Epidemiology of apparent life threatening events

Aims: To investigate the epidemiology and risk factors of apparent life threatening events (ALTE). Methods: A prospective study enrolled all live-born infants in the Tyrol (1993–2001). Information on pregnancy, sociodemographic characteristics, child care practices, and infant''s behaviour in the first four to six weeks of life was collected with a standardised questionnaire, and was available for 44 184 infants. ALTE was identified from hospital admission records. Results: During the study period 164 ALTE cases were identified, corresponding to an incidence of 2.46/1000 live births. In 73 of these infants no cause for the event and no comorbidity could be found (idiopathic ALTE). On average ALTE manifested ten weeks earlier than SIDS. Of various SIDS risk factors in the survey area, the prone sleeping position, smoking during pregnancy, low gestational age, profuse night sweating, and family history of infant death showed a moderate relation to the risk of overall ALTE, but only smoking maintained significance in the multivariate risk model. None of these variables was associated with idiopathic ALTE. In contrast to SIDS the frequency of ALTE did not change during the study period. None of the ALTE infants experienced SIDS later in life. Behavioural abnormalities such as feeding difficulties, episodes of pallor, cyanotic episodes, and repeated apnoea episodes were strongly associated with an increased risk of overall and idiopathic ALTE. Conclusions: Although there are some similarities in the clinical presentation and epidemiology of SIDS and ALTE, differences clearly predominate. Accordingly, ALTE and SIDS should not be considered different manifestations of the same disease process.     

Management of apparent life-threatening events (ALTE)

In contrast to sudden infant deaths, the incidence of apparent life-threatening events (ALTE) has remained rather constant at 0.6–2.5/1000. Identifying the underlying cause of an event is paramount, requires careful history taking and a variety of investigations, summarized in this review. If no preventable cause is found, infants should be placed on a memory monitor, which may help to identify the underlying pathophysiology from analysis of the traces potentially thus recorded. For example, a sudden increase in heart rate despite severe hypoxaemia may suggest an epileptic seizure, while certain inconsistencies between the data recorded and parental reports of the event may hint towards fabricated events. A consistent feature in recorded ALTE that remain unexplained is severe hypoxaemia, mostly without prolonged cessations in breathing movements, suggesting upper airway obstruction or intrapulmonary shunting. If no event occurs in hospital, infants should be discharged on a memory monitor. If no further events occur within 4–6 weeks of the initial event, recurrence risk is very low, and monitoring can be discontinued. A recently discovered entity are neonatal ALTE, which may be related to a potentially asphyxiating environment, e.g. during skin-to-skin contact in the prone position or breast feeding with a mother who is inexperienced in handling and assessing her newborn baby. These situations thus require parental education and careful observation of the newborn by health professionals.     

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.     

Epidemiology of apparent life threatening events.

AIMS: To investigate the epidemiology and risk factors of apparent life threatening events (ALTE). METHODS: A prospective study enrolled all live-born infants in the Tyrol (1993-2001). Information on pregnancy, sociodemographic characteristics, child care practices, and infant's behaviour in the first four to six weeks of life was collected with a standardised questionnaire, and was available for 44,184 infants. ALTE was identified from hospital admission records. RESULTS: During the study period 164 ALTE cases were identified, corresponding to an incidence of 2.46/1000 live births. In 73 of these infants no cause for the event and no comorbidity could be found (idiopathic ALTE). On average ALTE manifested ten weeks earlier than SIDS. Of various SIDS risk factors in the survey area, the prone sleeping position, smoking during pregnancy, low gestational age, profuse night sweating, and family history of infant death showed a moderate relation to the risk of overall ALTE, but only smoking maintained significance in the multivariate risk model. None of these variables was associated with idiopathic ALTE. In contrast to SIDS the frequency of ALTE did not change during the study period. None of the ALTE infants experienced SIDS later in life. Behavioural abnormalities such as feeding difficulties, episodes of pallor, cyanotic episodes, and repeated apnoea episodes were strongly associated with an increased risk of overall and idiopathic ALTE. CONCLUSIONS: Although there are some similarities in the clinical presentation and epidemiology of SIDS and ALTE, differences clearly predominate. Accordingly, ALTE and SIDS should not be considered different manifestations of the same disease process.     

Etiology of 19 infants with apparent life-threatening events: Relationship between apnea and esophageal dysfunction

There are various identifiable diseases or conditions that can cause apparent life-threatening events (ALTE; e.g. gastroesophageal reflux (GER) and seizures). Nineteen infants with ALTE (mean age: 4.3 months) were brought to our hospital between June 1986 and August 1991. The causes of these ALTE were investigated. Analysis of laboratory data, radiological studies and esophageal function tests led to the diagnosis of GER in six of 19 infants; pertussis in five; upper respiratory infection in three; vagotonia-like condition with esophageal dysfunction in two; laryngostenosis with cerebral palsy in two; choking on food or drink in two; and epilepsy in one infant. Two cases (one case of pertussis and one of vagotonia-like condition) were associated with GER. Some of the cases demonstrate that ALTE in infants may be induced by GER or some esophageal dysmotility. Further studies of ALTE are needed to ascertain how frequently GER or esophageal dysmotility is responsible for ALTE.     

Why do ALTE infants not die in SIDS?

Aim: To compare known risk factors for sudden infant death syndrome (SIDS) amongst infants with apparent life threatening events (ALTE) with their matched controls, and ALTE infants who subsequently died of SIDS with infants surviving an ALTE.
Methods: Questionnaires with replies were obtained from 58 ALTE infants and 56 sex and age matched ALTE control infants. 244 SIDS cases and 868 SIDS controls were used as comparison.
Results: The incidence of ALTE was found to be 1.9% among SIDS controls, but 7.4% among infants who later on died of SIDS. The parents sought medical advice in 0.9% vs 3.7%. ALTE infants did not differ from their matched controls. In the ALTE group 13.3% of the survivors had the combination of prone sleeping and maternal smoking compared with 33.3% of those who became SIDS victims.
Conclusions: Our results show some major differences between the ALTE infants and SIDS victims not supporting that these conditions belong to the same entity. However, we cannot exclude the possibility that there is a subpopulation of ALTE infants who did not die in SIDS due to that they were sleeping on the back and not exposed to nicotine.     

Cardiac tamponade presenting as an apparent life-threatening event

The initial emergency department (ED) evaluation of infants with an apparent life-threatening event (ALTE) often fails to identify a definitive cause for the event. Many children that present with an ALTE appear normal by the time they arrive to the ED. These factors can desensitize clinicians into prematurely discounting serious underlying causes of the ALTE or being less prompt in their evaluation of these patients. We present the case of a young infant who presented to an ED with an ALTE resulting from cardiac tamponade. Cardiac tamponade has not been reported as an underlying cause of infants presenting to the ED with an ALTE. Previously reported cases of cardiac tamponade in children have occurred as a complication of malignancies, cardiac surgery, trauma, infections, central venous catheter placement, rheumatologic, and autoimmune diseases. This case should serve as a reminder to clinicians to maintain a broad differential diagnosis and promptly evaluate all infants presenting with an ALTE.     

Obstructive sleep apnea in infants: relation to family history of sudden infant death syndrome, apparent life-threatening events, and obstructive sleep apnea

OBJECTIVES: Familial aggregation of obstructive sleep apnea (OSA) has been shown to be associated with sudden infant death syndrome (SIDS) and apparent life-threatening events (ALTE) in infants. We wanted to determine the incidence of OSA in infants with siblings with ALTE and SIDS referred to our sleep clinic and to ascertain whether OSA was more common in infants who have family histories of SIDS, ALTE, and OSA. STUDY DESIGN: We studied 125 infants (mean age, 11.5 +/- 0.6 weeks) who were separated into 2 groups on the basis of their family history; polysomnographic studies were performed on each infant. RESULTS: Twenty infants had a multiple family history of SIDS, ALTE, or OSA (group 1), whereas the other 105 infants (group 2) had only one case of SIDS or ALTE within the family and no known history of OSA. We found that 19 of 20 infants in group 1 had OSA, whereas only 31 of 105 infants in group 2 had OSA (chi-squared analysis, P <.05). The OSA recorded was more frequent in infants of group 1 than in those of group 2. Follow-up studies in some infants with OSA demonstrated a progressive decrease in OSA, which resolved between 6 and 12 months of age. CONCLUSION: We conclude that infants of families with multiple histories of SIDS, ALTE, and OSA are more likely to have OSA than infants of families with only one case of SIDS or ALTE.     

Factors involved in the pathogenesis of unexpected near miss events of infants (ALTE)

Near miss events or apparent life threatening events (ALTE) are considered preliminary stages of sudden infant death syndrome (SIDS). The current definition of near miss SIDS postulates that such an event happens unexpectedly and that no life threatening cause of disease can be detected. However in 32 of 34 observations of ALTE pathological changes actually could be identified by through investigations: 11 central nervous diseases, 10 respiratory tract disturbances, 5 metabolic abnormalities, 5 disturbances of the digestive tract and 1 cardiac disease. There were 22 morphologically manifested causes as opposed to 10 functional failures mainly respiratory control and oesophageal disturbances. Irrespective of the main diagnosis sleep apnea syndrome (SAS) could be detected in 17 of 28 infants combined with bradycardia in 5 cases, and oesophageal disturbances in 16 of 17 infants. Four babies later died, two of them suffered from carnitine deficiency and one from organic acidopathy. It is our conclusion that numerous, even banal causes of disease are able to trigger ALTE if there is a coincidence with phases of increased instability of vital regulatory mechanisms of autonomous centres in infants.     

Apparent Life-Threatening Events in the Young Infant and Neonate

An infant presenting to the ED with an ALTE remains a difficult clinical challenge. The history and physical examination are key to directing the diagnostic workup. There is no standard evaluation for an infant with an ALTE. Currently, in-hospital observation and monitoring remain an accepted treatment for young infants and especially for those with repeated ALTEs. In young infants, prematurity plays a significant role in the diagnostic possibilities that include GI, neurologic, and infectious disorders. The goal is to identify a treatable cause that will serve to define the expected natural history. Evidence is lacking regarding the true risk of subsequent events and death vs the perceived risk of death. Diagnosis and treatment are complicated by the heterogeneity of the group of infants with ALTE. Collaborative multicenter studies are needed to develop and refine best practice guidelines, to improve coding and diagnostic criteria for infants with ALTE, and to identify the true risk of adverse outcomes.     

Apparent life-threatening events in presumably healthy newborns during early skin-to-skin contact

The death or near death of a presumably healthy newborn in the delivery room is uncommon. We report here 6 cases of apparent life-threatening events (ALTEs) in the delivery room during the first 2 hours of life. In each case, the incident occurred in a healthy infant who was in a prone position on his or her mother's abdomen during early skin-to-skin contact. In most cases, the mother was primiparous, and in all cases the mother and infant were not observed during the initiation of skin-to-skin contact and breastfeeding. There are many benefits of early skin-to-skin contact and breastfeeding in the delivery room. However, in view of the risk of a rare but significant ALTE, we suggest that surveillance of newborns is needed. Although many ALTEs are apparently caused by obstruction, we suggest that a standardized investigational workup be performed after an ALTE.     

Early neonatal sudden death or near death syndrome. An epidemiological study of 29 cases

Early neonatal sudden death syndrome (SIDS) is a rare but well known disease entity. Between January 1975 and December 1991, 29 full-term newborn infants delivered in our maternity unit and, considered healthy at birth, suffered early SIDS ( n = 15) or early apparent life threatening events (ALTE) ( n = 14). Data from the whole population of live full-term infants born in our hospital during the past five years have been used as a reference (n = 27 841). The general rate of early SIDS was 0.14 per 1000 (15/107 263). Combining early ALTE cases, the overall rate was 0.27 per 1000 (291107263). A postmortem examination was performed for all infants who died (20/29): no cause of death could be determined, and we did not observe a single case with evident sequelae. There were 9 deaths (31 %) within the first hour after delivery and 12 deaths occurred in the early morning hours (04:00–08:00; RR = 3.76; p = 0.0008). The lowest incidence was in the spring (RR = 0.21; p = 0.03). There was a tendency for an increased incidence during the weekend and the summer. No influence of sex, maternal age, gestational age, infant weight presentation, delivery, anesthesia or presence of meconium-stained fluid was found. In our opinion, SIDS can take place even during the first hour of life and it is not possible to predict when a baby might be affected. Pediatrically trained caregivers, close observation by the mother during the first few days and resuscitation facilities in maternity wards may be the most important preventive measures to reduce the risk of early SIDS and the consequences of ALTE in the early newborn period.     

Apparent life-threatening episodes in children

An apparent life-threatening episode (ALTE) refers to a sudden and unexplained occurrence of breathing abnormality usually associated with colour change, choking or altered muscle tone. Most children are younger than 1 year old. ALTE is a cause for great concern to the parents and needs careful assessment to rule out any underlying serious illness. The evaluation of the affected child involves careful history taking, examination and relevant investigations. The most frequent causes are gastro-oesophageal reflux (GOR), respiratory infections including pertussis, seizures and urinary tract infections. Factitious illness is uncommon but well-recognised and needs to be considered, but no diagnosis is made for up to 50% of cases despite investigations. Most infants have no further episodes and remain well, but some have recurrent ALTE or may die and may be classified as sudden infant death syndrome (SIDS). Studies have failed to establish a clear association between ALTE and SIDS. Some children are discharged home with an apnoea monitor although there is no clear benefit in doing this. Adequate support to the family and follow-up is essential. Medical staff should be aware of the possibility of non-accidental injury and factitious illness.     

Respiratory and arousal responses to hypoxia in apnoeic infants reinvestigated

Respiratory and arousal responses to mild hypoxia (15% oxygen in nitrogen) were recorded in 18 healthy infants and 33 infants who had sustained severe sleep related apnoeic events (ALTE). Respiratory movements and transcutaneous gas pressures (tcPO₂ and tcPCO₂) were continuously monitored during the 10 min test. The changes in tcPCO₂ in relation to the decrease in tcPO₂ were used as an index of the ventilatory and metabolic responses to hypoxia. We found that the response of apnoeic infants was within the range of the controls although the distribution of the individual response slopes was shifted towards the lower end of the range. Arousal was observed in 33% of apnoeic infants and 32% of the controls. Regular periodic breathing occurred in 42% of apnoeic infants compared to 28% of controls. In contrast to the controls, periodic breathing in apnoeic infants was not associated with a drop in tcPCO₂ to below baseline levels. Apnoeic infants also alternated between regular and periodic breathing during the test. These findings are suggestive of a weak feed back control of breathing but do not support former views of a deficient hypoxic response in infants with ALTE.Abbreviations ALTE apparently life-threatening event - SID sudden infant death     

Gastroesophageal reflux associated with respiratory abnormalities during sleep

To determine whether gastroesophageal reflux (GER) might be a factor in the pathogenesis of apnea in certain infants, we analyzed the frequency of prolonged central apnea (greater than 15 s) and of numerous irregularly repeated short apneas (5-15 s) ("respiratory dysfunction") in infants with an apparent life-threatening event (ALTE) (group 1, n = 62), in control infants (group 2, n = 387), and in infants with GER pathologic findings (group 3, n = 60). Finally, the incidence of GER was analyzed in 76 infants with a respiratory dysfunction during sleep (group 4). Gastroesophageal reflux was investigated using 24-h esophageal pH monitoring; respiration during sleep was investigated by polysomnography. The pH monitoring data and results of sleep investigation were analyzed in a double-blind study. A great number of infants who had an ALTE appeared to suffer from GER (42%, 26 of 62 infants), especially if the ALTE occurred while the infant was awake (52%, 14 of 27 infants). In the control infants, pH monitoring data were abnormal in 8.5%; respiratory dysfunction was observed in 5%. In those with a respiratory dysfunction, GER was detected in 75% (15 of 20 infants). In those with GER, respiratory dysfunction was observed in 45% (15 of 33 infants). In groups 3 and 4, respiratory dysfunction was associated with abnormal pH data in 40-43%. If, in the infants with a respiratory dysfunction, the GER pathologic symptoms were treated efficiently (normalization of pH data), respiratory dysfunction disappeared in 92%.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of gastro-oesophageal reflux in the aetiology of SIDS

Gastro-oesophageal reflux (GOR) has been identified as a possible cause of SIDS. Several features of GOR unique to infants presenting with apparent life-threatening events (ALTEs) have led to its 'pathogenic' definition. One is that the life-threatening apnoea itself is initiated by GOR, another is that the ALTE relates to prolonged reflux during sleep, in a vulnerable sleep-state, and finally that the ALTE relates to excessive quantities of GOR. The presumption of GOR 'pathology' as a cause of SIDS however, is questionable in these susceptible infants for three reasons: firstly, GOR is physiological and occurs in most infants; secondly, there is no general consensus on what constitutes normal physiological reflux, and thirdly, variation in the recording technique and methods of data analysis and interpretation may account for the differences between study groups. It seems likely therefore if GOR is implicated in SIDS, additional factors are involved. Under certain circumstances, physiological GOR may trigger life-threatening apnoea in apparently healthy infants, that leads to SIDS. One mechanism that could explain such a death is reflex apnoea by stimulation of laryngeal chemoreceptors (LCR) during sleep. The conditions under which this could be fatal are the occurrence of gastric contents refluxed to the level of the pharynx during sleep, in the young infant who has depressed swallowing and arousal. That is, the occurrence of GOR to the level of the pharynx during sleep, an infrequent event that is usually innocuous, could be converted to a fatal event if swallowing is impaired and arousal depressed, by a variety of mediating factors such as prone sleeping, prematurity, sedatives, seizures or upper respiratory tract infections. The identification of LCR responses, particularly in prone sleeping and premature infants provide further evidence that this mechanism may be implicated in the aetiology of SIDS in apparently healthy infants.     

Parental compliance with home cardiorespiratory monitoring.

AIMS: To evaluate parental compliance with home cardiorespiratory monitoring of premature infants with apnoea, siblings of infants who died of sudden infant death syndrome (SIDS), and infants with an apparent life threatening event (ALTE), during the first month of use. METHODS: A retrospective review of the first month's recordings was conducted on 39 premature infants with apnoea, 13 siblings of SIDS, and 16 infants with ALTE. All infants were singletons. Recommendations during the study period (1992-1994) were for daily use for 23 hours per day. Measurements were average daily hours of use and consistency of use (daily or variable). Gestational age, maternal age, and socioeconomic status as measured by receipt of public assistance were also recorded. RESULTS: Siblings of SIDS were monitored for fewer hours than were premature or ALTE infants. Only 54% of sibings of SIDS were monitored daily, compared to 87% of premature infants and 93% of ALTEs. Within each diagnostic category socioeconomic status did not affect average hours of monitoring. Consistency of use was more evident in those with private insurance, although the trend did not reach significance. CONCLUSIONS: Parents of infants with apnoea of prematurity or ALTE are highly compliant with cardiorespiratory monitoring recommendations in the first month of monitor usage. Siblings of SIDS are monitored for fewer hours and are less likely to be monitored on a daily basis.     

Parental reported apnoea, admissions to hospital and sudden infant death syndrome

Three studies were undertaken: (i) a nation-wide case-control study for sudden infant death syndrome (SIDS), with 393 cases and 1592 controls, examined the association between parental reported apnoea and SIDS; (ii) a case-cohort study, with 84 cases of parental reported apnoea and 1502 controls, aimed to identify risk factors for apnoea; and (ii) national hospital admission data for ALTE and national SIDS mortality data were compared for the years 1986 to 1994. Parental reported apnoea was associated with a significant increased risk of SIDS [adjusted odds ratio (OR) 1.86; 95% confidence interval (CI) 1.12, 3.09]. The population attributable risk was 8%. There was a significant increased risk for parental reported apnoea in infants who did not die after adjustment for potential confounders with maternal smokers, short gestation and admission to the neonatal unit. There was no association with prone sleeping position, co-sleeping and bottle feeding. The mean annual admission rate for ALTE was 9.4/1000 live births. This did not change significantly over the study period (1986-1994). In contrast, the SIDS mortality rate decreased from over 4/1000 to 2.1/1000. Admission rates were higher for Maori infants and boys. Conclusion: It may be concluded that the relationship between parental reported apnoea and SIDS is tenuous.     

Colic medication and apparent life-threatening events

Eight infants with histories of apnea and cyanosis were referred to the Southwest SIDS Research Institute for evaluation of apparent life threatening events (ALTE). All of the infants had been treated for colic with a 1:1 concentration of dimenhydrinate (Dramamine) and phenobarbital, hyoscyamine sulfate, atropine sulfate and scopolamine hydrobromide (Donnatal). The medication was pre-mixed by local pharmacists. A comprehensive work-up failed to reveal a cause for the ALTE in any infant. The Dramamine/Donnatal mixture was withdrawn and polygraphic evaluation was conducted. Cardiorespiratory abnormalities were identified in all eight infants and significant gastroesophageal reflux (GER) was documented in four. The possibility that colic medication contributes to cardiorespiratory instability and GER in vulnerable infants requires serious consideration and further evaluation.     

Apparent life-threatening events presenting to a pediatric emergency department.

OBJECTIVE: To review the etiology, clinical decision-making process, and outcomes of apparent life-threatening events (ALTEs) presenting to a children's hospital emergency department (ED). DESIGN: Retrospective patient record review. SUBJECTS: One hundred thirty infants under the age of 1 year fulfilling the diagnostic definition of an apparent life-threatening event. RESULTS: In a calendar year, 130 infants presented to a large children's hospital ED. The total number of ALTEs studied was 196. The median age was 2 months, and 50% of infants had a normal clinical examination. Eighty-three percent of ALTEs resulted in admission to the hospital. The approach to investigation and management of an ALTE during admission appeared unstructured. Discharge diagnoses, both from the ED and the inpatient service, were numerous, the most common being convulsion, febrile convulsion, GOR, and lower respiratory tract infection. The diagnosis frequently changed in those attending more than once. Eighteen months after cessation of data collection, no infants had died. Follow-up information revealed a higher-than-expected prevalence of asthma and seizures. CONCLUSIONS: This is a diverse group of infants, many of whom appear normal following the ALTE. There are many possible diagnoses, but diagnosis correlates poorly with presenting symptoms. It also appears that many commonly performed investigations conducted in this group of infants may not be those that are most helpful for diagnosis, and doctors may be making diagnoses with little supportive evidence. Until research on this group of "first-presentation" infants provides management guidelines for family and emergency doctors, it may be prudent to advise that all such infants presenting with an ALTE should be admitted for a period of observation and further investigation. This would help ensure more accurate diagnosis, as well as provide reassurance for the family.