Non-invasive fetal electrocardiogram : analysis and interpretation

High-risk pregnancies are becoming more and more prevalent because of the progressively higher age at which women get pregnant. Nowadays about twenty percent of all pregnancies are complicated to some degree, for instance because of preterm delivery, fetal oxygen deficiency, fetal growth restriction, or hypertension. Early detection of these complications is critical to permit timely medical intervention, but is hampered by strong limitations of existing monitoring technology. This technology is either only applicable in hospital settings, is obtrusive, or is incapable of providing, in a robust way, reliable information for diagnosis of the well-being of the fetus. The most prominent method for monitoring of the fetal health condition is monitoring of heart rate variability in response to activity of the uterus (cardiotocography; CTG). Generally, in obstetrical practice, the heart rate is determined in either of two ways: unobtrusively with a (Doppler) ultrasound probe on the maternal abdomen, or obtrusively with an invasive electrode fixed onto the fetal scalp. The first method is relatively inaccurate but is non-invasive and applicable in all stages of pregnancy. The latter method is far more accurate but can only be applied following rupture of the membranes and sufficient dilatation, restricting its applicability to only the very last phase of pregnancy. Besides these accuracy and applicability issues, the use of CTG in obstetrical practice also has another limitation: despite its high sensitivity, the specificity of CTG is relatively low. This means that in most cases of fetal distress the CTG reveals specific patterns of heart rate variability, but that these specific patterns can also be encountered for healthy fetuses, complicating accurate diagnosis of the fetal condition. Hence, a prerequisite for preventing unnecessary interventions that are based on CTG alone, is the inclusion of additional information in diagnostics. Monitoring of the fetal electrocardiogram (ECG), as a supplement of CTG, has been demonstrated to have added value for monitoring of the fetal health condition. Unfortunately the application of the fetal ECG in obstetrical diagnostics is limited because at present the fetal ECG can only be measured reliably by means of an invasive scalp electrode. To overcome this limited applicability, many attempts have been made to record the fetal ECG non-invasively from the maternal abdomen, but these attempts have not yet led to approaches that permit widespread clinical application. One key difficulty is that the signal to noise ratio (SNR) of the transabdominal ECG recordings is relatively low. Perhaps even more importantly, the abdominal ECG recordings yield ECG signals for which the morphology depends strongly on the orientation of the fetus within the maternal uterus. Accordingly, for any fetal orientation, the ECG morphology is different. This renders correct clinical interpretation of the recorded ECG signals complicated, if not impossible. This thesis aims to address these difficulties and to provide new contributions on the clinical interpretation of the fetal ECG. At first the SNR of the recorded signals is enhanced through a series of signal processing steps that exploit specific and a priori known properties of the fetal ECG. More particularly, the dominant interference (i.e. the maternal ECG) is suppressed by exploiting the absence of temporal correlation between the maternal and fetal ECG. In this suppression, the maternal ECG complex is dynamically segmented into individual ECG waves and each of these waves is estimated through averaging corresponding waves from preceding ECG complexes. The maternal ECG template generated by combining the estimated waves is subsequently subtracted from the original signal to yield a non-invasive recording in which the maternal ECG has been suppressed. This suppression method is demonstrated to be more accurate than existing methods. Other interferences and noise are (partly) suppressed by exploiting the quasiperiodicity of the fetal ECG through averaging consecutive ECG complexes or by exploiting the spatial correlation of the ECG. The averaging of several consecutive ECG complexes, synchronized on their QRS complex, enhances the SNR of the ECG but also can suppress morphological variations in the ECG that are clinically relevant. The number of ECG complexes included in the average hence constitutes a trade-off between SNR enhancement on the one hand and loss of morphological variability on the other hand. To relax this trade-off, in this thesis a method is presented that can adaptively estimate the number of ECG complexes included in the average. In cases of morphological variations, this number is decreased ensuring that the variations are not suppressed. In cases of no morphological variability, this number is increased to ensure adequate SNR enhancement. The further suppression of noise by exploiting the spatial correlation of the ECG is based on the fact that all ECG signals recorded at several locations on the maternal abdomen originate from the same electrical source, namely the fetal heart. The electrical activity of the fetal heart at any point in time can be modeled as a single electrical field vector with stationary origin. This vector varies in both amplitude and orientation in three-dimensional space during the cardiac cycle and the time-path described by this vector is referred to as the fetal vectorcardiogram (VCG). In this model, the abdominal ECG constitutes the projection of the VCG onto the vector that describes the position of the abdominal electrode with respect to a reference electrode. This means that when the VCG is known, any desired ECG signal can be calculated. Equivalently, this also means that when enough ECG signals (i.e. at least three independent signals) are known, the VCG can be calculated. By using more than three ECG signals for the calculation of the VCG, redundancy in the ECG signals can be exploited for added noise suppression. Unfortunately, when calculating the fetal VCG from the ECG signals recorded from the maternal abdomen, the distance between the fetal heart and the electrodes is not the same for each electrode. Because the amplitude of the ECG signals decreases with propagation to the abdominal surface, these different distances yield a specific, unknown attenuation for each ECG signal. Existing methods for estimating the VCG operate with a fixed linear combination of the ECG signals and, hence, cannot account for variations in signal attenuation. To overcome this problem and be able to account for fetal movement, in this thesis a method is presented that estimates both the VCG and, to some extent, also the signal attenuation. This is done by determining for which VCG and signal attenuation the joint probability over both these variables is maximal given the observed ECG signals. The underlying joint probability distribution is determined by assuming the ECG signals to originate from scaled VCG projections and additive noise. With this method, a VCG, tailored to each specific patient, is determined. With respect to the fixed linear combinations, the presented method performs significantly better in the accurate estimation of the VCG. Besides describing the electrical activity of the fetal heart in three dimensions, the fetal VCG also provides a framework to account for the fetal orientation in the uterus. This framework enables the detection of the fetal orientation over time and allows for rotating the fetal VCG towards a prescribed orientation. From the normalized fetal VCG obtained in this manner, standardized ECG signals can be calculated, facilitating correct clinical interpretation of the non-invasive fetal ECG signals. The potential of the presented approach (i.e. the combination of all methods described above) is illustrated for three different clinical cases. In the first case, the fetal ECG is analyzed to demonstrate that the electrical behavior of the fetal heart differs significantly from the adult heart. In fact, this difference is so substantial that diagnostics based on the fetal ECG should be based on different guidelines than those for adult ECG diagnostics. In the second case, the fetal ECG is used to visualize the origin of fetal supraventricular extrasystoles and the results suggest that the fetal ECG might in future serve as diagnostic tool for relating fetal arrhythmia to congenital heart diseases. In the last case, the non-invasive fetal ECG is compared to the invasively recorded fetal ECG to gauge the SNR of the transabdominal recordings and to demonstrate the suitability of the non-invasive fetal ECG in clinical applications that, as yet, are only possible for the invasive fetal ECG

On the distinct differences in autonomic regulation between pregnant and non-pregnant women:a heart rate variability analysis

Objective. Appropriate adaptation of the maternal autonomic nervous system to progressing gestation is essential to a healthy pregnancy. This is partly evidenced by the association between pregnancy complications and autonomic dysfunction. Therefore, assessing maternal heart rate variability (HRV)—a proxy measure for autonomic activity—may offer insights into maternal health, potentially enabling the early detection of complications. However, identifying abnormal maternal HRV requires a thorough understanding of normal maternal HRV. While HRV in women of childbearing age has been extensively investigated, less is known concerning HRV during pregnancy. Subsequently, we investigate the differences in HRV between healthy pregnant women and their non-pregnant counterparts. Approach. We use a comprehensive suite of HRV features (assessing sympathetic and parasympathetic activity, heart rate (HR) complexity, HR fragmentation, and autonomic responsiveness) to quantify HRV in large groups of healthy pregnant (n = 258) and non-pregnant women (n = 252). We compare the statistical significance and effect size of the potential differences between the groups. Main results. We find significantly increased sympathetic and decreased parasympathetic activity during healthy pregnancy, along with significantly attenuated autonomic responsiveness, which we hypothesize serves as a protective mechanism against sympathetic overactivity. HRV differences between these groups typically had a large effect size (Cohen’s d &gt; 0.8), with the largest effect accompanying the significantly reduced HR complexity and altered sympathovagal balance observed in pregnancy (Cohen’s d &gt; 1.2). Significance. Healthy pregnant women are autonomically distinct from their non-pregnant counterparts. Subsequently, assumptions based on HRV research in non-pregnant women cannot be readily translated to pregnant women.</p

Bayesian approach to patient-tailored vectorcardiography

For assessment of specific cardiac pathologies, vectorcardiography is generally considered superior with respect to electrocardiography. Existing vectorcardiography methods operate by calculating the vectorcardiogram (VCG) as a fixed linear combination of ECG signals. These methods, with the inverse Dower matrix method the current standard, are therefore not flexible with respect to different body compositions and geometries. Hence, they cannot be applied with accuracy on patients that do not conform to the fixed standard. Typical examples of such patients are obese patients or fetuses. For the latter category, when recording the fetal ECG from the maternal abdomen the distance of the fetal heart with respect to the electrodes is unknown. Consequently, also the signal attenuation/transformation per electrode is not known. In this paper, a Bayesian method is developed that estimates the VCG and, to some extent, also the signal attenuation in multichannel ECG recordings from either the adult 12-lead ECG or the maternal abdomen. This is done by determining for which VCG and signal attenuation the joint probability over both these variables is maximal given the observed ECG signals. The underlying joint probability distribution is determined by assuming the ECG signals to originate from scaled VCG projections and additive noise. With this method, a VCG, tailored to each specific patient, is determined. The method is compared to the inverse Dower matrix method by applying both methods on standard 12-lead ECG recordings and evaluating the performance in predicting ECG signals from the determined VCG. In addition, to model nonstandard patients, the 12-lead ECG signals are randomly scaled and, once more, the performance in predicting ECG signals from the VCG is compared between both methods. Finally, both methods are also compared on fetal ECG signals that are obtained from the maternal abdomen. For patients conforming to the standard, both methods perform similarly, with the developed method performing marginally better. For scaled ECG signals and fetal ECG signals, the developed method significantly outperforms the inverse Dower matrix method

Fetal movement quantification by fetal vectrocardiography: a preliminary study.

Fetal movement is a valuable source of information to monitor the neurological development of the fetus and assess fetal health. Currently, fetal movement can be assessed by the mother or detected by analysis of ultrasound images. Long-term monitoring of movement is complicated with both these methods as maternal self-assessment has a relatively poor sensitivity and specificity and automatic analysis of ultrasound images is not available. Moreover, ultrasound transducers transmit energy into the body, potentially endangering fetal health. In this paper, an alternative method for fetal movement monitoring is presented. This method operates by estimating and analyzing the fetal vectorcardiogram (VCG) from non-invasive recordings on the maternal abdomen. The determined fetal movement is compared with that assessed from a simultaneously performed ultrasound recording; the results of the presented method are consistent with the ultrasound images. In addition, the presented method enables quantification of the rotation angles by means of analysis of the rotation matrix between consecutive fetal VCGs, providing a tool for long-term monitoring of fetal movement with increased specificity

QRS classification and spatial combination for robust heart rate detection in low-quality fetal ECG recordings

Non-invasive fetal electrocardiography (ECG) can be used for prolonged monitoring of the fetal heart rate (FHR). However, the signal-to-noise-ratio (SNR) of non-invasive ECG recordings is often insufficient for reliable detection of the FHR. To overcome this problem, source separation techniques can be used to enhance the fetal ECG. This study uses a physiology-based source separation (PBSS) technique that has already been demonstrated to outperform widely used blind source separation techniques. Despite the relatively good performance of PBSS in enhancing the fetal ECG, PBSS is still susceptible to artifacts. In this study an augmented PBSS technique is developed to reduce the influence of artifacts. The performance of the developed method is compared to PBSS on multi-channel non-invasive fetal ECG recordings. Based on this comparison, the developed method is shown to outperform PBSS for the enhancement of the fetal ECG