Uterine Overdistention Research Articles

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

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. 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.

Risk factors for postpartum hemorrhage caused by uterine atony

Pregnancy and childbirth are physiological processes experienced by women, but it does not rule out complications resulting in maternal death. One of the causes of maternal death is postpartum hemorrhage. Previous studies have found that postpartum hemorrhage is closely associated with uterine atony. This study aims to explore risk factors for postpartum hemorrhage caused by uterine atony. A case-control study design in Dr. Soetomo General-Academic Hospital. Patient medical records for a period of 2 years at the Dr. Academic General Hospital Soetomo Indonesia used and divided into case and control groups with a ratio of 1:2. Chi-square analyses odds ratios were calculated. A total of 32 patients with uterine atony and 64 medical records without uterine atony were studied. The results of statistical tests on several factors related to postpartum hemorrhage due to uterine atony showed that advanced maternal age (>35 years) (p= 0.763; 95% CI 0.474 – 2.768), grand multipara parity (p = 0.238; 95% CI 0.583-8.185), anemia with Hb <11 (p=0.027; OR=5.000. 95% CI 1.073–23.303), uterine overdistention including macrosomia, polyhydramnios, or gemelli (p=0.031; OR=2.647, 95% CI 1.081-6.482), accelerated labor (p=0.884, 95% CI 0.396-2.221, and previous history of postpartum hemorrhage (p=0.047; OR= 2.435, 95% CI 1.003 – 5.933). This case control study found that anemia, uterine overdistention, and a previous history of postpartum hemorrhage may increase the risk of postpartum hemorrhage due to uterine atony. Therefore, it is recommended to the public to increase awareness of the importance of early and regular pregnancy check-ups, especially in the management of anemia and to identify risk factors.

Korelasi Karakteristik dengan Penyebab Ketuban Pecah Dini pada Ibu Bersalin di RSUD Denisa Gresik

Premature rupture of membrane (PROM) is rupture of the membrane before the birth time. It can happen in the end of pregnancy as well as the early pregnancy (premature pregnancy). The incident of PROM at Denisa Public Hospital Gresik reach 31%. PROM is high risk pregnancy, it was caused of predisposition factors such as incompeten cervix, uterus overdistension, the abnormal position, CPD, and infection. The purpose of this research is to identify the correlation of characteristics with causes of PROM at Denisa Public Hospital Gresik. This research is using analytics method by using simple random sampling. The sampel has been taken of 59 respondents from 143 of population, it begining of march 2017 until march 2018. The variable of this research is characteristics and the causes of PROM. The measurement tools were used check list and data was analyzed using chi square test with the alpha of 5%. The result showed that the factors that cause premature rupture of membranes in this study include: incompetent cervix, uterine overdistention, location abnormalities, CPD and infection. Maternal age correlates with incompetent cervical events, CPD and infections, while maternal work is associated with location abnormalities. So that risk screening at the beginning of pregnancy and routine ANC examination is very necessary.

Path Analysis on Determinants of Postpartum Bleeding at Dr. Moewardi Hospital, Central Java

Background : Postpartum hemorrhage is bleeding that exceeds 500 ml after the baby is born. The main causes of postpartum bleeding are uterine atony, placental retention, birth canal laceration, and blood clotting abnormalities. Predisposing factors of postpartum hemorrhage are age, parity, anemia, premature rupture of membranes, preeclampsia, prolonged labor, uterine overdistention, labor of action, history of previous bleeding, and distance of pregnancy. Postpartum hemorrhage will cause maternal death if it is not treated immediately. This study aimed to analyze the determinants of postpartum hemorrhage. Subjects an d Met h od: This study used observational analytic with a case control approach. The study was conducted at Dr. Moewardi, Central Java, from April to May 2019. The total sample was 225 maternity mothers who were selected based on fixed disease sampling by using a ratio of 1: 2 between the case and control groups. The dependent variable was postpartum bleeding. The independent variables were age, parity, anemia, premature rupture of membranes, preeclampsia, prolonged labor, uterine overdistention, action delivery, obstetric history, uterine atony, placental retention, birth canal laceration, and pregnancy distance. Data collection techniques used secondary data medical record records which were analyzed by using path analysis. Results : Postpartum hemorrhage was directly and positively associated with atonia uterine (b= 2.46; 95% CI= 1.53 to 3.40; p<0.001), vaginal laceration (b= 1.76; 95% CI= 0.78 to 2.75; p <0.001), poor obstetric history (b= 0.93; 95% CI= 0.11 to 1.76; p= 0.026), and type of labor (b= 1.70; 95% CI= 0.94 to 2.46; p <0.001). It was indirectly affected by preeclampsia, parity, prolonged labor, premature rupture of membrane, age, anemia, uterine overdistention, birth spacing, and placental retention. Conclusion: Postpartum hemorrhage is directly and positively associated with atonia uterine, vaginal laceration, poor obstetric history, and type of labor. It is indirectly affected by pre­eclampsia, parity, prolonged labor, premature rupture of membrane, age, anemia, uterine overdistention, birth spacing, and placental retention. Keywords : Postpartum hemorrhage, placental retention, atonia uterine, path analysis Cor r esponden ce : Siti Nur Hidayati. Masters Program in Public Health, Universitas Sebelas Maret. Jl. Ir. Sutami 36A, Surakarta 57126, Central Java. Email: sitihidayati58@gmail.com. Mobile: 082133­679586. Journal of Maternal and Child Health (2019), 4(6): 35-47 https://doi.org/10.26911/thejmch.2019.04.06.04

Performing the Parryscope technique gently for office tubal patency assessment

To demonstrate a novel approach to office tubal patency assessment through infusing air into saline during flexible office hysteroscopy. We also provide data addressing pain and patient experience relative to hysterosalpingography (HSG). Video presentation of clinical technique with supportive crossover data (Canadian Task Force classification II-1). Its University of Mississippi Medical Center Institutional Review Board protocol number is 2013-0230. Academic hospital. Women undergoing office hysteroscopy and ultrasound, with a subsetalso having HSG. Air infusion into saline during office hysteroscopy. The focus is on demonstrating how the technique appears and is performed, with supplemental Likert data addressing subjective pain and preference relative to HSG. When performed as described, this office technique has 98.3%-100% sensitivity to tubal occlusion and 83.7% specificity. The gentle technique is central to accurate outcomes, which is facilitated through use of a small-caliber (<3 mm), flexible hysteroscope and avoiding uterine overdistention. Patients are far more likely to report maximum discomfort with HSG. Among patients who also had HSG, 92% somewhat or strongly prefer hysteroscopic assessment. Also, 96% of patients reporting maximum discomfort with HSG had mild to no discomfort with the described technique. Air-infused saline at flexible office hysteroscopy can accurately, gently, and rapidly assess tubal patency. Coupled with strong patient preference for this technique over HSG, it is a promising option for evaluating fertility. NCT02005263.

Uterine overdistention induces preterm labor mediated by inflammation: observations in pregnant women and nonhuman primates

Uterine overdistention is thought to induce preterm labor in women with twin and multiple pregnancies, but the pathophysiology remains unclear. We investigated for the first time the pathogenesis of preterm birth associated with rapid uterine distention in a pregnant nonhuman primate model. A nonhuman primate model of uterine overdistention was created using preterm chronically catheterized pregnant pigtail macaques (Macaca nemestrina) by inflation of intraamniotic balloons (N = 6), which were compared to saline controls (N = 5). Cesarean delivery was performed due to preterm labor or at experimental end. Microarray, quantitative reverse transcriptase polymerase chain reaction, Luminex (Austin, TX), and enzyme-linked immunosorbent assay were used to measure messenger RNA (mRNA) and/or protein levels from monkey (amniotic fluid, myometrium, maternal plasma) and human (amniocytes, amnion, myometrium) tissues. Statistical analysis employed analysis of covariance and Wilcoxon rank sum. Biomechanical forces were calculated using the law of Laplace. Preterm labor occurred in 3 of 6 animals after balloon inflation and correlated with greater balloon volume and uterine wall stress. Significant elevations of inflammatory cytokines and prostaglandins occurred following uterine overdistention in an "inflammatory pulse" that correlated with preterm labor (interleukin [IL]-1β, tumor necrosis factor [TNF]-α, IL-6, IL-8, CCL2, prostaglandin E2, prostaglandin F2α, all P < .05). A similar inflammatory response was observed in amniocytes in vitro following mechanical stretch (IL1β, IL6, and IL8 mRNA multiple time points, P < .05), in amnion of women with polyhydramnios (IL6 and TNF mRNA, P < .05) and in amnion (TNF-α) and myometrium of women with twins in early labor (IL6, IL8, CCL2, all P < .05). Genes differentially expressed in the nonhuman primate after balloon inflation and in women with polyhydramnios and twins are involved in tissue remodeling and muscle growth. Uterine overdistention by inflation of an intraamniotic balloon is associated with an inflammatory pulse that precedes and correlates with preterm labor. Our results indicate that inflammation is an early event after a mechanical stress on the uterus and leads to preterm labor when the stress is sufficiently great. Further, we find evidence of uterine tissue remodeling and muscle growth as a common, perhaps compensatory, response to uterine distension.

The Effect of an Oxytocin Receptor Antagonist (Retosiban, GSK221149A) on the Response of Human Myometrial Explants to Prolonged Mechanical Stretch.

Multiple pregnancy is a major cause of spontaneous preterm birth, which is related to uterine overdistention. The objective of this study was to determine whether an oxytocin receptor antagonist, retosiban (GSK221149A), inhibited the procontractile effect of stretch on human myometrium. Myometrial biopsies were obtained at term planned cesarean delivery (n = 12). Each biopsy specimen was dissected into 8 strips that were exposed in pairs to low or high stretch (0.6 or 2.4 g) in the presence of retosiban (1 μM) or vehicle (dimethylsulfoxide) for 24 hours. Subsequently, we analyzed the contractile responses to KCl and oxytocin in the absence of retosiban. We found that incubation under high stretch in vehicle alone increased the response of myometrial explants to both KCl (P = .007) and oxytocin (P = .01). However, there was no statistically significant effect of stretch when explants were incubated with retosiban (P = .3 and .2, respectively). Incubation with retosiban in low stretch had no statistically significant effect on the response to either KCl or oxytocin (P = .8 and >.9, respectively). Incubation with retosiban in high stretch resulted in a statistically significant reduction (median fold change, interquartile range, P) in the response to both KCl (0.74, 0.60-1.03, P = .046) and oxytocin (0.71, 0.53-0.91, P = .008). The greater the effect of stretch on explants from a given patient, the greater was the inhibitory effect of retosiban (r = -0.65, P = .02 for KCl and r= -0.73, P = .007 for oxytocin). These results suggest that retosiban prevented stretch-induced stimulation of human myometrial contractility. Retosiban treatment is a potential approach for preventing preterm birth in multiple pregnancy.

Fisiopatología del síndrome de parto pretérmino

El trabajo de parto pretérmino es un síndrome que puede estar asociado a nfección, injurias vasculares, sobredistensión uterina, un reconocimiento alogeneico anormal, estrés, alteraciones hormonales u otro proceso patológico aún no descrito. Las intervenciones orientadas a corregir el incremento en la contractibilidad uterina (tocólisis), cambios cervicales (cerclaje) o activación de las membranas y/o decidua en pacientes con parto pretérmino, sin considerar los mecanismos subyacentes, han sido responsables del limitado avance en la prevención y tratamiento del parto pretérmino. Esta es una breve revisión de la naturaleza sindrómica del parto pretérmino.

Synergy and interactions among biological pathways leading to preterm premature rupture of membranes.

Preterm premature rupture of membranes (PPROM) occurs in 1% to 2% of births. Impact of PPROM is greatest in low- and middle-income countries where prematurity-related deaths are most common. Recent investigations identify cytokine and matrix metalloproteinase activation, oxidative stress, and apoptosis as primary pathways to PPROM. These biological processes are initiated by heterogeneous etiologies including infection/inflammation, placental bleeding, uterine overdistention, and genetic polymorphisms. We hypothesize that pathways to PPROM overlap and act synergistically to weaken membranes. We focus our discussion on membrane composition and strength, pathways linking risk factors to membrane weakening, and future research directions to reduce the global burden of PPROM.

Global report on preterm birth and stillbirth (2 of 7): discovery science

BackgroundNormal and abnormal processes of pregnancy and childbirth are poorly understood. This second article in a global report explains what is known about the etiologies of preterm births and stillbirths and identifies critical gaps in knowledge. Two important concepts emerge: the continuum of pregnancy, beginning at implantation and ending with uterine involution following birth; and the multifactorial etiologies of preterm birth and stillbirth. Improved tools and data will enable discovery scientists to identify causal pathways and cost-effective interventions.Pregnancy and parturition continuumThe biological process of pregnancy and childbirth begins with implantation and, after birth, ends with the return of the uterus to its previous state. The majority of pregnancy is characterized by rapid uterine and fetal growth without contractions. Yet most research has addressed only uterine stimulation (labor) that accounts for <0.5% of pregnancy.EtiologiesThe etiologies of preterm birth and stillbirth differ by gestational age, genetics, and environmental factors. Approximately 30% of all preterm births are indicated for either maternal or fetal complications, such as maternal illness or fetal growth restriction. Commonly recognized pathways leading to preterm birth occur most often during the gestational ages indicated: (1) inflammation caused by infection (22-32 weeks); (2) decidual hemorrhage caused by uteroplacental thrombosis (early or late preterm birth); (3) stress (32-36 weeks); and (4) uterine overdistention, often caused by multiple fetuses (32-36 weeks). Other contributors include cervical insufficiency, smoking, and systemic infections. Many stillbirths have similar causes and mechanisms. About two-thirds of late fetal deaths occur during the antepartum period; the other third occur during childbirth. Intrapartum asphyxia is a leading cause of stillbirths in low- and middle-income countries.RecommendationsUtilizing new systems biology tools, opportunities now exist for researchers to investigate various pathways important to normal and abnormal pregnancies. Improved access to quality data and biological specimens are critical to advancing discovery science. Phenotypes, standardized definitions, and uniform criteria for assessing preterm birth and stillbirth outcomes are other immediate research needs.ConclusionPreterm birth and stillbirth have multifactorial etiologies. More resources must be directed toward accelerating our understanding of these complex processes, and identifying upstream and cost-effective solutions that will improve these pregnancy outcomes.

Prevention of spontaneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment

Prevention of spontaneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment

P26.17: Evaluation of the fetal urinary bladder and associated genitourinary anomalies

due to an enlarged uterus. A male fetus was noted to have a 4 cm × 5 cm solid tumor in the right retroperitoneal space. By 28 weeks, the mass had increased to 8 cm × 6 cm with extreme polyhydramnios. The mass originated in the renal fossa and extended to the level of the diaphragm and across the midline. The mass replaced the fetal right kidney. The left kidney appeared normal. Premature labor initiated hospitalization. A series of drainage amniocentesis were performed due to uterine overdistention and preterm labor. Chromosome analysis showed normal male karyotype. The patient delivered at 33w1d by Cesarean section due to sudden labor and dilitation with breech positioning. The mass measured 10 cm × 10 cm at birth. Surgical resection was performed on day 5. The diagnosis of mesoblastic nephroma was confirmed by histopathology. Cytogenetic studies of the tumor showed a hyperdiploid male karyotype with extra copies of chromosomes 7, 8, 11, 16, and 17. Trisomy 16 was observed in two cells from one isolated area. Parental origin of the extra copy of 11 was confirmed. The combination of three-dimensional ultrasound, pathology and genetic studies confirms diagnosis, treatment and further investigation of this congenital renal tumor.

Safety and efficacy of new drugs in preterm labor

The pathophysiological events that trigger spontaneous preterm birth (SPB) are largely unknown but include decidual hemorrhage (abruption), mechanical factors (uterine overdistention or cervical incompetence) and hormonal changes (perhaps mediated by fetal or maternal stress). In addition, several cervicovaginal infections have been associated with preterm labor. SPB is the leading cause of perinatal mortality and long-term morbidity, including neurodevelopmental handicap, cerebral palsy, seizure disorders, blindness, deafness and non-neurological disorders, such as bronchopulmonary dysplasia and retinopathy of prematurity. Delaying delivery may reduce the rate of long-term morbidity by facilitating the maturation of developing organs and systems. The benefits of administration of antepartum glucocorticosteroids to reduce the incidence and severity of respiratory distress syndrome may be exploited by delay. Delay may also permit transfer of the fetus in utero to a center with neonatal intensive care unit ...

Guidelines for the management of spontaneous preterm labor

Preterm birth is defined as delivery at <37 completed weeks of pregnancy (World Health Organization). Spontaneous preterm birth (SPB) includes preterm labor, preterm spontaneous rupture of membranes, preterm premature rupture of membranes (PPROM) and cervical weakness; it does not include indicated preterm delivery for maternal or fetal conditions. Early SPB (<32 weeks' gestation) is associated with an increased higher perinatal mortality rate, inversely proportional to gestational age. The pathophysiologic events that trigger SPB are largely unknown but include decidual hemorrhage (abruption), mechanical factors (uterine overdistention or cervical incompetence), and hormonal changes (perhaps mediated by fetal or maternal stress). In addition, several cervicovaginal infections have been associated with preterm labor. SPB is also the leading cause of long-term morbidity, including neurodevelopmental handicap, cerebral palsy, seizure disorders, blindness, deafness and non-neurological disorders, such as bronchopulmonary dysplasia and retinopathy of prematurity. Delaying delivery may reduce the rate of long-term morbidity by facilitating the maturation of developing organs and systems. The benefits of administration of antepartum glucocorticosteroids to reduce the incidence and severity of respiratory distress syndrome may be exploited by delay. Delay may also permit transfer of the fetus in utero to a center with neonatal intensive care unit facilities. There is considerable variation in the way that spontaneous preterm labor (SPTL) is diagnosed, managed and treated internationally. The development of clinical guidelines requires an evidence-based approach to improve outcome and allow more efficient use of resources. With recent advances in our understanding of the etiology and mechanisms of SPTL and the availability of safer, more specific tocolytics, it was felt that guidelines should be developed to achieve, if possible, an European consensus in patient diagnosis, management and treatment.

Immunoendocrinology of preterm labor: The link between corticotropin-releasing hormone and inflammation

Preterm labor is the final common pathway after several potential insults to the uterus or fetus. The preterm labor syndrome may be precipitated by several different pathophysiologic events, including intrauterine infection, uterine ischemia, uterine overdistention, hormonal disturbances, and other problems. Intrauterine infections (both clinically evident and subclinical) are associated with increased amniotic fluid concentrations of proinflammatory cytokines, and gestational tissues and the fetus are potential sources of these cytokines. In addition to culture-proven intrauterine infection, there may be an “intrauterine inflammatory response syndrome” that could account for cases of preterm labor in which no infectious organism can be identified. Because the immunologic and endocrinologic systems regulate each other extensively, there is potential for corticotropin-releasing hormone to regulate inflammatory responses and vice versa. The cytokine interleukin 1 stimulates production of corticotropin-releasing hormone, and corticotropin-releasing hormone in turn regulates cytokine production by immune effector cells. Because maternal stress is associated with preterm birth, abnormalities in the regulation of corticotropin-releasing hormone and the production of inflammatory cytokines may be a mechanism that could form the pathophysiologic basis for this association. (Am J Obstet Gynecol 1999;180:S251-6.)

Amnioinfusion

Amnioinfusion is a commonly practiced technique used for intrapartum improvement of the fetal condition. Room temperature normal saline (0.9 per cent) infused through an intrauterine pressure catheter has been used to alleviate variable decelerations, dilute thick meconium, and improve the intrauterine environment. Randomized studies comparing amnioinfusion to no therapy have shown that amnioinfusion is associated with lower cesarean delivery rates, decreased numbers of operative deliveries, and improved umbilical artery and venous blood gas values. Amnioinfusion also has been suggested as means to instill antibiotics into an infected uterine cavity, or the uterine cavity of a woman with preterm premature rupture of the membranes. Transabdominal amnioinfusion may be used to improved prenatal ultrasound evaluation in pregnancies associated with oligohydramnios. Complications of amnioinfusion include umbilical cord prolapse, uterine overdistention, fetal bradycardia, and one report of possible amniotic fluid embolism. Overall, amnioinfusion seems to be a safe and effective technique to improve the intrauterine milieu.

Effects of uterine overdistention on renal plasma flow, glomerular filtration rate, and filtration fraction: Experimental research in dogs

This study was undertaken to explore the concept of toxemia of pregnancy, elaborated by Spiegelberg and brought up to date by Sophian, who maintained that uterorenal reflex played a prominent part in the genesis of this disease. In the present study, the effects of uterorenal reflex on the partial function of the kidneys of 12 pregnant and 5 nonpregnant dogs are analyzed. After uterine distention, in the first group in 10 of 12 animals we observed a remarkable decrease in the renal plasma flow and a lesser decrease in the rate of glomerular filtration. In the nonpregnant group the changes were not significant. This study was undertaken to explore the concept of toxemia of pregnancy, elaborated by Spiegelberg and brought up to date by Sophian, who maintained that uterorenal reflex played a prominent part in the genesis of this disease. In the present study, the effects of uterorenal reflex on the partial function of the kidneys of 12 pregnant and 5 nonpregnant dogs are analyzed. After uterine distention, in the first group in 10 of 12 animals we observed a remarkable decrease in the renal plasma flow and a lesser decrease in the rate of glomerular filtration. In the nonpregnant group the changes were not significant.