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In infants the cardiorespiratory system undergoes significant functional maturation after birth and these changes are sleep-state dependent. Given the immaturity of these systems it is not surprising that infants are at risk of cardiorespiratory instability, especially during sleep. A failure of cardiovascular control mechanisms in particular is believed to play a role in the final event of Sudden Infant Death Syndrome (SIDS). The “triple risk model” describes SIDS as an event that results from the intersection of three overlapping factors: (1) a vulnerable infant, (2) a critical development period in homeostatic control, and (3) an exogenous stressor. This review summarises normal development of cardiovascular control during sleep in infants and describes the association of impaired cardiovascular control with the three overlapping factors proposed to be involved in SIDS pathogenesis.

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.

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.

Objective. The risk of becoming a victim of sudden infant death syndrome is increased in infants who sleep with their face under bedding items. The present study was designed to evaluate auditory arousal thresholds of infants who sleep with their face covered by bedclothes. Methods. Twenty healthy infants with a median age of 11.5 weeks (range: 4–22 weeks) were recorded polygraphically for 1 night. Although they slept in their usual supine position, a bed sheet was placed over their face for 60 minutes. Fifteen of the 20 infants were chosen at random and were exposed to white noises of increasing intensities to determine their auditory arousal thresholds. All infants were challenged with the face covered and with the face free during both rapid eye movement (REM) and non-REM (NREM) sleep. Seven infants were first challenged with the face covered, and 8 were challenged with the face free. The following variables were recorded simultaneously: electroencephalogram, breathing and heart rates, and rectal and pericephalic temperatures. In 5 infants who were not exposed to the auditory challenges, end tidal CO2 was recorded for 30 minutes while sleeping with the face covered. Results. During REM sleep, arousals occurred for significantly more intense auditory stimuli when the infant’s face was covered than when free. No significant difference was seen in NREM sleep. Compared with the face-free periods, the face-covered sleep periods were characterized by greater rectal and pericephalic temperatures, a greater density of body movements, and a decrease in NREM sleep. Respiratory frequency was increased during the face-covered periods in both REM and NREM sleep. No differences were seen in the frequency or duration of apnea. There was a tendency for heart rate to increase during both sleep stages when the face was covered, compared with the face-free periods, but the changes were not statistically significant. A positive correlation was found between pericephalic temperatures and arousal thresholds (r = 0.60) during REM sleep. End tidal CO2 values increased when the face was covered, reaching a maximum value during the first 5 minutes of the experiment. No fall in oxygen saturation was seen. Conclusions. Covering the infant’s face with a bed sheet was associated with a significant increase in auditory arousal threshold. The finding could be related to an elevation in temperatures within the infant’s microenvironment.

In order to assess the specific sympathetic reactivity in premature infants at term, we designed a study to evaluate the peripheral vasomotor response of such infants when exposed to auditory challenges. Testing was performed in 29 premature neonates at term in both quiet and active sleep during a morning session. Two types of noises were used (click and continuous tones) at three frequencies (250, 1,000 and 6,000 Hz) and at three intensities (60, 85 and 110 dBA). Vasomotor response was studied by analyzing with Mathlab® software the variability of the plethysmographic wave of the oxymetric pulse. No behavioral awakening was observed in response to any stimulation. When a tachycardia or a bradycardia reaction to the stimuli was observed, all neonates responded with a vasoconstriction. The global mean of the vasoconstrictive response was 18.45%. The overall ANOVA on the vasomotor response revealed significant effects for sleep stages (t: 1.98; p < 0.05), for frequency (t: 3.3; p < 0.001) and for intensity of noise (t: 3.01; p < 0.03) but no significant response with heart rate variability. From these results, we could conclude that the assessment of the vasomotor response is a very sensitive procedure to determine the reactivity of the autonomic nervous system in neonates, and could be used to study such vegetative responses in other stressful situations with good accuracy.

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.

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)

In this review, we discuss sleep recording techniques, normal sleep characteristics, and the effects of sleep deprivation. Sleep quality and quantity mature with development. Sleep-wake behaviors are described in fetuses, infants, preschool, and school-age children and adolescents. The short-term and medium-term effects of sleep deprivation are reviewed. While abundant literature exists on the physiology and characteristics of sleep in children, there is actually furthermore interest on the effects of sleep losses on the child’s physical, cognitive, mood, and mental health functions.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Sighs are important components of normal breathing. They occur isolated or associated with respiratory pauses. Functional residual capacity and lung compliance increase after sighs. Sighs have been shown to be part of an arousal reaction in infants and to induce heart rate modifications. We investigated the influence of sighs on the autonomic balance in infants. METHODS: 107 sighs (a single breath of at least twice the amplitude of the preceding breaths, not followed by an apnea) from 23 term infants were selected. The selection was made in conditions known not to interfere with spontaneous HR variability (quiet sleep,absence of movements, apnea or false detections of QRS during the 2 preceding and following minutes. Spectral analysis of RR variability was performed on the 2 minutes preceding and the 2 minutes following the sigh. To study the role of the ANS in the development of a sigh, spectral analysis of the period just before the sigh and of the 2 preceding minutes were compared. RESULTS: The 2 minutes following the sigh were characterized by an increased RR interval (p 0.001), an increased total power (p

Preventable risk factors for sudden infant death syndrome include the infant’s environment and response characteristics. Various infant and environmental factors thus modify the vital cardiocirculatory, respiratory and arousal controls in healthy infants. Similar changes in cardiorespiratory and autoresuscitative responses have been found in the analysis of sleep recordings of victims of sudden infant death syndrome. It is not known why some infants die, while others show similar changes but survive in the first year of life. The death could be due to the degree of the initial immature controls, to the severity of the additional challenge, or to a combined effect of inadequate autoresuscitative mechanisms and the cumulative influence of infant and/or environmental stressors.

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.

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.

1,3-Dimethyl-2-methylamino-1,3,2-diazaphospholidine-2,4,5-trione (1b) has been synthesized, and its solvolytic behaviour and X-ray crystal structure determined. Methanolysis of (1b) gives products of the cleavage of both imide P–N bonds, indicating that the ring opening in (1b) is much slower than the second P–N cleavage in the ring-opened intermediate. The low reactivity of (1b) is correlated with the small size (92.3°) of the endocyclic N–P–N angle, which suggests that not much energy is released upon the formation of the PV trigonal bipyramidal adduct. The molecular structure of (1b) reveals a high degree of coplanarity of the phospholidine ring with both imide N-methyl groups and both carbonyl oxygen atoms. The geometry indicates that the endocyclic nitrogen atoms in (1b) are involved in the resonance interactions not only with the adjacent carbonyl groups, but also with the phosphoryl centre.1,3-Dimethyl-2-phenoxy-1,3,2-diazaphospholidine-2,4,5-trione (1a) has been found to react with p-anisidine or ammonia exclusively at the phosphorus atom. In the reaction with p-anisidine both P–O bond cleavage (displacement of phenol) and ring P–N bond cleavage products were obtained; this is interpreted in terms of pseudorotation of the initially formed PV intermediate. Ammonia reacts with (1a) giving exclusively the ring-retained, P–OPh bond cleavage products. Our aminolysis results for (1a) contrast with those reported in the literature.