Dew-point hygrometry system for measurement of evaporative water loss in infants.

Evaporation of water from the skin is an important mechanism in thermal homeostasis. Resistance hygrometry, in which the water vapor pressure gradient above the skin surface is calculated, has been the measurement method of choice in the majority of pediatric investigations. However, resistance hygrometry is influenced by changes in ambient conditions such as relative humidity, surface temperature, and convection currents. We have developed a ventilated capsule method that minimized these potential sources of measurement error and that allowed second-by-second, long-term, continuous measurements of evaporative water loss in sleeping infants. Air with a controlled reference humidity (dew-point temperature = 0 degree C) is delivered to a small, lightweight skin capsule and mixed with the vapor on the surface of the skin. The dew point of the resulting mixture is measured by using a chilled mirror dew-point hygrometer. The system indicates leaks, is mobile, and is accurate within 2%, as determined by gravimetric calibration. Examples from a recording of a 13-wk-old full-term infant obtained by using the system give evaporative water loss rates of approximately 0.02 mgH2O.cm-2.min-1 for normothermic baseline conditions and values up to 0.4 mgH2O.cm-2. min-1 when the subject was being warmed. The system is effective for clinical investigations that require dynamic measurements of water loss.

Sleep state effects on nonpanting breathing during preoptic/anterior hypothalamic warming in cats and kittens.

Hypothalamic warming induces panting in cats; in young kittens, panting is interspersed with slower breathing periods. The nature of neural mechanisms underlying these interspersed periods of nonpanting polypnea is unclear. We determined developmental characteristics of nonpanting breathing during thermal stress in kittens and adult cats. Warming electrodes were surgically placed into the preoptic/anterior hypothalamus (POAH) of 19 kittens and six adult cats. After surgical recovery, the hypothalamus was warmed bilaterally during sleep in unrestrained animals. Epochs of nonpanting breathing during periods of POAH warming within quiet sleep (QS) and rapid eye movement sleep (REM) were compared to control periods. Nonpanting polypnea within QS showed inspiratory and expiratory time reductions in the same proportions as those of panting. During REM, increased breathing rates accompanied POAH warming, but inspiratory/expiratory timing characteristics did not differ significantly from those of baseline breathing, except in the youngest kittens. Breathing responses to POAH warming during QS showed significant change as the kittens matured; however, response characteristics during REM did not change significantly from 12 days to adulthood. Responses to thermal stress during QS appear to depend on maturation of neural mechanisms, while separate mechanisms appear to underlie the slight respiratory rate changes during REM.

Respiratory responses to preoptic/anterior hypothalamic warming during sleep in kittens.

The preoptic/anterior hypothalamic (POAH) area of 12-48-day-old unanaesthetized, unrestrained kittens was warmed with a diathermic probe to assess respiratory responses to a central thermal challenge during sleep. During quiet sleep (QS), warming of the POAH by 1.4-3.8 degrees C induced periods of tachypnoea (panting) interspersed with periods of slower respiration; the percentage of time spent in panting increased as the kittens matured. During rapid eye movement (REM) sleep, POAH warming induced a much smaller increase in respiratory rate and no sustained panting. Analysis of the dynamics of panting (in QS only, since panting did not occur in REM) revealed several changes from breathing patterns of normal respiration. During panting, the increased respiratory rate did not result from equal changes in inspiratory and expiratory times; inspiratory times accounted for a larger portion of the decline in total respiratory cycle time. Amplitude of diaphragmatic electromyographic activity showed an age-dependent response to thermal panting, which resulted in age-dependent changes in ventilation and inspiratory drive. The interspersion of slower with faster respiratory rates suggests a competition of thermoregulatory and respiratory homeostatic mechanisms. The age-dependent ventilatory responses to thermal panting suggest greater vulnerability to thermal stress at particular ages, and may have implications for the sudden infant death syndrome.

Biological rhythmicity in preterm infants prior to discharge from neonatal intensive care.

OBJECTIVE: The study of biological rhythms and the influence of environmental factors in the timing and synchronization of different rhythmic events have important implications for neonatal health. Preterm infants in the neonatal intensive care unit (NICU) are deprived of the patterned influences of maternal sleep, temperature, heart rate, and hormonal cycles. The impact of the NICU and nursing interventions on the development of the circadian system was studied in 17 stable preterm infants in the Intermediate Intensive Care Nursery at Stanford University for three consecutive days at about 35 weeks postconceptional age. OUTCOME MEASUREMENTS: Rectal temperature, abdominal skin temperature, heart rate, and activity were simultaneously recorded at 2-minute intervals during each 3-day study by a small microcomputer (Vitalog). RESULTS: Very low amplitude circadian rhythms were found for rectal and skin temperatures (maximum range 36.8 to 37.0 degrees C); population mean values for heart rate (158 bpm) and activity (3.5 counts per 2-min bin) did not differ significantly as a function of time of day. Rectal temperature, averaged in 6-hour bins over the 24-hour day as a function of both postconceptional age and postnatal age, was significantly higher during the first part of the circadian cycle. In all infants, rhythmicity in each variable was dominated by ultradian periodicities that were coincident with feedings and related interventions; moreover, several physiological variables charted during feeding differed significantly from values obtained during periods in which caregiving interventions did not occur. CONCLUSION: Quantitative data on the preterm infant circadian system may facilitate evaluation of factors that improve therapeutic responses, recovery, and outcome of neonatal intensive care patients.

Dynamic respiratory responses to preoptic/anterior hypothalamic warming in the sleeping cat.

Timing and amplitude characteristics of diaphragmatic muscle activity following bilateral local warming of the preoptic area/anterior hypothalamic region (POAH) were studied during sleep in free-moving, intact adult cats. Warming of the POAH increased local brain temperature by 1.4-3.7 degrees C and elicited thermal tachypnea (panting) during quiet sleep (QS). Following transition to rapid eye movement (REM) sleep, the tachypnea, initially induced by warming during QS, diminished, but respiratory rates remained above baseline REM levels, and an intermittent pattern of faster and slower breathing rates developed. In QS, tachypnea resulted primarily from a decline in inspiratory time (TI), whereas in REM sleep, reduction in expiratory time (TE) was more prominent. Although diaphragmatic electromyographic amplitude decreased by 40% during panting in QS, the much higher respiratory rates (+350%) resulted in apparent increases in relative ventilation and inspiratory drive. A less pronounced respiratory rate change (+46%) emerged during REM sleep, resulting in no significant changes in ventilation and inspiratory drive in response to warming in that state. The results suggest that descending thermal influences on respiratory patterning differ between QS and REM states in both overall respiratory rate and on relative TI and TE, and thus do not affect inspiratory drive exclusively.

Biological rhythmicity in normal infants during the first 3 months of life.

OBJECTIVE: The mammalian "biological clock," which resides in the hypothalamic suprachiasmatic nucleus, has an important role in both the timing and organization of sleep and in the coordination of sleep with other physiological rhythms such as temperature regulation and respiratory control. We wished to describe the development of the circadian system in normal infants during the first 3 months of life. METHODS: Ten healthy full term infants were studied in the infant's home for three consecutive days at 1 month and 3 months postnatal age. Rectal temperature, abdominal skin temperature, heart rate, and activity were recorded at 2-minute intervals during each study using a small microcomputer. RESULTS: Circadian periodicity for most variables was seen at 1 month of age and significantly increased at 3 months. Differences in the pattern of rhythmicity during these two developmental periods were highlighted by an increase in activity during the subjective day and a decrease in Trec during the subjective night at 3 months compared to 1 month. Correlational analysis revealed that all pairs of variables, exclusive of Tsk, showed a significantly higher association at 3 months relative to 1 month. The lengthening of the interfeeding interval at 3 months of age corresponded with an increased consolidation of sleep during the night and a relatively lower nocturnal body temperature minima compared to 1 month of age. CONCLUSION: The results of this study underscore the subtle changes in the nature and interaction of several infant variables during this critical developmental period, which may reflect maturation of the circadian system and its coupling with homeostatic effector systems that are developing in parallel.

Light variability in the modern neonatal nursery: chronobiologic issues.

The role that nursery light variability may play in modulating infant biological rhythms is being studied in Stanford Medical Center's Neonatal Intensive Care (NICU) and Intermediate Care (IN) Nurseries. In this investigation, spatial and temporal variability in illuminance was determined at 20 sites within each nursery over a 5-day period. The analysis of 240 measurements at 30 min intervals from each site revealed marked variability in illumination with respect to both time and position in the nursery. These aperiodic lighting patterns differed greatly from the published characterization of NICUs as having 'constant' illumination. Light pulses of variable frequency, intensity, and duration were common at each of the 40 bedsites studied. Given the powerful impact of light on circadian rhythmicity and sleep in adults, the results from this study suggest that modern NICU lighting, while implemented to facilitate intensive care, may have adverse effects on infant development. Future studies on the influence of light on biological rhythmicity and sleep are essential to provide a framework for clinical and environmental interventions, which may play a significant role in improving developmental outcome in hospitalized preterm or term infants.

Infant-parent co-sleeping in an evolutionary perspective: implications for understanding infant sleep development and the sudden infant death syndrome.

Evidence suggests that infant-parent co-sleeping represents the species-wide pattern of sleep in which human infant physiology evolved. The hypothesis evaluated in this manuscript is that the co-sleeping environment may foster development of optimal sleep patterning in infants and confer other benefits, including reducing the risk of the sudden infant death syndrome (SIDS). These postulations by McKenna are considered from different perspectives by the coauthors. Using evolutionary, cross-species, crosscultural, physiological and behavioral data, our objective was to present a conceptual framework for assessing the developmental consequences of solitary sleeping and infant-parent co-sleeping.

Incidence of bronchopulmonary dysplasia, growth failure, and pulmonary dysfunction assessed by clinical scoring.

A clinical scoring system was used to determine retrospectively whether the severity of bronchopulmonary dysplasia (BPD) in 67 preterm infants at 21 to 27 days of age would predict the need for home supplemental oxygen or growth retardation (weight less than 5th percentile at 12 months of age). The scoring system was composed of five variables, including fractional inspiratory oxygen, partial pressure of CO2, respiratory rate, chest retractions, and growth rate. The score did not predict the need for home supplemental oxygen or growth retardation (P = .87 and .79, respectively); in contrast, the number of hours of oxygen greater than 80% was significantly correlated with home O2 use (P = .0001) and growth retardation at 1 year of age (P = .013). Since there is no simple predictive score that can be used to determine the functional severity of BPD, each at-risk infant must be clinically evaluated for the degree of pulmonary dysfunction, the need for O2 supplementation, and other supportive pulmonary care prior to discharge.

Periodic breathing in preterm infants: incidence and characteristics.

The prevalence and characteristics of periodic breathing in preterm infants were measured by 24-hour impedance pneumograms in 66 preterm infants before discharge from the nursery. Four periodic breathing parameters (percentage of periodic breathing per quiet time, number of episodes of periodic breathing per 100 minutes of quiet time, mean duration of periodic breathing, and longest episode of periodic breathing) were compared to data available from healthy term infants and from term infants who subsequently died of sudden infant death syndrome (SIDS). Periodic breathing was found in all preterm infants studied and mean periodic breathing parameter values (12.0%, 8.6 episodes, 1.2 minutes, and 7.3 minutes, respectively) in our preterm population were substantially higher than values from healthy term infants and SIDS victims. Most periodic breathing parameters decreased significantly in infants studied at 39 to 41 weeks' postconceptional age compared with earlier postconceptional age groups. No relationship was found between central apneas of greater than or equal to 15 seconds' duration and postconceptional age or any periodic breathing parameter. Periodic breathing is a common respiratory pattern in preterm infants that is usually not of pathologic significance. Associations between elevated levels of periodic breathing and respiratory dysfunction or SIDS should be made with caution.

Periodic breathing cycle duration in preterm infants.

Periodic breathing cycle duration (PCD), the time interval from the beginning of one respiratory pause to the beginning of the next pause within an episode of periodic breathing (PB), was measured by examination of 24-h impedance pneumograms in 51 preterm infants. Calculations of the SD of PCD within a given PB episode (approximately 3 s) and comparison of PCD values between two PB episodes in each infant (r = 0.68) revealed considerable variability in PCD. This variability was not related to the number of cycles in the PB episode or to the amount of PB in the recording. Contrary to the decrease in PCD from 15.0 s at 1 wk to 12.4 s at 12 wk in term infants reported previously, PCD did not vary as a function of postconceptional, gestational, or postnatal age in our preterm population. PCD has limited value as an indicator of chemoreceptor maturation in the preterm infant, and most likely reflects transient adjustments in respiratory system control.

Periodic breathing parameter values depend on specific pneumogram scoring criteria.

Periodic breathing (PB) has been related to both normal and pathologic respiratory system control in infants. However, comparison of the results of separate studies has been limited by the variability in procedures used by different investigators to quantify PB. In this study we scored 15 24-hr impedance pneumograms using the criteria of Parmelee et al. (Neuropediatrie 3:294-304, 1972), Christova-Gueorguieva (Biology of the Neonate 44:325-332, 1983), and Curzi-Dascalova, Kelly and Shannon (Pediatrics 63:355-360, 1979) and analyzed the resulting differences in several commonly used PB parameters. Scoring criteria consistently and significantly influenced three PB parameters: the %PB, number of episodes of PB/100 min recording time, and mean duration of PB episode length showed average changes of 74%, 179%, and 36%, respectively, when the methods with the most extreme differences were compared. In contrast, the duration of the longest episode of PB showed no significant change as a function of scoring criteria. Awareness of the particular method of PB scoring is therefore essential in interpreting PB parameter values.

Periodic breathing in preterm infants: influence of bronchopulmonary dysplasia and theophylline.

Periodic breathing (PB) has been studied extensively in both normal term infants and term infants presumed to be at high risk for sudden infant death syndrome (SIDS); however, little is known about the incidence and significance of PB in preterm infants. Twenty-four hour impedance pneumograms were obtained from 108 preterm infants prior to their discharge from the nursery and four PB parameters (%PB, No. of episodes of PB/100 min, mean duration of PB episode length, and duration of the longest episode of PB) were quantified in each recording. Control infants who were asymptomatic for apnea had the highest PB parameter values (%PB, 12.0; No. episodes/100 min, 8.6; mean duration, 1.2 min; and longest episode, 7.3 min); infants with bronchopulmonary dysplasia (BPD) showed dramatic decreases in all PB parameters, with a median %PB of 1/16 of the control population. Theophylline use was associated with a significant decrease in PB parameter values only in infants without BPD. Central apneas greater than 15 s did not vary significantly as a function of BPD, theophylline, or postconceptional age. We conclude that the clinical status of preterm infants significantly influences PB parameter values and must be taken into account in the interpretation of pneumograms, for decision-making about home cardiorespiratory monitoring, and in assigning risk for SIDS.

Neuronal activity during sleep and complete bouts of hibernation.

Changes in arousal state in a euthermic mammal exert powerful influences on major neural regulatory systems. Changes in behavioral state occur at body temperature (Tb) greater than 25 degrees C during hibernation. However, no information exists regarding alterations in arousal states during deep torpor. In this study we used a combination of electroencephalographic, electromyographic, and posterior thalamic neuronal activity in ground squirrels (Spermophilus lateralis) to evaluate arousal states during deep hibernation. No state homologous to rapid-eye-movement sleep was observed below Tb = 21 degrees C during hibernation. However, the animals did continue to cycle through states homologous to electrophysiologically defined wakefulness (AW) and non-rapid-eye-movement (NREM) sleep at all temperatures examined (Tb = 14-36 degrees C). These results extend previous observations that hibernation is not a homogeneous state. Instead, deep torpor consists primarily of a state similar to NREM sleep, interrupted periodically by short intervals of a form of AW. These periodic alterations in state should be accompanied by changes in the properties of many regulatory systems and must be accounted for in any theory of the neural control of hibernation.

The influence of ambient temperature on sleep characteristics in the aged cat.

Sleep characteristics were compared in young adult and aged cats over a range of environmental temperatures from 5 to 35 degrees C. Although both groups exhibited sleep disruptions as ambient temperatures decreased, transient arousals were increased at temperature extremes in the aged group compared to young adults. Declining efficiency of thermoregulatory control and increased sensitivity to environmental temperature in the elderly may contribute to the changes in sleep quality which occur during the aging process.

Activity of suprachiasmatic and hypothalamic neurons during sleep and wakefulness in the rat.

Single unit activity was recorded from the suprachiasmatic nucleus (SCN) and preoptic/anterior hypothalamus (POAH) of unrestrained Wistar rats during sleep and wakefulness. Regularly firing cells, which are abundant in in vitro SCN preparations and have been considered the basis of a central neuronal oscillator, were conspicuously absent in this preparation and in other in vivo studies. Most of the 55 cells recorded in the SCN and POAH were characterized by spontaneous firing rates below 12 Hz and with heterogeneous patterns of changes in frequency with arousal states. In vivo neurophysiological studies of the SCN in which the anesthetic agent urethane is used should consider the effect of different levels of arousal, as indicated by the cortical EEG, in evaluating the relationship between sensory stimulation and single unit activity.

Absence of a circadian rhythm of protein synthesis in the rat suprachiasmatic nucleus.

Male Wistar rats chronically catheterized in the jugular vein were entrained to a 12 L:12 D (lights on at 07.00 h) photoperiod. [1-14C]Leucine was administered in behaving rats at either 10.00 (day) or 22.00 (night) h. After 45 min of incubation animals were sacrificed, brains frozen, sectioned, and autoradiographed. The relative amount of label in the hypothalamic suprachiasmatic nucleus (SCN) was measured as the ratio of the optical density (OD) of the image of the SCN on the autoradiograph to the OD of white matter. The relative incorporation of labelled leucine into protein did not differ in the SCN of day vs night animals. This finding is in contrast to the prominent circadian rhythm of glucose utilization which has been seen in the rat SCN at identical points in the circadian cycle.

Changes in the thermal characteristics of hypothalamic neurons during sleep and wakefulness.

The characteristics of the mammalian thermoregulatory system are dependent upon arousal state. During NREM sleep thermoregulatory mechanisms are intact but body temperature is regulated at a lower level than during wakefulness. In REM sleep thermoregulatory effector mechanisms are inhibited and thermal homeostasis is severely disrupted. Thermosensitivity of neurons in the preoptic/anterior hypothalamus (POAH) was determined for behaving kangaroo rats (Dipodomys deserti) during electrophysiologically defined wakefulness, NREM sleep and REM sleep to elucidate possible neural mechanisms for previous findings of state-dependent changes in thermoregulation. Thirty cells were tested during at least two arousal states. During wakefulness, 70% of the recorded cells were sensitive to changes in local temperature, with the number of warm-sensitive (W) cells outnumbering cold-sensitive (C) cells by 1.6:1. In NREM sleep, 43% of the cells were thermally sensitive, with the ratio of W:C remaining the same as in wakefulness. In REM sleep only two cells were thermosensitive (both W). The decrease in neuronal thermosensitivity of POAH cells during REM sleep parallels findings of inhibition of thermoregulatory effector responses during REM, although further work is necessary to determine the source and nature of the inhibition.

Influence of hypothalamic and ambient temperatures on sleep in kangaroo rats.

Unanesthetized, unrestrained kangaroo rats (Dipodomys) were studied to examine the changes in the frequency and duration of sleep states caused by long-term manipulations of hypothalamic temperature (Thy) at a thermoneutral (30 degrees C) and a low (20 degrees C) ambient temperature (Ta). A cold stimulus present in either the hypothalamus or the skin decreased both the total sleep time (TST) and the ratio of paradoxical sleep (PS) to TST. At a low Ta, TST, but not the PS-to-TST ratio, was increased by raising Thy, indicating that a cold peripheral stimulus could differentially inhibit PS. At a thermoneutral Ta, cooling Thy decreased both TST and the PS/TST. Changes in the amount of PS were due largely to changes in the frequency, but not the duration, of individual episodes of PS, suggesting that the transition to PS is partially dependent on the thermoregulatory conditions existing during slow-wave sleep (SWS). These results are consistent with the recent findings that the thermoregulatory system is functional during SWS but is inhibited or inactivated during PS.