Neonatal Heart Rate Variability Research Articles

Normalization of Autonomic Function in Children With Coarctation of the Aorta After Surgical Correction in Infancy

To the Editor: Systemic hypertension affects ≥20% of patients with coarctation of the aorta (CoA) by adolescence, despite early surgical repair.1 This leads to premature death and is arguably the most important outcome variable in these patients. We have previously demonstrated reduced spontaneous baroreceptor reflex sensitivity (BRS) and heart rate variability (HRV) in preoperative neonates with CoA compared with age-matched controls, suggesting early autonomic dysfunction.2 Altered BRS has also been demonstrated in older children after late surgical repair,3 however, little is known about BRS and autonomic function in younger patients after successful neonatal repair. In the current study, we re-evaluated spontaneous BRS, HRV, and blood pressure (BP) variability (BPV) from our initial cohort at 5 years on to determine whether there was persisting abnormality of cardiovascular autonomic variables as a precursor to arterial hypertension. We re-examined 6 of the 7 living CoA patients and 7 of the 12 living age- and sex-matched control patients from the initial cohort. The remaining 5 controls could no longer be traced, and 1 CoA patient was not included because of severe developmental delay. None of the subjects were taking medications. …

Effect of Phototherapy on Neonatal Heart Rate Variability and Complexity

Background: Phototherapy is a common mode of treatment for neonatal hyperbilirubinemia. However, phototherapy has been reported to alter cardiovascular function by causing increased peripheral blood flow, diminished cardiac output and increased sympathetic activity that may be of concern particularly in sick or premature newborns. The effects of phototherapy on the autonomic nervous system modulation of heart rate in term neonates have not yet been investigated. Objectives: The aim of the present study was to investigate the effects of phototherapy on the autonomic nervous system modulation of heart rate in healthy full-term jaundiced neonates. Methods: 30 full-term jaundiced infants were prospectively studied before and during phototherapy. Heart rate variability was analyzed with conventional time-domain, spectral, and time-dynamic techniques by using Poincaré plots. Results: Phototherapy was found to cause significant diminution in the short- and long-term variability of heart rate in newborns as documented by time-domain analysis of heart rate variability, and visually demonstrated by using Poincaré plots. Spectral indices and heart rate were unchanged during phototherapy. Conclusions: A significant diminution in heart rate variability was documented during phototherapy, a phenomenon assumed to be centrally mediated. The reasons for this decrease are yet unknown. The use of time-dynamic analysis methods may offer important details on the newborn’s physiology that cannot be revealed by traditional methods.

Time-variant parametric estimation of transient quadratic phase couplings between heart rate components in healthy neonates

The heart rate variability (HRV) can be taken as an indicator of the coordination of the cardio-respiratory rhythms. Bispectral analysis using a direct (fast Fourier transform based) and time-invariant approach has shown the occurrence of a quadratic phase coupling (QPC) between a low-frequency (LF: 0.1 Hz) and a high-frequency (HF: 0.4-0.6 Hz) component of the HRV during quiet sleep in healthy neonates. The low-frequency component corresponds to the Mayer-Traube-Hering waves in blood pressure and the high-frequency component to the respiratory sinus arrhythmia (RSA). Time-variant, parametric estimation of the bispectrum provides the possibility of quantifying QPC in the time course. Therefore, the aim of this work was a parametric, time-variant bispectral analysis of the neonatal HRV in the same neonates used in the direct, time-invariant approach. For the first time rhythms in the time course of QPC between the HF component and the LF component could be shown in the neonatal HRV.

Heart rate variability during extracorporeal membrane oxygenation and recovery in severe neonatal disease

Background Heart rate variability (HRV) reveals information on the functional state of the autonomic nervous system (ANS) in neonates. During severe illness, heart rate variability is impaired. Aim This study was initiated to measure the changes in HRV in neonates during extracorporeal membrane oxygenation (ECMO) and recovery from severe respiratory and circulatory failure. Moreover, we compared our data with HRV data of healthy newborns and we investigated the differences in HRV parameters between ECMO-survivors and non-survivors. Study design This study is of an observational character. We performed short-term recordings of heart rate variability in 14 neonates during ECMO and recovery. We computed time- and frequency-domain HRV parameters. Results ECMO significantly affects time-domain HRV parameters. Severe neonatal illness causes a significant reduction of all calculated HRV parameters; clinical recovery is accompanied by an increase of HRV. In comparison with normative data of healthy newborns, however, HRV remains impaired. The ECMO–development ratio separated the non-survivors from the survivors during ECMO therapy. Conclusions During severe neonatal illness, HRV is impaired. It remains to be clarified whether the impairment of HRV during severe illness can predict the neurological outcome. The ability of the E/D ratio as an HRV parameter to serve as a predictive tool has to be corroborated in larger group of patients.

Short term heart rate variability in healthy neonates: Normative data and physiological observations

The measurement of heart rate variability (HRV) reveals information on the functional state of the autonomic nervous system (ANS). Moreover, several diseases are known to be accompanied by a reduction in HRV. Currently, there are no data on HRV within larger samples of healthy neonates. This study was initiated to establish normative data of HRV parameters and to assess physiological observations in healthy newborn infants. We performed 10 min recordings of HRV in 80 healthy neonates. We computed time domain parameters. Furthermore power spectrum analysis was calculated by Fourier Transformation in 3 frequency bands. The total power as well as the peak frequencies was estimated for each band. The normative data of each HRV parameter for healthy newborns are presented as mean, standard deviation and the 5th and 95th percentiles. Increasing postnatal age is accompanied by a significant (p<0.05) elevation of HRV parameters. Baroreceptor loop fluctuations were delayed from 0.1 Hz (adults) to 0.07 Hz in healthy newborns. A respiratory peak according to respiratory sinus arrhythmia (RSA) as it is common in adults was not detectable. Normative data of HRV allows the interpretation of clinical data in neonatal diseases affecting the ANS. Moreover, we observed physiological deviations in healthy newborns in comparison to adults.

Customized spectral band analysis compared with conventional Fourier analysis of heart rate variability in neonates

A customized filtering technique is introduced and compared with fast Fourier transformation (FFT) for analyzing heart rate variability (HRV) in neonates from short-term recordings. FFT is classically the most commonly used spectral technique to investigate cardiovascular fluctuations. FFT requires stability of the physiological signal within a 300 s time window that is usually analyzed in adults. Preterm infants, however, show characteristics of rapidly fluctuating heart rate and blood pressure due to an immature autonomic regulation, resulting in non-stationarity of these signals. Therefore neonatal studies use (half-overlapping or moving) windows of 64 s length within a recording time of 2–5 min. The proposed filtering technique performs a filtering operation in the frequency range of interest before calculating the spectrum, which allows it to perform an analysis of shorter periods of only 42 s. The frequency bands of interest are 0.04–0.15 Hz (low frequency, LF) and 0.4–1.5 Hz (high frequency, HF). Although conventional FFT analysis as well as the proposed alternative technique result in errors in the estimation of LF power, due to spectral leakage from the very low frequencies, FFT analysis is more sensitive to this effect. The response times show comparable behavior for both the techniques. Applying both the methods to heart rate data obtained from a neonate before and after atropine administration (inducing a wide range of HRV), shows a very significant correlation between the two methods in estimating LF and HF power. We conclude that a customized filtering technique might be beneficial for analyzing HRV in neonates because it reduces the necessary time window for signal stability.

Spectral Analysis of Heart Rate Variability: An Emerging Tool for Assessing Stability During Transition to Extrauterine Life

Transition from fetal to neonatal life is likely the most physiologically demanding time of life. Complex changes in major organ system functioning and reorganization of metabolic processes must occur rapidly to achieve postnatal homeostasis. Identifying the neonate with subtle signs of unsuccessful transition is a challenge to the perinatal health care provider. Alterations in fetal or neonatal heart rate and heart rate variability may serve as an indicator of the neural control influencing cardiac function and a sensitive indicator of compromised health. Evaluation of the neural control of the heart can be done noninvasively and provides a discriminating measure of the level of stress vulnerability the fetus or newborn may be experiencing. This article reviews the origins of physiological variability of the fetal and neonatal heart rate in the transition to extrauterine life. The technique of spectral analysis as a new tool for surveillance of the at-risk fetus and neonate is then introduced, and implications for clinical practice and future research avenues are discussed.

Nonlinear analysis of heart rate variability in infants with apparent life-threatening events.

Some studies have shown that neonates having experienced an Apparent Life-Threatening Event (ALTE) have an increased risk of dying of the Sudden Infant Death Syndrome (SIDS). In this study the heart rate variability in neonates has been analyzed through a study of the long range correlations and scale invariance (self-similarity) in their cardiac rhythm. The goal is to see whether it is possible to distinguish normal infants from infants with ALTEs using the previously mentioned nonlinear measures of the heart rate variability. Twelve ALTE infants are included in this study. To determine the degree to which these neonates suffer from ALTEs two examinations are performed: a polysomnography and home monitoring. Using the nonlinear measures obtained from the nonlinear analysis of the heart rate variability, the group suffering most from ALTEs can clearly be separated from the other neonates.

Method for non-invasively recording electrocardiograms in conscious mice.

The rapid increase in the development of mouse models is resulting in a growing demand for non-invasive physiological monitoring of large quantities of mice. Accordingly, we developed a new system for recording electrocardiograms (ECGs) in conscious mice without anesthesia or implants, and created Internet-accessible software for analyzing murine ECG signals. The system includes paw-sized conductive electrodes embedded in a platform configured to record ECGs when 3 single electrodes contact 3 paws. With this technique we demonstrated significantly reduced heart rate variability in neonates compared to adult mice. We also demonstrated that female mice exhibit significant ECG differences in comparison to age-matched males, both at baseline and in response to beta-adrenergic stimulation. The technology we developed enables non-invasive screening of large numbers of mice for ECG changes resulting from genetic, pharmacological, or pathophysiological alterations. Data we obtained non-invasively are not only consistent with what have been reported using invasive and expensive methods, but also demonstrate new findings regarding gender-dependent and age-dependent variations in ECGs in mice.

Technique for the quantification of transient quadratic phase couplings between heart rate components.

A technique for the time-variant analysis of quadratic phase coupling (QPC) in heart rate data is introduced and tested in 6 human neonates during quiet sleep. The set up of the approach is based up on the assumption that QPCs in the heart rate variability (HRV) are related to amplitude modulation effects. The application of the biamplitude deals with the detection of the coupling pattern and the bicoherence is used for the statistical quantification of coupling. By means of the results of bispectral analysis the time-variant processing has been adapted. The frequency-selective complex demodulation of the HRV leads to the envelope of the respiratory sinus arrhythmia (RSA), this has been used as one input for a time-variant coherence analysis. The other input is the low-pass filtered 10-second-rhythm of the HRV. A time-continuous quantification of the QPC, caused by amplitude modulation (10-second-rhythm modulates the RSA), is possible using this approach. According to our observed results in neonatal HRV both a phase co-ordination between the 10-second-rhythm and RSA as well as a non-linear coupling (amplitude modulation) between these HRV components can be seen.

Heart rate variability in the neonate and infant: analytical methods, physiological and clinical observations

Naturally occurring oscillations in heart rate have long been considered to reflect the modulating influences of the autonomic nervous system. Individual reports of heart rate variability in healthy and sick neonates and infants have provided valuable information as to pathophysiological changes in autonomic cardiovascular control. It is evident that prematurity and poor health are reflected in attenuated heart rate variability. However, at present, there are few standard criteria for the analysis of heart rate variability, preventing precise comparisons among the various studies. Until recommendations for standardized analytical methods are made, clinical application of heart rate variability in neonatal and infant prognosis and therapy remains premature. □Heart rate variability, infant, maturation, neonate, power spectrum analysis, respiratory distress, sleep state, sudden infant death syndrome

The effect of thermal stimulation on the heart-rate variability in neonates.

Thermoregulation in humans can be divided into three broad mechanisms of control, namely: shivering, sweating and vasomotor activity. Previous investigations suggested the presence of an autonomic rhythm, originating in the central nervous system, possibly related to thermal vasomotor control and directly affecting heart rate by reflex changes in cardiac sympathetic and parasympathetic activity. The objective of the present work was to study the maturation process of the thermoregulatory system in newborns. We used peripheral thermal entrainment and focused on the reflections of vasomotor control in the heart-rate (HR) power spectrum (PS). The study included three groups of neonates at three different ages: 10 premature infants, 6 full-terms and 7 older infants (4 to 6 months). Thermal stimulation was achieved by placing a hot and cold surface on the subject's right palm alternately at three different rates: replacing the touching surface every 4 s (0.25 Hz), 7 s (0.14 Hz) and 10 s (0.1 Hz). 'Double period' stimulation was defined as the total duration of each period of hot and cold stimulation at the three rates, namely 8 s (0.125 Hz), 14 s (0.07 Hz), 20 s (0.05 Hz). The ECG of every infant was measured and recorded during the various stages of the experiment. The HR power spectrum from 0.02 Hz up to 2.00 Hz was considered, focusing on narrow ranges around the thermal stimulation frequencies. We found that in most subjects, clear peaks arise in the HR PS at the thermal entrainment frequency and its corresponding half frequency ('double period'). In premature infants, the reaction is best in response to the longest (10 s) stimulus (9 out of 10 prematures reacted positively), in group B (full-term infants) the reaction responds best to the 7-s stimulus (6 out of 6 reacted) and in older infants the reaction is slightly better at the 4-s stimulus. Since sympathetic control is slower, this ability to entrain the control system at increasing frequencies, might be related to the gradual maturation of parasympathetic control after birth. The different reaction of the three groups may help to understand the maturation process of the thermoregulation system.

Probing the order within neonatal heart rate variability.

The mechanism by which heart rate variability (HRV) changes during neonatal illness is not known. One possibility is that reduced HRV is merely a diminished or scaled-down version of normal. Another possibility is that there is a fundamental change in the mechanism underlying HRV, resulting in a change in the ordering of RR intervals. We investigated the nature and extents of order in RR interval time series from 25 Neonatal Intensive Care Unit patients with a spectrum of clinical illness severity and HRV. We measured predictability (deviation of predicted intervals from observed), and regularity (measured as approximate entropy) of RR interval time series showing different degrees of HRV. In RR interval time series where the effects of scaling were removed, we found 1) records showing normal HRV had more order than those showing low HRV; 2) the nature of the order was more like that of a periodic process with frequencies over a large range (time series whose log-log power spectrum had a 1/f distribution) than that of chaotic one (logistic map); and 3) the nature of order did not change greatly as HRV fell. We conclude that neonatal RR interval time series are ordered by periodic processes with frequencies over a large range, and that the extent of order is less during illness when HRV is low.

Quantification of Neonatal Heart Rate Variability From 26-35 Weeks Post-Conceptional Age Using the Fractal Dimension as Estimated by Dispersional Analysis 1172

Quantification of Neonatal Heart Rate Variability From 26-35 Weeks Post-Conceptional Age Using the Fractal Dimension as Estimated by Dispersional Analysis 1172

NEONATAL HEART RATE VARIABILITY CORRELATES WITH CLINICAL ILLNESS SEVERITY SCORES. † 1253

Heart rate variability (HRV) increases several-fold in newborn infants who recover from severe cardiorespiratory failure. To test further the hypothesis that neonatal HRV is an index of illness severity, we measured both HRV and an illness severity score at 81 times in 45 infants in the NICU. Heart rate and HRV were measured at 32 beat intervals over a 2 hour period: HRV is represented by coefficient of variation (CV; S.D./mean) of a moving window of 2048 beats. Clinical illness severity was determined using the Score for Acute Neonatal Physiology and Neonatal Therapeutic Intervention Scoring System. The plots relate heart rate and HRV to the sum of the two clinical scores. The top plot shows no correlation of heart rate with illness severity (p=NS; Pearson product moment correlation). The bottom plot, on the other hand, shows strong inverse correlation of HRV and illness severity (r=0.7; p< 10-6); as the illness severity increased, HRV decreased. We conclude that HRV correlates well with the severity of neonatal illness, while heart rate itself does not.Figure

Scaling and ordering of neonatal heart rate variability.

By analyzing cardiac beat-to-beat intervals and interbeat increments, we find that---unlike adults---the difference in the pattern of interbeat increments in healthy and sick newborn infants is more due to a change in the amplitude and much less to a change in the ordering of the interbeat increments. This suggests that very low-frequency elements of neonatal and adult heart rate variability rise from fundamentally different mechanisms.

The influence of artificial ventilation on heart rate variability in very preterm infants.

To study the influence of artificial ventilation rate on neonatal heart rate variability (HRV), ECG and respiratory impedance curves were recorded four times a day in 20 preterm infants (< 33 wk) during the first 3 d after birth while the infants were ventilated at a wide range of ventilator rates. The contents of selected frequency bands within the R-R interval power spectrum were calculated for 3-min periods. Respiratory distress syndrome severity was assessed at each measurement. Respiratory sinus arrhythmia (RSA) induced by the ventilator appeared to mimic spontaneous RSA. As in spontaneous respiration, the amount of RSA (power in a frequency band around the respiratory rate) increases as the ventilation rate decreases. This phenomenon is most probably due to entrainment with baroreflex-related fluctuations in the heart rate. Although the artificial ventilation rate influences RSA and thus high-frequency HRV, an increase in respiratory distress syndrome severity results in a decrease in low-frequency HRV. Thus, the attenuation of low-frequency HRV by respiratory distress syndrome is not likely to be due to artificial ventilation.

Continuous monitoring of heart rate variability in preterm infants

A method for continuous monitoring and recording of neonatal heart rate variability (HRV) and further physiological parameters in the intensive care unit is presented: 16 neonatal monitors were connected via two input/output processor boards to a personal computer. Patient data were processed by special software. Every day a 24-h record was printed for each infant, including a continuous registration of long-term (LTV) and short-term variability (STV) of heart rate along with baseline heart rate, respiratory rate, body temperature, temperature of the incubator and transcutaneous partial pressures of oxygen and carbon dioxide (tcPO 2 and tcPCO 2). For each parameter automatic artefact removal was implemented. Median and percentiles were computed once daily from all valid values. The influence of gestational and postnatal age and of respiratory distress syndrome (RDS) on HRV was studied in 105 preterm infants below 33 weeks of gestation during the first 7 days of life. An increase of both LTV and STV was seen with increasing gestational and postnatal age. In infants with RDS a decreased LTV was found in relation to the severity of the disease. HRV was also decreased in impaired brain function due to intraventricular hemorrhage, asphyxia or sedative treatment.

Heart rate variability in neonates with hyaline membrane disease: a longitudinal study: C.R. Thompson a, J.S. Brown b, H. Gee b, E.W. Taylor a, aSchool of Biological Sciences, bDepartment of Fetal Medicine, University of Birmingham, Birmingham, B15 2TT, UK

Heart rate variability in neonates with hyaline membrane disease: a longitudinal study: C.R. Thompson a, J.S. Brown b, H. Gee b, E.W. Taylor a, aSchool of Biological Sciences, bDepartment of Fetal Medicine, University of Birmingham, Birmingham, B15 2TT, UK

85 Assessment of Differences Between Fetal and Neonatal Heart Rate Variability by Power Spectral Analysis

85 Assessment of Differences Between Fetal and Neonatal Heart Rate Variability by Power Spectral Analysis