Responses to partial nasal obstruction in sleeping infants

Partial nasal obstruction was performed during a morning of quiet sleep (QS: non-REM) and active sleep (AS: REM) at ages 1 week, 2 weeks, 1, 2, 3, 4 and 6 months on 12 normal infants, 15 subsequent siblings of victims of the Sudden Infant Death Syndrome (SIDS) and 12 infants admitted for investigation of infant apnoea ('near-miss' SIDS). In all three groups the numbers failing to arouse after 240 s (FTA-240) in QS were significantly greater than those in AS. After 2 months of age all groups showed a decrease in the number FTA-240 in AS, whereas in QS the number did not change significantly. Subsequent siblings of SIDS had a significantly higher number FTA-240 in QS than controls. There was no significant difference in FTA-240 in QS between controls and infant apnoeas, although there was a trend for this to be higher in subsequent siblings of SIDS than infant apnoeas. It was concluded that arousal from AS is more marked than from QS, that after 2 months of age the ability to arouse from AS increases, and that in relation to SIDS, QS is the sleep state in which the infant is less able to arouse. Furthermore, subsequent siblings of SIDS differ from normal infants in their ability to arouse from QS.     

Responses to partial nasal obstruction in sleeping infants

Partial nasal obstruction was performed during a morning of quiet sleep (QS: non-REM) and active sleep (AS: REM) at ages 1 week, 2 weeks, 1, 2, 3, 4 and 6 months on 12 normal infants, 15 subsequent siblings of victims of the Sudden Infant Death Syndrome (SIDS) and 12 infants admitted for investigation of infant apnoea ('near-miss' SIDS). In all three groups the numbers failing to arouse after 240 s (FTA-240) in QS were significantly greater than those in AS. After 2 months of age all groups showed a decrease in the number FTA-240 in AS, whereas in QS the number did not change significantly. Subsequent siblings of SIDS had a significantly higher number FTA-240 in QS than controls. There was no significant difference in FTA-240 in QS between controls and infant apnoeas, although there was a trend for this to be higher in subsequent siblings of SIDS than infant apnoeas.
It was concluded that arousal from AS is more marked than from QS, that after 2 months of age the ability to arouse from AS increases, and that in relation to SIDS, QS is the sleep state in which the infant is less able to arouse. Furthermore, subsequent siblings of SIDS differ from normal infants in their ability to arouse from QS.     

The role of gastro-oesophageal reflux in the aetiology of SIDS

Gastro-oesophageal reflux (GOR) has been identified as a possible cause of SIDS. Several features of GOR unique to infants presenting with apparent life-threatening events (ALTEs) have led to its 'pathogenic' definition. One is that the life-threatening apnoea itself is initiated by GOR, another is that the ALTE relates to prolonged reflux during sleep, in a vulnerable sleep-state, and finally that the ALTE relates to excessive quantities of GOR. The presumption of GOR 'pathology' as a cause of SIDS however, is questionable in these susceptible infants for three reasons: firstly, GOR is physiological and occurs in most infants; secondly, there is no general consensus on what constitutes normal physiological reflux, and thirdly, variation in the recording technique and methods of data analysis and interpretation may account for the differences between study groups. It seems likely therefore if GOR is implicated in SIDS, additional factors are involved. Under certain circumstances, physiological GOR may trigger life-threatening apnoea in apparently healthy infants, that leads to SIDS. One mechanism that could explain such a death is reflex apnoea by stimulation of laryngeal chemoreceptors (LCR) during sleep. The conditions under which this could be fatal are the occurrence of gastric contents refluxed to the level of the pharynx during sleep, in the young infant who has depressed swallowing and arousal. That is, the occurrence of GOR to the level of the pharynx during sleep, an infrequent event that is usually innocuous, could be converted to a fatal event if swallowing is impaired and arousal depressed, by a variety of mediating factors such as prone sleeping, prematurity, sedatives, seizures or upper respiratory tract infections. The identification of LCR responses, particularly in prone sleeping and premature infants provide further evidence that this mechanism may be implicated in the aetiology of SIDS in apparently healthy infants.     

Potential Mechanisms of Failure in the Sudden Infant Death Syndrome

Current evidence suggests that multiple neural mechanisms contribute to the fatal lethal event in SIDS. The processes may develop from a range of otherwise seemingly-innocuous circumstances, such as unintended external airway obstruction or accidental extreme flexion of the head of an already-compromised structure of the infant upper airway. The fatal event may occur in a sleep state which can suppress muscle tone essential to restore airway patency or exert muscle action to overcome a profound loss of blood pressure. Neural processes that could overcome those transient events with reflexive compensation appear to be impaired in SIDS infants. The evidence ranges from subtle physiological signs that appear very early in life, to autopsy findings of altered neurotransmitter, including serotonergic, systems that have extensive roles in breathing, cardiovascular regulation, and thermal control. Determination of the fundamental basis of SIDS is critical to provide biologic plausibility to SIDS risk reduction messages and to develop specific prevention strategies.     

Apnoea of prematurity and arousal from sleep

The incidence of sudden infant death syndrome (SIDS) has been found to be consistently higher in preterm and low birth weight infants than in infants born at term and this increase is inversely related to gestational age. The incidence and severity of apnoea of prematurity, are also inversely related to gestational age. The aim of this study was to investigate whether a neonatal history of apnoea/bradycardia affected the maturation of arousal responses. Twenty-five premature infants were studied. A perinatal risk score was determined for each infant and infants were divided into those with a neonatal history of apnoea/bradycardia (n=16) and those without (n=9). All infants were studied using daytime polysomnography on three occasions: (a) a preterm study around 36 weeks gestation, (b) within 3 weeks of term, and (c) 2-3 months post-term. Multiple measurements of arousal threshold (cm H2O) in response to air-jet stimulation applied alternately to the nares were made in both active sleep (AS) and quiet sleep (QS). Arousal thresholds were elevated in apnoeic infants compared to control infants in both AS (P<0.05) and QS (P<0.001) at the term study and in QS at 2-3 months post-term (P<0.01). In addition, arousal thresholds were positively correlated with perinatal risk score in both sleep states, in all studies, with the exception of AS at 2-3 months when all infants were readily arouseable. We conclude that a history of prematurity with neonatal apnoea has a persisting effect on decreasing arousabilty from sleep and these infants may be at increased risk for SIDS.     

Distinct patterns of respiratory difficulty in young children with achondroplasia: a clinical, sleep, and lung function study

AIM: Achondroplasia can result in respiratory difficulty in early infancy. The aim of this study was to document lung growth during infancy, together with the cause of any cardiorespiratory and sleep dysfunction. PATIENTS AND METHODS: Seventeen prospectively ascertained infants (14 boys and three girls) with respiratory symptoms starting before 1 year of age underwent clinical, sleep, and lung function studies. RESULTS: Three distinct groups were identified. Group 1 (n = 6) were the least symptomatic and only had obstructive sleep apnoea. Group 2 (n = 6) had obstructive sleep apnoea of muscular aetiology and, neurologically, hydrocephalus and a small foramen magnum were common. Group 3 (n = 5), the most severely affected group, all developed cor pulmonale, with three deaths occurring as a result of terminal cardiorespiratory failure. All five had obstructive sleep apnoea with a muscular aetiology (a small foramen magnum predominated) with severe or moderately severe gastro-oesophageal reflux. Initially, lung function studies found no evidence of restriction or reduced lung volumes standardised according to weight. However, with growth these infants had worsening function, with raised airway resistance and severe reductions in respiratory compliance. CONCLUSIONS: These groups appear to be distinct phenotypes with distinct anatomical aetiologies: "relative" adenotonsillar hypertrophy, resulting from a degree of midfacial hypoplasia (group 1); muscular upper airway obstruction along with progressive hydrocephalus, resulting from jugular foramen stenosis (group 2); and muscular upper airway obstruction, but without hydrocephalus, resulting from hypoglossal canal stenosis with or without foramen magnum compression and no jugular foramen stenosis (group 3). The aetiology of these abnormalities is consistent with localised alteration of chondrocranial development: rostral, intermediary and caudal in groups 1, 2, and 3, respectively.     

Multiple causes of asphyxia in infants at high risk for sudden infant death.

A wide range of clinical findings was present in 58 near-miss sudden infant death syndrome (SIDS) infants and 6 surviving twins of SIDS siblings. Specific investigations included: studies of gastro-oesophageal reflux and aspiration (24-hour oesophageal pH recordings, barium swallow, radionuclide ''milk-scan''); polygraphic studies of breathing, reflux, and sleep state; studies of upper airways disease (lateral airways radiography and endoscopy); detection of seizure activity by electroencephalography; evaluation of thiamine status by erythrocyte transketolase activity of venous blood. Thiamine deficiency was found in 12 of 43 tested infants; 5 of the deficient infants had a familial history of SIDS. Many potential mechanisms for asphyxia were found: idiopathic central apnoea (7 infants), tracheal obstruction from minimal tracheomalacia or aberrant innominate artery (4 infants), temporal lobe or generalised seizures (6 infants), gastro-oesophageal reflux (55 infants) with intrapulmonary aspiration (11 infants). The high incidence, severity, and timing of reflux were new findings. Reflux occurred in active and indeterminate sleep, but not in quiet sleep. The depression of respiratory reflexes by active sleep stresses the vulnerability to asphyxia. Two factors suggest that near-miss episodes are related to SIDS: the similar age distribution but earlier occurrence of near-miss episodes compared with age at death of SIDS infants, and the subsequent sudden death of 2 infants whose necropsies were consistent with SIDS.     

Altered arousal response in infants exposed to cigarette smoke.

AIMS: A failure of the arousal mechanism is a key feature in the apnoea theory for sudden infant death syndrome (SIDS). In infants studied at an age when the incidence of SIDS is highest, we evaluated whether in utero smoke exposed infants have altered arousal response to standardised auditory stimuli, and/or sleep pattern, as recorded on overnight complex sleep polysomnography. METHODS: A standardised sequence of audiology stimuli was applied binaurally to 20 in utero smoke and non-smoke exposed infants aged 8-12 weeks during a rapid eye movement (REM) and NREM epoch, in a controlled (temperature, position, pacifier use, noise) sleep environment. Infants were monitored for 10-12 hours using complex sleep polysomnography. RESULTS: Five infants exposed to in utero tobacco smoke did not have behavioural arousal response, whereas all non-smoke exposed infants aroused during NREM (p = 0.016). There was, however, no difference in REM sleep, and the groups did not differ in routine overnight complex sleep polysomnography parameters. CONCLUSION: At the age when the incidence of SIDS is at its peak, infants of smoking mothers are less rousable than those of non-smoking mothers in NREM sleep; this may partly explain why such infants are more at risk of SIDS.     

Altered arousal response in infants exposed to cigarette smoke

Aims: A failure of the arousal mechanism is a key feature in the apnoea theory for sudden infant death syndrome (SIDS). In infants studied at an age when the incidence of SIDS is highest, we evaluated whether in utero smoke exposed infants have altered arousal response to standardised auditory stimuli, and/or sleep pattern, as recorded on overnight complex sleep polysomnography. Methods: A standardised sequence of audiology stimuli was applied binaurally to 20 in utero smoke and non-smoke exposed infants aged 8–12 weeks during a rapid eye movement (REM) and NREM epoch, in a controlled (temperature, position, pacifier use, noise) sleep environment. Infants were monitored for 10–12 hours using complex sleep polysomnography. Results: Five infants exposed to in utero tobacco smoke did not have behavioural arousal response, whereas all non-smoke exposed infants aroused during NREM (p = 0.016). There was, however, no difference in REM sleep, and the groups did not differ in routine overnight complex sleep polysomnography parameters. Conclusion: At the age when the incidence of SIDS is at its peak, infants of smoking mothers are less rousable than those of non-smoking mothers in NREM sleep; this may partly explain why such infants are more at risk of SIDS.     

Distinct patterns of respiratory difficulty in young children with achondroplasia: a clinical,sleep, and lung function study

AIM—Achondroplasia can result in respiratory difficulty in early infancy. The aim of this study was to document lung growth during infancy, together with the cause of any cardiorespiratory and sleep dysfunction.PATIENTS AND METHODS—Seventeen prospectively ascertained infants (14 boys and three girls) with respiratory symptoms starting before 1 year of age underwent clinical, sleep, and lung function studies.RESULTS—Three distinct groups were identified. Group 1 (n = 6) were the least symptomatic and only had obstructive sleep apnoea. Group 2 (n = 6) had obstructive sleep apnoea of muscular aetiology and, neurologically, hydrocephalus and a small foramen magnum were common. Group 3 (n = 5), the most severely affected group, all developed cor pulmonale, with three deaths occurring as a result of terminal cardiorespiratory failure. All five had obstructive sleep apnoea with a muscular aetiology (a small foramen magnum predominated) with severe or moderately severe gastro-oesophageal reflux. Initially, lung function studies found no evidence of restriction or reduced lung volumes standardised according to weight. However, with growth these infants had worsening function, with raised airway resistance and severe reductions in respiratory compliance.CONCLUSIONS—These groups appear to be distinct phenotypes with distinct anatomical aetiologies: "relative" adenotonsillar hypertrophy, resulting from a degree of midfacial hypoplasia (group 1); muscular upper airway obstruction along with progressive hydrocephalus, resulting from jugular foramen stenosis (group 2); and muscular upper airway obstruction, but without hydrocephalus, resulting from hypoglossal canal stenosis with or without foramen magnum compression and no jugular foramen stenosis (group 3). The aetiology of these abnormalities is consistent with localised alteration of chondrocranial development: rostral, intermediary and caudal in groups 1, 2, and 3,respectively.     

Effects of naloxone on apnoea duration during sleep in infants at risk for SIDS

The effects of intravenous injections of the opiate antagonist naloxone (0.005–0.4 mg/kg body weight) on respiratory pattern, apnoea duration and frequency were investigated in six infants with severe sleep apnoea syndrome. Since several authors found elevated plasma- and CSF-levels of endogenous opioids (endorphines) in infants with sleep apnoea syndrome, we wanted to determine whether the impairment of the control mechanisms of respiration during sleep is due to an effect of endogenous opioids.Independent of the dose, naloxone did not exert any effect on respiratory pattern and occurrence of periodic apnoea. We were unable to prove that endorphines play a major role in pathogenesis of sleep apnoea syndrome in infancy and possibly in sudden infant death syndrome (SIDS).We speculate that elevated levels of endorphines reported by some investigators rather seem to be a consequence of hypoxic stress than a cause for sleep apnoeas.Abbreviations SIDS sudden infant death syndrome - CSF cerebral spinal fluid Supported by the Austrian Research Fund     

A review of the anatomy of the upper airway in early infancy and its possible relevance to SIDS

BACKGROUND: Since the danger of prone sleeping in the first 6 months of life has been publicised, there has been a dramatic and consistent reduction in the incidence of sudden infant death syndrome (SIDS). However, unexpected infant deaths and apparent life-threatening events (ALTEs) continue to occur that are clearly not associated with known epidemiological risk factors. AIMS: To review the unique features of the anatomy and function of the upper airway of the young infant which contribute to increased vulnerability to hypoxia in this age group. We discuss the clinical identification of those infants at risk of obstruction or restriction of the upper airway and the management of the 'at risk' infant. CONCLUSIONS: In the era after the "back to sleep" campaigns, it is likely that an increasing proportion of cases of ALTEs and SIDS will be related to obstruction or limitation of upper airway size leading to sleep hypoxia/asphyxia. This type of problem may be anticipated by evaluation and investigation of infants with signs or a clinical history consistent with possible upper respiratory tract compromise, including micrognathia.     

What's new in paediatric sleep?

The major recent advance in our understanding of paediatric sleep is the publication of reference values for sleep in children aged 3.2-8.6 years. These data show developmental changes reflecting a subtle process of the maturation of the central nervous system with regard to sleep in childhood. In infants, a significant negative correlation has been observed between a snore-associated arousal index and an infant development scale, underlining that snoring is less innocent than has been suggested. A link between obstructive sleep apnoea (OSA) and airway inflammation has been demonstrated, with children with OSA having significantly higher expression of the leukotriene (LT) 1 and 2 receptors and higher concentrations of LT C4/D4/E4 and LT B4 in adenotonsillar tissues than children with recurrent rhinitis who have no OSA. This explains the efficacy of treatment for OSA with montelukast, a LT receptor antagonist, alone or in combination with corticosteroids. By using peripheral arterial tonometry, a noninvasive technique that allows the moment-to-moment measurement of sympathetic tone, persistent waking-associated autonomic nervous system dysfunction has been demonstrated in young children with sleep-disordered breathing (SDB). As such, SDB in childhood may represent a cardiovascular risk factor in adulthood.     

Effects of body position on sleep and arousal characteristics in infants

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.     

Motility and arousal in near miss sudden infant death syndrome

Developmental sleep patterns were compared in infants at known risk for "near-miss" sudden infant death syndrome and age-matched normal infants. Near-miss SIDS infants had significant differences suggestive of a temporary developmental delay. They retained rapid eye movement (REM) sleep at neonatal proportions, and stage 2 non-REM sleep appeared later. They also had a significantly increased apnea index. Twenty-four-hour recordings of sleep and respiratory patterns in near-miss SIDS infants from 3 weeks through 6 months of age showed a significant reduction in number of body movements in REM, non-REM, and total sleep time and in percentage of movement time at 3 weeks through 3 months of age. These findings can be used to address the role of arousal threshold in infants at risk for SIDS.     

Nocturnal sleep organization in infants "at risk" for sudden infant death syndrome

Nocturnal sleep organization was compared in normal infants and those "at risk" for sudden infant death syndrome (SIDS) (siblings and near-miss infants). Before 12 weeks of age, sleep modifications were observed in "at risk" infants. During their sleep they had a smaller percentage of intervening wakefulness with a higher amount of active sleep. Quiet and active sleep episodes had longer durations resulting in a longer sleep cycle. After 12 weeks, sleep organization tended to normalize. This fact is discussed as a possible factor for a SIDS event: a higher arousal threshold could play a critical role if homeostasy is disturbed during sleep, mainly at an age when the homeostatic control is not fully established.     

Influence of carotid denervation on the arousal and cardiopulmonary responses to upper airway obstruction in lambs

Experiments were done on five lambs to determine if carotid denervation influences the arousal and cardiopulmonary responses to upper airway obstruction during sleep. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electro-oculogram, nuchal and diaphragm electromyograms, and measurements of arterial blood pressure and arterial Hb oxygen saturation. A tracheotomy was done and a fenestrated tracheotomy tube placed in the trachea. During the study, a 5 F balloon-tipped catheter was inserted into the tracheotomy tube so that air flow could be obstructed by inflating the balloon. No sooner than 3 d after surgery, measurements were made in quiet sleep and active sleep during control periods when the animal was breathing room air and during experimental periods of upper airway obstruction. Carotid denervation significantly affected the arousal response to upper airway obstruction. Arousal occurred during 14 of 14 epochs in quiet sleep and during 12 of 13 epochs in active sleep before the arterial Hb oxygen saturation decreased to 30%. However, the time to arousal was increased and the arterial Hb oxygen saturation at arousal was decreased in carotid-denervated lambs compared with what we have previously observed in carotid-intact lambs. These data provide evidence that the carotid chemoreceptors and/or carotid baroreceptors play a major role in causing arousal from sleep during upper airway obstruction in lambs. Our results may have implications for sudden infant death syndrome, because it is possible that alterations in the arousal response to respiratory stimuli play a role in sudden infant death.     

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.     

Influence of repeated upper airway obstruction on the arousal and cardiopulmonary response to upper airway obstruction in lambs

Experiments were done on five lambs to determine if repeated obstruction of the upper airway influences the arousal and cardiopulmonary response to upper airway obstruction. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electrooculogram, nuchal and diaphragm electromyograms, and measurements of arterial blood pressure and arterial hemoglobin oxygen saturation. A tracheostomy was done and a fenestrated tracheostomy tube placed in the trachea. The animals were studied after a 3-day recovery period. During a study, a 5F balloon-tipped catheter was inserted into the tracheostomy tube so that air flow could be obstructed by inflating the balloon. The balloon was inflated each time the animal went to sleep for approximately 100 consecutive epochs (17 to 30 h) and the time to arousal and the arterial hemoglobin oxygen saturation at arousal were recorded. Upper airway obstruction was terminated by deflating the balloon once the animal aroused from sleep. Arousal occurred from both sleep states during upper airway obstruction but was delayed in active sleep compared to quiet sleep. The time to arousal and the decrease in arterial hemoglobin oxygen saturation were significantly increased with repeated upper airway obstruction only during active sleep. Inasmuch as it is possible that alterations in the arousal response to respiratory stimuli play a role in sudden infant death, studies to investigate the mechanisms of the state-specific changes in the arousal response to upper airway obstruction are warranted.     

Airway management in children with cleft palate and/or micrognathia

Cleft lip and/or palate is the commonest congenital craniofacial abnormality affecting approximately 1 in 700 newborns each year. It comprises of a heterogenous group of disorders affecting facial growth and cosmesis, that are associated with increased risk of airway obstruction, sleep disordered breathing (SDB), glue ear and chronic ear disease, feeding difficulties, and failure to thrive (FTT). Cleft palate (CP) can be accompanied by an abnormally undersized jaw, known as micrognathia; although micrognathia can also be found in isolation. The craniofacial abnormalities found in these children can lead to a reduction in airway size due to the tongue falling backwards. The risk of airway obstruction ranges from intermittent airway collapse during sleep (obstructive sleep apnoea, OSA) to potentially life-threatening airway compromise necessitating intubation or a tracheostomy. This paper sets out to describe the pathophysiology of airway compromise in these children, recognising clinical symptoms and appropriate referral strategy, as well as a broad range of management options.