A. Accidental and nonaccidental poisonings as a cause of apparent life- threatening events in infants. Pediatrics. 2008;122(2):e359- e62. 45. Hickson GB, Altemeier WA, Martin ED, Campbell PW. Parental administration of chemical agents: a cause of apparent life-threatening events. Pediatrics. 1989;83(5):772- 6. 46. Southall DP, Plunkett MC, Banks MW, Falkov AF, Samuels MP. Covert video recordings of life-threatening child abuse: lessons for child protection. Pediatrics. 1997;100(5):735-60. 47. Zuckerbraun NS, Zomorrodi A, Pitetti RD. Occurrence of serious bacterial infection in infants aged 60 days or younger with an apparent life-threatening event. Pediatr Emerg Care. 2009;25(1):19-25. 48. Mittal MK, Shofer FS, Baren JM. Serious bacterial infections in infants who have experienced an apparent life-threatening event. Ann Emerg Med. 2009;54(4):523-7. 49. Claudius I, Mittal MK, Murray R, Condie T, Santillanes G. Should infants presenting with an apparent life-threatening event undergo evaluation for serious bacterial infections and respiratory pathogens? J Pediatr. 2014;164(5):1231-3. e1. 50. Lombroso CT, Lerman P. Breathholding spells (cyanotic and pallid infantile syncope). Pediatrics. 1967;39(4):563-81. 51. DiMario FJ. Breath-holding spells in childhood. Am J Dis Child. 1992;146(1):125-31. 52. Evans OB. Breath-holding spells. Ann Pediatr J. 1997;26(7):410-4. 53. DiMario Jr FJ, Burleson JA. Autonomic nervous system function in severe breath-holding spells. Pediatr Neurol. 1993;9(4):268-74. 54. DiMario FJ. Prospective study of children with cyanotic and pallid breath-holding spells. Pediatrics. 2001;107(2):265- 9. 55. Stratton SJ, Taves A, Lewis RJ, Clements H, Henderson D, McCollough M. Apparent life-threatening events in infants: High risk in the out-of-hospital environment. Ann Emerg Med. 2004;43(6):711-7. 56. DeWolfe CC. Apparent life-threatening event: a review. Pediatr Clin North Am. 2005;52(4):1127-46. 57. McGovern M, Smith M. Causes of apparent life threatening events in infants: a systematic review. Arch Dis Child. 2004;89(11):1043-8. 58. Kadivar M, Yaghmaie B, Allahverdi B, Shahbaznejad L, Razi N, Mosayebi Z. Apparent Life-Threatening Events in Neonatal Period: Clinical Manifestations and Diagnostic Challenges in a Pediatric Referral Center. Iran J Pediatr. 2013;23(4):458. 59. Willwerth BM, Harper MB, Greenes DS. Identifying hospitalized infants who have bronchiolitis and are at high risk for apnea. Ann Emerg Med. 2006;48(4):441-7. 60. Poets C, Stebbens V, Alexander J, Arrowsmith W, Salfield S, Southall D. Hypoxaemia in infants with respiratory tract infections. Acta Paediatr. 1992;81(6‐7):536-41. 61. Southall D, Thomas M, Lambert H. Severe hypoxaemia in pertussis. Arch Dis Child. 1988;63(6):598-605. 62. Fu LY, Moon RY. Apparent Life-Threatening Events An Update. Pediatr Rev. 2012;33(8):361-9. 63. Shah S, Sharieff GQ. An update on the approach to apparent life-threatening events. Curr Opin Pediatr. 2007;19(3):288-94. 64. Nunez J, Cristofalo E, McGinley B, Katz R, Glen DR, Gauda E. Temporal association of polysomnographic cardiorespiratory events with GER detected by MII-pH probe in the premature infant at term. J Pediatr Gastroenterol Nutr. 2011;52(5):523- 31. 65. Tieder JS, Cowan CA, Garrison MM, Christakis DA. Variation in inpatient resource utilization and management of apparent life-threatening events. J Pediatr. 2008;152(5):629- 35. e2. 66. Vellody K, Freeto JP, Gage SL, Collins N, Gershan WM. Clues that aid in the diagnosis of nonaccidental trauma presenting as an apparent life-threatening event. Clin Pediatr (Phila). 2008. 67. Kaji AH, Claudius I, Santillanes G, et al. Apparent life- threatening event: multicenter prospective cohort study to develop a clinical decision rule for admission to the hospital. Ann Emerg Med. 2013;61(4):379-87. 68. Chu A, Hageman JR. Apparent Life-Threatening Events in Infancy. Pediatr Ann. 2013;42(2):78-83.