Assessment of Dispersion and Bubble Entropy Measures for Enhancing Preterm Birth Prediction Based on Electrohysterographic Signals

[EN] One of the remaining challenges for the scientific-technical community is predicting preterm births, for which electrohysterography (EHG) has emerged as a highly sensitive prediction technique. Sample and fuzzy entropy have been used to characterize EHG signals, although they require optimizing many internal parameters. Both bubble entropy, which only requires one internal parameter, and dispersion entropy, which can detect any changes in frequency and amplitude, have been proposed to characterize biomedical signals. In this work, we attempted to determine the clinical value of these entropy measures for predicting preterm birth by analyzing their discriminatory capacity as an individual feature and their complementarity to other EHG characteristics by developing six prediction models using obstetrical data, linear and non-linear EHG features, and linear discriminant analysis using a genetic algorithm to select the features. Both dispersion and bubble entropy better discriminated between the preterm and term groups than sample, spectral, and fuzzy entropy. Entropy metrics provided complementary information to linear features, and indeed, the improvement in model performance by including other non-linear features was negligible. The best model performance obtained an F1-score of 90.1 ± 2% for testing the dataset. This model can easily be adapted to real-time applications, thereby contributing to the transferability of the EHG technique to clinical practice.This work was supported by the Spanish Ministry of Economy and Competitiveness, the European Regional Development Fund (MCIU/AEI/FEDER, UE RTI2018-094449-A-I00-AR), and by the Generalitat Valenciana (AICO/2019/220)Nieto Del-Amor, F.; Beskhani, R.; Ye Lin, Y.; Garcia-Casado, J.; Díaz-Martínez, MDA.; Monfort-Ortiz, R.; Diago-Almela, VJ.... (2021). Assessment of Dispersion and Bubble Entropy Measures for Enhancing Preterm Birth Prediction Based on Electrohysterographic Signals. Sensors. 21(18):1-17. https://doi.org/10.3390/s21186071S117211

Assessment of Features between Multichannel Electrohysterogram for Differentiation of Labors

[EN] Electrohysterogram (EHG) is a promising method for noninvasive monitoring of uterine electrical activity. The main purpose of this study was to characterize the multichannel EHG signals to distinguish between term delivery and preterm birth, as well as deliveries within and beyond 24 h. A total of 219 pregnant women were grouped in two ways: (1) term delivery (TD), threatened preterm labor (TPL) with the outcome of preterm birth (TPL_PB), and TPL with the outcome of term delivery (TPL_TD); (2) EHG recording time to delivery (TTD) 24 h. Three bipolar EHG signals were analyzed for the 30 min recording. Six EHG features between multiple channels, including multivariate sample entropy, mutual information, correlation coefficient, coherence, direct partial Granger causality, and direct transfer entropy, were extracted to characterize the coupling and information flow between channels. Significant differences were found for these six features between TPL and TD, and between TTD 24 h. No significant difference was found between TPL_PB and TPL_TD. The results indicated that EHG signals of TD were more regular and synchronized than TPL, and stronger coupling between multichannel EHG signals was exhibited as delivery approaches. In addition, EHG signals propagate downward for the majority of pregnant women regardless of different labors. In conclusion, the coupling and propagation features extracted from multichannel EHG signals could be used to differentiate term delivery and preterm birth and may predict delivery within and beyond 24 h.This research was funded by the National Key R&D Program, grant number 2019YFC0119700, and the National Natural Science Foundation of China, grant number U20A20388.Zhang, Y.; Hao, D.; Yang, L.; Zhou, X.; Ye Lin, Y.; Yang, Y. (2022). Assessment of Features between Multichannel Electrohysterogram for Differentiation of Labors. Sensors. 22(9):1-18. https://doi.org/10.3390/s2209335211822

Electrohysterography in the diagnosis of preterm birth: a review

This is an author-created, un-copyedited versíon of an article published in Physiological Measurement. IOP Publishing Ltd is not responsíble for any errors or omissíons in this versíon of the manuscript or any versíon derived from it. The Versíon of Record is available online at http://doi.org/10.1088/1361-6579/aaad56.[EN] Preterm birth (PTB) is one of the most common and serious complications in pregnancy. About 15 million preterm neonates are born every year, with ratios of 10-15% of total births. In industrialized countries, preterm delivery is responsible for 70% of mortality and 75% of morbidity in the neonatal period. Diagnostic means for its timely risk assessment are lacking and the underlying physiological mechanisms are unclear. Surface recording of the uterine myoelectrical activity (electrohysterogram, EHG) has emerged as a better uterine dynamics monitoring technique than traditional surface pressure recordings and provides information on the condition of uterine muscle in different obstetrical scenarios with emphasis on predicting preterm deliveries. Objective: A comprehensive review of the literature was performed on studies related to the use of the electrohysterogram in the PTB context. Approach: This review presents and discusses the results according to the different types of parameter (temporal and spectral, non-linear and bivariate) used for EHG characterization. Main results: Electrohysterogram analysis reveals that the uterine electrophysiological changes that precede spontaneous preterm labor are associated with contractions of more intensity, higher frequency content, faster and more organized propagated activity and stronger coupling of different uterine areas. Temporal, spectral, non-linear and bivariate EHG analyses therefore provide useful and complementary information. Classificatory techniques of different types and varying complexity have been developed to diagnose PTB. The information derived from these different types of EHG parameters, either individually or in combination, is able to provide more accurate predictions of PTB than current clinical methods. However, in order to extend EHG to clinical applications, the recording set-up should be simplified, be less intrusive and more robust-and signal analysis should be automated without requiring much supervision and yield physiologically interpretable results. Significance: This review provides a general background to PTB and describes how EHG can be used to better understand its underlying physiological mechanisms and improve its prediction. The findings will help future research workers to decide the most appropriate EHG features to be used in their analyses and facilitate future clinical EHG applications in order to improve PTB prediction.This work was supported by the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund under grant DPI2015-68397-R.Garcia-Casado, J.; Ye Lin, Y.; Prats-Boluda, G.; Mas-Cabo, J.; Alberola Rubio, J.; Perales Marin, AJ. (2018). Electrohysterography in the diagnosis of preterm birth: a review. Physiological Measurement. 39(2). https://doi.org/10.1088/1361-6579/aaad56S39

A critical look at studies applying over-sampling on the TPEHGDB dataset

Preterm birth is the leading cause of death among young children and has a large prevalence globally. Machine learning models, based on features extracted from clinical sources such as electronic patient files, yield promising results. In this study, we review similar studies that constructed predictive models based on a publicly available dataset, called the Term-Preterm EHG Database (TPEHGDB), which contains electrohysterogram signals on top of clinical data. These studies often report near-perfect prediction results, by applying over-sampling as a means of data augmentation. We reconstruct these results to show that they can only be achieved when data augmentation is applied on the entire dataset prior to partitioning into training and testing set. This results in (i) samples that are highly correlated to data points from the test set are introduced and added to the training set, and (ii) artificial samples that are highly correlated to points from the training set being added to the test set. Many previously reported results therefore carry little meaning in terms of the actual effectiveness of the model in making predictions on unseen data in a real-world setting. After focusing on the danger of applying over-sampling strategies before data partitioning, we present a realistic baseline for the TPEHGDB dataset and show how the predictive performance and clinical use can be improved by incorporating features from electrohysterogram sensors and by applying over-sampling on the training set

Dispersion Entropy: A Measure of Electrohysterographic Complexity for Preterm Labor Discrimination

[EN] Although preterm labor is a major cause of neonatal death and often leaves health sequels in the survivors, there are no accurate and reliable clinical tools for preterm labor prediction. The Electrohysterogram (EHG) has arisen as a promising alternative that provides relevant information on uterine activity that could be useful in predicting preterm labor. In this work, we optimized and assessed the performance of the Dispersion Entropy (DispEn) metric and compared it to conventional Sample Entropy (SampEn) in EHG recordings to discriminate term from preterm deliveries. For this, we used the two public databases TPEHG and TPEHGT DS of EHG recordings collected from women during regular checkups. The 10th, 50th and 90th percentiles of entropy metrics were computed on whole (WBW) and fast wave high (FWH) EHG bandwidths, sweeping the DispEn and SampEn internal parameters to optimize term/preterm discrimination. The results revealed that for both the FWH and WBW bandwidths the best separability was reached when computing the 10th percentile, achieving a p-value (0.00007) for DispEn in FWH, c = 7 and m = 2, associated with lower complexity preterm deliveries, indicating that DispEn is a promising parameter for preterm labor prediction.This work was supported by the Spanish ministry of economy and competitiveness, the European Regional Development Fund (MCIU/AEI/FEDER, UE RTI2018-094449-A-I00-AR) and the Generalitat Valenciana (AICO/2019/220).Nieto-Del-Amor, F.; Ye Lin, Y.; Garcia-Casado, J.; Díaz-Martínez, MDA.; González Martínez, M.; Monfort-Ortiz, R.; Prats-Boluda, G. (2021). Dispersion Entropy: A Measure of Electrohysterographic Complexity for Preterm Labor Discrimination. SCITEPRESS. 260-267. https://doi.org/10.5220/0010316602600267S26026

Electrohysterogram for ANN-Based Prediction of Imminent Labor in Women with Threatened Preterm Labor Undergoing Tocolytic Therapy

[EN] Threatened preterm labor (TPL) is the most common cause of hospitalization in the second half of pregnancy and entails high costs for health systems. Currently, no reliable labor proximity prediction techniques are available for clinical use. Regular checks by uterine electrohysterogram (EHG) for predicting preterm labor have been widely studied. The aim of the present study was to assess the feasibility of predicting labor with a 7- and 14-day time horizon in TPL women, who may be under tocolytic treatment, using EHG and/or obstetric data. Based on 140 EHG recordings, artificial neural networks were used to develop prediction models. Non-linear EHG parameters were found to be more reliable than linear for differentiating labor in under and over 7/14 days. Using EHG and obstetric data, the <7- and <14-day labor prediction models achieved an AUC in the test group of 87.1 +/- 4.3% and 76.2 +/- 5.8%, respectively. These results suggest that EHG can be reliable for predicting imminent labor in TPL women, regardless of the tocolytic therapy stage. This paves the way for the development of diagnostic tools to help obstetricians make better decisions on treatments, hospital stays and admitting TPL women, and can therefore reduce costs and improve maternal and fetal wellbeing.This work was supported by the Spanish Ministry of Economy and Competitiveness, the European Regional Development Fund (MCIU/AEI/FEDER, UE RTI2018-094449-A-I00-AR) and by the Generalitat Valenciana (AICO/2019/220).Mas-Cabo, J.; Prats-Boluda, G.; Garcia-Casado, J.; Alberola Rubio, J.; Monfort-Ortiz, R.; Martinez-Saez, C.; Perales, A.... (2020). Electrohysterogram for ANN-Based Prediction of Imminent Labor in Women with Threatened Preterm Labor Undergoing Tocolytic Therapy. 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Design and Assessment of a Robust and Generalizable ANN-Based Classifier for the Prediction of Premature Birth by means of Multichannel Electrohysterographic Records

[EN] Preterm labor is one of the major causes of neonatal deaths and also the cause of significant health and development impairments in those who survive. However, there are still no reliable and accurate tools for preterm labor prediction in clinical settings. Electrohysterography (EHG) has been proven to provide relevant information on the labor time horizon. Many studies focused on predicting preterm labor by using temporal, spectral, and nonlinear parameters extracted from single EHG recordings. However, multichannel analysis, which includes information from the whole uterus and about coupling between the recording areas, may provide better results. The cross validation method is often used to design classifiers and evaluate their performance. However, when the validation dataset is used to tune the classifier hyperparameters, the performance metrics of this dataset may not properly assess its generalization capacity. In this work, we developed and compared different classifiers, based on artificial neural networks, for predicting preterm labor using EHG features from single and multichannel recordings. A set of temporal, spectral, nonlinear, and synchronization parameters computed from EHG recordings was used as the input features. All the classifiers were evaluated on independent test datasets, which were never ¿seen¿ by the models, to determine their generalization capacity. Classifiers¿ performance was also evaluated when obstetrical data were included. The experimental results show that the classifier performance metrics were significantly lower in the test dataset (AUC range 76-91%) than in the train and validation sets (AUC range 90-99%). The multichannel classifiers outperformed the single-channel classifiers, especially when information was combined into mean efficiency indexes and included coupling information between channels. Including obstetrical data slightly improved the classifier metrics and reached an AUC of for the test dataset. These results show promise for the transfer of the EHG technique to preterm labor prediction in clinical practice.This work was supported by the Spanish Ministry of Economy and Competitiveness, the European Regional Development Fund (DPI2015-68397-R, MINECO/FEDER, and RTI2018-094449-A-I00-AR); Generalitat Valenciana (AICO/2019/220); and the VLC/Campus (UPV-FE-2018-B03).Mas-Cabo, J.; Prats-Boluda, G.; Garcia-Casado, J.; Alberola Rubio, J.; Perales Marín, AJ.; Ye Lin, Y. (2019). Design and Assessment of a Robust and Generalizable ANN-Based Classifier for the Prediction of Premature Birth by means of Multichannel Electrohysterographic Records. Journal of Sensors. 2019:1-13. https://doi.org/10.1155/2019/5373810S1132019Goldenberg, R. L., Culhane, J. F., Iams, J. D., & Romero, R. (2008). Epidemiology and causes of preterm birth. 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Refined multiscale entropy using fuzzy metrics: validation and application to nociception assessmentt

The refined multiscale entropy (RMSE) approach is commonly applied to assess complexity as a function of the time scale. RMSE is normally based on the computation of sample entropy (SampEn) estimating complexity as conditional entropy. However, SampEn is dependent on the length and standard deviation of the data. Recently, fuzzy entropy (FuzEn) has been proposed, including several refinements, as an alternative to counteract these limitations. In this work, FuzEn, translated FuzEn (TFuzEn), translated-reflected FuzEn (TRFuzEn), inherent FuzEn (IFuzEn), and inherent translated FuzEn (ITFuzEn) were exploited as entropy-based measures in the computation of RMSE and their performance was compared to that of SampEn. FuzEn metrics were applied to synthetic time series of different lengths to evaluate the consistency of the different approaches. In addition, electroencephalograms of patients under sedation-analgesia procedure were analyzed based on the patient’s response after the application of painful stimulation, such as nail bed compression or endoscopy tube insertion. Significant differences in FuzEn metrics were observed over simulations and real data as a function of the data length and the pain responses. Findings indicated that FuzEn, when exploited in RMSE applications, showed similar behavior to SampEn in long series, but its consistency was better than that of SampEn in short series both over simulations and real data. Conversely, its variants should be utilized with more caution, especially whether processes exhibit an important deterministic component and/or in nociception prediction at long scalesPeer ReviewedPostprint (published version

Refined multiscale entropy using fuzzy metrics : validation and application to nociception assessment

The refined multiscale entropy (RMSE) approach is commonly applied to assess complexity as a function of the time scale. RMSE is normally based on the computation of sample entropy (SampEn) estimating complexity as conditional entropy. However, SampEn is dependent on the length and standard deviation of the data. Recently, fuzzy entropy (FuzEn) has been proposed, including several refinements, as an alternative to counteract these limitations. In this work, FuzEn, translated FuzEn (TFuzEn), translated-reflected FuzEn (TRFuzEn), inherent FuzEn (IFuzEn), and inherent translated FuzEn (ITFuzEn) were exploited as entropy-based measures in the computation of RMSE and their performance was compared to that of SampEn. FuzEn metrics were applied to synthetic time series of different lengths to evaluate the consistency of the different approaches. In addition, electroencephalograms of patients under sedation-analgesia procedure were analyzed based on the patient's response after the application of painful stimulation, such as nail bed compression or endoscopy tube insertion. Significant differences in FuzEn metrics were observed over simulations and real data as a function of the data length and the pain responses. Findings indicated that FuzEn, when exploited in RMSE applications, showed similar behavior to SampEn in long series, but its consistency was better than that of SampEn in short series both over simulations and real data. Conversely, its variants should be utilized with more caution, especially whether processes exhibit an important deterministic component and/or in nociception prediction at long scales