Presence Of Funisitis Research Articles

Two cases of Leukemoid reaction in premature infants caused by fetal inflammatory response syndrome

BackgroundFetal inflammatory response syndrome (FIRS) is a systemic inflammatory response caused by the activation of the fetal immune system. The serological diagnostic criterion for fetal inflammatory response syndrome is a cord blood interleukin-6 concentration that exceeds 11 pg/mL, while pathologic evidence indicates the presence of funisitis or chorionic vasculitis. It can affect all systems of the fetus. Alterations in patients’ hematopoietic system are primarily reflected by changes in peripheral blood leukocyte and neutrophil counts.Case presentationWe performed placental pathology to identify FIRS and showed two cases of neonatal leukemoid reaction caused by FIRS. These two babies’ alterations in hematopoietic system resolves spontaneously with the inflammation relief, without specific interventions. During the 16‑month and14- month follow‑up period, their motor and intellectual development was normal.Conclusions . Neonatal leukemoid reaction is a reactive disease characterized by abnormal blood parameters similar to those of leukemia, but not leukemia. It is an aberrant hematopoietic response that typically resolves spontaneously with cause relief without requiring specific interventions.

Association of Funisitis with Short-Term Outcomes of Prematurity: A Frequentist and Bayesian Meta-Analysis.

The fetal systemic inflammatory response associated with intra-amniotic inflammation may play a key role in the pathogenesis of complications of preterm birth. Funisitis is the histologic equivalent of the fetal inflammatory response, whereas chorioamnionitis represents a maternal inflammatory response. We conducted a frequentist and Bayesian model average (BMA) meta-analysis of studies investigating the effects of funisitis on short-term outcomes of prematurity. Thirty-three studies (12,237 infants with gestational age ≤ 34 weeks) were included. Frequentist meta-analysis showed that funisitis was associated with an increased risk of any bronchopulmonary dysplasia (BPD), moderate/severe BPD, retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), any sepsis, early-onset sepsis (EOS), and mortality. However, Bayesian meta-analysis showed that the evidence in favor of the alternative hypothesis (i.e., funisitis is associated with an increased risk of developing the outcome) was strong for any IVH, moderate for severe IVH and EOS, and weak for the other outcomes. When the control group was restricted to infants having chorioamnionitis without funisitis, the only outcome associated with funisitis was any IVH. In conclusion, our data suggest that the presence of funisitis does not add an additional risk to preterm birth when compared to chorioamnionitis in the absence of fetal inflammatory response.

Funisitis as a Risk Factor for Adverse Neonatal Outcomes in Twin Neonates with Spontaneous Preterm Birth: A Retrospective Cohort Study.

PurposeFunisitis, inflammation of the umbilical cord, is considered a strong risk factor for adverse neonatal outcomes; however, a clinical definition of funisitis has not been established. In this study, we aimed to determine the clinical significance of funisitis in twin neonates with spontaneous preterm birth.Materials and MethodsThe study included preterm twin neonates (<35 weeks) delivered after spontaneous preterm labor and/or preterm premature rupture of amniotic membranes. The presence of funisitis was examined in the umbilical cord of each twin. We analyzed the risk of adverse neonatal outcomes according to the presence and absence of funisitis. Adverse neonatal outcomes were defined as the occurrence of neonatal mortality, significant morbidity, or both.ResultsAmong 474 preterm neonates (237 twin pairs) included in this study, the frequency of funisitis was 6.5% (31 cases). Funisitis was significantly associated with neonatal mortality and adverse neonatal outcomes after adjustment for confounding variables [neonatal mortality, odds ratio (OR) 9.043, 95% confidence interval (CI) 2.620–31.204; adverse neonatal outcome, OR 2.445, 95% CI 1.017–5.875]. The concordance rate of funisitis between the twins was 10.7%, and in the absence of funisitis in one twin, the risk of neonatal mortality or adverse neonatal outcome was not influenced by the presence of funisitis in the other twin.ConclusionThe presence of funisitis appears to be associated with an increased risk for adverse neonatal outcomes in twin neonates with spontaneous preterm birth.

The fetal inflammatory response syndrome: the origins of a concept, pathophysiology, diagnosis, and obstetrical implications

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.

Association of Histological and Clinical Chorioamnionitis With Neonatal Sepsis Among Preterm Infants: A Systematic Review, Meta-Analysis, and Meta-Regression.

Chorioamnionitis (CA) is considered a key risk factor for very preterm birth and for developing early onset sepsis (EOS) in preterm infants, but recent data suggest that CA might be protective against late onset sepsis (LOS). We performed a systematic review and meta-analysis of studies exploring the association between CA and sepsis. A comprehensive literature search was performed in PubMed/MEDLINE and EMBASE, from their inception to December 1, 2018. A random-effects model was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Sources of heterogeneity were analyzed by subgroup and meta-regression analyses. The following categories of sepsis were analyzed: EOS, LOS, unspecified onset sepsis (UOS), culture-proven, and clinical sepsis. CA was subdivided into clinical and histological chorioamnionitis. Funisitis was also analyzed. We found 3,768 potentially relevant studies, of which 107 met the inclusion criteria (387,321 infants; 44,414 cases of CA). Meta-analysis showed an association between any CA and any EOS (OR 4.29, CI 3.63–5.06), any LOS (OR 1.29, CI 1.11–1.54), and any UOS (OR 1.59, CI 1.11–1.54). Subgroup analysis showed that CA was associated with culture-proven EOS (OR 4.69, CI 3.91–5.56), clinical EOS (OR 3.58, CI 1.90–6.76), and culture-proven LOS (OR 1.31, CI 1.12–1.53), but not with clinical LOS (OR 1.52, CI 0.78–2.96). The presence of funisitis did not increase the risk of either EOS or LOS when compared with CA without funisitis. CA-exposed infants had lower gestational age (−1.11 weeks, CI −1.37 to −0.84) than the infants not exposed to CA. Meta-regression analysis showed that the lower gestational age of the CA group correlated with the association between CA and LOS but not with the association between CA and EOS. In conclusion, our data suggest that the positive association between chorioamnionitis and LOS may be modulated by the effect of chorioamnionitis on gestational age.

Therapeutic interventions for fetal inflammatory response syndrome (FIRS)

Fetal inflammatory response syndrome (FIRS) is a condition defined by systemic inflammation in the fetus, a rapid increase of pro-inflammatory cytokines into the fetal circulation (including interleukin-1 and interleukin-6), as well as a cellular response (such as increased neutrophils, monocyte/macrophages, and T cells) and the presence of funisitis. FIRS can lead to death and multisystem organ damage in the fetus and newborn. Brain injuries and subsequent risk of cerebral palsy and cognitive impairments are the most threatening long-term complications. This paper reviews the definition of FIRS, summarizes its associated complications, briefly describes the available methods to study FIRS, and discusses in more detail the potential therapeutic candidates that have been so far studied to protect the fetus/newborn from FIRS and to alleviate its associated complications and sequelae.

Influence of foetal inflammation on the development of meconium aspiration syndrome in term neonates with meconium-stained amniotic fluid

BackgroundMeconium-stained amniotic fluid is observed in approximately 10–15% of all deliveries; however, only 5% of neonates with meconium-stained amniotic fluid develop meconium aspiration syndrome (MAS). Although foetal distress and subsequent sympathetic stimulation have been considered as the primary upstream events of MAS, this clinical complication sometimes occurs due to other pathologies, such as intraamniotic inflammation. The aim of this study was to investigate whether the incidence of MAS is associated with the presence of funisitis and chorioamnionitis in term neonates with meconium-stained amniotic fluid.MethodsBetween April 2013 and March 2015, a total of 95 term neonates with meconium-stained amniotic fluid, who were hospitalized at a neonatal intensive care unit, were enrolled in the study. The placenta and umbilical cord were histopathologically examined. Clinical variables and histopathological findings associated with the incidence of MAS were studied.ResultsA total of 36 neonates developed MAS. Univariate logistic regression analysis revealed that a heavier birth weight, male sex, 1-min Apgar score ≤ 7, funisitis (but not chorioamnionitis), and elevated acute-phase inflammatory reaction score were associated with increased incidence of MAS (all p < 0.05). The multivariate model comprised funisitis (OR = 5.03, 95% CI [1.63–15.5], 1-min Apgar score ≤ 7 (OR = 2.74, 95% CI [1.06–7.09], and male sex (OR = 3.4, 95% CI [1.24–9.34].ConclusionIn neonates with meconium-stained amniotic fluid, funisitis, as well as low 1-min Apgar score and male sex, was identified as an independent variable for MAS development. Intraamniotic inflammation might be involved in the pathological mechanisms of MAS.

Chorioamnionitis Is a Risk Factor for Intraventricular Hemorrhage in Preterm Infants: A Systematic Review and Meta-Analysis.

Although chorioamnionitis (CA) is a well-known risk factor for white matter disease of prematurity, the association with intraventricular hemorrhage (IVH) is controversial and has not been yet systematically reviewed. We performed a systematic review and meta-analysis of studies exploring the association between CA and IVH. A comprehensive literature search was conducted using PubMed/MEDLINE and EMBASE, from their inception to 1 July 2017. Studies were included if they examined preterm infants and reported primary data that could be used to measure the association between exposure to CA and the presence of IVH. A random-effects model was used to calculate odds ratios (OR) and 95% confidence intervals (CI). We found 1,284 potentially relevant studies, of which 85 met the inclusion criteria (46,244 infants, 13,432 CA cases). Meta-analysis showed that CA exposure was significantly associated with all grades IVH (OR 1.88, 95% CI 1.61–2.19), with grades 1–2 IVH (OR 1.69, 95% CI 1.22–2.34), and with grades 3–4 IVH (OR 1.62, 95% CI 1.42–1.85). Both clinical and histological CA were associated with an increased risk for developing IVH in very preterm infants. In contrast, the presence of funisitis did not increase IVH risk when compared to CA in the absence of funisitis (OR 1.22, 95% CI 0.89–1.67). Further meta-analyses confirmed earlier findings that CA-exposed infants have significantly lower gestational age (GA; mean difference [MD] −1.20 weeks) and lower birth weight (BW; MD −55 g) than the infants not exposed to CA. However, meta-regression and subgroup analysis could not demonstrate an association between the lower GA and BW and the risk of IVH in the CA-exposed infants. In conclusion, our data show that CA is a risk factor for IVH, but also a risk factor for greater prematurity and more clinical instability. In contrast to other complications of prematurity, such as patent ductus arteriosus, retinopathy of prematurity, or bronchopulmonary dysplasia, the effect of CA on IVH appears to be independent of CA as causative factor for very preterm birth.

Late preterm prelabor rupture of fetal membranes: fetal inflammatory response and neonatal outcome.

BackgroundTo characterize the influence of microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI) on the intensity of the fetal inflammatory response and the association between the presence of the fetal inflammatory response syndrome (FIRS) and short-term neonatal morbidity in the preterm prelabor rupture of membranes (PPROM) between the gestational ages of 34 and 37 weeks.MethodsOne hundred and fifty-nine women were included in the study. The umbilical cord blood interleukin (IL)-6 concentrations were determined using enzyme-linked immunosorbent assay kits. FIRS was defined based on the umbilical cord blood IL-6 concentration and the presence of funisitis and/or chorionic plate vasculitis.ResultsWomen with both MIAC and IAI had the highest median umbilical cord blood IL-6 concentrations and highest rates of FIRS. Women with FIRS had the higher rates of early-onset sepsis and intraventricular hemorrhage grades I and II when FIRS was characterized based on the umbilical cord blood IL-6 concentrations and the histopathological findings.ConclusionThe presence of both MIAC and IAI was associated with a higher fetal inflammatory response and a higher rate of FIRS. Different aspects of short-term neonatal morbidity were related to FIRS when defined by umbilical cord blood IL-6 concentrations and the histopathology of the placenta.

Maternal and Placental Factors Associated with Congenital Hearing Loss in Very Preterm Neonates

Sensorineural hearing loss (SNHL) is a multifactorial disease that more frequently affects preterm newborns. Although a number of maternal conditions have been reported to be associated with preterm birth, little information is available concerning maternal risk factors for the development of SNHL. We aimed to identify maternal and placental risk factors associated with a "refer" result on the newborn hearing screening (NHS) test and subsequently confirmed SNHL in very preterm neonates. This retrospective cohort study included 267 singleton neonates who were born alive after≤32weeks. Histopathologic examination of the placenta was performed, and clinical data were retrieved from a computerized perinatal database. Cases with two abnormal findings, "refer" on the NHS test, and presence of SNHL on the confirmation test were retrospectively reviewed based on electronic medical records. Forty-two neonates (15.7%) showed a "refer" result, and, on the confirmation test, permanent SNHL was identified in 1.87% (5/267) of all neonates. Multivariate regression analysis revealed that the presence of funisitis was independently associated with a "refer" on the NHS test, whereas use of antenatal corticosteroids was statistically significantly associated with a reduced incidence of "refer" on the screening test. Neither histologic chorioamnionitis nor prematurity (as defined by low gestational age and birth weight) was associated with a "refer" on the NHS test. By contrast, multivariate analysis with occurrence of SNHL as a dependent variable identified no significant associations with the parameters studied, probably owing to the small total number of neonates with permanent SNHL. Presence of funisitis was significantly and independently associated with increased risk of abnormal NHS results, while administration of antenatal corticosteroids was related to a normal NHS result. These findings support the hypothesis that a systemic fetal inflammatory response, manifested as funisitis, might play a role in the pathogenesis of SNHL in preterm neonates.

Risk factors for cerebral palsy in PPROM and preterm delivery with intact membranes

Objective: Gestational age (GA) at delivery and spontaneous prematurity are independent risk factors for cerebral palsy (CP). The aim of this study is to investigate perinatal risk factors for CP in spontaneous preterm delivery.Methods: A retrospective cohort study of all single pregnancies complicated by spontaneous preterm labor (PTL) or PPROM with delivery at <34 weeks from January 2006 to December 2012 was performed. We compared demographic, obstetric, neonatal, and placental histology variables in cases of spontaneous preterm birth in reference to the development of CP. Statistical analysis included chi-square, one-way ANOVA and logistic regression analysis. p < 0.05 was considered significant.Results: Two hundred sixty-one women were included for this study. Of 249 survivors, 5 babies died during the first year of life, 52 did not fulfill the inclusion criteria for neurologic follow-up, and 24 were lost to follow up. Thus 168 infants in the study cohort underwent neurologic follow-up. We observed 26 cases of CP. Factors related to CP were lower GA at PROM (p = 0.007) and longer latency from PPROM to delivery (p = 0.002) in the PPROM group, lower GA at delivery (p < 0.001) and presence of funisitis (p <0.001) in the PTL group.Conclusions: GA at membrane rupture in PPROM and GA at delivery in PTL are significantly associated with CP. A process leading to neurological damage may be initiated at the moment of membranes rupture in cases of PPROM and at the time of PTL in the group with intact membranes.

Funisitis is associated with adverse neonatal outcome in low-risk unselected deliveries at or near term.

This study aimed to determine the incidence and clinical outcomes for varying patterns of placental histological inflammation (consistent with fetal or maternal inflammatory response) in an unselected population of >1000 women with a singleton pregnancy resulting in live birth delivering at or near term. One thousand one hundred nineteen cases were studied in a blind, prospective, unselected study with placentas categorized into five histological subgroups reflecting underlying maternal or fetal inflammatory response. Clinical outcomes studied included interventional delivery, an Apgar score <7 at 1 min, neonatal acidosis (pH < 7.2) and admission to neonatal special care. One hundred eighty-eight placentas (17 %) showed histological evidence of acute inflammation: 64 with funisitis (with or without other inflammation; 6 %); 16 with extensive acute inflammation across the chorionic plate, free membranes and subchorionic fibrin (1 %); 28 with acute inflammation restricted to the chorionic plate (2 %); 12 with acute inflammation restricted to the free membranes (1 %) and 68 with acute inflammation restricted to the subchorionic fibrin (6 %). Features of extensive acute inflammation were significantly associated with increased rate of interventional delivery (assisted vaginal delivery or emergency caesarean section; P < 0.01). The presence of funisitis was significantly associated with interventional delivery and other adverse outcomes including an Apgar score <7 at 1 min, clinical evidence of sepsis and admission to the neonatal intensive care unit (P < 0.05 for all). The data represent a quantitative rather than purely qualitative analysis of the contribution of histological lesions related to inflammation on short-term adverse neonatal outcomes and interventional delivery. Funisitis and extensive inflammation are associated with adverse clinical outcomes, but the precise mechanism underlying these remains to be elucidated.

Cytokines in noninvasively obtained amniotic fluid as predictors of fetal inflammatory response syndrome

In patients with preterm premature rupture of membranes, intrauterine inflammation and/or infection is frequently present, can lead to fetal inflammatory response syndrome, and is associated with adverse neonatal outcome. Clinical decision making requires balancing the potential benefits of pregnancy prolongation against the risk of intrauterine infection. Diagnostic tests in maternal serum are of moderate prediction value and amniocentesis is an invasive procedure. Therefore, markers obtained noninvasively would be helpful in patients with expectant management. To determine the predictive values of amniotic fluid interleukin-6 and tumor necrosis factor-α in vaginal secretions for fetal inflammatory response syndrome and/or histologic funisitis and for adverse neonatal outcome in patients with preterm premature rupture of membranes. In this prospective multicenter case-control study, vaginal secretions were sampled daily with a noninvasive method from 99 women with preterm premature rupture of membranes and expectant management. Amniotic fluid interleukin-6 and tumor necrosis factor-α were measured by 2 different immunoassays (an automated chemiluminescent enzyme immunoassay and a lateral flow immunoassay). After delivery, patients were divided into a control or a fetal inflammatory response syndrome group according to neonatal interleukin-6 in cord plasma and/or the presence of funisitis. Univariate and multivariate regression analyses were performed and prediction models were developed by calculating receiver operating characteristic curves. Gestational age at delivery was lower and latency period was longer in the fetal inflammatory response syndrome group compared to the control group. The strongest risk factor for composite adverse neonatal outcome was fetal inflammatory response syndrome (odds ratio, 2.48; confidence interval, 1.40-4.38). The median concentrations of amnioticfluid interleukin-6 and tumor necrosis factor-α in vaginal secretions were significantly higher in the fetal inflammatory response groupcompared to the control group in both immunoassays (P < .001). The area under the curve of the clinical reference model (including common clinical parameters) was 0.66. Adding interleukin-6 and tumor necrosis factor-α into the model improved the area under the curve to 0.92 (in both assays, interleukin-6 IMMULITE and QuickLine); 0.87 (tumor necrosis factor-α IMMULITE) and 0.94 (tumor necrosis factor-α QuickLine), respectively. The strongest risk factor for worse neonatal outcome (composite neonatal outcome) was fetal inflammatory response syndrome. Amniotic fluid interleukin-6 and tumor necrosis factor-α seem to be good predictors for fetal inflammatory response syndrome and for histologic funisitis and may improve the clinical management of patients with preterm premature rupture of membranes. The noninvasive technique of sampling amniotic fluid from vaginal secretions facilitates daily measurements and bedside assessment of cytokines and is in this respect preferable to invasive amniocentesis.

Low level of tracheal cellular fibronectin in extremely premature infants with funisitis: Relationship with respiratory distress 1 month after birth

Funisitis reflects the fetal systemic inflammatory response in premature infants. Macrophages and neutrophils have been identified as key elements in the inflammatory process of the lungs, and secrete proteases that cause the destruction of the extracellular matrix (ECM). Fibronectin (FN) is the major constituent of the pulmonary ECM and exists in multiple isoforms arising from alternative RNA splicing. Extra domain A (EDA) is the major alternatively spliced segment, and the expression of EDA containing FN (EDA + FN) in the lungs is associated with distal pulmonary cell proliferation during alveolar formation. To study the relationship between the presence of funisitis and EDA + FN levels in the tracheal aspirate fluid (TAF) of infants of less than 28 weeks' gestation. The subjects included in this study were 26 extremely premature infants of <28 weeks' gestation at <24 hr of age, from whom the TAF was collected. These preterm infants were divided into two groups according to placental histology. The funisitis (+) group (n = 9) was compared with the funisitis (-) group (n = 17). The TAF supernatants were analyzed for IL-1β, IL-6, IL-8, neutrophil elastase, and EDA + FN using enzyme-linked immunosorbent assay (ELISA). There were no significant differences in gestational age or birthweight between these groups. The funisitis (+) group had a significantly higher ventilator setting (inspired O(2) × mean airway pressure) at Day 28 than the funisitis (-) group. In the TAF, the concentrations of IL-1β were significantly higher in the funisitis (+) group than in the funisitis (-) group, as were the concentrations of neutrophil elastase. The concentrations of EDA + FN were significantly lower in the funisitis (+) group than in the funisitis (-) group. Decreased EDA + FN in TAF might be one of the risk factors leading to respiratory distress in extremely premature infants with funisitis.

Amniotic fluid CD200 levels in pregnancies complicated by preterm prelabor rupture of the membranes

Objective: To determine the amniotic fluid CD200 levels in uncomplicated pregnancies and in preterm prelabor rupture of the membranes (PPROM) according to microbial invasion of the amniotic cavity and histological chorioamnionitis and its association with neonatal outcomes.Methods: One hundred and fifty-nine women with singleton pregnancies were included in this study. Amniotic fluid was collected, and CD200 levels were determined using ELISA.Results: No difference was found in CD200 levels between women in the second trimester and women at term without labor. Women at term with labor had higher CD200 levels than women in the second trimester and women at term without labor. The presence of funisitis in PPROM pregnancies was associated with higher CD200 levels independent of gestational age (with funisitis: median 197.5 pg/mL versus without funisitis: median 61.0 pg/mL; p = 0.003). The need for tracheal intubation and the development of bronchopulmonary dysplasia were associated with higher CD200 levels.Conclusions: Amniotic fluid CD200 levels remained stable in advanced pregnancy and they were increased during parturition. Elevated CD200 levels in the presence of funisitis suggest the involvement of negative regulatory mechanisms of innate immunity. CD200 may play a role in the development of pulmonary aspects of neonatal morbidity.

Maternal C-Reactive Protein at Hospital Admission Is a Simple Predictor of Funisitis in Preterm Premature Rupture of Membranes

Aim: To analyze the prognostic value of maternal serum C-reactive protein (CRP) in predicting funisitis in patients with preterm premature rupture of membranes (pPROM). Methods: 66 patients (gestational age 24–33 weeks) hospitalized 1–12 h after pPROM were enrolled. White blood cell count (WBC), platelet count (PLT) and plasma concentration of CRP were assessed every 3 days. Histological evidence of chorioamnionitis and funisitis was obtained post-partum. Receiver operating characteristic (ROC) curves were employed to evaluate the role of maternal CRP in predicting funisitis. Results: Funisitis was found in 24 patients (36.3%); 42 patients (63.7%) without funisitis were considered as controls. PLT and WBC at admission and before delivery did not show significant differences and were not statistically different between the two groups. Patients with funisitis had significantly higher CRP levels both at admission to hospital and 24– 48 h before delivery. ROC curve analysis showed that CRP at admission (area under the curve: 0.671, p = 0.021) and before delivery (area under the curve: 0.737, p = 0.001) are predictive of funisitis. Conclusions: High maternal serum CRP levels (>20,000 µg/l) in pPROM patients at admission to hospital may be an early marker which indicates, with a good diagnostic performance, the presence of funisitis.

Histological chorioamnionitis – implication for bacterial colonization, laboratory markers of infection, and early onset sepsis in very-low-birth-weight neonates

Objective. The objective of this study was to evaluate the relationship between histological chorioamnionitis and laboratory markers of infection and congenital sepsis in very-low-birth-weight (VLBW) premature neonates.Method. This study is a retrospective review of laboratory results of VLBW neonates with birth weight less than 1500 g in our neonatal intensive care unit (NICU) in the last 5 years.Results. Ninety-nine VLBW neonates had histological chorioamnionitis, and 50 of them further had funisitis. One hundred and sixty-two VLBW neonates did not have chorioamnionitis. The chorioamnionitis group was more likely than the ‘no chorioamnionitis’ group to have raised C-reactive proteins (23% versus 9.9%; p = 0.006) and neutrophilia (41% versus 4.3%; p < 0.001). White blood cells were more likely to be present in gastric lavage of the former group than the latter group (70% versus 50%; p = 0.002). Ear swab and gastric lavage were more likely to yield positive growth of micro-organisms from the former group than the latter group (34% versus 9.9% and 22% versus 2.7%; p < 0.001 and p < 0.001, respectively). Congenital sepsis proven by positive blood culture was also more likely to occur (3% versus 0%; p = 0.027). Presence of funisitis further increased the likelihood of the above abnormal laboratory results.Conclusions. Histological chorioamnionitis increases the likelihood of having markers of infection, bacterial colonization, and congenital sepsis. Only 3% of histological chorioamnionitis resulted in congenital sepsis confirmed by blood culture.

The presence of funisitis is associated with a decreased risk for the development of neonatal respiratory distress syndrome

Objectives Fetal lung maturation and respiratory outcomes are influenced by the exposure to intrauterine inflammation. Funisitis is considered as the histologic hallmark of fetal inflammatory response. This study was performed to determine if there is a difference in the rate of neonatal respiratory distress syndrome (RDS) according to the presence or absence of funisitis in preterm gestations. Study design The relationship between the presence of funisitis and the development of neonatal RDS was examined in 301 consecutive singleton preterm births (24–32 weeks’ gestation). Cases without placental histological examination and those with major congenital anomalies were excluded. Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton’s jelly on the placental histological examination. Results Funisitis was diagnosed in 25% and RDS was diagnosed in 46% of cases. The rate of RDS in babies with funisitis was lower than in those without funisitis (28.4% vs. 51.1%, p = 0.001). Logistic regression analysis demonstrated that the presence of funisitis was associated with a decreased risk for RDS after adjusting for confounding variables (Odds ratio = 0.44, 95% CI 0.22–0.90). The downward trend of the frequency of RDS was related to the presence of histologic chorioamnionitis and funisitis ( p < 0.001). Conclusions The presence of funisitis is associated with a decreased risk for the development of neonatal RDS in preterm gestations. Furthermore, this observation suggests that the fetal involvement of placental inflammation may be beneficial to the maturation of the fetal lung.

186: The presence of funisitis is associated with a decreased risk for the development of neonatal respiratory distress syndrome

Objectives: Fetal lung maturation and respiratory outcomes are influenced by the exposure to intrauterine inflammation. Funisitis is considered as the histologic hallmark of fetal inflammatory response. This study was performed to determine if there is a difference in the rate of neonatal respiratory distress syndrome (RDS) according to the presence or absence of funisitis in preterm gestations. Study design: The relationship between the presence of funisitis and the development of neonatal RDS was examined in 301 consecutive singleton preterm births (24e32 weeks’ gestation). Cases without placental histological examination and those with major congenital anomalies were excluded. Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton’s jelly on the placental histological examination. Results: Funisitis was diagnosed in 25% and RDS was diagnosed in 46% of cases. The rate of RDS in babies with funisitis was lower than in those without funisitis (28.4% vs. 51.1%, p ¼ 0.001). Logistic regression analysis demonstrated that the presence of funisitis was associated with a decreased risk for RDS after adjusting for confounding variables (Odds ratio ¼ 0.44, 95% CI 0.22e0.90). The downward trend of the frequency of RDS was related to the presence of histologic chorioamnionitis and funisitis (p < 0.001). Conclusions: The presence of funisitis is associated with a decreased risk for the development of neonatal RDS in preterm gestations. Furthermore, this observation suggests that the fetal involvement of placental inflammation may be beneficial to the maturation of the fetal lung.

Low maternal serum matrix metalloproteinase (MMP)-2 concentrations are associated with preterm labor and fetal inflammatory response

to assess the relationship between maternal and umbilical serum concentrations of matrix metalloproteinases (MMP)-2,8,9, the soluble receptor for advanced glycation end products (sRAGE) and IL-10 and premature delivery and fetal inflammation. maternal serum levels of MMPs, sRAGE, IL-10 and C-reactive protein (CRP) were determined in 67 women with preterm labor and in 38 healthy pregnant women of similar gestational age (GA). In the group with preterm labor we also determined umbilical concentrations of MMPs, IL-6 and sRAGE. The group with preterm labor was additionally divided based on the presence of funisitis and elevations of fetal umbilical IL-6 concentrations. maternal serum levels of MMP-2 and sRAGE were significantly lower in women with preterm labor compared to women with normal pregnancy. Additionally, within the group of women with preterm labor, maternal serum MMP-2 concentrations were significantly lower in the subgroup with funisitis and in the subgroup with elevated umbilical concentration of IL-6. our results demonstrate significantly different serum concentrations of MMP-2 and sRAGE in women with preterm labor compared to healthy pregnant patients of the same GA.