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.     

Cardiac contraction affects respiratory airflow in the term newborn infant

In studies in the newborn infant, it is often assumed that there are similarities in airflow in successive breaths, and, therefore, it is only necessary to measure parameters in a small number of breaths. However, other studies have shown considerable variability in breathing patterns in successive breaths. It was, therefore, decided to examine the variability in the patterns of airflow. By use of the trunk plethysmograph, tidal breathing was measured in 20 term newborn infants during quiet sleep in the first week after delivery; airflow was calculated by differentiating the tidal volume signal. The ECG was also recorded. In all infants, it was found that the shapes of both inspiratory and expiratory airflow showed considerable differences in successive breaths. Spectral analysis of airflow showed the presence of peaks not only in the respiratory rate, as expected, but also in the heart rate. In another five infants studied during episodes of periodic breathing, small fluctuations in airflow were found during the apneic intervals at the same rate as the heart rate. It was concluded that this is not an artifact, but that cardiac contraction modulates respiratory airflow in the term newborn infant, contributing significantly to breath-to-breath variability. These cardiac related changes in airflow amount to approximately one sixth of the tidal airflow.     

Respiratory modulation of heart rate in newborn infants

Spectral analysis was performed on ventilation and instantaneous heart rate data recorded in 15 term infants during quiet sleep in the first week after delivery, and in 11 of these infants during active sleep. There was a close relation between the main peaks of the ventilation spectra and the corresponding histograms of the reciprocals of Ttot. The spectra for instantaneous heart rate showed power at the rate of breathing (HF) and also at lower frequencies, 0.04-0.2 Hz (LF). During quiet sleep, the relative magnitudes of the HF and LF peaks for heart rate were found to depend on the respiratory rate and the variability of Ttot. During active sleep, most of the power in the heart rate spectrum was concentrated in the LF region. Weighted coherences between ventilation and heart rate were higher during quiet than active sleep, both in the HF and LF spectra. LF power was higher during active than quiet sleep in both ventilation and heart rate. The results suggest that the pattern of breathing has a marked effect on the shape of the heart rate spectrum. In most infants, however, there is no fixed phase relationship between oscillations in ventilation and heart rate, at high or low frequencies. These oscillations are affected by sleep state and hence, by implication, by central nervous system rhythm generators.     

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.     

Behaviour and physiological responses during prone and supine sleep in early infancy

AIMS: To study the effect of prone and supine sleep on infant behaviour, peripheral skin temperature, and cardiorespiratory parameters to aid understanding of why prone sleeping is associated with an increased risk of sudden infant death syndrome. METHODS: Of 33 enrolled infants, 32 were studied at 2.5 and 28 at 5 months of age. A computer aided multichannel system was used for polysomnographic recordings. Behaviour was charted separately. RESULTS: Prone REM (active) sleep was associated with lower frequencies of short arousals, body movements and sighs, and a shorter duration of apnoeas than supine REM sleep at both ages. At 2.5 months there were less frequent episodes of periodic breathing during prone sleep in non-REM (quiet) and REM sleep. Heart rate and peripheral skin temperature were higher in the prone position during both sleep states at both ages. CONCLUSIONS: The observation of decreased variation in behaviour and respiratory pattern, increased heart rate, and increased peripheral skin temperature during prone compared with supine sleep may indicate that young infants are less able to maintain adequate respiratory and metabolic homoeostasis during prone sleep.     

The prone sleeping position impairs arousability in term infants

OBJECTIVE: To investigate whether the prone sleeping position impaired arousal from sleep in healthy infants and whether this impairment was related to cardiorespiratory variables, temperature, or age.Study design: Healthy term infants (n = 24) were studied with daytime polysomnography on 3 occasions: 2 to 3 weeks after birth, 2 to 3 months after birth, and 5 to 6 months after birth. Multiple measurements of arousal threshold (cm H(2)O) in response to air-jet stimulation applied alternately to the nares were made in both active sleep and quiet sleep when infants slept both prone and supine. RESULTS: Arousal thresholds were significantly higher in both active sleep and quiet sleep when infants slept prone at 2 to 3 weeks and 2 to 3 months, but not at 5 to 6 months. These increases were independent of any sleep position-related change in either rectal or abdominal skin temperature, respiratory rate, oxygen saturation, or heart rate. CONCLUSIONS: The prone position significantly impairs arousal from both active sleep and quiet sleep in healthy term infants. This impairment in arousability occurred with no clinically significant changes in cardiorespiratory variables or body temperature. Decreased arousability from sleep in the prone position provides an important insight into its role as a risk factor for sudden infant death syndrome.     

Sleep apnoea in acute bronchiolitis.

Three- to 4-hour polygraphic sleep studies were carried out in 16 infants aged between 1 and 6 months during and after recovery from acute bronchiolitis. During bronchiolitis 35% of total sleep time was active sleep compared with 31% after recovery. Respiration rate was increased during bronchiolitis and was higher in active sleep and quiet sleep irrespective of the stage of the illness. Apnoeic pauses were invariably shorter than 15 seconds, the mean duration for active sleep and quiet sleep being similar during infection and after recovery. Apnoeic episodes were central in type and generally initiated by a sign or body movements. Preapnoea heart rate was significantly higher than during or after apnoea. Apnoea index (the percentage of time the baby spends apnoeic), apnoea attack rate (the number of episodes of apnoea per unit time), and apnoea percentage (the distribution of episodes of apnoea while in a given sleep state) were increased significantly in quiet sleep during the index illness. Transcutaneous oxygen tension was significantly reduced during the course of infection, but comparable values were obtained in active sleep and quiet sleep during initial and recovery periods. These results show that the main changes in respiration pattern during the course of acute bronchiolitis occur in quiet sleep.     

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.     

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.     

Polygraphic studies of normal infants during the first six months of life. I. Heart rate and variability as a function of state.

This study examined spontaneous heart rate (HR) and variability as a function of age and sleep state in eight normal full term infants from birth to 6 months of age. Heart rates recorded during sleep were lower and less regular at 1 week (quiet sleep (QS) mean rate= 128, interquartile range = 6.4 beats/min; rapid eye movement (REM) = 134.5, 11.6) than at 1 month (QS = 138.6, 3.4; REM 139.6, 4.2). Rate decreased sharply from 1 to 3 months (QS = 118; REM 123.8) and decreased only slightly therafter (6-month QS = 113.5; REM 118.9). Variability decreased rapidly in REM from 2 to 4 months (from 11.4 to 9.1) and less quickly from 4 to 6 months (from 9.1 to 8.2), while QS variability decreased at 1 month (from 6.4 to 5.7) and became stable from that point (6.0 at 6 months). Waking heart rate and variability were both relatively low at 1 week (163, 11.2 beats/min) and increased from that age to 1 month (167.4, 14.3). Rate decreased rapidly in waking at 3 months (152 beats/min) and more slowly therafter (152 beats/min at 4 months, 149 beats/min at 6 months), whereas variability remained elevated until after 3 months, becoming stable at a lower level during later infancy (3 months = 14.8,6 months 11.7). Lowest values of rate and variability were found in QS and the highest values were found in waking at all ages, except at 1 week. Heart rates during REM closely approximated those in QS, whereas variability values more closely resembled those of waking.     

Behaviour and physiological responses during prone and supine sleep in early infancy

Accepted 23 December 1996
AIMS—To study the effect of prone and supine sleep on infant behaviour, peripheral skin temperature, and cardiorespiratory parameters to aid understanding of why prone sleeping is associated with an increased risk of sudden infant death syndrome.
METHODS—Of 33 enrolled infants, 32 were studied at 2.5 and 28 at 5 months of age. A computer aided multichannel system was used for polysomnographic recordings. Behaviour was charted separately.
RESULTS—Prone REM (active) sleep was associated with lower frequencies of short arousals, body movements and sighs, and a shorter duration of apnoeas than supine REM sleep at both ages. At 2.5months there were less frequent episodes of periodic breathing during prone sleep in non-REM (quiet) and REM sleep. Heart rate and peripheral skin temperature were higher in the prone position during both sleep states at both ages.
CONCLUSIONS—The observation of decreased variation in behaviour and respiratory pattern, increased heart rate, and increased peripheral skin temperature during prone compared with supine sleep may indicate that young infants are less able to maintain adequate respiratory and metabolic homoeostasis during prone sleep.

     

Neonatal pattern of breathing during active and quiet sleep after maternal administration of meperidine.

The aim of this study was to reappraise the effects of maternal meperidine administration on breathing pattern during the first hours of life taking into account the state of alertness. Because breathing instability is more pronounced during active sleep, we hypothesized that meperidine administration might create a greater risk for respiratory instability during active sleep, the prominent sleep state in newborns. We studied eight full-term, healthy newborns whose mothers had received a continuous i.v. infusion of meperidine (81 +/- 9 mg) that was terminated 5.5 +/- 2.1 h before delivery. These infants were compared with a control group of eight full-term newborns whose mothers did not receive any opioids. In both groups, all babies were delivered vaginally after a normal labor and had Apgar scores of 9 or 10 at 1 and 5 min. Neonatal gastric secretion and maternal venous and umbilical venous blood were sampled at delivery for determination of meperidine concentration. From 60 to 300 min after delivery, behavioral sleep states and thoracic and abdominal movement as well as transcutaneous arterial oxygen saturation (SaO2) were monitored continuously. The number of apneic spells lasting more than 3 s during 100 min of recording and the percentage of time with SaO2 below 90% in each sleep state were recorded. During quiet sleep, all respiratory variables were similar in both groups. During active sleep, there were significantly more apneic episodes (37.1 +/- 25.1 versus 11.2 +/- 13.9) and a higher percentage of time with SaO2 less than 90% (14.3 +/- 16.7% versus 1.3 +/- 1.5%) in the meperidine group than in the control group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Sleep state, hypoxia and periodic breathing in the neonate

The influence of sleep state on hypoxia-induced periodic breathing was evaluated in full-term babies studied during the first week of life. Following exposure to 15% O2, periodic breathing occurred in 7 of 42 babies during quiet sleep, and 5 of 20 during active sleep (p less than 0.05). The median levels of transcutaneous pO2 at which periodic breathing occurred during hypoxia, and was abolished on reoxygenation were similar in each sleep state. The median duration of periodic apnoea was significantly greater in quiet than active sleep. In 7 babies the occurrence of periodic breathing during hypoxia was accompanied by a change in sleep state. This was probably coincidental in 3 cases, but in the other 4 babies hypoxia may have induced both the change in state and breathing pattern.     

Heart rate and respiratory rate differences between preterm and full-term infants during quiet sleep: possible implications for sudden infant death syndrome

The heart rate and respiratory rate of eight preterm (average gestational age, 33.3 +/- 2.2 weeks) and 13 full-term infants were determined during quiet sleep at home during the first year of life. Both heart rate and respiratory rate were greater in preterm infants throughout the first six months. The difference was maximum at age 10 weeks (21.2 beats per minute and 13.7 breaths per minute), with the difference being statistically significant, at least at the P less than .01 level at ages 10, 12 and 14 weeks, while P greater than or equal to .01 at all other ages. The 10- to 14-week period is precisely the same period during which the incidence of sudden infant death syndrome (SIDS) has been reported to be maximum. These results support the concept that SIDS is linked to a vulnerable phase of cardiorespiratory maturation.     

Sleep State, Hypoxia and Periodic Breathing in the Neonate

ABSTRACT. The influence of sleep state on hypoxia-induced periodic breathing was evaluated in full-term babies studied during the first week of life. Following exposure to 15% O₂, periodic breathing occurred in 7 of 42 babies during quiet sleep, and 5 of 20 during active sleep ( p < 0.05). The median levels of transcutaneous pO₂ at which periodic breathing occurred during hypoxia, and was abolished on reoxygenation were similar in each sleep state. The median duration of periodic apnoea was significantly greater in quiet than active sleep. In 7 babies the occurrence of periodic breathing during hypoxia was accompanied by a change in sleep state. This was probably coincidental in 3 cases, but in the other 4 babies hypoxia may have induced both the change in state and breathing pattern.     

Respiration during the first six months of life in normal infants: IV. Gender differences

Respiratory rates and breathing pauses of various durations were examined in 19 normal infants, 12 male and 7 female, during the first 6 months of life. Twelve-hour all-night polygraphic recordings were obtained during the first week of life and at 1, 2, 3, 4 and 6 months. A computer program and visual analysis were used to score sleep state and calculate respiratory rates and apnea densities. In the newborn period there were no gender differences. Males breathed faster and exhibited fewer breathing pauses between 2 and 5 sec from one month of age on. The close correlation between respiratory rate and short breathing pauses suggests that the latter are an integral part of normal respiratory regulation. These findings can be explained by gender-related differences in metabolic rate or maturation of the central nervous system.     

Breathing patterns and heart rates at ages 6 weeks and 2 years.

Forty-two randomly selected, full-term, healthy infants underwent 24-hour electrocardiographic recordings and breathing movements at about ages 6 weeks (median age, 43 days; range, 34 to 61 days) and 2 years (median age, 26 months; range, 21 to 35 months). The number and duration of apneic pauses of 3.6 seconds or longer were analyzed. Periodic apnea was defined as a sequence of three or more apneic pauses, each separated by fewer than 20 breaths. All other apneic pauses were defined as isolated. Median heart rates and respiratory rates, which were measured during regular breathing, decreased from 137/min and 35/min to 98/min and 21/min, respectively. The total duration of periodic apnea remained unchanged (median, 0.06 min/h vs 0.05 min/h). Although the median frequency of all isolated apneic pauses decreased from 3.6/h to 2.5/h, the number of those that were longer than 6 seconds increased from 0.37/h to 0.80/h, leading to an increase in the proportion of these pauses, among all isolated apneic pauses, from 10% at age 6 weeks to 32% at age 2 years. Only one apneic pause in one infant at age 6 weeks, but eight pauses in six children at age 2 years, were longer than 15 seconds. A knowledge of such normal variability in the duration of apneic pauses in older infants and young children is essential for the interpretation of pneumograms and alarms while monitoring breathing movements.     

Fighting the ventilator--are fast rates an effective alternative to paralysis?

We investigated the effect of increased ventilator rates on the respiratory activity of 17 infants, all actively expiring against the ventilator at conventional rates. Fast rate ventilation was rarely associated with apnoea (3 babies only) and the infant's respiratory efforts even at rates of 120/min had an important effect on tidal exchange. Seven infants altered their respiratory response to breathe in synchrony with the ventilator at 60 breaths/min and 5 maintained this at 120 breaths/min. Nine of the 17 infants continued to actively expire against positive pressure inflation at 60 breaths/min and in two this persisted at 120/min, the remaining 7 infants showed incoordinated breathing at that rate. We conclude that fast rate ventilation appears to have only limited success in suppressing respiratory activity in infants actively expiring against the ventilator.     

Thoracico-abdominal respiratory correlations in infants: constancy and variability in different sleep states.

28 polygraphic recordings were made in normal infants: 20 in full-term newborns and 8 in 2- to 10-wk-old babies. Data were analysed by 20-sec epochs. Relationships between thoracic (3rd-4th rib level) and abdominal respiratory movements were studied according to their maximum out-of-phase occurring (180 degrees maximum) in every 20-sec period. The thoracico-abdominal phase relationships according to sleep states do not change during the first trimester of life. In quiet sleep, while in-pase thoracico-abdominal respiration was the most frequent pattern, the out-of-phase one was also a possible pattern. In active sleep, out-of-phase respiration is characteristic, in-phase relation being a rare exception. In transitional sleep, respiratory relationships could be those appropriate for the preceding or the following sleep state. Nasal air flow always occurred in the phase with abdominal movements. Total flatteninf of thoracicorespiratory movements only were found in all sleep states; these thoracic flattenings must be differentiated from apnea. Transient fluctuations in the degree of phase relations are possible. There exists both interand intraindividual variability in normal infants. Variability of fusimotor system tonus is probably the neurological mechanism underling these phenomena.     

Oesophageal motor activity and sleep state in the newborn human infant

Oesophageal pressure and ventilation were recorded during sleep in healthy full-term neonates with sleep state defined by one of two methods; in 35 infants by combined behavioural and electroencephalographic criteria, and in a further 13 infants by behavioural criteria alone. Spontaneous oesophageal contractions occurred in all infants during active sleep but rarely during quiet sleep. The transition from active to quiet sleep was accompanied by a gradual reduction in the frequency of these contractions. Oesophageal contractions associated with sighs and contractions shortly following interruption of breathing suggestive of swallowing were also significantly more common in active sleep. In 13 infants who showed periodic breathing the same differences in prevalence of spontaneous oesophageal contractions in each sleep state were observed.