Ventilation and ventilatory pattern during sleep in aborted sudden infant death syndrome

To assess ventilatory control during sleep in infants at risk for the sudden infant death syndrome (SIDS), we made serial measurements of resting tidal volume (Vt), respiratory cycle time (Ttot), and the ventilatory changes resulting from inhalation of 2% CO2 in aborted SIDS infants in rapid eye movement and quiet sleep and compared them to a group of normal infants during the first 4 months of life. Ventilation was measured by the barometric method, and sleep was staged using electroencephalogram, electrooculogram, and electromyogram and behavioral criteria. Although resting instantaneous minute ventilation (Vt/Ttot) was virtually the same in both groups of infants, Vt tended to be smaller (by up to 50% in the first 2 months) and Ttot tended to be shorter in aborted SIDS than in normal infants in both rapid eye movement and quiet sleep. The increase in the mean Vt/Ttot with 2% CO2 is greater by about 5 to 20% in aborted SIDS than in normal infants at 3 and 4 months of age in both sleep states. These findings, together with our previous findings that aborted SIDS infants have an increase in heart rate and a shortening of the QT interval, provide indirect evidence that infants at high risk for SIDS may have increased sympathoadrenal activity.     

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.     

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.     

Normal Ranges of Heart Rate Variability During Infancy and Childhood

Heart rate variability is a noninvasive index of the neural activity of the heart. The present study examined heart rate variability indices in 210 infants and children aged 3 days to 14 years to obtain normal ranges for all age classes. Heart rate variability was measured by calculating mean RR interval over the length of the analysis, mean RR interval during quiet sleep, 5 time-domain (SDNN, SDNN-i, SDANN-i, r-MSSD, pNN50), and 4 frequency-domain (VLF, LF, HF, LF/HF ratio) indices. Our data show a significant positive correlation between all indices and the mean RR interval over the length of the analysis, except for the LF/HF ratio for which the correlation was binomial. A positive power correlation was also found between all parameters and age. The multiple correlation analysis confirmed the independent effect of age and mean RR interval on the heart rate variability. These data in a healthy pediatric population confirm a progressive maturation of the autonomic nervous system during childhood and may be utilized to examine the effects of underlying disease processes or therapeutic interventions on cardiac autonomic tone during infancy and childhood.     

Interaction of heart rate and respiration in newborn babies

Variability of heart rate (HRV) and transthoracic electric impedance respirogram (TEZ) were examined by spectral analysis in three groups of neonates: healthy term babies (22), healthy preterm babies (21), and preterm babies with respiratory distress syndrome (RDS) (11). Heart rate, TEZ, PtcO2, and PtcCO2 were monitored during quiet sleep on the 1st, 3rd, and 5th day of postnatal life. Autospectra for trend-corrected segments of heart rate and TEZ as well as their cross-spectral density was in less than 0.2 Hz [low frequency (LF)] area (less than 12 cycles/min) in all the neonates. Intergroup comparisons of average band-integrated spectra revealed that the LF spectral density of HRV was greater in the term babies than in the preterm babies on day 3. In the babies with RDS, both LF and high-frequency (HF, greater than 0.2 Hz) were abnormally low throughout the study. In the term infants, the TEZ amplitude spectrum was flat on day 1. On later days, a peak corresponding to the average respiratory rate emerged. In the healthy preterm babies, there was a LF peak in TEZ autospectrum on all days. In the babies with RDS, the peak of ventilator frequency was initially present; finally, the respiratory activity accumulated in the LF area. In the cross-spectra of term babies, there was a LF peak on all days. On day 5, an additional HF peak appeared, representing respiratory sinus arrhythmia. In the healthy preterm babies, only a LF peak was present.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of maternal smoking on autonomic nervous system in healthy infants

To determine the influence of maternal smoking on autonomic nervous system in healthy infants, 36 infants were recorded polygraphically for one night. Their mothers were defined, according to their smoking frequency during pregnancy, as "nonsmokers" (no cigarettes smoked during pregnancy) or "smokers" (10 or more cigarettes per day). The infants had a median postnatal age of 10.5 wk (range 6 to 16 wk); 18 were born to nonsmokers, and 18 to smokers. During the whole night, spectral analyses of heart rate (HR) were evaluated as a function of sleep stages. Two major peaks were recognizable: a low-frequency component (LF) related to sympathetic and parasympathetic activities and a high-frequency component (HF) reflecting parasympathetic tonus. The ratio of LF/HF powers was calculated as an index of sympathovagal interaction. In REM sleep, "smokers" infants were characterized by significantly lower HF powers and normalized HF powers, and higher LF/HF ratios than "nonsmokers." The finding did not reach statistical significance in NREM sleep. In conclusion, maternal smoking induced changes in autonomic control and maturation in infants. These effects of cigarette smoke exposure can be added to those already reported and offer additional evidence for counseling mothers to stop smoking.     

Characteristics of heart period variability in intubated very low birth weight infants with respiratory disease

BACKGROUND: Heart period variability provides a measure of balance between the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS). Since the PNS develops during the final weeks of gestation, premature infants have an overriding SNS. Spectral power analysis of heart period variability reveals two main frequency regions, the low frequency region (LF) representing primarily SNS activity and the high frequency region (HF) representing PNS activity. OBJECTIVES: To identify the characteristics of heart period power in the LF and HF regions in very low birth weight (VLBW) infants in the neonatal intensive care unit across gestational age groups and between sleep and awake states. METHODS: Data were collected from 16 intubated and mechanically ventilated VLBW infants with respiratory disease. Using spectral analysis techniques, heart period power in the two main frequency regions was extracted. RESULTS: HF power did not improve with gestational age as expected. LF power did increase with age, albeit nonsignificantly. LF and HF power were not significantly different between awake and sleep states. CONCLUSIONS: The results of this preliminary study suggest that PNS tone does not improve with gestational age in VLBW infants with respiratory disease. The intensive care environment may stimulate a sympathetic response in these infants and disrupt normal PNS development.     

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.     

Sudden infant death syndrome: abnormalities in short term fluctuations in heart rate and respiratory activity

In order to test the hypothesis that a defect in cardiorespiratory regulation contributes to death of infants from sudden infant death syndrome (SIDS), we analyzed the power spectra of heart rate and respiratory activity during 256-sec epochs of quiet sleep. Data were obtained from pneumogram recordings performed for 12 h at night on eight infants who subsequently died from SIDS and 22 age-matched control infants. We computed the heart rate and respiratory power spectra from a single epoch on each infant using an algorithm developed for an 8085 microprocessor system dedicated to this investigation. There was no statistically significant difference between SIDS and controls based on mean respiratory and heart rates. Spectral analysis revealed enhancement of low frequency power in the 0.02 to 0.1 Hz band in the heart rate power spectrum in the SIDS group compared to control (p less than 0.002) and dispersion in respiratory frequency as determined by the respiratory band width (p less than 0.00001). These data suggest that a predisposition to SIDS manifests itself in an abnormal pattern of fluctuations in heart rate and respiratory activity.     

Spectral analysis of heart variability in the newborn infant

We investigated the relationship between spectral power and both mean heart rate (HR) and heart rate variability (HRV). Spectral power was calculated using digital heart rate recordings from term infants. Regression analysis revealed a positive correlation between low-frequency (LF) sympathetic power and HR, and a negative correlation between high-frequency (HF) parasympathetic power and HR. HRV correlated positively in all regions of the power spectrum. In awake infants, the contribution of HF power to total power (HF/TP) was significantly decreased. LF power tended to be greater, however, this trend was not statistically significant. By following expected autonomic patterns, the findings of this study confirm that spectral analysis provides a noninvasive method for the assessment of autonomic activity influencing the newborn heart. The correlation between spectral power and HRV can serve as an additional tool in the study of autonomic dysfunction.     

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.     

Autoregressive analysis of cardiac RR intervals in preterm and full-term infants

For the purpose of obtaining information on the maturation process of the autonomic nervous system in pre- and full-term infants, polygraphs were recorded during sleep from a total of 52 appropriate-for-dates infants at a conceptional age of 28–41 weeks. The 104 RR interval time series was calculated by auto-regressive (AR) and component analysis. Histograms of damping frequencies obtained were divided into two frequency bands: low frequency fluctuations (LF) of less the 0.1 cycle/beat (c/b) and high frequency fluctuations (HF) of more than 0.15 c/b. Total power and LF power decreased with increases in the conceptional age or postnatal age at a significance level of 0.01, respectively. In addition, the HF amount of bio-informing activity increased (P< 0.001) and the damping time of HF also increased (P <0.01). From these results, it was speculated that the activity of the sympathetic system decreases with increases in conceptional or postnatal age. It was also speculated that increased regularity and oscillatory duration in HF might be caused by the development of the reciprocal response of respiration to heart rate variation.     

The development of autonomic cardiovascular control is altered by preterm birth

Objectives

Autonomic dysfunction, either sympathetic or parasympathetic, may explain the increased incidence of Sudden Infant Death Syndrome (SIDS) among preterm infants, as well as their subsequent heightened risk of hypertension in adulthood. As little is known about the development of autonomic function in preterm infants, we contrasted autonomic cardiovascular control across the first 6 months after term-corrected age (CA) in preterm and term infants.

Study design

Preterm (n = 25) and age matched term infants (n = 31) were studied at 2–4 weeks, 2–3 months and 5–6 months CA using daytime polysomnography. Blood pressure and heart rate were measured during quiet (QS) and active (AS) sleep. Autonomic control was assessed using spectral indices of blood pressure and heart rate variability (BPV and HRV) in ranges of low frequency (LF, reflecting sympathetic + parasympathetic activity), high frequency (HF, respiratory-mediated changes + parasympathetic activity), and LF/HF ratio (sympatho-vagal balance).

Results

In preterm infants, HF HRV increased, LF/HF HRV decreased and LF BPV decreased with age (p < 0.05); these changes were most evident in AS. Compared to term infants, preterm infants in QS exhibited lower LF, HF and total HRV at 5–6 months; higher HF BPV at all ages; and lower LF BPV at 2–4 weeks (p < 0.05).

Conclusions

With maturation, in preterm infants, parasympathetic modulation of the heart increases while sympathetic modulation of blood pressure decreases. Compared to term infants, preterm infants exhibit lesser parasympathetic modulation of the heart along with greater respiratory-mediated changes and lower sympathetic modulation of blood pressure. Impaired autonomic control in preterm infants may increase their risk of cardiovascular dysfunction later in life.     

Development of baroreflex influences on heart rate variability in preterm infants

To investigate developmental changes in autonomic cardiovascular reflexes in preterm infants, we used autoregressive power spectral analysis to analyze the effect of upright tilting on heart rate variability in preterm infants. Twenty-eight infants were studied in a longitudinal fashion beginning at 28-32 weeks postconceptional age (postnatal age 1-5 weeks). Each week, heart rate variability in the supine position and after 45 degrees head-up tilt was analyzed by spectral analysis. With the initial study of each infant, there was no significant change in heart rate following head-up tilt compared with baseline (-0.5+/-0.9 bpm). However, linear regression analysis revealed that with increasing postnatal age, the change in heart rate in response to tilting became more positive (mean slope of regressions 0.45+/-0.12 bpm/week, P<0.005). The power spectral density of R-R interval variability in the low-(LF; 0.02-0.15 Hz) and high-(HF; 0.15-1.5 Hz) frequency ranges were obtained and the values normalized by dividing each component by the total power. For measurements obtained in the supine position, the LF/HF ratio progressively decreased with increasing postnatal age, indicating a maturational change in sympathovagal balance. We used the difference in the LF/HF ratio between tilt and the recumbent position as a measure of the change in autonomic input to the heart in response to unloading of the arterial baroreceptors. No significant change in these ratios were observed when infants were first studied between 28 and 32 weeks postconceptional age, suggesting that the cardiac baroreflex is poorly developed at this stage of development. However, with postnatal maturation, the LF component of the power spectrum became progressively larger with tilt relative to the basal state, such that the difference between LF/HF(tilt) and LF/HF(base) became progressively more positive (P <0.006). These findings suggest that in premature infants, cardiac baroreceptor reflexes become more functional with postnatal development.     

Cardiovascular fluctuations and transfer function analysis in stable preterm infants

To examine the baroreceptor reflex function, a beat-to-beat analysis between systolic blood pressure (SBP) and R-R interval fluctuations was studied in 10 stable appropriate-for-gestational age preterm infants (range, 27.2-33.7 wk) in the first postnatal week during quiet sleep. Spectral power analysis, using fast Fourier transform, and transfer functions (gain and phase difference) between SBP and R-R fluctuations were estimated in a low-frequency band (LF, 0.03-0.2 Hz) and high-frequency band (HF defined as the frequency band between the 10th and 90th centiles of the individual respiratory frequency). The LF/HF ratio reflects the sympathovagal balance. The mean frequency (+/-SD) of LF peaks was centered at 0.07 +/- 0.02 Hz. The mean frequency (+/-SD) of the individual HF band was 0.82 +/- 0.21 Hz. The LF/HF ratio in the R-R interval series [median, 29; interquartile range (IQR), 16-40] was higher than in the SBP series (median, 8; IQR, 4-14). The gain between R-R interval and SBP fluctuations (median, 4.2 ms/mm Hg; IQR, 2.4-5.0) in the LF band was higher than in the HF band (median, 1.7 ms/mm Hg; IQR, 1.4-3.0). SBP fluctuations lead R-R interval fluctuations in the LF band with a median phase difference of +96 degrees (IQR, 67-132). At LF the fluctuations in SBP precede changes in R-R interval with a time delay of 3.8 s. These observations indicate a dominant role of the sympathetic system in stable preterm infants in comparison with published adult values. Cross-spectral analysis allows a test for tracking the development of the sympathetic system in neonates.     

Postural differences in cardiac dynamics during quiet and active sleep in low birthweight infants

To study the effects of body position (supine versus prone) on changes in cardiac inter-beat interval during quiet and active sleep, 6-h continuous electrocardiographic recordings and simultaneous minute-by-minute behavioural activity state assignments were made in 61 healthy, growing, low birthweight infants. The infants weighed 795-1600 g at birth and ranged between 30-38 wk in postconceptual age. Infants were randomly assigned to the supine or prone position for the first 3 h of each study; the position was reversed for the second 3 h. Higher heart rates and lower time and frequency domain measures of inter-beat interval variability were observed in the prone position as compared to the supine position, during both quiet and active sleep. In addition, an analysis of consecutive increases and decreases in the instantaneous heart rate revealed a lower incidence of sustained accelerations or decelerations in the prone position. Although consistent findings concerning inter-beat interval variability and sleeping position were obtained from all analytic techniques, the differences derived from analysis of consecutive inter-beat changes were the most robust. These differences in multiple measures of cardiac rate and rhythm between prone and supine positions suggest that autonomic control of the heart is altered by body position, the net effect on heart rate being increased sympathetic dominance.     

Abnormal heart rate response to hypercapnia in boys with an apparent life-threatening event

AIM: To determine instantaneous cardiac variability responses to increased carbon dioxide (CO2) during quiet sleep in infants who may be at risk for the Sudden Infant Death syndrome (SIDS). METHODS: The cardiac rate variability before, during and after a CO2 challenge was examined in 41 infants who had experienced an apparent life-threatening event (ALTE) and 41 gender- and age-matched control infants. RESULTS: The ALTE infants responded to CO2 breathing with a significant increase in R-R intervals, i.e. decreases in heart rate, compared to the controls (45.1% increase in R-R intervals vs. 41.4%; p = 0.005). The differences between ALTE infants and controls depended primarily on the boys' responses. CONCLUSION: ALTE infants, particularly ALTE boys, have an autonomic dysfunction-lower sympathetic stimulation and/or inhibited vagal withdrawal when stressed with CO2. The outcome might provide clues to the mechanisms underlying the cardiovascular processes contributing to the terminal event in SIDS.     

Heart rate variability in infants with apparent life-threatening events

Heart rate variability (HRV) is often used as an index of sympatho-vagal balance. A decreased HRV has been observed in patients with central hypoventilation and in infants who have later succumbed to sudden infant death syndrome (SIDS). The aim of the present study was to investigate whether HRV is altered in infants with apparent life-threatening events (ALTE), a group with an increased risk of SIDS. Fifty infants with ALTE were compared with 50 age- and sex-matched controls. ECG was recorded overnight in all infants. Two sequences of RR intervals free of artefacts were selected from each sleep state and spectral analysis of RR variability was performed. The mean and SD of RR and the low (LFPow) and high (HFPow) frequency power were analysed. In active sleep (AS) the LF/HF ratio was lower in ALTE infants, but no differences were seen in either the LFPow or the HFPow. In quiet sleep (QS), however, ALTE infants had higher SD-RR (p = 0.006), greater HFPow (p = 0.02) and VLFPow (very low frequency power, p = 0.02) than the control infants. The same results were seen when the two sleep states were combined for analysis, ALTE infants had higher SD-RR (p = 0.004), HFPow (p = 0.006) and VLFPow (p = 0.04). Conclusion: The different HRV pattern in ALTE infants compared to healthy controls suggests an altered autonomic control.     

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.     

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.