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Frontiers in Endocrinology 2023Preterm birth is one of the major causes of neonatal morbidity and mortality across the world. Both term and preterm labour are preceded by inflammatory activation in...
INTRODUCTION
Preterm birth is one of the major causes of neonatal morbidity and mortality across the world. Both term and preterm labour are preceded by inflammatory activation in uterine tissues. This includes increased leukocyte infiltration, and subsequent increase in chemokine and cytokine levels, activation of pro-inflammatory transcription factors as NF-κB and increased prostaglandin synthesis. Prostaglandin F2α (PGF2α) is one of the myometrial activators and stimulators.
METHODS
Here we investigated the role of PGF2α in pro-inflammatory signalling pathways in human myometrial cells isolated from term non-labouring uterine tissue. Primary myometrial cells were treated with G protein inhibitors, calcium chelators and/or PGF2α. Nuclear extracts were analysed by TranSignal cAMP/Calcium Protein/DNA Array. Whole cell protein lysates were analysed by Western blotting. mRNA levels of target genes were analysed by RT-PCR.
RESULTS
The results show that PGF2α increases inflammation in myometrial cells through increased activation of NF-κB and MAP kinases and increased expression of COX-2. PGF2α was found to activate several calcium/cAMP-dependent transcription factors, such as CREB and C/EBP-β. mRNA levels of NF-κB-regulated cytokines and chemokines were also elevated with PGF2α stimulation. We have shown that the increase in PGF2α-mediated COX-2 expression in myometrial cells requires coupling of the FP receptor to both Gαq and Gαi proteins. Additionally, PGF2α-induced calcium response was also mediated through Gαq and Gαi coupling.
DISCUSSION
In summary, our findings suggest that PGF2α-induced inflammation in myometrial cells involves activation of several transcription factors - NF-κB, MAP kinases, CREB and C/EBP-β. Our results indicate that the FP receptor signals via Gαq and Gαi coupling in myometrium. This work provides insight into PGF2α pro-inflammatory signalling in term myometrium prior to the onset of labour and suggests that PGF2α signalling pathways could be a potential target for management of preterm labour.
Topics: Infant, Newborn; Female; Humans; Dinoprost; NF-kappa B; Calcium; Premature Birth; Cyclooxygenase 2; Myometrium; Inflammation; Obstetric Labor, Premature; Cytokines; RNA, Messenger
PubMed: 37547305
DOI: 10.3389/fendo.2023.1150125 -
BMC Pregnancy and Childbirth Nov 2016Most European and North American clinical practice guidelines recommend screening for asymptomatic bacteriuria (ASB) as a routine pregnancy test. Antibiotic treatment of... (Review)
Review
BACKGROUND
Most European and North American clinical practice guidelines recommend screening for asymptomatic bacteriuria (ASB) as a routine pregnancy test. Antibiotic treatment of ASB in pregnant women is supposed to reduce maternal upper urinary tract infections (upper UTIs) and preterm labour. However, most studies supporting the treatment of ASB were conducted in the 1950s to 1980s. Because of subsequent changes in treatment options for ASB and UTI, the applicability of findings from these studies has come into question. Our systematic review had three objectives: firstly, to assess the patient-relevant benefits and harms of screening for ASB versus no screening; secondly, to compare the benefits and harms of different screening strategies; and thirdly, in case no reliable evidence on the overarching screening question was identified, to determine the benefits and harms of treatment of ASB.
METHODS
We systematically searched several bibliographic databases, trial registries, and other sources (up to 02/2016) for randomised controlled trials (RCTs) and prospective non-randomised trials. Two authors independently reviewed abstracts and full-text articles and assessed the risk of bias of the studies included. As meta-analyses were not possible, we summarised the results qualitatively.
RESULTS
We did not identify any eligible studies that investigated the benefits and harms of screening for ASB versus no screening or that compared different screening strategies. We identified four RCTs comparing antibiotics with no treatment or placebo in 454 pregnant women with ASB. The results of 2 studies published in the 1960s showed a statistically significant reduction in rates of pyelonephritis (odds ratio [OR] = 0.21, 95 % confidence interval [CI] 0.07-0.59) and lower UTI (OR = 0.10, 95 % CI 0.03-0.35) in women treated with antibiotics. By contrast, event rates reported by a recent study were not statistically significantly different, neither regarding pyelonephritis (0 % vs. 2.2 %; OR = 0.37, CI 0.01-9.25, p = 0.515) nor regarding lower UTI during pregnancy (10 % vs. 18 %; Peto odds ratio [POR] = 0.53, CI 0.16-1.79, p = 0.357). Data were insufficient to determine the risk of harms. As three of the four studies were conducted several decades ago and have serious methodological shortcomings, the applicability of their findings to current health care settings is likely to be low. The recent high-quality RCT was stopped early due to a very low number of primary outcome events, a composite of preterm delivery and pyelonephritis. Therefore, the results did not show a benefit of treating ASB.
CONCLUSIONS
To date, no reliable evidence supports routine screening for ASB in pregnant women.
Topics: Anti-Bacterial Agents; Asymptomatic Infections; Bacteriuria; Female; Humans; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Infectious; Prenatal Diagnosis
PubMed: 27806709
DOI: 10.1186/s12884-016-1128-0 -
International Journal of Environmental... Jan 2020Endometriosis may compromise the physiological course of pregnancy. The aim of this prospective observational study was to evaluate whether endometriosis causes a higher... (Observational Study)
Observational Study
Endometriosis may compromise the physiological course of pregnancy. The aim of this prospective observational study was to evaluate whether endometriosis causes a higher prevalence of obstetric and neonatal complications as well as a higher risk of caesarean section and to detect a possible correlation between the presence, type, and location of endometriosis and obstetric complications, previous surgery, and pregnancy outcome, as well as the influence of pregnancy on the course of the disease. We compared two cohorts of women with spontaneous pregnancy, with and without endometriosis. Obstetric and neonatal outcomes, mode of delivery, presence, type, and location of endometriotic lesions and the effect of pregnancy on the disease were analyzed. A total of 425 pregnancies were evaluated: 145 cases and 280 controls. Patients with endometriosis showed a higher incidence of miscarriage, threatened miscarriage, threatened preterm labor, preterm delivery, placental abruption, and a higher incidence of caesarean section. A significant correlation with pregnancy-induced hypertension and preeclampsia was found in the presence of adenomyosis. No difference in fetal outcome was found. One case of hemoperitoneum during pregnancy was observed. Pregnancy in women with endometriosis carries a higher risk of obstetric complications, such as miscarriage, threatened miscarriage, preterm labor, preterm birth, and a higher caesarean section rate. Endometriosis does not seem to influence fetal well-being.
Topics: Abortion, Spontaneous; Abruptio Placentae; Adult; Cesarean Section; Endometriosis; Female; Humans; Hypertension, Pregnancy-Induced; Infant, Newborn; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Prospective Studies
PubMed: 31936225
DOI: 10.3390/ijerph17020401 -
Medicina (Kaunas, Lithuania) May 2021: Therapeutic interventions targeting molecular factors involved in the transition from uterine quiescence to overt labour are not substantially reducing the rate of...
: Therapeutic interventions targeting molecular factors involved in the transition from uterine quiescence to overt labour are not substantially reducing the rate of spontaneous preterm labour. The identification of novel rational therapeutic targets are essential to prevent the most common cause of neonatal mortality. Based on our previous work showing that Tbx2 (T-Box transcription factor 2) is a putative upstream regulator preceding progesterone withdrawal in mouse myometrium, we now investigate the role of TBX2 in human myometrium. : RNA microarray analysis of (A) preterm human myometrium samples and (B) myometrial cells overexpressing TBX2 in vitro, combined with subsequent analysis of the two publicly available datasets of (C) Chan et al. and (D) Sharp et al. The effect of TBX2 overexpression on cytokines/chemokines secreted to the myometrium cell culture medium were determined by Luminex assay. : Analysis shows that overexpression of TBX2 in myometrial cells results in downregulation of TNFα- and interferon signalling. This downregulation is consistent with the decreased expression of cytokines and chemokines of which a subset has been previously associated with the inflammatory pathways relevant for human labour. In contrast, CXCL5 (C-X-C motif chemokine ligand 5), CCL21 and IL-6 (Interleukin 6), previously reported in relation to parturition, do not seem to be under TBX2 control. The combined bioinformatical analysis of the four mRNA datasets identifies a subset of upstream regulators common to both preterm and term labour under control of TBX2. Surprisingly, TBX2 mRNA levels are increased in preterm contractile myometrium. : We identified a subset of upstream regulators common to both preterm and term labour that are activated in labour and repressed by TBX2. The increased TBX2 mRNA expression in myometrium collected during a preterm caesarean section while in spontaneous preterm labour compared to tissue harvested during iatrogenic preterm delivery does not fit the bioinformatical model. We can only explain this by speculating that the in vivo activity of TBX2 in human myometrium depends not only on the TBX2 expression levels but also on levels of the accessory proteins necessary for TBX2 activity.
Topics: Cesarean Section; Female; Humans; Interleukin-6; Labor, Obstetric; Myometrium; Obstetric Labor, Premature; Pregnancy; T-Box Domain Proteins
PubMed: 34064060
DOI: 10.3390/medicina57060515 -
Acta Obstetricia Et Gynecologica... Dec 2014To give an overview of the methods available for biomechanical testing of the non-pregnant and pregnant uterine cervix in vivo. (Review)
Review
OBJECTIVE
To give an overview of the methods available for biomechanical testing of the non-pregnant and pregnant uterine cervix in vivo.
METHODS
The following databases were searched. PubMed, Embase, and Cochrane Library. Additional studies were identified from reference lists. Only studies on in vivo biomechanical testing on both pregnant and non-pregnant women were included.
MAIN OUTCOME MEASURES
Estimation of distensibility, compressibility, and biochemical composition of the uterine cervix.
RESULTS
The distensibility methods evaluated a physiologic variable and might serve as a gold standard; however, they may never be clinically useful as they involve instrumentation of the cervical canal. The compression methods evaluated an unphysiological variable but despite that, they seemed to evaluate biologically relevant figures and were non-invasive. Of the methods evaluating the biomechanical properties indirectly, those based on ultrasound may be clinically useful. Other indirect methods only measured variables within the most superficial layer of the distal uterine cervix, so further studies are needed to evaluate whether these measurements reflect the entire organ. Both compression methods and indirect methods were similar or superior to the Bishop score and to cervical length measurements regarding prediction of spontaneous preterm delivery and successful induction of labor in small studies.
CONCLUSION
The methods may have the potential to detect the biomechanical changes in the uterine cervix before the cervical length has shortened. The most promising methods need large-scale clinical testing regarding induction of labor and preterm delivery before they can be used in the clinic.
Topics: Biomechanical Phenomena; Cervical Ripening; Cervix Uteri; Diagnostic Techniques, Obstetrical and Gynecological; Elasticity Imaging Techniques; Female; Humans; In Vitro Techniques; Obstetric Labor, Premature; Palpation; Pregnancy
PubMed: 25174701
DOI: 10.1111/aogs.12483 -
Journal of Perinatal Medicine Jun 2022To determine whether placental vascular pathology and impaired placental exchange due to maturational defects are involved in the etiology of spontaneous preterm labor... (Observational Study)
Observational Study
OBJECTIVES
To determine whether placental vascular pathology and impaired placental exchange due to maturational defects are involved in the etiology of spontaneous preterm labor and delivery in cases without histologic acute chorioamnionitis.
METHODS
This was a retrospective, observational study. Cases included pregnancies that resulted in spontaneous preterm labor and delivery (<37 weeks), whereas uncomplicated pregnancies that delivered fetuses at term (≥37-42 weeks of gestation) were selected as controls. Placental histological diagnoses were classified into three groups: lesions of maternal vascular malperfusion, lesions of fetal vascular malperfusion, and placental microvasculopathy, and the frequency of each type of lesion in cases and controls was compared. Moreover, we specifically searched for villous maturational abnormalities in cases and controls. Doppler velocimetry of the umbilical and uterine arteries were performed in a subset of patients.
RESULTS
There were 184 cases and 2471 controls, of which 95 and 1178 had Doppler studies, respectively. The frequency of lesions of maternal vascular malperfusion was greater in the placentas of patients with preterm labor than in the control group [14.1% (26/184) vs. 8.8% (217/2471) (p=0.023)]. Disorders of villous maturation were more frequent in the group with preterm labor than in the control group: 41.1% (39/95) [delayed villous maturation in 31.6% (30/95) vs. 2.5% (13/519) in controls and accelerated villous maturation in 9.5% (9/95) vs. none in controls].
CONCLUSIONS
Maturational defects of placental villi were associated with approximately 41% of cases of unexplained spontaneous preterm labor and delivery without acute inflammatory lesions of the placenta and with delivery of appropriate-for-gestational-age fetuses.
Topics: Chorioamnionitis; Female; Gestational Age; Humans; Infant, Newborn; Obstetric Labor, Premature; Placenta; Placenta Diseases; Pregnancy
PubMed: 35246973
DOI: 10.1515/jpm-2021-0681 -
Seminars in Perinatology Dec 2014Despite advances in neonatal care, the burden of preterm birth remains high. Preterm birth is a multifactorial problem, and strategies to identify and treat medical risk... (Review)
Review
Despite advances in neonatal care, the burden of preterm birth remains high. Preterm birth is a multifactorial problem, and strategies to identify and treat medical risk factors in early pregnancy have not been effective in reducing preterm birth rates. In a sentinel clinical trial, prophylactic therapy with 17-hydoxyprogesterone caproate (17-OHPC) reduced the risk of recurrent, spontaneous preterm birth in 34% of women. As a result, clinical practice changed and extensive research on 17-OHPC followed. The increasing body of evidence demonstrated a variable efficacy of the drug. This review will examine the plausibility, pharmacology, clinical efficacy, and safety of 17-OHPC when used in the setting of preterm birth prevention. We will also discuss pharmacokinetic and pharmacodynamics data to highlight drug metabolism and mechanism of action, which will help clarify the variability in clinical outcomes and efficacy.
Topics: 17 alpha-Hydroxyprogesterone Caproate; Female; Humans; Hydroxyprogesterones; Obstetric Labor, Premature; Pregnancy; Premature Birth; Progestins
PubMed: 25256193
DOI: 10.1053/j.semperi.2014.08.013 -
Journal of Pregnancy 2017MicroRNAs are small, noncoding RNA molecules that regulate target gene expression in the posttranscriptional level. Unlike siRNA, microRNAs are "fine-tuners" rather than... (Review)
Review
MicroRNAs are small, noncoding RNA molecules that regulate target gene expression in the posttranscriptional level. Unlike siRNA, microRNAs are "fine-tuners" rather than "switches" in the regulation of gene expression; thus they play key roles in maintaining tissue homeostasis. The aberrant microRNA expression is implicated in the disease process. To date, numerous studies have demonstrated the regulatory roles of microRNAs in various pathophysiological conditions. In contrast, the study of microRNA in pregnancy and its associated complications, such as preeclampsia (PE), fetal growth restriction (FGR), and preterm labor, is a young field. Over the last decade, the knowledge of pregnancy-related microRNAs has increased and the molecular mechanisms by which microRNAs regulate pregnancy or its associated complications are emerging. In this review, we focus on the recent advances in the research of pregnancy-related microRNAs, especially their function in pregnancy-associated complications and the potential clinical applications. Here microRNAs that associate with pregnancy are classified as placenta-specific, placenta-associated, placenta-derived circulating, and uterine microRNA according to their localization and origin. MicroRNAs offer a great potential for developing diagnostic and therapeutic targets in pregnancy-related disorders.
Topics: Female; Fetal Growth Retardation; Gene Expression Regulation, Developmental; Humans; MicroRNAs; Obstetric Labor, Premature; Placenta; Pre-Eclampsia; Pregnancy; Uterus
PubMed: 28713594
DOI: 10.1155/2017/6972732 -
Maternal and Child Health Journal Jun 2015We utilized an updated nationally representative database to examine associations between maternal age and prevalence of maternal morbidity during complications of labor...
We utilized an updated nationally representative database to examine associations between maternal age and prevalence of maternal morbidity during complications of labor and delivery. We used hospital inpatient billing data from the 2009 United States Nationwide Inpatient Sample, part of the Healthcare Cost and Utilization Project. To determine whether the likelihood that maternal morbidity during complications of labor and delivery differed among age groups, separate logistic regression models were run for each complication. Age was the main independent variable of interest. In analyses that controlled for demographics and clinical confounders, we found that complications with the highest odds among women, 11-18 years of age, compared to 25-29 year old women, included preterm delivery, chorioamnionitis, endometritis, and mild preeclampsia. Pregnant women who were 15-19 years old had greater odds for severe preeclampsia, eclampsia, postpartum hemorrhage, poor fetal growth, and fetal distress. Pregnant women who were ≥35 years old had greater odds for preterm delivery, hypertension, superimposed preeclampsia, severe preeclampsia, and decreased risk for chorioamnionitis. Older women (≥40 years old) had increased odds for mild preeclampsia, fetal distress, and poor fetal growth. Our findings underscore the need for pregnant women to be aware of the risks associated with extremes of age so that they can watch for signs and symptoms of such complications.
Topics: Adolescent; Adult; Child; Female; Fetal Distress; Fetal Growth Retardation; Humans; Maternal Age; Obstetric Labor Complications; Obstetric Labor, Premature; Postpartum Hemorrhage; Pre-Eclampsia; Pregnancy; Risk Factors; Young Adult
PubMed: 25366100
DOI: 10.1007/s10995-014-1624-7 -
International Journal of Environmental... Aug 2021Adolescent pregnancy remains a health issue worldwide also in developed countries, since it has been associated with adverse maternal and neonatal outcomes. Some data... (Observational Study)
Observational Study
Adolescent pregnancy remains a health issue worldwide also in developed countries, since it has been associated with adverse maternal and neonatal outcomes. Some data suggest that very young adolescents have higher risk, likely due to immaturity. Therefore, we aimed to assess the influence of maternal age on complications during gestation and labor in pregnant women between 13 and 19 years of age. In particular, we evaluated the possible association between maternal age and obstetric, fetal and labor complications. This is a retrospective, observational and exploratory study conducted at Hospital Universitario La Paz (HULP, Madrid, Spain). The clinical history of 279 women who delivered between 2013 and 2018 was analyzed. Maternal age and the presence of maternal, fetal and labor complications, as well as risk of postpartum depression and breastfeeding intention, were recorded. General regression models were used to analyze the contribution of maternal age on each complication. The percentage of adolescent pregnancies at HULP between 2013 and 2018 was 0.9%. The risk of all the maternal complications analyzed decreased significantly with every year of age of the mother (hyperemesis, lower back pain, anemia, gestational diabetes mellitus, and threat of premature labor and premature rupture of membranes). Every year of maternal age decreased 0.8-fold [0.8; 0.9] the prevalence of fetal complications and also reduced the risk of C-section, postpartum hemorrhage and obstetrical hysterectomy. Furthermore, higher maternal age increased 1.1-fold [1.0; 1.2] the breastfeeding intention. In conclusion, young adolescents are at higher risk of complications during pregnancy and labor.
Topics: Adolescent; Adult; Cesarean Section; Female; Humans; Infant, Newborn; Obstetric Labor Complications; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy in Adolescence; Premature Birth; Retrospective Studies; Young Adult
PubMed: 34444266
DOI: 10.3390/ijerph18168514