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.     

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.     

The sleep state characteristics of apnea during infancy.

The sleep state characteristics of infant sleep apnea were studied in 36 twins examined by polygraphy at 40, 44, and 52 weeks after conception. The definition of sleep apnea is dependent upon the length of apnea, sleep state, and post-conceptional age. None of the infants had apnea longer than 20 seconds and apnea of 10 seconds or longer was uncommon. The attack rates for apneas 2 to 4.9 seconds long were highest in REM and lowest in qliet sleep. The attack rates for apneas 5 to 9.9 seconds long were equal in REM and indeterminate and lowest in quiet sleep. The percentage of infants with apnea of 10 seconds or longer at 40 weeks was highest in REM (27%) and indeterminate sleep (42%) and lowest in quiet sleep (12%). At 52 weeks, apnea 10 seconds or longer during REM decreased to 0%. The effect of maturation on apnea varies with sleep state. Over the period from 40 to 52 weeks, quiet sleep apnea was unchanged and indeterminate sleep apnea decreased only between 40 and 44 weeks. Although REM apnea 2 to 4.9 seconds long was unchanged, REM apnea 5 to 9.9 seconds long decreased between 40 and 44 weeks, and REM apnea of 10 seconds or longer decreased from 27% at 40 weeks to 0% at 52 weeks. This suggests that semi-independent apnea turn-on and turn-off mechanism operate during REM sleep. A correlation between brief apneas and the longer apneas was seen only during REM sleep. For all sleep states, there was no correlation between the levels of apnea of 5 seconds or longer at 40, 44, and 52 weeks.     

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.     

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.

     

Determination of sleep state in infants using respiratory variability

Sleep staging has been conventionally performed using neurophysiologic and behavioral criteria. However, these criteria may not always be available. Since it is known that cardiorespiratory variables in rapid eye movement (REM) sleep are different from those in quiet sleep, we asked whether such variables can be used for the determination of sleep state. We studied nine normal full-term infants at 1 and 4 months of life. Ventilation was measured using barometric plethysmography and the RR interval using a high accuracy R wave detector. Electroencephalogram, electrooculogram, and postural muscle electromyogram were recorded using surface electrodes and behavioral criteria applied. Means of RR interval, respiratory cycle time and tidal volume, and coefficients of variation of the same variables, were obtained for 30-s intervals throughout each sleep study. The Kolmogorov-Smirnov distances between REM and quiet sleep were larger for the coefficients of variation than for the means at both ages for all variables. Moreover, coefficient of variation of respiratory cycle time was found to provide the largest separation between REM and quiet sleep. In view of this result, we developed a statistical decision rule using coefficient of variation of respiratory cycle time for the classification of REM and quiet sleep in blocks of 5-min periods. Each study was divided into 5-min epochs and this rule was applied to each epoch. Of 85 epochs staged as quiet sleep by neurophysiologic and behavioral criteria, 79 epochs (or 93%) were classified correctly as quiet sleep using our decision rule. Of 85 epochs staged as REM sleep, 84 were classified as REM sleep and only one misclassified as quiet sleep.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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.     

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.     

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

ABSTRACT. Four term healthy infants had their respiratory pattern monitored during a 2-hour afternoon nap recording period at monthly intervals up to six months of age. The time spent asleep significantly decreased with a marked reduction in active sleep (66% to 10%) while maintaining one long epoch of quiet sleep (mean 31 mins). Mean breathing rate at one week was higher in active sleep than quiet sleep (47 vs 41 breaths/min.) and decreased by 6 months in both sleep states (31 breaths/min. in both). Variability of breathing rate at 1 week was significantly increased in active sleep compared to quiet sleep and both decreased by 6 months. These findings confirm a significant maturational change in the respiratory pattern and variability of normal infants in the afternoon nap from 1 to 6 months.     

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.     

Oral breathing in newborn infants

Newborn infants are considered obligate nasal breathers, hence dependent on a patent nasal airway for ventilation. The conditions under which oral breathing could occur and the contribution of oral ventilation to total ventilation were studied in 30 healthy term infants (aged 1 to 3 days). Nasal and oral airflow were measured using two resistance-matched pneumotachometers, and heart rate, tcPO2, etCO2, and sleep state were continuously recorded. In three of 10 infants studied in undisturbed sleep, spontaneous oronasal breathing was noted during both active and quiet sleep (mean duration 19 +/- 25 minutes), the distribution of tidal volume being 70% +/- 12% nasal and 30% +/- 12% oral. Episodes of oronasal breathing were also observed after crying in six infants (mean duration 21 +/- 19 seconds). In an additional 20 infants, multiple 15-second end-expiratory nasal occlusions were performed; eight (40%) of these infants initiated and sustained oral breathing in response to nasal occlusion. Respiratory rate, tidal volume, heart rate, and tcPO2 did not change when oral breathing occurred in response to nasal occlusion, although minute ventilation decreased from 265 to 199 ml/min/kg (P less than 0.05). These results demonstrate that newborn infants may use the oral airway for ventilation, both spontaneously and in response to complete nasal occlusion.     

Overnight central and peripheral temperature changes in normal infants

Aim: To explore the relationship between central and peripheral temperature in normal infants after being put down to sleep. Methods: Overnight shin and rectal temperatures of 21 normal infants were continuously recorded at home for three nights at 2 wk, 6 wk, 3 mo and 5 mo of age. Parents documented the start and end of feed/nappy changes during the night. Results: An initial fall in rectal temperature was recorded on 149 out of 161 nights. This was linearly correlated with a rise in shin temperature for 106/149 (71%) nights (median R[Formula: See Text] = 0.95, lower quartile 0.92, upper quartile 0.97). It was not possible to rule out a change in thermal insulation over the shins as a confounding variable in this strong association. However, a similar inverse relationship was seen between shin and rectal temperature during 111 of 121 (92%) feed/nappy changes.

Conclusion: The fall in rectal temperature after being put down to sleep may be due to redistribution of heat rather than decreased production or heat loss. If causal, the development in early infancy of an inverse relationship between shin and rectal temperature may be important for cardiovascular homeostasis. Further sleep laboratory work is required to distinguish peripheral temperature changes on falling asleep from those associated with changes in thermal insulation.     

Spontaneous awakenings from sleep in the first year of life.

Spontaneous awakenings from nocturnal sleep were studied in a sample of 48 healthy infants (M = 26, F = 22), in four age groups (1 to 7 weeks, 8 to 15 weeks, 17 to 22 weeks, 25 to 54 weeks). Consistent with previous data, the number of awakenings is reported less frequently at later ages, owing to a lower frequency of awakenings out of REM sleep. Like young adults, infants in all age groups awake more often from REM than from quiet sleep (QS); this is particularly evident in the first 6 months of life, less so in the second. The duration of the bouts of wakefulness following awakenings remains stable with age. Awakenings out of QS are followed by longer periods of wakefulness than those out of REM sleep, although in older infants the duration is considerably reduced. Night sleep first shows a decrease in the number of awakenings out of REM sleep and then continues after the sixth month of life with the shortening of the wakefulness after awakenings out of QS. In the two younger groups, the distribution of the awakenings shows two main peaks and one main peak differently located during the night; a polymodal pattern appears in group 3, and is even more evident in group 4. It should be stressed that several changes as a function of age occur in the second 6 months of life, indicating this as a period of intense developmental change in sleep-wake rhythms.     

Effect of sleep state on the QT interval in normal infants.

Twenty QT intervals selected at random from the middle periods of rapid eye movement (REM) and quiet sleep were measured in 12 normal infants studied at 2 weeks and 1, 2, 3, and 4 months of life. A digitizing system, consisting of a precision rotational potentiometer mounted on a pair of calipers and an A/D converter, was used for measurements. An accuracy of +/- 2 msec was achieved by high resolution of the digitized signal and calibration of each QT measurement with an accurately generated time code. Sleep staging was done visually using an electroencephalogram (EEG), an electrooculogram (EOG), a submental electromyogram (EMG), and behavioral criteria. Our results show that the QT index (QTc = QT/square rootRR) was significantly greater during quiet sleep (mean = 0.439) than during REM sleep (mean = 0.433) (P less than 0.01) and that this difference existed at all ages studied.     

The relationship between environmental temperature, metabolic rate, sleep state, and evaporative water loss in infants from birth to three months.

We have investigated the effect of changing environmental temperature on metabolic rate, sleep state, and water loss in a longitudinal study of 22 lightly clothed babies from 2 d to 3 mo of age. Studies were performed in a modified barometric plethysmograph while recording sleep state, oxygen consumption, and skin and axillary temperatures. Oxygen consumption was higher in rapid eye movement sleep than in quiet sleep at all ages and varied widely between infants at each temperature. Within the first week, there was a 19% rise in oxygen consumption on cooling to 19-22 degrees C during rapid eye movement sleep and a 6% rise during quiet sleep. The median duration of quiet sleep periods was reduced from 17 to 12 min on cooling within the first week. No such change was seen at 1, 2, and 3 mo. Axillary temperature was reduced at 3 mo during cooling. This may be a part of normal patterns of change in temperature during sleep, unrelated to cooling. At each age, total evaporative water loss fell linearly with falling environmental temperature both within and below the temperature range at which metabolic rate was minimal. The evaporative water losses were greater than expected and suggested that sweating was occurring, both at temperatures at which metabolic rate was minimal and at those at which it was increased. The metabolic response to cooling and the process of sweating appear to be in dynamic equilibrium across this temperature range. Thus, it was not possible to define a temperature range over which both metabolic rate and evaporative water loss were at minimum values.     

Maturation of cardiac control in full-term and preterm infants during sleep

ECG and respiration were recorded from 13 full-term and 8 preterm infants at 2–5-week intervals during sleep at home in the first year of life. Average pulse interval in both quiet and active sleep was minimum at postnatal ages between 4 and 10 weeks, with the minimum during quiet sleep being significantly smaller for preterm (409 ±22 (SE) msec) than for full-term (445 ±9 msec) infants. The minimum average pulse interval of preterm infants was smaller than the pulse interval of full-term infants at any postconceptional age, and a smaller average pulse interval and smaller variations in pulse interval in preterm infants during quiet sleep persisted until a postnatal age of 7 months. The pulse interval variations attributable to respiration varied substantially with age. The results indicate that developmental changes in cardiac rate control are functions of both postnatal and postconceptional age, with the post-conceptional age at birth setting the mean level of pulse interval, a level which is then altered by development linked to postnatal age.     

The QT interval in aborted sudden infant death syndrome infants.

The QT interval was measured in 12 normal and 7 aborted sudden infant death syndrome (SIDS) infants in rapid eye movement (REM) and quiet sleep at monthly intervals through the age of 4 months. An accuracy of better than 2 msec was assured by high resolution of the digitized signal and calibration of each QT measurement with an accurately generated time code. In contrast to current speculations, the QT index was significantly smaller in the infants with aborted SIDS than in the normal infants in both REM and quiet sleep (P less than 0.05). In addition, as in normal infants, the QTc was smaller in REM than in quiet sleep (P less than 0.01). Although these results offer no support for the hypothesis that SIDS results from prolongation of the QT interval, they suggest that aborted SIDS infants have a functional abnormality in the autonomic nervous system.     

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.