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Biology of Reproduction Nov 2019Preterm labor (PTL) is the predominant cause of childhood morbidity and mortality. It has several phenotypes, each with a distinct etiology often involving inflammation....
Preterm labor (PTL) is the predominant cause of childhood morbidity and mortality. It has several phenotypes, each with a distinct etiology often involving inflammation. Here, in samples of reproductive tissues obtained in early PTL from women with phenotypically defined PTL, we examined the presence and distribution of inflammation and its relationship with prolabor gene expression. In chorioamnionitis (CA-PTL), cytokine protein concentrations were increased across all tissues; in idiopathic (I-PTL), the inflammatory changes were limited to the choriodecidua; inflammation was not a feature of placental abruption (PA-PTL). CA-PTL was associated with activation of p65 in the myometrium and AP-1 in the choriodecidua, and PA-PTL with CREB in the choriodecidua. In the myometrium, PGHS-2 mRNA level was increased in CA- and I-PTL; in the amnion, PGHS-2 mRNA level was higher in PA- and I-PTL, while in CA-PTL, OT, OTR mRNA, and CX-43 expression were increased. In the choriodecidua, PGHS-2 mRNA level was unchanged, but in CA and I-PTL, OT mRNA level were increased and OTR was reduced. These data show that CA-PTL is associated with widespread inflammation and prolabor gene expression. In contrast, in I-PTL, inflammation is limited to the choriodecidua, with discrete increases in PGHS-2 in the amnion and OT in the choriodecidua. Inflammation is not a feature of PA-PTL, which is associated with increased OT and OTR in the amnion.
Topics: Adult; Chorioamnionitis; Extraembryonic Membranes; Female; Humans; Inflammation; Obstetric Labor, Premature; Pregnancy; Transcriptome; Uterine Contraction
PubMed: 31411323
DOI: 10.1093/biolre/ioz144 -
Infectious Diseases in Obstetrics and... Sep 2005Premature delivery is still a significant problem in obstetrics, and chorioamnionitis is an unwelcome complication. C-reactive protein (CRP) is a circulating marker of... (Review)
Review
Premature delivery is still a significant problem in obstetrics, and chorioamnionitis is an unwelcome complication. C-reactive protein (CRP) is a circulating marker of low-grade inflammation and the role of its measurement in clinical practice remains unclear for many conditions. It has been claimed that estimation of CRP is helpful in the diagnosis of chorioamnionitis, and this study aims to appraise such claims. Following review of the literature, six reports were recruited for further metanalysis, including 466 cases. The overall prevalence of chorioamnionitis was 41% (191/466). The overall diagnostic activity showed sensitivity, specificity, false-positives and false-negatives of 72.8%, 76.4%, 23.6% and 27.2%, respectively. Therefore, we can conclude that estimation of maternal CRP is not helpful in the detection of chorioamnionitis, compared with standard investigations.
Topics: C-Reactive Protein; Chorioamnionitis; False Negative Reactions; False Positive Reactions; Female; Humans; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications; Sensitivity and Specificity
PubMed: 16126504
DOI: 10.1080/10647440500068321 -
American Journal of Physiology. Lung... Aug 2022Secretory phospholipase A2 (sPLA2) regulates the first step of inflammatory cascade and is involved in several pathological processes. sPLA2 also plays a role in preterm...
Secretory phospholipase A2 (sPLA2) regulates the first step of inflammatory cascade and is involved in several pathological processes. sPLA2 also plays a role in preterm labor and parturition, since they are triggered by inflammatory mediators such as prostaglandins. Interestingly, chorioamnionitis (i.e., the presence of intrauterine inflammation) is also often associated with preterm birth. We aimed to verify if chorioamnionitis with fetal involvement modifies sPLA2 activity and expression profile in mothers and neonates delivered prematurely. We collected maternal plasma and amniotic fluid, as well as bronchoalveolar lavage fluid from preterm neonates born to mothers with or without clinical chorioamnionitis with fetal involvement. We measured concentrations of sPLA2 subtype-IIA and -IB, total enzyme activity, and proteins. Urea ratio was used to obtain epithelial lining fluid concentrations. Enzyme activity measured in maternal plasma ( < 0.001) and amniotic fluid ( < 0.001) was higher in chorioamnionitis cases than in controls. This was mainly due to the increased production of sPLA2-IIA, as the subtype -IB was present in a smaller amount and was similar between the two groups; sPLA2-IIA was increased in epithelial lining fluid ( = 0.045) or increased, although without statistical significance, in maternal plasma ( = 0.06) and amniotic fluid ( = 0.08) of chorioamnionitis cases. Cytokines that are known to increase sPLA2-IIA expression (TNF-α and IL-1β) or whose expression was increased by sPLA2-IIA (IL-8) were higher in histologically confirmed chorioamnionitis [TNF-α ( = 0.028), IL-1β ( < 0.001), and IL-8 ( = 0.038)]. These data represent the basis for future studies on sPLA2-IIA inhibition to prevent deleterious consequences of chorioamnionitis and preterm birth.
Topics: Chorioamnionitis; Female; Humans; Infant, Newborn; Interleukin-8; Phospholipases A2, Secretory; Pregnancy; Premature Birth; Tumor Necrosis Factor-alpha
PubMed: 35762614
DOI: 10.1152/ajplung.00516.2021 -
Frontiers in Immunology 2021Intra-amniotic infection and inflammation (IAI) affect fetal development and are highly associated with preterm labor and premature rupture of membranes, which often... (Review)
Review
Intra-amniotic infection and inflammation (IAI) affect fetal development and are highly associated with preterm labor and premature rupture of membranes, which often lead to adverse neonatal outcomes. Human amniotic membrane (hAM), the inner part of the amnio-chorionic membrane, protects the embryo/fetus from environmental dangers, including microbial infection. However, weakened amnio-chorionic membrane may be breached or pathogens may enter through a different route, leading to IAI. The hAM and human amniotic fluid (hAF) respond by activation of all components of the innate immune system. This includes changes in 1) hAM structure, 2) presence of immune cells, 3) pattern recognition receptors, 4) cytokines, 5) antimicrobial peptides, 6) lipid derivatives, and 7) complement system. Herein we provide a comprehensive and integrative review of the current understanding of the innate immune response in the hAM and hAF, which will aid in design of novel studies that may lead to breakthroughs in how we perceive the IAI.
Topics: Amnion; Amniotic Fluid; Animals; Bacteria; Bacterial Infections; Chorioamnionitis; Female; Host-Pathogen Interactions; Humans; Immunity, Innate; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Infectious; Premature Birth; Signal Transduction
PubMed: 34745106
DOI: 10.3389/fimmu.2021.735324 -
Oxidative Medicine and Cellular... 2022Chorioamnionitis is associated with an increased risk of preterm birth and aggravates adverse outcomes such as BPD. Development of BPD is associated with chronic...
Chorioamnionitis is associated with an increased risk of preterm birth and aggravates adverse outcomes such as BPD. Development of BPD is associated with chronic inflammatory reactions and oxidative stress in the airways which may be antenatally initiated by chorioamnionitis. A20 is an immunomodulatory protein involved in the negative feedback regulation of inflammatory reactions and is a possible regulator protein in oxidative stress reactions. The influence of chorioamnionitis on A20 gene regulation in the fetal lung is unknown. We characterized the influence of LPS and proinflammatory cytokines on A20 expression in human lung endothelial (HPMEC-ST1.6R) and epithelial (A549) cells by real-time PCR and/or western blotting and used a sheep model of LPS-induced chorioamnionitis for studies. To study the functional role of A20, endogenous A20 was overexpressed in HPMEC-ST1.6R and A549 cells. LPS induced proinflammatory cytokines in HPMEC-ST1.6R and A549 cells. Both LPS and/or proinflammatory cytokines elevated A20 at transcriptional and translational levels. Intra-amniotic LPS transiently increased IL-1, IL-6, IL-8, and TNF- mRNA levels in fetal lamb lungs, associated with an increase in A20 mRNA and protein levels. Overexpression of A20 reduced proinflammatory cytokines in vitro. Repeated LPS exposure induced LPS tolerance for proinflammatory cytokines and A20 and . Antenatal inflammation induced a transient increase in proinflammatory cytokines in the preterm fetal lung. The expression of proinflammatory cytokines increased expression of A20. Elevated A20 may have a protective role by downregulating chorioamnionitis-triggered fetal lung inflammation. A20 may be a novel target for pharmacological interventions to prevent chorioamnionitis-induced airway inflammation and lung damage, which can result in BPD later in life.
Topics: Animals; Chorioamnionitis; Disease Models, Animal; Female; Fetus; Humans; Lung; Pregnancy; Sheep; Tumor Necrosis Factor alpha-Induced Protein 3
PubMed: 35096271
DOI: 10.1155/2022/6421419 -
Taiwanese Journal of Obstetrics &... Jan 2023The prognosis of preterm premature rupture of membranes (PPROM) combined with chorioamnionitis is often unsatisfactory for both mother and newborn. Although tragic...
OBJECTIVE
The prognosis of preterm premature rupture of membranes (PPROM) combined with chorioamnionitis is often unsatisfactory for both mother and newborn. Although tragic outcomes can be avoided if treated early, no effective prediction method for decision-making is available currently. This study aimed to establish an effective method with maternal inflammation indexes to predict preterm premature rupture of membranes with concomitant chorioamnionitis.
MATERIALS AND METHODS
This retrospective study examined the data of 206 singleton PPROM cases and 60 normal full-term cases. The PPROM cases included 93 cases of PPROM with chorioamnionitis and 113 cases of PPROM without chorioamnionitis based on clinical manifestations, laboratory examinations, and histopathological diagnosis. Normal full-term cases were included as the control group. Peripheral blood levels of selected inflammatory indicators were observed 12 h after fetal membrane rupture. Associations between selected inflammatory indicators and chorioamnionitis diagnosis were analyzed.
RESULTS
Selected factors except for procalcitonin predicted chorioamnionitis in PPROM patients. Combined results of C-reactive protein and white blood cell (WBC) count showed best predictive ability with area under curve, sensitivity, and specificity of 0.702, 60.22%, and 76.11%, respectively. Furthermore including Interleukine-6 and neutrophil count provided similar predictive results.
CONCLUSIONS
The best predictive factor combinations for PPROM-CAM were C-reactive protein and white blood cell count. Results of this study provide a useful clinical reference for PPROM-CAM and may improve maternal and infant prognostic outcomes.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Chorioamnionitis; Retrospective Studies; C-Reactive Protein; Fetal Membranes, Premature Rupture
PubMed: 36720521
DOI: 10.1016/j.tjog.2022.11.006 -
BMC Pregnancy and Childbirth Mar 2021Intrauterine inflammation affects short- and long-term neonatal outcomes. Histological chorioamnionitis and funisitis are acute inflammatory responses in the fetal...
BACKGROUND
Intrauterine inflammation affects short- and long-term neonatal outcomes. Histological chorioamnionitis and funisitis are acute inflammatory responses in the fetal membranes and umbilical cord, respectively. Although labor dystocia includes a potential risk of intrauterine inflammation, the risk of histological chorioamnionitis and funisitis of labor dystocia has not been evaluated yet. This study aimed to examine the association between labor dystocia and risk of histological chorioamnionitis and funisitis.
METHODS
In this retrospective cohort study, the cases who underwent histopathological examinations of the placenta and umbilical cord at Fukushima Medical University Hospital, Japan, between 2015 and 2020, were included. From the dataset, the pathological findings of the patients with labor dystocia and spontaneous preterm birth were reviewed. Based on the location of leukocytes, the inflammation in the placenta (histological chorioamnionitis) and umbilical cord (funisitis) was staged as 0-3. Multiple logistic regression analysis was performed to evaluate the risk of histological chorioamnionitis, histological chorioamnionitis stage ≥2, funisitis, and funisitis stage ≥2.
RESULT
Of 317 women who met the study criteria, 83 and 144 women had labor dystocia and spontaneous preterm birth, respectively, and 90 women were included as controls. Labor dystocia was a risk factor for histological chorioamnionitis (adjusted odds ratio, 6.3; 95% confidential interval, 1.9-20.5), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 6.0; 95% confidence interval, 1.7-21.8), funisitis (adjusted odds ratio, 15.4; 95% confidence interval, 2.3-101.3), and funisitis stage ≥2 (adjusted odds ratio, 18.5; 95% confidence interval, 2.5-134.0). Spontaneous preterm birth was also a risk factor for histological chorioamnionitis (adjusted odds ratio, 3.7; 95% confidence interval, 1.7-7.8), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 3.0; 95% confidence interval, 1.2-7.9), and funisitis (adjusted odds ratio, 6.6; 95% confidence interval, 1.4-30.6). However, the adjusted odds ratio was smaller in spontaneous preterm births than in labor dystocia.
CONCLUSION
Labor dystocia is a risk factor for severe histological chorioamnionitis and funisitis. Further studies are required to evaluate the effects of histological chorioamnionitis and funisitis on long-term neonatal outcomes.
Topics: Adult; Chorioamnionitis; Datasets as Topic; Dystocia; Female; Humans; Infant, Newborn; Japan; Placenta; Pregnancy; Premature Birth; Retrospective Studies; Risk Factors; Severity of Illness Index; Tertiary Care Centers; Umbilical Cord
PubMed: 33784970
DOI: 10.1186/s12884-021-03719-3 -
Frontiers in Endocrinology 2022To determine the birth prevalence of perinatal stroke in term born infants at our high-volume delivery center and assess the frequency of both gross and histologic...
OBJECTIVE
To determine the birth prevalence of perinatal stroke in term born infants at our high-volume delivery center and assess the frequency of both gross and histologic placental pathologies associated with perinatal stroke using the Amsterdam Placental Workshop Group Consensus Statement guidelines and definitions.
STUDY DESIGN
A single-center retrospective cohort study spanning 2010-2020.
RESULTS
There were 129,759 live births at Parkland Hospital during the study period and a total of 18 term born infants leading to a birth prevalence of 1 in 6,829 infants. Perinatal risk factors were found in all but one patient, and 74% presented with seizures. Pathologic placental examination was available in 56% of the cohort and only one patient had normal placental examination. Acute histologic chorioamnionitis was described in five placentas (50%) and an additional two had isolated umbilical and/or chorionic plate vasculitis with or without funisitis compared to a rate of 28% with acute inflammation in a Control group. Chronic inflammation in the form of villitis of unknown etiology was described in three of the acutely inflamed placentas and was high-grade in each of those while none of the placentas from our Control group showed evidence of any chronic lesion.
CONCLUSION
Both acute and chronic placental inflammation are common in perinatal stroke; placental examination should be considered an essential component to the diagnostic workup.
Topics: Chorioamnionitis; Female; Humans; Infant, Newborn; Inflammation; Placenta; Pregnancy; Retrospective Studies; Stroke
PubMed: 36157451
DOI: 10.3389/fendo.2022.920680 -
Neonatology 2014The role of chorioamnionitis (CA) in the development of retinopathy of prematurity (ROP) has not been well established. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The role of chorioamnionitis (CA) in the development of retinopathy of prematurity (ROP) has not been well established.
OBJECTIVE
To conduct a systematic review and meta-analysis of the association between CA and ROP in preterm infants.
DATA SOURCES
The authors searched MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials and PubMed, reviewed reference lists of relevant articles, abstracts and conference proceedings (Society for Pediatric Research, European Society for Paediatric Research 1990-2012), sought results of unpublished trials, and contacted the primary authors of relevant studies.
STUDY SELECTION
Studies were included if they had a comparison group, examined preterm infants, and reported primary data that could be used to measure the association between exposure to CA and the development of ROP.
DATA EXTRACTION
Two reviewers independently screened the search results, applied inclusion criteria and assessed methodological quality using the Newcastle-Ottawa Scale. One reviewer extracted data and a second reviewer checked data extraction. Summary relative risks (RRs) were calculated using a random effects model.
DATA SYNTHESIS
We identified 1,249 potentially relevant studies from the electronic databases. Twenty-seven studies involving 10,590 preterm neonates with 2,562 cases of ROP were included. Taking into account all included studies without adjusting for gestational age (GA), CA was significantly associated with ROP (any stage) [summary RR 1.33 (95% CI 1.14-1.55, I(2) = 77%, pheterogeneity < 0.0001)], and a borderline significant association was observed for severe ROP (stage ≥3) [summary RR 1.27 (95% CI 0.99-1.63, I(2) = 74%, pheterogeneity < 0.0001)]. There was no publication bias with Begg's test. However, subgroup analysis of studies adjusting for GA showed no significant association on CA with ROP [summary RR 0.98 (95% CI 0.77-1.26, I(2) = 0%, pheterogeneity = 0.89)].
CONCLUSION
Unadjusted analyses showed that CA was significantly associated with ROP (any stage) as well as with severe ROP (stage ≥ 3). However, the association disappeared on analysis of studies adjusting for GA. Hence, CA cannot be definitively considered as a risk factor for ROP, and further studies should adjust for potential confounding factors and report results by stage to clarify the association with severe ROP.
Topics: Chorioamnionitis; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Odds Ratio; Pregnancy; Retinopathy of Prematurity; Risk Assessment; Risk Factors; Severity of Illness Index
PubMed: 24481268
DOI: 10.1159/000357556 -
BMC Pregnancy and Childbirth Apr 2021Necrotising funisitis (NF) is a rare, chronic stage of funisitis, a severe inflammation of the umbilical cord and an important risk factor for fetal adverse outcomes. NF... (Review)
Review
BACKGROUND
Necrotising funisitis (NF) is a rare, chronic stage of funisitis, a severe inflammation of the umbilical cord and an important risk factor for fetal adverse outcomes. NF is characterized by yellow-white bands running parallel to the umbilical blood vessels. These bands consist of inflammatory cells, necrotic debris, and calcium deposits. Calcification is visible in ultrasonography, which makes it possible to suspect NF when umbilical vascular wall calcification is detected by prenatal ultrasonography.
CASE PRESENTATION
Ultrasonography revealed calcification of the umbilical venous wall in an expectant 31-year-old woman who was gravida 1, para 0. The woman required emergency cesarean section because of fetal distress and suspected umbilical cord torsion at 31 weeks gestation. The root of the umbilical cord was quite fragile and broke during the operation. The pathological results on the placenta showed histologic chorioamnionitis and NF. The infant was diagnosed to have neonatal sepsis and acidosis after delivery but was discharged without severe complications after a one-month hospitalization that included antibiotic and supportive therapy.
CONCLUSION
NF is a rare and severe inflammation of the umbilical cord. Umbilical vascular wall calcification discovered in prenatal ultrasonography is diagnostically helpful.
Topics: Adult; Cesarean Section; Chorioamnionitis; Female; Humans; Imaging, Three-Dimensional; Infant, Newborn; Infant, Very Low Birth Weight; Male; Necrosis; Pregnancy; Severity of Illness Index; Treatment Outcome; Ultrasonography, Doppler, Color; Ultrasonography, Prenatal; Umbilical Cord; Umbilical Veins; Vascular Calcification
PubMed: 33845786
DOI: 10.1186/s12884-021-03743-3