Incidence and mechanism of bradycardia during apnoea in preterm infants.

Bradycardia occurred during 363 of 1520 apnoeas of 10 seconds'' duration recorded in 28 preterm infants. The incidence increased with increasing duration of apnoea (10% of 10-14 seconds, 34% of 15-20 seconds, and 75% of greater than 20 seconds, p less than 0.001). This was similar for each type of apnoea--central, mixed, and obstructive. During 133 apnoeas in five infants the time from the start of the apnoea to the onset in the fall in oxygen saturation (mean 6.9 seconds) was significantly related to the onset of the fall in heart rate (mean 9.3 seconds) (r = 0.67, p less than 0.001). Recovery in heart rate coincided with resumption of air flow rather than breathing efforts and preceded the recovery in oxygen saturation. These results suggest that bradycardia occurs during apnoea as a response to falling oxygen saturation, probably through a peripheral chemoreceptor reflex that is manifest when breathing efforts are absent or ineffective.     

The maturation of respiratory patterns in normal full term infants during the first six postnatal months. II: Sleep states and apnoea

ABSTRACT. Four term healthy infants had their respiratory pattern monitored during a 2-hour afternoon nap period at monthly intervals up to six months of age. Apnoeas 4 seconds or more at 1 week expressed as a percentage of breaths were significantly more frequent in active sleep than quiet sleep (2.1% vs 0.6%) and increased at 2 months in both sleep states (8.0% and 8.5% respectively) due to the onset of periodic breathing. Apnoeas then decreased in frequency up to 6 months in both sleep states (3.8% and 0.8% respectively). In the first month a startle and/or sigh occurred in 78% of apnoeas in quiet sleep, and gross body movement in 72% of apnoeas in active sleep. Between 4 to 6 months all apnoeas in quiet sleep were preceded by a startle and/or sigh, in contrast to active sleep, where the incidence of gross body movement and apnoea decreased (49%) and apnoea alone increased (48%). These findings confirm a maturational change in the incidence and pattern of apnoea in normal infants from 1 to 6 months.     

The febrile stress of routine vaccination does not increase central apnoea in normal infants

Abstract We tested the hypothesis that the febrile stress of routine vaccination would increase central apnoea in normal infants. Twenty-one normal infants had continuous overnight breathing and temperature recorded at home, before and after 58 routine vaccination episodes. Central apnoea, of at least 5 sec duration, was detected by computer algorithm and confirmed by human inspection. The longest recorded apnoea was 16 sec ( n = 1) during 3629 h of sleep. Overnight rectal temperature increased after vaccination (median 0.52°C, 95% CI 0.40, 0.65). Apnoea density reduced on 46/53 vaccination nights (median -29%, 95% CI -20, -37) followed by an increase on subsequent nights (median +10%, 95% CI +1%, +21%). Overall, apnoea density was similar during the 3 nights preceding and 4 nights following vaccination (median +1%, 95% CI +9,-6). The febrile stress of routine vaccination did not increase central apnoea in normal infants.     

The role of the upper airway in neonatal apnoea

Up to 50% of apnoeic episodes are obstructive or mixed apnoeas in which, by definition, there is upper airway obstruction. The other 50% of apnoeas are central in origin, but in 40% of these there is evidence of upper airway obstruction, which also occurs in periodic breathing. The obstruction occurs in the upper pharynx. It is due to a failure of activation of the muscles, including the genioglossus, which support the compliant pharynx and normally prevent its collapse. Fibreoptic studies have demonstrated obstruction also at the entrance to the larynx by the arytenoid masses and the aryepiglottic folds. There is some evidence that inspiring against a closed airway can induce central apnoea, possibly via the intercostal-phrenic inhibitory reflex. Upper airway secretions can trigger obstruction. Continuous positive airway pressure distends both the pharynx and laryngeal aperture and so prevents mixed and obstructive apnoeas, but has no effect on central apnoea.     

Observations on gastro-oesophageal reflux,central apnoea and heart rate in infants

Respiratory movements and heart rate were monitored continuously during the course of 2 h radionuclide studies to detect gastro-oesophageal reflux (GOR) in 22 infants following a milk feed. Twenty infants had GOR, to upper oesophageal/pharyngeal level in 19, and 17 had central apnoea between 3 and 15s. Prolonged central apnoea (greater than 20s) was not observed. Bradycardia, defined as a heart rate less than 80 beats/min for 10s or more, was observed in only 1 infant who did not have GOR. No correlation was found between the number or duration of reflux episodes and the frequency of respiratory pauses between 3 and 17s. When data from individual infants were examined a possible temporal relation between the occurrence of GOR and central apnoea was seen in only two infants; in each case, detailed examination suggested that apnoea was more closely associated with sleep than with GOR. Although the respiratory monitoring system did not include airflow sensors, the almost complete absence of bradycardia suggested that prolonged obstructive apnoeas did not occur. We conclude that any relation between GOR and central apnoeas less than 15 s is not of a direct cause/effect nature.     

Sleep-disordered breathing in overweight and obese children and adolescents: prevalence, characteristics and the role of fat distribution.

AIMS: To determine the prevalence of sleep-disordered breathing (SDB) in a clinical sample of overweight and obese children and adolescents, and to examine the contribution of fat distribution. METHODS: Consecutive subjects without chronic lung disease, neuromuscular disease, laryngomalacia, or any genetic or craniofacial syndrome were recruited. All underwent measurements of neck and waist circumference, waist-to-hip ratio, % fat mass and polysomnography. Obstructive apnoea index > or =1 or obstructive apnoea-hypopnoea index (OAHI) > or =2, further classified as mild (2< or =OAHI<5) or moderate-to-severe (OAHI> or =5), were used as diagnostic criteria for obstructive sleep apnoea (OSA). Central sleep apnoea was diagnosed when central apnoeas/hypopnoeas > or =10 s were present accompanied by >1 age-specific bradytachycardia and/or >1 desaturation <89%. Subjects with desaturation < or =85% after central events of any duration were also diagnosed with central sleep apnoea. Primary snoring was diagnosed when: snoring was detected by microphone and normal obstructive indices and saturation. RESULTS: 27 overweight and 64 obese subjects were included (40 boys; mean (standard deviation (SD)) age 11.2 (2.6) years). Among the obese children, 53% were normal, 11% had primary snoring, 11% had mild OSA, 8% had moderate-to-severe OSA and 17% had central sleep apnoea. Half of the patients with central sleep apnoea had desaturation <85%. Only enlarged tonsils were predictive of moderate-to-severe OSA. On the other hand, higher levels of abdominal obesity and fat mass were associated with central sleep apnoea. CONCLUSION: SDB is very common in this clinical sample of overweight children. OSA is not associated with abdominal obesity. On the contrary, higher levels of abdominal obesity and fat mass are associated with central sleep apnoea.     

Pneumographic studies: predictors of future apnoeas but not sudden infant death in asymptomatic infants

Pneumograms were performed on 401 asymptomatic infants: 322 siblings, 15 cousins and 24 twins of sudden infant death syndrome (SIDS) victims; 14 siblings of near-miss SIDS victims, and 26 infants of anxious parents. The infants of anxious parents had significantly fewer abnormalities than siblings of SIDS victims. In 222 infants subsequently monitored at home, the pneumogram as a predictor of future apnoea had a sensitivity rate of 97.5% and a specificity rate of 72% (P less than 0.001). Infants who were to experience future apnoeas had a significantly higher percentage of time in periodic breathing and a higher density of apnoeas in their original pneumograms. However, the abnormal pneumogram did not predict SIDS, because the eight infants who died all had normal pneumograms.     

Pneumographic studies: Predictors of future apnoeas but not sudden infant death in asymptomatic infants

Abstract Pneumograms were performed on 401 asymptomatic infants: 322 siblings, 15 cousins and 24 twins of sudden infant death syndrome (SIDS) victims; 14 siblings of near-miss SIDS victims, and 26 infants of anxious parents. The infants of anxious parents had significantly fewer abnormalities than siblings of SIDS victims. In 222 infants subsequently monitored at home, the pneumogram as a predictor of future apnoea had a sensitivity rate of 97.5% and a specificity rate of 72% ( P < 0.001). Infants who were to experience future apnoeas had a significantly higher percentage of time in periodic breathing and a higher density of apnoeas in their original pneumograms. However, the abnormal pneumogram did not predict SIDS, because the eight infants who died all had normal pneumograms.     

Effects of nasal continuous positive airway pressure on apnoea index and sleep in infants

Objectives: We examined the effectiveness of nasal continuous positive airway pressure (CPAP) for treatment of sleep apnoea in infants.
Methodology: We studied five infants who all had significant central and mixed apnoea and severe sleep fragmentation. Polysomnographic recordings were performed on 2 consecutive nights in these infants. One night was used as a control study and during the second night nasal CPAP was applied throughout the night
Results: Nasal CPAP significantly reduced apnoea in each infant, with the apnoea index (apnoeas/h) decreasing from 65.6± 14.6 during the control study to 10.5± 14.6 during CPAP in non-rapid eye movement (non-REM) sleep, and from 106± 13.9 during the control study to 26.6± 13.9 during CPAP in REM sleep. Nasal CPAP also improved the sleep fragmentation markedly; REM sleep increased from 14.2± 1.2% of sleep during the control study to 27.1 ± 1.2% of sleep during CPAP.
Conclusions: We conclude that nasal CPAP is an effective treatment for infantile apnoea. Sleep apnoea in these infants is associated with profound sleep fragmentation, which is reversed by nasal CPAP.     

Monitoring for central apnoea in infancy--limitations of single channel recordings.

Apparent central apnoea (absent breathing movements) detected by monitoring movement of the thoracic wall was compared with simultaneous detection by abdominal wall movement. Eighteen infants provided one or more 24 hour recording of heart rate (electrocardiography), thoracic respiration (transthoracic impedance), and abdominal wall movement (pressure sensitive capsule distortion). Detection of true apnoea, recognition of artefact, and measurement of the duration of true apnoea were all improved when two channels of respiratory monitoring were used in combination. We recommend that any study purporting to observe breathing patterns by indirect recording of respiratory movement will be more reliable if more than one channel of respiratory movements is recorded simultaneously. Further, in infants no estimation of duration of central apnoea can be made on the basis of either a transthoracic impedance record alone or an abdominal wall movement sensor alone. Comparison of findings among studies using different single channel recordings are unlikely to be meaningful.     

Effect of nursing position on incidence, type, and duration of clinically significant apnoea in preterm infants.

AIM--To investigate whether nursing position has any effect on the frequency, type, and duration of apnoeas in preterm infants. METHOD--Thirty five preterm infants were entered into a crossover study and underwent polygraphic monitoring in each of two positions, prone and supine, the initial position being randomly allocated. Four parameters were recorded: nasal airflow, respiratory effort, electrocardiogram (ECG), and oxygen saturation. Each infant was studied in the two positions on the same day and each infant was studied only once. The studies were carried out on the neonatal intensive care unit. RESULTS--The infants were found to have significantly more central and mixed apnoeas in the supine than in the prone position. In addition, the severity of mixed apnoeas in terms of the duration of accompanying bradycardias and desaturations was greater in the supine than in the prone position (median difference 5.1 seconds in both instances). When considering the type of apnoea in relation to the duration, it was found that of those less than 20 seconds in duration there was a greater proportion that were central (25%) compared with the proportion of central (5%) apnoeas that were longer than 20 seconds. Of all the apnoeas that were less than 20 seconds in length, 16% were obstructive and 59% were mixed, whereas of the apnoeas greater than 20 seconds, 13% were obstructive and 82% were mixed. CONCLUSIONS--It appears that in addition to improving measures of lung function, the adoption of the prone nursing position for preterm infants may reduce associated problems of apnoea of prematurity.     

Cerebral oxygenation in children with sleep-disordered breathing

Sleep-disordered breathing (SDB) is associated with neurocognitive and behavioral dysfunction, and structural brain abnormalities. Near infrared spectroscopy allows a continuous and non-invasive monitoring of brain tissue oxygenation, giving insight in some pathophysiological mechanisms potentially associated with SDB-related neurocognitive dysfunction. The present review summarizes the finding of studies describing brain tissue oxygenation in adults and children with SDB. Contrary to adults, mean nocturnal tissue oxygenation index (TOI) during sleep does not seem to be different in children with SDB as compared to healthy controls. During respiratory events such as apnoeas and hypopnoeas, the decrease in TOI precedes the peripheral, systemic desaturation. The decrease in TOI has been shown to be greater during apnoeas as compared to hypopnoeas, during rapid-eye movement sleep as compared to other sleep stages, in younger children as compared to their older counterparts, and in those with a high apnoea–hypopnoea index as compared with a low apnoea–hypopnoea index. Studies analyzing the association between repetitive changes in TOI and neurocognitive and behavioral dysfunction may help to decipher the pathophysiology of neurocognitive dysfunction associated with SDB in children.     

Management of apnoea and bradycardia in the newborn

Apnoea and associated bradycardia are common in preterm newborn infants. Apnoea of prematurity is a developmental disorder, which requires careful evaluation to exclude other pathological causes contributing to the apnoeas. The long-term effects of apnoea and bradycardia are unclear, but may be associated with long-term neurodevelopmental problems. Severe apnoeas may need resuscitation, mechanical ventilation or CPAP. Caffeine is currently the drug of choice for treatment of apnoea of prematurity. The effects of may other interventions, including stimulation, Kangaroo care, RBC transfusion, etc need further evaluation. Further research into the pathophysiological mechanisms underlying apnoeas, neurodevelopmental effects and long-term follow up of affected infants will help in optimizing management strategies for apnoea of prematurity.     

Model of normal prepubertal growth

Overheating may cause terminal apnoea and cot death. Rectal temperature and breathing patterns were examined in normal infants at home during the first 6 months of life. Twenty one infants had continuous overnight rectal temperature and breathing recordings for 429 nights (mean 20.4 nights, range 7-30) spaced over the first six months of life. Periods when breathing was 'regular' were directly marked on single night records. Sleep state was determined from respiratory variables. 'Regular' breathing was a reliable marker of 'quiet' sleep (specificity 93%). The duration of 'quiet' sleep increased from 6 to 22 minutes from two weeks to three months of age and then remained static, as did the proportion of sleep spent in the quiet phase (9% to 34%). Rectal temperature fell during 66% of quiet sleep and usually rose during rapid eye movement (REM) sleep. The drop in rectal temperature was maximal at the start of quiet sleep, whereas the maximum rise during REM sleep was reached after 10 to 15 minutes. Oscillations in rectal temperature are associated with changes in sleep and breathing state. The maturation of rectal temperature patterns during the first six months of life are closely related to a maturation of sleep state and breathing patterns.     

Effects of bottle feeding and two different methods of gavage feeding on oxygenation and breathing patterns in preterm infants

Objective To determine the effect of bottle feeding, as compared to two methods of gavage feeding, on apnoea, bradycardia and oxygen desaturation frequency. Patients : Thirty preterm infants breathing room air; gestational age 28.6 ± 2.1 weeks at birth and 34 ± 1.4 weeks at study (mean ± SD). Methods : Nine-hour recordings of pulse oximeter saturation (SpO₂), pulse waveforms, electrocardiogram, breathing movements and nasal airflow. Administration of 21 ± 1.5 ml/kg of milk/feed in 3-h intervals using three different feeding techniques in random order: bottle feeding, bolus gavage feeding, and slow gavage feeding (1 h). Analysis of recordings for apnoeas (≥4 s, bradycardias (heart rate < 2/3 of baseline), and episodic desaturation (SpO₂≤ 80%). Results : There were three times more desaturations with bottle feeding than with bolus gavage feeding ( p < 0.001), but no further reduction with slow gavage feeding. With all three feeding techniques, there were significantly more desaturations in the hour when the feeds were given than during the following 2 h. The deleterious effects of bottle feeding were most evident during the hour of feeding, but desaturation frequency remained significantly higher than with gavage feeding during the following 2h. There was no significant effect of feeding technique on the frequency of apnoea or bradycardia. Conclusions : Preterm infants who are normally oxygenated in room air may have significant desaturation during bottle feeding. Such desaturation can be effectively reduced by gavage feeding. Slow gavage feeding offers no advantage over bolus gavage feeding with respect to the avoidance of hypoxaemia.     

Characteristics of respiratory syncytial virus-related apnoea in three infants

Apnoea is a common sign in respiratory syncytial virus (RSV) infections in young infants and can be the first presentation of an acquired RSV infection. We describe polysomnographic recordings of three infants revealing prolonged RSV-related apnoea before RSV infection was diagnosed. The apnoeas were of central origin. The caregivers had not noted any apparent life-threatening events (ALTE) prior to the polysomnography. Cardiorespiratory monitoring after the acute infection did not reveal any further apnoeas.
Conclusion : Central, prolonged apnoea can be the first sign of an acquired RSV infection in young infants in the absence of other respiratory symptoms and without any previous observation of apnoea by the caregivers.     

Sleep apnoea in babies born after in vitro fertilization

Babies born after in vitro fertilisation (IVF) are increasing in number, and, although these babies are considered as very precious, no data are available regarding their risk for sudden infant death or apnoea. To evaluate the respiratory maturity of IVF babies, we evaluated the incidence of apnoea during an 8-h polysomnography in 50 consecutively presented IVF babies and in a group of 50 unselected naturally conceived babies. All infants were in good health and matched for term (born >38 weeks of gestation), birth weight, sex and age at the time of investigation (6–11 weeks post term, median 8.0). There were 24 twins in the IVF and 6 twins in the control group. The incidence of obstructive and isolated central apnoea was comparable in the IVF and control group. However, IVF babies had significantly more periodic breathing episodes than control babies (median 2.30 (range 0–15.30) in IVF, and 1.02 (range 0–11.2) in control babies;P<0.01). This difference was not related to the higher number of twins in the IVF group. Single IVF babies had significantly more short central apnoeas (5–10s) than IVF twins (5–10s) (mean 38.80±18.63 and 22.33±13.35;P<0.001). This difference between single and twin babies was not found in the control group.Conclusion IVF babies have more periodic breathing episodes indicating an immature respiratory pattern than normally conceived babies.     

Central apnoeas in infants with bronchiolitis admitted to the paediatric intensive care unit

Aim: To further characterize apnoea(s) complicating bronchiolitis because of respiratory syncytial virus (RSV), to describe the incidence of this complication and identify possible risk factors for apnoea(s) and its development. Methods: The files of infants admitted to the paediatric intensive care unit (PICU) for RSV bronchiolitis during three bronchiolitis seasons (2004–2007) were reviewed for demographic, clinical and laboratory parameters. Parameters were compared between patients with and without apnoeas. Results: Seventy‐nine patients met the study criteria: 43 were admitted to the PICU for central apnoeas and the remainder for respiratory distress or failure. The percentage of infants admitted for apnoea increased during the study period (28.6 to 77.1%, p = 0.004). The overall prevalence of apnoea in this population was 4.3%. Possible risk factors for apnoea(s) were younger age (1.3 vs. 4.3 months, p = 0.002), lower admission weight (3.3 vs. 5 kg, p < 0.001), lower gestational age (35.8 vs. 37.8 weeks, p = 0.01), admission from the emergency room (50% vs. 9.1%, p < 0.001) and lack of hyperthermia (p < 0.001). Respiratory acidosis was found to be a protective factor on logistic regression analysis. Conclusion: The prevalence of apnoea in infants admitted to the PICU for RSV bronchiolitis in our centre may be increasing. Preterm, younger infants with no fever are at relatively high risk of apnoea at presentation, while older infants with fever are at lower risk.     

The diagnosis of sleep apnea--possibility for the prevention of SID?

Groups of children with a statistically enhanced risk for SIDS: siblings of SIDS-victims and other full-term and preterm infants with anamnestic signs for an enhanced risk of SIDS and a control group of healthy infants without anamnestic signs of risk were polysomnographically investigated in the first year of life. The mean apnoea duration (MA-value estimated by frequency and length of apnoeas greater than or equal to 3s) in the sleep states active and quiet sleep was calculated. During active sleep there is a significant inverse correlation between MA and postnatal age in the full-term and preterm SIDS-risk infants but not in the controls and siblings of SIDS-victims. In all age groups there are some children in the full-term and preterm infants with extremely enhanced MA-values. For 6 age groups of the first year of life the 90% percentile of the MA-value was calculated separately in the sleep states active and quiet sleep to select infants with an abnormal breathing pattern. This limit could be a help for the decision on therapy.     

Breathing,sleep state,and rectal temperature oscillations.

Overheating may cause terminal apnoea and cot death. Rectal temperature and breathing patterns were examined in normal infants at home during the first 6 months of life. Twenty one infants had continuous overnight rectal temperature and breathing recordings for 429 nights (mean 20.4 nights, range 7-30) spaced over the first six months of life. Periods when breathing was ''regular'' were directly marked on single night records. Sleep state was determined from respiratory variables. ''Regular'' breathing was a reliable marker of ''quiet'' sleep (specificity 93%). The duration of ''quiet'' sleep increased from 6 to 22 minutes from two weeks to three months of age and then remained static, as did the proportion of sleep spent in the quiet phase (9% to 34%). Rectal temperature fell during 66% of quiet sleep and usually rose during rapid eye movement (REM) sleep. The drop in rectal temperature was maximal at the start of quiet sleep, whereas the maximum rise during REM sleep was reached after 10 to 15 minutes. Oscillations in rectal temperature are associated with changes in sleep and breathing state. The maturation of rectal temperature patterns during the first six months of life are closely related to a maturation of sleep state and breathing patterns.