Labor Uterine Contractions Research Articles

Uterine activity modifies the response of the fetal autonomic nervous system at preterm active labor.

The autonomic nervous system of preterm fetuses has a different level of maturity than term fetuses. Thus, their autonomic response to transient hypoxemia caused by uterine contractions in labor may differ. This study aims to compare the behavior of the fetal autonomic response to uterine contractions between preterm and term active labor using a novel time-frequency analysis of fetal heart rate variability (FHRV). We performed a case-control study using fetal R-R and uterine activity time series obtained by abdominal electrical recordings from 18 women in active preterm labor (32-36 weeks of gestation) and 19 in active term labor (39-40 weeks of gestation). We analyzed 20 minutes of the fetal R-R time series by applying a Continuous Wavelet Transform (CWT) to obtain frequency (HF, 0.2-1Hz; LF, 0.05-0.2Hz) and time-frequency (Flux0, Flux90, and Flux45) domain features. Time domain FHRV features (SDNN, RMSSD, meanNN) were also calculated. In addition, ultra-short FHRV analysis was performed by segmenting the fetal R-R time series according to episodes of the uterine contraction and quiescent periods. No significant differences between preterm and term labor were found for FHRV features when calculated over 20 minutes. However, we found significant differences when segmenting between uterine contraction and quiescent periods. In the preterm group, the LF, Flux0, and Flux45 were higher during the average contraction episode compared with the average quiescent period (p<0.01), while in term fetuses, vagally mediated FHRV features (HF and RMSSD) were higher during the average contraction episode (p<0.05). The meanNN was lower during the strongest contraction in preterm fetuses compared to their consecutive quiescent period (p=0.008). The average autonomic response to contractions in preterm fetuses shows sympathetic predominance, while term fetuses respond through parasympathetic activity. Comparison between groups during the strongest contraction showed a diminished fetal autonomic response in the preterm group. Thus, separating contraction and quiescent periods during labor allows for identifying differences in the autonomic nervous system cardiac regulation between preterm and term fetuses.

Collagen bundling and alignment in equibiaxially stretched human amnion

We study irreversible collagen arrangement processes in ex-vivo human amnions subjected to inflation tests, which simulate the mechanical conditions prior to and during the initiation of labor uterine contractions. The investigation is focused on the center of the membrane where the stresses are maximal and equibiaxial. Second harmonic generation reveals an unexpected collagen rearrangement in the compact layer that is responsible for the structural integrity of the fetal membrane. The observed bundling and alignment of the collagen fibers indicate a deviation from the expected equibiaxial stress state. The statistical analysis of the fiber orientations provides information on two driving forces for collagen alignment: microscale flaws and macroscale deviation from the equibiaxial strain. As the pressure increases, the macroscale effect becomes dominant, and a high density of fibers that are aligned along a specific direction is observed. A model that explains these observations and relates them to the material properties is presented. The results of this study indicate that a temporal increase in intrauterine pressure or uterine cervix dilatation causes irreversible changes in collagen molecular connections that may lead to biological changes, such as the initiation of term and preterm labor.

Histological Chorioamnionitis as a Risk Factor for Preterm Birth without Disturbing Fetal Heart Rate: A Case-Control Study.

Histological chorioamnionitis (CAM) is one form of intrauterine inflammation that is often seen in cases of preterm birth and are usually confirmed based on pathological examination after delivery. Histological CAM is related to significant neonatal morbidity and mortality; however, its etiology is unknown. The objective of this study was to determine the risk factors for histological CAM, using medical background, including fetal heart rate (FHR) patterns in preterm birth cases. The preterm birth cases delivered between 28 and 36 weeks were categorized into two groups according to the presence of histological CAM. Ninety-five preterm infants were included: 48 infants without histological CAM and 47 cases with histological CAM. The odds ratio for histological CAM was adjusted for FHR patterns, gestational age, and delivery mode (vaginal delivery or Caesarean section). Logistic regression analysis showed that vaginal delivery and gestational age were associated with histological CAM (odds Ratio [OR]: 3.1, 95% confidence interval [CI]: 1.0-9.4, p < 0.05, and OR: 0.8, 95% CI: 0.6-0.9, p < 0.05, respectively). However, there were no specific FHR patterns associated with histological CAM. Our study indicates that in preterm birth cases, histological CAM is not related to any specific FHR pattern. However, labor uterine contraction and immature gestational age at the delivery are related to histological CAM. These results may provide better delivery management methods for preterm birth cases.

Current Perspectives in Uterine Research: Reviews From the Society for Gynecologic Investigation Myometrium and Parturition Satellite Symposia

It is difficult to imagine examples of greater physiological adaptations than those of the uteroplacental unit during pregnancy. The sheer scale of molecular, cellular and tissue remodeling, organogenesis, and organism development in a relatively short period of time seems the epitome of ‘‘systems biology.’’ The processes are challenging to comprehend, and investigate experimentally, but undoubtedly fascinating. Efforts to understand the physiology and pathology of these phenomena are of prime importance due to the considerable health and socioeconomic pressures brought to bear by the high incidences of compromised pregnancies and, especially, preterm birth (PTB). The World Health Organization-sponsored studies equate the worldwide incidence of PTB to be approximately 13 million births per year with approximately 1 million neonatal deaths attributable to PTB. If improved diagnosis and therapeutic treatment of PTB are to be achieved, an integrated understanding of the physiological basis of pregnancy and parturition is required. With this in mind, each year the Myometrium and Parturition Satellite Symposium of the Society for Gynecologic Investigation meeting gathers international experts in this field to share their experimental findings. We are delighted that several plenary speakers from the 2011 and 2012 symposia have provided reviews on their topics for this issue of Reproductive Sciences. The articles provide an up-to-date compendium that integrates many of the important facets of uteroplacental remodeling and function leading to term and preterm labor. Jerome Strauss (Virginia) introduces the importance of dynamic remodeling of the extracellular matrix (ECM) and its molecular components in uteroplacental tissues. With a focus on fetal membrane interfaces, he summarizes the ECMs’ multiplicity of roles including receptor signaling, cytokine/ growth factor sequestration, and tensile strength. Among the important molecular components are fetal fibronectin, hyaluronan, and up to 28 collagens, regulated by different metallomatrix proteinases. Mutations in many genes encoding such ECM proteins are associated with increased incidence of preterm premature rupture of membranes and the roles of environmental and/or epigenetic factors are being increasingly elucidated. In a similar vein, Shynlova et al (Toronto, Canada) describe pregnancy in terms of progressive changes of tissue remodeling under the control of localized inflammatory events (physiological inflammation). The authors posit a carefully structured theory whereby spatially restricted inflammatory events are under the influence of ever-changing endocrine (and a focus is given to the role of progesterone) and mechanical inputs activating a rich milieu of chemokine/cytokine signaling. These, in turn, serve to coordinate diverse processes such as decidualization, myometrial cell proliferation and growth, leukocyte migration, cervical remodeling, and postparturient involution. Olcese et al (Tallahassee, USA) review an oft-neglected consideration of the mechanisms responsible for the timing of parturition. They too give credence to the notion that pregnancy and parturition involve dynamic physiological adaptations—in this case that uterine contractions of labor may be initiated by activity of the central circadian oscillator of the maternal hypothalamic suprachiasmatic nuclei via the feedback ‘‘gating’’ actions of neuroendocrine outputs. Of key importance may well be circadian secretion of melatonin given recent interest in the uterotonic actions of this hormone and uterine expression of melatonin receptors. Regulation of contractile activity of the uterus is also the focus of reviews by Europe-Finner et al (Newcastle, UK) and Wim Lammers (Al Ain, UAE). The former concentrates on intracellular signaling and describes the possibility that posttranslational modification by acetylation may be a mechanism of wider significance to the uterus than first realized when considering ‘‘‘only’’ nuclear events of histone modification, chromatin remodeling, and gene transcription. They suggest

Uterine Contractions in Normal Labor Developed by a Positive Feed-back and Oscillation

Aim: To clarify the developing mechanism of regular uterine contractions in the labor. Methods: The similarity of normal regular labor contractions of the uterus to the electrical oscillation was studied. The electrical oscillation technique was adapted to regular labor contraction of the uterus, where innervations between the uterus and brain were reported in animals in four papers. Results: Interval between peaks of contractions was 2 min and the amniotic pressure was 40 mmHg in typical labor contractions. Labor contractions were repeated from the onset of labor until the delivery of fetus. Attachment of reverse contraction curve to normal contraction curves formed sine wave-like repetition, similar closely to electrical oscillation waves. A positive feed-back was estimated from the uterus to the amplifying input Comments: A biological amplifier is the hypothalamic center-hypophysis-oxitocin secretion, its output is uterine labor contraction, and its positive feed-back loop to the amplifier input is the innervations between the uterus and hypothalamus, of which presence was reported in animals. The biological positive feed-back loop produces oscillationlike regular uterine contractions, of which wave length is 2 min, frequency 0.008 Hz and amplitude 40 mmHg. Conclusion: Regular stable labor contractions of uterus is formed in the oscillation by the positive feed-back system composed of hypothalamus-hypophysis-oxitocin secretion, uterine contractions and uterus-brain innervations.

A Functional Fetal HSD11B2[CA]n Microsatellite Polymorphism is Associated with Maternal Serum Cortisol Concentrations in Pregnant Women

Background/Aims: Cortisol plays an important role during pregnancy. It controls maternal glucose metabolism and fetal development. Cortisol metabolism is partially controlled by the 11b-HSD2. This enzyme is expressed in the kidney and human placenta. The activity of the enzyme is partially controlled by functional polymorphisms: the HSD11B2[CA]n microsatellite polymorphism. The impact of this functional gene polymorphism on cortisol metabolism and potential effects on the newborn's is unknown so far. Methods: In the current prospective birth cohort study in southern Asia, we analyzed the association of the HSD11B2[CA]n microsatellite polymorphisms in 187 mothers and their newborn's on maternal and newborn's serum cortisol concentrations. Results: Using multivariable regression analyses considering known confounding (gestational age, newborn's gender, the labor uterine contraction states and the timing during the day of blood taking), we showed that the fetal HSD11B2[CA]n microsatellite polymorphisms in the first intron was related to maternal cortisol concentration (R2=0.26, B=96.27, p=0.007), whereas as the newborn's cortisol concentrations were independent of fetal and maternal HSD11B2[CA]n microsatellite polymorphism. Conclusions: Our study showed for the first time that the fetal HSD11B2[CA]n microsatellite polymorphism of the HSD11B2 gene in healthy uncomplicated human pregnancy is associated with maternal cortisol concentration. This indicates that fetal genes controlling cortisol metabolism may affect maternal cortisol concentration and hence physiology in healthy pregnant women.

Induction of labor in prolonged pregnancy with unfavorable cervix: comparison of sequential intracervical Foley catheter–intravaginal misoprostol and intravaginal misoprostol alone

To compare the outcome of induced labor at term using sequential intracervical Foley catheter with intravaginal misoprostol versus intravaginal misoprostol alone. A prospective matched case control study among parturient with prolonged pregnancy and unfavorable cervix at a tertiary hospital in Nigeria. The study population was 100 with a mean age of 29.46 ± 3.88 years. Parturient with prior cervical priming using intracervical Foley catheter had significantly lower oxytocin augmentation of uterine contractions in labor (44 vs. 64%, P = 0.045), shorter mean insertion to active phase labor duration (233 ± 98 vs. 354 ± 154 min, P = 0.0001), shorter insertion to delivery interval (514 ± 175 vs. 627 ± 268, P = 0.014), more vaginal delivery <12 h (92.5 vs. 60%, P = 0.001) and less delivery by caesarean section (20 vs. 40%, P = 0.029). The sequential combination of intracervical Foley catheter and intravaginal misoprostol for cervical ripening and induction of labor appears to be a safe and more effective method compared to intravaginal misoprostol in parturient at term with unfavorable cervices.

Tocolytic effect of a selective FP receptor antagonist in rodent models reveals an innovative approach to the treatment of preterm labor

BackgroundManagement of preterm labor by tocolysis remains an unmet medical need. Prostaglandins play a major role in regulation of uterine activity and in molecular mechanisms of human labor and parturition. There is some circumstantial evidence that prostaglandin F2α by action through the prostaglandin receptor subtype FP is effective in key events during labor uterine contraction, rupture of membranes and cervical dilation. This role of FP is briefly reviewed. In this study, we tested the hypothesis that an orally active and selective FP antagonist may arrest labor and delay parturition in animal models.MethodsWe examined the effects of a small molecule selective antagonist of the FP receptor (AS604872) in inhibition of spontaneous uterine contraction in pregnant rat near term. We tested AS604872 for its ability to delay preterm birth in a mouse model in which the anti-progestin agent RU486 triggered parturition.ResultsBy oral or intravenous dosing AS604872 reduced markedly and dose-dependently the spontaneous uterine contractions in late-term pregnant rats at gestational days 19–21. In pregnant mice, AS604872 delayed the preterm birth caused by RU486 administration. The effect was dose-dependent with a significant increase in the mean delivery time of 16 and 33 hours at oral doses of 30 mg/kg and 100 mg/kg, respectively, in the case of labor triggered at gestational day 14. In both models AS604872 appeared more effective than the β-agonist ritodrine.ConclusionThe tocolytic activity displayed by a selective FP receptor antagonist supports a key role for the FP receptor in the pathophysiology of premature birth and demonstrates the therapeutic potential of an FP antagonist for the treatment of preterm labor cases in which uterine hyperactivity plays a dominant role.

Dynamics of Cervical Remodeling during Pregnancy and Parturition: Mechanisms and Current Concepts

The cervix serves as a protective barrier from invading microorganisms and as a structural barrier to delivery of the fetus. Among all biological processes, the phenomenal connective tissue remodeling that occurs in the cervix during and after parturition is unparalleled in scope and magnitude. The process of connective tissue remodeling in the cervix during pregnancy occurs in four stages: softening, ripening, dilation, and repair. Although overlapping in time, each stage is uniquely regulated. Results from studies using serial measurements of cervical length indicate that cervical ripening precedes myometrial contractions of labor by several weeks, suggesting that parturition in women is a process of long duration and that uterine contractions of labor are late events in the parturition process. A clear understanding of the biologic mechanisms that regulate cervical remodeling during pregnancy is needed to influence the preterm birth rate and to develop strategies to prevent preterm dilation of the cervix.

Meloxicam effectively inhibits preterm labor uterine contractions in a chronically catheterized pregnant sheep model: Impact on fetal blood flow and fetal-maternal physiologic parameters

Preterm birth occurs in 5% to 10% of all pregnancies and is associated with considerable neonatal mortality and morbidity. Effective and safe drugs to prevent preterm labor are not currently available. We have hypothesized that the nonsteroidal anti-inflammatory drug meloxicam, a more selective cyclooxygenase-2 inhibitor will successfully inhibit labor but avoid the complications associated with inhibition of cyclooxygenase-1. Preterm labor was induced in chronically catheterized sheep by RU486 administration. Animals were then randomized to receive maternal infusions of saline (n = 5) or meloxicam (n = 4) for 48 hours or until delivery when the animals were killed and tissues and blood samples collected. Maternal infusion of meloxicam inhibited uterine contractions, increasing contraction duration, and attenuating frequency and amplitude. Saline-treated animals progressed to delivery. Administration of meloxicam was not associated with any change in fetal or maternal blood gas status, osmolality, arterial pressure, heart rate, or fetal blood flows. Meloxicam may represent a potentially safe and effective tocolytic agent.

Cardiovascular changes during pregnancy

Cardiovascular alterations during pregnancy are characterized by an increased vascular volume, cardiac output, and heart rate, with a marked fall in vascular resistance. Cardiac output is about 40-50% higher during the third trimester. Even higher values of cardiac output are observed during uterine contractions in labor. In general, arterial blood pressure remains unaffected or demonstrates some tendency toward lower diastolic pressure. The higher blood volume is associated with a slight increase in left ventricular dimensions. Left ventricular contraction force and its first derivative remain unchanged. Many symptoms and findings during pregnancy are caused by the described changes, such as dyspnea on exertion, presyncope due to pressure on the inferior vena cava resulting in a decreased venous return to the heart, prominent jugular venous pulsation, leg edema, and ejection murmurs over the aorta and pulmonary artery. Paroxysmal nocturnal dyspnea, anginal chest pain, syncopy, anasarca, and diastolic heart murmurs require further evaluation.

Failure of magnesium sulfate infusion to inhibit uterine activity in pregnant sheep

OBJECTIVES: Our purpose was to determine the effect of magnesium sulfate infusion on nonlabor uterine contractures and corticotropin-induced preterm uterine contractions in pregnant sheep.STUDY DESIGN: Fetal and maternal vascular catheters and uterine electromyographic electrodes were surgically placed in 15 pregnant sheep between 118 and 125 days' gestation. After 3 to 5 days of recovery, magnesium sulfate was infused into 7 ewes with a 0.11 gm/kg bolus over 20 minutes, followed by 0.08 gm/kg/hr. In 8 animals labor was induced with use of an intrafetal corticotropin infusion, after which 4 ewes received magnesium sulfate and 4 received saline solution. Continuous recordings of uterine electromyographic activity, amniotic pressure, fetal heart rate, blood pressure, and tracheal pressure were made. Maternal and fetal magnesium, calcium, albumin concentrations, and blood gases were determined before and during the infusion.RESULTS: Maternal magnesium concentrations increased from an average of 0.94 ± 0.03 mmol/L to 2.73 ± 0.1 mmol/L at the end of the bolus, remaining elevated (2.44 ± 0.17 mmol/L) for 8 hours. Fetal magnesium concentrations (0.89 ± 0.03 mmol/L before the bolus) did not change with the maternal infusion. In ewes not in labor, uterine contractures occurred 3.7 ± 0.7 times per 2 hours before and did not change significantly with the infusion of magnesium sulfate. During corticotropin-induced preterm labor uterine contractions were present 13 ± 3.2 times per hour before infusions and were unchanged by infusion of magnesium sulfate to the ewes.CONCLUSIONS: Magnesium sulfate infusion in pregnant sheep has no effect on either nonlabor uterine contractures or on corticotropin-induced preterm uterine contractions. (Am J Obstet Gynecol 1997;177:185-9.)

Fetal movement during labor

The prognostic significance of antepartum fetal movement is well known; therefore it may be a variable in intrapartum fetal well-being. We report the simultaneous observation of fetal movement with fetal heart rate and uterine contractions by processed Doppler actograph signals during spontaneous labor of 22 normal women with normal fetal outcome. The mean percent incidence of fetal movement during labor was 17.3%. The percentage occurring during uterine contractions was 65.9%. Of all uterine contractions, 89.8% were associated with fetal movement. The proportion of time the fetus spent moving during uterine contractions (21.4%) was higher than between uterine contractions (12.9%). Uterine contractions associated with fetal movement were significantly longer than those not associated with fetal movement (p \\lt 0.0001). Mean percent incidence of fetal movement did not differ significantly between latent and active-phase labor. This study demonstrates a clear relationship between fetal movement and uterine contractions in labor.

Inhibition of spontaneous uterine contractions during the last trimester in pregnant baboons by an oxytocin antagonist

The effect of a potent oxytocin antagonist, produced in our laboratories, on spontaneous uterine contractions in the pregnant baboon was examined. Three types of uterine contractions were studied: immediately after operation, during the nocturnal period, and near or at labor. Bolus intravenous injections of oxytocin antagonist were given and uterine activity was examined ± 1 hour after the injection. The oxytocin antagonist caused a precipitate decrease (approximately 70%) in contractile force (mean amplitude x frequency) in the first 15 minutes after injection (p<0.05); this force diminished to approximately 90% at the end of 1 hour for both nocturnal and labor contractions. In contrast, uterine contractions immediately after operation were diminished by only 60% within 60 minutes after the oxytocin antagonist. These results indicate that the oxytocin antagonist is a potent inhibitor and suggest that oxytocin is a primary regulator of spontaneous nocturnal and labor uterine contractions in the pregnant baboon.

Plasma prostaglandin F2 alpha and plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha levels in women during induction of labor with i.v. infusion of prostaglandin F2 alpha in relation to uterine contractions.

The concentrations of plasma PGF2 alpha and its main metabolite, 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were measured in serial samples of blood collected in 10 pregnant women at term who were given iv infusions of low doses of PGF2 alpha for induction of labor. Six other women served as controls and were given saline infusions. Uterine contractions began with a mean latency of 62 min in the PGF2 alpha infused women, in controls uterine activity remained unchanged. Plasma PGFM levels had increased significantly 30 min after PGF2 alpha infusion began, rising thereafter in a dose dependent manner. Plasma PGF2 alpha also rose reaching a steady state at 2 hours. No significant changes were observed in the controls. The 6-h infusion resulted in delivery in 5 of the 10 women, in the 5 others the cervical scores increased only by 1.25 points on the average and further treatment was needed to achieve delivery, although prostanoid levels rose to similar levels in all. The data show that when uterine contractions are induced by systemic PGF2 alpha, the levels of PGFM are significantly raised. In spontaneous labor uterine contractions begin long before plasma PGFM rises. Thus, if endogenous PGF2 alpha generation is involved in the initiation of uterine contractions during spontaneous labor, it must be synthetized in the myometrium at quantities too low to raise the levels of circulating PGFM.

Maternal Hypothalamic Control of Labor

This chapter focuses on the maternal hypothalamic control of labor. Three links between the maternal hypothalamus and the uterine contractions of labor can be established—namely, (1) anterior pituitary, ovary, estrogen and progesterone, (2) posterior pituitary, oxytocin and the Ferguson reflex, (3) autonomic nervous system, catecholamines and stress. The contractions of the uterus, as expressed in labor, are subject to a variety of physical, hormonal and neural constraints. Hippocrates expressed remarkable foresight on postulating a role for the fetus in the organization of birth. The physical task of delivering the young is still the prerogative of the mother. The role of mother is far from “passive” and control is exercised to determine the exact hour of birth on that final day of gestation. Such dual control embodies a most sound rationale. The fetus is the best judge of its own maturity (or viability); the mother has the faculties to assess the environmental factors which will govern survival at the time of birth.

INTRAVENOUS USE OF OXYTOCIN (PITOCIN) FOR INDUCTION OF LABOR

Clyman, Martin; Pakter, Jean; Jacobziner, Harold; Greenstein, Freida Author Information

Intravenous use of oxytocin (pitocin) for induction of labor.

The extent to which oxytocin is being used to initiate or stimulate uterine contractions in labor was investigated by analyzing certain information on birth and fetal death certificates in New York City. Of 165,150 live births in 1955, 7,694 (4.7%) were induced with intravenously given oxytocin. In 1956 the over-all reported incidence rose to 5.0%. Three case-histories are given to illustrate the irrational use of this drug. The data showed that its use was influenced by the season of the year and by the socioeconomic status of the patient and that in cesarean sections and breech deliveries the prior use of oxytocin increased the infant mortality.

Syringomyelia complicating pregnancy and labor with report of a case

A case of syringomyelia, with a cavity in the cervical and upper dorsal regions complicating pregnancy, and presenting no complications in labor that could be ascribed to the spinal disease, is reported.Experimental evidence leads us to believe that in lower animals, the uterine contractions of labor are purely myogenic, and that pregnancy and spontaneous rapid labor can occur when all nervous connections of the uterus are severed. Under normal conditions, the uterus is influenced by the central nervous system through its extrinsic nerves.The review of the clinical and pathologic literature shows that pregnancy and labor are largely independent of spinal cord disease. Spinal cord disease, in the absence of other complications, need not be a cause for termination of pregnancy. In tabes and in transverse lesions above the lumbosacral cord enlargement despite the lack of voluntary abdominal muscle action, the labor is apt to be not only spontaneous but precipitous; in disease of the anterior horn cells as in poliomyelitis in the lumbosacral region and in transverse lesions of the sacral area, obstetric assistance may be required although these lesions do not abolish the uterine contractions.