Multicentric intelligent cardiotocography signal interpretation using deep semi-supervised domain adaptation via minimax entropy and domain invariance.

BACKGROUND AND OBJECTIVE: Obstetricians use Cardiotocography (CTG), which is the continuous recording of fetal heart rate and uterine contraction, to assess fetal health status. Deep learning models for intelligent fetal monitoring trained on extensively labeled and identically distributed CTG records have achieved excellent performance. However, creation of these training sets requires excessive time and specialist labor for the collection and annotation of CTG signals. Previous research has demonstrated that multicenter studies can improve model performance. However, models trained on cross-domain data may not generalize well to target domains due to variance in distribution among datasets. Hence, this paper conducted a multicenter study with Deep Semi-Supervised Domain Adaptation (DSSDA) for intelligent interpretation of antenatal CTG signals. This approach helps to align cross-domain distribution and transfer knowledge from a label-rich source domain to a label-scarce target domain. METHODS: We proposed a DSSDA framework that integrated Minimax Entropy and Domain Invariance (DSSDA-MMEDI) to reduce inter-domain gaps and thus achieve domain invariance. The networks were developed using GoogLeNet to extract features from CTG signals, with fully connected, softmax layers for classification. We designed a Dynamic Gradient-driven strategy based on Mutual Information (DGMI) to unify the losses from Minimax Entropy (MME), Domain Invariance (DI), and supervised cross-entropy during iterative learning. RESULTS: We validated our DSSDA model on two datasets collected from collaborating healthcare institutions and mobile terminals as the source and target domains, which contained 16,355 and 3,351 CTG signals, respectively. Compared to the results achieved with deep learning networks without DSSDA, DSSDA-MMEDI significantly improved sensitivity and F1-score by over 6%. DSSDA-MMEDI also outperformed other state-of-the-art DSSDA approaches for CTG signal interpretation. Ablation studies were performed to determine the unique contribution of each component in our DSSDA mechanism. CONCLUSIONS: The proposed DSSDA-MMEDI is feasible and effective for alignment of cross-domain data and automated interpretation of multicentric antenatal CTG signals with minimal annotation cost.

Machine learning on cardiotocography data to classify fetal outcomes: A scoping review.

INTRODUCTION: Uterine contractions during labour constrict maternal blood flow and oxygen delivery to the developing baby, causing transient hypoxia. While most babies are physiologically adapted to withstand such intrapartum hypoxia, those exposed to severe hypoxia or with poor physiological reserves may experience neurological injury or death during labour. Cardiotocography (CTG) monitoring was developed to identify babies at risk of hypoxia by detecting changes in fetal heart rate (FHR) patterns. CTG monitoring is in widespread use in intrapartum care for the detection of fetal hypoxia, but the clinical utility is limited by a relatively poor positive predictive value (PPV) of an abnormal CTG and significant inter and intra observer variability in CTG interpretation. Clinical risk and human factors may impact the quality of CTG interpretation. Misclassification of CTG traces may lead to both under-treatment (with the risk of fetal injury or death) or over-treatment (which may include unnecessary operative interventions that put both mother and baby at risk of complications). Machine learning (ML) has been applied to this problem since early 2000 and has shown potential to predict fetal hypoxia more accurately than visual interpretation of CTG alone. To consider how these tools might be translated for clinical practice, we conducted a review of ML techniques already applied to CTG classification and identified research gaps requiring investigation in order to progress towards clinical implementation. MATERIALS AND METHOD: We used identified keywords to search databases for relevant publications on PubMed, EMBASE and IEEE Xplore. We used Preferred Reporting Items for Systematic Review and Meta-Analysis for Scoping Reviews (PRISMA-ScR). Title, abstract and full text were screened according to the inclusion criteria. RESULTS: We included 36 studies that used signal processing and ML techniques to classify CTG. Most studies used an open-access CTG database and predominantly used fetal metabolic acidosis as the benchmark for hypoxia with varying pH levels. Various methods were used to process and extract CTG signals and several ML algorithms were used to classify CTG. We identified significant concerns over the practicality of using varying pH levels as the CTG classification benchmark. Furthermore, studies needed to be more generalised as most used the same database with a low number of subjects for an ML study. CONCLUSION: ML studies demonstrate potential in predicting fetal hypoxia from CTG. However, more diverse datasets, standardisation of hypoxia benchmarks and enhancement of algorithms and features are needed for future clinical implementation.

Anaphylaxis-induced premature uterine contractions: a case report and literature review.

BACKGROUND: Preterm labor is caused by multiple etiologies, including intra-amniotic infection and/or intra-amniotic inflammation, vascular disorders, cervical disease, decidual senescence, and breakdown of maternal-fetal tolerance. Accumulating evidence in vivo and in vitro has shown that an allergic reaction, including anaphylaxis, can induce preterm uterine contractions. This report describes a case of a pregnant woman who developed anaphylaxis and regular uterine contractions after the ingestion of a strawberry-coated biscuit. We also review the mechanism of allergic reaction (hypersensitivity)-induced preterm labor. Case presentation A 31-year-old woman (gravida 1, para 0) at 30+2 weeks of gestation was admitted to the labor and delivery unit with regular uterine contractions and anaphylactic symptoms after she ingested a strawberry-coated biscuit as a snack. The uterine contractions resolved after the treatment of anaphylaxis by administering antihistamines and epinephrine. The patient subsequently delivered at 39+3 weeks of gestation. The amniotic fluid profile showed no infection or inflammation. A postpartum skin-prick test confirmed a positive type 1 hypersensitivity reaction to the strawberry-coated biscuit. CONCLUSIONS: We report a case of anaphylaxis-induced uterine contractility in which uterine contractions subsided after the treatment of anaphylaxis. The absence of intra-amniotic infection and/or intra-amniotic inflammation and the cause of the anaphylaxis were confirmed. Our findings indicate that maternal allergic reactions may be one of the mechanisms of preterm labor.

Multichannel mapping of in vivo rat uterine myometrium exhibits both high and low frequency electrical activity in non-pregnancy.

The uterus exhibits intermittent electrophysiological activity in vivo. Although most active during labor, the non-pregnant uterus can exhibit activity of comparable magnitude to the early stages of labor. In this study, two types of flexible electrodes were utilized to measure the electrical activity of uterine smooth muscle in vivo in anesthetized, non-pregnant rats. Flexible printed circuit electrodes were placed on the serosal surface of the uterine horn of six anesthetized rats. Electrical activity was recorded for a duration of 20-30 min. Activity contained two components: high frequency activity (bursts) and an underlying low frequency 'slow wave' which occurred concurrently. These components had dominant frequencies of 6.82 ± 0.63 Hz for the burst frequency and 0.032 ± 0.0055 Hz for the slow wave frequency. There was a mean burst occurrence rate of 0.76 ± 0.23 bursts per minute and mean burst duration of 20.1 ± 6.5 s. The use of multiple high-resolution electrodes enabled 2D mapping of the initiation and propagation of activity along the uterine horn. This in vivo approach has the potential to provide the organ level detail to help interpret non-invasive body surface recordings.

In vitro inhibition of uterine contractions using electrospun nanofibers loaded with nifedipine and ML7.

OBJECTIVE: To formulate a nanofiber-based controlled drug delivery system that could be effective in preventing uterine contractions and can be used for the treatment of preterm labor. PATIENTS AND METHODS: We utilized uterine tissue samples obtained from ten pregnant women who underwent cesarean section at term to investigate the effect of nanofibers on spontaneous and induced myometrial contractions. We prepared nifedipine and ML7-loaded nanofibers using the electrospinning method with Poly(D,L-lactide-co-glycolide) (PLGA) polymer, resulted in seven groups of nanofibers, including a control group. Group I served as the control, Group II was non-drug loaded nanofiber, Group III was nifedipine (10-5 M) loaded nanofiber, Group IV was ML7 (3x10-5 M) loaded nanofiber, Group V was ML7 (3x10-5 M) and nifedipine (10-5 M) nanofiber, Group VI was ML7 (3x10-5 M) and nifedipine (3x10-5 M) nanofiber, and Group VII was ML7 (3x10-5 M) and nifedipine (10-4 M) nanofiber. To evaluate the contractile response, the nanofibers loaded with different doses of ML7 and nifedipine were applied onto the tissue strips, and in vitro organ bath experiments were performed. Full-thickness uterine samples were cleared of the serosa and surrounding tissues, and eight strips (3x10 mm) were prepared from each sample. The seven different nanofiber formulations were gently placed and sutured onto the strips, with one strip always kept as the time control. We recorded spontaneous, KCl-induced, and stimulated cumulative oxytocin-induced contractions from all samples in all groups. After completing all experiments, the viability of the strips was checked, and weight measurement was recorded. RESULTS: The administration of drug-loaded polymers resulted in a significant decrease in both the frequency and intensity of spontaneous and induced contractions in all groups (p<0.01). No significant difference was observed between the control group and the non-drug-loaded nanofiber group in post hoc analysis (p=0.704). In terms of amplitude and frequency of contractions, the most significant decrease was observed in group VII at cumulative oxytocin doses compared to the control and non-drug-loaded nanofiber groups (p<0.05). Moreover, group VI also showed a significant decrease in contraction intensity and frequency compared to the control and non-drug-loaded nanofiber groups (p<0.05). While the use of nifedipine and/or ML7-loaded nanofibers decreased both intensity and frequency of contraction, this attenuation was not significant compared to the control and empty polymer groups. However, a more significant inhibition was observed when ML7 was used with nifedipine at doses of 3x10-5 M and 10-4 M. CONCLUSIONS: The results indicate that human uterine contractions can be inhibited using calcium channel blocker (nifedipine) and myosin light chain kinase inhibitor (ML7) loaded nanofibers in uterine tissue strips. These results strongly suggested the potential for the development of locally effective and safe controlled drug release systems to prevent premature birth.

Myometrium infection decreases TREK1 through NHE1 and increases contraction in pregnant mice.

Intrauterine infection during pregnancy can enhance uterine contractions. A two-pore K+ channel TREK1 is crucial for maintaining uterine quiescence and reducing contractility, with its properties regulated by pH changes in cell microenvironment. Meanwhile, the sodium hydrogen exchanger 1 (NHE1) plays a pivotal role in modulating cellular pH homeostasis, and its activation increases smooth muscle tension. By establishing an infected mouse model of Escherichia coli (E. coli) and lipopolysaccharide (LPS), we used Western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence to detect changes of TREK1 and NHE1 expression in the myometrium, and isometric recording measured the uterus contraction. The NHE1 inhibitor cariporide was used to explore the effect of NHE1 on TREK1. Finally, cell contraction assay and siRNA transfection were performed to clarify the relationship between NHE1 and TREK1 in vitro. We found that the uterine contraction was notably enhanced in infected mice with E. coli and LPS administration. Meanwhile, TREK1 expression was reduced, whereas NHE1 expression was upregulated in infected mice. Cariporide alleviated the increased uterine contraction and promoted myometrium TREK1 expression in LPS-injected mice. Furthermore, suppression of NHE1 with siRNA transfection inhibited the contractility of uterine smooth muscle cells and activated the TREK1. Altogether, our findings indicate that infection increases the uterine contraction by downregulating myometrium TREK1 in mice, and the inhibition of TREK1 is attributed to the activation of NHE1.NEW & NOTEWORTHY Present work found that infection during pregnancy will increase myometrium contraction. Infection downregulated NHE1 and followed TREK1 expression and activation decrease in myometrium, resulting in increased myometrium contraction.

Optimal starting dosing regimen of intravenous oxytocin for labor induction based on the population kinetic-pharmacodynamic model of uterine contraction frequency.

BACKGROUND: Intravenous oxytocin is commonly used for labor induction. However, a consensus on the initial dosing regimen is lac with conflicting research findings and varying guidelines. This study aimed to develop a population kinetic-pharmacodynamic (K-PD) model for oxytocin-induced uterine contractions considering real-world data and relevant influencing factors to establish an optimal starting dosing regimen for intravenous oxytocin. METHODS: This retrospective study included pregnant women who underwent labor induction with intravenous oxytocin at Peking University Third Hospital in 2020. A  population K-PD model was developed to depict the time course of uterine contraction frequency (UCF), and covariate screening identified significant factors affecting the pharmacokinetics and pharmacodynamics of oxytocin. Model-based simulations were used to optimize the current starting regimen based on specific guidelines. RESULTS: Data from 77 pregnant women with 1095 UCF observations were described well by the K-PD model. Parity, cervical dilation, and membrane integrity are significant factors influencing the effectiveness of oxytocin. Based on the model-based simulations, the current regimens showed prolonged onset times and high infusion rates. This study proposed a revised approach, beginning with a rapid infusion followed by a reduced infusion rate, enabling most women to achieve the target UCF within approximately 30 min with the lowest possible infusion rate. CONCLUSION: The K-PD model of oxytocin effectively described the changes in UCF during labor induction. Furthermore, it revealed that parity, cervical dilation, and membrane integrity are key factors that influence the effectiveness of oxytocin. The optimal starting dosing regimens obtained through model simulations provide valuable clinical references for oxytocin treatment.

Changes in the conflicting nongenomic effects of progesterone in rat myometrium during pregnancy.

AIMS: Although the functions of progesterone in the myometrium are well-established, the nongenomic effects of progesterone in pregnant myometrial contractions are still unclear. Therefore, this study aimed to investigate changes in the nongenomic effects of progesterone during pregnancy. MAIN METHODS: Myometrial strips were obtained from non-pregnant, pregnant, and postpartum rats, and the nongenomic effects of progesterone in the myometrium during pregnancy were examined. Additionally, the influence of actinomycin D and cycloheximide and the effects of Org OD-02-0 (a specific membrane progesterone receptor (mPR) agonist) in the myometrium were investigated. Moreover, DNA microarray and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to identify genes involved in progesterone-induced effects in the myometrium. KEY FINDINGS: Progesterone did not cause rhythmic contractions in non-pregnant myometrium but induced rhythmic contractions in pregnant myometrium, with the effects peaking at 20 d + 8 h of pregnancy. However, myometrial contractions decreased after delivery and were restored to non-pregnant levels at 7 d postpartum. Additionally, progesterone stably inhibited high KCl-induced myometrial contractions during pregnancy. Moreover, the nongenomic effects of progesterone were unaffected by actinomycin D or cycloheximide, and Org OD-02-0 effectively mimicked these effects. DNA microarray analysis and qRT-PCR revealed a significant increase in mPRß gene expression during pregnancy. However, mPRα, mPRγ, mPRδ, and mPRε expression levels remained unchanged. SIGNIFICANCE: The stimulatory nongenomic effect of progesterone, which was inducible and mPRß-dependent during pregnancy, may be involved in parturition. The inhibitory effect, which was constitutive and depended on other mPRs, may be involved in pregnancy maintenance.

Phenanthroline relaxes uterine contractions induced by diverse contractile agents by decreasing cytosolic calcium concentration.

Uterine contractions during labor and preterm labor are influenced by a complex interplay of factors, including hormones and inflammatory mediators. This complexity may contribute to the limited efficacy of current tocolytics for preterm labor, a significant challenge in obstetrics with 15 million cases annually and approximately 1 million resulting deaths worldwide. We have previously shown that the myometrium expresses bitter taste receptors (TAS2Rs) and that their activation leads to uterine relaxation. Here, we investigated whether the selective TAS2R5 agonist phenanthroline can induce relaxation across a spectrum of human uterine contractions and whether the underlying mechanism involves changes in intracellular Ca2+ signaling. We performed experiments using samples from pregnant women undergoing scheduled cesarean delivery, assessing responses to various inflammatory mediators and oxytocin with and without phenanthroline. Our results showed that phenanthroline concentration-dependently inhibited contractions induced by PGF2α, U46619, 5-HT, endothelin-1 and oxytocin. Furthermore, in hTERT-infected human myometrial cells exposed to uterotonics, phenanthroline effectively suppressed the increase in intracellular Ca2+ concentration induced by PGF2α, U46619, oxytocin, and endothelin-1. These results suggest that the selective TAS2R5 agonist may not only significantly reduce uterine contractions but also decrease intracellular Ca2+ levels. This study highlights the potential development of TAS2R5 agonists as a new class of uterine relaxants, providing a novel avenue for improving the management of preterm labor.

Real-time ultrasound demonstration of uterine isthmus contractions during pregnancy.

BACKGROUND: Asymptomatic isthmic contractions are a frequent physiological phenomenon in pregnancy, sometimes triggered by bladder voiding. They can interfere with proper cervical length assessment and may lead to false images of placenta previa. However, there is limited research on the prevalence and characteristics of these contractions. OBJECTIVE: This study aimed to determine the prevalence and characteristics of isthmic contractions after bladder voiding in the second trimester of pregnancy, to evaluate their effect on cervical length assessment, and to propose a new method for the objective assessment of the presence and intensity of isthmic contractions. STUDY DESIGN: In this prospective observational study, long videos of the uterine cervix were recorded in 30 singleton pregnancies during the second trimester of pregnancy after bladder voiding. Isthmic length and cervicoisthmic length changes were assessed over time. The isthmic length was measured using a new approach, which involved calculating the distance from the base of the cervix to the internal os, including the isthmus. RESULTS: Isthmic contractions were observed in 43% of pregnant women (95% confidence interval, 26%-62%) after bladder voiding. The median time for complete isthmus relaxation was 19.7 minutes (95% confidence interval, 15.0 to not available). No substantial differences in maternal characteristics were found between individuals with and without contractions. The proposed method for measuring isthmic length provided an objective assessment of the presence and intensity of isthmic contractions. A cutoff of 18 mm in isthmic length allowed for the distinction of pregnant women presenting a contraction. In addition, the study identified a characteristic undulatory pattern in the relaxation of the isthmus in half of the cases with contractions. CONCLUSION: Isthmic contractions are a common occurrence after bladder voiding in the second trimester of pregnancy and may interfere with proper cervical length assessment. We recommend performing cervical assessment at least 20 minutes after bladder voiding to reduce the risk of bias in cervical length measurement and to avoid false images of placenta previa. The new method for measuring isthmic length provides an objective way to assess the presence and intensity of isthmic contractions. Further research is needed to understand the role of isthmic contractions in the physiology of pregnancy and birth.

Multiphysics and multiscale modeling of uterine contractions: integrating electrical dynamics and soft tissue deformation with fiber orientation.

The development of a comprehensive uterine model that seamlessly integrates the intricate interactions between the electrical and mechanical aspects of uterine activity could potentially facilitate the prediction and management of labor complications. Such a model has the potential to enhance our understanding of the initiation and synchronization mechanisms involved in uterine contractions, providing a more profound comprehension of the factors associated with labor complications, including preterm labor. Consequently, it has the capacity to assist in more effective preparation and intervention strategies for managing such complications. In this study, we present a computational model that effectively integrates the electrical and mechanical components of uterine contractions. By combining a state-of-the-art electrical model with the Hyperelastic Mass-Spring Model (HyperMSM), we adopt a multiphysics and multiscale approach to capture the electrical and mechanical activities within the uterus. The electrical model incorporates the generation and propagation of action potentials, while the HyperMSM simulates the mechanical behavior and deformations of the uterine tissue. Notably, our model takes into account the orientation of muscle fibers, ensuring that the simulated contractions align with their inherent directional characteristics. One noteworthy aspect of our contraction model is its novel approach to scaling the rest state of the mesh elements, as opposed to the conventional method of applying mechanical loads. By doing so, we eliminate artificial strain energy resulting from the resistance of soft tissues' elastic properties during contractions. We validated our proposed model through test simulations, demonstrating its feasibility and its ability to reproduce expected contraction patterns across different mesh resolutions and configurations. Moving forward, future research efforts should prioritize the validation of our model using robust clinical data. Additionally, it is crucial to refine the model by incorporating a more realistic uterus model derived from medical imaging. Furthermore, applying the model to simulate the entire childbirth process holds immense potential for gaining deeper insights into the intricate dynamics of labor.

BKCa channels are involved in spontaneous and lipopolysaccharide-stimulated uterine contraction in late gestation mice†.

The large-conductance, voltage-gated, calcium (Ca2+)-activated potassium channel (BKCa) is one of the most abundant potassium channels in the myometrium. Previous work conducted by our group has identified a link between inflammation, BKCa channels and excitability of myometrial smooth muscle cells. Here, we investigate the role of BKCa channels in spontaneous and lipopolysaccharide (LPS)-stimulated uterine contraction to gain a better understanding of the relationship between the BKCa channel and uterine contraction in basal and inflammatory states. Uteri of C57BL/6 J mice on gestational day 18.5 (GD18.5) were obtained and either fixed in formalin or used immediately for tension recording or isolation of primary myocytes for patch-clamp. Paraffin sections were used for immunofluorescenctdetection of BKCa and Toll-like receptor (TLR4). For tension recordings, LPS was administered to determine its effect on uterine contractions. Paxilline, a BKCa inhibitor, was used to dissect the role of BKCa in uterine contraction in basal and inflammatory states. Finally, patch-clamp recordings were performed to investigate the relationship between LPS, the BKCa channel and membrane currents in mouse myometrial smooth muscle cells (mMSMCs). We confirmed the expression of BKCa and TLR4 in the myometrium of GD18.5 mice and found that inhibiting BKCa channels with paxilline suppressed both spontaneous and LPS-stimulated uterine contractions. Furthermore, application of BKCa inhibitors (paxilline or iberiotoxin) after LPS inhibited BKCa channel activity in mMSMCs. Moreover, pretreatment with BKCa inhibitor or the TLR4 inhibitor suppressed LPS-activated BKCa currents. Our study demonstrates that BKCa channels are involved in both basal and LPS-stimulated uterine contraction in pregnant mice.

Serpin family E member 1 enhances myometrium contractility by increasing ATP production during labor.

The uterine contraction during labor, a process with repetitive hypoxia and high energy consumption, is essential for successful delivery. However, the molecular mechanism of myometrial contraction regulation is unknown. Serpin family E member 1 (SERPINE1), one of the most upregulated genes in laboring myometrium in both transcriptome and proteome, was highlighted in our previous study. Here, we confirmed SERPINE1 is upregulated in myometrium during labor. Blockade of SERPINE1 using small interfering RNA (siRNA) or inhibitor (Tiplaxtinin) under hypoxic conditions in myocytes or myometrium in vitro showed a decrease contractility, which was achieved by regulating ATP production. Chromatin immunoprecipitation (ChIP-seq), Co-immunoprecipitation (Co-IP), and glutathione-S-transferase (GST) pull down explored that the promoter of SERPINE1 is directly activated by hypoxia-inducible factor-1α (HIF-1α) and SERPINE1 interacts with ATP Synthase Peripheral Stalk Subunit F6 (ATP5PF). Together they enhance hypoxia driven myometrial contraction by maintaining ATP production in the key oxidative phosphorylation pathway. The results provide new insight for uterine contraction regulation, and potential novel therapeutic targets for labor management.

Machine Learning to Classify Cardiotocography for Fetal Hypoxia Detection.

Fetal hypoxia can cause damaging consequences on babies' such as stillbirth and cerebral palsy. Cardiotocography (CTG) has been used to detect intrapartum fetal hypoxia during labor. It is a non-invasive machine that measures the fetal heart rate and uterine contractions. Visual CTG suffers inconsistencies in interpretations among clinicians that can delay interventions. Machine learning (ML) showed potential in classifying abnormal CTG, allowing automatic interpretation. In the absence of a gold standard, researchers used various surrogate biomarkers to classify CTG, where some were clinically irrelevant. We proposed using Apgar scores as the surrogate benchmark of babies' ability to recover from birth. Apgar scores measure newborns' ability to recover from active uterine contraction, which measures appearance, pulse, grimace, activity and respiration. The higher the Apgar score, the healthier the baby is.We employ signal processing methods to pre-process and extract validated features of 552 raw CTG. We also included CTG-specific characteristics as outlined in the NICE guidelines. We employed ML techniques using 22 features and measured performances between ML classifiers. While we found that ML can distinguish CTG with low Apgar scores, results for the lowest Apgar scores, which are rare in the dataset we used, would benefit from more CTG data for better performance. We need an external dataset to validate our model for generalizability to ensure that it does not overfit a specific population.Clinical Relevance- This study demonstrated the potential of using a clinically relevant benchmark for classifying CTG to allow automatic early detection of hypoxia to reduce decision-making time in maternity units.

Empirical Mode Decomposition Based Measures for Investigating the Progression of Pregnancy from Uterine EMG.

The objective of this study is to analyze the uterine electromyography (uEMG) signals to study the progression of pregnancy under term condition (gestational age > 36 weeks) using EMD-based time-frequency features. uEMG signals are obtained from the multiple public datasets during two conditions, namely T1 (acquired < 26 gestational weeks) and T2 (acquired ≥ 26 gestational weeks). The considered signals are preprocessed. Empirical mode decomposition is applied to decompose the signals and time-frequency features, such as median frequency (MDF), mean frequency (MNF), peak frequency and peak magnitude, are extracted from each intrinsic mode functions and statistically analyzed. The results depict that the obtained time-frequency features are able to distinguish between T1 and T2 conditions. The extracted features, namely MNF and MDF, are observed to decrease from T1 to T2 conditions. These features are found to have higher effect size, confirming the better differentiation between T1 and T2 conditions. It appears that EMD-based time-frequency features can aid in studying the evolving changes in uterine contractions towards labor.

Multi-channel electrohysterography enabled uterine contraction characterization and its effect in delivery assessment.

Uterine contractions are routinely monitored by tocodynamometer (TOCO) at late stage of pregnancy to predict the onset of labor. However, TOCO reveals no information on the synchrony and coherence of contractions, which are important contributors to a successful delivery. The electrohysterography (EHG) is a recording of the electrical activities that trigger the local muscles to contract. The spatial-temporal information embedded in multiple channel EHG signals make them ideal for characterizing the synchrony and coherence of uterine contraction. To proceed, contractile time-windows are identified from TOCO signals and are then used to segment out the simultaneously recorded EHG signals of different channels. We construct sample entropy SamEn and Concordance Correlation based feature ψ from these EHG segments to quantify the synchrony and coherence of contraction. To test the effectiveness of the proposed method, 122 EHG recordings in the Icelandic EHG database were divided into two groups according to the time difference between the gestational ages at recording and at delivery (TTD). Both SamEn and ψ show clear difference in the two groups (p<10-5) even when measurements were made 120 h before delivery. Receiver operating characteristic curve analysis of these two features gave AUC values of 0.834 and 0.726 for discriminating imminent labor defined with TTD ≤ 24 h. The SamEn was significantly smaller in women (0.1433) of imminent labor group than in women (0.3774) of the pregnancy group. Using an optimal cutoff value of SamEn to identify imminent labor gives sensitivity, specificity, and accuracy as high as 0.909, 0.712 and 0.743, respectively. These results demonstrate superiority in comparing to the existing SOTA methods. This study is the first research work focusing on characterizing the synchrony property of contractions from the electrohysterography signals. Despite the very limited dataset used in the validation process, the promising results open a new direction to the use of electrohysterography in obstetrics.

Detection of postpartum uterine activity with electrohysterography.

OBJECTIVE: Uterine contractions are essential for childbirth, but also for expulsion of the placenta and for limiting postpartum blood loss. Postpartum hemorrhage is associated with almost 25% of the maternal deaths worldwide and the leading cause of maternal death in most low-income countries. Little is known about the physiology of the uterus postpartum, particularly due to the lack of an accurate measurement tool. The primary objective of this pilot study is to explore the potential of using electrohysterography to detect postpartum uterine contractions. If postpartum uterine activity can be objectified, this could contribute to understanding the physiology of the uterus and improve diagnosis and treatment of postpartum hemorrhage. STUDY DESIGN: In this observational study we included women aiming for a vaginal birth in two large maternity clinics in the Netherlands, Amphia Hospital Breda (group A, N2018-0161) and Máxima Medical Center Veldhoven (group B, N17.149). An electrode patch was placed on the maternal abdomen to record real-time electrical uterine activity until one hour postpartum continuously. In group A, the placement of the patch was lower than in group B. For analysis, tracings were divided into five different phases (1: dilatation until start pushing, 2: from start pushing until childbirth, 3: from childbirth until placental expulsion, 4: first hour after placental expulsion and 5: after one hour postpartum). Readability, signal quality and contraction frequency per hour were assessed. Additionally, patient satisfaction was evaluated through a survey. RESULTS: In total 91 pregnant women were included of whom 45 in group A and 46 women in group B. Complete registrations were obtained throughout the five labor phases with very little artefacts or signal loss. The readability of the tracings decreased after childbirth. A significantly better readability was found in tracings where the patch placement was lower on the abdomen for phases 4 and 5. Contraction frequency was highest during phase 2 and decreased towards phase 5. Women rated the satisfaction with electrohysterography as high and mostly did not notice the patch. CONCLUSION: It is possible to detect uterine activity postpartum with electrohysterography. Further investigation is recommended to improve diagnosis and treatment of postpartum hemorrhage.

Upregulated TIMP1 facilitates and coordinates myometrial contraction by decreasing collagens and cell adhesive capacity during human labor.

Myometrial contraction is one of the key events involved in parturition. Increasing evidence suggests the importance of the extracellular matrix (ECM) in this process, in addition to the functional role of myometrial smooth muscle cells, and our previous study identified an upregulated tissue inhibitor of metalloproteinase 1 (TIMP1) in human laboring myometrium compared to nonlabor samples. This study aimed to further explore the potential role of TIMP1 in myometrial contraction. First, we confirmed increased myometrial TIMP1 levels in labor and during labor with cervical dilation using transcriptomic and proteomic analyses, followed by real-time PCR, western blotting, and immunohistochemistry. Then, a cell contraction assay was performed to verify the decreased contractility after TIMP1 knockdown in vitro. To further understand the underlying mechanism, we used RNA-sequencing analysis to reveal the upregulated genes after TIMP1 knockdown; these genes were enriched in collagen fibril organization, cell adhesion, and ECM organization. Subsequently, a human matrix metalloproteinase (MMP) array and collagen staining were performed to determine the TIMPs, MMPs and collagens in laboring and nonlabor myometrium. A real-time cell adhesion assay was used to detect cell adhesive capacity. The results showed upregulated MMP8 and MMP9, downregulated collagens, and attenuated cell adhesive capacity in laboring myometrium, while lower MMP levels and higher collagen levels and cell adhesive capacity were observed in nonlabor. Moreover, TIMP1 knockdown led to restoration of cell adhesive capacity. Together, these results indicate that upregulated TIMP1 during labor facilitates and coordinates myometrial contraction by decreasing collagen and cell adhesive capacity, which may provide effective strategies for the regulation of myometrial contraction.