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Background: The risk of various complications, such as neonatal death, early onset sepsis, and chronic lung disease, is increased in infants born to mothers with chorioamnionitis (CAM). However, predicting the diagnosis of histological CAM (hCAM) in the early postnatal period is challenging for clinicians due to pathological considerations. Therefore, an early diagnostic tool for hCAM is needed. Gastric fluid at birth is considered a suitable biomarker for predicting the intrauterine environment because most of its components are from amniotic fluid, and the sampling technique is less invasive. This study aimed to evaluate the clinical utility of cytokines in the gastric fluid of preterm infants at birth as predictors of hCAM., Methods: We retrieved gastric fluid and serum from 21 preterm infants with a gestational age of ≤ 32 weeks within 1 h after birth and used cytometric bead array to measure the concentrations of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha, and interferon-gamma. We compared the cytokine concentrations in the gastric fluid and serum of the preterm infants born to mothers with or without hCAM., Results: The gastric fluid, serum IL-6, and serum IL-10 concentrations were significantly higher in the hCAM group than that in the non-hCAM group. The best cutoff values for predicting hCAM was > 2,855 pg/mL and > 315 pg/mL for IL-6 in the gastric fluid and serum, respectively. Receiver operating characteristic curves showed that gastric fluid IL-6 concentrations correlated more strongly with the presence of hCAM than serum IL-6 concentrations., Conclusion: IL-6 in the gastric fluid at birth may be a more promising biomarker for predicting the presence of hCAM than that in serum. IL-6 concentration analysis in the gastric fluid at birth might help to diagnose hCAM immediately after birth and improve the prognosis of preterm infants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Preterm infants are at high risk of infection and have distinct pathogen recognition responses. Suggested mechanisms include soluble mediators that enhance cellular levels of cAMP. The aim of this study was to assess the relationship between blood cAMP concentrations and TLR-mediated cytokine production in infants during the first month of life., Methods: Cord and serial peripheral blood samples (days of life 1-28) were obtained from a cohort of very preterm (<30 weeks' gestational age) and term human infants. Whole-blood concentrations of cAMP and FSL-1 and LPS in vitro stimulated cytokine concentrations were measured by ELISA and multiplex bead assay., Results: cAMP concentrations were higher in cord than in peripheral blood, higher in cord blood of female preterm infants, and lower at Days 1 and 7 in infants exposed to chorioamnionitis, even after adjusting for leukocyte counts. TLR2 and TLR4-mediated TNF-α, IL-1β, IL-6, IL-12p70, and IL-10 production in vitro increased over the first month of life in preterm infants and were positively correlated with leukocyte-adjusted cAMP levels and reduced by exposure to chorioamnionitis., Conclusions: The ontogeny of blood cAMP concentrations and associations with chorioamnionitis and TLR-mediated production of cytokines suggest that this secondary messenger helps shape distinct neonatal pathogen responses in early life.

Introduction: Preterm birth is a heterogeneous phenotype, with placental abnormalities underlying many cases. The etiology of preterm births that occur in the absence of placental abnormalities, however, remain enigmatic and we considered that early pregnancy biomarkers may provide clues., Methods: Women from a hospital-based cohort (2008-2012, n = 397) were randomly selected within 6 strata of term and preterm birth with and without placental decidual vasculopathy (arteriopathy), intrauterine inflammation/infection (acute chorioamnionitis), or no lesions. Lipids and inflammatory markers were analyzed in first trimester samples (12.5 ± 0.6 weeks) and related to outcome groups (referent, term births with no lesions). Factor analysis then clustered analytes and related these to preterm birth groups, adjusted for covariates and stratified by pre-pregnancy obesity., Results: Three biomarker patterns were identified. Immune activation cytokines (33% of the variance) were associated with preterm birth with no lesions (aOR 1.5, 95%CI 1.1-2.1), particularly among obese women. In contrast, inflammatory chemokines (9% of variance) were associated with term and preterm vasculopathy among non-obese women (aOR 2.6 [1.3, 4.7] and 2.0 [1.1, 3.0], respectively)., Discussion: The early pregnancy maternal immune profile is related to preterm births classified according to placental lesions, and these associations vary according to obesity status., Competing Interests: Declaration of competing interest There are no conflicts to report., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the relationships between serum cytokine concentrations and chorioamnionitis (CAM) and CAM-related bronchopulmonary dysplasia (BPD) in premature infants., Methods: Serum was collected at 0 and 7 days after birth from 36 premature infants born at <32 weeks of gestation. We examined the relationships between 30 cytokine concentrations and CAM, BPD, and other perinatal factors., Results: On day 0, GM-CSF, IL-15, IL-17, IL-2, IL-2R, VEGF, and MIG concentrations were significantly higher in the CAM group (n = 17) than in the non-CAM group (n = 19). These concentrations had decreased by day 7 and were similar in both groups. The IL-12p70 concentration on day 0 was significantly lower in the BPD group (n = 16) than in the non-BPD group (n = 15). BPD incidence was similar between the CAM and non-CAM groups., Conclusions: These data support the hypothesis that intrauterine inflammation is not a primary risk factor for BPD. The immunological environment at birth or soon after, rather than intrauterine fetal inflammation (e.g., CAM), is a primary risk factor for BPD onset in preterm infants. Decreased inflammatory responses are particularly relevant, as indicated by the relationship between BPD and low serum IL-12p70 concentrations on day 0.

Introduction: Fever is a major criterion for clinical chorioamnionitis; yet, many patients with intrapartum fever do not have demonstrable intra-amniotic infection. Some cytokines, such as interleukin (IL)-1, IL-6, interferon-gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α), can induce a fever. The objective of this study was to determine whether maternal plasma concentrations of cytokines could be of value in the identification of patients with the diagnosis of clinical chorioamnionitis at term who have microbial-associated intra-amniotic inflammation., Methods: A retrospective cross-sectional study was conducted, including patients with clinical chorioamnionitis at term (n=41; cases) and women in spontaneous labor at term without clinical chorioamnionitis (n=77; controls). Women with clinical chorioamnionitis were classified into three groups according to the results of amniotic fluid culture, broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS), and amniotic fluid IL-6 concentration: 1) no intra-amniotic inflammation; 2) intra-amniotic inflammation without detectable microorganisms; or 3) microbial-associated intra-amniotic inflammation. The maternal plasma concentrations of 29 cytokines were determined with sensitive and specific V-PLEX immunoassays. Nonparametric statistical methods were used for analysis, adjusting for a false discovery rate of 5%., Results: 1) The maternal plasma concentrations of pyrogenic cytokines (IL-1β, IL-2, IL-6, IFN-γ, and TNF-α) were significantly higher in patients with clinical chorioamnionitis at term than in those with spontaneous term labor without clinical chorioamnionitis; 2) the maternal plasma concentrations of cytokines were not significantly different among the three subgroups of patients with clinical chorioamnionitis (intra-amniotic inflammation with and without detectable bacteria and those without intra-amniotic inflammation); and 3) among women with the diagnosis of clinical chorioamnionitis, but without evidence of intra-amniotic inflammation, the maternal plasma concentrations of pyrogenic cytokines were significantly higher than in patients with spontaneous labor at term. These observations suggest that a fever can be mediated by increased circulating concentrations of these cytokines, despite the absence of a local intra-amniotic inflammatory response., Conclusions: 1) The maternal plasma concentrations of pyrogenic cytokines (e.g. IL-1β, IL-2, IL-6, IFN-γ, and TNF-α) are higher in patients with intra-partum fever and the diagnosis of clinical chorioamnionitis at term than in those in spontaneous labor at term without a fever; and 2) maternal plasma cytokine concentrations have limited value in the identification of patients with bacteria in the amniotic cavity. Accurate assessment of the presence of intra-amniotic infection requires amniotic fluid analysis.

Objective: Microbial invasion of the fetus due to intra-amniotic infection can lead to a systemic inflammatory response characterized by elevated concentrations of cytokines in the umbilical cord plasma/serum. Clinical chorioamnionitis represents the maternal syndrome often associated with intra-amniotic infection, although other causes of this syndrome have been recently described. The objective of this study was to characterize the umbilical cord plasma cytokine profile in neonates born to mothers with clinical chorioamnionitis at term, according to the presence or absence of bacteria and/or intra-amniotic inflammation., Materials and Methods: A cross-sectional study was conducted, including patients with clinical chorioamnionitis at term (n=38; cases) and those with spontaneous term labor without clinical chorioamnionitis (n=77; controls). Women with clinical chorioamnionitis were classified according to the results of amniotic fluid culture, broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) and amniotic fluid interleukin (IL)-6 concentration into three groups: 1) no intra-amniotic inflammation; 2) intra-amniotic inflammation without detectable microorganisms; or 3) microbial-associated intra-amniotic inflammation. A fetal inflammatory response syndrome (FIRS) was defined as an umbilical cord plasma IL-6 concentration >11 pg/mL. The umbilical cord plasma concentrations of 29 cytokines were determined with sensitive and specific V-PLEX immunoassays. Nonparametric statistical methods were used for analysis, adjusting for a false discovery rate of 5%., Results: 1) Neonates born to mothers with clinical chorioamnionitis at term (considered in toto) had significantly higher median umbilical cord plasma concentrations of IL-6, IL-12p70, IL-16, IL-13, IL-4, IL-10 and IL-8, but significantly lower interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF)-α concentrations than neonates born to mothers with spontaneous term labor without clinical chorioamnionitis; 2) neonates born to mothers with clinical chorioamnionitis at term but without intra-amniotic inflammation had higher concentrations of IL-6, IL-12p70, IL-13, IL-4, IL-5, and IL-8, but lower IFN-γ, than neonates not exposed to clinical chorioamnionitis, suggesting that maternal fever in the absence of intra-amniotic inflammation leads to a change in the fetal cytokine network; 3) there were significant, positive correlations between maternal and umbilical cord plasma IL-6 and IL-8 concentrations (IL-6: Spearman correlation=0.53; P<0.001; IL-8: Spearman correlation=0.42; P<0.001), consistent with placental transfer of cytokines; 4) an elevated fetal plasma IL-6 (>11 pg/mL), the diagnostic criterion for FIRS, was present in 21% of cases (8/38), and all these neonates were born to mothers with proven intra-amniotic infection; and 5) FIRS was associated with a high concentration of umbilical cord plasma IL-8, IL-10 and monocyte chemoattractant protein (MCP)-1., Conclusions: Neonates born to mothers with clinical chorioamnionitis at term had higher concentrations of umbilical cord plasma cytokines than those born to mothers without clinical chorioamnionitis. Even neonates exposed to clinical chorioamnionitis but not to intra-amniotic inflammation had elevated concentrations of multiple cytokines, suggesting that intrapartum fever alters the fetal immune response.

Background: Preterm prelabor rupture of the fetal membranes (PPROM) is a significant contributor to the morbidity and mortality of preterm birth, particularly in the setting of chorioamnionitis. No sensitive or specific diagnostic or predictive test currently exists for the accurate diagnosis of chorioamnionitis. Our aim was to measure messenger RNA (mRNA) coding cytokines in the maternal blood and examine whether they were increased in association with chorioamnionitis at delivery., Methods/results: We performed a prospective cohort study of women recruited with PPROM at a mean gestational age of 28.9 weeks at risk of developing chorioamnionitis. Blood was sampled from participants, and the expression of mRNA coding for proinflammatory genes was measured in women with and without chorioamnionitis at the time of delivery as well as gestation-matched healthy controls. Expression was measured using quantitative polymerase chain reaction (PCR) and also digital PCR. Interleukin 1β (IL1B) mRNA expression in maternal blood was elevated in women with chorioamnionitis compared to gestation-matched controls. Importantly, among women admitted with PPROM, digital PCR confirmed a significant increase in IL1B expression in maternal blood in women with chorioamnionitis compared to women without chorioamnionitis. Polymerase chain reaction array revealed that CD14, nuclear factor of κ light polypeptide gene enhancer in B-cells 1 (NFKB1), and tumor necrosis factor receptor super family-interacting serine-threonine kinase 1 mRNA were significantly increased in women with chorioamnionitis compared to controls. Digital PCR confirmed that NFKB1 mRNA was significantly increased in patients with chorioamnionitis compared to controls and that CD14 levels increased over time in patients with PPROM having chorioamnionitis., Conclusion: Measuring circulating proinflammatory mRNA in women with PPROM may distinguish those with chorioamnionitis from those without, in turn providing better targeted therapies and appropriate timing of delivery., (© The Author(s) 2015.)

Background: Inflammatory mechanisms involved in the onset and progression of labor at term may affect the fetal compartment impacting neonatal outcomes., Study Design: Umbilical cord blood collected from umbilical cords after delivery of the fetus and again after delivery of the placenta in low-risk non-laboring and laboring patients was analyzed for blood gases/pH and multiple cytokines., Results: Umbilical cord levels of IL-6, IL-8 and IL-10 were increased 6, 2 and 1.5 fold, respectively, in laboring patients without placental inflammation, and for IL-6 and IL-8 a further 12 and 6 fold, respectively, in laboring patients showing histologic chorioamnionitis, but with no evident effect of nuchal cord with FHR decelerations, fetal acidemia, nor of labor duration. For laboring patients, umbilical vein levels of IL-10 and MIP-1α were increased compared to arterial levels indicating net flux from the placenta, while umbilical artery levels of IL-6 and IL-8 were increased compared to venous levels indicating net flux from fetal sources. Placental cord levels of IL-6, IL-10, MIP-1α and MIP-1β were also increased compared to respective umbilical cord levels, confirming placental release of these cytokines into cord blood after delivery of the fetus., Conclusion: Labor in low-risk patients at term will result in increased cytokines in umbilical cord blood and moreso when associated with histologic chorioamnionitis with the potential to impact neonatal outcomes. IL-6 and IL-8 as the primary cytokines increased in cord blood may act synergistically in promoting the inflammatory response with labor, and are likely released from both placental and fetal tissues contributing to widespread distribution through the fetal circulation., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

Little evidence is available to document that mechanical ventilation is an antecedent of systemic inflammation in preterm humans. We obtained blood on postnatal day 14 from 726 infants born before the 28th week of gestation and measured the concentrations of 25 inflammation-related proteins. We created multivariable models to assess the relationship between duration of ventilation and protein concentrations in the top quartile. Compared to newborns ventilated for fewer than 7 days (N=247), those ventilated for 14 days (N=330) were more likely to have elevated blood concentrations of pro-inflammatory cytokines (IL-1β, TNF-α), chemokines (IL-8, MCP-1), an adhesion molecule (ICAM-1), and a matrix metalloprotease (MMP-9), and less likely to have elevated blood concentrations of two chemokines (RANTES, MIP-1β), a matrix metalloproteinase (MMP-1), and a growth factor (VEGF). Newborns ventilated for 7-13 days (N=149) had systemic inflammation that approximated the pattern of newborns ventilated for 14 days. These relationships were not confounded by chorioamnionitis or antenatal corticosteroid exposure, and were not altered appreciably among infants with and without bacteremia. These findings suggest that 2 weeks of ventilation are more likely than shorter durations of ventilation to be accompanied by high blood concentrations of pro-inflammatory proteins indicative of systemic inflammation, and by low concentrations of proteins that might protect from inflammation-mediated organ injury., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To determine whether neonatal intensive care unit (NICU) admission hypothermia is associated with an intrauterine inflammatory response., Methods: 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., Results: 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., Conclusions: 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.

Intrauterine inflammation is followed by elevated concentrations of inflammation-related proteins in the newborn's blood. Many of these proteins have short half-lives. The persistence of this postnatal inflammation has not previously been investigated. In a sample of 834 infants born before the 28th week of gestation, 12% (103) had grade 1 or 2, and 17% (142) had grade 3, 4, or 5 umbilical cord inflammation. Concentrations of nine proteins previously shown to be associated with umbilical cord inflammation at birth were measured on the first postnatal day and at two weekly intervals after birth. We evaluated the hypothesis that children who had umbilical cord inflammation were no more likely than others to have elevated concentrations of inflammation-related proteins in postnatal blood. The concentrations of seven of the nine proteins [C-reactive protein (CRP), myeloperoxidase (MPO), IL1β, IL8, TNFα, intercellular adhesion molecule-1 (ICAM3), and matrix metalloproteinase (MMP9)] showed a tendency to be elevated on day 7 among infants with funisitis. Adjusting for gestational age, growth restriction, and three postnatal exposures (ventilation on day 7, presumed and definite early bacteremia, and Bell stage III necrotizing endocolitis) did not diminish the elevated odds ratios of concentrations in the top quartile (for gestational age and day the specimen was obtained) of MPO, IL1β, TNFα, IL8, ICAM3, and MMP9. The persistence of a relationship between umbilical cord inflammation and elevated blood concentrations of inflammation-related proteins on postnatal day 7 suggests the existence of phenomena that contribute to a reinforcement loop and thereby sustained systemic inflammation., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

Objective: To evaluate the effects of a neutrophil elastase inhibitor, sivelestat sodium hydrate, in a sheep model of intra-amniotic infection(IAI) induced by lipopolysaccharide (LPS) injected into the intra-amniotic compartment., Methods: We examined 15 chronically instrumented ewes, the ewes were assigned randomly as group A (five ewes) administered an antibiotic after LPS administration, group B (five ewes) administered a neutrophil elastase inhibitor (0.2 mg/kg/h) with an antibiotic after LPS administration, and group C (five ewes) a sham operation group. Uterine contraction was evaluated by fetal tracheal pressure and concentrations of PGE2, IL-6, IL-8, TNF-α in maternal and fetal blood before and after LPS administration were measured chronologically., Results: (1) All ewes of group A delivered within 72  h, but only one ewe of group B delivered. Uterine contraction of group B was suppressed about 60% in comparison with group A. (2) Maternal blood concentrations of PGE2, IL-6, IL-8, and TNF-α level of group A increased chronologically and when compared with groups B and C the increase was significantly higher. (3) There were no significant changes in the fetal blood cytokines in any of the three groups., Conclusion: Administration of neutrophil elastase inhibitor might suggest a useful strategy to prevent premature delivery resulting from intrauterine infection.

Objective: The goal was to develop multivariate logistic regression models for the outcome of bronchopulmonary dysplasia and/or death at postmenstrual age of 36 weeks by using clinical and cytokine data from the first 28 days., Methods: For 1067 extremely low birth weight infants in the Neonatal Research Network of the National Institute of Child Health and Human Development, levels of 25 cytokines were measured in blood collected within 4 hours after birth and on days 3, 7, 14, and 21. Stepwise regression analyses using peak levels of the 25 cytokines and 15 clinical variables identified variables associated with bronchopulmonary dysplasia/death. Multivariate logistic regression analysis was performed for bronchopulmonary dysplasia/death by using variables selected through stepwise regression. Similar analyses were performed by using average cytokine values from days 0 to 21, days 0 to 3, and days 14 to 21., Results: Of 1062 infants with available data, 606 infants developed bronchopulmonary dysplasia or died. On the basis of results from all models combined, bronchopulmonary dysplasia/death was associated with higher concentrations of interleukin 1beta, 6, 8, and 10 and interferon gamma and lower concentrations of interleukin 17, regulated on activation, normal T cell expressed and secreted, and tumor necrosis factor beta. Compared with models with only clinical variables, the addition of cytokine data improved predictive ability by a statistically significant but clinically modest magnitude., Conclusions: The overall cytokine pattern suggests that bronchopulmonary dysplasia/death may be associated with impairment in the transition from the innate immune response mediated by neutrophils to the adaptive immune response mediated by T lymphocytes.

Objective: To evaluate the influence of chorioamnionitis (CA) on plasma cytokines and the cytokine-associated risk of bronchopulmonary dysplasia (BPD) during the perinatal period., Study Design: Eleven cytokines from 128 very low gestational age infants were analyzed from cord blood and from plasma at ages 1 day and 7 days after birth. The diagnosis of CA was based on histology of the placenta, fetal membranes, and umbilical cord. Neonatal risk factors were recorded., Results: In the 48 infants born with CA, high concentrations of inflammatory cytokines in cord blood decreased during the first postnatal day. Inflammatory cytokines in cord blood was associated with the severity of CA. At 1 day after birth, the concentration of interleukin (IL)-8 predicted the risk of BPD. For the 75 infants born without CA, cytokine concentrations increased after birth. For the 128 infants born with or without CA, at 1 day after birth, the concentrations of IL-8, granulocyte colony-stimulating factor, and anti-inflammatory IL-10 were associated with the risk of BPD, after adjustment for the duration of gestation and severity of respiratory distress during the first day., Conclusions: In infants exposed to CA, insufficient inhibition of high fetal inflammatory cytokine response shortly after birth may increase the risk of BPD.

The purpose of this study was to determine cord blood cytokine levels and their relationship with morbidity and mortality in neonates with prolonged, premature rupture of membranes (PPROM). Forty two premature neonates of 29-35 weeks gestational age with PPROM exceeding 24 hours were considered as the PPROM group and simultaneously, 41 premature neonates without PPROM were considered as the control group. All the neonates were admitted to the Neonatology Unit for further evaluation of subsequent complications such as early neonatal sepsis, pneumonia, intraventicular haemorrhage (IVH), respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC) and chronic lung disease (CLD). Cord blood and mothers' blood samples were obtained during delivery in both groups and tested for IL-6, IL-8 and TNF-alpha levels. Twenty one percent of patients with PPROM had histological chorioamnionitis. The risk for developing early neonatal sepsis increased significantly in neonates whose mothers had histological chorioamnionitis (p < 0.05). There was a statistically significant relationship between PPROM and risk of developing NEC (p < 0.05); no significant increase was seen as regards early neonatal sepsis, IVH, RDS, pneumonia, or BPD. The mean IL-8 levels in cord blood and mothers' serum were significantly higher in the PPROM group (p < 0.001, p< 0.005). In addition, IL-6 levels found in mothers' serum were significantly higher than those found in the control group (p < 0.01). However, levels in cord blood were similar (p > 0.05). TNF-alpha levels were similar in both groups (p > 0.05). Neonates who developed NEC had higher IL-8 levels in their cord blood when compared to those without NEC (p < 0.05). In conclusion, the presence of PPROM increases the risk of chorioamnionitis. In addition, PPROM increases the risk of NEC, and patients who developed NEC had significantly higher cord blood IL-8 values. We may conclude that patients with PPROM and higher IL-8 levels in cord blood might be considered as at possible risk of NEC.

Objectives: To evaluate the role of interleukins (IL-1, IL-6), tumor necrosis factor alpha (TNFalpha) and for the first time interferon gamma (IFNgamma) and epidermal growth factor (EGF) in the pathogenesis of premature rupture of membranes (PROM) with and without confirmed intrauterine infection., Methods: Amniotic fluid was retrieved by transabdominal amniocentesis from 30 patients with PROM and 20 normal pregnant women with intact membranes of matched gestational age. Microbial state of amniotic cavity included culture for aerobic and anaerobic bacteria, mycoplasmas and ureaplasma whether or not clinical signs of chorioamnionitis were present. Maternal serum and amniotic fluid IL-1, IL-6, TNFalpha and IFNgamma concentrations were determined by the corresponding immunoradiometric assay, whereas EGF concentration was determined by a specific radioimmunoassay., Results: Nearly all cases of PROM with infection revealed elevated amniotic fluid cytokines (IL-1beta, IL-6, TNFalpha, IFNgamma, EGF) whereas half of them revealed elevated serum cytokines. In cases of PROM without confirmed infection, there were no significant changes of maternal serum cytokines, whereas two-thirds of them revealed elevated amniotic fluid cytokines., Conclusions: The rise of cytokines in amniotic fluid of cases of PROM with infection may represent: (a) enhanced macrophage activity for immunosurveillance of the fetus; (b) a preparatory step for the initiation of labor; and (c) a valuable tests for diagnosing chorioamnioitis. The mechanism responsible for PROM in the presence or absence of infection is likely to be of different nature.

Objective: To study 1. whether leucocyte infiltration in placenta tissues is associated with elevated umbilical serum levels of inflammatory mediators, and 2. whether leucocyte infiltration in the presence of neonatal disease is associated with additional increase in mediator levels., Setting: University hospital., Population: Two groups of women with either normal delivery (n = 82) or delivery complicated by prolonged rupture of the membranes, clinical signs of intrauterine infection or preterm labour (n = 139)., Methods: Umbilical cord blood and placenta tissues were collected after delivery. Placentas were classified as non-inflamed (i.e. without leucocyte infiltration, n = 74), or as mild (n = 84), or severe chorioamnionitis (n = 63). Mediator levels were compared between groups., Results: Severe chorioamnionitis was associated with elevated levels of tumour necrosis factor (TNF)alpha, interleukin (IL)-1beta, IL-6, IL-8, soluble TNF receptor p55 and p75, IL-1 receptor antagonist (IL-IRA), and C-reactive protein compared with non-inflamed placentas (all P < 0.05). No differences were found between mild chorioamnionitis and placentas without infiltration. In all, 49 babies suffered from various perinatal diseases, such as clinical sepsis, respiratory distress and asphyxia, and 172 were healthy. Severe chorioamnionitis with subsequent neonatal disease (n = 23) had higher levels of all mediators, except IL-1beta and C-reactive protein, than severe chorioamnionitis without neonatal disease (n = 40, all P < 0.01), but severe chorioamnionitis was also accompanied by a more intense and widely distributed leucocyte infiltration when neonatal disease developed., Conclusion: High grade leucocyte infiltration in placenta tissues is associated with elevated levels of TNFalpha, IL-1beta, IL-6, IL-8, p55, p75, IL-IRA and C-reactive protein in umbilical serum. The presence of neonatal disease is associated with advanced chorioamnionitis, and highly elevated levels of both pro- and antiinflammatory mediators in umbilical serum.

Unlabelled: The purpose of our study was to compare maternal serum levels of interleukin-6, interleukin-8, tumor necrosis factor-alpha and interferon-gamma in gravidities, during spontaneous term and preterm labor and their relation to histologic chorioamnionitis., Methods: We investigated 61 women: 10 in preterm labor, 36 in term labor and 15 healthy pregnant nonlabouring controls. Venous bloods for cytokines determinations were obtained during the first stage of labor and during routine screening tests. Titers of cytokines were measured by means of ELISA technique. All births after preterm deliveries were examined to establish histologic chorioamnionitis., Results: Serum levels of IL-6 and IL-8 were significantly elevated both in term (mean: IL-6: 17.5 +/- 58 pg/ml; IL-8: 148 +/- 215 pg/ml) and preterm labor (IL-6: 23 +/- 44 pg/ml; IL-8: 332 +/- 389 pg/ml) when compared to nonlabouring gravidities (IL-6: 5 +/- 7 pg/ml; IL-8: 14 +/- 11 pg/ml). IL-6 and IL-8 titers were statistically similar in term and preterm labors and in patients with and without histologic chorioamnionitis. TNF-alpha and IFN-gamma were not statistically analyzed because only a few patients had detectable serum levels of these cytokines., Conclusion: Serum levels of IL-6 and IL-8 in both: term and preterm labor are elevated in comparison to nonlabouring gravidities. The elevated levels of these cytokines are not connected with coexisting chorioamnionitis.