Fetal Inflammatory Response Syndrome Research Articles

The Consequences of Chorioamnionitis: Preterm Birth and Effects on Development

Preterm birth is a major cause of perinatal mortality and long-term morbidity. Chorioamnionitis is a common cause of preterm birth. Clinical chorioamnionitis, characterised by maternal fever, leukocytosis, tachycardia, uterine tenderness, and preterm rupture of membranes, is less common than subclinical/histologic chorioamnionitis, which is asymptomatic and defined by inflammation of the chorion, amnion, and placenta. Chorioamnionitis is often associated with a fetal inflammatory response. The fetal inflammatory response syndrome (FIRS) is defined by increased systemic inflammatory cytokine concentrations, funisitis, and fetal vasculitis. Clinical and epidemiological studies have demonstrated that FIRS leads to poor cardiorespiratory, neurological, and renal outcomes. These observations are further supported by experimental studies that have improved our understanding of the mechanisms responsible for these outcomes. This paper outlines clinical and experimental studies that have improved our current understanding of the mechanisms responsible for chorioamnionitis-induced preterm birth and explores the cellular and physiological mechanisms underlying poor cardiorespiratory, neural, retinal, and renal outcomes observed in preterm infants exposed to chorioamnionitis.

White matter injury following fetal inflammatory response syndrome induced by chorioamnionitis and fetal sepsis: Lessons from experimental ovine models

Chorioamnionitis and fetal sepsis can induce a fetal inflammatory response syndrome (FIRS) which is closely related to the development of white matter injury in the fetal brain. Large epidemiological studies support the link between FIRS and fetal brain injury with a clear association between the presence of in utero inflammation and neurodevelopmental complications such as cerebral palsy, autism and cognitive impairments later in life.Translational animal models of chorioamnionitis and fetal sepsis are essential in understanding the underlying pathophysiological mechanisms of fetal brain injury after exposure to intra-uterine inflammation. Concerning this aspect, ovine models have high translational value since neurodevelopment in sheep closely resembles the human situation.In this article, we will review clinical and experimental evidence for the link between FIRS and white matter injury in the fetal brain. With respect to experimental findings, we will particularly focus on the lessons learned from ovine models of chorioamnionitis and fetal sepsis. We also highlight two key players implied in the pathophysiology of white matter injury after in utero exposure to inflammation.

A6 Fetal inflammatory response syndrome and chronic respiratory disorders in preterms: does it really matter?

A6 Fetal inflammatory response syndrome and chronic respiratory disorders in preterms: does it really matter?

Association Between the Markers of FIRS and the Morphologic Alterations in the Liver of Neonates Autopsied in the Perinatal Period

Markers of fetal inflammatory response syndrome (FIRS) can influence the morphologic alterations in liver of autopsied neonates. The IL-6, TNF-α, and C-reactive protein (CRP) expression in liver fragments were marked by immunohistochemistry and the intensity of steatosis, percentage of fibrosis, and the number of foci of extramedullary erythropoiesis were evaluated. The degree of steatosis correlated positively with IL-6 (p = 0.06), positively with CRP (p ≤ 0.001), and negatively with TNF-α (p = 0.06). The collagen percentage correlated positively with IL-6 (p = 0.055) and positively with TNF-α (p ≤ 0.001). Erythropoiesis correlated positively with IL-6 (p ≤ 0.001) and negatively with CRP (p = 0.00754). The analyzed markers of FIRS have an important role in triggering hepatic morphologic alterations.

Interleukin-19 in fetal systemic inflammation

Objective: The fetal inflammatory response syndrome (FIRS) is considered the fetal counterpart of the systemic inflammatory response syndrome (SIRS), which can be caused by infection and non-infection-related insults. Although the initial response is mediated by pro-inflammatory signals, the control of this response is achieved by anti-inflammatory mediators which are essential for the successful outcome of the affected individual. Interleukin (IL)-19 is capable of stimulating the production of IL-10, a major anti-inflammatory cytokine, and is a potent inducer of the T-helper 2 (Th2) response. The aim of this study was to determine if there is a change in umbilical cord plasma IL-19 and IL-10 concentrations in preterm neonates with and without acute funisitis, the histologic counterpart of FIRS. Methods: A case-control study was conducted including 80 preterm neonates born after spontaneous labor. Neonates were classified according to the presence (n = 40) or absence of funisitis (n = 40), which is the pathologic hallmark of FIRS. Neonates in each group were also matched for gestational age. Umbilical cord plasma IL-19 and IL-10 concentrations were determined by ELISA. Results: 1) The median umbilical cord plasma IL-19 concentration was 2.5-fold higher in neonates with funisitis than in those without funisitis (median 87 pg/mL; range 20.6–412.6 pg/mL vs. median 37 pg/mL; range 0–101.7 pg/mL; p < 0.001); 2) newborns with funisitis had a significantly higher median umbilical cord plasma IL-10 concentration than those without funisitis (median 4 pg/mL; range 0–33.5 pg/mL vs. median 2 pg/mL; range 0–13.8 pg/mL; p < 0.001); and 3) the results were similar when we included only patients with funisitis who met the definition of FIRS by umbilical cord plasma IL-6 concentrations ≥ 17.5 pg/mL (p < 0.001). Conclusion: IL-19 and IL-10 are parts of the immunologic response of FIRS. A subset of fetuses with FIRS had high umbilical cord plasma IL-19 concentrations. In utero exposure to high systemic concentrations of IL-19 may reprogram the immune response.

Umbilical cord blood procalcitonin as a risk factor for mortality in very premature infants

Fetal inflammatory response syndrome is implicated as a cause of fetal or neonatal injury. We analyzed the relationship between the procalcitonin umbilical cord blood level and neonatal outcome. A total of 237 preterms born in a level III perinatal medicine unit of a French university hospital were enrolled in a prospective observational study. Measurement of the procalcitonin umbilical cord blood level was performed at birth. After hospitalization, surviving infants were enrolled in the regional follow-up program. Outcome data were recorded on standardized questionnaires. The main outcome measures were neonatal mortality and impaired functional outcome at 2years of corrected age. The terciles of procalcitonin levels were calculated. Preterm infants of the third tercile were defined as infants with elevated procalcitonin. Among the 237 infants, 13 (5.5%) died during the neonatal period, 20 (8.4%) were lost to follow-up, and 31 (13.1%) were classified as having an impaired functional outcome. After adjustment, elevated cord blood procalcitonin (>0.33ng/ml) was significantly associated with an increase in mortality (adjusted odds ratio [aOR] = 8.3 [1.4-48]; p = 0.018), but not with the 2-year impaired functional outcome (aOR = 1.0 [0.4-2.5]; p = 0.93). Elevated umbilical blood cord procalcitonin concentration is an independent risk factor of mortality in preterm infants at less than 33weeks' gestation.

599: Differential responses to Toll-like receptor (TLR) ligands in Hofbauer cells (HBCs: placental macrophages), placental fibroblasts (FIBs) and human umbilical vein endothelial cells (HUVECs): implications for the genesis of fetal inflammatory response syndrome (FIRS)

599: Differential responses to Toll-like receptor (TLR) ligands in Hofbauer cells (HBCs: placental macrophages), placental fibroblasts (FIBs) and human umbilical vein endothelial cells (HUVECs): implications for the genesis of fetal inflammatory response syndrome (FIRS)

Choriodecidual group B streptococcal inoculation induces fetal lung injury without intra-amniotic infection and preterm labor in Macaca nemestrina.

BackgroundEarly events leading to intrauterine infection and fetal lung injury remain poorly defined, but may hold the key to preventing neonatal and adult chronic lung disease. Our objective was to establish a nonhuman primate model of an early stage of chorioamnionitis in order to determine the time course and mechanisms of fetal lung injury in utero.Methodology/Principal FindingsTen chronically catheterized pregnant monkeys (Macaca nemestrina) at 118–125 days gestation (term = 172 days) received one of two treatments: 1) choriodecidual and intra-amniotic saline (n = 5), or 2) choriodecidual inoculation of Group B Streptococcus (GBS) 1×106 colony forming units (n = 5). Cesarean section was performed regardless of labor 4 days after GBS or 7 days after saline infusion to collect fetal and placental tissues. Only two GBS animals developed early labor with no cervical change in the remaining animals. Despite uterine quiescence in most cases, blinded review found histopathological evidence of fetal lung injury in four GBS animals characterized by intra-alveolar neutrophils and interstitial thickening, which was absent in controls. Significant elevations of cytokines in amniotic fluid (TNF-α, IL-8, IL-1β, IL-6) and fetal plasma (IL-8) were detected in GBS animals and correlated with lung injury (p<0.05). Lung injury was not directly caused by GBS, because GBS was undetectable in amniotic fluid (∼10 samples tested/animal), maternal and fetal blood by culture and polymerase chain reaction. In only two cases was GBS cultured from the inoculation site in low numbers. Chorioamnionitis occurred in two GBS animals with lung injury, but two others with lung injury had normal placental histology.Conclusions/SignificanceA transient choriodecidual infection can induce cytokine production, which is associated with fetal lung injury without overt infection of amniotic fluid, chorioamnionitis or preterm labor. Fetal lung injury may, thus, occur silently without symptoms and before the onset of the fetal systemic inflammatory response syndrome.

Blood pH and gases in fetuses in preterm labor with and without systemic inflammatory response syndrome

Objective: Fetal hypoxemia has been proposed to be one of the mechanisms of preterm labor (PTL) and delivery. This may have clinical implications since it may alter: (i) the method/frequency of fetal surveillance and (ii) the indications and duration of tocolysis to an already compromised fetus. The aim of this study was to examine whether there is a difference in the fetal blood gas analysis [pH, PaO2 and base excess (BE)] and in the prevalence of fetal acidemia and hypoxia between: (i) patients in PTL who delivered within 72 hours vs. those who delivered more than 72 hours after cordocentesis and (ii) patients with fetal inflammatory response syndrome (FIRS) vs. those without this condition. Study design: Patients admitted with PTL underwent amniocentesis and cordocentesis. Ninety women with singleton pregnancies and PTL were classified according to (i) those who delivered within 72 hours (n = 30) and after 72 hours of the cordocentesis (n = 60) and (ii) with and without FIRS. FIRS was defined as a fetal plasma concentration of IL-6 > 11 pg/mL. Fetal blood gases were determined. Acidemia and hypoxemia were defined as fetal pH and PaO2 below the 5th percentile for gestational age, respectively. For comparisons between the two study groups, ΔpH and ΔPaO2 were calculated by adjusting for gestational age (Δ = observed value – mean for gestational age). Non-parametric statistics were employed. Results: No differences in the median Δ pH (−0.026 vs. −0.016), ΔPaO2 (0.25 mmHg vs. 5.9 mmHg) or BE (−2.4 vs. −2.6 mEq/L) were found between patients with PTL who delivered within 72 hours and those who delivered 72 hours after the cordocentesis (p > 0.05 for all comparisons). Fetal plasma IL-6 concentration was determined in 63% (57/90) of fetuses and the prevalence of FIRS was 28% (16/57). There was no difference in fetal pH, PaO2 and BE between fetuses with and without FIRS (p > 0.05 for all comparisons). Moreover, there was no difference in the rate of fetal acidemia between fetuses with and without FIRS (6.3 vs. 9.8%; p > 0.05) and fetal hypoxia between fetuses with or without FIRS (12.5 vs. 19.5%; p > 0.05). Conclusions: Our data do not support a role for acute fetal hypoxemia and metabolic acidemia in the etiology of PTL and delivery.

Chorioamnionitis and Chronic Lung Disease of Prematurity: A Path Analysis of Causality

Current evidence suggests that additional pathogenetic factors could play a role in the development of chronic lung disease of prematurity, other than mechanical ventilation and free radical injury. The introduction of the concept of "fetal inflammatory response syndrome" offers a new perspective on the pathogenesis of chronic lung disease of prematurity. New statistical approaches could be useful tools in evaluating causal relationships in the development of chronic morbidity in preterm infants. The aim of this study was to test a new statistical framework incorporating path analysis to evaluate causality between exposure to chorioamnionitis and fetal inflammatory response syndrome and the development of chronic lung disease of prematurity. We designed a prospective cohort study that included consecutively born premature infants less than 32 weeks of gestation whose placentas were collected for histological analysis. Histological chorioamnionitis, clinical data, and neonatal outcomes were related to chronic lung disease. Along with standard statistical methods, a path analysis was performed to test the relationship between histological chorioamnionitis, gestational age, mechanical ventilation, and development of chronic lung disease of prematurity. Among the newborns enrolled in the study, 69/189 (36%) had histological chorioamnionitis. Of those with histological chorioamnionitis, 28/69 (37%) were classified as having fetal inflammatory response syndrome, according to the presence of severe chorioamnionitis and funisitis. Histological chorioamnionitis was associated with a lower birth weight, shorter gestation, higher frequency of patent ductus arteriosus, greater use of surfactant, and higher frequency of chronic lung disease of prematurity. Severe chorioamnionitis and funisitis were significantly associated with lower birth weight, lower gestational age, lower Apgar score at 5 minutes, more frequent use of mechanical ventilatory support and surfactant, as well as higher frequency of patent ductus arteriosus and chronic lung disease. The results of the path analysis showed that fetal inflammatory response syndrome has a significant direct (0.66), indirect (0.11), and overall (0.77) effect on chronic lung disease. This study demonstrated a strong positive correlation between exposure of the fetus to a severe inflammatory response and the development of chronic lung disease of prematurity.

Myocardial Response to Chorioamnionitis in Preterm Fetal Sheep

Background and aims: Exposure of the fetus to antenatal inflammation can occur from chorioamnionitis which may progress to a systemic fetal inflammatory response syndrome (FIRS). It is not known whether the fetal myocardium participates in this FIRS. We hypothesized that the myocardium would have indicators of inflammation and injury.Methods: Fetal sheep were exposed to intra-amniotic (IA) endotoxin or saline 2d or 7d before preterm delivery at 124 ± 1 days gestational age of gestation (term 150 days). Protein and mRNA levels in hearts were determined by real-time PCR, Western blotting and immunohistochemistry.Results: After IA exposure 2d before delivery, mRNA decreased compared to controls (100%) for hypoxia-inducible factor (HIF)-1α (18%), inducible NO-synthase (iNOS) (5%), toll-like receptor 2 (TLR2) (12%) and TLR4 (16%). Interleukin (IL)-6 mRNA increased to 146% after 2d and 390% after 7d. Protein levels of phosphorylated signal transducer and activator of transcription (STAT)-3 were decreased to 37% after 7d. HIF-1α protein level in cardiomyocytes decreased to 17 % after 2d. Fetal plasma level of cardiac troponin I decreased at both time points (21%, 47%).Conclusions: Acute (2d) endotoxin-induced chorioamnionitis suppressed mediators of cellular inflammatory response whereas a 7d exposure to endotoxin caused mild cardiac inflammation. There was no indication of severe cardiac injury.

White Blood Cells Count as a Predictor of Bronchopulmonary Dysplasia in VLBW Infants with Histological Chorioamnionitis

Background and Aims: Chorioamnionitis is an antenatal inflammatory state: it can induce fetal inflammatory response syndrome and postnatal leukemoid reaction which have been associated to chronic lung disease of preterm infants. The aim of this study was to evaluate if the measure of neonatal WBC, a widely used marker of inflammation, may predict bronchopulmonary dysplasia (BPD) in VLBW infants with histological chorioamnionitis (HCAM).

Assessment of Stages of Fetal Inflammatory Response Syndrome by Early Postnatal Interleukin-6 and C-Reactive Protein Levels in Preterm Infants

Assessment of Stages of Fetal Inflammatory Response Syndrome by Early Postnatal Interleukin-6 and C-Reactive Protein Levels in Preterm Infants

Hematologic profile of the fetus with systemic inflammatory response syndrome

The fetal inflammatory response syndrome (FIRS) is associated with impending onset of preterm labor/delivery, microbial invasion of the amniotic cavity and increased perinatal morbidity. FIRS has been defined by an elevated fetal plasma interleukin (IL)-6, a cytokine with potent effects on the differentiation and proliferation of hematopoietic precursors. The objective of this study was to characterize the hematologic profile of fetuses with FIRS. Fetal blood sampling was performed in patients with preterm prelabor rupture of membranes and preterm labor with intact membranes (n=152). A fetal plasma IL-6 concentration ≥ 11 pg/mL was used to define FIRS. Hemoglobin concentration, platelet count, total white blood cell (WBC) count, differential count, and nucleated red blood cell (NRBC) count were obtained. Since blood cell count varies with gestational age, the observed values were corrected for fetal age by calculating a ratio between the observed and expected mean value for gestational age. 1) The prevalence of FIRS was 28.9% (44/152); 2) fetuses with FIRS had a higher median corrected WBC and corrected neutrophil count than those without FIRS (WBC: median 1.4, range 0.3-5.6, vs. median 1.1, range 0.4-2.9, P=0.001; neutrophils: median 3.6, range 0.1-57.5, vs. median 1.8, range 0.2-13.9, P<0.001); 3) neutrophilia (defined as a neutrophil count >95th centile of gestational age) was significantly more common in fetuses with FIRS than in those without FIRS (71%, 30/42, vs. 35%, 37/105; P<0.001); 4) more than two-thirds of fetuses with FIRS had neutrophilia, whereas neutropenia was present in only 4.8% (2/42); 5) FIRS was not associated with detectable changes in hemoglobin concentration, platelet, lymphocyte, monocyte, basophil or eosinophil counts; and 6) fetuses with FIRS had a median corrected NRBC count higher than those without FIRS. However, the difference did not reach statistical significance (NRBC median 0.07, range 0-1.3, vs. median 0.04, range 0-2.3, P=0.06). The hematologic profile of the human fetus with FIRS is characterized by significant changes in the total WBC and neutrophil counts. The NRBC count in fetuses with FIRS tends to be higher than fetuses without FIRS.

Myocardial Response in Preterm Fetal Sheep Exposed to Systemic Endotoxinaemia

Exposure of the fetus to antenatal inflammation can occur from chorioamnionitis, which may progress to a fetal inflammatory response syndrome (FIRS) and to fetal sepsis. We tested whether the fetal myocardium responded to systemic Gram-negative endotoxinaemia. We hypothesized that the myocardium would respond to inflammation by changes in hypoxia-inducible factor-α (HIF-1α), inducible NO-synthase (iNOS), Toll-like receptors 2 and 4 (TLR2 and TLR4), IL-6, and phosphorylated signal transducer and activator of transcription-3 (pSTAT3). To model systemic endotoxinaemia, fetal sheep were exposed to Gram-negative endotoxin or saline i.v. 3 d before preterm delivery at 113 d of gestation (term = 147 d). All endotoxin-exposed animals developed cardiac dysfunction within these 72 h. Cardiac mRNA and protein levels of HIF-1α and TLR2 and TLR4 mRNA increased, whereas STAT3 phosphorylation decreased significantly. IL-6 and iNOS mRNA remained unchanged. Fetal systemic endotoxinaemia induced myocardial inflammation by activating TLR2 and 4. The following cardiac dysfunction seems not to be mediated via cardiac iNOS.

Pulmonary and systemic inflammatory responses to intra-amniotic IL-1α in fetal sheep

Clinical and epidemiological studies implicate IL-1 as an important mediator of perinatal inflammation. We tested the hypothesis that intra-amniotic IL-1α would induce pulmonary and systemic fetal inflammatory responses. Sheep with singleton fetuses were given an intra-amniotic injection of recombinant sheep IL-1α (100 μg) and were delivered 1, 3, or 7 days later, at 124 ± 1 days gestation ( n=5–8/group). A separate group of sheep were given two intra-amniotic IL-1α injections (100 μg dose each): 7 days and again 1 day prior to delivery. IL-1α induced a robust increase in monocytes, neutrophils, lymphocytes, and IL-8 protein in bronchoalveolar lavage fluid. H2O2secretion was increased in inflammatory cells isolated from lungs of IL-1α-exposed lambs upon LPS challenge in vitro compared with control monocytes. T lymphocytes were recruited to the lung. IL-1β, cyclooxygenase-1, and cyclooxygenase-2 mRNA expression increased in the lung 1 day after intra-amniotic IL-1α exposure. Lung volumes increased 7 days after intra-amniotic IL-1α exposure, with minimal anatomic changes in air space morphology. The weight of the posterior mediastinal lymph node draining the lung and the gastrointestinal tract doubled, inducible nitric oxide synthase (NOSII)-positive cells increased, and Foxp3-positive T-regulatory lymphocytes decreased in the lymph node after IL-1α exposure. In the blood, neutrophil counts and plasma haptoglobin increased after IL-1α exposure. Compared with a single exposure, exposure to intra-amniotic IL-1α 7 days and again 1 day before delivery had a variable effect (increases in some inflammatory markers, but not pulmonary cytokines). IL-1α is a potent mediator of the fetal inflammatory response syndrome.

Neutrophil defensins but not interleukin‐6 in vaginal fluid after preterm premature rupture of membranes predict fetal/neonatal inflammation and infant neurological impairment

To determine whether neutrophil defensins (HNP1-3) and interleukin-6 (IL-6) in vaginal fluid after preterm premature rupture of membranes predict fetal inflammatory response syndrome (FIRS), neurological impairment or chorioamnionitis. Prospective study. Tertiary referral university hospital. Forty-two patients with preterm premature rupture of membranes at <32 weeks. Levels of HNP1-3 and IL-6 were measured in vaginal fluid obtained by swabs. Mann-Whitney U-test was used to compare HNP1-3 and IL-6 levels in groups with vs. without FIRS, infant death or neurological impairment, and chorioamnionitis (p<0.05 significant). Logistic regression was used to control for potential confounders. Diagnostic accuracies of HNP1-3 and IL-6 were determined by receiver operator characteristics analysis. Fetal inflammatory response syndrome was defined as neonatal inflammation within 72 hours postpartum. Neurological impairment was defined as motor and/or tone abnormalities at one year of corrected age. Chorioamnionitis was diagnosed histologically. Levels of HNP1-3, but not IL-6, were higher in 12 cases of FIRS (p=0.019 and p=0.256, respectively). Levels of HNP1-3, but not IL-6, were higher in 14 cases of infant death or neurological impairment (p=0.015 and p=0.100, respectively) and, when only survivors were analyzed, in nine cases of neurological impairment (p=0.030 and p=0.187, respectively). Levels of HNP1-3 and IL-6 were higher in 29 cases of chorioamnionitis (p=0.005 and p=0.003, respectively). The differences remained significant after adjustment for gestational age. Levels of HNP1-3 predicted FIRS, infant death or neurological impairment and chorioamnionitis with an area under the curve of 0.75, 0.79 and 0.78, respectively. Elevated vaginal fluid HNP1-3 and IL-6 levels are associated with histological chorioamnionitis. Elevated HNP1-3 can also identify FIRS and predict infant death or neurological impairment.

The role of granulocyte colony-stimulating factor in the neutrophilia observed in the fetal inflammatory response syndrome.

Fetal neutrophilia is present in two-thirds of cases with the fetal inflammatory response syndrome (FIRS). The mechanisms responsible for this finding have not been elucidated. Granulocyte colony-stimulating factor (G-CSF) is the primary physiologic regulator of neutrophil production and plays a key role in the rapid generation and release of neutrophils in stressful conditions (i.e., infection). The objective of this study was to determine: 1) whether FIRS was associated with changes in fetal plasma G-CSF concentrations; and 2) if fetal plasma G-CSF concentrations correlated with fetal neutrophil counts, chorioamnionitis, neonatal morbidity/mortality and cordocentesis-to-delivery interval. Percutaneous umbilical cord blood sampling was performed in a population of patients with preterm labor (n=107). A fetal plasma interleukin-6 (IL-6) concentration >11 pg/mL was used to define FIRS. Cord blood G-CSF was measured by a sensitive and specific immunoassay. An absolute neutrophil count was determined and corrected for gestational age. Receiver operating characteristic (ROC) curve, survival analysis and Cox proportional hazard model were employed. 1) G-CSF was detected in all fetal blood samples; 2) fetuses with FIRS had a higher median fetal plasma G-CSF concentration than those without FIRS (P<0.001); 3) a fetal plasma G-CSF concentration ≥134 pg/mL (derived from an ROC curve) was associated with a shorter cordocentesis-to-delivery interval, a higher frequency of chorioamnionitis (clinical and histological), intra-amniotic infection, and composite neonatal morbidity/mortality than a fetal plasma concentration below this cut-off; and 4) a fetal plasma G-CSF concentration ≥134 pg/mL was associated with a shorter cordocentesis-to-delivery interval (hazard ratio 3.2; 95% confidence interval 1.8-5.8) after adjusting for confounders. 1) G-CSF concentrations are higher in the peripheral blood of fetuses with FIRS than in fetuses without FIRS; and 2) a subset of fetuses with FIRS with elevated fetal plasma G-CSF concentrations are associated with neutrophilia, a shorter procedure-to-delivery interval, chorio-amnionitis and increased perinatal morbidity and mortality.

13: IL6 antagonist: a dangerous solution for mothers and pups in animal model of fetal inflammatory response syndrome (FIRS) induced by LPS

The fetal inflammatory response syndrome (FIRS) characterized by an elevation of fetal plasma IL6, is a risk factor for the development of long-term neurological sequel. We hypothesized that blocking the inflammatory cascade with anti-IL6Ra could prevent neurological lesions associated with in utero inflammation.

NICU admission hypothermia, chorioamnionitis, and cytokines

To determine whether neonatal intensive care unit (NICU) admission hypothermia is associated with an intrauterine inflammatory response. We analyzed a cohort of 309 very low birthweight infants to determine relationships between admission hypothermia, chorioamnionitis, and serum and cerebrospinal fluid (CSF) interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. Admission hypothermia <36°C occurred in 72% of patients <26 weeks and 44% of patients ≥26 weeks gestational age. NICU admission hypothermia was not associated with histologic chorioamnionitis or with elevated serum cytokine concentrations. CSF IL-6 concentrations ≥6.3 pg/mL were associated with admission hypothermia in infants <26 weeks' gestation. Clinical chorioamnionitis was associated with a lower risk of admission hypothermia, while cesarean section delivery was associated with increased risk. NICU admission hypothermia is common among preterm infants and is not associated with the fetal inflammatory response syndrome. Hypothermia is less common in the setting of clinical chorioamnionitis and more common in cesarean section deliveries, identifying two groups in whom extra attention to appropriate thermoregulation is warranted.