Apparent Life-threatening Events Research Articles

Factors associated with infant death after apparent life-threatening event (ALTE)

To detect factors associated with greater risk of death in infants after an apparent life-threatening event (ALTE). This cross-sectional, retrospective, descriptive and analytic study evaluated infants younger than 12 months who had a sudden event of cyanosis, pallor, hypotonia or apnea and were seen in the emergency department of a tertiary university hospital. Forward stepwise logistic regression (Wald) was used to calculate and adjust odds ratios to evaluate associations. Mean age of the 145 patients included in the study was 105 days (median = 65 days). Eleven (7.6%) died, and their mean age was 189 days (median = 218 days). Mean age of survivors was 98 days (median = 62 days) (p = 0.003). Activity before the event, prematurity and number of events were not associated with death. A significant association was found with pallor. Of the 11 infants, 3 had spontaneous resolution of ALTE, whereas 8 patients [27.6%; p < 0.001; OR = 14.3 (95%CI 3.51-58.3)] did not. The associations with respiratory or cardiovascular disease were also significant. In multivariate analysis, immediate spontaneous resolution [p = 0.015; OR = 6.06 (95%CI 1.02-35.94)] and diagnosis of cardiovascular disease [p = 0.047; OR = 164.27 (95%CI 7.34-3.673.78)] remained statistically significant. Infants who experienced an ALTE had a higher risk of subsequent death when their age was greater than 6 months and the event had a long duration, particularly when ALTE was associated with cardiovascular disease.

Apparent life-threatening events: Assessment, Risks, Reality

Apparent life-threatening events (ALTEs), because of their prevalence as well as their potential to hide serious diseases and consume significant medical resources, remain a challenge for physicians caring for infants. In this review, we focused on the assessment of the well-appearing infant for the most serious diagnoses, namely serious bacterial infections, seizure disorders, child abuse, metabolic disorders and severe apnoea with hypoxemia. Our extensive review of the literature has highlighted the difficulties physicians are facing in this evaluation, especially for the youngest infants (aged less than 2 months). Large-scale prospective studies are needed to identify risk factors and to guide physicians as to who should be investigated and the minimal investigation needed to avoid missing such conditions as serious bacterial infection, abusive head injury or repeated severe cardiorespiratory events. While infants with severe forms of metabolic disorders typically present with evident signs and symptoms, less severe forms of metabolic disorders, seizure disorders, and some forms of child abuse will often be diagnosed only when recurrent events are investigated.

Genes versus environment in cystic fibrosis

vember 2010 A retrospective study to assess the rates of abusive head trauma in patients presenting with an apparent life threatening event (ALTE) was performed at the University of Utah from 1999-2003 by Guenther et al. The results show that 1.4% of ALTE cases were diagnosed with abusive head trauma. A history of a documented 911 call, vomiting, or irritability was significantly associated with abusive head trauma. The possible reasons for these associations are discussed by the authors. Article page 821 <

ALTEs and abusive head trauma

vember 2010 A retrospective study to assess the rates of abusive head trauma in patients presenting with an apparent life threatening event (ALTE) was performed at the University of Utah from 1999-2003 by Guenther et al. The results show that 1.4% of ALTE cases were diagnosed with abusive head trauma. A history of a documented 911 call, vomiting, or irritability was significantly associated with abusive head trauma. The possible reasons for these associations are discussed by the authors. Article page 821 <

Update on the use of melatonin in pediatrics

Melatonin, an endogenously produced indoleamine, is a highly effective antioxidant, free radical scavenger, and a primary circadian regulator. Melatonin has important antioxidant properties owing to direct and indirect effects. It directly scavenges reactive oxygen and reactive nitrogen species, prevents molecular oxidation, improves mitochondrial physiology, and restores glutathione homeostasis. Its indirect antioxidant effects stem from its ability to stimulate the activities of the enzymes involved in the glutathione cycling and production. Melatonin, by reducing free radical damage, may be an effective protective agent for the fetus as it is in adults. Several clinical studies on melatonin have shown that it reduces oxidative stress in human newborns with sepsis, hypoxic distress, or other conditions, where there is excessive free radical generation. A role of melatonin in infant development has also been suggested. Pineal dysfunction may be associated with deleterious outcomes in infants and may contribute to an increased prevalence of sudden infant death syndrome. Delayed melatonin production is evident in infants who had experienced an apparent life-threatening event. Melatonin has been used as a pharmacologic treatment for insomnias associated with shift work, jet lag, and delayed sleep onset in adults for decades. In children as well, melatonin has value as a sleep-promoting agent. Evidence suggests that melatonin has utility as an analgesic agent presumably related to its ability to release β-endorphin. The data support the notion that melatonin, or one of its analogs, might find use as an anesthetic agent in children.

Upper airway reflexes in response to gastric reflux

Gastric reflux, and especially laryngopharyngeal reflux, occur several times a day in every infant. Most often, this does not pose any problem. However, in certain conditions, the contact between the refluxate and the upper airway mucosa can trigger several reflexes leading to cardiorespiratory inhibition. This is especially true for the laryngeal chemoreflexes, which are triggered by laryngeal penetration of gastric refluxate. The laryngeal chemoreflexes are held responsible for a subset of apnoeas of prematurity, many apparent life-threatening events, and probably some cases of sudden infant death syndrome. Although a number of experiments in newborn animals, as well as a few clinical studies in human infants, have been performed in the last 40 years to evaluate laryngeal chemoreflexes, their true role in neonatal cardiorespiratory events is still highly debated. In addition, many uncertainties persist with regard to treatment and prevention of their potentially dramatic consequences.

The Eye Examination in the Evaluation of Child Abuse

Retinal hemorrhage is an important indicator of possible abusive head trauma, but it is also found in a number of other conditions. Distinguishing the type, number, and pattern of retinal hemorrhages may be helpful in establishing a differential diagnosis. Identification of ocular abnormalities requires a full retinal examination by an ophthalmologist using indirect ophthalmoscopy through a pupil that has been pharmacologically dilated. At autopsy, removal of the eyes and orbital tissues may also reveal abnormalities not discovered before death. In previously well young children who experience unexpected apparent life-threatening events with no obvious cause, children with head trauma that results in significant intracranial hemorrhage and brain injury, victims of abusive head trauma, and children with unexplained death, premortem clinical eye examination and postmortem examination of the eyes and orbits may be helpful in detecting abnormalities that can help establish the underlying etiology.

Abusive Head Trauma in Children Presenting with an Apparent Life-Threatening Event

To identify rates of abusive head trauma and associated clinical risk factors in patients with an apparent life-threatening event (ALTE). Retrospective study of infants, 0 to 12 months, admitted for an apparent life-threatening event (ALTE; 1999-2003). Patients with abusive head trauma were identified at presentation or on follow-up; statistical analysis identified characteristics associated with abusive head trauma. Of 627 patients with ALTE, 48% were male. Nine (1.4%) were diagnosed with abusive head trauma, of whom 5 were diagnosed in the emergency department. All cases detected in the emergency department had physical examination findings indicative of abusive head trauma. Patient age, male sex, or ethnicity were not significantly different between those with and without abusive head trauma. More children with abusive head trauma had a documented 911 call (56% vs 22%, P = .029), vomiting (56% vs 19%, P = .018), or irritability (22% vs 3%, P = .033). Multivariate analysis revealed odds ratio for abusive head trauma were 4.9 with a 911 call (P = .037), 5.3 with vomiting (P = .024), and 11.9 with irritability (P = .0197). Abusive head trauma is in the differential for infants with an ALTE, although almost half of the cases are missed by current emergency department management. Vomiting, irritability, or a call to 911 are significantly associated with heightened risk for abusive head trauma.

Autonomic dysfunction with early respiratory syncytial virus-related infection

Background Apparent life-threatening events (ALTE) and/or prolonged apnoea have been well-documented during respiratory syncytial virus (RSV) infection in infants less than 2 months of age but fundamental mechanisms remain unclear. The possibility of a central origin for the development of severe cardiac and respiratory events encouraged us, to explore the autonomic nervous system (ANS) profile of infected infants, since ANS activity may contribute to the constellation of symptoms observed during severe forms of RSV bronchiolitis. Methods Eight infants (2 preterm and 6 full-term) less than 2 months of age and presenting with severe and apnoeic forms of RSV infection were evaluated using non-invasive electrophysiological monitoring obtained simultaneously for approximately 2 consecutive hours, including a quiet sleep period. Eight control subjects, paired for gestational and postnatal age, were also evaluated. ANS status was monitored using electrocardiogram recordings and quantified through a frequency-domain analysis of heart rate variability (HRV). This included sympathetic (VLF and LF) and parasympathetic (HF) indices as well as a measure of baroreflex sensitivity (BRS) obtained using non-invasive continuous arterial pressure. Results Regardless of gestational and postnatal age, heart rate variability components (Ptot, VLF, LF, and HF) and baroreflex components (α LF, α HF and sBR) were found to be significantly lower in the RSV-infected group than in the control group ( p < 0.05). Conclusion RSV infection in neonates is associated with profound central autonomic dysfunction. The potentially fatal consequence stresses the importance of maintaining prolonged cardiopulmonary monitoring.

Apparent life‐threatening event

Apparent life‐threatening event

Postnatal autonomic activity in the preterm lamb

Background Early postnatal abnormalities of autonomic nervous system (ANS) activity, including at baseline and following cardiorespiratory challenge, are involved in apneas–bradycardias of prematurity, apparent life-threatening events of infancy and sudden infant death syndrome. Literature data suggest that baseline ANS activity does not mature normally after premature birth. Objectives This study performed in preterm lambs was aimed at assessing ANS maturation at baseline and following laryngeal chemoreflexes (LCR), a group of reflexes triggered by the contact of liquids with the laryngeal mucosa. Methods Heart rate variability (HRV) and baroreflex sensitivity (BRs) were measured at baseline and after LCR during polysomnographic recordings performed in five non-sedated lambs born 15 days prematurely. Laryngeal chemoreflexes were induced by distilled water or acid (pH 2) during sleep and wakefulness on postnatal days 7 (D7) and 14 (D14, full-term equivalence). Results While the life-threatening cardiorespiratory events of the LCR observed at D7 were no longer present at D14, baseline and post-LCR HRV and BRs indices were significantly lower at D14 compared to D7 (up to p < 0.001). These results suggest that an initial autonomic overactivity was present at D7 and normalized at D14. Conclusion The autonomic cardiac and baroreflex control appears to follow a specific evolution in the preterm compared to the full-term newborn lamb, with an important initial autonomic stress, which normalizes at an age equivalent to full-term. Potential relevance of these findings in relation to anomalies of cardiac control in the early postnatal period, such as apneas–bradycardias of prematurity, apparent life-threatening events of infancy and sudden infant death syndrome, awaits further studies.

Risk of Serious Bacterial Infection in ALTEs

Source: Mittal M, Shofer F, Baren J. Serious bacterial infection in infants who have experienced an apparent life-threatening event. Ann Emerg Med. 2009; 54:(4) 523– 527; doi: 10.1016/j.annemergmed.2008.12.037To determine the incidence of serious bacterial infection (SBI) among infants who experience an apparent life-threatening event (ALTE), investigators at the Children’s Hospital of Philadelphia performed a prospective observational study. Between June 2006 and May 2007, infants younger than 12 months presenting to the emergency department (ED) with a history of ALTE were prospectively enrolled. The National Institutes of Health consensus statement was used to define ALTE,1 characterized by some combination of apnea, color change, choking, gagging, or marked change in muscle tone. Infants with a clear alternative medical diagnosis at the time of presentation (eg, febrile seizure or bronchiolitis) were excluded.A standardized interview of parents or guardians of enrolled infants was conducted and the physical examination performed by the ED physician was recorded. Medical records were reviewed to establish the hospital course and final diagnosis. The primary outcome of SBI was defined as detection of a bacterial pathogen in blood, urine, or cerebrospinal fluid. Parents or guardians of all enrolled infants were surveyed by telephone four weeks after the ED visit to detect missed cases of SBI.During the study period, 228 infants met the study definition for ALTE. Parents or guardians of 12 infants refused consent and 18 infants were missed. The median age of enrolled infants was 49.5 days and 34% were born prematurely. The rate of hospital admission was 76%. While only 4.5% of infants experienced fever during the ED visit, 22% underwent some component of an evaluation for SBI (19% had a blood culture, 18% had a urine culture, and 9% had a cerebrospinal fluid culture). There were no true positive culture results. Of the 154 infants who did not undergo any component of SBI evaluation, none were found to have an SBI during the four-week follow-up interview. Only 1 of the 198 families was unable to be reached for telephone follow-up. This infant was 3 days old with hyperbilirubinemia at the time of ED evaluation and had negative blood and urine cultures. Two other infants with ALTE were diagnosed with enteroviral meningitis (8-week-old premature twins) and did undergo a full evaluation for SBI which was negative. Approximately 9% of infants in the cohort were found to have evidence of a viral infection.The authors report that the incidence of SBI among infants presenting to the ED with a history of ALTE is very low (95% CI, 0%–1.8%). Therefore, the investigators conclude that routine full evaluation for SBI in well-appearing infants is unnecessary.ALTEs occur at an estimated frequency of 2.46 per 1,000 live births2 and are a common cause of ED visits in young infants. The diagnostic evaluation and management of infants presenting with a history of ALTE varies widely.3 (For information about risk factors for extreme events in infants hospitalized for ALTE, see AAP Grand Rounds, June 2009;21:66.4)While participating pediatric emergency medicine physicians ordered testing for SBI less frequently than previously reported,5 the study’s conclusions are strengthened by the excellent rate of follow-up. The authors acknowledge that although no infant in the study was found to have a urinary tract infection (UTI), rates of UTI among infants with ALTE range from 0% to 8% in the existing literature.6–8Even though this study was performed at a single institution, both its large size and prospective methodology provide practitioners with further evidence that most infants with ALTE need not undergo invasive testing for bacterial illness with blood and cerebrospinal fluid cultures. Physicians should continue to evaluate infants experiencing ALTE who appear ill or have other signs of infection for SBI as clinically warranted.

Use of a Homeopathic Preparation for “Infantile Colic” and an Apparent Life-Threatening Event

An apparent life-threatening event (ALTE) caused by ingestion of drugs or toxins has been reported rarely among infants. None of these agents was homeopathic medication. We report 11 infants who presented with an ALTE after ingestion of Gali-col Baby, a homeopathic agent indicated for "infantile colic." A retrospective case-control study was conducted. Charts of all infants who were younger than 1 year and were admitted with an ALTE from January 2005 through August 2008 to the pediatric division at the Barzilai Medical Center were reviewed. Age-matched infants who were admitted on the same dates for a reason other than ALTE served as a control group. Information on medications administered before admission was recorded. During the study period, 36 635 children visited the pediatric emergency department of the Barzilai Medical Center. There were 11 057 admissions to the pediatric division during this period, 115 of which were because of an ALTE. Eleven of these infants received Gali-col Baby before the event as opposed to none in the control group (P < .005). Three infants received a significant overdose, compared with the manufacturer's recommended dosage. After a thorough investigation, no other presumptive causes for ALTE were found among the 11 infants. Gali-col Baby is associated with an ALTE in some infants. There are no published controlled trials on the efficacy or safety of its use; therefore, better control and supervision of Gali-col Baby and probably other homeopathic medications are needed to prevent possible serious adverse effects.

Retinal Hemorrhages and Apparent Life-Threatening Events

To determine the prevalence of retinal hemorrhages in apparent life-threatening events (ALTEs) with the purpose of facilitating the differential diagnosis of the cases of nonaccidental head trauma. Prospective study on children aged 15 days to 2 years admitted to our hospital with a diagnosis of an ALTE over a period of 2 years (May 2004-May 2006). All the children underwent detailed ophthalmologic examination within 72 hours of admission. If retinal hemorrhages were detected, further investigation was undertaken to rule out systemic disorder or maltreatment. One hundred eight children with an ALTE were examined. No patient was found to have retinal hemorrhages nor was any found to have experienced child abuse. Therefore, using the Hanley rule of 3, we can be confident to an upper limit of 95% that the chance of retinal hemorrhages occurring as a result of an ALTE alone is at the most 0.028. Apparent life-threatening events alone are unlikely to cause retinal hemorrhages in children younger than 2 years. Therefore, if retinal hemorrhages are detected, investigation into the possibility of nonaccidental injury is essential.

Thalamic infarct presenting as apparent life‐threatening event in infants

Thalamic infarction with distinct manifestations is well-described in adults but less well-delineated in children. We report two infants who presented with an apparent life-threatening event (ALTE) with very early magnetic resonance imaging (MRI) demonstrating a unilateral thalamic infarction. Subsequent MRI demonstrated bilateral changes in the brain stem and basal ganglia, which were in keeping with profound hypoxic ischaemic injury. We propose the thalamic infarction to be the primary event precipitating a profound hypoxic ischaemic injury as an alternative explanation to the neuroimaging observation. Thalamic infraction may have a causal role in ALTE. Early and appropriate neuroimaging is required to detect these changes.

Características epidemiológicas y factores de riesgo de los episodios aparentemente letales

Introduction To report our experience with a guideline approach for the assessment of apparent life-threatening events (ALTE) in our pediatric emergency departments (PED), to know their incidence, epidemiological characteristics and the yield of laboratory investigations (LI). Patients and methods Prospective, case-control study of a guideline approach for infants under age 12 months who suffered an ALTE between 01/06/06 and 31/05/07 and were attended at our PEDs. We ordered LI as a function of the clinical history. All the cases were admitted for a minimum of 12 h. We conducted a telephone interview at 12 months. Results Fifty ALTE were included, corresponding to an incidence of 5‰ live births. The median age was 8.46±8.7 weeks. Compared to controls they had significantly more primogenits and previous behavioral abnormalities. Only 13 presented significant abnormalities at examination, and 6 had recurrent ALTE at the PED. LI were abnormal in 41 (82%), but only in 8 cases did they contribute to a secondary diagnosis. There were 29 idiopathic ALTE (58%). Twenty one (42%) had associated conditions, who had smoked significantly more during pregnancy, age older than 12 weeks and abnormalities at examination. Four had recurrence of the episodes: one suffered a sudden infant death syndrome (SIDS). At 12 months the cases had a significantly higher incidence of recurrent vomiting, breath holding spells and weight-psychomotor retardation. Conclusions The ALTE incidence was 5‰ live births. Primogenits and/or behavioral abnormalities were most frequent during the first weeks after birth and/or thereafter at 12 months of age. A total of 42% had a related diagnosis: associated with age older than 12 weeks, maternal smoking habits and abnormalities at examination. There was one case of SIDS. Laboratory investigations had a low yield.

Cholinergic and oxidative stress mechanisms in sudden infant death syndrome

Aim:To determine whether biochemical parameters of cholinergic and oxidative stress function including red cell acetylcholinesterase (AChE), serum/plasma thyroglobulin, selenium, iron, ferritin, vitamins C, E, and A affect risk in apparent life-threatening event (ALTE), sudden infant death syndrome (SIDS), and sudden unexpected death in infancy (SUDI). To assess these biochemical parameters as a function of age; and for influence of pharmacology and epidemiology, including infant health, care, and feeding practices.Methods:A multicentre, case–control study with blood samples from 34 ALTE and 67 non-ALTE (control) infants matched for age, and 30 SIDS/SUDI and four non-SIDS/non-SUDI (post-mortem control) infants.Results:Levels/activity of the biochemical parameters were not significantly different in ALTE vs. control infants, with the exception of higher vitamin C levels in the ALTE group (p = 0.009). In ALTE and control groups, AChE and thyroglobulin levels increased and decreased respectively from birth to attain normal adult levels from 6 months. Levels of iron and ferritin were higher in the first 6 month period for all infant groups studied, intersecting with vitamin C levels peaking around 4 months of age.Conclusion:Lower AChE levels and higher combined levels of iron and vitamin C in the first 6 months of life may augment cholinergic and oxidative stress effect, particularly at the age when SIDS is most prevalent. This may contribute to risk of ALTE and SIDS/SUDI events during infancy.

Prevalence of epilepsy and seizure disorders as causes of apparent life- threatening event (ALTE) in children admitted to a tertiary hospital

To determine the prevalence and describe clinical characteristics of seizure disorders and epilepsy as causes of apparent life- threatening event (ALTE) in children admitted at the emergency and followed in a tertiary hospital. Cross-sectional study with prospective data collection using specific guidelines to determine the etiology of ALTE. During the study, 30 (4.2%) children admitted to the hospital had a diagnosis of ALTE. There was a predominance of males (73%) and term infants (70%). Neonatal neurological disorders and neuropsychomotor development delay were found respectively in 13.4% and 10% of the cases. Etiological investigation revealed that 50% of the cases were idiopathic, and 13.4% were caused by epilepsy or seizure disorders. Although all patients had recurrent ALTE events, epilepsy had not been previously suspected. Epilepsy should be included in the differential diagnosis of ALTE, particularly when events are recurrent.

Perfil epidemiológico de crianças com Apparent Life Threatening Event (ALTE) e avaliação prospectiva da etiologia determinante do episódio

OBJETIVO: determinar a causa de ALTE (apparent life threatening events - eventos com aparente risco de vida) em crianças encaminhadas à emergência de hospital terciário e sua associação com características clínicas, recorrência e morbidade. MÉTODOS: estudo transversal com coleta prospectiva de dados através de anamnese, exame físico e aplicação de protocolo específico para identificação etiológica de ALTE. Após inclusão no estudo os pacientes foram seguidos ambulatorialmente para verificação de morte súbita inexplicada. As variáveis com significância estatística foram incluídas em modelo de regressão linear. RESULTADOS: trinta crianças foram incluídas entre setembro de 2004 e março de 2006, constituindo 4,2% das internações pediátricas no mesmo período. Houve predomínio no sexo masculino (73%) e nascidos a termo (70%). Em 80% dos pacientes o primeiro episódio foi observado até os três meses de idade, predominantemente em vigília (83%). Dos casos estudados, 50% foram considerados ALTE idiopático, 20% causados pelo refluxo gastroesofágico (RGE) e 10%, por epilepsia. O seguimento evidenciou um caso de recorrência e óbito. CONCLUSÕES: a prevalência, etiologia e frequência de casos de ALTE encontradas assemelham-se aos da literatura. As variáveis estudadas não foram preditivas quanto à recorrência do episódio, mas o tratamento específico foi determinante no seu controle.

Surveillance study of apparent life-threatening events (ALTE) in the Netherlands

SIDS and ALTE are different entities that somehow show some similarities. Both constitute heterogeneous conditions. The Netherlands is a low-incidence country for SIDS. To study whether the same would hold for ALTE, we studied the incidence, etiology, and current treatment of ALTE in The Netherlands. Using the Dutch Pediatric Surveillance Unit, pediatricians working in second- and third-level hospitals in the Netherlands were asked to report any case of ALTE presented in their hospital from January 2002 to January 2003. A questionnaire was subsequently sent to collect personal data, data on pregnancy and birth, condition preceding the incident, the incident itself, condition after the incident, investigations performed, monitoring or treatment initiated during admission, any diagnosis made at discharge, and treatment or parental support offered after discharge. A total of 115 cases of ALTE were reported, of which 110 questionnaires were filled in and returned (response rate 97%). Based on the national birth rate of 200,000, the incidence of ALTE amounted 0.58/1,000 live born infants. No deaths occurred. Clinical diagnoses could be assessed in 58.2%. Most frequent diagnoses were (percentages of the total of 110 cases) gastro-esophageal reflux and respiratory tract infection (37.3% and 8.2%, respectively); main symptoms were change of color and muscle tone, choking, and gagging. The differences in diagnoses are heterogeneous. In 34%, parents shook their infants, which is alarmingly high. Pre- and postmature infants were overrepresented in this survey (29.5% and 8.2%, respectively). Ten percent had recurrent ALTE. In total, 15.5% of the infants were discharged with a home monitor. In conclusion, ALTE has a low incidence in second- and third-level hospitals in the Netherlands. Parents should be systematically informed about the possible devastating effects of shaking an infant. Careful history taking and targeted additional investigations are of utmost importance.