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Pediatric Research Jan 2022Chorioamnionitis or intrauterine inflammation is a frequent cause of preterm birth. Chorioamnionitis can affect almost every organ of the developing fetus. Multiple... (Review)
Review
Chorioamnionitis or intrauterine inflammation is a frequent cause of preterm birth. Chorioamnionitis can affect almost every organ of the developing fetus. Multiple microbes have been implicated to cause chorioamnionitis, but "sterile" inflammation appears to be more common. Eradication of microorganisms has not been shown to prevent the morbidity and mortality associated with chorioamnionitis as inflammatory mediators account for continued fetal and maternal injury. Mounting evidence now supports the concept that the ensuing neonatal immune dysfunction reflects the effects of inflammation on immune programming during critical developmental windows, leading to chronic inflammatory disorders as well as vulnerability to infection after birth. A better understanding of microbiome alterations and inflammatory dysregulation may help develop better treatment strategies for infants born to mothers with chorioamnionitis.
Topics: Chorioamnionitis; Cytokines; Female; Humans; Infant, Newborn; Male; Pregnancy; Pregnancy Outcome; Premature Birth
PubMed: 34211129
DOI: 10.1038/s41390-021-01633-0 -
Clinics in Perinatology Jun 2010Chorioamnionitis is a common complication of pregnancy associated with significant maternal, perinatal, and long-term adverse outcomes. Adverse maternal outcomes include... (Review)
Review
Chorioamnionitis is a common complication of pregnancy associated with significant maternal, perinatal, and long-term adverse outcomes. Adverse maternal outcomes include postpartum infections and sepsis whereas adverse infant outcomes include stillbirth, premature birth, neonatal sepsis, chronic lung disease, and brain injury leading to cerebral palsy and other neurodevelopmental disabilities. Research in the past 2 decades has expanded understanding of the mechanistic links between intra-amniotic infection and preterm delivery as well as morbidities of preterm and term infants. Recent and ongoing clinical research into better methods for diagnosing, treating, and preventing chorioamnionitis is likely to have a substantial impact on short and long-term outcomes in the neonate.
Topics: Chorioamnionitis; Diagnosis, Differential; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Risk Factors
PubMed: 20569811
DOI: 10.1016/j.clp.2010.02.003 -
American Journal of Obstetrics and... Oct 2015Acute inflammatory lesions of the placenta consist of diffuse infiltration of neutrophils at different sites in the organ. These lesions include acute chorioamnionitis,... (Review)
Review
Acute inflammatory lesions of the placenta consist of diffuse infiltration of neutrophils at different sites in the organ. These lesions include acute chorioamnionitis, funisitis, and chorionic vasculitis and represent a host response (maternal or fetal) to a chemotactic gradient in the amniotic cavity. While acute chorioamnionitis is evidence of a maternal host response, funisitis and chorionic vasculitis represent fetal inflammatory responses. Intraamniotic infection generally has been considered to be the cause of acute chorioamnionitis and funisitis; however, recent evidence indicates that "sterile" intraamniotic inflammation, which occurs in the absence of demonstrable microorganisms induced by "danger signals," is frequently associated with these lesions. In the context of intraamniotic infection, chemokines (such as interleukin-8 and granulocyte chemotactic protein) establish a gradient that favors the migration of neutrophils from the maternal or fetal circulation into the chorioamniotic membranes or umbilical cord, respectively. Danger signals that are released during the course of cellular stress or cell death can also induce the release of neutrophil chemokines. The prevalence of chorioamnionitis is a function of gestational age at birth, and present in 3-5% of term placentas and in 94% of placentas delivered at 21-24 weeks of gestation. The frequency is higher in patients with spontaneous labor, preterm labor, clinical chorioamnionitis (preterm or term), or ruptured membranes. Funisitis and chorionic vasculitis are the hallmarks of the fetal inflammatory response syndrome, a condition characterized by an elevation in the fetal plasma concentration of interleukin-6, and associated with the impending onset of preterm labor, a higher rate of neonatal morbidity (after adjustment for gestational age), and multiorgan fetal involvement. This syndrome is the counterpart of the systemic inflammatory response syndrome in adults: a risk factor for short- and long-term complications (ie, sterile inflammation in fetuses, neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, and cerebral palsy). This article reviews the definition, pathogenesis, grading and staging, and clinical significance of the most common lesions in placental disease. Illustrations of the lesions and diagrams of the mechanisms of disease are provided.
Topics: Acute Disease; Bacterial Infections; Candidiasis; Chemokines; Chorioamnionitis; Female; Gestational Age; Humans; Neutrophils; Pregnancy; Premature Birth; Prevalence; Term Birth; Terminology as Topic
PubMed: 26428501
DOI: 10.1016/j.ajog.2015.08.040 -
Pediatrics and Neonatology Jun 2018Chorioamnionitis is a common cause of preterm birth and may cause adverse neonatal outcomes, including neurodevelopmental sequelae. Chorioamnionitis has been marked to a... (Review)
Review
Chorioamnionitis is a common cause of preterm birth and may cause adverse neonatal outcomes, including neurodevelopmental sequelae. Chorioamnionitis has been marked to a heterogeneous setting of conditions characterized by infection or inflammation or both, followed by a great variety in clinical practice for mothers and their newborns. Recently, a descriptive term: "intrauterine inflammation or infection or both" abbreviated as "Triple I" has been proposed by a National Institute of Child Health and Human Development expert panel to replace the term chorioamnionitis. It is particularly important to recognize that an isolated maternal fever does not automatically equate to chorioamnionitis. This article will review the current literature on chorioamnionitis, and introduce the concept of Triple I, as well as recommendations for assessment and management of pregnant women and their newborns with a diagnosis of Triple I.
Topics: Biomarkers; Chorioamnionitis; Female; Humans; Infant, Newborn; Infections; Inflammation; Pregnancy; Premature Birth
PubMed: 29066072
DOI: 10.1016/j.pedneo.2017.09.001 -
Obstetrics and Gynecology Jun 2021To estimate the risk of maternal and neonatal sepsis associated with chorioamnionitis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate the risk of maternal and neonatal sepsis associated with chorioamnionitis.
DATA SOURCES
PubMed, BIOSIS, and ClinicalTrials.gov databases were systematically searched for full-text articles in English from inception until May 11, 2020.
METHODS OF STUDY SELECTION
We screened 1,251 studies. Randomized controlled trials, case-control, or cohort studies quantifying a relationship between chorioamnionitis and sepsis in mothers (postpartum) or neonates born at greater than 22 weeks of gestation were eligible. Studies were grouped for meta-analyses according to exposures of histologic or clinical chorioamnionitis and outcomes of maternal or neonatal sepsis.
TABULATION, INTEGRATION, AND RESULTS
One hundred three studies were included, and 55 met criteria for meta-analysis (39 studies of preterm neonates, 10 studies of general populations of preterm and term neonates, and six studies of late preterm and term neonates). Study details and quantitative data were abstracted. Random-effects models were used to generate pooled odds ratios (ORs); most studies only reported unadjusted results. Histologic chorioamnionitis was associated with confirmed and any early-onset neonatal sepsis (unadjusted pooled ORs 4.42 [95% CI 2.68-7.29] and 5.88 [95% CI 3.68-9.41], respectively). Clinical chorioamnionitis was also associated with confirmed and any early-onset neonatal sepsis (unadjusted pooled ORs 6.82 [95% CI 4.93-9.45] and 3.90 [95% CI 2.74-5.55], respectively). Additionally, histologic and clinical chorioamnionitis were each associated with higher odds of late-onset sepsis in preterm neonates. Confirmed sepsis incidence was 7% (early-onset) and 22% (late-onset) for histologic and 6% (early-onset) and 26% (late-onset) for clinical chorioamnionitis-exposed neonates. Three studies evaluated chorioamnionitis and maternal sepsis and were inconclusive.
CONCLUSION
Both histologic and clinical chorioamnionitis were associated with early- and late-onset sepsis in neonates. Overall, our findings support current guidelines for preventative neonatal care. There was insufficient evidence to determine the association between chorioamnionitis and maternal sepsis.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42020156812.
Topics: Chorioamnionitis; Female; Gestational Age; Humans; Incidence; Infant, Newborn; Neonatal Sepsis; Postpartum Period; Pregnancy; Premature Birth; Sepsis; Term Birth; Time Factors
PubMed: 33957655
DOI: 10.1097/AOG.0000000000004377 -
Seminars in Immunopathology Aug 2020Almost half of all preterm births are caused or triggered by an inflammatory process at the feto-maternal interface resulting in preterm labor or rupture of membranes... (Review)
Review
Almost half of all preterm births are caused or triggered by an inflammatory process at the feto-maternal interface resulting in preterm labor or rupture of membranes with or without chorioamnionitis ("first inflammatory hit"). Preterm babies have highly vulnerable body surfaces and immature organ systems. They are postnatally confronted with a drastically altered antigen exposure including hospital-specific microbes, artificial devices, drugs, nutritional antigens, and hypoxia or hyperoxia ("second inflammatory hit"). This is of particular importance to extremely preterm infants born before 28 weeks, as they have not experienced important "third-trimester" adaptation processes to tolerate maternal and self-antigens. Instead of a balanced adaptation to extrauterine life, the delicate co-regulation between immune defense mechanisms and immunosuppression (tolerance) to allow microbiome establishment is therefore often disturbed. Hence, preterm infants are predisposed to sepsis but also to several injurious conditions that can contribute to the onset or perpetuation of sustained inflammation (SI). This is a continuing challenge to clinicians involved in the care of preterm infants, as SI is regarded as a crucial mediator for mortality and the development of morbidities in preterm infants. This review will outline the (i) role of inflammation for short-term consequences of preterm birth and (ii) the effect of SI on organ development and long-term outcome.
Topics: Chorioamnionitis; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Inflammation; Obstetric Labor, Premature; Pregnancy; Premature Birth
PubMed: 32661735
DOI: 10.1007/s00281-020-00803-2 -
American Journal of Obstetrics and... Oct 2015Chronic inflammatory lesions of the placenta are characterized by the infiltration of the organ by lymphocytes, plasma cells, and/or macrophages and may result from... (Review)
Review
Chronic inflammatory lesions of the placenta are characterized by the infiltration of the organ by lymphocytes, plasma cells, and/or macrophages and may result from infections (viral, bacterial, parasitic) or be of immune origin (maternal anti-fetal rejection). The 3 major lesions are villitis (when the inflammatory process affects the villous tree), chronic chorioamnionitis (which affects the chorioamniotic membranes), and chronic deciduitis (which involves the decidua basalis). Maternal cellular infiltration is a common feature of the lesions. Villitis of unknown etiology (VUE) is a destructive villous inflammatory lesion that is characterized by the infiltration of maternal T cells (CD8+ cytotoxic T cells) into chorionic villi. Migration of maternal T cells into the villi is driven by the production of T-cell chemokines in the affected villi. Activation of macrophages in the villi has been implicated in the destruction of the villous architecture. VUE has been reported in association with preterm and term fetal growth restriction, preeclampsia, fetal death, and preterm labor. Infants whose placentas have VUE are at risk for death and abnormal neurodevelopmental outcome at the age of 2 years. Chronic chorioamnionitis is the most common lesion in late spontaneous preterm birth and is characterized by the infiltration of maternal CD8+ T cells into the chorioamniotic membranes. These cytotoxic T cells can induce trophoblast apoptosis and damage the fetal membranes. The lesion frequently is accompanied by VUE. Chronic deciduitis consists of the presence of lymphocytes or plasma cells in the basal plate of the placenta. This lesion is more common in pregnancies that result from egg donation and has been reported in a subset of patients with premature labor. Chronic placental inflammatory lesions can be due to maternal anti-fetal rejection, a process associated with the development of a novel form of fetal systemic inflammatory response. The syndrome is characterized by an elevation of the fetal plasma T-cell chemokine. The evidence that maternal anti-fetal rejection underlies the pathogenesis of many chronic inflammatory lesions of the placenta is reviewed. This article includes figures and histologic examples of all chronic inflammatory lesions of the placenta.
Topics: CD8-Positive T-Lymphocytes; Chemokines; Chorioamnionitis; Chorionic Villi; Chronic Disease; Decidua; Female; Histocompatibility, Maternal-Fetal; Humans; Inflammation; Macrophages; Plasma Cells; Pregnancy
PubMed: 26428503
DOI: 10.1016/j.ajog.2015.08.041 -
Obstetrics and Gynecology Mar 2016In January 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development invited an expert panel to a workshop to address numerous knowledge...
In January 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development invited an expert panel to a workshop to address numerous knowledge gaps and to provide evidence-based guidelines for the diagnosis and management of pregnant women with what had been commonly called chorioamnionitis and the neonates born to these women. The panel noted that the term chorioamnionitis has been used to label a heterogeneous array of conditions characterized by infection and inflammation or both with a consequent great variation in clinical practice for mothers and their newborns. Therefore, the panel proposed to replace the term chorioamnionitis with a more general, descriptive term: "intrauterine inflammation or infection or both," abbreviated as "Triple I." The panel proposed a classification for Triple I and recommended approaches to evaluation and management of pregnant women and their newborns with a diagnosis of Triple I. It is particularly important to recognize that an isolated maternal fever is not synonymous with chorioamnionitis. A research agenda was proposed to further refine the definition and management of this complex group of conditions. This article provides a summary of the workshop presentations and discussions.
Topics: Anti-Infective Agents; Biomarkers; Chorioamnionitis; Disease Management; Female; Humans; Infant, Newborn; Pregnancy; Terminology as Topic
PubMed: 26855098
DOI: 10.1097/AOG.0000000000001246 -
American Journal of Obstetrics &... Jul 2023Various prophylactic antibiotic regimens are used in the management of preterm premature rupture of membranes. We investigated the efficacy and safety of these regimens... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Various prophylactic antibiotic regimens are used in the management of preterm premature rupture of membranes. We investigated the efficacy and safety of these regimens in terms of maternal and neonatal outcomes.
DATA SOURCES
We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to July 20, 2021.
STUDY ELIGIBILITY CRITERIA
We included randomized controlled trials involving pregnant women with preterm premature rupture of membranes before 37 weeks of gestation and a comparison of ≥2 of the following 10 antibiotic regimens: control/placebo, erythromycin, clindamycin, clindamycin plus gentamicin, penicillins, cephalosporins, co-amoxiclav, co-amoxiclav plus erythromycin, aminopenicillins plus macrolides, and cephalosporins plus macrolides.
METHODS
Two investigators independently extracted published data and assessed the risk of bias with a standard procedure following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Network meta-analysis was conducted using the random-effects model.
RESULTS
A total of 23 studies that recruited a total of 7671 pregnant women were included. Only penicillins (odds ratio, 0.46; 95% confidence interval, 0.27-0.77) had significantly superior effectiveness for maternal chorioamnionitis. Clindamycin plus gentamicin reduced the risk of clinical chorioamnionitis, with borderline significance (odds ratio, 0.16; 95% confidence interval, 0.03-1.00). By contrast, clindamycin alone increased the risk of maternal infection. For cesarean delivery, no significant differences were noted among these regimens.
CONCLUSION
Penicillins remain the recommended antibiotic regimen for reducing maternal clinical chorioamnionitis. The alternative regimen includes clindamycin plus gentamicin. Clindamycin should not be used alone.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Clindamycin; Chorioamnionitis; Amoxicillin-Potassium Clavulanate Combination; Network Meta-Analysis; Anti-Bacterial Agents; Premature Birth; Erythromycin; Macrolides; Gentamicins; Cephalosporins
PubMed: 37094635
DOI: 10.1016/j.ajogmf.2023.100978 -
Seminars in Fetal & Neonatal Medicine Aug 2020The fetus can deploy a local or systemic inflammatory response when exposed to microorganisms or, alternatively, to non-infection-related stimuli (e.g., danger signals...
The fetus can deploy a local or systemic inflammatory response when exposed to microorganisms or, alternatively, to non-infection-related stimuli (e.g., danger signals or alarmins). The term "Fetal Inflammatory Response Syndrome" (FIRS) was coined to describe a condition characterized by evidence of a systemic inflammatory response, frequently a result of the activation of the innate limb of the immune response. FIRS can be diagnosed by an increased concentration of umbilical cord plasma or serum acute phase reactants such as C-reactive protein or cytokines (e.g., interleukin-6). Pathologic evidence of a systemic fetal inflammatory response indicates the presence of funisitis or chorionic vasculitis. FIRS was first described in patients at risk for intraamniotic infection who presented preterm labor with intact membranes or preterm prelabor rupture of the membranes. However, FIRS can also be observed in patients with sterile intra-amniotic inflammation, alloimmunization (e.g., Rh disease), and active autoimmune disorders. Neonates born with FIRS have a higher rate of complications, such as early-onset neonatal sepsis, intraventricular hemorrhage, periventricular leukomalacia, and death, than those born without FIRS. Survivors are at risk for long-term sequelae that may include bronchopulmonary dysplasia, neurodevelopmental disorders, such as cerebral palsy, retinopathy of prematurity, and sensorineuronal hearing loss. Experimental FIRS can be induced by intra-amniotic administration of bacteria, microbial products (such as endotoxin), or inflammatory cytokines (such as interleukin-1), and animal models have provided important insights about the mechanisms responsible for multiple organ involvement and dysfunction. A systemic fetal inflammatory response is thought to be adaptive, but, on occasion, may become dysregulated whereby a fetal cytokine storm ensues and can lead to multiple organ dysfunction and even fetal death if delivery does not occur ("rescued by birth"). Thus, the onset of preterm labor in this context can be considered to have survival value. The evidence so far suggests that FIRS may compound the effects of immaturity and neonatal inflammation, thus increasing the risk of neonatal complications and long-term morbidity. Modulation of a dysregulated fetal inflammatory response by the administration of antimicrobial agents, anti-inflammatory agents, or cell-based therapy holds promise to reduce infant morbidity and mortality.
Topics: Adult; Chorioamnionitis; Cytokines; Female; Fetus; Humans; Infant, Newborn; Infant, Premature, Diseases; Interleukin-6; Obstetric Labor, Premature; Pregnancy; Systemic Inflammatory Response Syndrome
PubMed: 33164775
DOI: 10.1016/j.siny.2020.101146