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Despite the dramatic decline in the incidence of sudden infant death syndrome (SIDS) by 50–90% over the past two decades, SIDS continues to be the leading cause of death in infants aged between 1 month and 1 year in developed countries.

Study objective Compared with control infants, those who will be future victims of sudden infant death syndrome (SIDS) show a decreased arousability during sleep, with fewer cortical arousals and more-frequent subcortical activations. These findings suggest an incomplete arousal process in victims of SIDS. Prone sleep position, a major risk factor for SIDS, has been reported to reduce arousal responses during sleep. The present study was undertaken to evaluate whether the prone sleep position impairs the arousal process in healthy infants. Methods Twenty-four healthy infants were studied polygraphically during 1 night; 12 infants regularly slept supine and 12 infants regularly slept prone. Infants were matched for sex, gestational age, and age at recording. Arousals were differentiated into subcortical activations or cortical arousals, according to the presence of autonomic and/or electroencephalographic changes. Frequencies of subcortical activations and cortical arousals were compared in the prone- and the supine-sleeping infants. Results Compared with supine sleepers, prone sleepers had significantly fewer cortical arousals during rapid eye movement (REM) sleep (p = .043). There were no significant differences in cortical arousals between the 2 groups during non-REM sleep. No significant differences were seen in the frequencies of subcortical activations during both REM and non-REM sleep between supine and prone sleepers. The ratio of cortical arousal to subcortical activation showed no significant differences between the prone and the supine sleepers. Conclusions Prone sleep position decreased the frequency of cortical arousals but did not change the frequency of subcortical activations, as has been previously found in SIDS victims. These results suggest specific pathways for impairment of the arousal process in SIDS victims.

Resume Les campagnes de prevention contre la Mort Subite du Nourrisson (MSN) ont conduit a une diminution significative du nombre de deces inattendus et inexpliques du nourrisson pendant le sommeil. Malgre une recherche intensive dans ce domaine, la comprehension des mecanismes responsables d’une MSN est encore incomplete. Les resultats des recherches epidemiologiques, genetiques, efectrophysio-logiques et anatomopathologiques les plus recentes seront revus. De ces donnees, un modele pour la MSN peut etre elabore : le deces resulterait de la survenue concomitante de trois facteurs (une vulnerabilite prenatale, une periode critique du developpement et des facteurs de stress postnataux) et de 3 mecanismes potentiels (une deficience respiratoire, autonome et des mecanismes d’eveil). Le reveil etant souvent la derniere chance de survie d’un individu soumis a un stress vital, une deficience de ce mecanisme pourrait etre un des facteurs cles du processus conduisant a une MSN. Un nourrisson dont les controles cardiorespiratoires et les mecanismes d’eveil sont alteres peut etre a risque de MSN. Des facteurs genetiques, metaboliques, nutritionnels ou toxiques pourraient etre responsables de lesions prenatales du systeme nerveux central et en particulier du tronc cerebral. Ces deficiences resteraient latentes dans les premieres semaines de vie, jusqu’a une periode du developpement particulierement critique entre 2 et 6 mois, quand des changements significatifs surviennent au niveau de la structure du sommeil, des controles respiratoire et cardiaque. L’incident a de grande chance de survenir lorsque l’enfant est expose a une infection ou a un milieu environnemental defavorable qui aggravera l’instabilite des controles cardiorespiratoires et d’eveils.

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.

Study objectives When infants have been swaddled and sleep supine, their risk of dying from sudden infant death syndrome (SIDS) is reduced with an odds ratio of 0.64 to 0.69. Alternatively, the risk for SIDS in swaddled infants shows a 3-fold increase in the prone position. The protective role of swaddling during supine sleep has remained unexplained. This study was designed to evaluate the effects of swaddling on cardiac reactivity to auditory stimuli during sleep in both the prone and the supine position. Design Thirty healthy infants with a median age of 11 weeks (range 8 to 15 weeks) were studied polygraphically for 1 night while sleeping successively prone and supine, or vice versa. The infants were studied while swaddled and nonswaddled in both positions. Heart rates were studied during rapid eye movement sleep, before and after exposure to 90 dB(A) of white-noise. Results Ten infants were excluded from the study because they woke up during the position change or the auditory challenge. Before the administration of the noise stimulus, swaddling decreased values of basal heart rates in the supine position only (P = .049). Following swaddling, the values of basal heart rate were significantly lower in the supine than in the prone position (P = .003). Auditory challenges were followed by a greater increase in heart rate when the supine sleeping infants were swaddled than when not swaddled (P = .018). When swaddled, beat-to-beat heart-rate variability increased following auditory stimulation in the supine position only (P = .012). Conclusion When sleeping supine, swaddled infants had greater cardiac autonomic changes in response to noise challenges than when they were not swaddled.

Background: The sudden infant death syndrome (SIDS) is still the main cause of postneonatal infant death and its cause is still unknown. Recently, the medullary serotonergic network deficiency theory has been proposed and an association between SIDS and neuronal plasticity has also been suggested. The growth-associated phosphoprotein 43 (GAP43) is a marker of synaptic plasticity and is critical for normal development of the serotonergic innervation. Therefore, the characteristics of GAP43-positive elements and their association with serotonergic neurons were here investigated in the brainstem of SIDS victims. Materials and methods: The materials of this study included 26 cases of SIDS and 12 control cases. The brainstem material was collected and the immunohistochemistry of GAP43 and tryptophan hydroxylase (TrypH) carried out. The density of GAP43-positive neurons and dendrites and of TrypH-positive neurons were measured quantitatively. Non-parametric analyses of GAP43 between SIDS and non-SIDS and correlation analyses between GAP43 and TrypH were performed. Results: No significant difference in GAP43-associated findings was found between SIDS and non-SIDS nor any significant correlation between GAP43-associated findings and TrypH-positive neurons. Conclusions: The results of this study were not in agreement with the association of GAP43 with SIDS and with serotonergic innervation in SIDS. © 2004 Elsevier Ireland Ltd. All rights reserved.

Background : Substance P (SP) is a neuropeptide transmitter found in sensory neurons of the central nervous system and related to pain sensation and respiratory regulation. Some reports claim an increase in SP in the brains of SIDS victims, so the correlation between SP and sleep apnea was investigated here. Materials and methods : Among 27,000 infants studied prospectively to characterize their sleep–wake behavior, 38 infants died under 6 months of age, which included 26 cases of Sudden Infant Death Syndrome (SIDS). All the infants had been recorded during one night in a pediatric sleep laboratory some 3 to 12 weeks before death. The frequency and duration of sleep apnea were analyzed. Brainstem material was collected and immunohistochemistry for SP was carried out. The density of SP positive fibers was measured in the nucleus spinal and mesencephalic nervi trigemini and nucleus parabranchialis in the brainstem of abovementioned cases. Correlation analyses were carried out between the density of SP and the data of sleep apnea. Results : There was no SIDS specific correlation of SP through the above-listed parts of the midbrain with frequency and duration of sleep apnea. Conclusions : There was no significant association between the SP findings and apnea data in SIDS; this is not in agreement with the association of apnea in pathophysiology of SIDS.

Background: In the sudden infant death syndrome (SIDS), a medullary serotonergic network deficiency theory has been proposed, amongst many other hypotheses. The correlation between serotonergic neurons or dendritic spines in the brainstem of SIDS and sleep apnea was investigated here. Materials and methods: Twenty-seven thousand infants were studied prospectively to characterize their sleep-wake behavior. Of these, 38 infants died under 6 months of age, including 26 cases of SIDS. The frequency and duration of sleep apnea were analyzed. Brainstem material was collected and immunohistochemistry for tryptophan hydroxylase (TrypH) carried out. The density of TrypH-positive neurons was measured quantitatively. Correlation analyses were carried out between the TrypH-associated pathological data and the physiological data of sleep apnea. Results: One significant positive correlation between the density of TrypH-positive neurons in the dorsal raphe nucleus of the midbrain and the duration of central apnea ( P =0.027) was found in SIDS victims. Conclusions: Some of serotonergic facts could be involved in the pathophysiology of SIDS.

Background: Microtubule-associated protein 2 (MAP2), a cytoskeletal protein of the neuron, is a marker of early ischemic neuronal damage. As a chronic hypoxic situation exists in the brains of victims of the sudden infant death syndrome (SIDS), the correlation between MAP2-positive neurons or dendritic spines in the brainstem and sleep apnea was investigated in SIDS, which is still the main cause of postneonatal infant death. Materials and methods: Twenty-seven thousand infants were studied prospectively to characterize their sleep–wake behavior and amongst these, 38 infants died under 6 months of age. They included 26 cases of SIDS. The frequency and duration of sleep apneae were analyzed. The brainstem material was collected and immunohistochemistry of MAP2 was carried out. The density of MAP2-positive neurons, dendrites, and dendritic spines were measured quantitatively. Correlation analyses were carried out between the MAP2-associated pathological data and the physiological data of sleep apnea. Results: One negative correlation between the density of MAP2-positive endrites in the pars compacta of pedunculo-pontine tegmentum nucleus (PPTNc) and the duration of obstructive apnea ( P =0.017) and two SIDS-specific positive correlations between the density of MAP2-positive dendrites in the pars dissipata of pedunculo-pontine tegmentum nucleus (PPTNd) and the duration of central apnea ( P =0.005) and between the dorsal raphe and the frequency of obstructive apnea were found in SIDS victims. The density of MAP2-positive dendritic spines in PPTNc was significantly higher in SIDS than in control ( P =0.034). Conclusions: The significant correlations with the MAP2-positive findings in the midbrain arousal pathway and the characteristics of sleep apnea in SIDS victims were in agreement with the association with apnea and arousal-deficiency in SIDS.

Background : The sudden infant death syndrome (SIDS) is still the main cause of postneonatal infant death and its etiology has stimulated many competing theories, among which is the role of hypoxia and brainstem abnormalities. One report claims an increased in ubiquitin in the liver of SIDS victims, ubiquitin being one of the heat-shock proteins. The correlation between ubiquitin in the brainstem and sleep apnea in SIDS was investigated here. Materials and methods : Among 27,000 infants studied prospectively to characterize their sleep–wake behavior, 38 infants died under 6 months of age, including 26 cases of SIDS. All the infants had been recorded during one night in a pediatric sleep laboratory some 3–12 weeks before death. The frequency and duration of sleep apnea were analyzed. Brainstem material was collected at autopsy and examined immunohistochemically for ubiquitin. The density of ubiquitin-positive elements was measured semiquantitatively. Correlation analyses were carried out between the density of ubiquitin-positive elements and the data on sleep apnea. Results : In the victims of SIDS, a statistically significant positive correlation was found between the density of ubiquitin-positive neuronal factors in the pons and the frequency of obstructive apnea ( p =0.001) and statistically significant negative correlations were seen between the density of ubiquitin-positive cells in the ependyma in the pons and the duration of obstructive apnea ( p =0.044) and between the density of ubiquitin-positive cells in the subependyma in the medulla and the frequency of central apnea ( p =0.024). Conclusions : It was found that three significant associations existed between the pathological data referring to ubiquitin and physiological data in SIDS victims. These facts are in agreements with the association of sleep apnea in SIDS.

Background : The Ki-67 antigen appears in all human proliferating cells during late G1, S, M and G2 phases of the cell cycle, but is consistently absent in the G o phase (noncycling) cells. The correlation between Ki-67 in the brainstem and sleep apnea in victims of the sudden infant death syndrome (SIDS) was investigated to elucidate cell kinetics in the brainstem of this condition, which is still the main cause of postneonatal infant death. Materials and Methods : Twenty-six cases of SIDS occurred among 38 infants dying under 6 months of age in a cohort of 27,000 infants studied prospectively to characterize their sleep–wake behavior. All the infants had been recorded during one night in a pediatric sleep laboratory some 3 to 12 weeks before death. The frequency and duration of sleep apnea were analyzed. At autopsy, brainstem material was collected and immunohistochemistry for Ki-67 was carried out. The density of Ki-67-positive neurons was measured semiquantitatively. Correlation analyses were carried out between the density of Ki-67-positive neurons and the data on sleep apnea. Results : Except in two cases in SIDS victims and in one control, the detection of Ki-67 was negative. No correlation analysis between the Ki-67 and of sleep apnea was found. Conclusions : There were no abnormal cell kinetics detected by the demonstration of Ki-67 antigen in the brainstems of SIDS victims.

Background: Recently, the appearance of beta-amyloid precursor protein (APP) has been demonstrated in the neonatal brain following hypoxic–ischaemic injury. As chronic hypoxia is one of the favoured theories of causation in the sudden infant death syndrome (SIDS), the correlation between APP in the brainstem and sleep apnea in SIDS was investigated. Materials and methods: Among 27,000 infants studied prospectively to characterize their sleep–wake behavior, 38 infants died under 6 months of age, which included 26 cases of SIDS. All the infants had been recorded during one night in a pediatric sleep laboratory, some 3–12 weeks before death. The frequency and duration of sleep apnea were analyzed. The brainstem material was collected and immunohistochemistry with anti-Alzheimer precursor protein A4 (APP) was carried out. The density of APP-positive elements was measured semi-quantitatively. Correlation analyses were carried out between the density of APP-positive elements and the data on sleep apnea. Results: No correlation was found. Conclusion: No correlation between pathological data of APP and physiological data of sleep apnea was not in agreement with the association of sleep apnea in pathophysiology of SIDS.

Objective: To evaluate the influence of a brief period of sleep deprivation on cardiac autonomic controls during sleep in healthy infants. Design: Twelve healthy infants with a median age of 8 weeks (range, 7 to 18 weeks) were recorded polygraphically during a morning and an afternoon nap in a sleep laboratory. They were sleep deprived for approximately 2 hours, either in the morning or in the afternoon, before being allowed to fall asleep. Six infants were sleep deprived before the morning nap, and 6 before the afternoon nap. During both naps, their sleep, breathing, and heart-rate characteristics were continuously recorded. Spectral analysis of heart rate was evaluated as a function of sleep stages. Two major peaks were recognizable: a low-frequency component related to sympathetic and parasympathetic activities and a high-frequency component reflecting parasympathetic tonus. The ratio of low-frequency to high-frequency powers was calculated as an index of sympathovagal interaction. Results: When sleep deprived, the infants had an increase in basal heart rate during non-rapid eye movement sleep (P=.021). With sleep deprivation, the ratio of low-frequency to high-frequency powers increased in non-rapid eye movement sleep (P=.005). These findings were consistent with an increase in sympathetic tone. Conclusion: Infants exposed to short-term sleep deprivation manifest changes in cardiac autonomic controls during sleep. These findings could be relevant to mechanisms associated with the sudden infant death syndrome.

Objective : Among 27,000 infants studied prospectively to characterize their sleep–wake behavior, 38 infants died under 6 months of age (including 26 infant victims of sudden infant death syndrome (SIDS), five with congenital cardiac abnormalities, two from infected pulmonary dysplasia, two from septic shock with multi-organ failure, one with a prolonged seizure, one from prolonged neonatal hypoxemia and one from meningitis and brain infarction). Method : The frequency and duration of sleep apnea events recorded some 3–12 weeks before the infants' deaths were analyzed. Brainstem material from these 38 infants was studied in an attempt to elucidate the relationship between sleep apnea and neuronal pathological changes in the arousal pathway. The histochemical analyses included Bielschowsky staining and the immunohistochemical analyses included the evaluation of growth-associated phosphoprotein 43 (GAP43) and of synaptophysin as markers for synaptic plasticity. Neurofibrae with positive pathological reactions were quantitatively analyzed. Pathological and physiological data were linked for each infant. Results : The correlation between sleep apnea and neuronal plasticity in the arousal pathway of the SIDS victims was not seen in the control infants and the correlation between sleep apnea and neuronal plasticity in the arousal pathway found in the control infants was not seen in the SIDS victims. Conclusion : These findings suggest that neuronal plasticity in the brainstem arousal pathway is related with SIDS.

The prone sleeping position has been identified in world-wide epidemiological studies as a major risk factor for sudden infant death syndrome (SIDS). Public awareness campaigns throughout the western world have led to an over 50% reduction in postneonatal mortality and frequency of SIDS. This reduction in mortality has been mainly attributed to the avoidance of the prone sleep position. Various mechanisms have been postulated to explain the increased risk of SIDS associated with prone sleeping, among these, impairment of arousal from sleep. This paper reviews the effects of prone sleeping on infant sleep architecture, arousability from sleep and cardiorespiratory controls. Sleeping in the prone position has been shown to increase the amount of time spent sleeping, particularly time spent in quiet sleep (QS). Sleeping prone has also been demonstrated to be associated with a reduced responsiveness to a variety of arousal stimuli. Such impairment of arousal has been demonstrated to be associated with changes in control of autonomic cardiac function. During arousal, heart rate, blood pressure and breathing movements increase, while gross body movements occur to avoid the stimulus. Any impairment in arousability from sleep such as could occur when infants sleep in the prone position, could possibly contribute to the final pathway to SIDS.

The aim of the study was to determine whether in infants, the evaluation of thoracoabdominal movements alone, with no measurement of airflow, could be used to identify obstructive sleep apnea events (OA). Two different methods were used: first, we initially quantified thoracoabdominal asynchrony. Although 79.3% of OAs showed a significant increase of thoracoabdominal asynchrony, only 10.9% of the events scored by the identification of phase opposition were true OAs. Next, we developed two artificial neural networks (ANNs) as classifiers for the study of the thoracoabdominal signals. The first network was trained to locate obstructive and central apnea events. It correctly detected 75% of the OAs; however, only 6.2% of the detected events were true OAs. When a second network was used, OAs could not be discriminated from other portions of the signals showing similar phase characteristics. It was concluded that the information available in uncalibrated signals of thoracic and abdominal respiratory movements was insufficient to unambiguously detect OA events in sleeping infants.

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

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.

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.

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.

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. (J Pediatr 1999;135:34-8)

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. (J Pediatr 1998;132:240-3).

The sudden and unexplained death of sleeping infants aged less than 1 year, the sudden infant death syndrome (SIDS), is still the principal cause of postneonatal mortality in many industrialized countries. Since initiation of education and information campaigns to inform the public on preventable risk factors, SIDS incidence has dropped significantly in most countries. Questions have, however, been raised on the physiological mechanisms underlying the environmental factors increasing the risk for SIDS. From the scientific literature, it appears that various mechanisms responsible for the control of respiratory, cardiac, thermoregulation, neurovegetative, and waking systems could be impaired before or after birth of future victims of SIDS. To understand how various factors contribute to SIDS deaths, we studied the characteristics of sleeping infants in two different populations, in future SIDS victims and in healthy infants exposed to conditions known to favor SIDS. This paper will review research carried out by our laboratory over the past 20 years.

Objective. To evaluate the relationship between body position during sleep and the infants' cardiac responses to auditory stimulation. Methods. Thirty healthy infants with a median age of 11 weeks were studied polygraphically for one night, while sleeping successively prone and supine, or vice versa. Their behavioral and cardiac responses were recorded during rapid eye movement (REM) sleep, both before and after exposure to 90 dB (A) of white-noise. Results. Ten infants were excluded from the study, because they woke up during the challenge. For the 20 infants included in the analysis, no significant difference was seen between the prone and the supine position for total sleep time, sleep efficiency, percent of REM and nonrapid eye movement sleep, number of gross body movements, transcutaneous oxygen saturation levels, mean cardiac rate, heart rate variability, number of heart rate drops; mean respiratory rate, and number or duration of central or obstructive apneas. Auditory challenges induced significantly less overall changes in heart rate, less heart rate drops, less heart rate variability, as well as fewer and shorter central apneas in the prone than in the supine position. Autoregressive power spectral analysis of the heart rate was consistent with a possible increase in orthosympathetic tone in the prone position. Conclusion. Prone sleeping was associated with a decrease in cardiac responses to auditory stimulation and a possible increase in orthosympathetic activity. Prone positioning could favor a reduced reactivity to danger-signaling stimuli during REM sleep.

Sudden infant death syndrome (SIDS) victims had exhibited during sleep a reduction in cortical arousals despite an increase in subcortical activation. Arousal deficiency in SIDS victims was partial. We could suggest the latent existence of inadequate noradrenergic neuronal plasticity as the background of this partial arousal deficiency of SIDS victims.

Major speech impairment is a cardinal feature of Rett syndrome. Epilepsy, of variable presentation, is also frequently described. We report a girl who presented rapid speech regression while EEG showed continuous spikes and waves during slow sleep. The clinical picture was consistent with Rett syndrome, confirmed by MECP2 mutation R133C. We hypothesized that speech regression was partially related to nocturnal epileptic activity. Several antiepileptic drugs were used unsuccessfully but valproic acid was accompanied by improvement of verbal fluency, social interaction and manual abilities as measured by the Quebec Scale of Adaptive Behaviors and the Rett syndrome adapted Kerr scale. Continuous spikes and waves during slow sleep are unexpected in the early stages of Rett syndrome. This report suggests that it might contribute to the clinical impairment, in particular communicative capabilities, and that adequate antiepileptic treatment may be beneficial.

Publisher Summary Sudden infant death syndrome (SIDS) is defined as the sudden death of an infant less than 1 year of age that remains unexplained after a complete postmortem examination, including an investigation of the death scene, and a review of the case history. A complete pathologic examination is required for the diagnosis of SIDS, including microscopic, toxicological, microbiological, immunohistochemical, molecular, and metabolic exams. Case-control reviews on sleeping position and SIDS showed that the relative risk for SIDS increased 4–9 fold when infants sleep prone than when they sleep supine. The chapter discusses the various mechanisms to explain the association of prone sleeping and SIDS. The chapter presents the three basic mechanisms to cause SIDS: the breathing control hypothesis; the autonomic control hypothesis; and the sleep and arousal hypothesis. An infant could be vulnerable for SIDS because of a deficiency in cardiorespiratory controls during sleep, favoring the development of recurrent episodes of hypoxemia.

STUDY OBJECTIVES A deficit in arousal process has been implicated as a mechanism of sudden infant death syndrome (SIDS). Compared with control infants, SIDS victims showed significantly more subcortical activations and fewer cortical arousals than matched control infants. Apparent life-threatening event (ALTE) is often considered as an aborted SIDS event. The aim of this study was to study the arousal characteristics of ALTE infants during the first months of life. DESIGN 35 ALTE infants were studied with nighttime polysomnography at 2-3, 5-6, and 8-9 months of age. Eighteen of the infants had mothers who smoked. The infants were born full term and were usually supine sleepers. Sleep state and cardiorespiratory parameters were scored according to recommended criteria. Arousals were differentiated into subcortical activations or cortical arousals, according to the presence of autonomic and/or electroencephalographic changes. The results were compared with those of 19 healthy infants with nonsmoking mothers. RESULTS During NREM sleep, the ALTE infants had fewer total arousals, cortical arousals, and subcortical activations at 2-3 and 5-6 months (P < 0.001) than control infants. ALTE infants with smoking mothers had more obstructive apnea (P = 0.009) and more subcortical activations during REM sleep at 2-3 months of age (P < 0.001) than ALTE infants with nonsmoking mothers. CONCLUSIONS Spontaneous arousals were differently altered in ALTE infants than in SIDS infants, suggesting an entity different from SIDS. ALTE infants with smoking mothers had arousal and respiratory characteristics that were similar to future SIDS victims, suggesting some common abnormalities in brainstem dysfunction.

Mutations in the lamin A/C gene determine a heterogeneous group of congenital diseases, termed laminopathies, consisting of more than 15 phenotypes, including autosomal dominant Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy type 1B. Early onset in infancy has been described in these muscular dystrophies. Reported here is a 7-year-old male with congenital muscular dystrophy. Remarkably, muscle weakness and wasting affected predominantly axial muscles as well as proximal upper and distal lower extremities. The patient rapidly developed joint contractures and spine rigidity with the head only mildly flexed. Serum creatine kinase was moderately elevated. Muscle biopsy indicated a dystrophic pattern with normal immunochemical findings. A novel, de novo missense substitution p.Asn39Tyr within the lamin A/C gene confirmed the diagnosis of a laminopathy. This report broadens the spectrum of lamin A/C gene mutations and illustrates the phenotypic variability of laminopathies with early onset congenital muscular dystrophy. Mutations in the lamin A/C gene should be sought in any infant with dystrophic features and normal tissue immunochemical studies; especially in the presence of moderately elevated serum creatine kinase, predominant axial and humeroperoneal weakness, spine rigidity, and joint contractures.

International audience; OBJECTIVE: Previous data have suggested that a prolonged QTc interval during the first days of life can be associated with some cases of sudden infant death syndrome (SIDS). Analysis of heart rate variability during sleep in future SIDS victims has shown findings compatible with an imbalance in autonomic tone. We hypothesized that some future SIDS infants could have longer QTc intervals during sleep, compared with healthy control infants, and that this difference would correlate with the autonomic imbalance already found in these infants. METHODS: QTc intervals and a heart rate autoregressive power spectral analysis were calculated during the same periods in the polysomnographic sleep recordings of 18 infants who eventually died of SIDS and of 18 control infants. The control infants were matched for sex, gestational age, postnatal age, birth weight, and sleep position. The median postnatal age was 8 weeks. RESULTS: Compared with control infants, future SIDS victims were characterized by having longer QTc intervals during total sleep (P = 0.019), rapid eye movement sleep (P = 0.045) and non-rapid eye movement sleep (P = 0.029). When the night was divided into 3 equal parts, this difference was always present but was most marked during the last part of the night. There was, respectively, a negative and a positive correlation between parasympathetic activity and sympathovagal balance and median and maximum QTc interval values. CONCLUSION: Compared with QTc intervals in matched control infants, QTc intervals were increased in future SIDS victims. Such a prolongation could be related to the autonomic dysfunction already reported in these patients.

International audience; OBJECTIVE: The propensity to arouse from sleep is an integrative part of the sleep structure and can have direct implications in various clinical conditions. This study was conducted to evaluate the maturation of spontaneous arousals during the first year of life in healthy infants. DESIGN: Nineteen infants were studied with nighttime polysomnography on 3 occasions: aged 2 to 3 months, 5 to 6 months, and 8 to 9 months. Ten infants with a median age of 3 weeks were added to the main study to assess the maturation of arousals from birth. The infants were born full-term, were healthy at the time of study, and had no history of apnea. Sleep-state and cardiorespiratory parameters were scored according to recommended criteria. Arousals were differentiated into subcortical activations or cortical arousals, according to the presence of autonomic and/or electroencephalographic changes. Frequencies of subcortical activations and cortical arousals were studied at different ages in both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. RESULTS: During sleep time, the frequency of total arousals, cortical arousals, and subcortical activations decreased with age. The maturation of the arousal events differed according to sleep states and types of arousals. With age, cortical arousals increased in REM sleep (P = 0.006) and decreased in NREM sleep (P = 0.01). Subcortical activations decreased with age in REM (P < 0.001) and NREM sleep (P < 0.001). CONCLUSIONS: During total sleep time, the frequency of cortical arousals and subcortical activations decreased with maturation. However, the maturation process was different between cortical arousals and subcortical activations. This finding suggests a difference in the maturational sequence of the different brain centers regulating arousals.

Celiac disease may be associated with various neurologic manifestations, most commonly cerebellar ataxia. This report describes a 2-year-old male who presented with opsoclonus-myoclonus syndrome including action myoclonus, palpebral flutter, opsoclonus, and ataxia. Given the severity of ataxia, the child was unable to sit or walk independently. Brain magnetic resonance imaging was normal on two occasions (4-week interval). Oligoclonal bands were found in the cerebrospinal fluid. Blood and serum examinations were unremarkable, with no evidence of infectious seroconversion. However autoantibody testing indicated the presence of antigliadin antibodies of immunoglobulin A subtype, anti-endomysial antibodies, and anti-CV2 antibodies that were not, however, detected in the cerebrospinal fluid. Duodenal biopsy documented villous atrophy confirming the diagnosis of celiac disease. This case confirms that initial presentation of celiac disease may be restricted to neurologic features. We suggest that a search for evidence for celiac disease should be included in the evaluation of opsoclonus-myoclonus., Case Reports, Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

Objective. Swaddling is an old infant care practice. It was reported to favor sleep and to reduce crying among irritable infants. There are few data on the physiologic effects of swaddling on infants' sleep-wake characteristics. This study was conducted to evaluate whether swaddling influences infants' arousal thresholds for environmental auditory stress.Design. Sixteen healthy infants, with a median age of 10 weeks (range: 6–16 weeks), underwent polygraphic recording in their usual supine position during one night. The infants were successively recorded swaddled and nonswaddled, or vice versa. In both conditions, the infants were exposed to white noise of increasing intensity, from 50 to 100 dB(A), during rapid eye movement sleep, to determine their arousal thresholds.Results. Swaddling was associated with increases in the infants' sleep efficiency and in the time spent in non–rapid eye movement sleep. When swaddled, the infants awakened spontaneously less often. However, significantly less-intense auditory stimuli were needed during rapid eye movement sleep to induce cortical arousals when swaddled than when not swaddled.Conclusions. Swaddling promotes more-sustained sleep and reduces the frequency of spontaneous awakenings, whereas induced cortical arousals are elicited by less-intense stimuli. These findings could indicate that, although swaddling favors sleep continuity, it is associated with increased responsiveness to environmental auditory stress.

Sudden infant death syndrome remains a leading cause of postneonatal mortality in developed countries. Its etiopathogenic mechanisms are unknown. In this neuropathologic study, we noticed that the weights of the brains of infants who died from sudden infant death syndrome ( n = 97) were invariably heavier in comparison with those of a group of age-matched controls ( n = 23) issuing from the same local population. Brain edema was not a major element, and there were no significant microscopic or macroscopic cerebral anomalies in the brains from either of the study groups. Head circumference did not show a parallel increase in infants with sudden infant death syndrome. The excessive brain weight might reflect abnormal cerebral development and could be detrimental to vital neural control. In a previous study, we disclosed cytokine overexpression in the brains of these victims. Whether increased brain weight is linked to cytokine up-regulation remains, however, a moot case and merits further exploration.

Various definitions of arousals have been used in infants. An international group of experts has worked on a consensus for the scoring of arousals in healthy infants, aged between 1 and 6 months. This opinion paper summarizes the consensus statement on the scoring of arousal. The paper reviews recommended techniques for the recording of arousal in infants. Scoring includes the differentiation between subcortical activation, with no visible change n the electroencephalograph (EEG) recording, and cortical arousals associated with EEG changes. The arousals are further scored as spontaneous or induced, according to environmental conditions. Potential limitations to the method are discussed, with the hope that this document could contribute to promote further progresses in the scoring of infants arousals from sleep.

Objective. Sleep deprivation is a risk factor for sudden infant death syndrome (SIDS). Recent changes in normal life routines were more common among SIDS victims, compared with control infants. Sleep deprivation can result from handling conditions or from sleep fragmentation attributable to respiratory or digestive conditions, fever, or airway obstructions during sleep. Compared with matched control infants, future SIDS victims exhibited fewer complete arousals by the end of the night, when most SIDS cases occur. Arousal from sleep could be an important defense against potentially dangerous situations during sleep. Because the arousal thresholds of healthy infants were increased significantly under conditions known to favor SIDS, we evaluated the effects of a brief period of sleep deprivation on sleep and arousal characteristics of healthy infants.Design. Fourteen healthy infants, with a median age of 8 weeks (range: 6–18 weeks), underwent polygraphic recording during a morning nap and an afternoon nap, in a sleep laboratory. The infants were sleep-deprived for 2 hours before being allowed to fall asleep. Sleep deprivation was achieved by keeping the infants awake, with playing, handling, and mild tactile or auditory stimulations, for as long as possible beyond their habitual bedtimes. To avoid any confounding effect attributable to differences in sleep tendencies throughout the day, sleep deprivation was induced before either the morning nap or the afternoon nap. Seven infants were sleep-deprived before the morning nap and 7 before the afternoon nap. The sleep and arousal characteristics of each infant were compared for the non-sleep-deprived condition (normal condition) and the sleep-deprived condition. During each nap, the infants were exposed, during rapid eye movement (REM) sleep, to white noise of increasing intensity, from 50 dB(A) to 100 dB(A), to determine their arousal thresholds. Arousal thresholds were defined on the basis of the lowest auditory stimuli needed to induce arousal. After the induced arousal, the infants were allowed to return to sleep to complete their naps.Results. Sleep deprivation lasted a median of 120 minutes (range: 90–272 min). Most sleep characteristics were similar for the normal and sleep-deprived conditions, including sleep efficiency, time awake, percentages of REM sleep and non-REM sleep, frequency and duration of central apnea and of periodic breathing, duration of obstructive apnea, mean heart rate and variability, and mean breathing rates during REM sleep and non-REM sleep. After sleep deprivation, the duration of the naps increased, whereas there were decreases in the latency of REM sleep and in the density of body movements. More-intense auditory stimuli were needed for arousal when the infants were sleep-deprived, compared with normal nap sleep. Sleep deprivation was associated with a significant increase in the frequency of obstructive sleep apnea episodes, especially during REM sleep. No significant differences were noted when the effects of morning and afternoon sleep deprivation were compared. No correlation was found between the duration of sleep deprivation and either the frequency of obstructive apnea or the changes in arousal thresholds, although the infants who were more sleep-deprived exhibited tendencies toward higher auditory arousal thresholds and shorter REM sleep latencies, compared with less sleep-deprived infants. There were tendencies for a negative correlation between the auditory arousal thresholds and REM sleep latencies and for a positive correlation between the auditory arousal thresholds and the frequencies of obstructive apnea during REM sleep.Conclusions. Short-term sleep deprivation among infants is associated with the development of obstructive sleep apnea and significant increases in arousal thresholds. As already reported, sleep deprivation may induce effects on respiratory control mechanisms, leading to impairment of ventilatory and arousal responses to chemical stimulation and decreases in genioglossal electromyographic activity during REM sleep. These changes in respiratory control mechanisms could contribute to the development of obstructive apnea. The relationship between the development of obstructive apnea and increases in arousal thresholds remains to be evaluated. Adult subjects with obstructive sleep apnea exhibited both sleep fragmentation and increases in arousal thresholds. Conversely, sleep deprivation increased the frequency and severity of obstructive sleep apnea. In this study, the increases in arousal thresholds and the development of obstructive apnea seemed to result from the preceding sleep deprivation. The depressed arousals that follow sleep deprivation have been attributed to central mechanisms, rather than decreases in peripheral sensory organ function. Such mechanisms could include disturbances within the reticular formation of the brainstem, which integrates specific facilitory inputs, such as ascending pathways from auditory receptors, and inhibitory inputs from the cortex. It remains to be determined whether the combination of upper airway obstruction and depressed arousability from sleep contributes to the increased risk of sudden death reported for sleep-deprived infants.

Since the reduction in the incidence of the prone sleeping position, maternal cigarette smoking has become the strongest modifiable risk factor for Sudden Infant Death Syndrome (SIDS). This risk is dose dependent. Various mechanisms have been postulated to explain the increased risk of SIDS associated with maternal smoking, among these, impairment of arousal from sleep. This paper reviews the effects of maternal smoking on infant arousability from sleep, cardiorespiratory controls and sleep architecture. Infants exposed to maternal smoking have been shown to have both decreased spontaneous and evoked arousability from sleep. Such impairment of arousal has been demonstrated to be associated with changes in control of autonomic cardiac function. Sleep architecture appears not to be altered by smoking. During arousal, heart rate, blood pressure and breathing movements increase, while gross body movements occur to avoid the stimulus. Any impairment in arousability from sleep could occur when infants are exposed to maternal cigarette smoking, and could possibly contribute to the final pathway to SIDS.

Objective: The risk for sudden infant death (SIDS) was postulated to decrease with the use of a pacifier and by conditions increasing parasympathetic tonus during sleep. We evaluated the influence of a pacifier on cardiac autonomic controls in healthy infants. Study design: Thirty-four healthy infants were studied polygraphically during one night: 17 infants regularly used a pacifier during sleep and 17 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 6-18 weeks). Autonomic nervous system (ANS) was evaluated by spectral analysis of the heart rate (HR). The high frequency component of HR spectral analysis reflected parasympathetic tonus and the low frequency on high frequency ratio corresponded to the sympathovagal balance. Results: Most infants (63.6%) lost their pacifier within 30 min of falling asleep. Sucking periods were associated with increases in cardiac sympathovagal balance. During non-sucking periods, in both REM and NREM sleep, infants using a pacifier were characterized by lower sympathetic activity and higher parasympathetic tonus compared with non-pacifier users. Conclusions: The use of pacifiers modifies cardiac autonomic controls during both sucking and non-sucking sleep periods. Non-nutritive sucking could regulate autonomic control in infants. These findings could be relevant to mechanisms implicated in the occurrence of sudden infant deaths during sleep. © 2004 Elsevier Ireland Ltd. All rights reserved.

Background: Recently it has been reported that serotonin and related matters are associated with the sudden infant death syndrome (SIDS), which is still the main cause of postneonatal infant death. To further explore this claim, the correlation between serotonin receptors in the brainstem and sleep apnea in SIDS victims was investigated. Materials and methods: Among 27,000 infants studied prospectively to characterize their sleep-wake behavior, 38 infants died under 6 months of age including 26 cases of SIDS. All the infants had been recorded during one night in a pediatric sleep laboratory some 3-12 weeks before death. The frequency and duration of sleep apnea were analyzed. Brainstem material was collected and immunohistochemistry on 5-hydroxy tryptamine 1A (5HT1A) receptor was carried out. The density of 5HT1A receptor-positive neurons was measured quantitatively. Nonparametric analysis of the density of 5HT1A receptor-positive neurons was carried out between SIDS and non-SIDS cases. Correlation analyses were performed between the density of 5HT1A receptor-positive neurons and the data on sleep apnea. Results: There was no correlation between the pathological data on 5HT1A receptors and the physiological data on sleep apnea in SIDS victims. Conclusions: No correlation between pathological findings of serotonin and physiological findings of sleep apnea were not in agreement with the association of sleep apnea in pathophysiology of SIDS. © 2003 Elsevier. Ireland Ltd. All rights reserved.

The sudden infant death syndrome (SIDS) is still the main cause of postneonatal infant death and its cause is still unknown. A chronic hypoxic situation has been shown to exist in the brains of SIDS victims and apoptosis has been demonstrated in hypoxic situations. In this study, the correlation between apoptotic neurons or glias and sleep apnea in SIDS was investigated in the brainstem of SIDS victims. Materials and methods : In a cohort of 27,000 infants studied prospectively to characterize their sleep–wake behavior, 38 infants died under 6 months of age. They included 26 cases of SIDS. The frequency and duration of sleep apnea were analyzed. The brainstem material was collected and terminal-deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method was carried out. The density of TUNEL-positive neurons or glias was measured quantitatively. Correlation analyses were carried out between the apoptosis-associated pathological data and the physiological data of sleep apnea. Results : No significant negative or positive correlation between the density of TUNEL-positive neurons or glias and the characteristics of sleep apnea was observed in SIDS victims. No statistically significant differences associated with apoptotic neurons and glias were observed between SIDS and non-SIDS. Conclusions : The pathological findings of apoptosis were not in agreement with the hypothesis refer to apnea and arousal phenomenon in pathophysiology of 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 microenvironment, 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.

Objective Sigh, defined as an isolated breath with an increased tidal volume, can be associated with abrupt changes in heart rate (HR) or blood oxygenation. Sigh may be followed by a central apnea. As impairment of autonomic control was postulated in future SIDS victims, we hypothesized that their autonomic responses to sighs were different from those of healthy control infants. Methods Sighs followed by central apnea were studied in the sleep recordings of 18 infants who eventually died of SIDS and of 18 control infants. The infants of the two groups were matched for sex, gestational age, postnatal age, weight at birth and sleep position during sleep recording. HR autoregressive power spectral analysis was performed on RR intervals preceding and following sighs. Results In all infants, most sighs followed by an apnea were found in NREM sleep. Compared to the control infants, the future SIDS victims were characterized by a greater sympathovagal balance and a lower parasympathetic tonus before the sighs. Following the sighs, no more differences were found in NREM sleep. Conclusion Based on the present findings, it can be postulated that sighs contribute to reset autonomic tonus during NREM sleep.

Objective : Changes in blood pressure (BP) were measured following auditory stimuli in the prone and the supine position to study the correlation between arousal from sleep and autonomic responses. Method : Two newborns born at term, two infants and four children were recorded polygraphically during one night, while sleeping in the prone and the supine position. They were exposed to white noises of increasing intensities during both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep in each position. BP changes were measured by Finapress in the children and by pulse transient time (PTT) in the infants and newborns. Results : Basal systolic BP pressures were lower ( P P =0.008) in the prone than in the supine position in children and in infants. Following the auditory stimulations, the increases in systolic BP ( P =0.024) and the decreases in PTT ( P =0.006) were smaller in prone than in supine position. During cortical arousals, the same findings were found, independently of sleep stages. Conclusion : Compared with when they are sleeping supine, children and infants sleeping prone had lower basal BP and higher PTT and smaller changes in BP and PTT after auditory stimulation. Reduced BP changes to stimuli could be implicated in the increased arousal thresholds in prone position.

Infants who became victims of sudden infant death syndrome (SIDS) aroused less from sleep than control infants. This study was conducted to determine the characteristics of arousal from sleep of infants who eventually died of SIDS. Sixteen infants were monitored some days or weeks before they died of SIDS. Their polygraphic sleep recordings were compared with those of matched control infants. Arousals were scored as subcortical activation (incomplete arousals) or cortical arousal (complete arousals). Cortical arousals were significantly less frequent in the victims who would succumb to SIDS in the future than in the control infants during both REM and non-REM sleep (p = 0.039). The frequency (p = 0.017) and duration (p = 0.005) of subcortical activation were significantly greater in the infants who died of SIDS than in the control infants during REM sleep. Compared with the control infants, the infants who later died of SIDS had more frequent subcortical activation in the first part of the night, between 9:00 P.M. and 12:00 A.M. (p = 0.038), and fewer cortical arousals during the latter part of the night, between 3:00 and 6:00 A.M. (p = 0.011). The present data are suggestive of incomplete arousal processes in infants who eventually died at a time they were presumed to have been asleep.

Summary The risk of Sudden Infant Death Syndrome is increased in infants sleeping with their head covered by bedding items. This study was designed to evaluate cardiac autonomic nervous controls in infants sleeping with the head covered by bedclothes. Sixteen healthy infants with a median age of 12 weeks (range 9–13 weeks) were recorded polygraphically for one night. While they slept in their usual supine position, a bedsheet was placed over their head for about 45 min. All infants were challenged with the head covered and with the head free during both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. Sleep, breathing and heart rate (HR) characteristics were recorded simultaneously, together with rectal and pericephalic temperatures. In both head-free and head-covered conditions, autoregressive spectral analysis of HR was evaluated as a function of sleep stages. During the head-covered periods, parasympathetic tonus decreased and sympathetic activity increased in both REM and NREM sleep. Compared with the head-free periods, the head-covered sleep periods were characterized by greater rectal (P = 0.012) and pericephalic temperatures (P = 0.002). Covering the infant's head with a bedsheet was associated with significant changes in autonomic balance. The finding could be related to an elevation in temperatures within the infant's microenvironment.

Among 27,000 infants studied prospectively to characterize their sleep–wake behavior, 38 infants died suddenly and unexpectedly under 6 months of age. Of these, 26 died from sudden infant death syndrome (SIDS), 5 from congenital cardiac abnormalities, 2 from infected pulmonary dysplasia, 2 from septic shock with multi-organ failure, 1 from a prolonged seizure, 1 from prolonged neonatal hypoxemia, and 1 from meningitis and brain infarction. The frequency and duration of apneas recorded some 3–12 weeks prior to the infants’ death were analyzed. The brainstem materials were collected and studied in an attempt to elucidate the relationship between sleep apnea, and prone sleep position and gliosis in some nuclei associated with cardiorespiratory characteristics, such as nucleus ambiguus in the medulla oblongata and the solitary nucleus, as well as structures associated with arousal phenomenon, such as the reticular formation, the superior central nucleus and the nucleus raphe magnus in the pons, the dorsal raphe nuclei in the midbrain and medulla oblongata, periaqueductal gray matter in midbrain, and locus ceruleus. Gliosis was estimated as the density of glial fibrillary acidic protein (GFAP)-positive reactive astrocytes. Variant–covariant analyses were carried out using the characteristics of apnea as an independent variable and sleep position and gliosis as dependent variables. A significant association was found only in the frequency of obstructive apnea and prone position (P

Among 27,000 infants studied prospectively to characterize their sleep-wake behavior, 38 infants died under 6 months of age. They included 26 cases of sudden infant death syndrome (SIDS). Five infants who died from congenital cardiac abnormalities, two from infected pulmonary dysplasia, two from septic shock with multi-organ failure, one during a prolonged seizure, one from a prolonged neonatal hypoxemia, one from meningitis with brain infarction. All the infants had been recorded during one night in a pediatric sleep laboratory some 3-12 weeks before death. The frequency and duration of sleep apneas were analyzed. The infants' brain stem material was collected and immunohistochemistry of glial fibrillary acidic protein (GFAP) was carried out. The density of GFAP-positive reactive astrocytes was measured in the cardiorespiratory and arousal pathway. Akaike information criterion statistics (AIC) were calculated to elucidate the relationship between the epidemiological data on sleep position, the physiological data and the pathological data in SIDS victims. The duration of obstructive apnea was the most significant variable to differentiate between SIDS victims and control infants. In conclusion, the present study sustains the possibility of an organic fragility within the arousal pathway in SIDS victims with repetitive sleep apneas.