ALTEs: Still a Puzzle after All These Years

ALTEs: Still a Puzzle after All These Years

The authors’ main conclusions are sound; identification of obesity based on measured weight and height demonstrates higher prevalence and different ut...

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The authors’ main conclusions are sound; identification of obesity based on measured weight and height demonstrates higher prevalence and different utilization patterns than identification of obesity from ICD-9 codes. The better validity of measured obesity is obvious. But this measure could be used more effectively in 2 ways: first, by documenting BMI in all hospitalized patients, which would extend the recent inclusion of BMI as a Healthcare Effectiveness Data and Information Set (HEDIS) measure in outpatient care, and second, by grading severity within the large group of children with BMI ⬎95th percentile. To tap the potential of measured obesity, the variables related to BMI status also need to be more precise than the broad diagnosis categories used here. Electronic health records hold promise for better database research on disease and utilization because their purpose— health assessment and care—is more closely aligned to questions of obesity and health status than

administrative databases. But they remain subject to human bias, and thus findings must be interpreted cautiously. Sarah E. Barlow, MD, MPH Baylor College of Medicine Texas Children’s Hospital Houston, Texas

REFERENCES 1. Woo JG, Zeller MH, Wilson K, Inge T. Obesity identified by discharge ICD-9 codes underestimates the true incidence of obesity in hospitalized children. J Pediatr 2009;154:327-31. 2. Wang G, Dietz WH. Economic burden of obesity in youths aged 6 to 17 years: 1979-1999. Pediatrics 2002;109:e81. 3. Cook S, Weitzman M, Auinger P, Barlow SE. Screening and counseling associated with obesity diagnosis in a national survey of ambulatory pediatric visits. Pediatrics 2005;116:112-6. 4. Hampl SE, Carroll CA, Simon SD, Sharma V. Resource utilization and expenditures for overweight and obese children. Arch Pediatr Adolesc Med 2007;161:11-4.

ALTEs: Still a Puzzle after All These Years

or more than 20 years, the clinical definitions of an apparent life-threatening event (ALTE), central, mixed, and obstructive apnea, apnea of infancy, and pathologic apnea suggested by the 1986 National Institutes of Health consensus development conference on Infantile Apnea and Home Monitoring,1 continue to be used by most clinicians. An ALTE contains features that are frightening to the observer; some combination of apnea (central or obstructive), color change (usually cyanosis or pallor, but occasionally plethora), a marked change in muscle tone (usually limpness), choking, or gagging. It was also suggested in the consensus development conference report that the term ALTE should replace older terms, including “near-miss SIDS” (sudden infant death syndrome) and “aborted crib death.” Although there have been advances in understanding this complex collection of symptoms, perhaps better termed a description than a diagnosis, research has been hampered by the small number of infants and the rather broad definition that includes causes ranging from severe apnea of infancy to a choking spell during feeding. Determination of the cause of an ALTE is further complicated because infants with ALTE often appear normal after arriving at the hospital. Determining the severity of the event often depends entirely on the historical description of caretakers, who are usually not experienced medical observers. Published reviews indicate that digestive problems, including gastroesophageal reflux (GER), account for 30% to 50% of the diagnoses, neurologic prob-




Apparent life-threatening event Collaborative Infant Home Monitoring Evaluation Gastroesophageal reflux Postconceptional age Sudden infant death syndrome

lems, including seizures, for 10% to 20%, respiratory problems including viral infections for 20%, cardiovascular issues for 5%, metabolic or endocrine for ⬍5%, and other causes, including child abuse and Munchausen-by-proxy, for another ⬍5%. In most studies, about 50% of ALTEs fail to be explained after a full workup and period of observation and have been labeled “idiopathic ALTE.”2,3 In the past, ALTEs were commonly called “near-miss” SIDS, but the heterogeneity of both ALTE and SIDS renders any comparison between them difficult. Comparative studies of ALTE infants are complicated by varied presentation and terminology, incomplete histories, inconsistent efforts to identify causes for the events, dependence on untrained observers, validity of caretakers to correctly perceive a true life-threatening event, and lack of adequate follow-up.2 Although there is some overlap in the risk factors for ALTEs and SIDS, notably smoking during pregnancy, there are distinct differences. ALTEs have been described as early as ⬍2 hours of age4 and as late as 1 year of age, but most occur at ⬍2 months of age, compared with 2 to 3 months peak incidence for SIDS. Up to 52% of ALTEs occur during See related article, p 332 wakefulness, whereas most infants with SIDS die during sleep.5 The Reprint requests: Robert A. Darnall, MD, Department of Pediatrics, Dartmouth Medincidence of SIDS has ical School, Dartmouth-Hitchcock Medical declined since the instiCenter, 1 Medical Center Dr, Lebanon, NH 03756. tution of the Back-toJ Pediatr 2009;154:317-9 Sleep program, but 0022-3476/$ - see front matter there has been no simiCopyright © 2009 Mosby Inc. All rights lar decrease for the incireserved. dence of ALTE. 10.1016/j.jpeds.2008.09.041 317

How many infants die of SIDS after having experienced an ALTE? Some have suggested that infants with an ALTE are at increased risk for child abuse and adverse neurologic outcomes but are at minimum risk for death.6 However, studies of infants who subsequently died of SIDS have shown that ⬍10% of SIDS victims had presented with a cyanotic or pale episode at some time before death.2 Although the number of infants with ALTE who subsequently die is small, it is perhaps misleading to conclude that there is no relationship between an ALTE and SIDS. More accurately, a subset of infants who have had a life-threatening event at home may be at increased risk for sudden death. The focus, then, should be on identifying those infants with ALTE who are most at risk. Interestingly, in one of the few prospective studies of ALTEs, Kiechl-Kohlendorfer et al7 reported that of those ALTE events that could not be explained (ie, idiopathic ALTE), there were significant correlations between early behavioral characteristics, including repeated apnea, cyanotic or pallid episodes, and feeding difficulties and the ALTE. This suggests that some ALTEs are a repeat occurrence of similar previous events but are now severe enough to require intervention. Moreover, the examination of monitor records of infants who have died while attached to their monitors have also demonstrated in many cases periods of apnea, bradycardia and tachycardia in the weeks and even months before death.8 In addition, of the infants enrolled in the Collaborative Infant Home Monitoring Evaluation (CHIME) multicenter study supported by the National Institute for Child Health and Human Development carried out between 1994 and 1998,9 1 of the 6 infants who died was classified as having experienced an idiopathic ALTE. Apnea, is a common feature (by definition) of all ALTEs, regardless of whether a cause is identified. Indeed, most of the common diagnoses applied to ALTEs can be associated with apnea, most notably GER, choking episodes, and respiratory infections, especially respiratory syncytial virus and pertussis. Thus most infants with idiopathic ALTE have unexplained apnea, and in some cases, the ALTE was not an isolated event. It is also possible that infants who have apnea that precipitated the ALTE from other causes, including respiratory infections, may go on to have repeated episodes that potentially could be life-threatening. Are infants who present to the hospital with an ALTE at increased risk to experience future significant apneic events? In this issue of The Journal, Al-Kindy et al10 examine risk factors for “Extreme Events” in infants that were hospitalized for ALTEs. The term “extreme event” was coined by the CHIME study and was defined as an apnea of at least 30 seconds duration or, for infants ⬍44 weeks postconceptional age (PCA), bradycardia (⬍60 beats/min) lasting 10 seconds or more, and for infants ⱖ44 weeks PCA bradycardia (⬍50 beats/min) lasting for at least 10 seconds. In the CHIME study, compared with healthy term infants, only infants with ALTE (all idiopathic ALTE) who were born at ⱕ37 weeks gestation age were at higher risk to have at least 1 extreme event during a 180-day monitoring period, whereas infants with idiopathic ALTE who were born at term were not at increased risk for extreme events.9 318


A previous study conducted by one of the authors (A.C.) showed that events recorded in the hospital were associated with an increased recurrence rate at home, but that study did not differentiate between moderate and extreme events, and oxygen saturation data were often not available. In the current study, 10 years of experience with infants presenting with ALTE were reviewed to determine whether known risk factors for cardiorespiratory illnesses could help identify infants who would experience extreme events during an admission for ALTE or later at home. With relevant ICD codes, a total of 748 cases admitted to the hospital between April 1996 and March 2006 were reviewed (⬃71% of infants who were seen for an ALTE in the emergency room were admitted to the hospital). A total of 625 patients were retained, excluding 92 who did not fit the ALTE criteria and 31 who had preexisting disease. All of the cases were first observed with a non-recording cardiorespiratory monitor and in most cases a pulse-oximeter. A total of 338 infants (54%) were subsequently monitored with an event-recording device and, if recurrent events were detected, pulse oximetry. In addition, all infants with idiopathic ALTE (those without an identified cause) and other infants with ALTE with significant cardiorespiratory events in the hospital were monitored at home after discharge from the hospital. Forty-six infants of the 338 monitored with a recording monitor experienced extreme events in the hospital, all but 7 in the first 24 hours of monitoring. Most extreme events (43/46 infants) included a desaturation below 80% for ⬎10 seconds, with most lasting for 20 seconds or more, often after a central apnea. The authors estimate that if the oximeter had not been used, extreme events in 14 infants would have been missed. Twenty-seven infants had central apneas exceeding 30 seconds. Importantly, almost 90% of these infants did not appear “sick” on presentation to the emergency department. On the basis of the event recordings of the 338 infants, the significant risk factors for having extreme events in the hospital were (1) prematurity, (2) age less than 43 weeks PCA, and (3) symptoms of an upper respiratory tract infection on admission. Male sex and having an ALTE during the winter months did not increase the risk for extreme events. However, male infants who were also less than 43 weeks PCA at the time of the ALTE did have increased risk for extreme events, but this was not the case for male infants who were born prematurely or who had upper respiratory symptoms. A total of 88 infants were sent home on home monitors, including all but 7 of the infants who had extreme events. Of those 88 infants, 7 had extreme events at home, and all of these had extreme events recorded in the hospital as well. Two infants had a diagnosis of pertussis, 4 had recurrent events associated with an upper respiratory infection (1 with respiratory syncytial virus). The last infant had recurrent events for months and was subsequently diagnosed with nemaline rod myopathy. Consistent with most other studies, 20% of all infants admitted for an ALTE (122/625) had symptoms of an upper respiratory tract infection. However, almost two thirds of the 46 infants with extreme events had URI symptoms. The incidence of URI may even be greater because some infants The Journal of Pediatrics • March 2009

developed symptoms of URI after admission, but were not classified as having URI symptoms at admission. Five infants were diagnosed with GER (11%) and 8 infants represented idiopathic ALTE (17%). A recent study in The Journal, examining the relationship between GER and apnea in infants with ALTE found that when there was a relationship between apnea and GER, apnea preceded the GER in more than 90% of the episodes.11 Thus some infants with GER might have otherwise been classified as having idiopathic ALTE rather than GER. However, of the 7 infants who had extreme events documented at home, all but 1 had a respiratory infection. One important conclusion from this study is that most of the extreme events in infants with ALTE were associated with respiratory infections, and that many of these infants continued to be at risk for extreme events with future infections. These data are also consistent with the results of a recent examination of infants with bronchiolitis showing that young age and being born prematurely increase the risk for apneas.12 What about infants who have no identified cause for their ALTE and have extreme events in the hospital. Are they at risk for events at home? Data from the CHIME study showed that of the 272 infants with idiopathic ALTE monitored at home, only the preterm infants with ALTE (n ⫽ 45) had rates of extreme events that were greater than for healthy term infants. In these infants the chance of having an extreme event was approximately as great as premature infants who were having apnea of prematurity at discharge (symptomatic preterm infants). The chance of having an extreme event, similar to the premature infants without ALTE approached the rate of healthy term infants by about 43 weeks PCA.9 This study was not designed to answer the important question of whether infants who have repeated extreme events are at increased risk for sudden death. Nevertheless, information about the importance of upper respiratory tract infections in predicting continuing periods of apnea and hypoxia and the usefulness of pulse oximetry in the evaluation of ALTE

infants brings us a little closer to solving the puzzle. A standardized approach to the diagnosis, management, and follow-up of these infants would be an important improvement in our current practice and would be a first step in identifying those ALTE infants who are at risk for subsequent sudden death. Robert A. Darnall, MD Department of Pediatrics Dartmouth Medical School Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire

REFERENCES 1. National Institutes of Health Consensus Development Conference on Infantile Apnea and Home Monitoring. Pediatrics 1987;79:292-9. 2. Kahn A. Recommended clinical evaluation of infants with an apparent lifethreatening event. Consensus document of the European Society for the Study and Prevention of Infant Death, 2003. Eur J Pediatr 2004;163:108-15. 3. McGovern MC, Smith MBH. Causes of apparent life threatening events in infants: a systematic review. Arch Dis Child 2004;89:1043-8. 4. Dageville C, Pignol J, De Smet S. Very early neonatal apparent life-threatening events and sudden unexpected deaths: Incidence and risk factors. Acta Paediatr 2008;97:866-9. 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;152:365-70. 6. Bankowsky JL, Guenther E, Filloux FM, Srivastava R. Death, Child abuse, and adverse neurological outcome of infants after an apparent life-threatening event. Pediatrics 2008;122:125-31. 7. Kiechl-Kohlendorfer U, Hof D, Peglow UP, Travweger-Ravanelli B, Kiechl S. Epidemiology of apparent life threatening events. Arch Dis Child 2004;90:297-300. 8. Meny RG, Carroll JL, Carbone MT, Kelly DH. Cardiorespiratory recordings from infants dying suddenly and unexpectedly at home. Pediatrics 1994;93:44-9. 9. Ramanathan R, Corwin MJ, Hunt CE, Lister G, Tinsley LR, Baird T, et al. Cardiorespiratory events recorded on home monitors: Comparison of healthy infants with those at increased risk for SIDS. JAMA 2001;285:2199-207. 10. Al-Kindy HA, Gelinas J, Hatsakis G, Côté A. Risk factors for extreme events in infants hospitalized for apparent life-threatening events. J Pediatr 2009;154:322-7. 11. Arad-Cohen N, Cohen A, Tirosh E. The relationship between gastroesophageal reflux and apnea in infants. J Pediatr 2000;137:321-6. 12. Willwerth BM, Harper MB, Greenes DS. Identifying hospitalized infants who have bronchiolitis and are at high risk for apnea. Ann Emergency Med 2006;48:441-7.

Establishing a Translational Science for Autistic Spectrum Disorders for Children and Their Families: Optimizing Function, Participation, and Well-Being

n the United States, there are ⬎20 million children aged 2 to 6 years. Community studies have demonstrated that between 1 in 150 and 1 in 300 of these preschool children have criteria for an Autism spectrum disorder (ASD).1 Thus, ⬎125 000 children have challenges in communication, social skills, and adaptive behaviors. Dissemination of the developmental checklist (eg, First Signs: and American Academy of Pediatrics Autism Tool Kit) has




Applied behavior interventions Autism spectrum disorder Physiotherapy Evidence Database

increased the early diagnosis of children with ASD.2 However, health professionals and the families they serve often face challenges in accessing developmental and behavior interventions that may optimize learning, functioning, and participation.

See related article, p 338 Supported in part by a Maternal and Child Health Grant, “Illinois Lend” (HRSA-08-148). Reprint requests: Michael E. Msall, MD, University of Chicago Pritzker School of Medicine, 950 E 61st St, SSC Rm 207, Chicago, IL 60637. E-mail: [email protected] J Pediatr 2009;154:319-21 0022-3476/$ - see front matter Copyright © 2009 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2008.10.039