Spectral analysis of heart rate variability and respiration during sleep in cocaine-exposed neonates.

This study's objective was to examine the autonomic control of heart rate and respiration during the neonatal period in human infants with prenatal exposure to cocaine. Four-hour daytime recordings of the electrocardiogram (ECG) were obtained from 15 cocaine-exposed and 13 non-exposed full-term neonates at 2 weeks of age during quiet sleep (QS) and active sleep (AS). For each 1-min epoch of sleep, the power spectrum of the R-R intervals was computed from the ECG to obtain the total power (0-2 Hz), and spectral power in the high-frequency (HFP, 0.3-2 Hz), mid-frequency (MFP, 0.1-0.2 Hz), and low-frequency (LFP, 0.03-0.1 Hz) bands. Respiration was also monitored and processed using similar spectral analysis procedures. Cocaine-exposed neonates showed enhanced heart rate variability reflected by an increase in spectral power across all frequency bands. Spectral power in LFP and MFP was higher in cocaine-exposed neonates during both sleep states, but only in HFP during QS. There were no respiratory patterning differences between the groups to account for these findings. The index of sympathovagal balance (LFP + MFP)/HFP, showed no differences between the groups. We conclude that infants exposed to cocaine in utero show differences in the modulation of heart rate reflecting an increase in both vagal and sympathetic influences.

Nonlinear dynamics of heart rate variability in cocaine-exposed neonates during sleep.

The aim of this study was to determine the effects of prenatal cocaine exposure (PCE) on the dynamics of heart rate variability in full-term neonates during sleep. R-R interval (RRI) time series from 9 infants with PCE and 12 controls during periods of stable quiet sleep and active sleep were analyzed using autoregressive modeling and nonlinear dynamics. There were no differences between the two groups in spectral power distribution, approximate entropy, correlation dimension, and nonlinear predictability. However, application of surrogate data analysis to these measures revealed a significant degree of nonlinear RRI dynamics in all subjects. A parametric model, consisting of a nonlinear delayed-feedback system with stochastic noise as the perturbing input, was employed to estimate the relative contributions of linear and nonlinear deterministic dynamics in the data. Both infant groups showed similar proportional contributions in linear, nonlinear, and stochastic dynamics. However, approximate entropy, correlation dimension, and nonlinear prediction error were all decreased in active versus quiet sleep; in addition, the parametric model revealed a doubling of the linear component and a halving of the nonlinear contribution to overall heart rate variability. Spectral analysis indicated a shift in relative power toward lower frequencies. We conclude that 1) RRI dynamics in infants with PCE and normal controls are similar; and 2) in both groups, sympathetic dominance during active sleep produces primarily periodic low-frequency oscillations in RRI, whereas in quiet sleep vagal modulation leads to RRI fluctuations that are broadband and dynamically more complex.

Developmental patterns of heart rate and variability in infants with persistent apnea of infancy.

During periods of regular breathing, heart rate is slower and more variable in healthy (no history of respiratory distress syndrome) prematurely born infants with persistent apnea, relative to full-term control infants of comparable post-conceptional ages. We tested the hypothesis that the cardiovascular differences may be linked to the persistent apnea, rather than premature birth, by assessing heart rate and variability in full-term infants with persistent apnea. Thus, resting heart rate and variability were compared in full-term infants with apnea of infancy, prematurely born infants with persistent apnea, and full-term control infants. Full-term infants with persisting apnea showed slower heart rates than control infants, beginning at 4 months after birth, and enhanced heart rate variability beginning at 6 months. Healthy prematurely born infants with persistent apnea showed cardiovascular alterations similar to those of full-term infants with apnea; these alterations differed from those observed in very premature infants with histories of respiratory distress. The postnatal development of cardiovascular aberrations in infants with persistent apnea suggests that mechanisms accompanying apneic events may contribute to long-term alterations in autonomic control.

Heart rate variability in children with obstructive sleep apnea.

Adults with obstructive sleep apnea syndrome (OSAS) display substantial heart rate changes associated with obstructive events, and recent reports suggest similar heart rate changes in children with OSAS. These rate changes could assist screening of young patients for OSAS. Six-hour polysomnographic recordings were obtained from seven children with OSAS (mean age: 4.5 years; apnea index: 19.5 +/- 5.1) and from seven primary snorers without OSAS who served as controls (mean age: 4.7; apnea index: 0). Scatterplots of each cardiac R-R interval against the preceding interval (Poincaré plots) were used to assess beat-to-beat cardiac variability at different heart rates. Beat-to-beat variation at slow rates was significantly increased in children with OSAS relative to controls, while variation at fast and intermediate heart rates was significantly reduced in these children. We conclude that OSAS alters beat-to-beat variation in characteristic fashions in children, that the variability changes occur at all heart rates but are most significant at slow heart rates, and that these heart rate patterns could assist in screening of suspected cases of OSAS.

Developmental patterns of heart rate and variability in prematurely-born infants with apnea of prematurity.

At equivalent post-conceptional ages, prematurely-born infants have higher heart rates and reduced heart rate variability, relative to full-term neonates. Premature birth might exert long-lasting effects on central and peripheral mechanisms that control cardiovascular activity. We assessed development of heart rate and heart rate variability in symptomatic preterm infants up to 6 months of age. Fifty 6.5-h evening recordings of EKG and breathing were obtained from prematurely-born infants (gestational ages: 24-35 weeks). Cardiac R-R intervals were captured with a resolution of +/- 0.5 msec. One-min epochs were selected from three periods of regular respiration in recordings from premature infants and 72 recordings of full-term infants at comparable post-conceptional ages. Mean heart rate and heart rate variability were determined for each recording. At 40 weeks post-conception, prematurely-born infants with apnea of prematurity showed higher heart rates and reduced heart rate variability than did full-term neonates. These differences between premature and full-term infants persisted throughout the next 6 months in those infants born prior to 30 weeks gestation, and in those infants born at 30-35 weeks who experienced respiratory distress syndrome (RDS) during the neonatal period. The findings suggest that premature delivery, or complications thereof, exerts long-lasting effects on cardiac control.

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.

Dynamics of respiratory patterning in normal infants and infants who subsequently died of the sudden infant death syndrome.

Despite evidence that respiratory control mechanisms may be altered in infants who succumb to the sudden infant death syndrome (SIDS), overall respiratory variability in SIDS victims is comparable to that of control infants. We assessed dynamic characteristics of breathing in 16 recordings of apparently healthy infants who subsequently died of SIDS, and 35 recordings of age-matched control infants. Each breath-to-breath interval in 10-min epochs of quiet sleep and rapid eye movement sleep was plotted against the previous interval. Dispersion of next-intervals was determined after short, intermediate, and long interbreath intervals. In SIDS victims, dispersion after long intervals (slow respiratory rates) was significantly restricted relative to control infants. Moreover, after long breath-to-breath intervals, SIDS victims showed smaller mean breath-to-breath changes in respiratory rate than did controls. The findings indicate that breath-to-breath respiratory patterns differ in infants who succumb to SIDS, and the differences occur preferentially at low respiratory rates.

Cardiac and respiratory patterns during sleep in cocaine-exposed neonates.

Four-hour recordings of heart rate and respiration during spontaneous sleep and wakefulness were obtained from 17 cocaine-exposed and 14 control infants at 2 weeks of age. The median values for heart and respiratory rate and variability were determined for each 1-min epoch of quiet and active sleep. Overall mean rates and variabilities were determined for each state. The cocaine-exposed infants showed significantly greater sleep state effects on heart rate relative to the control infants. Recency of cocaine exposure was not a factor in the differences; even those cocaine-exposed infants who tested negative for the drug perinatally differed significantly from those who had never been exposed. Heart rate variability was increased in cocaine-exposed infants relative to controls in both sleep states. Respiratory rate and variability were not significantly different in the cocaine-exposed and control infants. These results suggest differences in cardiovascular control in infants of cocaine-abusing mothers compared to infants without cocaine exposure. The mechanism responsible for these differences is unclear and may reflect cocaine-induced changes in the autonomic physiology of developing infants or some indirect effect of maternal cocaine use.

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.

Aberrant temporal patterning of slow-wave sleep in siblings of SIDS victims.

We assessed the patterning of slow-wave EEG activity during sleep in siblings of sudden infant death syndrome (SIDS) victims over the first 6 months of life. Twelve hour overnight physiologic recordings were obtained from 25 apparently healthy subsequent siblings of SIDS victims and 25 control infants at 1 week, and 1, 2, 3, 4 and 6 months of age. The EEG activity was electronically bandpass filtered, leaving primarily activity ranging from 0.5 to 2.5 Hz (the delta frequency), and the filtered traces were full-wave rectified and integrated over 1 min periods. The recordings were divided into four 3 h segments beginning at sleep onset, and the mean integrated delta activity during quiet sleep was determined for each segment of the night. At 3 and 4 months postnatal age, SIDS siblings displayed increased integrated delta amplitude in the early morning hours relative to control infants. Most SIDS deaths occur in the early morning hours during the 2-4 month age range. We thus speculate that increased delta activity may be indicative of increased arousal thresholds in the early morning, which may contribute to SIDS deaths.

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.

Distribution of slow-wave EEG activity across the night in developing infants.

Adults show distinctive patterns of slow-wave (delta) electroencephalogram (EEG) activity across each sleep cycle and across the night. We examined the ontogeny of slow-wave EEG patterning in infants. Twelve-hour overnight physiological recordings were obtained from 25 normal infants at 1 week and 1, 2, 3, 4 and 6 months of age. The EEG activity was band-pass filtered, leaving primarily activity ranging from 0.5 to 2.5 Hz (the delta frequency). Filtered EEG traces were full-wave rectified and integrated over 1-minute periods. Nighttime recordings were divided into four 3-hour segments, beginning at sleep onset, and the mean integrated delta activity during quiet sleep was determined for each segment of the night. In addition, patterns of delta activity across extended periods of quiet sleep (15 minutes or longer) were determined. Beginning at 2 months of age, integrated delta activity declined significantly over the night. Moreover, beginning at 3 months of age, delta activity increased significantly over individual periods of quiet sleep; in neonates up to 1 month of age, delta activity decreased significantly within epochs of quiet sleep. Beginning at 2-3 months of age, infants show patterns of delta activity similar to those found in adults.

Development of heart rate dynamics during sleep-waking states in normal infants.

Previous studies show alterations in the dynamic patterns of cardiac rate in several "at-risk" populations, including apparently healthy infants who subsequently die of the sudden infant death syndrome. In the present study, we examined the maturation of cardiac rate dynamics in normal infants during sleep-waking states over the first 6 mo of life. Instantaneous changes in cardiac R-R intervals were examined in 12-h recordings of 24 normal full-term infants; each infant was recorded at 1 wk and at 1, 2, 3, 4, and 6 mo of age. Scatter plots, consisting of each cardiac R-R interval plotted as a function of the previous interval (Poincaré plots), were constructed for each sleep-waking state in each recording. Analyses of variance were performed on the dispersion of intervals after long and short R-R intervals. In neonates, Poincaré plots showed significantly more next-interval dispersion after a long R-R interval than after a short interval, a pattern similar to those observed in older infants and in healthy adults. However, between 1 wk and 1 mo of age, this pattern disappeared and returned gradually beginning at 2 mo of age. The scatter of points in Poincaré plots of infants 1 mo of age approached the patterns of at-risk populations, including infants who subsequently died of the sudden infant death syndrome. These patterns at 1 mo may be indicative of increased vulnerability in normal infants after the neonatal period.

Respiratory patterning following cerebral ventricular administration of cocaine.

Intravenous (IV) cocaine in the conscious cat causes extreme tachypnea and reduction in breath-to-breath variability. In this study, we examined respiratory patterning following administration of cocaine into the cerebral ventricles. Intraventricular cocaine elicited a tachypnea that was nearly identical to that for IV cocaine. At the high dose, peak respiratory rate increased by 380%. Breath-to-breath variability was dramatically reduced by cocaine, especially in the early stages of the intoxication; during these stages, the tachypnea was occasionally interrupted by prolonged inspiratory efforts. Procaine was administered as a control for the anesthetic effects of cocaine and caused an initial tachypnea that was similar to that for cocaine. For both cocaine and procaine, the mean ratios of inspiratory to expiratory durations were unaffected, indicating that the tachypnea was accomplished by approximately equal reductions in inspiratory and expiratory durations. We conclude that the tachypnea following cocaine administration results principally from central rather than peripheral mechanisms. In addition, the data suggest that anesthetic actions mediate the principal respiratory effects of cocaine.

Analysis of beat-to-beat heart rate changes during sleep-waking states in normal infants.

Summary measures of heart rate variation describe those aspects of heart rate change that can be averaged over relatively long periods of time. We examined the postnatal maturation of a dynamic feature of cardiac rate--the dependency of each beat-to-beat change in cardiac interbeat interval on the previous beat-to-beat change. In each sleep-waking state, the number of delta RR (the difference between two successive R-R intervals) 4msec was determined as a percent of the total number of intervals (delta RR > 4ms/total delta RR), and each pair of successive interval differences was categorized based on the directions of the two changes (whether they reflected increases or decreases in cardiac intervals). Analysis of variance was used to identify alterations in the proportion of interval differences exceeding the minimum over ages and sleep-waking states, and to describe developments in the temporal patterns of cardiac interval changes. At all ages, infants showed fewer beat-to-beat interval changes during waking than during either sleep state. In all states, older infants showed significantly more beat-to-beat cardiac interval changes and a higher proportion of sustained changes (intervals increasing or decreasing consistently over several beats) than did young infants. Furthermore, infants 2 months and younger showed significantly more sustained increases than decreases in interbeat intervals, indicating gradual declines in heart rate and rapid increases, while older infants showed the opposite pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Minute-by-minute association of heart rate variation with basal heart rate in developing infants.

Particular types of heart rate variation are enhanced during periods of slow heart rate and diminished when heart rate is high. We examined how the correlations between heart rate and various types of heart rate variation developed in normal infants. Polygraphic recordings were obtained from 25 infants at 1 week and at 1, 2, 3, 4 and 6 months of age. Median heart rate and the extents of heart rate variation at three distinct frequencies were determined for each 1-minute epoch. Pearson's r was used to assess the correlation of median heart rate in each epoch with each of three types of heart rate variation. For each recording, correlations were assessed separately for quiet sleep, rapid eye movement (REM) sleep and waking. The maturational patterns of heart rate by heart rate variation correlations were strongly influenced by sleep-waking state and were dissimilar to those previously reported for correlations between cardiac and respiratory measures. The findings suggest dissimilar developmental patterns for autonomic and somatic motor systems, and include a discontinuity in autonomic development at approximately 1 month of age. We speculate that these trends reflect a change in the nature of sleep states as forebrain connections develop.

Dynamic analysis of cardiac R-R intervals in normal infants and in infants who subsequently succumbed to the sudden infant death syndrome.

Infants who subsequently succumb to the sudden infant death syndrome (SIDS) have higher heart rates and reduced heart rate variation compared with other infants. We examined dynamic changes in cardiac interbeat intervals to explore these differences in cardiac control. Recordings of electrocardiographic activity and respiratory movement were acquired from 13 SIDS victims before their deaths. Moment-to-moment changes in R-R intervals during quiet sleep, rapid eye movement sleep, and waking were compared with values of 13 matched control infants. For each sleep-waking state, every R-R interval was plotted against the previous interval (Poincaré plots), and each change in interbeat interval was plotted against the previous change. Dispersion of interbeat intervals at different heart rates was reduced in SIDS victims, resulting in Poincaré plots markedly different from those of controls. The dispersion, sampled at the 10th and 90th percentiles of heart rates, was reduced across all sleep-waking states in SIDS victims. At high heart rates, the difference between groups disappeared after correcting for basal rate; however, the reduced range at low heart rates was independent of basal rate. SIDS victims also showed smaller beat-to-beat changes in heart rate and fewer sustained runs of consistent heart rate changes during waking relative to controls. The differences in cardiac rate dynamics suggest altered autonomic control in infants who succumb to SIDS. We speculate that the autonomic disturbance may lead to cardiac instability or may indicate CNS alterations with the potential to affect other vital functions.

Sleep state organization in normal infants and victims of the sudden infant death syndrome.

Infants at increased risk of the sudden infant death syndrome (SIDS) show abnormal patterning of sleep-waking states. It was hypothesized that infants who were to die of SIDS would show abnormalities of sleep state distribution prior to their deaths. Twenty-two 12-hour recordings were obtained from infants who subsequently died of SIDS, and sleep state patterns were compared in these records and 66 records of age-matched control infants. Each 1-minute epoch was classified as quiet sleep, rapid eye movement (REM) sleep, waking, indeterminate state, or artifact-contaminated. Victims of SIDS showed less waking and more sleep than control infants during the early-morning hours. Victims of SIDS younger than 1 month of age showed significantly more epochs classified as REM sleep across the night and significantly fewer epochs contaminated by artifacts relative to control infants. Further analysis indicated that the increased number of REM epochs resulted from fewer artifact-contaminated epochs, suggesting reduced motility during REM sleep in the SIDS victims compared with the control infants. The finding of decreased waking time during the early morning is of particular importance since most SIDS deaths occur during this portion of the day. The findings of altered sleep patterns in SIDS victims suggest that central neural changes are associated with SIDS risk.