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| Abstract |
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Objective To describe heart period variability in intubated very-low-birth-weight infants during incubator care and during maternal skin-to-skin holding.
Design/Methods An experimental, interrupted time series, crossover design was used; infants served as their own controls. Infants were randomly assigned to treatment order: 2 hours of intermittent skin-to-skin holding for 2 consecutive days followed by 2 days of incubator care or vice versa. The analog signal representing heart period was sampled and quantized at 5 Hz via a dedicated computer system in multiple 300-second epochs each day.
Results Fourteen infants with similar characteristics completed the protocol. The mean interbeat interval was 332 ms during skin-to-skin care and 368 ms during incubator care. Power within the low-and high-frequency regions of heart period was not significantly different between skin-to-skin holding and incubator care. Mean low-frequency power was 124.6 ms2 during skin-to-skin holding and ranged from 51.9 ms2 to 71.4 ms2 during all periods of incubator care. Mean high-frequency power was similar during skin-to-skin holding and incubator care (8.8 ms2 and 6.1 ms2). Infants of 32 to 34 weeks corrected gestational age had increased power in the low- and high-frequency regions.
Conclusions Heart period variability did not improve during skin-to-skin holding. Gestationally older infants had increased power in the low- and high-frequency regions, suggesting a maturing autonomic nervous system.
| Background and Significance |
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Various investigators reported mean heart rates within the accepted range of 120/min to 160/min during skin-to-skin care; however, the healthy, nonintubated, premature infants studied also had increases in heart rates during skin-to-skin care that were greater than the accepted normal high heart rate of 160/min.610 Some infants had heart rates as high as 179/min to 197/min, suggesting increased activity from the sympathetic nervous system stimulating the heart and contributing to physiological instability.7,8,10
Two groups of investigators reported an increased number of bradycardic episodes during skin-to-skin care.4,7 In 8 premature VLBW infants, the mean number of bradycardic events during skin-to-skin care was 2.9 (SD = 3.2), double the number of events that occurred during routine incubator care.6 Of these 8 infants, 7 were receiving continuous positive airway pressure via nasal prongs, and 1 was receiving oxygen via face mask.6 Similar findings were reported in 22 spontaneously breathing VLBW premature infants in a study that compared skin-to-skin care with incubator or crib care.4 These findings suggest that the studied infants had physiological instability during skin-to-skin care. One group of 15 intubated VLBW infants had increased heart rates during the transfer to and from skin-to-skin care, suggesting increased physiological instability during the transfer.11 Heart rate and number of bradycardic events are gross measures of physiological stability and are not sensitive enough for use in evaluating the underlying maturation of the autonomic nervous system in control of the heart. Measurement of heart period variability is a novel method that can be used to evaluate the maturity of the autonomic nervous system in premature infants.
Although frequently used as an indicator of physiological stability, general changes in heart rate (bradycardia or tachycardia) may not be sensitive enough to completely identify all stressful events in very-low-birth-weight infants.
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| Heart Period Variability |
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Heart period variability is useful in evaluating the balance between the parasympathetic and the sympathetic branches of the autonomic nervous system. As such, heart period variability is a sensitive and useful measure for determining maturity of the autonomic nervous system and an infants ability to adapt to external events, maintain homeostasis, and conserve energy specifically during skin-to-skin care.18,19 The development of the autonomic nervous system is incomplete at birth. Sympathetic tone is dominant in premature infants, and parasympathetic tone (specifically vagus nerve tone) increases with gestational age.15,16,20,21 Improved parasympathetic tone may promote growth and restoration and conserve energy.19 Therefore, determining the balance between the parasympathetic and sympathetic nervous systems by measuring heart period variability becomes useful as a measure of physiological stability.
Power spectra can be derived from heart period time series and are statistically useful in determining the balance between the sympathetic and the parasympathetic nervous systems. The power spectra have been divided into 2 frequency regions of activity, with each region influenced by different physiological phenomena.13,20,22 For the purposes of this study, the frequency regions as defined by Chatow et al20 were used. These frequency regions are (1) a low-frequency region from 0.02 Hz to 0.2 Hz and (2) a high-frequency region from greater than 0.2 Hz to 2.0 Hz (Figure 1
). The frequency regions are influenced by specific branches of the autonomic nervous system, and the ratio of low-frequency to high-frequency power indicates sympathovagal balance.20
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In summary, the analysis of mean heart rate in intubated infants during incubator care and skin-to-skin care may not be a sensitive enough measure of the infants response to skin-to-skin care. Heart period variability with spectral power analysis and time-domain analysis provides information about control of the heart by the autonomic nervous system and may be a more sensitive measure of an infants response to skin-to-skin care than is mean heart rate. Power spectral analysis provides descriptive information about sympathetic and parasympathetic tone, whereas time-domain analysis provides information about overall maturity of the autonomic nervous system and the response to skin-to-skin care. The following research questions guided this study:
| Design and Methods |
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Heart period variability was used to compare VLBW infants physiologic stability during skin-to-skin holding and incubator care.
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Sample and Setting
A purposive sample of 14 infants in a level III neonatal intensive care unit at the University of Utah Hospitals and Clinics was used.1 In the planning phase of the study, a projection indicated that a sample size of 13 infants was necessary to detect a medium effect size of 0.56 with a power of 80% at an
threshold of .05. This sample size was based on a power analysis that assumed a repeated-measures analysis and a mean correlation among heart period measures of 0.80.23 The more conservative sample size of 14 was used. Inclusion and exclusion criteria are in Table 1
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Procedure and Data Collection
Approval was obtained from the institutional review board before the start of the study. Informed consent was obtained from the mother of each infant no earlier than 10 days after delivery of the infant. Only mothers were selected for the skin-to-skin care intervention, in an effort to control for physical differences between mothers and fathers, which may influence infants responses to skin-to-skin care. For each infant, the study protocol was started when the infant weighed at least 750 g.
Each morning before data collection, the electrocardiographic electrodes were replaced with new electrodes (Klear-Trace No. 4800-S; CAS Medical Systems, Inc, Branford, Conn). Two electrodes were placed on the thorax, 1 at the right midclavicular line just below the clavicle and 1 at the left midclavicular line lateral to the left nipple. The ground lead was placed on the infants abdomen in the left-lower quadrant. The leads were adjusted on the thorax until an axis providing a clear signal was achieved.
Heart period (interbeat interval) data were acquired in multiple 300-second epochs at a frequency of 5 Hz (ie, 5 times per second) during each study day. The sampling rate was determined by using the Nyquist theorem24 and previous knowledge of the typical range of heart rates for VLBW infants. Four 300-second epochs of heart period were acquired at 30-minute intervals around 3 consecutive feeding times for a total of 12 heart period epochs each study day. A total of 48 heart period epochs were acquired for each infant, 24 during the skin-to-skin care phase and 24 during the incubator phase.
During the skin-to-skin care phase of the protocol, infants were held during the midday feeding. For example, an infant fed at noon was transferred to the mother at 11:15 AM and was held until 1:15 PM. Thus, 1 heart period epoch was collected 30 minutes before feeding, 1 epoch during the feeding, and 2 epochs after the feeding. Feedings were either 24-calorie premature formula or 24-calorie breast milk fortified with human milk fortifier. Feedings were warmed in a water bath per the standard of care of the neonatal intensive care unit and were given via nasal or oral gastric tubes. Feedings were via gravity and lasted 20 to 30 minutes. When the infants were in the incubators, nurses gave the feedings. During incubator care, infants were positioned prone on the mattress with their heads positioned to the side and elevated. Mothers were present only during skin-to-skin holding. A standardized transfer protocol was used to transfer infants to and from the incubator during the skin-to-skin care phase of the study.25 Each infant was prone and upright on the mothers chest during skin-to-skin care, with the infants head turned to one side; the infant remained in that position for the duration of skin-to-skin holding.
Statistical Methods
Data were analyzed by using S-PLUS 200026 and SPSS 10.0 for Windows.27 Demographic data were analyzed by using SPSS 10.0 to determine measures of central tendency and dispersion.
Heart period data were examined for aberrant data caused by signal interruption or electronic noise. Aberrant data points were isolated and were deleted from the data file as recommended by Kamath and Fallen.28 Deletion and local interpolation of small sections of grossly aberrant data for heart period were used rather than mean substitution, because surrounding interbeat intervals are better predictors of individual heart periods than are regional means or medians.29 The mean amount of aberrant data in all of the heart period files was 1.1%, less than the recommended threshold of no greater than 20%.30 After the data were cleaned, each heart period epoch used in the analysis was 256 seconds long.20
Time-domain and frequency-domain (spectral) analyses of heart period were done by using S-PLUS 2000. Time series plots of the interbeat intervals across time were generated for each heart period epoch for each infant. Power spectral density plots were generated from each epochs 1280-point time series data for heart period by using an autoregressive spectral model with a fixed model order of 30.31 The autoregressive model was selected over its common alternative, the Fourier model, because autoregressive models tend to be more statistically stable when applied to short time series.31 Akaike information criterion analyses31 were done for each epochs time series, and the resulting estimates of optimal model order for the individual segments ranged from 11 to 28. For consistency, a fixed model order of 30 was then used for the autoregressive analyses of all the segments. Although this value might be considered a relatively high model order for an autoregressive analysis, the ratio of data points to coefficients (1280/30 = 42.7) in each segment is large enough to make reliance on asymptotic statistical theory credible. The power spectral density graph is a type of variance histogram that depicts the strength of physiological rhythms (y-axis) as a function of their periodicity or frequency (x-axis).31 The y-axis can be expressed in natural power/variance units (for heart period time series, typically in milliseconds squared), or logarithmic units (log of milliseconds squared, or decibels: dB [ms2] = 10 x log10[ms2]). The amount of power in the low- and high-frequency regions was obtained from the power spectral densities by integrating the power within the bands. These within-subject summaries were further analyzed in a multi-subject design by using repeated-measures multivariate analysis of variance (MANOVA) in SPSS 10.0.
| Results |
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Of the 14 infants, 11 were white and 3 were of mixed ethnicity. All infants were cared for in double-walled incubators with a mean air temperature in the incubators of 30.9°C (SD = 1.1°C) during both phases of the study. Characteristics of the infants did not differ significantly between crossover order groups (Table 2
).
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Repeated-Measures MANOVA. Heart period data were analyzed for differences between the 2 phases and among 6 periods by using repeated-measures MANOVA. Aggregated means of power in the low-frequency region, power in the high-frequency region, and the ratio of low- to high-frequency power for 14 infants were entered into the repeated-measures MANOVA model. Crossover order was entered into the analysis as a between-subjects factor. No significant crossover-order effect was detected; therefore, crossover order was removed from further analyses.
The repeated-measures omnibus multivariate F test revealed no significant within-subjects effects of phase (incubator care vs skin-to-skin care: F3,11 = 1.77, P > .05), time (morning, midday, afternoon: F6,8 = 5.47, P > .05), or phase by time interaction (F6,8 = 2.62, P > .05) on mean low-frequency power, mean high-frequency power, or mean ratio of low- to high-frequency power. The mean low-frequency power, the mean high-frequency power, and the mean ratio of low- to high-frequency power were higher during skin-to-skin care than during incubator care, but this difference was not significant.
Mean low-frequency power was 124.6 ms2 (SEM = 52.0 ms2) during skin-to-skin care, 70.3 ms2 (SEM = 18.0 ms2) during incubator care before skin-to-skin care, and 71.4 ms2 (SEM = 17.8 ms2) during incubator care after skin-to-skin care (Figure 4
). Mean low-frequency power during the incubator phase was between 51.9 ms2 (SEM = 8.4 ms2) and 61.7 ms2 (SEM = 9.1 ms2).
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Because of the influence of gestational age on maturation of the autonomic nervous system, the infants were grouped by corrected gestational age. Heart period data were subsequently analyzed across corrected gestational age groups during incubator care and skin-to-skin care. The corrected gestational age groups were (1) 28 to 29 weeks (n = 3), (2) 30 to 31 weeks (n = 8), and (3) 32 to 34 weeks (n = 3). Mean low- and high-frequency power were similar across all time periods in the 28 to 29 weeks old group and the 30 to 31 weeks old group. The mean low- and high-frequency power and the mean ratio of low- to high-frequency power were higher during incubator care and skin-to-skin care in the 32 to 34 weeks old group than in the 28 to 29 weeks old group or the 30 to 31 weeks old group (Table 3
). None of these differences were significant. These results are most likely due to the small numbers of infants in each gestational age group and the large variances among the low-and high-frequency regions.
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| Discussion |
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The infants in the study did not have any significant differences in heart period variability between incubator care and skin-to-skin care. A number of factors may have influenced these results. First, the low-frequency region of heart period variability is influenced not only by the sympathetic branch of the autonomic nervous system, but somewhat by the parasympathetic branch.22 Second, body temperature, sleep state, and the infants position, respiration, and gestational age may influence heart period variability through the effect they have on the autonomic nervous system.13,20,33 The potential effect of these variables on the autonomic nervous system as measured by heart period variability are addressed in the following paragraphs.
The infants in the study had significantly higher body temperature and fraction of inspired oxygen required during skin-to-skin care than during standard incubator care, along with lower (albeit not significantly lower) oxygen saturation.1 Increased environmental air temperature increases infants central and peripheral body temperatures, with a concurrent increase in low-frequency power.34 The increase in low-frequency power during periods when the infants body temperatures were higher suggests increased activity from the sympathetic nervous system. The ratio of low- to high-frequency power is useful in determining balance between the sympathetic and parasympathetic branches of the autonomic nervous system. The ratio of low- to high-frequency power was minimal at environmental temperatures that maintain infants temperatures within the low normal range.34 A temperature stimulus applied to extremities of premature infants increases power within the heart period power spectra, suggesting entrainment of the autonomic nervous system to external thermal stimuli.35,36 However, a temperature stimulus alters peripheral vasomotor tone, which may also influence power in the heart period power spectra. Infants in the study reported here had increased low-frequency power during periods of increased temperature, similar to findings in previous studies, suggesting increased sympathetic activity.
In one study,37 during deep sleep, healthy infants and children had increased power in the high-frequency region, suggesting dominant parasympathetic tone during this stage of sleep. Porges et al38 concluded that infants have greater vagal tone during quiet sleep, with a decrease in vagal activity as active sleep occurs. Infants in my study were in an irregular sleep state during the periods that heart period was measured in both phases of the study.25 Irregular sleep state was defined as irregular breathing with no movement or slight movement of the forearm, lower leg, toes, hands, or fingers.25 It is not surprising that the power within the high-frequency region was similar, because of the similarity in sleep states across all periods. However, sleep state does not account for the differences in variance across all time periods, specifically, the increased variance in heart period during skin-to-skin care compared with the other periods when the infants were in the incubator.
Differences in heart period variability were not found between skin-to-skin holdiing and incubator care.
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Infants have significantly less variability in heart period (ie, a significantly smaller SD) when positioned prone than when positioned supine.39 Although the variability in heart period differed, the variability was not quantified by frequency region, which made extrapolation of the findings to maturation of the autonomic nervous system difficult. Infants in my study were positioned upright on their mothers chests during skin-to-skin care, a position different from the slight elevation of the head of the bed while the infants were in the incubators. Further study of the effect that an infants position has on heart period variability is needed before conclusions can be drawn about the effect of position on heart period.
Gestational age influences heart period variability. Premature infants between 31 and 36 weeks corrected gestational age have less power in the low-frequency region than do term infants.21 Chatow et al20 described the increase in heart period variability, specifically vagal tone, in premature infants as the infants approach term. My results contribute to the knowledge that as an infants gestational age approaches term, vagal tone increases, thus promoting balance between the sympathetic and parasympathetic branches of the autonomic nervous system.
Heart period variability is influenced by respiration and mechanical ventilation.4,4043 Frazier et al41 reported that heart period variability in the low-frequency range increased significantly, with a concurrent decrease in power in the high-frequency range, in dogs treated with a combination of positive pressure and continuous positive airway pressure. Preterm infants in my study all received pressure-support ventilation with positive end-expiratory pressure. These infants had similar variabilities in heart period, except for the infants of 32 to 34 weeks gestational age, who had greater variability than the other infants. The infants of younger gestational age may be more sensitive than the infants of older gestational age to the influence of mechanical ventilation on heart period variability. However, this area of research must yet be explored. Heart period variability in the low-frequency region is influenced by the severity of respiratory distress in preterm infants, whereas ventilator rate reportedly influences the high-frequency region of heart period variability.42 Infants in my study were all receiving mechanical ventilation, which probably influences the power within the low- and high-frequency regions of heart period variability.
| Limitations and Recommendations |
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The second limitation of the study is the number of infant covariates, such as temperature, oxygenation, position, gender, feeding, and awake-sleep state. These variables may have influenced the amount of power in the low- and high-frequency regions at any given time. A secondary analysis of the relationship between the confounding variables and heart period variability is needed to determine which variables have the strongest relationship to heart period variability and to identify the region (low or high frequency) of influence.
| Conclusions |
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This study is a beginning step in identifying ways to specifically and accurately assess stressful events in VLBW infants.
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| ACKNOWLEDGMENTS |
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Commentary by Mary Jo Grap (see shaded boxes).
To purchase reprints, contact The InnoVision Group, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 809-2273 or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, reprints{at}aacn.org.
| REFERENCES |
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This article has been cited by other articles:
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M. Neu, M. L. Laudenslager, and J. Robinson Coregulation in Salivary Cortisol During Maternal Holding of Premature Infants Biol Res Nurs, January 1, 2009; 10(3): 226 - 240. [Abstract] [PDF] |
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S L Smith, A K Doig, and W N Dudley Impaired parasympathetic response to feeding in ventilated preterm babies Arch. Dis. Child. Fetal Neonatal Ed., November 1, 2005; 90(6): F505 - F508. [Abstract] [Full Text] [PDF] |
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