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American Journal of Reproductive... Mar 2017Chorioamnionitis is an acute inflammation of the gestational (extraplacental) membranes, most commonly caused by ascending microbial infection. It is associated with... (Review)
Review
Chorioamnionitis is an acute inflammation of the gestational (extraplacental) membranes, most commonly caused by ascending microbial infection. It is associated with adverse neonatal outcomes including preterm birth, neonatal sepsis, and cerebral palsy. The decidua is the outermost layer of the gestational membranes and is likely an important initial site of contact with microbes during ascending infection. However, little is known about how decidual stromal cells (DSCs) respond to microbial threat. Defining the contributions of individual cell types to the complex medley of inflammatory signals during chorioamnionitis could lead to improved interventions aimed at halting this disease. We review available published data supporting the role for DSCs in responding to microbial infection, with a special focus on their expression of pattern recognition receptors and evidence of their responsiveness to pathogen sensing. While DSCs likely play an important role in sensing and responding to infection during the pathogenesis of chorioamnionitis, important knowledge gaps and areas for future research are highlighted.
Topics: Chorioamnionitis; Decidua; Female; Host-Pathogen Interactions; Humans; Immunity, Innate; Immunity, Maternally-Acquired; Infections; Maternal-Fetal Exchange; Molecular Targeted Therapy; Nod1 Signaling Adaptor Protein; Nod2 Signaling Adaptor Protein; Pregnancy; Receptors, Pattern Recognition; Stromal Cells
PubMed: 28044385
DOI: 10.1111/aji.12623 -
Reproductive Sciences (Thousand Oaks,... Oct 2017Inflammasomes are cytosolic multiprotein complexes that orchestrate inflammation in response to pathogens and endogenous danger signals. Herein, we determined whether...
Inflammasomes are cytosolic multiprotein complexes that orchestrate inflammation in response to pathogens and endogenous danger signals. Herein, we determined whether the chorioamniotic membranes from women in spontaneous preterm labor with acute histologic chorioamnionitis (1) express major inflammasome components; (2) express caspase (CASP)-1 and CASP-4 as well as their active forms; (3) exhibit apoptosis-associated speck-like protein containing a CARD (ASC)/CASP-1 complex formation; and (4) release the mature forms of interleukin (IL)-1β and IL-18. We utilized quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, immunoblotting, and immunohistochemistry to determine the messenger RNA (mRNA) and protein expression of major inflammasome components, nucleotide-binding oligomerization domain (NOD) proteins, and the pro- and mature/active forms of CASP-1, CASP-4, IL-1β, and IL-18. The ASC/CASP-1 complex formation was determined using an in situ proximity ligation assay. When comparing the chorioamniotic membranes from women in spontaneous preterm labor with acute histologic chorioamnionitis to those without this placental lesion, we found that (1) the mRNA of NLR family pyrin domain-containing protein ( NLRP) 1, NLRP3, NLR family CARD domain-containing protein 4 ( NLRC4), and NOD2 were higher; (2) the NLRP3 protein was increased; (3) the mRNA and active form (p10) of CASP-1 were greater; (4) the mRNA and active form of CASP-4 were increased; (5) the mRNA and mature form of IL-1β were higher; (6) the mature form of IL-18 was elevated; and (7) ASC/CASP-1 complex formation was increased. In conclusion, spontaneous preterm labor with acute histologic chorioamnionitis is characterized by an upregulation of NLRP3 and the active form of CASP-4, as well as increased ASC/CASP-1 complex formation, which may participate in the activation of CASP-1 and the maturation of IL-1β and IL-18 in the chorioamniotic membranes. These findings provide the first evidence that supports a role for the inflammasome in the pathological inflammation implicated in spontaneous preterm labor with acute histologic chorioamnionitis.
Topics: Adult; Amnion; Caspases; Cell Death; Chemokines; Chorioamnionitis; Chorion; Cytokines; Female; Humans; Inflammasomes; Inflammation; Labor, Obstetric; Obstetric Labor, Premature; Pregnancy; Young Adult
PubMed: 28122480
DOI: 10.1177/1933719116687656 -
Stem Cell Research & Therapy Nov 2017Despite advances in neonatal care, bronchopulmonary dysplasia (BPD) remains a significant contributor to infant mortality and morbidity. While human amnion epithelial...
BACKGROUND
Despite advances in neonatal care, bronchopulmonary dysplasia (BPD) remains a significant contributor to infant mortality and morbidity. While human amnion epithelial cells (hAECs) have shown promise in small and large animal models of BPD, there is scarce information on long-term benefit and clinically relevant questions surrounding administration strategy remain unanswered. In assessing the therapeutic potential of hAECs, we investigated the impact of cell dosage, administration routes and timing of treatment in a pre-clinical model of BPD.
METHODS
Lipopolysaccharide was introduced intra-amniotically at day 16 of pregnancy prior to exposure to 65% oxygen (hyperoxia) at birth. hAECs were administered either 12 hours (early) or 4 days (late) after hyperoxia commenced. Collective lung tissues were subjected to histological analysis, multikine ELISA for inflammatory cytokines, FACS for immune cell populations and 3D lung stem cell culture at neonatal stage (postnatal day 7 and 14). Invasive lung function test and echocardiography were applied at 6 and 10 weeks of age.
RESULTS
hAECs improved the tissue-to-airspace ratio and septal crest density in a dose-dependent manner, regardless of administration route. Early administration of hAECs, coinciding with the commencement of postnatal hyperoxia, was associated with reduced macrophages, dendritic cells and natural killer cells. This was not the case if hAECs were administered when lung injury was established. Fittingly, early hAEC treatment was more efficacious in reducing interleukin-1β, tumour necrosis factor alpha and monocyte chemoattractant protein-1 levels. Early hAEC treatment was also associated with reduced airway hyper-responsiveness and normalisation of pressure-volume loops. Pulmonary hypertension and right ventricle hypertrophy were also prevented in the early hAEC treatment group, and this persisted until 10 weeks of age.
CONCLUSIONS
Early hAEC treatment appears to be advantageous over late treatment. There was no difference in efficacy between intravenous and intratracheal administration. The benefits of hAEC administration resulted in long-term improvements in cardiorespiratory function.
Topics: Acute Disease; Amnion; Animals; Cell- and Tissue-Based Therapy; Cells, Cultured; Chronic Disease; Disease Models, Animal; Female; Humans; Infant, Newborn; Lung Injury; Mice; Mice, Inbred C57BL; Pregnancy
PubMed: 29126435
DOI: 10.1186/s13287-017-0689-9 -
BMC Pregnancy and Childbirth Mar 2024This systematic review and meta-analysis investigated whether the use of azithromycin during labour or caesarean section reduces the incidence of sepsis and infection... (Meta-Analysis)
Meta-Analysis
Can the use of azithromycin during labour reduce the incidence of infection among puerperae and newborns? A systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
This systematic review and meta-analysis investigated whether the use of azithromycin during labour or caesarean section reduces the incidence of sepsis and infection among mothers and newborns.
DATA SOURCES
We independently searched the PubMed, Web of Science, Cochrane Library and EMBASE databases for relevant studies published before February, 2024.
METHODS
We included RCTs that evaluated the effect of prenatal oral or intravenous azithromycin or placebo on intrapartum or postpartum infection incidence. We included studies evaluating women who had vaginal births as well as caesarean sections. Studies reporting maternal and neonatal infections were included in the current analysis. Review Manager 5.4 was used to analyse 6 randomized clinical trials involving 44,448 mothers and 44,820 newborns. The risk of bias of each included study was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions.Primary outcomes included the incidence of maternal sepsis and all-cause mortality and neonatal sepsis and all-cause mortality; secondary outcomes included maternal (endometritis, wound and surgical site infections, chorioamnionitis, and urinary tract infections) and neonatal outcomes (infections of the eyes, ears and skin). A random-effects model was used to test for overall effects and heterogeneity.
RESULTS
The pooled odds ratios (ORs) were as follows: 0.65 for maternal sepsis (95% CI, 0.55-0.77; I, 0%; P < .00001); 0.62 for endometritis (95% CI, 0.52-0.74; I, 2%; P < .00001); and 0.43 for maternal wound or surgical site infection (95% CI, 0.24-0.78; P < .005); however, there was great heterogeneity among the studies (I, 75%). The pooled OR for pyelonephritis and urinary tract infections was 0.3 (95% CI, 0.17-0.52; I, 0%; P < .0001), and that for neonatal skin infections was 0.48 (95% CI, 0.35-0.65; I, 0%, P < .00001). There was no significant difference in maternal all-cause mortality or incidence of chorioamnionitis between the two groups. No significant differences were observed in the incidence of neonatal sepsis or suspected sepsis, all-cause mortality, or infections of the eyes or ears.
CONCLUSION
In this meta-analysis, azithromycin use during labour reduced the incidence of maternal sepsis, endometritis, incisional infections and urinary tract infections but did not reduce the incidence of neonatal-associated infections, except for neonatal skin infections. These findings indicate that azithromycin may be potentially beneficial for maternal postpartum infections, but its effect on neonatal prognosis remains unclear. Azithromycin should be used antenatally only if the clinical indication is clear and the potential benefits outweigh the harms.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Azithromycin; Neonatal Sepsis; Cesarean Section; Chorioamnionitis; Endometritis; Incidence; Randomized Controlled Trials as Topic; Sepsis; Puerperal Infection; Surgical Wound Infection; Urinary Tract Infections
PubMed: 38486177
DOI: 10.1186/s12884-024-06390-6 -
Placenta Jan 2020To determine 3D growth of amnion membrane cells using soft substrate plates of various rigidities.
INTRODUCTION
To determine 3D growth of amnion membrane cells using soft substrate plates of various rigidities.
METHODS
Amnion epithelial (AEC) and mesenchymal cells (AMC) were cultured on 6-well soft substrate plates coated with matrigel and elastomer with rigidities of 0.5, 2, 8, 16, and 64 kPa (n = 3 each). Controls were cells in standard culture conditions. Cell morphology, spheroids' and sheets' formations and viability (bright field microscopy and crystal violet staining), and cellular transitions (vimentin/cytokeratin-18 [CK-18] ratios) were analyzed. A Student t-test was used for statistical analyses.
RESULTS
AECs in substrate rigidities between 2 and 8 kPa formed 3D features (spheroids and sheets) while retaining viability. Two kPa produced spheroids with epithelial characteristics (decrease in vimentin), and 8 kPa favored sheets. Transplantation and culture of AEC sheets with no matrix or elastomers, retained AECs' viability and maintained their epithelial characteristics. Optimum AMC growth was also between 2 and 8 kP A, with predominance of vimentin; however, AMCs did not form 3D structures. Lower and higher rigidities transitioned AMCs into AECs (decrease in vimentin).
DISCUSSION
Matrix rigidities between 2 and 8 kPa produced 3D structures of AECs (spheroids and sheets), resembling amnion membranes' morphology and exhibiting regenerative capacity in utero. Although AMCs grew in similar rigidities, a lack of 3D structures support their dispersed character in the membrane matrix. Extreme rigidities transitioned AMCs into AECs, suggesting that AMCs are transient cells (reservoirs) in the matrix required for remodeling. Compromises in matrix rigidity can cause membrane dysfunction and lead to adverse pregnancy outcomes.
Topics: Amnion; Cell Culture Techniques; Cell Membrane; Cell Proliferation; Cells, Cultured; Epithelial Cells; Extracellular Matrix; Female; Humans; Pregnancy; Vimentin
PubMed: 32056556
DOI: 10.1016/j.placenta.2019.12.008 -
BioMed Research International 2018Preterm birth is the primary cause of perinatal morbidity and mortality worldwide. Inflammation induces a cascade of events leading to preterm birth by activating...
Preterm birth is the primary cause of perinatal morbidity and mortality worldwide. Inflammation induces a cascade of events leading to preterm birth by activating nuclear factor-B (NF-B). In nongestational tissues, downstream regulatory element antagonist modulator (DREAM) regulates NF-B activity. Our aims were to analyse DREAM expression in myometrium and fetal membranes obtained at term and preterm and to determine the effect of DREAM inhibition on prolabour mediators in primary myometrial and amnion cells. DREAM mRNA expression was significantly higher in fetal membranes obtained after spontaneous labour compared to nonlabour and in amnion from women with histological preterm chorioamnionitis when compared to amnion from women without chorioamnionitis. In primary myometrial and amnion cells, the effect of DREAM silencing by siRNA was a significant decrease in the expression of proinflammatory cytokine IL-6, the chemokines IL-8 and MCP-1, the adhesion molecule ICAM-1, MMP-9 mRNA expression and activity, and NF-B transcriptional activity when stimulated with the proinflammatory cytokine IL-1, the bacterial products fsl-1 or flagellin, or the viral dsRNA analogue poly(I:C). These data suggest that, in states of heightened inflammation, DREAM mRNA expression is increased and that, in myometrial and amnion cells, DREAM regulates proinflammatory and prolabour mediators which may be mediated via NF-B.
Topics: Amnion; Chemokine CCL2; Chorioamnionitis; Extraembryonic Membranes; Female; Flagellin; Humans; Inflammation; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interleukin-1beta; Interleukin-6; Interleukin-8; Kv Channel-Interacting Proteins; Matrix Metalloproteinase 9; Myometrium; NF-kappa B; Pregnancy; Premature Birth; RNA, Messenger; RNA, Small Interfering; Term Birth
PubMed: 29682558
DOI: 10.1155/2018/8237087 -
American Journal of Obstetrics and... Sep 2015The purpose of this study was to develop an animal model for intrapartum inflammation at term to investigate the interactions between maternal and fetal inflammatory...
OBJECTIVE
The purpose of this study was to develop an animal model for intrapartum inflammation at term to investigate the interactions between maternal and fetal inflammatory responses and adverse neurologic outcome.
STUDY DESIGN
Lipopolysaccharide (160, 320, or 640 μg/kg) was administered intraperitoneally to day 20 term-pregnant Sprague Dawley rat dams 2, 4, and 6 hours before sample collection. Maternal outcomes included dam core temperature and plasma interleukin 6 (IL-6). Fetal outcomes included plasma IL-6, brain IL-6 messenger RNA expression, and brain IL-6 protein expression. Primary cortical cell cultures were prepared to examine neuronal morphologic condition. Neurite counts were obtained with the use of automated Sholl analysis.
RESULTS
Maternal plasma IL-6 levels peaked 2 hours after lipopolysaccharide stimulus and rapidly resolved, except for an observed low level persistence at 6 hours with 640 μg/kg. Fetal plasma and placental IL-6 expression also peaked rapidly but only persisted in placental samples. Fetal brain IL-6 RNA and protein expression was significantly higher than control litters at 6 hours after the exposure to both 320 μg/kg (P ≤ .05) and 640 μg/kg (P ≤ .01). Cortical cells from fetuses that were exposed for 6 hours to maternal systemic inflammation showed reduced neurite number and neurite length (P < .001) with increasing lipopolysaccharide dose.
CONCLUSION
Our results demonstrate that fetal brain injury follows isolated systemic maternal inflammation and that fetal brain inflammation lags after maternal stimulus, which creates a potential 4-hour clinical window for therapeutic intervention.
Topics: Animals; Biomarkers; Blotting, Western; Body Temperature; Brain; Cells, Cultured; Chorioamnionitis; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique; Interleukin-6; Lipopolysaccharides; Polymerase Chain Reaction; Pregnancy; Rats; Rats, Sprague-Dawley
PubMed: 25979619
DOI: 10.1016/j.ajog.2015.05.007 -
BMC Pregnancy and Childbirth Mar 2021Chorioamnionitis may cause serious perinatal and neonatal adverse outcomes, and group B streptococcus (GBS) is one of the most common bacteria isolated from human... (Observational Study)
Observational Study
BACKGROUND
Chorioamnionitis may cause serious perinatal and neonatal adverse outcomes, and group B streptococcus (GBS) is one of the most common bacteria isolated from human chorioamnionitis. The present study analyzed the impact of GBS infection and histological chorioamnionitis (HCA) on pregnancy outcomes and the diagnostic value of various biomarkers.
METHODS
Pregnant women were grouped according to GBS infection and HCA detection. Perinatal and neonatal adverse outcomes were recorded with a follow-up period of 6 weeks. The white blood cell count (WBC), neutrophil ratio, and C-reactive protein (CRP) level from peripheral blood and soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 8 (IL-8), and tumor necrosis factor α (TNF-α) levels from cord blood were assessed.
RESULTS
A total of 371 pregnant women were included. Pregnant women with GBS infection or HCA had a higher risk of pathological jaundice and premature rupture of membranes and higher levels of sICAM-1, IL-8, and TNF-α in umbilical cord blood. Univariate and multivariate regression analysis revealed that sICMA-1, IL-8, TNF-α, WBC, and CRP were significantly related to an increased HCA risk. For all included pregnant women, TNF-α had the largest receiver operating characteristic (ROC) area (area: 0.841; 95% CI: 0.778-0.904) of the biomarkers analyzed. TNF-α still had the largest area under the ROC curve (area: 0.898; 95% CI: 0.814-0.982) for non-GBS-infected pregnant women, who also exhibited a higher neutrophil ratio (area: 0.815; 95% CI: 0.645-0.985) and WBC (area: 0.849; 95% CI: 0.72-0.978), but all biomarkers had lower value in the diagnosis of HCA in GBS-infected pregnant women.
CONCLUSION
GBS infection and HCA correlated with several perinatal and neonatal adverse outcomes. TNF-α in cord blood and WBCs in peripheral blood had diagnostic value for HCA in non-GBS-infected pregnant women but not GBS-infected pregnant women.
Topics: Adult; Biomarkers; Case-Control Studies; Chorioamnionitis; Female; Fetal Blood; Follow-Up Studies; Humans; Infant, Newborn; Leukocyte Count; Placenta; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; ROC Curve; Risk Assessment; Streptococcal Infections; Streptococcus agalactiae; Tumor Necrosis Factor-alpha; Umbilical Cord; Young Adult
PubMed: 33765949
DOI: 10.1186/s12884-021-03731-7 -
Neonatology 2011Chorioamnionitis as a major risk factor for spontaneous preterm birth, especially at earlier gestational ages, contributes to prematurity-associated mortality and... (Review)
Review
Chorioamnionitis as a major risk factor for spontaneous preterm birth, especially at earlier gestational ages, contributes to prematurity-associated mortality and morbidity. A gestation-independent effect of chorioamnionitis on neonatal outcome is much more difficult to assess. The influence of chorioamnionitis on neonatal outcome has become less evident with advances in neonatal care. A short-term beneficial effect of histological, but not clinical chorioamnionitis on incidence and severity of respiratory distress syndrome in preterm infants is evident. This maturational effect is accompanied by a susceptibility of the lung for further postnatal injury, which predisposes for bronchopulmonary dysplasia. Chorioamnionitis is associated with cystic periventricular leukomalacia, intraventricular hemorrhage and cerebral palsy in preterm infants, but its association with noncystic white matter disease is not clear yet. Prenatal inflammation/infection has been shown a risk factor for neonatal sepsis. A single course of antenatal steroids can be regarded safe in clinical as well as histological chorioamnionitis.
Topics: Chorioamnionitis; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Pregnancy; Risk Factors
PubMed: 20881433
DOI: 10.1159/000320170 -
The Journal of Obstetrics and... Apr 2018We aimed to clarify the usefulness of procalcitonin (PCT) in the evaluation of histological chorioamnionitis (CAM) and in the prediction of neonatal and infantile...
AIM
We aimed to clarify the usefulness of procalcitonin (PCT) in the evaluation of histological chorioamnionitis (CAM) and in the prediction of neonatal and infantile outcomes as a reference of interleukin-6 (IL-6).
METHODS
Subjects were 36 singleton pregnant women delivered at 22-37 weeks' gestation due to threatened premature delivery and/or preterm premature rupture of membranes. Cases were classified into the CAM and non-CAM groups, according to Blanc's criteria. Comparisons were made on umbilical venous and amniotic fluid PCT levels among the groups. The relations between umbilical venous PCT and IL-6 levels and neonatal and infantile outcomes were also analyzed.
RESULTS
The umbilical venous PCT level in the CAM group (240.2 pg/mL, 125.4-350.3 pg/mL: median, first quartile-third quartile) was higher than that in the non-CAM group (105.1, 50.2-137.5 pg/mL; P = 0.0006). There were no differences in the amniotic fluid PCT levels between the groups. There was a strong correlation between umbilical venous PCT and IL-6 levels (correlation coefficient: 0.793). Among 10 cases with an umbilical venous PCT level of ≥170.0 pg/mL and six cases with IL-6 ≥ 11.0 pg/mL, six (60.0%) and five cases (83.3%), respectively, had adverse neonatal and infantile outcomes. Among seven cases with adverse neonatal and infantile outcomes, six (85.7%) and five (71.4%) cases showed umbilical venous PCT levels of ≥170.0 pg/mL and IL-6 levels of ≥11.0 pg/mL, respectively.
CONCLUSION
Similar to IL-6, the umbilical venous PCT level is a promising parameter for predicting histological CAM and adverse neonatal and infantile outcomes related to in utero inflammatory status.
Topics: Amniotic Fluid; Calcitonin; Chorioamnionitis; Female; Fetal Blood; Humans; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy
PubMed: 29315994
DOI: 10.1111/jog.13573