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1.
BMC Pregnancy Childbirth ; 24(1): 311, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724897

RESUMO

AIM: The purpose of this study is to evaluate the oral probiotic effect on pregnancy outcomes in pregnant women undergoing cerclage compared to placebo. METHODS: This study was a double-blind randomized clinical trial undertaken in Yasuj, Iran. 114 eligible participants who have undergone cerclage were randomly divided to either receive probiotic adjuvant or 17α-OHP (250 mg, IM) with placebo from the 16th -37th week of pregnancy by "block" randomization method. Our primary outcomes were preterm labor (PTB) (late and early) and secondary outcomes were other obstetrical and neonatal outcomes included preterm pre-labor rupture of membranes (PPROM), pre-labor rupture of membranes (PROM), mode of delivery, and neonatal outcomes including anthropometric characterize and Apgar score (one and fifth-minute). RESULTS: Results show that there are no statistically significant differences between the two groups in terms of PTB in < 34th (15.51% vs. 17.86%; P = 0.73) and 34-37th weeks of pregnancy (8.7% vs. 16.1%; P = 0.22), and mode of delivery (P = 0.09). PPROM (8.7% vs. 28.5%; P = 0.006) PROM (10.3% vs. 25%; P = 0.04) was significantly lower in patients receiving probiotic adjuvant compared to the control group. After delivery, the findings of the present study showed that there were no significant differences in newborn's weight (3082.46 ± 521.8vs. 2983.89 ± 623.89), head circumstance (36.86 ± 1.53vs. 36.574 ± 1.52), height (45.4 ± 5.34 vs. 47.33 ± 4.92) and Apgar score in one (0.89 ± 0.03 vs. 0.88 ± 0.05) and five minutes (0.99 ± 0.03vs. 0.99 ± 0.03) after birth. CONCLUSION: Our result has shown that the consumption of Lactofem probiotic from the 16th week until 37th of pregnancy can lead to a reduction of complications such as PPROM and PROM.


Assuntos
Cerclagem Cervical , Resultado da Gravidez , Probióticos , Humanos , Gravidez , Feminino , Probióticos/uso terapêutico , Probióticos/administração & dosagem , Método Duplo-Cego , Adulto , Irã (Geográfico) , Cerclagem Cervical/métodos , Recém-Nascido , Ruptura Prematura de Membranas Fetais , Adulto Jovem , Nascimento Prematuro/prevenção & controle , Trabalho de Parto Prematuro/prevenção & controle , Administração Oral
2.
Clin Perinatol ; 51(2): 379-389, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38705647

RESUMO

Spontaneous preterm birth (sPTB) is a complex and clinically heterogeneous condition that remains incompletely understood, leading to insufficient interventions to effectively prevent it from occurring. Cell-free ribonucleic acid signatures in the maternal circulation have the potential to identify biologically relevant subtypes of sPTB. These could one day be used to predict and prevent sPTB in asymptomatic individuals, and to aid in prognosis and management for individuals presenting with threatened preterm labor and preterm prelabor rupture of membranes.


Assuntos
Ácidos Nucleicos Livres , Nascimento Prematuro , Humanos , Feminino , Gravidez , Ácidos Nucleicos Livres/sangue , Nascimento Prematuro/prevenção & controle , Ruptura Prematura de Membranas Fetais , Recém-Nascido , Trabalho de Parto Prematuro/diagnóstico , Prognóstico , Biomarcadores/sangue
3.
Clin Perinatol ; 51(2): 497-510, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38705654

RESUMO

This review examines the complexities of preterm birth (PTB), emphasizes the pivotal role of inflammation in the pathogenesis of preterm labor, and assesses current available interventions. Antibiotics, progesterone analogs, mechanical approaches, nonsteroidal anti-inflammatory drugs, and nutritional supplementation demonstrate a limited efficacy. Tocolytic agents, targeting uterine activity and contractility, inadequately prevent PTB by neglecting to act on uteroplacental inflammation. Emerging therapies targeting toll-like receptors, chemokines, and interleukin receptors exhibit promise in mitigating inflammation and preventing PTB.


Assuntos
Nascimento Prematuro , Tocolíticos , Humanos , Gravidez , Feminino , Nascimento Prematuro/prevenção & controle , Tocolíticos/uso terapêutico , Recém-Nascido , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Trabalho de Parto Prematuro/prevenção & controle
4.
Int J Mol Sci ; 25(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612564

RESUMO

This systematic review delves into the connections between microRNAs and preterm labor, with a focus on identifying diagnostic and prognostic markers for this crucial pregnancy complication. Covering studies disseminated from 2018 to 2023, the review integrates discoveries from diverse pregnancy-related scenarios, encompassing gestational diabetes, hypertensive disorders and pregnancy loss. Through meticulous search strategies and rigorous quality assessments, 47 relevant studies were incorporated. The synthesis highlights the transformative potential of microRNAs as valuable diagnostic tools, offering promising avenues for early intervention. Notably, specific miRNAs demonstrate robust predictive capabilities. In conclusion, this comprehensive analysis lays the foundation for subsequent research, intervention strategies and improved outcomes in the realm of preterm labor.


Assuntos
Aborto Espontâneo , Diabetes Gestacional , Hipertensão , Trabalho de Parto Prematuro , Feminino , Gravidez , Recém-Nascido , Humanos , Trabalho de Parto Prematuro/genética , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/genética
5.
Eur Rev Med Pharmacol Sci ; 28(6): 2403-2408, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38567603

RESUMO

OBJECTIVE: Inflammation has been reported to increase zonulin levels, a protein that regulates intestinal permeability. The aim of this study was to investigate the association of serum zonulin levels with preterm labor in pregnant women. PATIENTS AND METHODS: A total of 180 pregnant women between 32-42 weeks of gestation were included in the study. Among those whose gestational week is less than 37, preterm labor (group 1), normal course pregnant (group 2), and gestational weeks between 37-42 pregnant women with normal course (group 3), term labor (group 4) groups were formed. RESULTS: Zonulin levels were not statistically different between groups. Among the inflammation markers, only C-reactive protein levels were significantly higher in group 1 compared to groups 2 and 3. There were a total of 18/90 (20%) pregnant women with premature rupture of membranes (PROM) in the delivery groups. The mean zonulin level was higher in those with PROM (155.3±50.2 ng/ml) than those without PROM (128.8±59 ng/ml). However, there was no statistically significant difference between them. CONCLUSIONS: In conclusion, serum zonulin levels were not useful as a marker for predicting preterm labor. However, examining large-scale studies about the relationship between PROM and zonulin is still needed.


Assuntos
Ruptura Prematura de Membranas Fetais , Haptoglobinas , Trabalho de Parto Prematuro , Recém-Nascido , Gravidez , Feminino , Humanos , Trabalho de Parto Prematuro/diagnóstico , Precursores de Proteínas , Inflamação , Idade Gestacional
6.
Medicina (Kaunas) ; 60(4)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38674294

RESUMO

Aerobic vaginitis (AV) is a distinct clinical entity characterized by inflammation and abnormal vaginal microflora. Often mistaken for bacterial vaginosis, AV remains relatively unknown and underdiagnosed. AV's understanding is evolving, with some experts suggesting it may primarily be an immunological disorder, the prevalence of which has a range of 7-13% in non-pregnant women and 4.1-8.3% during pregnancy. Pregnancy can affect susceptibility to vaginal infections, leading to adverse outcomes for the woman and the newborn. This review summarizes the correlation between AV and adverse pregnancy outcomes, particularly preterm birth, the leading cause of morbidity and mortality among neonates. An improved understanding of AV's impact on pregnancy outcomes can lead to early recognition, proper management, and effective interventions. While some studies support an association between AV and preterm labor, the existing knowledge of this relationship remains limited. The evidence suggests that AV may contribute to adverse pregnancy outcomes, mainly preterm birth, but further research is needed to establish a definitive link. Further studies are needed to investigate the underlying mechanisms and clarify AV's role in premature labor. A comprehensive understanding of AV's impact on pregnancy outcomes is crucial for early recognition, appropriate management, and effective interventions.


Assuntos
Trabalho de Parto Prematuro , Humanos , Feminino , Gravidez , Vaginite/diagnóstico , Vaginite/microbiologia , Nascimento Prematuro , Resultado da Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Vaginose Bacteriana/diagnóstico , Vaginose Bacteriana/complicações , Recém-Nascido
7.
BMC Pregnancy Childbirth ; 24(1): 318, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664622

RESUMO

BACKGROUND: Some studies have compared the efficacy of nifedipine with that of other tocolytic drugs in the treatment of preterm labor, but the reported results are conflicting. OBJECTIVE: To compare the efficacy of nifedipine with that of ritodrine, nitroglycerine and magnesium sulfate for the management of preterm labor. METHODS: In this systematic review and meta-analysis, PubMed/MEDLINE, Scopus, Clarivate Analytics Web of Science, and Google Scholar were searched until April 3,2024 using predefined keywords. Randomized controlled trials (RCTs) and clinical trials that compared the efficacy of nifedipine with that of ritodrine, nitroglycerine and magnesium sulfate for the management of preterm labor were included. Two authors independently reviewed the articles, assessed their quality and extracted the data. The quality of the included RCTs based on the Cochrane Risk of Bias Tool 1 for clinical trial studies. The risk difference (RD) with the associated 95% confidence interval (CI) was calculated. A forest plot diagram was used to show the comparative point estimates of nifedipine and other tocolytic drugs on the prevention of preterm labor and their associated 95% confidence intervals based on the duration of pregnancy prolongation. Study heterogeneity was evaluated by the I2 index, and publication bias was evaluated by Egger's test. RESULTS: Forty studies enrolling 4336 women were included. According to our meta-analysis, there was a significant difference in the prolongation of preterm labor within the first 48 h between the nifedipine group and the nitroglycerine group (RD, -0.04; 95% CI, -0.08 to -0.00; I2: 32.3%). Additionally, there were significant differences between nifedipine and ritodrine (RD, 0.11; 95% CI, 0.02 to 0.21; I2, 51.2%) for more than one week RD, 0.10; 95% CI, 0.03 to 0.19; I2, 33.2%) and for 34 weeks and more. The difference between nifedipine and magnesium sulfate was not significant in any of the four time points. CONCLUSIONS: Considering the superiority of nifedipine over ritodrine and nitroglycerine and its similar efficacy to magnesium sulfate for tocolysis, it seems that the side effects of these options determine the first drug line.


Assuntos
Sulfato de Magnésio , Nifedipino , Nitroglicerina , Trabalho de Parto Prematuro , Ritodrina , Tocolíticos , Humanos , Nifedipino/uso terapêutico , Feminino , Gravidez , Trabalho de Parto Prematuro/tratamento farmacológico , Sulfato de Magnésio/uso terapêutico , Ritodrina/uso terapêutico , Tocolíticos/uso terapêutico , Nitroglicerina/uso terapêutico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
BMC Pregnancy Childbirth ; 24(1): 197, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481196

RESUMO

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


Assuntos
Anafilaxia , Corioamnionite , Trabalho de Parto , Trabalho de Parto Prematuro , Nascimento Prematuro , Feminino , Recém-Nascido , Gravidez , Humanos , Adulto , Anafilaxia/induzido quimicamente , Anafilaxia/complicações , Trabalho de Parto Prematuro/diagnóstico , Contração Uterina , Líquido Amniótico/metabolismo , Inflamação , Corioamnionite/metabolismo
10.
BMC Pregnancy Childbirth ; 24(1): 213, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509456

RESUMO

BACKGROUND: Ritodrine hydrochloride is a widely used beta-adrenergic agonist used to stop preterm labor in Taiwan. Many side effects causing maternal morbidity and mortality have been reported. We report a case complicated with ritodrine-induced side effects and mirror syndrome that was associated with placental chorioangioma. CASE PRESENTATION: A 36-year-old singleton pregnant woman at 25 6/7 weeks of gestation, with an undiagnosed placental chorioangioma, underwent tocolysis due to preterm uterine contractions. Her clinical condition deteriorated, attributed to mirror syndrome and adverse events induced by ritodrine. An emergency cesarean section was performed at 27 1/7 weeks of gestation, delivering an infant with generalized subcutaneous edema. A placental tumor measuring 8.5 cm was discovered during the operation, and pathology confirmed chorioangioma. Gradual improvement in her symptoms and laboratory data was observed during the postpartum period. Identifying mirror syndrome and ritodrine-induced side effects poses challenges. Therefore, this case is educational and warrants discussion. CONCLUSION: Our case demonstrates mirror syndrome induced by chorioangioma, which is rare, and ritodrine-induced side effects. The cessation of intravenous ritodrine and delivery are the best methods to treat maternal critical status due to fluid overload.


Assuntos
Hemangioma , Trabalho de Parto Prematuro , Ritodrina , Recém-Nascido , Gravidez , Feminino , Humanos , Adulto , Ritodrina/efeitos adversos , Hidropisia Fetal/induzido quimicamente , Cesárea/efeitos adversos , Placenta , Trabalho de Parto Prematuro/tratamento farmacológico , Hemangioma/complicações , Hemangioma/tratamento farmacológico , Síndrome
11.
BMC Med Genomics ; 17(1): 72, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443884

RESUMO

BACKGROUND: Globally, preterm birth remains the leading cause of death in children younger than 5 years old. Spontaneous preterm birth is comprised of two events that may or may not occur simultaneously: preterm labor and preterm prelabor rupture of membranes (PPROM). To further explore the concept that spontaneous preterm birth can result from the initializing of two separate but overlapping pathological events, we compared fetal membrane tissue from preterm labor deliveries to fetal tissue from preterm labor with PPROM deliveries. We hypothesized that the fetal membrane tissue from preterm labor with PPROM cases will have an RNA-seq profile divergent from the fetal membrane tissue from preterm labor controls. METHODS: Chorioamnion, separated into amnion and chorion, was collected from eight gestationally age-matched cases and controls within 15 min of birth, and analyzed using RNA sequencing. Pathway enrichment analyses and functional annotations of differentially expressed genes were performed using KEGG and Gene Ontogeny Pathway enrichment analyses. RESULTS: A total of 1466 genes were differentially expressed in the amnion, and 484 genes were differentially expressed in the chorion (log2 fold change > 1, FDR < 0.05) in cases (preterm labor with PPROM), versus controls (preterm labor only). In the amnion, the most significantly enriched (FDR < 0.01) KEGG pathway among down-regulated genes was the extracellular matrix receptor interaction pathway. Seven of the most significantly enriched pathways were comprised of multiple genes from the COL family, including COL1A, COL3A1, COL4A4, and COL4A6. In the chorion, the most significantly enriched KEGG pathways in up-regulated genes were chemokine, NOD receptor, Toll-like receptor, and cytokine-cytokine receptor signaling pathways. Similarly, KEGG pathway enrichment analysis for up-regulated genes in the amnion included three inflammatory pathways: cytokine-cytokine interaction, TNF signaling and the CXCL family. Six genes were significantly up regulated in chorionic tissue discriminated between cases (preterm labor with PPROM) and controls (preterm labor only) including GBP5, CXCL9, ALPL, S100A8, CASP5 and MMP25. CONCLUSIONS: In our study, transcriptome analysis of preterm fetal membranes revealed distinct differentially expressed genes for PPROM, separate from preterm labor. This study is the first to report transcriptome data that reflects the individual pathophysiology of amnion and chorion tissue from PPROM deliveries.


Assuntos
Ruptura Prematura de Membranas Fetais , Trabalho de Parto Prematuro , Nascimento Prematuro , Recém-Nascido , Criança , Feminino , Humanos , Pré-Escolar , Nascimento Prematuro/genética , Membranas Extraembrionárias , Trabalho de Parto Prematuro/genética , Perfilação da Expressão Gênica , Transcriptoma , Citocinas
12.
Eur J Obstet Gynecol Reprod Biol ; 295: 48-52, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38335584

RESUMO

OBJECTIVE: Premature births are a health problem arising in triplet pregnancies, resulting in high levels of morbidity and mortality. The objective of this study is to evaluate the utility of cervical pessaries in reducing prematurity (<34 weeks) in triplet pregnancies. METHODS: This is a single-center, retrospective case-control study regarding triplet pregnancies with follow-up at the La Paz University Hospital between 2000 and 2023. Maternal characteristics, obstetric and perinatal outcomes, and the use of cervical pessaries were examined. RESULTS: 165 triplet pregnancies were analyzed: 87 (52.7 %) in the case group (premature triplet pregnancies) and 78 in the control group (non-premature triplet pregnancies). A cervical pessary was inserted in 15 (17.2 %) triplet pregnancies in the case group and in 12 (16.7 %) triplet pregnancies in the control group (p = 0.92; OR = 1.04 (0.46-2.35)). A pessary was later inserted in the non-premature group (p = 0.01). The risk of preterm labor and the use of tocolytics ± glucocorticoids were found to be significantly more frequent in the premature group, with p = 0.01; OR = 2.30 (1.21-4.36) and p < 0.01; OR = 2.36 (1.23-4.44), respectively. Protocol-based cesarean sections were more frequent in the non-premature group (p < 0.01), while cesarean sections due to maternal complications (p < 0.01) and premature membrane rupture (p < 0.01) were more frequent in the premature group. CONCLUSION: The cervical pessary is not useful in preventing preterm births (< 34 weeks) in triplet pregnancies. It is likely that being pregnant with triplets is a powerful independent factor associated with prematurity, despite other pregnancy conditions. Women who are pregnant with triplets and at risk of preterm labor and those taking tocolytics ± glucocorticoids may benefit from pessary insertion.


Assuntos
Trabalho de Parto Prematuro , Gravidez de Trigêmeos , Nascimento Prematuro , Tocolíticos , Gravidez , Recém-Nascido , Feminino , Humanos , Nascimento Prematuro/prevenção & controle , Estudos Retrospectivos , Pessários , Estudos de Casos e Controles , Colo do Útero
13.
BMC Pediatr ; 24(1): 106, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341578

RESUMO

BACKGROUND: Preterm labor (PTL) is a common and serious pregnancy disorder that can cause long-term neurological issues in the infant. There are conflicting studies concerning whether sildenafil citrate (SC) reduces preterm labor complications. Therefore, the meta-analysis aimed to examine the clinical outcomes in women with threatened PTL who received nifedipine plus SC therapy versus only nifedipine. METHODS: For the original articles, six databases were searched using relevant keywords without restriction on time or language until January 13, 2024. The Cochrane risk-of-bias tool for randomized trials (RoB) and the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) were both used to assess the risk of bias in randomized and non-randomized studies, and GRADE determined the quality of our evidence. Meta-analysis of all data was carried out using Review Manager (RevMan) version 5.1. RESULTS: Seven studies with mixed quality were included in the meta-analysis. The study found that combining nifedipine and SC resulted in more prolongation of pregnancy (MD = 6.99, 95% CI: 5.32, 8.65, p < 0.00001), a lower rate of delivery in the 1st to 3rd days after hospitalization (RR = 0.62, 95% CI: 0.50, 0.76, p < 0.00001), a higher birth weight (252.48 g vs. nifedipine alone, p = 0.02), and the risk ratio of admission to the neonatal intensive care unit (NICU) was significantly lower (RR = 0.62, 95% CI: 0.50, 0.76, p < 0.00001) compared to nifidepine alone. The evidence was high for prolongation of pregnancy, delivery rate 24-72 h after admission, and NICU admission, but low for newborn birth weight. CONCLUSIONS: Given the effectiveness of SC plus nifedipine in increased prolongation of pregnancy and birth weight, lower delivery in the 1st to 3rd days after hospitalization, and NICU admission, Gynecologists and obstetricians are suggested to consider this strategy for PTL management, although additional article rigor is required to improve the quality of the evidence.


Assuntos
Trabalho de Parto Prematuro , Nascimento Prematuro , Tocolíticos , Gravidez , Recém-Nascido , Feminino , Humanos , Nifedipino/uso terapêutico , Citrato de Sildenafila/uso terapêutico , Tocolíticos/uso terapêutico , Peso ao Nascer , Trabalho de Parto Prematuro/tratamento farmacológico , Trabalho de Parto Prematuro/prevenção & controle
14.
BMJ Case Rep ; 17(2)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38320830

RESUMO

Ruptured renal angiomyolipoma in pregnancy is uncommon. Pregnant women may present with nonspecific symptoms such as flank or abdominal pain, contraction pain and haematuria. A thorough assessment is needed to reach the correct diagnosis. Management varies between conservative measures, radiological intervention or surgery depending on the patient's haemodynamic status and foetal condition. We present a case of a woman in her 30s, gravida 5 para 3+1 at 28 weeks of gestation, who presented with pain. The pain worsened, and she went into hypovolaemic shock. An exploratory laparotomy and emergency caesarean section were done. Retroperitoneal haematoma was found intraoperatively, but the source of bleeding was difficult to determine. An abdominal CT angiogram subsequently revealed an ongoing bleeding from a ruptured angiomyolipoma. An emergency nephrectomy was performed, and the bleeding was secured.


Assuntos
Angiomiolipoma , Hamartoma , Neoplasias Renais , Trabalho de Parto , Trabalho de Parto Prematuro , Complicações Neoplásicas na Gravidez , Feminino , Humanos , Gravidez , Angiomiolipoma/diagnóstico , Angiomiolipoma/diagnóstico por imagem , Cesárea , Hemorragia Gastrointestinal , Neoplasias Renais/diagnóstico , Neoplasias Renais/diagnóstico por imagem , Dor , Complicações Neoplásicas na Gravidez/diagnóstico por imagem , Complicações Neoplásicas na Gravidez/cirurgia , Ruptura Espontânea/diagnóstico por imagem , Ruptura Espontânea/cirurgia , Adulto
15.
Sci Rep ; 14(1): 4234, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378749

RESUMO

During labor, monocytes infiltrate massively the myometrium and differentiate into macrophages secreting high levels of reactive oxygen species and of pro-inflammatory cytokines (i.e. IL-1ß), leading to myometrial contraction. Although IL-1ß is clearly implicated in labor, its function and that of the inflammasome complex that cleaves the cytokine in its active form, has never been studied on steps preceding contraction. In this work, we used our model of lipopolysaccharide-induced preterm labor to highlight their role. We demonstrated that IL-1ß was secreted by the human myometrium during labor or in presence of infection and was essential for myometrial efficient contractions as its blockage with an IL-1 receptor antagonist (Anakinra) or a neutralizing antibody completely inhibited the induced contractions. We evaluated the implication of the inflammasome on myometrial contractions and differentiation stages of labor onset. We showed that the effects of macrophage-released IL-1ß in myometrial cell transactivation were blocked by inhibition of the inflammasome, suggesting that the inflammasome by producing IL-1ß was essential in macrophage/myocyte crosstalk during labor. These findings provide novel innovative approaches in the management of preterm labor, specifically the use of an inflammasome inhibitor to block the precursor stages of labor before the acquisition of the contractile phenotype.


Assuntos
Trabalho de Parto , Trabalho de Parto Prematuro , Feminino , Humanos , Recém-Nascido , Gravidez , Células Cultivadas , Citocinas/genética , Inflamassomos , Interleucina-1beta/genética , Miométrio
16.
Sci Rep ; 14(1): 4033, 2024 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-38369585

RESUMO

The labor is a physiological event considered to have its own circadian (diurnal) rhythm, but some of the data remain conflicting, especially for preterm births. In this retrospective study, we analyzed the circadian trends of labor onset times in the Slovenian birth cohort from 1990 to 2018 with over 550,000 cases of singleton births. The number of term and preterm labor onsets was calculated for each hour in a day and circadian trends were evaluated for each of the study groups by modeling with a generalized Poisson distribution linked with the cosinor regression model using logarithmic link function. The induced labors were taken as the control group since the timing of labor depends mostly on the working schedule of personnel and not on the intrinsic rhythmic characteristics. For induced labors, the main peak in the number of labor cases was observed in the late morning hours (around 10 AM) for all gestational ages. The prominence of this peak becomes smaller in spontaneous premature labors with gradually disrupting rhythmicity in very preterm and extremely preterm cases. Labors starting with spontaneous contractions peak between 6 and 7 AM and lose the rhythmicity at 35 weeks of gestation while labors starting with a spontaneous rupture of membranes peak at 1 AM and lose the rhythmicity at 31 weeks of gestation, suggesting differences in underlying mechanisms. According to our knowledge, this is the first study that shows differences of circadian trends between different types of spontaneous labors, i.e., labors initiated with contraction and labors initiated with a spontaneous rupture of membranes. Moreover, the obtained results represent evidence of gradual disruption of rhythmicity from mild to extreme prematurity.


Assuntos
Trabalho de Parto , Trabalho de Parto Prematuro , Nascimento Prematuro , Gravidez , Recém-Nascido , Feminino , Humanos , Estudos Retrospectivos , Ruptura Espontânea , Recém-Nascido Prematuro , Idade Gestacional
18.
Reproduction ; 167(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38271800

RESUMO

In brief: The cervix plays a crucial role not only in the maintenance of pregnancy but also during delivery, when it undergoes extensive changes. This study highlights the involvement of the endocannabinoidome in cervical remodeling, emphasizing its relevance in the shift from a nonpregnant to pregnant state and its potential contribution to preterm delivery in inflammatory contexts. Abstract: During pregnancy, the main role of the cervix is to isolate the fetus from outside pathogens and maintain the relatively closed system of uterine gestation. Conversely, toward the end of pregnancy, the cervix must be remodeled to increase flexibility and allow the delivery. This process is called cervical remodeling and dysregulation of the process plays a role in premature delivery. The endocannabinoidome plays an important role in several reproductive events; however, its function on cervical tissue throughout pregnancy is poorly understood. The goal of this study was to evaluate the presence and participation of the endocannabinoidome in lipopolysaccharide (LPS)-induced cervical changes. Therefore, we evaluated key components of the endocannabinoidome in cervical tissue from nonpregnant mice and pregnant mice with and without LPS treatment. Using mass spectrometric analysis, we found an increase in anandamide and 2-arachidonoylglycerol in the cervix of pregnant mice when compared to nonpregnant mice. We have also found a reduction in FAAH protein expression in these tissues. Furthermore, when treated with LPS, we observed a reduction in the cervical immunostaining with anti-CB1 and anti-CB2 antibodies. Likewise, using cervix explants from pregnant mice, we found that LPS significantly increased cervical metalloprotease activity and cyclooxygenase 2, which were subsequently modulated by cannabinoid receptor antagonists. Collectively, our findings suggest that an LPS-induced imbalance of cervix endocannabinoidome likely contributes to premature cervical remodeling, which is part of the key components that contribute to premature delivery.


Assuntos
Trabalho de Parto Prematuro , Nascimento Prematuro , Gravidez , Humanos , Feminino , Camundongos , Animais , Colo do Útero/fisiologia , Endocanabinoides/farmacologia , Lipopolissacarídeos/farmacologia , Útero/metabolismo , Trabalho de Parto Prematuro/metabolismo , Nascimento Prematuro/metabolismo
19.
Eur J Pharmacol ; 968: 176343, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38281680

RESUMO

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


Assuntos
Trabalho de Parto Prematuro , Contração Uterina , Recém-Nascido , Feminino , Gravidez , Humanos , Cálcio/farmacologia , Ocitocina/farmacologia , Fenantrolinas/farmacologia , Dinoprosta , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Endotelina-1/farmacologia , Miométrio
20.
Am J Obstet Gynecol MFM ; 6(3): 101289, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38280551

RESUMO

BACKGROUND: Recent research suggests that children born after suspected preterm labor may observe a potential cluster with different attention deficit hyperactivity disorder features, depending on the time of birth. However, the evolution of symptoms and their predictors remain unknown in this population. OBJECTIVE: This study aimed to examine the trajectories of attention deficit hyperactivity disorder symptoms of children born after suspected preterm labor, between ages 2 and 6 years, considering prematurity condition and comparing with controls. In addition, this study aimed to find potential modifiable predictors of evolution to enhance prognosis. STUDY DESIGN: In this prospective cohort study, 119 mother-child pairs who experienced suspected preterm labor and 60 controls were included. Patients were divided according to prematurity condition in full term (n=27), late preterm (n=55), and very preterm (n=37). Attention deficit hyperactivity disorder symptoms were assessed at ages 2 and 6 years. The association between potential modifying factors (group, time of assessment, sex, birthweight percentile, maternal history of trauma, maternal anxiety at diagnosis, and maternal anxiety during the children's assessments) and disorder trajectories was assessed by adjusting the Bayesian mixed linear models. All analyses were performed in R (version 4.3.0; R Foundation for Statistical Computing, Vienna, Austria). RESULTS: An interaction emerged between time and group, with late-preterm neonates born after suspected preterm labor being the only group to improve from ages 2 to 6 years (-2.26 points in Conners scale per percentile decrease and 0.98 probability of effect). Another interaction between time and maternal anxiety at postnatal time assessments intensified over time (0.07 and 0.84). Predictors of symptom severity included lower weight percentile at birth (-0.2 and 0.96), male sex (-2.99 and <0.99), higher maternal anxiety at diagnosis (+0.08 and 0.99), and maternal history of trauma (+0.23 and 0.98). CONCLUSION: Unlike very-preterm and full-term children, those born late preterm showed an improvement over time, probably because late-preterm children do not carry the sequelae derived from severe prematurity but benefit from close monitoring. As maternal psychopathology emerged as a determinant modifier of course and severity, it is crucial to develop targeted psychological interventions for pregnant individuals and reevaluate monitoring programs for their offspring, regardless of prematurity.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Doenças do Recém-Nascido , Trabalho de Parto Prematuro , Recém-Nascido , Gravidez , Feminino , Humanos , Masculino , Estudos de Coortes , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Estudos Prospectivos , Teorema de Bayes , Trabalho de Parto Prematuro/diagnóstico , Trabalho de Parto Prematuro/epidemiologia , Trabalho de Parto Prematuro/etiologia
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