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We exploit time reversibility analysis, checking the invariance of statistical features of a series after time reversal, to detect temporal asymmetries of short-term heart period variability series. Reversibility indexes were extracted from 22 healthy fetuses between 16th to 40th wk of gestation and from 17 healthy humans (aged 21 to 54, median = 28) during graded head-up tilt with table inclination angles randomly selected inside the set {15, 30, 45, 60, 75, 90}. Irreversibility analysis showed that nonlinear dynamics observed in short-term heart period variability are mostly due to asymmetric patterns characterized by bradycardic runs shorter than tachycardic ones. These temporal asymmetries were 1) more likely over short temporal scales than over longer, dominant ones; 2) more frequent during the late period of pregnancy (from 25th to 40th week of gestation); 3) significantly present in healthy humans at rest in supine position; 4) more numerous during 75 and 90[degrees] head-up tilt. Results suggest that asymmetric patterns observable in short-term heart period variability might be the result of a fully developed autonomic regulation and that an important shift of the sympathovagal balance toward sympathetic predominance (and vagal withdrawal) can increase their presence. heart rate variability; autonomic nervous system; head-up tilt; fetal maturation; nonlinear dynamics

Abstract Background The univariate approaches used to analyze heart rate variability have recently been extended by several bivariate approaches with respect to cardiorespiratory coordination. Some approaches are explicitly based on mathematical models which investigate the synchronization between weakly coupled complex systems. Others use an heuristic approach, i.e. characteristic features of both time series, to develop appropriate bivariate methods. Objective In this study six different methods used to analyze cardiorespiratory coordination have been quantitatively compared with respect to their performance (no. of sequences with cardiorespiratory coordination, no. of heart beats coordinated with respiration). Five of these approaches have been suggested in the recent literature whereas one method originates from older studies. Results The methods were applied to the simultaneous recordings of an electrocardiogram and a respiratory trace of 20 healthy subjects during night-time sleep from 0:00 to 6:00. The best temporal resolution and the highest number of coordinated heart beats were obtained with the analysis of 'Phase Recurrences'. Apart from the oldest method, all methods showed similar qualitative results although the quantities varied between the different approaches. In contrast, the oldest method detected considerably fewer coordinated heart beats since it only used part of the maximum amount of information available in each recording. Conclusions The method of 'Phase Recurrences' should be the method of choice for the detection of cardiorespiratory coordination since it offers the best temporal resolution and the highest number of coordinated sequences and heart beats. Excluding the oldest method, the results of the heuristic approaches may also be interpreted in terms of the mathematical models.

Abstract Background Magnetocardiography enables the precise determination of fetal cardiac time intervals (CTI) as early as the second trimester of pregnancy. It has been shown that fetal CTI change in course of gestation. The aim of this work was to investigate the dependency of fetal CTI on gestational age, gender and postnatal biometric data in a substantial sample of subjects during normal pregnancy. Methods A total of 230 fetal magnetocardiograms were obtained in 47 healthy fetuses between the 15th and 42nd week of gestation. In each recording, after subtraction of the maternal cardiac artifact and the identification of fetal beats, fetal PQRST courses were signal averaged. On the basis of therein detected wave onsets and ends, the following CTI were determined: P wave, PR interval, PQ interval, QRS complex, ST segment, T wave, QT and QTc interval. Using regression analysis, the dependency of the CTI were examined with respect to gestational age, gender and postnatal biometric data. Results Atrioventricular conduction and ventricular depolarization times could be determined dependably whereas the T wave was often difficult to detect. Linear and nonlinear regression analysis established strong dependency on age for the P wave and QRS complex (r2 = 0.67, p < 0.001 and r2 = 0.66, p < 0.001) as well as an identifiable trend for the PR and PQ intervals (r2 = 0.21, p < 0.001 and r2 = 0.13, p < 0.001). Gender differences were found only for the QRS complex from the 31st week onward (p < 0.05). The influence on the P wave or QRS complex of biometric data, collected in a subgroup in whom recordings were available within 1 week of birth, did not display statistical significance. Conclusion We conclude that 1) from approximately the 18th week to term, fetal CTI which quantify depolarization times can be reliably determined using magnetocardiography, 2) the P wave and QRS complex duration show a high dependency on age which to a large part reflects fetal growth and 3) fetal gender plays a role in QRS complex duration in the third trimester. Fetal development is thus in part reflected in the CTI and may be useful in the identification of intrauterine growth retardation.

Unlabelled: It has been shown that short-term direct interaction between maternal and fetal heart rates may take place and that this interaction is affected by the rate of maternal respiration. The aim of this study was to determine the effect of maternal aerobic exercise during pregnancy on the occurrence of fetal-maternal heart rate synchronization., Methods: In 40 pregnant women at the 36th week of gestation, 21 of whom exercised regularly, we acquired 18 min. RR interval time series obtained simultaneously in the mothers and their fetuses from magnetocardiographic recordings. The time series of the two groups were examined with respect to their heart rate variability, the maternal respiratory rate and the presence of synchronization epochs as determined on the basis of synchrograms. Surrogate data were used to assess whether the occurrence of synchronization was due to chance., Results: In the original data, we found synchronization occurred less often in pregnancies in which the mothers had exercised regularly. These subjects also displayed higher combined fetal-maternal heart rate variability and lower maternal respiratory rates. Analysis of the surrogate data showed shorter epochs of synchronization and a lack of the phase coordination found between maternal and fetal beat timing in the original data., Conclusion: The results suggest that fetal-maternal heart rate coupling is present but generally weak. Maternal exercise has a damping effect on its occurrence, most likely due to an increase in beat-to-beat differences, higher vagal tone and slower breathing rates.

The influence of maternal respiration on the occurrence of short-term fetal--maternal heart-rate coordination was examined using a model, which considers both heart-rate characteristics and effects of maternal respiratory sinus arrhythmia. Epochs of fetal--maternal heart-rate coordination were identified in model data produced at varying respiratory rates and compared with epochs found in real data acquired in mother-fetus pairs. The model results suggest that the low incidence of epochs found in the real data at low-breathing rates may be explained by heart-rate characteristics, but that the higher incidence at fast rates must be due to other factors.

Background and Aim: Fetal behavioural states have been defined on the basis of eye movements, body movements and heart rate patterns as presented by cardiotocography (CTG). The aim of this work was to determine whether behavioural states can be distinguished on the basis of heart rate features alone using high resolution beat-to-beat fetal magnetocardiography., Study Design: Five minute magnetocardiograms were recorded at a sampling rate of 1 kHz in 40 healthy fetuses (36th-41st week of gestation). In the reconstructed RR interval time series, 256-beat epochs corresponding to the behavioural states 1F, 2F and 4F were visually identified according to heart rate patterns as defined for CTG. These epochs were then quantified using mean RR interval, its standard deviation (SDNN), its root mean square of successive difference (RMSSD) and on the basis of symbolic dynamics of short 8 beat trains., Results: Pairwise comparison between the behavioural states showed that the values of each of these measures differed significantly between the states. Quadratic discriminant analysis further revealed that mean RR interval and SDNN sufficed to classify state with a correct classification of 92%., Conclusions: The results suggest that measures that quantify overall aspects of heart rate can distinguish RR interval time series which were classified into different fetal behavioural states. The differences in short-term variability as quantified by RMSSD and symbolic dynamics may help reveal new aspects of these states.

Fetal magnetocardiography (fMCG) has been shown to augment fetal ultrasound evaluation for high-risk conditions, but the clinical utility of fMCG depends on the reliability of the cardiac traces reconstructed. We performed a methodological study to examine the influence of gestational age on the properties of the fetal magnetocardiograms extracted with two methods of signal reconstruction: the template matching technique (TMT), which extracts the maternal components from the signal using only temporal information, and independent component analysis (ICA), which separates the fetal signals by using information on the spatial distribution of the mixed source signals in addition to higher order temporal statistics. Efficiency and accuracy were evaluated in terms of fetal beat detection, signal characteristics, and duration of cardiac time intervals (CTIs) on the averaged traces. ICA outperformed TMT with regard to beat detection and signal-to-noise ratio. The timing of the heartbeats and the duration of the CTIs were essentially the same, whereas some alterations in signal morphology were observed in the ICA traces. We conclude that ICA may be useful in early gestation when the signals are noisy, while TMT may be preferred when accurate beat morphology is required for diagnostic purposes.

We present a case of supraventricular tachycardia affecting one fetus in a twin pregnancy. Before and after treatment with flecainide and cardioversion, we examined conduction times and heart rate variability (HRV) in both twins on the basis of magnetocardiography. Cardiac conduction times increased in both fetuses but HRV showed opposing effects with a number of HRV measures. This case demonstrates that magnetocardiography not only enables identification of fetal arrhythmia, but also permits the investigation of the effects of antiarrhythmic treatment on the conductive system as well as on interaction with the autonomic nervous system.

We compared the stability and discriminatory power of different methods of determining cardiac magnetic field map (MFM) orientation within the context of coronary artery disease (CAD). In 27 healthy subjects and 24 CAD patients, multichannel magnetocardiograms were registered at rest. MFM orientation was determined during QT interval using: (a) locations of the positive and negative centres-of-gravity, (b) locations of the field extrema and (c) the direction of the maximum field gradient. Deviation from normal orientation quantified the ability of each approach to discriminate between healthy and CAD subjects. Although the course of orientation was similar for all methods, receiver operating characteristic analysis showed the best discrimination of CAD patients for the centre-of-gravity approach (area-under-the-curve = 86%), followed by the gradient (84%) and extrema (76%) methods. Consideration of methodological and discriminatory advantages with respect to noninvasive diagnosis of CAD suggests that the centres-of-gravity method is the most suited one.

Background: Heart rate variability (HRV) is becoming increasingly important in the analysis of prepartal cardiotocography (CTG). Dawes and Redmann have developed a computer algorithm which can calculate short-term variability on the basis of CTG data. In dealing with artefacts, CTG monitors average heart rate values over several beats which makes the use of standard measures of HRV such as the root mean square of successive differences (RMSSD) inappropriate. Fetal magnetocardiography (FMCG) enables the registration of signals similar to the electrocardiogram and this permits the precise determination of heart beat duration and, in consequence, of measures of fetal HRV., Methods: In this study we applied both methods--CTG and FMCG--sequentially and simultaneously in healthy pregnancies. Fetal short-term HRV was estimated on the basis of RMSSD values for both methods., Results: The RMSSD values of the FMCG data were generally higher and showed a wider dynamic range than those of the CTG. The direct comparison of the simultaneously acquired data demonstrated that the data processing of the CTG signal leads to a suppression of essential aspects of short-term HRV., Conclusion: FMCG permits a substantially more differentiated examination of fetal HRV and offers new possibilities in the analysis of fetal cardiac activity.

Fetal heart rate complexity was examined on the basis of RR interval time series obtained in the second and third trimester of pregnancy. In each fetal RR interval time series, short term beat-to-beat heart rate changes were coded in 8 bit binary sequences. Redundancies of the 2(8) different binary patterns were reduced by two different procedures. The complexity of these sequences was quantified using the approximate entropy (ApEn), resulting in discrete ApEn values which were used for classifying the sequences into 17 pattern sets. Also, the sequences were grouped into 20 pattern classes with respect to identity after rotation or inversion of the binary value. There was a specific, nonuniform distribution of the sequences in the pattern sets and this differed from the distribution found in surrogate data. In the course of gestation, the number of sequences increased in seven pattern sets, decreased in four and remained unchanged in six. Sequences that occurred less often over time, both regular and irregular, were characterized by patterns reflecting frequent beat-to-beat reversals in heart rate. They were also predominant in the surrogate data, suggesting that these patterns are associated with stochastic heart beat trains. Sequences that occurred more frequently over time were relatively rare in the surrogate data. Some of these sequences had a high degree of regularity and corresponded to prolonged heart rate accelerations or decelerations which may be associated with directed fetal activity or movement or baroreflex activity. Application of the pattern classes revealed that those sequences with a high degree of irregularity correspond to heart rate patterns resulting from complex physiological activity such as fetal breathing movements. The results suggest that the development of the autonomic nervous system and the emergence of fetal behavioral states lead to increases in not only irregular but also regular heart rate patterns. Using symbolic dynamics to examine the cardiovascular system may thus lead to new insight with respect to fetal development.

Background: In fetal surveillance, fetal heart rate changes are assessed using cardiotocography (CTG). Standard procedures used in the quantification of heart rate variability (HRV) are seldom applied as CTG does not deliver beat interval durations with the same accuracy as the electrocardiogram (ECG). Thus little is known about the interdependency of standard HRV measures prenatally., Materials and Methods: Using fetal magnetocardiography (FMCG: the magnetic equivalent of the fetal ECG), we investigated standard HRV measures in a homogenous group of 20 healthy fetuses. Ten HRV measures were analyzed in 60 five-minute RR interval time series derived from FMCG acquisitions (16th-40th week of gestation)., Results: Using regression analysis, we found a clear dependency on gestational age and mean RR interval for measures from the time and frequency domains as well as for a measure for complexity. Correlation analysis revealed a strong interdependency of the measures, in particular within the specific domains. An adequate description of fetal HRV may be achieved using the standard deviation from the time domain, the high frequency band (0.15-0.40 Hz) from the frequency domain and approximate entropy as a complexity measure., Conclusion: The results indicate that different characteristics of fetal HRV are embedded in the different domains.

Northern-temperate male birds show seasonal changes in testosterone concentrations with a peak during the breeding season. Many tropical birds express much lower concentrations of testosterone with slight elevations during breeding. Here we describe testosterone and corticosterone concentrations of male stonechats from equatorial Kenya during different substages of breeding and molt. This tropical species has a short breeding season of approximately 3 months. We compare their hormone concentrations to previously published data of males of a northern-temperate relative, the European stonechat, also a seasonal breeder but with a breeding season of approximately 5 months. Equatorial stonechats show a pronounced peak of testosterone during the nest-building and laying stage. During all other stages, testosterone concentrations are low, similar to other year-round territorial tropical bird species. Corticosterone concentrations peak also during the nest-building and laying stage suggesting that this period of maximum female fecundity is a demanding period for the male. Equatorial stonechats have significantly lower concentrations of testosterone than European stonechats during all stages, except during the nest-building and laying stage. During this stage of maximum female fertility, testosterone levels tend to be higher in equatorial than in European stonechats. Our results suggest that equatorial stonechats belong to a group of tropical bird species that are characterized by a short breeding season and a brief high peak of testosterone during the female's fertile period. Such brief, but substantial peaks of testosterone may be common in tropical birds, but they may easily be missed if the exact breeding stage of individual birds is not known.

Prenatal growth deficiencies as well as gender have been associated with cardiovascular disease in later life. It is also known that the duration of fetal cardiac time intervals (CTI) are dependent on fetal development. The aim of this work was to examine the relationship between fetal CTI in healthy and intrauterine growth retardation (IUGR) fetuses, taking gender into account. A total of 269 magnetocardiograms (MCG) were obtained in 47 healthy and 27 IUGR pregnancies. In each signal-averaged MCG, durations of CTI were determined. Age- and heart rate-corrected values were compared between normal and IUGR fetuses separately with respect to gender. Overall, there was an association between atrial and ventricular conduction times and estimated fetal body weight. In female fetuses, IUGR was associated with shorter P WAVE, PQ segment, PR interval, and QRS complex and longer STT and QT intervals. For males, this was so only for P wave, QRS complex, and STT interval. The shortening of conduction times in IUGR may be explained by reduced cardiac muscle mass associated with lower body weight. On the other hand, the gender-specific differences, particularly in the IUGR fetuses may be due to hormonal factors.

Fetal magnetocardiography has shown that fetal P wave and QRS complex durations increase with gestational age, reflecting change in cardiac muscle mass. The latter should, in principle, be associated with an increase in signal strength. We examined two approaches for determining QRS signal strength in a healthy fetus on a weekly basis in the second and third trimester. Twenty-two fetal magnetocardiograms of the same fetus were obtained using a 61 channel Magnes 1300 biomagnetometer (20th-42nd week of gestation). In the signal averaged fetal beat produced at each week, signal strength was assessed on the basis of 1) peak-to-peak QRS signal amplitudes and 2) strength of an equivalent current dipole (ECD) computed at R peak. The results were assessed on the basis of correlation to week of gestation and by comparison to changes in QRS interval duration. All values increased with advancing gestation and regression analysis suggested a nonlinear dependency on age. ECD strength reflected gestational age slightly more reliably (r2=0.93) than signal amplitude values (mean, median, maximum: r2=089, 0.88, 0.85, respectively). ECD strength and mean signal amplitude also correlated well (r=0.97, p<0.0005) Values calculated from QRS complexes determined immediately before and after a clear change in fetal position (acquisition week 24) demonstrated a certain instability in both approaches. Nonetheless, the overall correlation of the amplitude to gestational age compared favorably with that of QRS complex duration. This indicates that not only magnetocardiographically determined fetal cardiac time intervals but also signal strength may be used to assess fetal growth.

Background: The univariate approaches used to analyze heart rate variability have recently been extended by several bivariate approaches with respect to cardiorespiratory coordination. Some approaches are explicitly based on mathematical models which investigate the synchronization between weakly coupled complex systems. Others use an heuristic approach, i.e. characteristic features of both time series, to develop appropriate bivariate methods., Objective: In this study six different methods used to analyze cardiorespiratory coordination have been quantitatively compared with respect to their performance (no. of sequences with cardiorespiratory coordination, no. of heart beats coordinated with respiration). Five of these approaches have been suggested in the recent literature whereas one method originates from older studies., Results: The methods were applied to the simultaneous recordings of an electrocardiogram and a respiratory trace of 20 healthy subjects during night-time sleep from 0:00 to 6:00. The best temporal resolution and the highest number of coordinated heart beats were obtained with the analysis of 'Phase Recurrences'. Apart from the oldest method, all methods showed similar qualitative results although the quantities varied between the different approaches. In contrast, the oldest method detected considerably fewer coordinated heart beats since it only used part of the maximum amount of information available in each recording., Conclusions: The method of 'Phase Recurrences' should be the method of choice for the detection of cardiorespiratory coordination since it offers the best temporal resolution and the highest number of coordinated sequences and heart beats. Excluding the oldest method, the results of the heuristic approaches may also be interpreted in terms of the mathematical models.

BACKGROUND: Magnetocardiography enables the precise determination of fetal cardiac time intervals (CTI) as early as the second trimester of pregnancy. It has been shown that fetal CTI change in course of gestation. The aim of this work was to investigate the dependency of fetal CTI on gestational age, gender and postnatal biometric data in a substantial sample of subjects during normal pregnancy. METHODS: A total of 230 fetal magnetocardiograms were obtained in 47 healthy fetuses between the 15th and 42nd week of gestation. In each recording, after subtraction of the maternal cardiac artifact and the identification of fetal beats, fetal PQRST courses were signal averaged. On the basis of therein detected wave onsets and ends, the following CTI were determined: P wave, PR interval, PQ interval, QRS complex, ST segment, T wave, QT and QTc interval. Using regression analysis, the dependency of the CTI were examined with respect to gestational age, gender and postnatal biometric data. RESULTS: Atrioventricular conduction and ventricular depolarization times could be determined dependably whereas the T wave was often difficult to detect. Linear and nonlinear regression analysis established strong dependency on age for the P wave and QRS complex (r2 = 0.67, p < 0.001 and r2 = 0.66, p < 0.001) as well as an identifiable trend for the PR and PQ intervals (r2 = 0.21, p < 0.001 and r2 = 0.13, p < 0.001). Gender differences were found only for the QRS complex from the 31st week onward (p < 0.05). The influence on the P wave or QRS complex of biometric data, collected in a subgroup in whom recordings were available within 1 week of birth, did not display statistical significance. CONCLUSION: We conclude that 1) from approximately the 18th week to term, fetal CTI which quantify depolarization times can be reliably determined using magnetocardiography, 2) the P wave and QRS complex duration show a high dependency on age which to a large part reflects fetal growth and 3) fetal gender plays a role in QRS complex duration in the third trimester. Fetal development is thus in part reflected in the CTI and may be useful in the identification of intrauterine growth retardation.

We investigated several factors which may affect the accuracy of fetal cardiac time intervals (CTI) determined in magnetocardiographic (MCG) recordings: observer differences, the number of available recording sites and the type of sensor used in acquisition. In 253 fetal MCG recordings, acquired using different biomagnetometer devices between the 15th and 42nd weeks of gestation, P-wave, QRS complex and T-wave onsets and ends were identified in signal averaged data sets independently by different observers. Using a defined procedure for setting signal events, interobserver reliability was high. Increasing the number of registration sites led to more accurate identification of the events. The differences in wave morphology between magnetometer and gradiometer configurations led to deviations in timing whereas the differences between low and high temperature devices seemed to be primarily due to noise. Signal-to-noise ratio played an important overall role in the accurate determination of CTI and changes in signal amplitude associated with fetal maturation may largely explain the effects of gestational age on reproducibility. As fetal CTI may be of value in the identification of pathologies such as intrauterine growth retardation or fetal cardiac hypertrophy, their reliable estimation will be enhanced by strategies which take these factors into account.

Objective: The aim of this study was to examine changes in the heart rate variability based on the frequency power spectrum of healthy fetuses during the second and third trimester of pregnancy., Methods: We analyzed 222 fetal magnetocardiograms recorded in 49 healthy singleton pregnancies between the 16th and 42nd week. Discrete Fourier transformation was performed on the time-based step function of the RR-intervals. Changes of spectral density in the frequency spectrum in various bands between 0.003 to 1 Hz, including low-frequency (LF: 0.04-0.15 Hz) and high-frequency (HF: 0.15-0.40 Hz) bands, were examined as a function of gestational age., Results: Spectral density between 0.003 to 1.0 Hz increased with gestational age with large changes, in particular, at lower frequencies. At approximately the 32nd week, the rate of increase in power slowed substantially. Prior to this time, the rates of change in power were different for the bands 0.003 to 0.40 Hz, 0.40 to 0.60 Hz and 0.60 to 1.0 Hz. LF and HF showed similar development, with HF increasing slightly more rapidly., Conclusion: We conclude that characteristic spectral bands that increase in spectral density at different rates during the second and third trimester may be identified. They most likely reflect developmental changes and behavioral states during pregnancy., (Copyright 2003 John Wiley & Sons, Ltd.)

Background: The prenatal condition offers a unique possibility of examining physiological interaction between individuals. Goal of this work was to look for evidence of coordination between fetal and maternal cardiac systems., Methods: 177 magnetocardiograms were recorded in 62 pregnancies (16th-42nd week of gestation). Fetal and maternal RR interval time series were constructed and the phases, i.e. the timing of the R peaks of one time series in relation to each RR interval of the other were determined. The distributions of these phases were examined and synchrograms were constructed for real and surrogate pairs of fetal and maternal data sets. Synchronization epochs were determined for defined n:m coupling ratios., Results: Differences between real and surrogate data could not be found with respect to number of synchronization epochs found (712 vs. 741), gestational age, subject, recording or n:m combination. There was however a preference for the occurrence of synchronization epochs in specific phases in real data not apparent in the surrogate for some n:m combinations., Conclusion: The results suggest that occasional coupling between fetal and maternal cardiac systems does occur.

Biological systems exhibit numerous rhythmic processes. In the human, rhythms produced by e.g. the cardiac and respiratory systems show signs of synchronisation, reflecting a physiological coupling of the underlying oscillating processes. When examining such rhythms for evidence of coupling, it is difficult to distinguish between epochs of coincidental (numerical) and real (physiological) synchronisation. The objective of this study was to simulate model rhythms in order to examine the conditions under which coupling may be recognised and the influence of noise on this recognition. Different model rhythms with adjustable noise were implemented. The synchronisation between pairs of such rhythms was examined with the help of synchrograms. Functions were used to simulate coupling. The results of the simulation were compared to real fetal-maternal cardiac rhythms. The simulation showed that heart rate variability may be an important factor in distinguishing between coincidental and real synchronisation.