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Seminars in Fetal & Neonatal Medicine Aug 2020The fetal inflammatory response syndrome (FIRS) is a condition whereby the fetus mounts an inflammatory response to intrauterine infection/inflammation. Clinical... (Review)
Review
The fetal inflammatory response syndrome (FIRS) is a condition whereby the fetus mounts an inflammatory response to intrauterine infection/inflammation. Clinical consequences include preterm premature rupture of membranes (PPROM), spontaneous preterm delivery, neonatal sepsis, bronchopulmonary dysplasia, and brain and other organ injury. Mechanisms leading to brain injury in FIRS have been investigated in animal and human studies. We review the neuroimaging findings of brain injury in FIRS, which overlap those of hypoxic-ischemic injury, and clinical correlation is necessary for a correct diagnosis. FIRS should be considered the primary diagnosis when neuroimaging findings such as periventricular leukomalacia are identified in preterm children born as a consequence of PPROM and spontaneous preterm labor. Additionally, FIRS should be considered in term infants who do not have the most common features of HIE (e.g. a sentinel event). Systematic histopathologic examination of the placenta and umbilical cord and/or detection of characteristic inflammatory markers in such cases are needed to establish the correct diagnosis.
Topics: Brain Injuries; Child; Chorioamnionitis; Female; Fetal Blood; Humans; Infant; Infant, Newborn; Neuroimaging; Obstetric Labor, Premature; Placenta; Pregnancy; Premature Birth; Systemic Inflammatory Response Syndrome
PubMed: 32800654
DOI: 10.1016/j.siny.2020.101143 -
Midwifery Apr 2022To describe the development of evidence-based recommendations on screening and managing women at risk for chorioamnionitis in resource-constrained healthcare settings. (Review)
Review
OBJECTIVE
To describe the development of evidence-based recommendations on screening and managing women at risk for chorioamnionitis in resource-constrained healthcare settings.
DESIGN
A qualitative study, using data from an integrative literature review to develop the evidence-based recommendations was conducted. The NICE guideline development principles were followed to format the recommendations, which were reviewed by expert reviewers using the AGREE II tool.
FINDINGS
Four main recommendations were developed, which were: screening by clinical signs and symptoms; screening by causative factors of chorioamnionitis; screening of obstetric history; and prevention and management of chorioamnionitis. A screening tool and algorithm based on the recommendations were also developed.
KEY CONCLUSIONS
Recommendations will assist midwives in identifying women at risk for chorioamnionitis and managing them before referral. The recommendations contribute to the quality care of women who are at risk for chorioamnionitis. The developed screening tool and algorithm based on the recommendations provide user-friendly guides for midwives in similar, resource-constrained settings, such as in South Africa, where these recommendations were developed. Screening using the recommended screening tool, therefore, is by far the least expensive tool when considering treatment costs and legal compensation for preventable deaths related to chorioamnionitis.
Topics: Chorioamnionitis; Delivery of Health Care; Female; Health Facilities; Humans; Midwifery; Pregnancy; Qualitative Research
PubMed: 35183873
DOI: 10.1016/j.midw.2022.103287 -
American Journal of Obstetrics &... Nov 2023Intraamniotic inflammation is associated with preterm birth, especially in cases occurring before 32 weeks' gestation, and is causally linked with an increased risk for...
BACKGROUND
Intraamniotic inflammation is associated with preterm birth, especially in cases occurring before 32 weeks' gestation, and is causally linked with an increased risk for neonatal mortality and morbidity. Targeted anti-inflammatory interventions may assist in improving the outcomes for pregnancies impacted by intrauterine inflammation. Interleukin-1 is a central upstream mediator of inflammation. Accordingly, interleukin-1 is a promising candidate target for intervention therapies and has been targeted previously using the interleukin-1 receptor antagonist, anakinra. Recent studies have shown that the novel, noncompetitive, allosteric interleukin-1 receptor inhibitor, rytvela, partially resolved inflammation associated with preterm birth and fetal injury. In this study, we used a preterm sheep model of chorioamnionitis to investigate the anti-inflammatory efficacy of rytvela and anakinra, administered in the amniotic fluid in the setting of intraamniotic Escherichia coli lipopolysaccharide exposure.
OBJECTIVE
We hypothesized that both rytvela and anakinra would reduce lipopolysaccharide-induced intrauterine inflammation and protect the fetal brain.
STUDY DESIGN
Ewes with a singleton fetus at 105 days of gestation (term is ∼150 days) were randomized to one of the following groups: (1) intraamniotic injections of 2 mL saline at time=0 and time=24 hours as a negative control group (saline group, n=12); (2) intraamniotic injection of 10 mg Escherichia coli lipopolysaccharide in 2 mL saline and intraamniotic injections of 2 mL saline at time=0 hours and time=24 hours as an inflammation positive control group (lipopolysaccharide group, n=11); (3) intraamniotic injection of Escherichia coli lipopolysaccharide in 2 mL saline and intraamniotic injections of 2.5 mg rytvela at time=0 hours and time=24 hours to test the anti-inflammatory efficacy of rytvela (lipopolysaccharide + rytvela group, n=10); or (4) intraamniotic injection of Escherichia coli lipopolysaccharide in 2 mL saline and intraamniotic injections of 100 mg anakinra at time=0 hours and time=24 hours to test the anti-inflammatory efficacy of anakinra (lipopolysaccharide + anakinra group, n=12). Amniotic fluid was sampled at time 0, 24, and 48 hours (ie, at each intervention and at delivery). Fetal umbilical cord blood was collected at delivery for differential blood counts and chemical studies. Inflammation was characterized by the analysis of fetal tissue cytokine and chemokine levels using quantitative polymerase chain reaction, enzyme-linked inmmunosorbent assay, and histology. The primary study outcome of interest was the assessment of anakinra and rytvela brain-protective effects in the setting of Escherichia coli lipopolysaccharide-induced intrauterine inflammation. Secondary outcomes of interest were to assess protection from fetal and intrauterine (ie, amniotic fluid, chorioamnion) inflammation.
RESULTS
Intraamniotic administration of lipopolysaccharide caused inflammation of the fetal lung, brain, and chorioamnionitis in preterm fetal sheep. Relative to treatment with saline only in the setting of lipopolysaccharide exposure, intraamniotic administration of both rytvela and anakinra both significantly prevented periventricular white matter injury, microglial activation, and histologic chorioamnionitis. Anakinra showed additional efficacy in inhibiting fetal lung myeloperoxidase activity, but its use was associated with metabolic acidaemia and reduced fetal plasma insulin-like growth factor-1 levels at delivery.
CONCLUSION
Intraamniotic administration of rytvela or anakinra significantly inhibited fetal brain inflammation and chorioamnionitis in preterm fetal sheep exposed to intraamniotic lipopolysaccharide. In addition, anakinra treatment was associated with potential negative impacts on the developing fetus.
Topics: Animals; Female; Pregnancy; Amniotic Fluid; Anti-Inflammatory Agents; Chorioamnionitis; Escherichia coli; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Lipopolysaccharides; Neuroinflammatory Diseases; Premature Birth; Receptors, Interleukin-1; Sheep; Disease Models, Animal; Animals, Newborn
PubMed: 37597799
DOI: 10.1016/j.ajogmf.2023.101124 -
European Journal of Obstetrics,... May 2015A histologic response of histologic chorioamnionitis (HCA) is defined as an intrauterine inflammatory condition characterized by acute granulocyte infiltration into the... (Review)
Review
A histologic response of histologic chorioamnionitis (HCA) is defined as an intrauterine inflammatory condition characterized by acute granulocyte infiltration into the fetal-maternal or the fetal tissues. Prevalence of HCA is inversely correlated with gestational age, occurring in 50% of preterm birth and in up to 20% of deliveries at term. Regardless of these standard definitions, understanding HCA is challenging as it reflects a heterogeneous condition. A histologic response of HCA from term placentas often does not correspond to a clinical presentation; in this context, the present review aims to analyze main characteristics of this condition, in particular focusing on mechanisms and birth outcomes.
Topics: Brain; Chorioamnionitis; Female; Fetal Growth Retardation; Gestational Age; Humans; Infant, Newborn; Lung Diseases; Placenta; Pregnancy; Pregnancy Complications, Infectious; Premature Birth; Prenatal Exposure Delayed Effects; Stillbirth; Term Birth
PubMed: 25770845
DOI: 10.1016/j.ejogrb.2015.02.034 -
Journal of Perinatal Medicine Jan 2016
Topics: Chorioamnionitis; Female; Humans; Infant, Newborn; Obstetrics; Pregnancy
PubMed: 26756087
DOI: 10.1515/jpm-2015-0366 -
Histopathology May 2024Histological chorioamnionitis (HCA) is a condition linked to preterm birth and neonatal infection and its relationship with various pathological stages in extremely...
AIMS
Histological chorioamnionitis (HCA) is a condition linked to preterm birth and neonatal infection and its relationship with various pathological stages in extremely preterm neonates, and with their associated short- and long-term consequences, remains a subject of research. This study investigated the connection between different pathological stages of HCA and both short-term complications and long-term outcomes in preterm infants born at or before 32 weeks of gestational age.
METHODS
Preterm infants born at ≤ 32 weeks of gestation who underwent placental pathology evaluation and were followed-up at 18-24 months of corrected age were included. Neonates were classified based on their exposure to HCA and were further subdivided into different groups according to maternal inflammatory responses (MIR) and fetal inflammatory responses (FIR) stages. We compared short-term complications during their hospital stay between the HCA-exposed and -unexposed groups and examined the influence of HCA stages on long-term outcomes.
RESULTS
The HCA group exhibited distinct characteristics such as higher rates of premature rupture of membranes > 18 h, reduced amniotic fluid, early-onset sepsis, bronchopulmonary dysplasia and intraventricular haemorrhage (IVH) grades III-IV (P < 0.05). The moderate-severe HCA group displayed lower gestational age, lower birth weight and higher incidence of IVH (grades III-IV) and preterm sepsis compared with the mild HCA group (P < 0.05). After adjusting for confounders, the MIR stages 2-3 group showed associations with cognitive impairment and cerebral palsy (P < 0.05), and the FIR stages 2-3 group also showed poor long-term outcomes and cognitive impairment (P < 0.05).
CONCLUSIONS
Moderate-severe HCA was associated with increased early-onset sepsis, severe IVH and poor long-term outcomes, including cognitive impairment and cerebral palsy. Vigilant prevention strategies are warranted for severe HCA cases in order to mitigate poorer clinical outcomes.
Topics: Infant; Infant, Newborn; Humans; Female; Pregnancy; Infant, Premature; Chorioamnionitis; Placenta; Fetal Membranes, Premature Rupture; Cerebral Palsy; Premature Birth; Risk Factors; Gestational Age; Sepsis
PubMed: 38253913
DOI: 10.1111/his.15147 -
American Journal of Obstetrics &... Mar 2023Data regarding the microbiome of the gestational membranes are emerging and conflicting. Shifts in the microbial communities in the setting of labor, rupture of...
BACKGROUND
Data regarding the microbiome of the gestational membranes are emerging and conflicting. Shifts in the microbial communities in the setting of labor, rupture of membranes, and intraamniotic infection are yet to be understood.
OBJECTIVE
This study aimed to characterize the microbiome of the gestational membranes of women in labor or with ruptured membranes, including those with and without intraamniotic infection.
STUDY DESIGN
Women with a singleton pregnancy at ≥28 weeks' gestation undergoing unscheduled cesarean delivery in the setting of labor or rupture of membranes were included. Demographic and clinical variables were collected. We defined suspected intraamniotic infection by standard clinical criteria; placentae and gestational membranes were also reviewed for histologic evidence of infection. Sterile swabs were collected from membranes at the time of delivery. Bacteria were cultured from the swabs, and the isolates were sequenced. DNA extraction and 16S sequencing of the swabs were also performed. Bacterial taxonomy was assigned to each sequence. Alpha diversity indices and beta-diversity metrics were calculated to test for differences in microbial community diversity and composition between uninfected and infected groups. Differential abundance of bacteria between infected and uninfected groups was tested at the class, family, and genus level.
RESULTS
Samples were collected from 34 participants. Clinical intraamniotic infection was diagnosed in 38% of participants, although 50% of placentae and membranes demonstrated histologic signs of infection. Of all samples, 68% grew bacteria on culture; this included 62% of the uninfected samples and 77% of the infected samples (P=.83). Multiple measures of alpha diversity were not significantly different between uninfected and infected groups. Similarly, analysis of beta diversity revealed that the microbial community was not significantly different between the uninfected and infected group. Several bacteria traditionally characterized as pathogenic, including Actinomyces and Streptococcus agalactiae, were identified in both infected and uninfected samples.
CONCLUSION
The pathogenesis and clinical implications of intraamniotic infection remain poorly understood. Diverse bacteria are present in both infected and uninfected gestational membranes. A unique microbiologic signature may exist among the gestational membranes following labor or rupture of membranes, and further characterization of the pathogens specifically implicated in intraamniotic infection may allow for targeted therapy.
Topics: Pregnancy; Female; Humans; Chorioamnionitis; Amniotic Fluid; Fetal Membranes, Premature Rupture; Placenta; Microbiota
PubMed: 36623808
DOI: 10.1016/j.ajogmf.2022.100837 -
European Journal of Obstetrics,... May 2021To assess the cardiotocographic changes and maternal and neonatal outcomes in cases of chorioamnionitis and or funisitis confirmed on histopathology.
OBJECTIVE
To assess the cardiotocographic changes and maternal and neonatal outcomes in cases of chorioamnionitis and or funisitis confirmed on histopathology.
STUDY DESIGN
A retrospective analysis of histopathology reports confirming chorioamnionitis and/or funisitis was carried out from 2014 to 2020 in a single centre. The preterm births (<37 weeks) were excluded. The maternal records were reviewed to determine the maternal and neonatal outcomes such as the mode of delivery, intrapartum and postpartum complications, umbilical cord arterial pH, and admission to the special care baby unit (SCBU). The CTG features were analysed on admission and during the intrapartum period. The study was approved by the Audit and Clinical Effectiveness department within the centre.
RESULTS
Out of the 57 cases of histologically confirmed chorioamnionitis and/or funisitis, 42 women (73.7 %) had intrapartum pyrexia and none of the mothers had an increased temperature at the point of fetal tachycardia (persistent increase in baseline fetal heart rate (FHR) by >10 % compared to the original baseline FHR). 43 (75.4 %) CTGs showed evidence of uterine tachysystole or hyperstimulation. 15 (26.3 %) cases had meconium stained amniotic fluid (MSAF). 54 (94.7 %) women had a caesarean section, and their babies were admitted to special care baby unit after delivery. 54 (94.7 %) babies had an umbilical artery of more than 7.1. 47 (87 %) of the women were readmitted with wound infection. All CTG traces showed a > 10 % increase in the baseline FHR and variable decelerations with overshoot were noted in cases where funisitis was confirmed in 25 cases (92.6 %). Loss of cycling was noted in 54 CTGs (94.7 %) and a sinusoidal pattern was identified in 27 (47.3 %).
CONCLUSION
Rising (>10 %) baseline during labour along with loss of cycling with or without features of tachysystole or hyperstimulation should be considered in labour as features of ongoing chorioamnionitis. Chorioamnionitis confirmed on histopathology is associated with an increase in caesarean section rate due to fetal heart rate changes, increased risk of wound infection in mothers, and increased admission of the babies to SCBU.
Topics: Cardiotocography; Cesarean Section; Chorioamnionitis; Female; Heart Rate, Fetal; Humans; Infant, Newborn; Pregnancy; Retrospective Studies
PubMed: 33838555
DOI: 10.1016/j.ejogrb.2021.03.029 -
Seminars in Fetal & Neonatal Medicine Aug 2020Clinical signs and neuroimaging patterns associated with the fetal inflammatory response syndrome (FIRS) worsen or mimic the clinical repertoire after intrapartum... (Review)
Review
Clinical signs and neuroimaging patterns associated with the fetal inflammatory response syndrome (FIRS) worsen or mimic the clinical repertoire after intrapartum hypoxic-ischemic encephalopathy (HIE) during labor and/or parturition. Diagnostic considerations expressed as neonatal encephalopathy (NE) must consider chronic as well as acute factors associated with FIRS. Trimester-specific factors adversely alter the interactions of the maternal/placental/fetal (MPF) triad and influence the postnatal phenotype of FIRS. Anticipatory guidance for families by clinicians caring for survivors with FIRS, as well as researchers, must consider acute and chronic effects that influence neurologic outcome. Novel neurotherapeutic interventions must include prenatal preventive as well as peripartum/postnatal rescue and repair strategies to effectively reduce the presence and severity of sequelae from FIRS.
Topics: Adult; Chorioamnionitis; Female; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Pregnancy Outcome
PubMed: 33158496
DOI: 10.1016/j.siny.2020.101137 -
Clinical Microbiology Reviews Jan 2017The human Ureaplasma species are the most frequently isolated microorganisms from the amniotic fluid and placentae of women who deliver preterm and are also associated... (Review)
Review
The human Ureaplasma species are the most frequently isolated microorganisms from the amniotic fluid and placentae of women who deliver preterm and are also associated with spontaneous abortions or miscarriages, neonatal respiratory diseases, and chorioamnionitis. Despite the fact that these microorganisms have been habitually found within placentae of pregnancies with chorioamnionitis, the role of Ureaplasma species as a causative agent has not been satisfactorily explained. There is also controversy surrounding their role in disease, particularly as not all women infected with Ureaplasma spp. develop chorioamnionitis. In this review, we provide evidence that Ureaplasma spp. are associated with diseases of pregnancy and discuss recent findings which demonstrate that Ureaplasma spp. are associated with chorioamnionitis, regardless of gestational age at the time of delivery. Here, we also discuss the proposed major virulence factors of Ureaplasma spp., with a focus on the multiple-banded antigen (MBA), which may facilitate modulation/alteration of the host immune response and potentially explain why only subpopulations of infected women experience adverse pregnancy outcomes. The information presented within this review confirms that Ureaplasma spp. are not simply "innocent bystanders" in disease and highlights that these microorganisms are an often underestimated pathogen of pregnancy.
Topics: Chorioamnionitis; Female; Humans; Infant, Newborn; Obstetric Labor, Premature; Pregnancy; Ureaplasma; Ureaplasma Infections; Virulence Factors
PubMed: 27974410
DOI: 10.1128/CMR.00091-16