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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 -
Seminars in Fetal & Neonatal Medicine Aug 2020Fetal Inflammatory Response Syndrome (FIRS) is the fetal counterpart of systemic inflammatory response syndrome (SIRS) described in adults. When the fetus is directly... (Review)
Review
Fetal Inflammatory Response Syndrome (FIRS) is the fetal counterpart of systemic inflammatory response syndrome (SIRS) described in adults. When the fetus is directly exposed to inflammation of the fetal membranes or the placental-fetal circulation, and organs are adversely affected, the disorder is known as FIRS. This syndrome can significantly affect multiple organs with significant short and long term implications for the newborn. In cases of neonatal encephalopathy when no obvious etiology is identified, FIRS needs to be considered. Based on the significant incidence of chorioamnionitis and its potential effects on the newborn, any evidence of maternal, fetal, or neonatal infection should mandate further evaluation of the placenta and membrane histopathology.
Topics: Adult; Chorioamnionitis; Female; Fetal Blood; Humans; Infant, Newborn; Placenta; Pregnancy; Systemic Inflammatory Response Syndrome
PubMed: 32912755
DOI: 10.1016/j.siny.2020.101142 -
Current Opinion in Pediatrics Apr 2017The association between maternal chorioamnionitis and early-onset sepsis in the newborn has long been recognized, and established guidelines recommend treating all... (Review)
Review
PURPOSE OF REVIEW
The association between maternal chorioamnionitis and early-onset sepsis in the newborn has long been recognized, and established guidelines recommend treating all exposed infants with broad-spectrum antibiotics until infection can be ruled out. However, recent data suggest that close observation of well appearing term and late-preterm newborns may be a preferable alternative. The present review addresses the evidence in favor of newly proposed changes to the diagnosis and management of women and newborns following a maternal diagnosis of chorioamnionitis. Potential implications of these new practice guidelines will also be discussed.
RECENT FINDINGS
A panel of experts assembled in 2015 to provide updated, evidence-based guidelines for the diagnosis and management of women and newborns following a maternal diagnosis of chorioamnionitis. Revised terminology and diagnostic criteria were proposed as well as changes in the management of newborns of mothers with suspected intrauterine infection, most notably a recommendation to observe (rather than treat) well appearing term and late-preterm newborns.
SUMMARY
A management strategy consisting of close observation of well appearing term and late-preterm infants exposed to suspected intrauterine infection is preferable to empiric antimicrobial therapy. Large prospective epidemiologic studies will be needed to ascertain the impact of these new practice guidelines on the outcomes of infants exposed to intrauterine infection and/or inflammation. Improved precision in the clinical diagnosis of intrauterine infection should improve both the quality and reproducibility of data generated from future studies.
Topics: Anti-Bacterial Agents; Chorioamnionitis; Evidence-Based Medicine; Female; Gestational Age; Humans; Infant Health; Infant, Newborn; Male; Needs Assessment; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Risk Assessment; Treatment Outcome; United States
PubMed: 28134708
DOI: 10.1097/MOP.0000000000000466 -
Journal of Biomaterials Applications Mar 2023The developing fetus is wrapped by a human amniotic membrane or amnion. Amnion is a promising human tissue allograft in clinical application because of its chemical... (Review)
Review
The developing fetus is wrapped by a human amniotic membrane or amnion. Amnion is a promising human tissue allograft in clinical application because of its chemical composition, collagen-based, and mechanical properties of the extracellular matrix. In addition, amnion contains cells and growth factors; therefore, meets the essential parameters of tissue engineering. No donor morbidity, easy processing and storage, fewer ethical issue, anti-inflammatory, antioxidant, antibacterial, and non-immunogenic properties are other advantages of amnion usage. For these reasons, amnion can resolve some bottlenecks in the regenerative medicine issues such as tissue engineering and cell therapy. Over the last decades, biomedical applications of amnion have evolved from a simple sheet for skin or cornea repair to high-technology applications such as amnion nanocomposite, powder, or hydrogel for the regeneration of cartilage, muscle, tendon, and heart. Furthermore, amnion has anticancer as well as drug/cell delivery capacity. This review highlights various ancient and new applications of amnion in research and clinical applications, from regenerative medicine to cancer therapy, focusing on articles published during the last decade that also revealed information regarding amnion-based products. Challenges and future perspectives of the amnion in regenerative medicine are also discussed.
Topics: Humans; Amnion; Regenerative Medicine; Tissue Engineering; Skin
PubMed: 36331116
DOI: 10.1177/08853282221137609 -
Reproduction in Domestic Animals =... Dec 2015Foetal membranes are essential tissues for embryonic development, playing important roles related to protection, breathing, nutrition and excretion. The amnion is the... (Review)
Review
Foetal membranes are essential tissues for embryonic development, playing important roles related to protection, breathing, nutrition and excretion. The amnion is the innermost extraembryonic membrane, which surrounds the foetus, forming an amniotic sac that contains the amniotic fluid (AF). In recent years, the amniotic membrane has emerged as a potential tool for clinical applications and has been primarily used in medicine in order to stimulate the healing of skin and corneal diseases. It has also been used in vaginal reconstructive surgery, repair of abdominal hernia, prevention of surgical adhesions and pericardium closure. More recently, it has been used in regenerative medicine because the amniotic-derived stem cells as well as AF-derived cells exhibit cellular plasticity, angiogenic, cytoprotective, immunosuppressive properties, antitumoural potential and the ability to generate induced pluripotent stem cells. These features make them a promising source of stem cells for cell therapy and tissue engineering. In this review, we discussed the development of the amnion, AF and amniotic cavity in different species, as well as the applicability of stem cells from the amnion and AF in cellular therapy.
Topics: Amnion; Amniotic Fluid; Animals; Cell Differentiation; Cell- and Tissue-Based Therapy; Female; Humans; Mesenchymal Stem Cells; Pregnancy; Regenerative Medicine
PubMed: 26510939
DOI: 10.1111/rda.12633 -
Free Radical Biology & Medicine Oct 2019The dynamic field of perinatology entails ever-increasing search for molecular mechanisms of neonatal diseases, especially in the domain of fetal growth and... (Review)
Review
The dynamic field of perinatology entails ever-increasing search for molecular mechanisms of neonatal diseases, especially in the domain of fetal growth and neurodevelopmental outcome. There is an urgent need for new molecular biomarkers, to early identify newborn at high risk for developing diseases and to provide new treatment targets. The interest in biomarkers of oxidative stress in perinatal period have begun to grow in the last century, when it was evidenced the importance of the free radicals generation underlying the various disease conditions. To date, interesting researches have been carried out, representing milestones for implementation of oxidative stress biomarkers in perinatal medicine. Use of a panel of "oxidative stress biomarkers", particularly non protein bound iron, advanced oxidative protein products and isoprostanes, may provide valuable information regarding functional pathways underlying free radical mediated diseases of newborns and their early identification and prevention. Here, we will review recent advances and the current knowledge on the application of biomarkers of oxidative stress in neonatal/perinatal medicine including novel biomarker discovery, defining yet unrecognized biologic therapeutic targets, and linking of oxidative stress biomarkers to relevant standard indices and long-term outcomes.
Topics: Advanced Oxidation Protein Products; Biomarkers; Chorioamnionitis; Female; Fetal Growth Retardation; Fetus; Humans; Infant, Newborn; Isoprostanes; Oxidative Stress; Oxygen; Perinatology; Pre-Eclampsia; Pregnancy; Reactive Oxygen Species
PubMed: 30954545
DOI: 10.1016/j.freeradbiomed.2019.03.034 -
Clinics in Perinatology Mar 2015Chorioamnionitis (CA) is characterized by inflammation of the fetal membranes. The incidence increases with decreasing gestational age at birth. When suspected on... (Review)
Review
Chorioamnionitis (CA) is characterized by inflammation of the fetal membranes. The incidence increases with decreasing gestational age at birth. When suspected on clinical criteria, pathologic assessment of the placenta should be performed. Although the mechanisms are not entirely clear, CA predisposes to premature birth, neonatal sepsis, and intraventricular hemorrhage. Its role in respiratory distress syndrome, bronchopulmonary dysplasia, and neurodevelopmental impairment is mixed. Prevention and treatment are ill-defined; antibiotics for preterm premature rupture of membranes reduce the incidence and increase the length of time to delivery. Antibiotics are recommended for infants exposed to CA while laboratory studies are being performed.
Topics: Anti-Bacterial Agents; Bronchopulmonary Dysplasia; Cerebral Hemorrhage; Chorioamnionitis; Female; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Placenta; Pregnancy; Premature Birth; Respiratory Distress Syndrome, Newborn; Risk Factors; Sepsis
PubMed: 25678002
DOI: 10.1016/j.clp.2014.10.011 -
American Journal of Obstetrics and... Jan 2023Spontaneous preterm birth accounts for most preterm births and leads to significant morbidity in the newborn and childhood period. This subtype of preterm birth...
BACKGROUND
Spontaneous preterm birth accounts for most preterm births and leads to significant morbidity in the newborn and childhood period. This subtype of preterm birth represents an increasing proportion of all preterm births when compared with medically indicated preterm birth, yet it is understudied in omics analyses. The placenta is a key regulator of fetal and newborn health, and the placental transcriptome can provide insight into pathologic changes that lead to spontaneous preterm birth.
OBJECTIVE
This analysis aimed to identify genes for which placental expression was associated with spontaneous preterm birth (including early preterm and late preterm birth).
STUDY DESIGN
The ECHO PATHWAYS consortium extracted RNA from placental samples collected from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood and the Global Alliance to Prevent Prematurity and Stillbirth studies. Placental transcriptomic data were obtained by RNA sequencing. Linear models were fit to estimate differences in placental gene expression between term birth and spontaneous preterm birth (including gestational age subgroups defined by the American College of Obstetricians and Gynecologists). Models were adjusted for numerous confounding variables, including labor status, cohort, and RNA sequencing batch. This analysis excluded patients with induced labor, chorioamnionitis, multifetal gestations, or medical indications for preterm birth. Our combined cohort contained gene expression data for 14,023 genes in 48 preterm and 540 term samples. Genes and pathways were considered statistically significantly different at false discovery rate-adjusted P value of <.05.
RESULTS
In total, we identified 1728 genes for which placental expression was associated with spontaneous preterm birth with more differences in expression in early preterm samples than late preterm samples when compared with full-term samples. Of those, 9 genes were significantly decreased in both early and late spontaneous preterm birth, and the strongest associations involved placental expression of IL1B, ALPL, and CRLF1. In early and late preterm samples, we observed decreased expression of genes involved in immune signaling, signal transduction, and endocrine function.
CONCLUSION
This study provides a comprehensive assessment of the differences in the placental transcriptome associated with spontaneous preterm birth with robust adjustment for confounding. Results of this study are in alignment with the known etiology of spontaneous preterm birth, because we identified multiple genes and pathways for which the placental and chorioamniotic membrane expression was previously associated with prematurity, including IL1B. We identified decreased expression in key signaling pathways that are essential for placental growth and function, which may be related to the etiology of spontaneous preterm birth. We identified increased expression of genes within metabolic pathways associated exclusively with early preterm birth. These signaling and metabolic pathways may provide clinically targetable pathways and biomarkers. The findings presented here can be used to understand underlying pathologic changes in premature placentas, which can inform and improve clinical obstetrics practice.
Topics: Child, Preschool; Infant, Newborn; Pregnancy; Female; Humans; Premature Birth; Placenta; Transcriptome; Infant, Premature; Chorioamnionitis
PubMed: 35868418
DOI: 10.1016/j.ajog.2022.07.015 -
Archives of Iranian Medicine Jul 2020Chorioamnionitis (CAM) is one of the major risk factors for neonatal early-onset sepsis (EOS). Different international guidelines have been developed for diagnosis and...
BACKGROUND
Chorioamnionitis (CAM) is one of the major risk factors for neonatal early-onset sepsis (EOS). Different international guidelines have been developed for diagnosis and care of such neonates. This research aimed to evaluate our neonates and compare them with the guidelines.
METHODS
This prospective cohort study was conducted during five years (March 2012 to March 2017), and comprised of neonates (any gestational age) born to mothers with CAM (any criteria). The neonates' clinical findings and interventions were collected and analyzed.
RESULTS
In total, out of 28,988 live born neonates, CAM was found in mothers of 169 neonates (1.7%). Among the studied neonates, 30.8% were born ≤34 week of gestation, 39% had birth weight <2500 g, and 58.6% were asymptomatic. Out of 99 asymptomatic neonates, 47 were observed near mothers and 52 admitted to the neonatal intensive care unit (NICU). The frequency of abnormal tests was 23.07% in asymptomatic vs. 35.7% in symptomatic neonates; three neonates developed culture positive EOS (2.75%) and 68.05% of the neonates received antibiotics. The length of stay was 2.59 ± 1.13 (median = 2.00, IQR = 1.00) days in asymptomatic vs. 15.15 ± 13.67 (median = 7.00, IQR = 15.25) days in symptomatic neonates (P<0.001).
CONCLUSION
The use of guidelines increased the length of stay, lab tests, and antibiotics in asymptomatic and neonates with negative blood culture. In addition to the mother-neonate separation, these guidelines may increase nosocomial infection, antibiotic resistance, and costs; therefore, new guidelines are needed to be developed.
Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Chorioamnionitis; Female; Gestational Age; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Length of Stay; Male; Neonatal Sepsis; Practice Guidelines as Topic; Pregnancy; Prospective Studies; Risk Assessment; Risk Factors
PubMed: 32657599
DOI: 10.34172/aim.2020.45 -
Midwifery Oct 2022This integrative literature review provides an overview of current best research evidence on the screening and diagnosis of women for chorioamnionitis, as no current... (Review)
Review
OBJECTIVE
This integrative literature review provides an overview of current best research evidence on the screening and diagnosis of women for chorioamnionitis, as no current review has been conducted. An overview of best practices on screening and diagnosis of women for chorioamnionitis can assist midwives with an accurate diagnosis, allowing for early referral and adequate management of this infection.
DESIGN
An integrative literature review was conducted using a systematic electronic literature search through EBSCOhost (CINAHL with Full Text, e-Book Collection, Health Source: Nursing/Academic Edition, MEDLINE, Open Dissertations and PsycINFO), Cochrane Online, PubMed, Scopus, followed by a manual search for grey literature using Google and a citation search. Guidelines, research studies, and reports in English related to chorioamnionitis from 2008 up until 2020 were included in the study.
FINDINGS
After critical appraisal, using the Joanna Briggs Institution's checklists, Evaluation Tool for Quantitative Research Studies' tool and the Appraisal of Guidelines for Research & Evaluation instrument, 31 articles were included. More than half (64%) of the literature included ranked on the three highest levels of evidence (Level I, II and III). Data extracted regarding screening and diagnosis of women for chorioamnionitis was synthesised into four themes, namely: screening by clinical signs and symptoms, screening by causative factors of chorioamnionitis, screening of obstetric history, and essential biomarkers to diagnose chorioamnionitis.
KEY CONCLUSIONS
Screening and recording of any risk factors will assist midwives in providing tailored health education to possibly prevent causative factors that could lead to chorioamnionitis. Although matrix-metalloproteinase-8 (MMP-8) seems the most suitable test to use for screening, an accurate diagnosis of chorioamnionitis requires a combination of screening methods and tests, such as clinical signs and symptoms, maternal biomarkers, amniotic fluid testing and histology. Screening for chorioamnionitis, particularly the parameters for maternal fever as a clinical symptom of chorioamnionitis, contributing factors and microbes responsible for chorioamnionitis, the usability of MMP-8 and the development of rapid, inexpensive, easy-to-use techniques for screening and diagnosis of chorioamnionitis, warrants further research.
IMPLICATIONS FOR PRACTICE
Findings can be used by midwives in the screening and diagnosis of women for chorioamnionitis which allows for early referral and adequate management before maternal and neonatal complications arise.
Topics: Biomarkers; Chorioamnionitis; Female; Humans; Infant, Newborn; Matrix Metalloproteinase 8; Midwifery; Pregnancy; Pregnancy Complications
PubMed: 35863118
DOI: 10.1016/j.midw.2022.103417