Phase-rectified Signal Averaging Research Articles

The impact of controlled breathing on autonomic nervous system modulation: analysis using phase-rectified signal averaging, entropy and heart rate variability

Objective.The present study investigated how breathing stimuli affect both non-linear and linear metrics of the autonomic nervous system (ANS).Approach.The analysed dataset consisted of 70 young, healthy volunteers, in whom arterial blood pressure (ABP) was measured noninvasively during 5 min sessions of controlled breathing at three different frequencies: 6, 10 and 15 breaths min-1. CO2concentration and respiratory rate were continuously monitored throughout the controlled breathing sessions. The ANS was characterized using non-linear methods, including phase-rectified signal averaging (PRSA) for estimating heart acceleration and deceleration capacity (AC, DC), multiscale entropy, approximate entropy, sample entropy, and fuzzy entropy, as well as time and frequency-domain measures (low frequency, LF; high-frequency, HF; total power, TP) of heart rate variability (HRV).Main results.Higher breathing rates resulted in a significant decrease in end-tidal CO2concentration (p< 0.001), accompanied by increases in both ABP (p <0.001) and heart rate (HR,p <0.001). A strong, linear decline in AC and DC (p <0.001 for both) was observed with increasing breathing rate. All entropy metrics increased with breathing frequency (p <0.001). In the time-domain, HRV metrics significantly decreased with breathing frequency (p <0.01 for all). In the frequency-domain, HRV LF and HRV HF decreased (p= 0.038 andp= 0.040, respectively), although these changes were modest. There was no significant change in HRV TP with breathing frequencies.Significance.Alterations in CO2levels, a potent chemoreceptor trigger, and changes in HR most likely modulate ANS metrics. Non-linear PRSA and entropy appear to be more sensitive to breathing stimuli compared to frequency-dependent HRV metrics. Further research involving a larger cohort of healthy subjects is needed to validate our observations.

Maternal cardiorespiratory coupling: differences between pregnant and nonpregnant women are further amplified by sleep-stage stratification.

Pregnancy complications are associated with abnormal maternal autonomic regulation. Subsequently, thoroughly understanding maternal autonomic regulation during healthy pregnancy may enable the earlier detection of complications, in turn allowing for the improved management thereof. Under healthy autonomic regulation, reciprocal interactions occur between the cardiac and respiratory systems, i.e., cardiorespiratory coupling (CRC). Here, we investigate, for the first time, the differences in CRC between healthy pregnant and nonpregnant women. We apply two algorithms, namely, synchrograms and bivariate phase-rectified signal averaging, to nighttime recordings of ECG and respiratory signals. We find that CRC is present in both groups. Significantly less (P < 0.01) cardiorespiratory synchronization occurs in pregnant women (11% vs. 15% in nonpregnant women). Moreover, there is a smaller response in the heart rate of pregnant women corresponding to respiratory inhalations and exhalations. In addition, we stratified these analyses by sleep stages. As each sleep stage is governed by different autonomic states, this stratification not only amplified some of the differences between groups but also brought out differences that remained hidden when analyzing the full-night recordings. Most notably, the known positive relationship between CRC and deep sleep is less prominent in pregnant women than in their nonpregnant counterparts. The decrease in CRC during healthy pregnancy may be attributable to decreased maternal parasympathetic activity, anatomical changes to the maternal respiratory system, and the increased physiological stress accompanying pregnancy. This work offers novel insight into the physiology of healthy pregnancy and forms part of the base knowledge needed to detect abnormalities in pregnancy.NEW & NOTEWORTHY We compare CRC, i.e., the reciprocal interaction between the cardiac and respiratory systems, between healthy pregnant and nonpregnant women for the first time. Although CRC is present in both groups, CRC is reduced during healthy pregnancy; there is less synchronization between maternal cardiac and respiratory activity and a smaller response in maternal heart rate to respiratory inhalations and exhalations. Stratifying this analysis by sleep stages reveals that differences are most prominent during deep sleep.

Comparison of phase rectified signal averaging and short term variation in predicting perinatal outcome in early onset fetal growth restriction.

To compare short term variation (STV) and phase rectified signal averaging (PRSA) and their association with fetal outcome in early onset fetal growth restriction (FGR). Data were used from a retrospective cohort study of women who were admitted for FGR and/or pre-eclampsia and who were delivered by pre-labor Cesarean section or had a fetal death before 32 weeks' gestation. Computerized cardiotocography (cCTG) registrations of the 5 days before delivery or fetal death were used for calculation of STV and PRSA. PRSA was expressed as the average acceleration capacity (AAC) and average deceleration capacity (ADC). FHR decelerations were classified visually as absent, 1-2 per hour or recurrent. Abnormality of STV and of PRSA was either analyzed as a single parameter or in combination with recurrent decelerations. Endpoints were defined as composite adverse condition at birth consisting of fetal death, low Apgar score, low umbilical pH, the need for resuscitation after birth and as major neonatal morbidity or neonatal death. Included were 367 pregnancies of which 20 resulted in fetal death. An abnormal cCTG with either recurrent decelerations and/or low STV or recurrent decelerations and/or low PRSA were similarly associated with composite adverse condition at birth (n=99), but neither with major neonatal morbidity. PRSA and STV have similar efficacy for measuring fetal heart rate variation in early onset FGR. An increased risk of a composite adverse condition at birth is indicated by a low value of either parameter and/or the presence of recurrent decelerations.

Maternal autonomic responsiveness is attenuated in healthy pregnancy: a phase rectified signal averaging analysis.

Autonomic regulation is essential in enabling a healthy pregnancy. In fact, several pregnancy complications are associated with autonomic dysfunction. Better understanding of the maternal autonomic state during healthy pregnancy may aid in the early detection of such complications. One aspect of autonomic regulation is autonomic responsiveness, which can by assessed by phase rectified signal averaging (PRSA). While other areas of research have found blunted physiological responses in pregnancy, this paper presents the first investigation of maternal autonomic responsiveness as assessed by PRSA. We find significantly reduced rates of responses, as well as an attenuated capacity for heart rate acceleration when comparing pregnant women to non-pregnant controls. We hypothesize that this attenuated autonomic control may serve to protect the mother against her imbalanced autonomic state, as increased sympathetic and decreased parasympathetic modulation accompany healthy pregnancies. Clinical Relevance- Maternal autonomic responsiveness is attenuated in pregnancy in comparison to non-pregnant women. Understanding maternal autonomic state not only improves our knowledge of gestational physiology but also forms the basis for the early detection of pregnancy complications associated with maternal autonomic dysfunction.

IMPROVING PHASE-RECTIFIED SIGNAL AVERAGING FOR FETAL HEART RATE ANALYSIS.

Low umbilical artery pH is a marker for neonatal acidosis and is associated with an increased risk for neonatal complications. The phase-rectified signal averaging (PRSA) features have demonstrated superior discriminatory or diagnostic ability and good interpretability in many biomedical applications including fetal heart rate analysis. However, the performance of PRSA method is sensitive to values of the selected parameters which are usually either chosen based on a grid search or empirically in the literature. In this paper, we examine PRSA method through the lens of dynamical systems theory and reveal the intrinsic connection between state space reconstruction and PRSA. From this perspective, we then introduce a new feature that can better characterize dynamical systems comparing with PRSA. Our experimental results on an open-access intrapartum Cardiotocography database demonstrate that the proposed feature outperforms state-of-the-art PRSA features in pH-based fetal heart rate analysis.

The Reconstruction of Causal Networks in Physiology.

We systematically compare strengths and weaknesses of two methods that can be used to quantify causal links between time series: Granger-causality and Bivariate Phase Rectified Signal Averaging (BPRSA). While a statistical test method for Granger-causality has already been established, we show that BPRSA causality can also be probed with existing statistical tests. Our results indicate that more data or stronger interactions are required for the BPRSA method than for the Granger-causality method to detect an existing link. Furthermore, the Granger-causality method can distinguish direct causal links from indirect links as well as links that arise from a common source, while BPRSA cannot. However, in contrast to Granger-causality, BPRSA is suited for the analysis of non-stationary data. We demonstrate the practicability of the Granger-causality method by applying it to polysomnography data from sleep laboratories. An algorithm is presented, which addresses the stationarity condition of Granger-causality by splitting non-stationary data into shorter segments until they pass a stationarity test. We reconstruct causal networks of heart rate, breathing rate, and EEG amplitude from young healthy subjects, elderly healthy subjects, and subjects with obstructive sleep apnea, a condition that leads to disruption of normal respiration during sleep. These networks exhibit differences not only between different sleep stages, but also between young and elderly healthy subjects on the one hand and subjects with sleep apnea on the other hand. Among these differences are 1) weaker interactions in all groups between heart rate, breathing rate and EEG amplitude during deep sleep, compared to light and REM sleep, 2) a stronger causal link from heart rate to breathing rate but disturbances in respiratory sinus arrhythmia (breathing to heart rate coupling) in subjects with sleep apnea, 3) a stronger causal link from EEG amplitude to breathing rate during REM sleep in subjects with sleep apnea. The Granger-causality method, although initially developed for econometric purposes, can provide a quantitative, testable measure for causality in physiological networks.

A machine learning algorithm for electrocardiographic fQRS quantification validated on multi-center data

Fragmented QRS (fQRS) is an electrocardiographic (ECG) marker of myocardial conduction abnormality, characterized by additional notches in the QRS complex. The presence of fQRS has been associated with an increased risk of all-cause mortality and arrhythmia in patients with cardiovascular disease. However, current binary visual analysis is prone to intra- and inter-observer variability and different definitions are problematic in clinical practice. Therefore, objective quantification of fQRS is needed and could further improve risk stratification of these patients. We present an automated method for fQRS detection and quantification. First, a novel robust QRS complex segmentation strategy is proposed, which combines multi-lead information and excludes abnormal heartbeats automatically. Afterwards extracted features, based on variational mode decomposition (VMD), phase-rectified signal averaging (PRSA) and the number of baseline-crossings of the ECG, were used to train a machine learning classifier (Support Vector Machine) to discriminate fragmented from non-fragmented ECG-traces using multi-center data and combining different fQRS criteria used in clinical settings. The best model was trained on the combination of two independent previously annotated datasets and, compared to these visual fQRS annotations, achieved Kappa scores of 0.68 and 0.44, respectively. We also show that the algorithm might be used in both regular sinus rhythm and irregular beats during atrial fibrillation. These results demonstrate that the proposed approach could be relevant for clinical practice by objectively assessing and quantifying fQRS. The study sets the path for further clinical application of the developed automated fQRS algorithm.

Diagnosing antenatal fetal distress.

The values of acceleration capacity and deceleration capacity are known to capture fetal neurological development. The fetal growth restriction was found to be featured by decreased variables of phase rectified signal averaging. We have speculated that acceleration capacity and deceleration capacity could be of use in the detection of antenatal fetal distress during fetal growth restriction. The study was focused on the detection of the accuracy of acceleration capacity and deceleration capacity in diagnosing fetal distress. In total, 124 pregnant women at 26-36 weeks of gestation were included in the study. The patients with appropriate to gestational age fetuses (n = 32) were enrolled in Group I. The patients with fetal growth restriction and an absence of fetal distress (n = 48) were observed in Group II. Lastly, the patients with fetal growth restriction and fetal distress (n = 44) were included in Group III. Fetal cardiosignals were obtained via non-invasive fetal electrocardiography. The maximally decreased acceleration capacity and deceleration capacity values were found in Group III. A correlation was found between umbilical artery resistance index and acceleration capacity and deceleration capacity variables in all study groups. We have found that the application of phase rectified signal averaging in the antenatal period showed high sensitivity and specificity in fetal distress detection. Fetal acceleration capacity and deceleration capacity is a prospective option for the detection of fetal compromise during fetal growth restriction.

The Impact of Gestational Diabetes in Pregnancy on the Cardiovascular System of Children at One Year of Age.

Gestational diabetes mellitus (GDM) is a common complication in pregnancy. The effect of GDM on the cardiovascular system after birth is still unclear. Between August 2015 and December 2018, 205 pregnant women were included in the prospective controlled observational study. Patients with GDM were assigned to the study group (n = 99), whereas (n = 107) healthy women served as controls. Postnatal follow up of their offspring was performed at 12 months of age. All included children (n = 125) underwent a specific standardized protocol including anthropometric data, such as weight, height, body mass index (BMI), blood pressure (BP) recordings and ultrasound measurements of the abdominal aortic intima-media-thickness (IMT). Furthermore, at least 10 min 3-channel electrocardiogram recording was done to evaluate the autonomic nervous system (ANS) by phase rectified signal averaging. There were no significant differences in anthropometric data between the groups, neither in the blood pressure nor in the intima-media-thickness of the aorta abdominals. However, in the study group, significantly lower average acceleration capacity (AAC) (study group −20.10 ± 3.04 ms, control group −18.87 ± 4.00 ms, p = 0.02) was found, indicating ANS activation at one year of age. Further studies are required to determine if these results are persistent and if these findings have long-term effects.

Relationship Between Deceleration Morphology and Phase Rectified Signal Averaging-Based Parameters During Labor.

During labor, uterine contractions trigger the response of the autonomic nervous system (ANS) of the fetus, producing sawtooth-like decelerations in the fetal heart rate (FHR) series. Under chronic hypoxia, ANS is known to regulate FHR differently with respect to healthy fetuses. In this study, we hypothesized that such different ANS regulation might also lead to a change in the FHR deceleration morphology. The hypothesis was tested in an animal model comprising nine normoxic and five chronically hypoxic fetuses that underwent a protocol of umbilical cord occlusions (UCOs). Deceleration morphologies in the fetal inter-beat time interval (FRR) series were modeled using a trapezoid with four parameters, i.e., baseline b, deceleration depth a, UCO response time τu and recovery time τr. Comparing normoxic and hypoxic sheep, we found a clear difference for τu (24.8±9.4 vs. 39.8±9.7 s; p < 0.05), a (268.1±109.5 vs. 373.0±46.0 ms; p < 0.1) and Δτ = τu − τr (13.2±6.9 vs. 23.9±7.5 s; p < 0.05). Therefore, the animal model supported the hypothesis that hypoxic fetuses have a longer response time τu and larger asymmetry Δτ as a response to UCOs. Assessing these morphological parameters during labor is challenging due to non-stationarity, phase desynchronization and noise. For this reason, in the second part of the study, we quantified whether acceleration capacity (AC), deceleration capacity (DC), and deceleration reserve (DR), computed through Phase-Rectified Signal Averaging (PRSA, known to be robust to noise), were correlated with the morphological parameters. DC, AC and DR were correlated with τu, τr and Δτ for a wide range of the PRSA parameter T (Pearson's correlation ρ > 0.8, p < 0.05). In conclusion, deceleration morphologies have been found to differ between normoxic and hypoxic sheep fetuses during UCOs. The same difference can be assessed through PRSA based parameters, further motivating future investigations on the translational potential of this methodology on human data.

Abstract 11025: Markers of Heart Rate Variability Represent Strong and Independent Predictors of All-Cause Death in Heart Failure - Results from the Myovasc Study

Introduction: Although different measures of heart rate variability (HRV) have been proposed as markers of autonomic dysfunction (AD) in heart failure (HF), evidence on their clinical relevance is limited. Methods: Data from the MyoVasc study (NCT04064450; N=3,289), a prospective cohort study on chronic HF, were analyzed. Study participants received a highly standardized, 5-hour examination including 24-hour Holter ECG recording. RR intervals were extracted to evaluate HRV markers from time and frequency domain analyses, and non-linear markers derived via phase space reconstruction, phase-rectified signal averaging, and entropy analyses. HRV markers of interest were selected using a systematic literature screen, and a random survival forest model predicting cardiac death. Reference values were determined in a healthy subsample. To evaluate clinical relevance, HRV markers were investigated in multivariable Cox regression analyses for their relationship to all-cause death considering potential confounders and mediators. Results: Holter ECG recordings were available for analysis in 1,001 study participants (mean age 64.5±10.5 years; female sex: 35.4%). While the top 10 most frequently reported HRV markers in literature screen were from the time and frequency domains, the data-driven approach revealed predominantly non-linear HRV measures. Values outside reference ranges for SDANN, rMSSD, frequency bands (i.e., ULF, VLF, LF, total power, ULF MED wavelet ), acceleration capacity (AC), deceleration capacity (DC), and time lag, were strong predictors of all-cause death in Cox regression analysis (median follow-up time: 6.1 [IQR 4.7/7.1] years) adjusted for age, sex, clinical profile and medication. In linear Cox regression analyses of the total sample, LF/HF (hazard ratio per SD (HR SD ) 0.78 [95% confidence interval (CI) 0.62, 0.98], p=0.034), time lag (HR SD 1.23 [95%CI 1.05, 1.44], p=0.0095), AC (HR SD : 1.57 [95%CI 1.24, 1.99], p=0.0002), and DC (HR SD 0.67 [95%CI 0.53, 0.85], p=0.0012) were strong predictors for all-cause mortality independent of age, sex, clinical profile and medication. Conclusions: HRV markers reflecting AD are strong predictors of all-cause death in HF, suggesting clinical relevance and potential for intervention.

Interlimb Coordination: A New Order Parameter and a Marker of Fatigue During Quasi-Isometric Exercise?

Although exercise-induced fatigue has been mostly studied from a reductionist and component-dominant approach, some authors have started to test the general predictions of theories of self-organized change during exercises performed until exhaustion. However, little is known about the effects of fatigue on interlimb coordination in quasi-isometric actions. The aim of this study was to investigate the effect of exercise-induced fatigue on upper interlimb coordination during a quasi-isometric exercise performed until exhaustion. In order to do this, we hypothesized an order parameter that governs the interlimb coordination as an interlimb correlation measure. In line with general predictions of theory of phase transitions, we expected that the locally averaged values of the order parameter will increase as the fatigue driven system approaches the point of spontaneous task disengagement. Seven participants performed a quasi-isometric task holding an Olympic bar maintaining an initial elbow flexion of 90 degrees until fatigue induced spontaneous task disengagement. The variability of the elbow angle was recorded through electrogoniometry and the obtained time series were divided into three segments for further analysis. Running correlation function (RCF) and adopted bivariate phase rectified signal averaging (BPRSA) were applied to the corresponding initial (30%) and last (30%) segments of the time series. The results of both analyses showed that the interlimb correlation increased between the initial and the final segments of the performed task. Hence, the hypothesis of the research was supported by evidence. The enhancement of the correlation in the last part means a less flexible coordination among limbs. Our results also show that the high magnitude correlation (%RCF > 0.8) and the %Range (END-BEG) may prove to be useful markers to detect the effects of effort accumulation on interlimb coordination. These results may provide information about the loss of adaptability during exercises performed until exhaustion. Finally, we briefly discuss the hypothesis of the inhibitory percolation process being the general explanation of the spontaneous task disengagement phenomenon.

A randomized controlled trial studying the effect of maternal hyperoxygenation on fetal heart rate in suspected fetal distress

Objective: To investigate the effect of maternal hyperoxygenation on fetal heart rate (FHR) when applied for suspected fetal distress during the second stage of term labor. Approach: A single-center randomized controlled trial was conducted in a tertiary care hospital in The Netherlands. Participants were included during the second stage of labor in case of an intermediary or abnormal FHR pattern. Patients were randomized to receive either 100% oxygen at 10 l/min until delivery, or conventional care without additional oxygen. The primary outcome was the change in FHR pattern before and after the onset of the study, measured as the change in depth and duration of FHR decelerations. Secondary outcome measures were features based on phase-rectified signal averaging (PRSA), baseline assignability, and deceleration characteristics of the FHR pattern. Main results: Between March 2016 and April 2018, 117 women were included. The FHR pattern could be analyzed for 71 participants, the other 46 women delivered before the end of the post time-frame. A 2.3% reduction in depth and duration of FHR decelerations was found after maternal hyperoxygenation, compared to a 10% increase in the control group (p = 0.24). Maternal hyperoxygenation had a significantly positive effect on PRSA metrics, with a decrease in PRSA-acceleration capacity (p = 0.03) and PRSA-deceleration capacity (p = 0.02) in the intervention group compared to the control group. Significance: The difference in depth and duration of decelerations after the start of the study was not significantly different between both study groups. A statistically significant positive effect on PRSA-deceleration capacity and PRSA-acceleration capacity was found after maternal hyperoxygenation, which might be associated with a positive effect on neonatal outcome.

Analysis of the fetal cardio-electrohysterographic coupling at the third trimester of gestation in healthy women by Bivariate Phase-Rectified Signal Averaging.

IntroductionThe fetal cardio-electrohysterographic coupling (FCEC) is defined as the influence of the uterine electrical activity on fetal heart rate. FCEC has been mainly evaluated by visual analysis of cardiotocographic data during labor; however, this physiological phenomenon is poorly explored during the antenatal period. Here we propose an approach known as Bivariate Phase-Rectified Signal Averaging analysis (BPRSA) to assess such FCEC in the late third trimester of low-risk pregnancies. We hypothesized that BPRSA is a more reliable measure of FCEC than visual analysis and conventional measures such as cross-correlation, coherence, and cross-sample entropy. Additionally, by using BPRSA it is possible to detect FCEC even from the third trimester of pregnancy.Material and methodsHealthy pregnant women in the last third trimester of pregnancy (36.6 ± 1.8 gestational weeks) without any clinical manifestation of labor were enrolled in the Maternal and Childhood Research Center (CIMIGen), Mexico City (n = 37). Ten minutes of maternal electrohysterogram (EHG) and fetal heart rate (FHR) data were collected by a transabdominal non-invasive device. The FCEC was quantified by the coefficient of coherence, the maximum normalized cross-correlation, and the cross-sample entropy obtained either from the EHG and FHR raw signals or from the corresponding BPRSA graphs.ResultsWe found that by using BPRSA, the FCEC was detected in 92% cases (34/37) compared to 48% cases (18/37) using the coefficient of coherence between the EHG and FHR raw signals. Also, BPRSA indicated FCEC in 82% cases (30/37) compared to 30% cases (11/37) using the maximum normalized cross-correlation. By comparing the analyses, the BPRSA evidenced higher FCEC in comparison to the coupling estimated from the raw EHG and FHR signals.ConclusionsOur results support the consideration that in the third trimester of pregnancy, the fetal heart rate is also influenced by uterine activity despite the emerging manifestation of this activity before labor. To quantify FCEC, the BPRSA can be applied to FHR and EHG transabdominal signals acquired in the third trimester of pregnancy.

Brief Report: Can a Composite Heart Rate Variability Biomarker Shed New Insights About Autism Spectrum Disorder in School-Aged Children?

Several studies show altered heart rate variability (HRV) in autism spectrum disorder (ASD), but findings are neither universal nor specific to ASD. We apply a set of linear and nonlinear HRV measures-including phase rectified signal averaging-to segments of resting ECG data collected from school-age children with ASD, age-matched typically developing controls, and children with other psychiatric conditions characterized by altered HRV (conduct disorder, depression). We use machine learning to identify time, frequency, and geometric signal-analytical domains that are specific to ASD (receiver operating curve area = 0.89). This is the first study to differentiate children with ASD from other disorders characterized by altered HRV. Despite a small cohort and lack of external validation, results warrant larger prospective studies.

Preprocessing Unevenly Sampled RR Interval Signals to Enhance Estimation of Heart Rate Deceleration and Acceleration Capacities in Discriminating Chronic Heart Failure Patients from Healthy Controls.

Objective. The deceleration capacity (DC) and acceleration capacity (AC) of heart rate, which are recently proposed variants to the heart rate variability, are calculated from unevenly sampled RR interval signals using phase-rectified signal averaging. Although uneven sampling of these signals compromises heart rate variability analyses, its effect on DC and AC analyses remains to be addressed. Approach. We assess preprocessing (i.e., interpolation and resampling) of RR interval signals on the diagnostic effect of DC and AC from simulation and clinical data. The simulation analysis synthesizes unevenly sampled RR interval signals with known frequency components to evaluate the preprocessing performance for frequency extraction. The clinical analysis compares the conventional DC and AC calculation with the calculation using preprocessed RR interval signals on 24-hour data acquired from normal subjects and chronic heart failure patients. Main Results. The assessment of frequency components in the RR intervals using wavelet analysis becomes more robust with preprocessing. Moreover, preprocessing improves the diagnostic ability based on DC and AC for chronic heart failure patients, with area under the receiver operating characteristic curve increasing from 0.920 to 0.942 for DC and from 0.818 to 0.923 for AC. Significance. Both the simulation and clinical analyses demonstrate that interpolation and resampling of unevenly sampled RR interval signals improve the performance of DC and AC, enabling the discrimination of CHF patients from healthy controls.

Fetal heart rate variability responsiveness to maternal stress, non-invasively detected from maternal transabdominal ECG.

Prenatal stress (PS) during pregnancy affects in utero- and postnatal child brain-development. Key systems affected are the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS). Maternal- and fetal ANS activity can be gauged non-invasively from transabdominal electrocardiogram (taECG). We propose a novel approach to assess couplings between maternal (mHR) and fetal heart rate (fHR) as a new biomarker for PS based on bivariate phase-rectified signal averaging (BPRSA). We hypothesized that PS exerts lasting impact on fHR. Prospective case-control study matched for maternal age, parity, and gestational age during the third trimester using the Cohen Perceived Stress Scale (PSS-10) questionnaire with PSS-10 over or equal 19 classified as stress group (SG). Women with PSS-10 < 19 served as control group (CG). Fetal electrocardiograms were recorded by a taECG. Coupling between mHR and fHR was analyzed by BPRSA resulting in fetal stress index (FSI). Maternal hair cortisol, a memory of chronic stress exposure for 2-3months, was measured at birth. 538/1500 pregnant women returned the questionnaire, 55/538 (10.2%) mother-child pairs formed SG and were matched with 55/449 (12.2%) consecutive patients as CG. Maternal hair cortisol was 86.6 (48.0-169.2) versus 53.0 (34.4-105.9) pg/mg (p = 0.029). At 36 + 5weeks, FSI was significantly higher in fetuses of stressed mothers when compared to controls [0.43 (0.18-0.85) versus 0.00 (- 0.49-0.18), p < 0.001]. Prenatal maternal stress affects the coupling between maternal and fetal heart rate detectable non-invasively a month prior to birth. Lasting effects on neurodevelopment of affected offspring should be studied. Clinical trial registration: NCT03389178.

Theoretical Value of Deceleration Capacity Points to Deceleration Reserve of Fetal Heart Rate.

The interpretation of Average Acceleration and Deceleration Capacities (AC/DC), computed through Phase-Rectified Signal Averaging (PRSA), in intrapartum fetal heart rate (FHR) monitoring is still matter of investigation. We aimed to elucidate some behaviors of AC/DC. We derived the theoretical value of PRSA for stationary stochastic Gaussian processes and proved that for these time series AC and DC are necessarily identical in absolute value. The difference between DC and AC, termed Deceleration Reserve (DR), was introduced to detect signal's asymmetric trends. DR was tested on FHR signals from: near-term pregnant sheep model of labor consisting of chronically hypoxic and normoxic fetuses with both groups developing acidemia due to umbilical cord occlusions (UCO); and the CTU-UHB dataset containing fetal CTG recordings collected during labor of newborns that resulted acidotic and non-acidotic, respectively. DR was compared with AC and DC in terms of discriminatory power (AUC), between the groups, after correcting for signal power or deceleration area, respectively. DR displayed higher discriminatory power on the animal model during severe acidemia, with respect to AC/DC ( ) but also distinguished correctly all chronically hypoxic from normoxic fetuses at baseline prior to UCO. DR also outperformed AC/DC on the CTU-UHB dataset in distinguishing acidemic fetuses at birth (AUC: 0.65). Theoretical results motivated the introduction of DR, that proved to be superior than AC/DC for risk stratification during labor. DR, measured during labor, might permit to distinguish acidemic fetuses due to their different autonomic regulation, paving the way for new monitoring strategies.

Evaluation of Methods to Characterize the Change of the Respiratory Sinus Arrhythmia with Age in Sleep Apnea Patients.

The High Frequency (HF) band of the power spectrum of the Heart Rate Variability (HRV) is widely accepted to contain information related to the respiration. However, it is known that this often results in misleading estimations of the strength of the Respiratory Sinus Arrhythmia (RSA). In this paper, different approaches to characterize the change of the RSA with age, combining HRV and respiratory signals, are studied. These approaches are the bandwidths in the power spectral density estimations, bivariate phase rectified signal averaging, information dynamics, a time-frequency representation, and a heart rate decomposition based on subspace projections. They were applied to a dataset of sleep apnea patients, specifically to periods without apneas and during NREM sleep. Each estimate reflected a different relationship between RSA and age, suggesting that they all capture the cardiorespiratory information in a different way. The comparison of the estimates indicates that the approaches based on the extraction of respiratory information from HRV provide a better characterization of the age-dependent degradation of the RSA.

Characterization of the Asymmetry of the Cardiac and Sympathetic Arms of the Baroreflex From Spontaneous Variability During Incremental Head-Up Tilt.

Hysteresis of the baroreflex (BR) is the result of the different BR sensitivity (BRS) when arterial pressure (AP) rises or falls. This phenomenon has been poorly studied and almost exclusively examined by applying pharmacological challenges and static approaches disregarding causal relations. This study inspects the asymmetry of the cardiac BR (cBR) and vascular sympathetic BR (sBR) in physiological closed loop conditions from spontaneous fluctuations of physiological variables, namely heart period (HP) and systolic AP (SAP) leading to the estimation of cardiac BRS (cBRS) and muscle sympathetic nerve activity (MSNA) and diastolic AP (DAP) leading to the estimation of vascular sympathetic BRS (sBRS). The assessment was carried out in 12 young healthy subjects undergoing incremental head-up tilt with table inclination gradually increased from 0 to 60°. Two analytical methods were exploited and compared, namely the sequence (SEQ) and phase-rectified signal averaging (PRSA) methods. SEQ analysis is based on the detection of joint causal schemes representing the HP and MSNA burst rate delayed responses to spontaneous SAP and DAP modifications, respectively. PRSA analysis averages HP and MSNA burst rate patterns after aligning them according to the direction of SAP and DAP changes, respectively. Since cBRSs were similar when SAP went up or down, hysteresis of cBR was not detected. Conversely, hysteresis of sBR was evident with sBRS more negative when DAP was falling than rising. sBR hysteresis was no longer visible during sympathetic activation induced by the orthostatic challenge. These results were obtained via the SEQ method, while the PRSA technique appeared to be less powerful in describing the BR asymmetry due to the strong association between BRS estimates computed over positive and negative AP variations. This study suggests that cBR and sBR provide different information about the BR control, sBR exhibits more relevant non-linear features that are evident even during physiological changes of AP, and the SEQ method can be fruitfully exploited to characterize the BR hysteresis with promising applications to BR branches different from cBR and sBR.