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.

The Rate of Cesarean Section and Newborn Apgar score In Two Types Of Physiological Delivery and Facilitated Delivery in Mothers with First Pregnancy.

INTRODUCTION: Labor pain is often severe and its lack of relief can have a bad effect on the mother's physiological condition. Accurate measurement and appropriate treatment of pain is an important problem. There are several choices for the control of labor pain, however, each method has its own risks and benefits regarding its efficiency and availability; therefore, the aim of this study was to compare the rate of cesarean section and newborn Apgar in two types of physiological delivery and facilitated delivery among mothers with first delivery. MATERIALS AND METHODS: This case-control study was conducted on mothers aged 18-35 who went to the hospital to give birth. In the present study, 8 sessions (90 minutes each session) were held to prepare mothers from 20 to 37 weeks of pregnancy. Candidate mothers for physiological labor were hospitalized without intervention and in the active phase of labor, and their labor stages were planned physiologically. The pain intensity of mothers was asked using a scale (VAS) during labor every half hour (according to the pain scale from 0 to 10). The average score of pain during the first and second stages, type of delivery, amount of postpartum bleeding, length of the stage of delivery, infection, and fever after delivery, Apgar score of the baby, perineal status, mother's satisfaction and the rate of hospitalization of the baby in NICU were recorded. Furthermore, the level of satisfaction with childbirth was evaluated with the help of Mackey's standard satisfaction questionnaire. RESULTS: The average age of the physiological delivery and facilitated delivery groups was 26.37 ± 5.23 years and 26.58 ± 5.79 years, respectively. Physiological delivery significantly required less conversion to cesarean section. The most common etiology was caesarean section in the physiologic labor group, and a drop in NST was reported in the facilitated group. The analysis of the results demonstrated no significant difference between the etiology of cesarean section and the study groups. The Apgar score in the physiological group was significantly better than the facilitated group. There is no significant relationship between the study group and the amount of bleeding during delivery. Furthermore, there was no significant relationship between the study group and the incidence of postpartum infection. The rate of NICU admission in the facilitated group was found to be significantly higher than physiological delivery. CONCLUSION: The results of this study revealed that the rate of caesarean section, the rate of need for NICU, newborns' Apgar score, and the rate of mothers' satisfaction in physiological delivery group were significantly different from the other groups, but the rate of wound infection and the amount of postpartum bleeding in the two groups showed a significant difference.

The physiology and pharmacology of oxytocin in labor and in the peripartum period.

Oxytocin is a reproductive hormone implicated in the process of parturition and widely used during labor. Oxytocin is produced within the supraoptic nucleus and paraventricular nucleus of the hypothalamus and released from the posterior pituitary lobe into the circulation. Oxytocin is released in pulses with increasing frequency and amplitude in the first and second stages of labor, with a few pulses released in the third stage of labor. During labor, the fetus exerts pressure on the cervix of the uterus, which activates a feedforward reflex-the Ferguson reflex-which releases oxytocin. When myometrial contractions activate sympathetic nerves, it decreases oxytocin release. When oxytocin binds to specific myometrial oxytocin receptors, it induces myometrial contractions. High levels of circulating estrogen at term make the receptors more sensitive. In addition, oxytocin stimulates prostaglandin synthesis and release in the decidua and chorioamniotic membranes by activating a specific type of oxytocin receptor. Prostaglandins contribute to cervical ripening and uterine contractility in labor. The oxytocin system in the brain has been implicated in decreasing maternal levels of fear, pain, and stress, and oxytocin release and function during labor are stimulated by a social support. Moreover, studies suggest, but have not yet proven, that labor may be associated with long-term, behavioral and physiological adaptations in the mother and infant, possibly involving epigenetic modulation of oxytocin production and release and the oxytocin receptor. In addition, infusions of synthetic oxytocin are used to induce and augment labor. Oxytocin may be administered according to different dose regimens at increasing rates from 1 to 3 mIU/min to a maximal rate of 36 mIU/min at 15- to 40-minute intervals. The total amount of synthetic oxytocin given during labor can be 5 to 10 IU, but lower and higher amounts of oxytocin may also be given. High-dose infusions of oxytocin may shorten the duration of labor by up to 2 hours compared with no infusion of oxytocin; however, it does not lower the frequency of cesarean delivery. When synthetic oxytocin is administered, the plasma concentration of oxytocin increases in a dose-dependent way: at infusion rates of 20 to 30 mIU/min, plasma oxytocin concentration increases approximately 2- to 3-fold above the basal level. Synthetic oxytocin administered at recommended dose levels is not likely to cross the placenta or maternal blood-brain barrier. Synthetic oxytocin should be administered with caution as high levels may induce tachystole and uterine overstimulation, with potentially negative consequences for the fetus and possibly the mother. Of note, 5 to 10 IU of synthetic oxytocin is often routinely given as an intravenous or intramuscular bolus administration after delivery to induce uterine contractility, which, in turn, induces uterine separation of the placenta and prevents postpartum hemorrhage. Furthermore, it promotes the expulsion of the placenta.

Artificial intelligence based cardiotocogram assessment during labor.

OBJECTIVE: To assess whether artificial intelligence, inspired by clinical decision-making procedures in delivery rooms, can correctly interpret cardiotocographic tracings and distinguish between normal and pathological events. STUDY DESIGN: A method based on artificial intelligence was developed to determine whether a cardiotocogram shows a normal response of the fetal heart rate to uterine activity (UA). For a given fetus and given the UA and previous FHR, the method predicts a fetal heart rate response, under the assumption that the fetus is still in good condition and based on how that specific fetus has responded so far. We hypothesize that this method, when having only learned from fetuses born in good condition, is incapable of predicting the response of a compromised fetus or an episode of transient fetal distress. The (in)capability of the method to predict the fetal heart rate response would then yield a method that can help to assess fetal condition when the obstetrician is in doubt. Cardiotocographic data of 678 deliveries during labor were selected based on a healthy outcome just after birth. The method was trained on the cardiotocographic data of 548 fetuses of this group to learn their heart rate response. Subsequently it was evaluated on 87 fetuses, by assessing whether the method was able to predict their heart rate responses. The remaining 43 cardiotocograms were segment-by-segment annotated by three experienced gynecologists, indicating normal, suspicious, and pathological segments, while having access to the full recording and neonatal outcome. This future knowledge makes the expert annotations of a quality that is unachievable during live interpretation. RESULTS: The comparison between abnormalities detected by the method (only using past and present input) and the annotated CTG segments by gynecologists (also looking at future input) yields an area under the curve of 0.96 for the distinction between normal and pathological events in majority-voted annotations. CONCLUSION: The developed method can distinguish between normal and pathological events in near real-time, with a performance close to the agreement between three gynecologists with access to the entire CTG tracing and fetal outcome. The method has a strong potential to support clinicians in assessing fetal condition in clinical practice.

Failure to progress or just normal? A constructivist grounded theory of physiological plateaus during childbirth.

BACKGROUND AND PROBLEM: During childbirth, one of the most common diagnoses of pathology is 'failure to progress', frequently resulting in labour augmentation and intervention cascades. However, failure to progress is poorly defined and evidence suggests that some instances of slowing, stalling and pausing labour patterns may represent physiological plateaus. AIM: To explore how midwives conceptualise physiological plateaus and the significance such plateaus may have for women's labour trajectory and birth outcome. METHODS: Twenty midwives across Australia participated in semi-structured interviews between September 2020 and February 2022. Constructivist grounded theory methodology was applied to analyse data, including multi-phasic coding and application of constant comparative methods, resulting in a novel theory of physiological plateaus that is firmly supported by participant data. FINDINGS: This study found that the conceptualisation of plateauing labour depends largely on health professionals' philosophical assumptions around childbirth. While the Medical Dominant Paradigm frames plateaus as invariably pathological, the Holistic Midwifery Paradigm acknowledges plateaus as a common and valuable element of labour that serves a self-regulatory purpose and results in good birth outcomes for mother and baby. DISCUSSION: Contemporary medicalised approaches in maternity care, which are based on an expectation of continuous labour progress, appear to carry a risk for a misinterpretation of physiological plateaus as pathological. CONCLUSION: This study challenges the widespread bio-medical conceptualisation of plateauing labour as failure to progress, encourages a renegotiation of what can be considered healthy and normal during childbirth, and provides a stimulus to acknowledge the significance of childbirth philosophy for maternity care practice.

Re-evaluating fetal scalp pH thresholds: An examination of fetal pH variations during labor.

INTRODUCTION: Since the 1970s, fetal scalp blood sampling (FSBS) has been used as a second-line test of the acid-base status of the fetus to evaluate fetal well-being during labor. The commonly employed thresholds that delineate normal pH (>7.25), subnormal (7.20-7.25), and pathological pH (<7.20) guide clinical decisions. However, these experienced-based thresholds, based on observations and common sense, have yet to be confirmed. The aim of the study was to investigate if pH drop rate accelerates at the common thresholds (7.25 and 7.20) and to explore the possibility of identifying more accurate thresholds. MATERIAL AND METHODS: A retrospective study was conducted at a tertiary maternity hospital between June 2017 and July 2021. Patients with at least one FSBS during labor for category II fetal heart rate and delivery of a singleton cephalic infant were included. The rate of change in pH value between consecutive samples for each patient was calculated and plotted as a function of pH value. Linear regression models were used to model the evolution of the pH drop rate estimating slope and standard errors across predefined pH intervals. Exploration of alternative pH action thresholds was conducted. To explore the independence of the association between pH value and pH drop rate, multiple linear regression adjusted on age, body mass index, parity, oxytocin stimulation and suspected small for gestational age was performed. RESULTS: We included 2047 patients with at least one FSBS (total FSBS 3467); with 2047 umbilical cord blood pH, and a total of 5514 pH samples. Median pH values were 7.29 1 h before delivery, 7.26 30 min before delivery. The pH drop was slow between 7.40 and 7.30, then became more pronounced, with median rates of 0.0005 units/min at 7.25 and 0.0013 units/min at 7.20. Out of the alternative pH thresholds, 7.26 and 7.20 demonstrated the best alignment with our dataset. Multiple linear regression revealed that only pH value was significantly associated to the rate of pH change. CONCLUSIONS: Our study confirms the validity and reliability of current guideline thresholds for fetal scalp pH in category II fetal heart rate.

An Update of Our Understanding of Fetal Heart Rate Patterns in Health and Disease.

UNDERSTANDING FETAL HEART RATE PATTERNS THAT MAY PREDICT ANTENATAL AND INTRAPARTUM NEURAL INJURY: Christopher A. Lear, Jenny A. Westgate, Austin Ugwumadu, Jan G. Nijhuis, Peter R. Stone, Antoniya Georgieva, Tomoaki Ikeda, Guido Wassink , Laura Bennet , Alistair J. Gunn Seminars in Pediatric Neurology Volume 28, December 2018, Pages 3-16 Electronic fetal heart rate (FHR) monitoring is widely used to assess fetal well-being throughout pregnancy and labor. Both antenatal and intrapartum FHR monitoring are associated with a high negative predictive value and a very poor positive predictive value. This in part reflects the physiological resilience of the healthy fetus and the remarkable effectiveness of fetal adaptations to even severe challenges. In this way, the majority of "abnormal" FHR patterns in fact reflect a fetus' appropriate adaptive responses to adverse in utero conditions. Understanding the physiology of these adaptations, how they are reflected in the FHR trace and in what conditions they can fail is therefore critical to appreciating both the potential uses and limitations of electronic FHR monitoring.

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.

Progesterone control of myometrial contractility.

During pregnancy, the primary function of the uterus is to be quiescent and not contract, which allows the growing fetus to develop and mature. A uterine muscle layer, myometrium, is composed of smooth muscle cells (SMCs). Before the onset of labor contractions, the uterine SMCs experience a complex biochemical and molecular transformation involving the expression of contraction-associated proteins. Labor is initiated when genes in SMCs are activated in response to a combination of hormonal, inflammatory and mechanical signals. In this review, we provide an overview of molecular mechanisms regulating the process of parturition in humans, focusing on the hormonal control of the myometrium, particularly the steroid hormone progesterone. The primary reason for discussing the regulation of myometrial contractility by progesterone is the importance of the clinical problem of preterm birth. It is thought that the hormonal mechanisms regulating premature uterine contractions represent an untimely triggering of the normal events occurring during term parturition. Yet, our knowledge of the complex and redundant hormonal pathways controlling uterine contractile activity leading to delivery of the neonate remains incomplete. Finally, we introduce recent animal studies using a novel class of drugs, Selective Progesterone Receptor Modulators, targeting progesterone signaling to prevent premature myometrial contractions.

Double-sided asymmetric method for automated fetal heart rate baseline calculation.

The fetal heart rate (FHR) signal is used to assess the well-being of a fetus during labor. Manual interpretation of the FHR is subject to high inter- and intra-observer variability, leading to inconsistent clinical decision-making. The baseline of the FHR signal is crucial for its interpretation. An automated method for baseline determination may reduce interpretation variability. Based on this claim, we present the Auto-Regressed Double-Sided Improved Asymmetric Least Squares (ARDSIAsLS) method as a baseline calculation algorithm designed to imitate expert obstetrician baseline determination. As the FHR signal is prone to a high rate of missing data, a step of gap interpolation in a physiological manner was implemented in the algorithm. The baseline of the interpolated signal was determined using a weighted algorithm of two improved asymmetric least squares smoothing models and an improved symmetric least squares smoothing model. The algorithm was validated against a ground truth determined from annotations of six expert obstetricians. FHR baseline calculation performance of the ARDSIAsLS method yielded a mean absolute error of 2.54 bpm, a max absolute error of 5.22 bpm, and a root mean square error of 2.89 bpm. In a comparison between the algorithm and 11 previously published methods, the algorithm outperformed them all. Notably, the algorithm was non-inferior to expert annotations. Automating the baseline FHR determination process may help reduce practitioner discordance and aid decision-making in the delivery room.

Efficacy of Propranolol to Reduce Cesarean Delivery in Prolonged Labor: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the rates of cesarean delivery in patients with prolonged labor randomized to receive intravenous (IV) propranolol compared with placebo. METHODS: A double-blind, placebo-controlled, randomized trial was conducted at two hospitals within a large academic health system. Eligible patients were at 36 weeks or more with a singleton gestation and prolonged labor , defined as: 1) prolonged latent phase of labor (dilation less than 6 cm after 8 hours or more with ruptured membranes and receiving oxytocin infusion) or 2) prolonged active phase of labor (dilation 6 cm or greater and less than 1-cm cervical dilation change over 2 hours or more with ruptured membranes and receiving oxytocin infusion). Patients were excluded for severe preeclampsia, maternal heart rate less than 70 beats per minute, maternal blood pressure less than 90/50 mm Hg, asthma, diabetes requiring insulin during labor, or a cardiac contraindication to ß-blockade. Patients were randomized to propranolol (2 mg IV) compared with placebo (2 mL normal saline IV), with one possible repeat dose. The primary outcome was cesarean delivery; secondary outcomes included labor duration, shoulder dystocia, and maternal and neonatal morbidity. With an estimated cesarean delivery rate of 45%, α 0.05, and 80% power, we required 163 patients per group to detect a 15% absolute reduction in cesarean delivery rate. A planned interim analysis was performed, and the trial was stopped for futility. RESULTS: From July 2020 to June 2022, 349 patients were eligible and approached; 164 were enrolled and randomized, with 84 in the propranolol group and 80 in the placebo group. The rate of cesarean delivery was not different between groups (57.1% propranolol vs 57.5% placebo, relative risk [RR] 0.99, 95% CI 0.76-1.29). Results were similar by subgroup of prolonged latent (n=123) and active (n=41) phases of labor and nulliparous (n=137) and multiparous (n=27) patients. Though not statistically significant, the frequency of postpartum hemorrhage was higher in the propranolol group (20% vs 10%, RR 2.02, 95% CI 0.93-4.43). CONCLUSION: In this multisite, double-blind, placebo-controlled randomized trial, there was no difference in cesarean delivery rate for patients who received propranolol compared with those who received placebo for management of prolonged labor. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04299438.

Continuous fetal cerebral blood flow monitoring during labor: A feasibility study.

BACKGROUND: Current methods for fetal surveillance during labor have significant limitations. Since continuous fetal cerebral blood flow velocity (CBFV) monitoring during labor may add valuable information about fetal well-being, we developed a new ultrasound system called VisiBeam. VisiBeam consists of a flat probe (diameter 11 mm) with a cylindric plane wave beam, a vacuum attachment (diameter 40 mm), a scanner, and a display. AIMS: To assess the feasibility of VisiBeam for continuous fetal CBFV monitoring during labor, and to study changes in CBFV during uterine contractions. STUDY DESIGN: Descriptive observational study. SUBJECTS: Twenty-five healthy women in labor with a singleton fetus in cephalic presentation at term. A transducer was placed over a fontanelle and attached to the fetal head with vacuum suction. OUTCOME MEASURES: Achievement of continuous good quality fetal CBFV measures, such as peak systolic velocity, time averaged maximum velocity and end diastolic velocity. Trend plots of velocity measures display changes in CBFV between and during uterine contractions. RESULTS: Good quality recordings during and between contractions were achieved in 16/25 fetuses. In twelve fetuses, CBFV measures were stable during uterine contractions. Four fetuses showed patterns of reduced CBFV velocity measures during contractions. CONCLUSIONS: Continuous fetal CBFV monitoring by VisiBeam was feasible in 64 % of the subjects during labor. The system displayed variations of fetal CBFV not available by today's monitoring techniques and motivates for further studies. However, improvement of the probe attachment is required to ensure good quality signal in a higher proportion of fetuses during labor.

Implementation of the combined use of non-invasive fetal electrocardiography and electrohysterography during labor: A prospective clinical study.

INTRODUCTION: Fetal electrocardiography (NI-fECG) and electrohysterography (EHG) have been proven more accurate and reliable than conventional non-invasive methods (doppler ultrasound and tocodynamometry) and are less affected by maternal obesity. It is still unknown whether NI-fECG and EHG will eliminate the need for invasive methods, such as the intrauterine pressure catheter and fetal scalp electrode. We studied whether NI-fECG and EHG can be successfully used during labor. MATERIAL AND METHODS: A prospective clinical pilot study was performed in a tertiary care teaching hospital. A total of 50 women were included with a singleton pregnancy with a gestational age between 36+0 and 42+0 weeks and had an indication for continuous intrapartum monitoring. The primary study outcome was the percentage of women with NI-fECG and EHG monitoring throughout the whole delivery. Secondary study outcomes were reason and timing of a switch to conventional monitoring methods (i.e., tocodynamometry and fetal scalp electrode or doppler ultrasound), repositioning of the abdominal electrode patch, success rates (i.e., the percentage of time with signal output), and obstetric and neonatal outcomes. CLINICAL TRIAL REGISTRATION: Dutch trial register (NL8024). RESULTS: In 45 women (90%), NI-fECG and EHG monitoring was used throughout the whole delivery. In the other five women (10%), there was a switch to conventional methods: in two women because of insufficient registration quality of uterine contractions and in three women because of insufficient registration quality of the fetal heart rate. In three out of five cases, the switch was after full dilation was reached. Repositioning of the abdominal electrode patch occurred in two women. The overall success rate was 94.5%. In 16% (n = 8) of women, a cesarean delivery was performed due to non-progressing dilation (n = 7) and due to suspicion of fetal distress (n = 1). Neonatal metabolic acidosis did not occur. Two neonates (4%) were admitted to the neonatal intensive care unit for complications not related to intrapartum monitoring. CONCLUSIONS: NI-fECG and EHG can be successfully used during labor in 90% of women. Future research is needed to conclude whether implementation of electrophysiological monitoring can improve obstetric and neonatal outcomes.

The evolution of the labor curve and its implications for clinical practice: the relationship between cervical dilation, station, and time during labor.

The assessment of labor progress is germane to every woman in labor. Two labor disorders-arrest of dilation and arrest of descent-are the primary indications for surgery in close to 50% of all intrapartum cesarean deliveries and are often contributing indications for cesarean deliveries for fetal heart rate abnormalities. Beginning in 1954, the assessment of labor progress was transformed by Friedman. He published a series of seminal works describing the relationship between cervical dilation, station of the presenting part, and time. He proposed nomenclature for the classification of labor disorders. Generations of obstetricians used this terminology and normal labor curves to determine expected rates of dilation and fetal descent and to decide when intervention was required. The analysis of labor progress presents many mathematical challenges. Clinical measurements of dilation and station are imprecise and prone to variation, especially for inexperienced observers. Many interrelated factors influence how the cervix dilates and how the fetus descends. There is substantial variability in when data collection begins and in the frequency of examinations. Statistical methods to account for these issues have advanced considerably in recent decades. In parallel, there is growing recognition among clinicians of the limitations of using time alone to assess progress in cervical dilation in labor. There is wide variation in the patterns of dilation over time and most labors do not follow an average dilation curve. Reliable assessment of labor progression is important because uncertainty leads to both over-use and under-use of cesarean delivery and neither of these extremes are desirable. This review traces the evolution of labor curves, describes how limitations are being addressed to reduce uncertainty and to improve the assessment of labor progression using modern statistical techniques and multi-dimensional data, and discusses the implications for obstetrical practice.

Monitoring uterine contractions during labor: current challenges and future directions.

Organ-level models are used to describe how cellular and tissue-level contractions coalesce into clinically observable uterine contractions. More importantly, these models provide a framework for evaluating the many different contraction patterns observed in laboring patients, ideally offering insight into the pitfalls of currently available recording modalities and suggesting new directions for improving recording and interpretation of uterine contractions. Early models proposed wave-like propagation of bioelectrical activity as the sole mechanism for recruiting the myometrium to participate in the contraction and increase contraction strength. However, as these models were tested, the results consistently revealed that sequentially propagating waves do not travel long distances and do not encompass the gravid uterus. To resolve this discrepancy, a model using 2 mechanisms, or a "dual model," for organ-level signaling has been proposed. In the dual model, the myometrium is recruited by action potentials that propagate wave-like as far as 10 cm. At longer distances, the myometrium is recruited by a mechanotransduction mechanism that is triggered by rising intrauterine pressure. In this review, we present the influential models of uterine function, highlighting their main features and inconsistencies, and detail the role of intrauterine pressure in signaling and cervical dilation. Clinical correlations demonstrate the application of organ-level models. The potential to improve the recording and clinical interpretation of uterine contractions when evaluating labor is discussed, with emphasis on uterine electromyography. Finally, 7 questions are posed to help guide future investigations on organ-level signaling mechanisms.

Prolonged stretching of rat uteri causes hypoxia and inhibits contractility via potassium channel TREK1.

In brief: During pregnancy, uterine kept quiescence along with uterine overdistention before labor. Prolonged stretching induced uterus myometrial hypoxia, increased TREK1 expression, and relaxed the myometrium, which may contribute to uterine quiescence and atony during pregnancy. Abstract: The mechanisms underlying pre-labor uterine quiescence and uterine atony during overdistention are unclear. TREK1 (a two-pore domain potassium channel) and hypoxia-inducible factor-1α (HIF-1α) are activated by mechanical stretch, and their expression is upregulated by decreased uterine contractility. HIF-1α is a nuclear factor which regulates numerous target proteins, but whether it regulates TREK1 during the uterine stretch to cause uterine quiescence and/or atony is unclear. We investigated uterine contractility at different gestational stages in rats, as well as in non-pregnant uteri, which were induced by prolonged stretching and hypoxia. We also assessed the effects of incubating the uteri with or without echinomycin or l-methionine. Moreover, we analyzed HIF-1α and TREK1 expression levels in each group, as well as at various gestational stages of pregnant human uteri. We found that contractility was significantly decreased in pregnant uteri when compared with non-pregnant uteri, and this decrease was associated with increases in HIF-1α and TREK1 expression levels. HIF-1α and TREK1 expression levels in human uteri increased with the gestational length. Decreased uterine contractility and increased HIF-1α and TREK1 expression levels were also observed in non-pregnant rat uteri under 8 g of stretching tension or hypoxia. Inhibition of hypoxia with echinomycin restored normal uterine contractility, while HIF-1α and TREK1 protein expression remained reduced. TREK1 inhibition with l-methionine also restored uterine contractility under tension or hypoxia. In conclusion, we demonstrated that prolonged stretching induces myometrial hypoxia, increases TREK1 expression, and relaxes the myometrium, which may contribute to uterine quiescence and atony.

Use of External Uterine Electromyography Across Stage I Labor.

INTRODUCTION: Highly sensitive, external uterine electromyography (EMG) measures myometrial electrical activity and is noninvasive compared with the clinical intrauterine pressure catheter. Most experimental studies have measured EMG in 30-minute epochs, limiting the utility of this instrumentation in intrapartum clinical practice. To test proof of concept, surface uterine EMG contraction activity was continuously collected throughout the first stage of labor from healthy women at term gestation with (n = 3) and without (n = 1) epidural or combined spinal-epidural analgesia for a maximal length of 11 hours and 24 minutes. METHODS: EMG activity was recorded concurrently with tocodynamometer (toco) signals, using a pair of electrodes on the left and right sides of the maternal umbilicus with grounds attached to both hips of the reclining woman in labor. The preamplifier cutoff frequency settings were appropriate to monitor smooth muscle contraction in labor, with the analog high-pass filter set at 0.05 Hz and the low-pass filter at 1.50 Hz. Signals were sampled at 100 Hz, transmitted to a computer, and visualized by Chart 4.2 software. EMG data from epochs at baseline, during the pre-epidural fluid bolus and at the 60-minute post-epidural test dose, and at 3, 5, 6, and 8 cm dilatation were analyzed for burst power spectrum peak frequency (Hz), burst power spectrum amplitude (mV2 ), and burst duration (seconds). RESULTS: Uterine EMG contractile bursts were preceded and followed by a stable baseline and coincided with toco contractions. Movement artifacts were negligible, and large movement artifacts were easily distinguishable. The EMG bursts and toco contractions remained clearly identifiable, even when one woman without epidural analgesia stood beside the bed laboring for approximately 10 minutes. Burst spectral components fell within the expected 0.34-to-1.00 Hz range for term labor. DISCUSSION: High-quality data demonstrate that EMG instrumentation effectively and accurately measures uterine contraction parameters across the first stage of term labor.

Maternal heart rate variability patterns associated with maternal hypotension and non-reassuring fetal heart rate patterns following initiation of combined spinal-epidural labor analgesia: a prospective observational trial.

BACKGROUND: We evaluated whether baseline maternal heart rate variability (HRV), including the Analgesia Nociception Index (ANI), is associated with maternal hypotension and fetal heart rate (FHR) abnormalities following combined spinal-epidural (CSE) labor analgesia. METHODS: Laboring women were enrolled in this prospective observational study. The primary endpoint was maternal hypotension. The secondary endpoint was FHR abnormalities within 30 min following CSE analgesia initiated with intrathecal plain bupivacaine 1.0 mg and fentanyl 20 µg. The maternal ANI, electrocardiogram, blood pressure, heart rate, oxygen saturation, and FHR tracings were recorded 15 min before and 30 min after CSE. Parturients were grouped based on presence of hypotension and FHR abnormalities. Patient demographics and HRV metrics were compared. Receiver operating characteristics (ROC) curves were constructed for the prediction of hypotension and FHR abnormalities. RESULTS: No significant intergroup differences were detected in patient characteristics. Several baseline HRV metrics and ANI differed significantly between the normotensive (n = 50) and hypotensive (n = 31) groups and between parturients showing FHR abnormalities (n = 19) and those showing reassuring FHR traces (n = 62). The area under the ROC curve (AUC) for predicting hypotension of the baseline low-frequency (LF)/high-frequency (HF) ratio was 0.677 (95% CI 0.55 to 0.80), and that of the ANI was 0.858 (95% CI 0.78 to 0.94). For predicting non-reassuring FHR patterns, the AUC of the LF/HF ratio was 0.77 (95% CI 0.65 to 0.89), and that of the ANI was 0.833 (95% CI 0.72 to 0.94). CONCLUSIONS: The ANI can predict the propensity for maternal hypotension and non-reassuring FHR patterns following CSE.

Improved obstetric management after implementation of a scaled-up quality improvement intervention: A nested before-after study in three public hospitals in Nepal.

BACKGROUND: We assessed the change in obstetric management after implementation of a quality improvement intervention, the Nepal Perinatal Quality Improvement Package (NePeriQIP). METHODS: The Nepal Perinatal Quality Improvement Package was a stepped-wedge cluster-randomized controlled trial conducted in 12 public hospitals in Nepal between April 2017 and October 2018. In this study, three hospitals allocated at different time points to the intervention were selected for a nested before-after analysis. We used bivariate and multivariate analyses to compare obstetric management in the control vs intervention group. RESULTS: There were 25 977 deliveries in the three hospitals during the study period: 10 207 (39%) in the control and 15 770 (61%) in the intervention group. After adjusting for maternal age, ethnicity, education, gestational age, stage of labor at admission, complications during labor, and birthweight, the intervention group had a higher proportion of fetal heart rate monitoring performed as per protocol (adjusted odds ratio [aOR] 1.19, 95% confidence interval [CI] 1.12-1.27), shorter time intervals between each fetal heart rate monitoring (aOR 2.09, 95% CI 1.96-2.23), a higher likelihood of abnormal fetal heart rate being detected (aOR 1.53, 95% CI 1.25-1.68), progress of labor more often being recorded immediately after per vaginal examination (aOR 2.73, 95% CI 2.55-2.93), and partograph filled as per standards (aOR 3.18, 95% CI 2.98-3.50). The cesarean birth rate was 2.5% in the control group and 8.2% in the intervention group (aOR 3.12, 95% CI 2.64-3.68). CONCLUSIONS: The NePeriQIP intervention has potential to improve obstetric care, especially intrapartum fetal surveillance, in similar low-resource settings.

MYB and ELF3 differentially modulate labor-inducing gene expression in myometrial cells.

Spontaneous uterine contractions are initiated when smooth muscle cells (SMCs) within the uterine muscle, or myometrium, transition from a functionally dormant to an actively contractile phenotype at the end of the pregnancy period. We know that this process is accompanied by gestational time point-specific differences in the SMC transcriptome, which can be modulated by the activator protein 1 (AP-1), nuclear factor kappa beta (NF-κß), estrogen receptor (ER), and progesterone receptor (PR) transcription factors. Less is known, however, about the additional proteins that might assist these factors in conferring the transcriptional changes observed at labor onset. Here, we present functional evidence for the roles of two proteins previously understudied in the SMC context-MYB and ELF3-which can contribute to the regulation of labor-driving gene transcription. We show that the MYB and ELF3 genes exhibit elevated transcript expression levels in mouse and human myometrial tissues during spontaneous term labor. The expression of both genes was also significantly increased in mouse myometrium during preterm labor induced by the progesterone antagonist mifepristone (RU486), but not during infection-simulating preterm labor induced by intrauterine infusion of lipopolysaccharide (LPS). Furthermore, both MYB and ELF3 proteins affect labor-driving gene promoter activity, although in surprisingly opposing ways: Gja1 and Fos promoter activation increases in the presence of MYB and decreases in the presence of ELF3. Collectively, our study adds to the current understanding of the transcription factor network that defines the transcriptomes of SMCs during late gestation and implicates two new players in the control of labor timing.