An apparent life threatening event (ALTE) is defined as “an episode that is frightening to the observer and that is characterised by some combination of apnoea (central or occasionally obstructive), colour change (usually cyanotic or pallid but occasionally erythematous or plethoric), marked change in muscle tone (usually marked limpness), choking, or gagging”.¹ Each year many infants with clinical features compatible with these diagnostic criteria are admitted to hospital.² Resuscitation is sometimes necessary, ranging from mild stimulation to full cardiorespiratory support measures. Some of these infants die and may be classified as SIDS, which raises the possibility that ALTE and the sudden infant death syndrome (SIDS) are different expressions of the same disease. A number of previous studies reported that up to 12% of SIDS victims had experienced one or more prior episodes of ALTE.^3–,⁷

We performed a large prospective cohort study to examine whether there is an association between SIDS and ALTE in terms of shared risk factors and other common demographic characteristics.

METHODS

The survey area of this study is the Tyrol, a federal state in the western part of Austria with 630 000 inhabitants and an area of 12 650 km². It is a mountainous region located in the Alps. Main sources of income are light industry, agriculture, and tourism. The population in the Tyrol is only Caucasian. Data on child care practices were prospectively collected four to six weeks after birth for all live-born infants in the study period between 1993 and 2001. The participation rate was 86% among ALTE infants (141 of 164) and 66% among controls (44 184 of 66 549). The following variables were assessed in a standardised questionnaire completed by the infant’s mother: (a) infant’s data: age, sex, birth weight, and gestation; (b) sociodemographic background: maternal educational level, marital status; (c) pregnancy characteristics: mother’s age at delivery, number of previous pregnancies, maternal smoking habits during pregnancy; (d) postnatal factors: infant medical history and child care practices such as usual sleeping position, feeding practices; (e) infant behaviour: apnoea, repeated cyanotic episodes, remarkably pallid, profuse sweating during night. The prospective questionnaire used in the current study is part of the public health programme in Tyrol and was approved by the appropriate committee of the local Board of Health.

In accordance with usual practice, low birth weight was defined as a birth weight <2500 g and preterm delivery as <37 completed weeks of gestation. Maternal age at delivery was subdivided into two groups: <23 years and ⩾23 years; educational level was documented in years of education (<12 years v ⩾12 years). Smoking during pregnancy and thereafter was assessed in terms of “number of cigarettes smoked per day”. The infant’s usual sleeping position was classified as prone (on stomach), lateral (on side), or supine (on back). Feeding practice during the first four to six weeks of life was coded as “bottle fed”, or “breast fed” if the main type of milk given was breast milk. Feeding difficulties such as frequent vomiting after feeds or difficulties with swallowing were also carefully assessed. Mothers also reported whether they had repeatedly (that is, more than once) seen their infant “turn blue”, “turn pale”, or “stop breathing“. A minimal duration of 8–10 seconds was mentioned in the questionnaire as a crude guideline for the definition of apnoea. “Profuse sweating during sleep” was assessed when the infant’s pyjamas and/or bed sheets were regularly soaked with sweat. To test for a possible genetic predisposition, parents were asked to report unexpected and unexplained deaths that had occurred in children under 1 year of age among their first and second degree relatives.

Data on all public hospital admissions of infants aged less than 1 year in the survey area were extracted from hospital computer databases (1993–2001). A search was made of various principal and also subsidiary diagnoses under which such infants might be classified, and included the ICD-9 codes 798.4 (ALTE) and 786.0 and 786.9 (dyspnoea and respiratory abnormalities). In 2001 the ICD-10 classification was introduced, which no longer lists a specific ALTE code. Therefore, a search was made for R06.0 (dyspnoea), R06.8 (respiratory abnormalities, apnoea), and P28.4 (apnoea in the neonatal period). In a second step a definite classification was established by means of a critical review of the hospital medical records. To assess the incidence of ALTE the number of live births was used as the denominator. Associations between baseline variables and ALTE were analysed by means of the χ² test. Relative risks were calculated by dividing the incidence of ALTE among infants with a potential risk condition by the incidence among those without. Multivariate relative risks were estimated by logistic regression modelling.

RESULTS

During the study period between 1993 and 2001 a total of 164 infants met the diagnostic criteria for ALTE, corresponding to a mean incidence of 2.46 per 1000 live births. There was no clear tendency of disease rates over the time period, especially no change parallel to the substantial drop in the SIDS rate after 1994 when the SIDS prevention programme was initiated in Tyrol (fig 1⇓). Of note, none of the ALTE infants died from SIDS later in life. The median age-at-event for overall and idiopathic ALTE was 8 weeks compared to 18 weeks in SIDS infants (p < 0.001, Mann-Whitney U test). Age distributions are depicted in fig 2⇓. Clinical comorbidity was detected in 91 of the 164 ALTE cases (55%). In descending order of priority, disturbances of the respiratory (29%) and the digestive tract (22%), congenital cardiac malformations (2%), inborn metabolic errors (1%), and convulsions (1%) were observed. In several infants ALTE was the initial clinical presentation of severe airway infection, especially respiratory syncytial virus bronchiolitis and pneumonia. Disturbances of the digestive tract included gastro-oesophageal reflux as well as aspiration or choking during feeding. In 73 infants no cause for the event and no concomitant disease were identified. These events were called “idiopathic ALTE”.

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Figure 1

 (A) Rates (per 1000 live births) and 95% CI of ALTE in Tyrol. (B) Rates (per 1000 live births) and 95% CI of SIDS in Tyrol.

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Figure 2

 Age distribution of infants admitted to hospital with ALTE and those who died from SIDS, 1993–2001.

Potential association with SIDS risk factors was tested in 141 of the 164 ALTE cases (86%) for whom prospectively collected questionnaires were available. In the univariate analysis, ALTE was significantly associated with family history of infant death, single parenthood, profuse night sweating, as well as smoking during pregnancy (all p < 0.001), and less so with prone sleeping, low birth weight, or low gestational age. The latter associations lost significance once accounting for the multiple comparisons performed. In terms of absolute frequencies, the three main SIDS risk factors in the survey area (prone sleeping, lack of breast feeding, smoking in pregnancy) were much more prevalent among SIDS than ALTE infants. Of note, infant behavioural characteristics in the first weeks of life, such as repeated apnoeas and cyanotic episodes, a positive history of pallor, and feeding difficulties, were strongly related to the risk for ALTE. At least one of these characteristics was detected in about two thirds of infants who suffered an ALTE later on in life (66.4% v 29.9% in controls; p < 0.001). The difference was even more pronounced when feeding difficulties were not included in the calculation (50.7% v 16.9% in controls; p < 0.001). In a multivariate analysis allowing for all variables listed in table 1⇓ (stepwise selection procedure with standard inclusion and exclusion criteria p_E < 0.1 and p_R < 0.15) the ALTE risk profile was composed of single parenthood, parent reported apnoeas, cyanotic episodes, episodes of pallor, feeding difficulties (p < 0.01 each), maternal smoking (p = 0.036), and family history of infant death (p = 0.094) (table 2⇓).

When the analyses were restricted to cases of idiopathic ALTE, only behavioural characteristics qualified as significant risk indicators. Demographic characteristics and SIDS risk factors all did not achieve significance after accounting for the multiple comparisons performed (table 1⇑) and did not enter the multivariate risk models (table 2⇑).

DISCUSSION

Infants suffering from ALTE usually present with an acute and unexpected change in behaviour that alarmed the caregiver. The initial episodes can occur during sleep, when the infant is awake, or sometimes during feeding. The clinical appearance is defined by a combination of apnoea, colour change (cyanotic or pallid), marked change in muscle tone (limpness, rarely rigidity), choking, or gagging.¹ Resuscitation may be necessary and range from mild stimulation to full cardiorespiratory support measures. ALTE is associated with or caused by a variety of diseases, but in 30–70%^7–,¹⁰ and 45% in our survey, the cause of the event remains undetermined and the event is then termed “idiopathic ALTE”.

In various large population surveys, in which hospital records served as the source of information for case ascertainment, the frequency of ALTE was estimated to be between 0.46 and 10.0 per 1000 live births.^11–,¹⁴ The incidence of 2.46 per 1000 live births in our study fits very well into this range. Other evaluations, in which the ALTE classification relied on the parents’ response to questions such as whether they observed episodes of lifelessness or unusual respiratory events (apnoea, cyanosis, irregular respiration), reported incidence rates as high as 3–6%.^6,15

In contrast to SIDS, data on potential risk factors of ALTE are sparse. So far, only two prospective studies are available, one from Sweden¹¹ and one from Tasmania.¹⁶ In the Swedish study, epidemiological features of SIDS cases and cases of an attack of lifelessness, which comes close to our ALTE definition, were well documented, but comparable data were not available from healthy control infants in the same region.¹¹ In the Tasmanian study the cohort cannot be regarded as representative of the general infant population, because only the one-fifth of live births with the highest SIDS risk scores were enrolled.¹⁶ Our study is the first prospectively designed and population based study to examine the epidemiology of ALTE, its potential relation to SIDS, and behavioural abnormalities.