REM sleep prevents sudden infant death syndrome

Near-miss events were observed to occur in indeterminate sleep in a preterm infant reaching term at 6 weeks after birth. Moreover, prolonged sleep apnea and periodic respiration were frequently encountered in non-REM sleep. In view of the observation that pathologic sleep apnea occurs in non-REM sleep and the apparently contradictory findings of respiratory depression and more frequent apneas during REM sleep, apneic episodes during REM sleep were analysed in relation to phasic REM events. The frequent occurrence of respiratory pauses in REM burst-free periods of REM sleep suggests that tonic REM mechanisms inhibit respiratory neurons, while phasic REM mechanisms are facilitatory and protect an infant from prolonged sleep apnea.     

Gastroesophageal reflux and apnea in prematurely born infants during wakefulness and sleep

The hypothesis that acid gastroesophageal reflux may be responsible for the persistence of apnea was tested on 20 prematurely born infants, at a median conceptional age of 38.7 weeks. Gastroesophageal reflux was identified using distal esophageal pH monitoring. Apneas of durations greater than 10 seconds were identified and classified as either central or obstructive and mixed, using recordings of respiration. Wakefulness, active sleep, and quiet sleep were identified using electroencephalography and by assessing eye movements. Of 134 episodes of acid gastroesophageal reflux in the 20 subjects, more occurred during wakefulness and during active sleep than during quiet sleep. A total of 139 apneas, predominantly of the obstructive and mixed type, occurred. No relationship could, however, be demonstrated, in this rather small number of patients, between the occurrence of gastroesophageal reflux and that of apneas.     

Central hypoventilation during quiet sleep in two infants.

Expired ventilation (VE), tidal volume (VT), frequency (f), and alveolar PCO2 (PACO2) were examined in six normal infants at 41 to 52 weeks post-conceptional age and in two infants who were apneic at birth. Their response to breathing 5% carbon dioxide in air and to 100% oxygen in quiet sleep were compared to those in rapid eye movement (REM) sleep. VE in normal infants was 259 ml/kg/min in REM and 200.2 ml/kg/min in quiet sleep with the difference being due to decreased carbon dioxide production and to decreased dead space. VE increased 34.4 ml/kg/min/mm Hg of PCO2 elevation with 5% carbon dioxide breathing during REM and was not significantly different during quiet sleep. During oxygen breathing VE fell by 32.7% at 30 seconds before increasing again. In the affected infants, VE and PACO2 during REM at 1 and 4 months were normal. At 1 month, during quiet sleep, each infant became apneic and PACO2 rose 9 and 8 mm Hg/min respectively. At this time mechanical ventilation was begun. At 4 months, during quiet sleep, VE was 0.064 and 0.063 ml/kg/min at PACO2 of 66 mm Hg in each infant. The change was due entirely to a decrease in VT to 2.3 and 2.5 ml/kg. At this time 5% carbon dioxide breathing given during normal ventilation in REM produced an abrupt fall in VT to 2.0 and 2.2 ml/kg with no change in frequency. Oxygen breathing during REM at one month had no effect but at 4 months produced apnea requiring mechanical ventilation after one minute. The findings suggest that the ventilatory response to carbon dioxide is (1) important in initiation of extrauterine ventilation and (2) in sustaining ventilation particularly in quiet sleep. It is not necessary in sustaining ventilation awake or in REM sleep and it represents a balance between the stimulatory and depressant effects of carbon dioxide on the central nervous system.     

Sleep-related abdominal muscle behavior during partial or complete obstructed breathing in prepubertal children

We have evaluated the influence of nonrapid eye movement (NREM), REM sleep, and arousal on abdominal muscle contractions during snoring and/or obstructive apnea in 10 prepubertal children. All children were known habitual snorers and eight had a sleep apnea index above 10. During stage 3-4 non-REM sleep, non-apneic breathing with snoring was always associated with the presence of expiratory abdominal muscle electromyogram (EMG) discharges. During non-REM sleep apneas, abdominal muscle EMG discharges increased from the beginning to the end of each apnea. Termination of non-REM sleep apnea was marked by an "EEG arousal" in 12% of the apneic events and by a "movement arousal" in the other 88%. The highest abdominal muscle EMG discharge was always observed during the arousal response. During "phasic" REM sleep, abdominal muscle EMG discharges were absent during both nonapneic breathing (with or without snoring) and obstructive apneas. All REM sleep apneas ended with a "movement arousal," during which abdominal muscle EMG discharges were observed. Thus, abdominal muscle EMG discharges associated with "arousal" were seen independent of the immediately preceding sleep state.     

Apnea recordings of healthy infants at 40, 44, and 52 weeks postconception.

A total of 129 recordings of the respiratory activity of 46 normal full-term infants were obtained continuously for 24 hours in the hospital nursery at 3 days of life and in the home environment at 4 weeks and 12 weeks after birth. The pediatric pneumogram (PPG) technique, an impedance method, was used. Pneumogram data over longer than 16 hours was obtained on 77% of infants monitored. No infants experienced apnea longer than 15 seconds in duration at 40 and 44 weeks postconception, or greater than 11 seconds at 52 weeks postconception. Twenty-four hour plots of hourly apnea frequency revealed a marked variability, with evidence of clustering of apneic episodes during periods of reported sleep. Longest apnea time and hourly frequency of apneic episodes were highly correlated.     

Hypoxic and hypercapneic arousal responses and prediction of subsequent apnea in apnea of infancy

Hypoxic and hypercapneic arousal responses from quiet sleep were tested in 56 infants with apnea of infancy (one or more episodes of cyanosis, limpness, and apnea requiring vigorous stimulation or resuscitation with no treatable cause; age 6.8 +/- 1.1 [SEM] months). Responses were compared with those of nine control infants ranging from 1 to 25 months of age. To assess hypercapneic arousal, the inspired PCO2 was rapidly increased during quiet sleep to 60 mm Hg or until arousal (restlessness, agitation, eye opening) occurred. All control infants and those with apnea of infancy aroused to hypercapnea, but control infants aroused at a lower inspired PCO2 (inspired PCO2 40.1 +/- 2.6 mm Hg) than those with apnea of infancy (inspired PCO2 46.9 +/- 1.5 mm Hg, P less than .05). To assess hypoxic arousal, the inspired PO2 was rapidly decreased during quiet sleep to 80 mm Hg or until arousal occurred. All control infants aroused to hypoxia (inspired PO2 78.3 +/- 2.1 mm Hg). However, only 38% of those with apnea of infancy aroused (inspired PO2 78.1 +/- 0.8 mm Hg), indicating an abnormality in recognition of hypoxia, or central brainstem response to hypoxia. During the 10.4 +/- 1.2 months of follow-up, there was a high incidence of subsequent apneas (greater than 20 seconds) during sleep at home in 50 apneic infants. Infants with abnormal hypoxic arousal responses had more severe subsequent apneas than those with normal hypoxic arousal responses (P less than .05).     

Sleep-disordered breathing in children with congenital muscular dystrophies

ObjectiveMost types of neuromuscular diseases are known to be associated with a high risk of sleep-disordered breathing. We performed a prospective study in a well individualized group of muscular disorders, congenital muscular dystrophies (CMD), to characterize the frequency of sleep-disordered breathing and thereby to determine the potential usefulness of sleep studies in such patients.MethodsTwenty CMD children (12 F, 8 M, aged 4–17 years) were included. Using overnight polysomnography, we determined the following parameters: sleep stages, sleep latency, sleep efficiency index, wake time duration, total sleep time (TST), apnea/hypopnea index (AHI), arterial blood oxygen saturation, and nocturnal paroxysmal EEG activity.ResultsAs compared to healthy controls, we detected in our study group frequent awakenings, a decreased TST (mean 448 ± 44.4 min) and a decreased REM duration (mean 11.5 ± 3.5% of TST). Significant increase in wake time duration (28–90 min) and decrease in REM duration were observed in 12 patients. An apnea/hypopnea syndrome was detected in 13 patients (65%) with central apneas in 8, obstructive apneas in 2 and 3 mixed apneas in 3 patients. AHI was >10 in 3 cases, <10> 5 in 4 cases and were concomitant with blood oxygen de-saturation in four cases. NPA were detected in 10 patients ranging from 10 to 40% of TST.InterpretationOur results confirm the high incidence of sleep disordered breathing in children with CMD, and thereby, the usefulness of overnight polysomnography recordings in such patients.     

Sleep apneas and acid esophageal reflux in control infants and in infants with an apparent life-threatening event

Clinical experience shows that episodes of apnea can occur during regurgitations or vomiting. We questioned whether sleep apneas could be related temporally to documented falls in esophageal pH, when no clinical symptoms of emesis are witnessed. Twenty infants admitted after an apparently life-threatening event ('ALTE') during sleep, but with no clinical symptoms of vomiting or regurgitations at the time of the event, and ten control infants were studied. All infants had occasional episodes of regurgitations. Polygraphic monitoring of state of alertness, cardiorespiratory activity and low esophageal pH was performed continuously during 1 night. The data were analyzed blindly. A total of 334 central and 36 obstructive apneas were monitored, mainly in the ALTE group, during NREM sleep. A total of 116 falls in esophageal pH below 4 units were seen in 18 infants; 50% occurred during wakefulness, and 31% in REM sleep. Arousals or body movements preceded the pH fall in 50% of the cases. Within 5 min following the reflux onset, 18 central apneas (7.2% of the apneas) were seen. There was no correlation between the duration, or the lowest values of esophageal pH measured, and the number or duration of apneas. No obstructive apnea, bradycardia or arousal followed the falls in esophageal pH. Acid esophageal reflux did not play a significant role in the development of apnea in our population.     

Sleep disorders in succinic semialdehyde dehydrogenase deficiency: A family report

BackgroundSuccinic semialdehyde dehydrogenase deficiency (SSADH) is a rare neurometabolic disorder involving the degradation of γ-aminobutyric acid. Clinically, SSADH deficiency causes progressive or static encephalopathy with late infantile to early childhood onset. It is known that sleep disorders are a common clinical finding in these patients. However, very few studies have investigated sleep disorders with polysomnographies.Aim of the studyTo analyze sleep disorders breathing, sleep architecture and paroxysmal EEG activity through polysomnographic recordings of two siblings suffering from SSADH deficiencyMethodEach patient underwent laboratory diurnal and overnight video-polysomnographic recordings in a room specially dedicated to mothers and their children.ResultsThe background EEG activity during quiet wakefulness consisted in abnormal, diffuse, low-voltage, disorganized slow theta waves. In both patients there was a general disorganisation of the sleep architecture with an increase of light sleep and a decrease of REM sleep. In patient 1, during sleep, there were 36 hypopneas, 13 central apneas and one obstructive apnea with a variable duration of 7–30 s. The apnea/hypopnea index (AHI) was 7/h and oxygen saturation dropped to 80% during the respiratory events. In patient 2, the respiratory events consisted in 8 central apneas and 23 hypopneas of 6–20 s; no obstructive apneas or hypopneas were observed. The oxygen saturation dropped to 90% during the apneas and the AHI was 5/h.ConclusionSleep-disordered breathing (SDB) is a common finding in patients with SSADH deficiency and polysomnography recording is a useful tool for its diagnosis.     

Polysomnographic studies of infants who subsequently died of sudden infant death syndrome

The polygraphic findings from 11 future victims of sudden infant death syndrome (SIDS) are reported and compared with those of matched pairs of control infants. The recordings had been done to alleviate parental anxiety about sleep apnea. Four infants had siblings who were victims of SIDS. Two infants were studied 3.5 to 9.5 weeks before their deaths because of an unexplained apparent life-threatening event that had occurred during sleep. For each victim of SIDS, two control infants were selected from the 2,000 infants who had been tested in the same hospitals. They were matched for sex, gestational age, postnatal age, and weight at birth with the SIDS victims. Their polygraphic recordings had been performed within similar conditions. Each record was allocated a random code number and was analyzed without knowledge of the patient's identity by two independent scorers. Most sleep and cardiorespiratory variables studied did not differentiate SIDS victims from control infants. Only four variables significantly characterized the future SIDS victims: the maximal duration of central apneas, the number of sighs followed by a central apnea, the presence of obstructive apneas, and the presence of mixed apneas. Central apneas were longer during all sleep states in the SIDS victims compared with their matched controls, but none exceeded 14 seconds. Sighs immediately followed by an apnea were significantly less frequent in the future SIDS group. Obstructive and mixed sleep apneas were seen in eight of 11 SIDS victims and in only three of 22 control infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Infant sleep apnea profile: preterm vs. term infants

By means of polygraphic sleep recording, the sleep apnea profile with respect to the number and duration of inactive, obstructive and mixed apneic episodes as well as periodic breathing has been investigated in infants born preterm at 40, 52 and 64 weeks conceptional age and compared to that of term infants. At 40 weeks preterm infants showed significantly more apnea and periodic breathing compared to term infants. The difference was essentially due to obstructive and mixed apnea in non-REM sleep.There was a sharp decrease in all apneic variables—inactive, obstructive and mixed apnea as well as of periodic breathing—at 52 weeks conceptional age in infants that were previously preterm. Both groups exhibited a rather identical sleep apnea profile at 64 weeks. Two prospectively studied infants in the preterm group later became SIDS victims. One of them might have been identified as being at risk on the basis of his apnea profile compared to the normative data now available.Abbreviations REM rapid eye movements     

Relationship between functional residual capacity and oxygen desaturation during short central apneic events during sleep in "late preterm" infants

Apneic episodes are frequent in the preterm neonate and particularly in active sleep (AS), when functional residual capacity (FRC) can be decreased. Furthermore, FRC may be inversely correlated with the speed of blood-O(2)-desaturation. We evaluated the potential involvement of FRC in the mechanisms responsible for blood-O(2)-desaturation during short central apneic events (>3 s) in "late-preterm" infants and analyzed the specific influence of sleep state. Apneic events were scored in 29 neonates (postmenstrual age: 36.1 +/- 1.2 wk) during AS and quiet sleep (QS). FRC was measured during well-established periods of regular breathing. Apneas with blood-O(2)-desaturation (drop in SpO(2) >5% from the baseline, lowest SpO(2) during apnea: 91.4 +/- 1.8%) were more frequent in AS than in QS, whereas no difference was seen for apneas without desaturation. The magnitude of the FRC did not depend on the sleep state. In AS only, there was a negative relationship between FRC and the proportion of apneas with desaturation. Even in late preterm infants who do not experience long-lasting apnea, blood-O(2)-desaturation during short apneic events is related (in AS but not QS) to a low baseline FRC. Sleep stage differences argue for a major role of AS-related mechanisms in the occurrence of these apneas.     

Apneic spells and sleep states in preterm infants.

The incidence of apneic spells during different sleep states active sleep, quiet sleep, and undifferentiated sleep was determined in eight preterm infants of 30 to 35 weeks' conceptional age, by means of a polygraphic recording technique. They were free of perinatal and postnatal complications other than apnea. During their active or rapid eye movement (REM) sleep they showed significantly more apneic episodes which were also longer lasting and they were accompanied by bradycardia of a greater severity. The organization of the immature nervous system with a preponderance of inhibitory synaptic connections and the additional inhibition of spinal motoneurons during REM sleep are likely to be the cause of apneic spells in otherwise "normal" preterm infants.     

A developmental study on types and frequency distribution of short apneas (3 to 15 seconds) in term and preterm infants

We measured the frequency distribution and the ventilatory correlates of the various types of apneas 3 to 15 s long during sleep in eight term infants (birth weight 3.65 +/- 0.16 kg; gestational age 39.5 +/- 0.3 wk) and eight preterm infants (birth weight 2.07 +/- 0.18 kg; gestational age 34.3 +/- 0.4 wk). Each infant was studied on five to seven occasions from birth to 56 wk of postconceptual age using a modified flow-through system. Sixty-six paired epochs of quiet sleep (1163 min) and rapid eye movement sleep (829 min) were analyzed in term infants and 85 paired epochs of quiet sleep (1553 min) and rapid eye movement sleep (1328 min) in preterm infants. Of the 783 apneas recorded in term infants 82% were central, 1.5% obstructive, 0.5% mixed, and 16% were of the breath-holding type; the corresponding figures for the 4086 apneas recorded in preterm infants were 93, 0.5, 1.0, and 5.5%. This distribution was similar in the two sleep states but term infants had a higher percentage of breath-holding apneas than preterm infants (p less than 0.01). In preterm infants the rate of central apneas decreased with postnatal age (p less than 0.01); in term infants the rate did not change significantly. The duration of apneas showed a modal distribution for central apneas at about 8 s for both groups during the 1st month of life (p less than 0.05). The findings suggest: 1) apneas in the newborn and early infancy are primarily central and are more frequent in preterm than in term infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Control of breathing in the central alveolar hypoventilation syndrome with and without a phrenic pacemaker

Primary central alveolar hypoventilation (CAHV) is a rare disorder described in newborns, children, and adults. We report a 2 9/12 year old child with CAHV of unknown etiology. The evaluation of her ventilatory control system showed abnormalities awake and in the different sleep states. Hypoventilation was found to be more severe during non-REM sleep than during REM sleep and awake state. She had central apnea, an irregular respiratory rhythm in the non-REM sleep too, and diminished ventilatory response to inhaled 5%-6% CO2 in both REM and non-REM sleep. Her ventilation decreased when she was breathing 50% and 100% oxygen. During breathing 15% oxygen she did not arouse in spite a transcutaneous pO2 of 10 mmHg. She was first treated with mechanical ventilation during sleep and has now received bilateral simultaneous phrenic pacemaker support during quiet sleep for about one year. With the phrenic pacemaker she has normal minute volume and transcutaneous blood gases during sleep. During a respiratory infection she needed again mechanical ventilation via her tracheostoma 24 hours a day for one week. This case of a CAHV demonstrates a dysfunction of the central and partially also of the peripheral chemoreceptors. The abnormalities of the ventilation were demonstrable not only in the non-REM sleep but also in the REM sleep and awake state.     

Obstructive sleep apnea syndrome in a child with trisomy 21

Pulmonary hypertension without any cardiovascular malformation was diagnosed by heart catheterization in a 4 year old girl with trisomy 21. A suspected obstructive sleep apnea syndrome was confirmed by polysomnography which revealed numerous obstructive apneas and hypopneas (apnea-index 23/h) with marked oxygen desaturation and a disturbed sleep pattern. Three months after adenotonsillectomy the mother reported her daughter having a quiet sleep without snoring. Polysomnography did not show any apnea nor any oxygen desaturation below 90%. A decrease of the pulmonary artery pressure was documented. Facial dysmorphias and muscle hypotonia predispose patients with trisomy 21 to obstructive sleep apnea, especially if hypertrophy of tonsills and adenoids coexist. Frequent arousals and hypoxia during sleep can result in failure to thrive and pulmonary hypertension. These consequences can be prevented by early diagnosis and treatment.     

Patterns of EEG frequency, movement, heart rate, and oxygenation after isolated short apneas in infants

Patterns of events occurring at the end of apneas have rarely been reported in infants. No previous studies have compared these patterns to those of spontaneous events during sleep. We examined 163 isolated apneas in 17 infants (47 +/- 4 wk postconceptional age) who underwent polysomnography for suspected upper airway problems. Mean apnea duration was 6.5+/-1.5 s (range, 5 to 11.5 s), 78% of apneas occurred in active sleep, and 67% of apneas were obstructive. We recorded the occurrence of body movement or augmented breath and analyzed changes in EEG frequency > or = 1 s, heart rate, and oxygen saturation value at the end of apneas and of a control ventilatory period defined as a period of breathing equal in duration to the apnea and preceding the apnea by 1 min. We found that 7.9% of apneas and 11.6% of control periods were followed by an augmented breath and that 14.1% of apneas and 0.5% of control periods were followed by a body movement. The percentages of motor events or no event differed significantly after the apneas (p = 0.008) compared with the control periods. A significant increase in EEG frequency was observed at the end of the apneas compared with the control periods (p < 0.04). EEG frequency increased after 61% of the apneas. Neither heart rate nor oxygen saturation value changed after the control periods. Heart rate decreased significantly after the apneas not followed by a motor event (p = 0.02) but not after the apneas followed by a body movement. We conclude that 1) at termination of isolated apneas in infants, a motor event was rare, whereas an EEG frequency increase was common; 2) event patterns at apnea termination differed from those at control period termination.     

Respiratory and motor events in sleeping infants: their correlation with thoracico-abdominal respiratory relationships.

28 polygraphic recordings were made in normal infants: 20 in full-term newborns and 8 in 2- to 10-wk-old babies. In full-term newborns sighs and apneas (greater than 5 sec) were significantly more numerous in active (REM) sleep, while startles prevailed in quiet (NREM) sleep. The incidence of all these events diminished with age. Important interindividual differences of their frequency were noted in normal babies. There were not time correlations between the apneas (decreasing from newborns to 2-10 wk of age) and out-of-phase respiration in active sleep (no changing during the same period). Sighs, apneas, startles and limb movements did not modify phase relationships between thoracic and abdominal movements. Where movements were out of phase, only body movements involving the thorax were followed by transient period with in phase respiratory movements. Coincidences between occurrence of sighs, apneas, startles, gross body movements and respiratory amplitude diminution were calculated. There was no constant parallelism between out-of-phase thoracico-abdominal respiration and tonic chin activity inhibition nor respiratory rate irregularity. A hypothesis on neurological mechanism underlining these phenomena is proposed.     

Obstructive sleep apnea: a polysomnographic study of sleep apnea before and after tonsillectomy and adenoidectomy

We report about polysomnographic studies including EEG, EOG, EMG, ECG, measurement of oropharyngeal airflow, recording of chest wall movements and transcutaneous measurements of pO2 and pCO2 in a 4-year-old girl with severe obstructive sleep apnea. Her sleep profile was characterized by a disturbed cyclic pattern of sleep stages with onset of sleep at stage 4, shortening of REM-sleep periods and of sleep stages 1 and 2, and an increased quantity of sleep stage 4. The total time spent in apneic episodes was 11.3% of the total sleep period (only obstructive events). Apneic attacks were recorded mainly in REM and light NREM sleep states. Tonsillectomy and adenoidectomy resulted in marked improvement without further evidence of abnormal sleeping pattern or of sleep apneas.