Longitudinal assessment of heart rate variability in very low birth weight infants during their NICU stay☆
Introduction
Heart rate variability (HRV) reflects autonomic responses to different stimuli and conditions [1]. The most prominent of these conditions is the influence of breathing on the change in interbeat intervals [2], also known as the respiratory sinus arrhythmia (RSA). It has been classically described as the effect on reflex centers from lung, atrium or the aortic stretch sensors, but it might also be due to coupling of respiratory and cardiac vagal medullary motoneurons [3]. Heart period variability reflects the balance between the parasympathetic and sympathetic branches of the autonomic nervous system. Short-term variability, i.e., the change in successive interbeat intervals, is thought to be a result of innervation by the vagal nerve [4], [5].
Although frequently used as an indicator of physiologic 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 (VLBW) infants. Heart period variability, used as a method to measure physiologic stability, may provide more specific and more sensitive information about stressful events in VLBW infants and the impact of different treatments in this population [6], [7]. Both short- and long-term stabilities have been shown for HRV measurements [8]. Heart rate variability and cardiac vagal tone at birth have been associated with better long-term outcomes in cognitive processing, social skills, motor skills and behavioral adjustment [9], [10], [11], [12]. Hanna et al. [13] showed that HRV was correlated to the type of brain injury, length of hospital stay and neurodevelopmental function assessed at 1 year of age in VLBW infants from 32 to 37 weeks of corrected gestational age. Griffin et al. [14] showed that HRV could be used as a tool to monitor and identify premature infants at risk for sepsis or sepsis like illness. Low levels of HRV may also serve as an indicator of outcome in congenital diaphragmatic hernia [15].
Heart rate variability has been evaluated in several studies in relatively stable preterm infants > 30 weeks post-menstrual age [2], [9], [10], [11]. It was suggested from cross sectional data that the high frequency (HF) power or vagal tone progressively increased with increasing gestational age past 32 weeks [9]. Longitudinal studies following fetal HRV during pregnancy have reached diverse conclusions. One group [16] found that spectral power in the band between 0.003 and 1.0 Hz increased until the 32nd week after which the rate of increase in power slowed substantially, while others [17], [18] have found progressively increasing power in the low frequency (LF) band suggesting maturing sympathetic system and decreasing power in the HF band during the third trimester. Heart rate variability, has not been longitudinally evaluated in critically ill VLBW infants < 30 weeks post-menstrual age from birth through discharge. Also, the effect of intubation on HRV is not known. The objective of this study was to characterize developmental changes in the autonomic nervous system activity of sick VLBW infants from 23 weeks through 38 weeks post-menstrual age or hospital discharge by measuring HRV.
Section snippets
Methods
This was a prospective cohort study following VLBW (< 1500 g) infants from 23 to 38 weeks post-menstrual age. All infants admitted to Children's Memorial Hermann Hospital NICU < 30 weeks post-menstrual age at birth were eligible for the study except those with major congenital anomalies. Following informed consent, infants were enrolled in the study within 72 h of birth and then longitudinally followed weekly through 30 weeks and biweekly thereafter. Infants were studied between 2 and 6 a.m.
Results
The study cohort consisted of 38 high-risk VLBW infants. Their demographics are shown in Table 1. In 1 of the 38 infants, reliable data was available only for one recording, so the subject was not included in the longitudinal analysis. The analysis is based on 201 data sets from 37 infants. Infants were intubated during collection of 92 data sets and were breathing without assistance for the other 109 recordings. Intubated VLBW infants had median intubation duration of 40 days (mean = 57 days;
Significance
Our study characterized heart rate variability in high-risk very premature infants. Longitudinal and cross-sectional analyses agree with the fetal data from term deliveries that LF power increases with increasing post conceptional age [16], [17], [18]. The rate of increase of LF power is 0.50 dB/week. However, our data showed a non-significant, mild rather than the marked increase in HF power past 32 weeks that had been previously shown by other authors [9], [29]. Specifically, HF power
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Supported by NICHD R01 HD42639 and R01 HD36767.