QT interval prolongation in future SIDS victims: a polysomnographic study.

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.

Maturation of spontaneous arousals in healthy infants.

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.

Spontaneous arousability in prone and supine position in healthy infants.

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.

Epidemiology of dog bites: a Belgian experience of canine behaviour and public health concerns.

This paper reviews three studies that have been conducted in Belgium on dog bites on children. (1) A telephone study revealed that 22/1000 children <15 years of age were victims of dog bites annually. (2) Data on the characteristics of dog bites were collected prospectively over a period of 8.5 months in six hospital emergency departments. "Dangerous dogs" were not responsible for the majority of the accidents. In 67/100, incidents documented, the bites appeared to be triggered by an interaction of the child. Education appeared to be the preventive measure with the highest priority. (3) Among 22 child victims of dog bites, 12 had symptoms of post-traumatic stress disorders some seven months following the accident. Based on these local studies, several initiatives have been undertaken to favour both primary and secondary prevention measures. An appropriate psychological preventive intervention should be offered to all victims of dog bites.

Influence of swaddling on sleep and arousal characteristics of healthy infants.

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.

Incongruent cerebral growth in sudden infant death syndrome.

Sudden infant death syndrome remains a leading cause of post-neonatal 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.

Decreased arousals among healthy infants after short-term sleep deprivation.

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.

Influences of maternal cigarette smoking on infant arousability.

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.

Pacifier use modifies infant's cardiac autonomic controls during sleep.

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.

Posttraumatic stress disorder after dog bites in children.

Of 22 children who were victims of dog bite, 12 had symptoms of posttraumatic stress disorder 2 to 9 months after the bite. Violent dog attacks inflicting multiple and/or deep wounds were associated with risk of posttraumatic stress disorder.

Increased cardiac autonomic responses to auditory challenges in swaddled infants.

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.

Recommended clinical evaluation of infants with an apparent life-threatening event. Consensus document of the European Society for the Study and Prevention of Infant Death, 2003.

UNLABELLED: Infants with an apparent life-threatening event (ALTE) should not be treated nor monitored without a detailed medical evaluation, as different medical causes may be responsible for the initial clinical presentation. Standard and specific evaluation procedures are listed to help identify a cause for the ALTE. The most frequent problems associated with an ALTE are digestive (about 50%), neurological (30%), respiratory (20%), cardiovascular (5%), metabolic and endocrine (under 5%), or diverse other problems, including child abuse. Up to 50% of ALTEs remain unexplained. The finding of medical or surgical anomalies leads to specific treatments. Surveillance programmes with the use of home monitoring devices may be undertaken, preferably with cardiorespiratory monitors, and when possible, with event monitors, although no currently available home monitoring device is free of false alarms or offers complete protection. Long-term follow-up programmes of infants with an apparent life-threatening event contribute to adapt medical attitudes to the child's needs and to confirm the medical diagnosis. CONCLUSION: a systematic diagnostic evaluation, together with a comprehensive treatment programme, increases survival and quality of life for most affected infants.

Clinicopathological correlation between brainstem gliosis using GFAP as a marker and sleep apnea in the sudden infant death syndrome.

BACKGROUND: Chronic hypoxia, leading to brainstem gliosis, has been postulated as a factor in the sudden infant death syndrome (SIDS), which is still the main cause of postneonatal infant death. Gliosis detected by immunohistochemistry of glial fibrillary acidic protein (GFAP) is a marker of apoptosis. The correlation between GFAP-positive reactive astrocytes 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, including 26 cases of SIDS. The frequency and duration of sleep apnea were analyzed. Brainstem material was collected and immunohistochemistry of GFAP carried out. The density of GFAP-positive reactive astrocytes was measured quantitatively. Correlation analyses were carried out between the data on gliosis and the physiological data of sleep apnea. RESULTS: A SIDS-specific negative correlation between the density of gliosis in the dorsal vagus nucleus in the medulla oblongata and the frequency of obstructive apnea (p=0.022) was found. CONCLUSIONS: A significant SIDS-specific correlation with gliosis in the dorsal vagus nucleus and the characteristics of sleep apnea might invite the cardiorespiratory changes in SIDS.

Pathological data on apoptosis in the brainstem and physiological data on sleep apnea in SIDS victims.

UNLABELLED: 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.

Investigation into the correlation in SIDS victims between Alzheimer precursor protein A4 in the brainstem and sleep apnea.

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 to 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.

The correlation between serotonergic neurons in the brainstem and sleep apnea in SIDS victims.

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.

Catecholaminergic neurons in the brain-stem and sleep apnea in SIDS victims.

BACKGROUND: Tyrosine hydroxylase (TH) is a specific marker for catecholaminergic neurones. Some reports have demonstrated a decrease of TH in the Sudden Infant Death Syndrome (SIDS) compared with controls. To further investigate this, the correlation between TH 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. They included 26 cases of 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 the duration of sleep apnea were analyzed. The brain stem material was collected and subjected to immunohistochemical studies for TH. The density of TH-immunoreactive neurons was measured in the nucleus hypoglossus, nervus vagus dorsalis, solitary and ambiguous and the ventrolateral medulla (VLM) in the medulla oblongata. Correlation analyses were carried out between the density of TH-immunoreactive neurons and the data from the sleep apnea studies. RESULTS: There was no SIDS specific correlation between TH-immunoreactive neurons in the nucleus hypoglossus, nervus vagus dorsalis, solitary and ambiguous and the ventrolateral medulla (VLM) in the medulla oblongata and the frequency and duration of sleep apnea. CONCLUSIONS: No significant association between the pathological data and the physiological data refers to TH positive neurons in the medulla oblongata in SIDS victims.

Substance P in the midbrains of SIDS victims and its correlation with sleep apnea.

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.

Partial arousal deficiency in SIDS victims and noradrenergic neuronal plasticity.

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.