Apnea, glial apoptosis and neuronal plasticity in the arousal pathway of victims of SIDS.

Of 27,000 infants whose sleep-wake characteristics were studied under the age of 6 months, 38 died unexpectedly 2-12 weeks after the sleep recording in a pediatric sleep laboratory. Of these infants, 26 died of sudden infant death syndrome (SIDS), and 12 of definitely identified causes. The frequency and duration of sleep apneas were analysed. Sleep recordings and brainstem histopathology were studied to elucidate the possible relationship between sleep apnea and neuropathological changes within the arousal system. Immunohistochemical analyses were conducted using tryptophan hydroxylase (TrypH), a serotonin synthesizing enzyme, and growth-associated phosphoprotein 43 (GAP43), a marker of synaptic plasticity. The terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method was used for apoptosis. The pathological and physiological data were correlated for each infant. In the SIDS victims, statistically significant positive correlations were seen between the number of TrypH-positive neurons in the dorsal raphe nucleus of the midbrain and the duration of central apneas (p = 0.03), between the number of TUNEL-positive glial cells in the pedunculopontine tegmental nucleus (PPTN) and the average number of spines in GAP43-positive neurons in the PPTN (p = 0.04). These findings in the dorsal raphe nucleus of the midbrain and PPTN, that play important roles in the arousal pathway suggest a possible link between changes in arousal and SIDS.

Sudden infant deaths: stress, arousal and SIDS.

The prevalence of the Sudden Infant Death Syndrome (SIDS) has dropped in most countries following the development of education campaigns on the avoidance of preventable risk factors for SIDS. These include factors in the infant's micro environment, such as prenatal passive smoking, administration of sedative drugs, prone sleep, high ambient temperature or sleeping with the face covered. Sleep laboratory studies have shown that these risk conditions contribute to the development of respiratory and autonomic disorders and reduce the child's arousability. The opposite effects were seen when studying factors protective from SIDS, such as breastfeeding or the use of a pacifier. In victims of SIDS, similar breathing, autonomic and arousal characteristics were recorded days or weeks before their death. It is concluded that in some infants, already immature control mechanisms can be aggravated by environmental factors.

Sudden infant deaths: from epidemiology to physiology.

The incidence of sudden infant death syndrome (SIDS) has dropped significantly in most countries following the development of education campaigns on the avoidance of risk factors for SIDS. However, questions have been raised about the physiological mechanism responsible for the effects of these environmental risk factors. Since 1985, a series of prospective, multicentric studies have been developed to address these questions; over 20,000 infants were recorded during one night in a sleep laboratory and among these, 40 infants eventually died of SIDS. In this review, the following methods were employed: sleep recordings and analysis, monitoring procedure, data analysis of sleep stages, cardiorespiratory and oxygen saturation, scoring of arousals, spectral analysis of the heart rate and the determination of arousal thresholds, and statistical analysis and the results including sleep apneas, arousals and heart rate and autonomic controls in both future SIDS victims and normal infants were introduced separately. In addition, the physiological effect of prenatal risk factors (maternal smoking during gestation) and postnatal risk factors (administration of sedative drugs, prone sleeping position, ambient temperature, sleeping with the face covered by a bed sheet, pacifiers and breastfeeding) in normal infants were analyzed. In conclusion, the physiological studies undertaken on the basis of epidemiological findings provide some clues about the physiological mechanisms linked with SIDS. Although the description of the mechanisms responsible for SIDS is still far from complete, it appears to involve both arousal responses and cardiac autonomic controls during sleep-wake processes.

Developmental characteristics of apnea in infants who succumb to sudden infant death syndrome.

We compared the breathing characteristics of 40 infants who subsequently died of sudden infant death syndrome (SIDS) with those of 607 healthy infants matched for sex and age. The infants were between 2 and 19 wk old at the time of recording. Compared with the control group, the infants who died of SIDS experienced significantly more frequent episodes of obstructive and mixed sleep apnea. The duration of the apneic episodes did not exceed 15 s. Moreover, the SIDS group had a greater proportion of infants with obstructive and mixed apneic episodes than did the control group. In both groups, the frequency of episodes among male infants with apnea was greater than that among female infants. After the age of 9 wk, the proportion of male infants with episodes of obstructive apnea was greater in the SIDS group than in the control group. The frequency of apneic episodes decreased with age. The rate of decrease was significantly greater in the control subjects than in the SIDS group. This finding was made mainly in male infants. The present study provides further indirect evidence for a slower maturation of respiratory control in some infants who ultimately die of SIDS.

Maternal education and risk factors for sudden death in infants. Working Group of the Groupe Belge de Pédiatres Francophones.

UNLABELLED: To monitor infant care practices associated with risks for sudden infant death, 400 Belgian families with infants less than 6 months old were questioned by 21 paediatricians during routine visits to local paediatric practices and well baby services (11 in urban centres, 10 in rural areas). Because of incomplete information, 35 families were excluded. Of the 365 mothers included in the study, 36.1% had under 7 years of schooling, 38.4% less than 13 years, and 25.5% had a professional school or a university degree. Risk factors for sudden infant death were found in 208 (56.9%) families: a usual non-supine sleep position (31.5% of the infants); sleeping under a duvet (24.1%); mothers smoking during and after gestation (16.4%); a high room temperature (6.6%); use of sedatives (3.8%); necklaces or plastic film in the cot (2.5%); and soft beddings (2.2%). Maternal education, but not the fathers' profession was significantly related to the number of risk factors (mean odds ratio of 4.4; 95% CI: 1.5 to 5.3; P = 0.001). A stepwise logistic regression analysis identified the mother's length of schooling as the single most significant independent factor for the presence of risk (P < 0.005). CONCLUSION: Less educated mothers reported having been informed of risk-reducing recommendations as frequently as better educated mothers. It can be concluded that future reduction in risks for sudden infant death syndrome should include new strategies designed to modify infant care practices.

Ambient temperature is associated with changes in infants' arousability from sleep.

STUDY OBJECTIVE: To evaluate the influence of ambient temperature on infants' arousability from sleep. DESIGN: Two groups of healthy infants with a median age of 11 weeks were recorded polygraphically during one night: 31 infants were studied at 24 degreesC and 31 infants at 28 degreesC. To determine their arousal thresholds, the infants were exposed to white noises of increasing intensities during REM and NREM sleep. Arousal thresholds were defined by the auditory stimuli needed to induce arousals. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The arousal thresholds decreased across the night in the infants sleeping at 24 degreesC (p=.017). The finding was not found for the infants sleeping at 28 degreesC. When analyzing the arousal responses according to time of the night, it was found that the auditory thresholds were significantly higher at 28 degreesC than at 24 degreesC between 03:00 hr and 06:00 hr (p=.003). These findings were only seen in REM sleep. CONCLUSION: High ambient temperature could add to the difficulty to arouse from REM sleep in the late hours of the night.

Reduced arousals following obstructive apneas in infants sleeping prone.

A decreased arousability and an increased risk for sudden infant death syndrome (SIDS) have been shown in infants sleeping prone. Obstructive apnea, a known risk factor for SIDS, is less often terminated by an arousal reaction in infants than in adults. The effect of body position on the arousal reaction to spontaneous respiratory events had not been previously studied in infants. The aim of our study was to see if body position has an influence on the frequency and delay of the arousal reaction to obstructive apnea. All obstructive events recorded during two successive nights in 20 infants sleeping one night prone and one night supine were studied. During the supine recording 153 obstructive events were detected, and 217 were detected during the prone session. Prone sleep was not associated with an increased frequency of obstructive apneas. Total sleep time was 382 min (range, 283-456) supine and 423 min (range, 325-521) prone (p = 0.003). Obstructive events duration was 6.5 s (range, 3-21.5) when sleeping supine and 8 s (range, 3.5-30.5) when prone (p = 0.002). Behavioral arousal were found in 57.5 % of obstructive events recorded supine and in 31.3 % of those seen prone (p < 0.001). Arousal occurred after 8 s (range, 0-21) from the start of the obstructions when supine and 10.5 s (range, 3.5-23.5) when prone (p = 0.001). Sighs were found in 34 % of supine obstructive events and in 44.7 % of those prone (p = 0.040). A reaction, i.e. arousal or sigh, was found in 91.5 % of supine events and 76 % of those prone (p < 0.001). We conclude that when sleeping supine, infants arouse to obstructive events more often and after shorter delay than when prone.

Factors influencing the determination of arousal thresholds in infants - a review.

Objective: To review the major confounding factors that influence the determination of arousal thresholds in infants.Review of confounding factors: The determination of arousal thresholds in infants measures their arousability from sleep. The evaluation is influenced by various conditions. The infant's arousability is decreased by maternal factors, such as exposure to cigarette smoke, alcohol, illegal drugs or medications during gestation or breastfeeding. The levels of arousal thresholds also depend on the age of the infant and on experimental conditions, such as previous sleep deprivation, type of arousal challenges, time of administration of the arousal challenge, sleep stage, body position, room temperature, use of a pacifier, bed sharing, or type of feeding. In addition, spontaneous arousals can occur and modify the infant's response to external arousal challenges.Conclusions: Factors known to modify infants' arousability from sleep should be controlled during studies designed to determine arousal thresholds.

The influence of a pacifier on infants' arousals from sleep.

OBJECTIVE: The risk of sudden infant death during sleep was postulated to decrease with the use of a pacifier and by conditions facilitating arousals from sleep. We evaluated the influence of a pacifier on arousal from sleep in healthy infants. STUDY DESIGN: Fifty-six healthy infants were studied with polygraphy during 1 night; 36 infants used a pacifier regularly during sleep, and 20 never used a pacifier. Thumb users or occasional pacifier users were not included in the study. The infants were recorded at a median age of 10 weeks (range 6 to 19 weeks). To evaluate auditory arousal thresholds, the infants were exposed to white noise of increasing intensity during rapid eye movement sleep. RESULTS: Polygraphic arousals occurred at significantly lower auditory stimuli in pacifier users than in nonusers (P =.010). Compared with nonusers, pacifier users were more frequently bottle-fed than breast-fed (P =. 036). Among infants sleeping without a pacifier, breast-fed infants had lower auditory thresholds than bottle-fed infants (P =.049). CONCLUSIONS: Infants using pacifiers during sleep had lower auditory arousal thresholds than those who did not use a pacifier during sleep. Breast-feeding could be a further factor contributing to lower arousal thresholds. These findings could be relevant to the occurrence of sudden infant deaths during sleep.

Naso-oesophageal probes decrease the frequency of sleep apnoeas in infants.

The objective of the study was to determine whether a naso-oesophageal probe modifies sleep and cardiorespiratory patterns in infants with repeated obstructive apnoeas. Two polygraphic recording sessions were conducted in random order for 2 nights on 35 infants suspected to have repeated obstructive sleep apnoeas. One sleep study was performed with a pH probe inserted through the nasal passage down to the distal portion of the oesophagus. The other session was conducted without any naso-oesophageal probe (the baseline study). For the 25 infants who presented repeated obstructive apnoeas during baseline studies, the presence of the probe was associated with a small, but significant, decrease in the number of central apnoeas (median frequency of 18.5 apnoeas per hour without a probe; 16.1 per hour with the probe; P=0.040), and obstructive apnoeas (median of 1.9 apnoeas per hour without a probe; 0.6 per hour with the probe; P=0.016). The presence of the probe was also associated with a small increase in percentage non-rapid eye movement (NREM) sleep frequency. The changes were statistically significant only for infants who had no obstructive apnoea during baseline studies (29 vs. 31%). The presence of a naso-oesophageal probe significantly modifies the infants' respiratory characteristics during sleep. These findings should be considered when reporting and interpreting sleep studies in infants.

Frequency of obstructive and mixed sleep apneas in 1,023 infants.

STUDY OBJECTIVES: To collect normative data on the frequency of obstructive and mixed sleep apneas in healthy infants. STUDY DESIGN: 1100 infants were recorded during one night in a sleep laboratory. SETTING: the recordings were performed in an infant sleep laboratory. PATIENTS: The recordings of 1023 infants were used for analysis, the data of 77 infants being excluded because of poor recording quality. The infants were born full-term, were healthy at the time of study, had no history of apnea and were aged between 2 and 28 weeks. The polysomnographic recordings were analyzed visually and were subdivided according to the age of the subjects into 2-7 weeks, 8-11 weeks, 12-15 weeks, 16-19 weeks and 20-27 weeks of life. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: At 2-7 weeks of life, obstructive apneas (p=.013) and mixed apneas (p=.004) were significantly more frequent than at any other age group. At 8 to 11 weeks of life, obstructive apneas were significantly more frequent in boys than girls (p=.016). CONCLUSIONS: The present findings add to our knowledge of infants' respiratory characteristics during sleep.

[Autopsy practices in cases of sudden infant death syndrome in the French-speaking community of Belgium and comparison with other European countries]. / Pratiques d'autopsie en cas de mort subite du nourrisson en Communauté francophone de Belgique et comparaison avec différents pays européens.

This work summarises the current difficulties encountered in performing autopsies in cases of sudden unexplained infant deaths in Belgium. Over the last few years, the incidence of postneonatal deaths in most European countries has significantly decreased, probably due to prevention campaigns. However, there are still many difficulties encountered in systematically including autopsies in the general strategy for managing this public health problem. The analysis of autopsy practices in Belgium in cases of unexplained infants' deaths and their comparison with other European countries' practices give us the opportunity to propose changes in order to improve policies and the overall understanding of these unexplained deaths.

Prenatal exposure to cigarette smoking is associated with a decrease in arousal in infants.

OBJECTIVE: Sudden infant death syndrome has been related to both exposure to prenatal cigarette smoke and impaired arousability from sleep. We evaluated whether healthy infants born to mothers who smoked during pregnancy had higher auditory arousal thresholds than those born to mothers who did not smoke and whether the effects of smoking occurred before birth. STUDY DESIGN: Twenty-six newborns were studied with polygraphic recordings for 1 night: 13 were born to mothers who did not smoke, and 13 were born to mothers who smoked (>9 cigarettes per day). Other infants with a median postnatal age of 12 weeks were also studied, 21 born to nonsmoking mothers and 21 born to smoking mothers. White noise of increasing intensity was administered during rapid eye movement sleep to evaluate arousal and awakening thresholds. RESULTS: More intense auditory stimuli were needed to induce arousals in newborns (P =.002) and infants (P =. 044) of smokers than in infants of nonsmokers. Behavioral awakening occurred significantly less frequently in the newborns of smokers (P =.002) than of nonsmokers. CONCLUSIONS: Newborns and infants born to smoking mothers had higher arousal thresholds to auditory challenges than those born to nonsmoking mothers. The impact of exposure to cigarette smoke occurred before birth.

Auditory arousal thresholds are higher when infants sleep in the prone position.

OBJECTIVE: To evaluate the possibility that infants sleeping in the prone position have higher arousal thresholds to auditory challenges than when sleeping in the supine position. STUDY DESIGN: Polygraphic recordings were performed for 1 night in 25 healthy infants with a median age of 9 weeks. The infants were exposed to white noises of increasing intensities while sleeping successively in the prone and supine positions, or vice versa. Arousal thresholds were defined by the auditory stimuli needed to induce polygraphic arousals. RESULTS: Three infants were excluded from the study because they awoke while their position was being changed. For the 22 infants included in the analysis, more intense auditory stimuli were needed to arouse the infants in the prone position than those in the supine body position (p = 0.011). Arousal thresholds were higher in the prone than in the supine position in 15 infants; unchanged in 4 infants; and lower in the prone position in 3 infants (p = 0.007). CONCLUSIONS: Infants show higher arousal thresholds to auditory challenges when sleeping in the prone position than when sleeping in the supine position. The finding could be relevant to mechanisms concerned with the reported association between sudden deaths and the prone sleeping position in infants.

Development of cardiopulmonary integration and the role of arousability from sleep.

The recent literature on cardiopulmonary integration in infants is surveyed here, focusing on arousals from sleep. Recent studies reported that the ontogenicity of cardiopulmonary integration cannot be evaluated independently from that of sleep-wake cycles. The issue is of importance for researchers and clinicians evaluating cardiorespiratory characteristics in infants. It also has significant implications in the understanding of clinical conditions, such as parasomnias, obstructive sleep apneas, or some cases of sudden infant death syndrome. The propensity to arouse can be evaluated by exposing the sleeper to awakening challenges. Arousal thresholds are determined by measuring the intensity of the stimulus needed to induce arousals. However, these studies are complicated by factors such as the scoring of the arousal responses. Another difficulty lies in the choice and modality of the arousal stimulus. Noise, gases, light, and nociceptive, mechanical, chemical, or temperature stimuli have all been used to induce arousals. Confounding factors modify the sleeper's responses to a given stimulus. Prenatal drug, alcohol, or cigarette use and the infant's age or, previous sleep deprivation also modify thresholds. Other confounding factors include time of the night, sleep stages, the sleeper's body position, and sleeping conditions. Arousal can also occur spontaneously because of endogenous stimuli. The literature surveyed here also covers such unresolved issues as the clinical significance of aborted arousals, or the mechanisms responsible for the arousal reactions.