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A case-control study of chorioamnionic infection and histologic chorioamnionitis in prematurity.

To study the role of infection in prematurity, we studied the demographic and obstetrical characteristics, chorioamnionic cultures, and placental histologic features of women who delivered prematurely and compared these findings with those in women who delivered at term. Microorganisms were isolated from the area between the chorion and the amnion (chorioamnion) in 23 of 38 placentas (61 percent) from women with preterm labor who delivered before 37 weeks' gestation and in 12 (21 percent) of 56 placentas from women without preterm labor who delivered at term (odds ratio, 5.6; 95 percent confidence interval, 2.1 to 15.6). The most frequent isolates from the placentas of those whose infants were delivered prematurely were Ureaplasma urealyticum (47 percent) and Gardnerella vaginalis (26 percent). The recovery of any organism from the chorioamnion was strongly associated with histologic chorioamnionitis (odds ratio, 7.2; 95 percent confidence interval, 2.7 to 19.5) and with bacterial vaginosis (odds ratio, 3.2; 95 percent confidence interval, 1.1 to 6.6). When multiple logistic regression was used to control for demographic and obstetrical variables, premature delivery was still related to the recovery of organisms from the chorioamnion (odds ratio, 3.8; 95 percent confidence interval, 1.5 to 9.9) and with chorioamnionitis (odds ratio, 5.0; 95 percent confidence interval, 1.6 to 15.3). The proportion of placentas with evidence of infection was highest among those who delivered at the lowest gestational age. We conclude that infection of the chorioamnion is strongly related to histologic chorioamnionitis and may be a cause of premature birth.

Adult↗

The relationship of amniotic fluid cytokines and preterm delivery, amniotic fluid infection, histologic chorioamnionitis, and chorioamnion infection.

OBJECTIVE: To assess the association between cytokines in the amniotic fluid (AF) and preterm delivery, the isolation of bacteria from the AF or chorioamnion, and histologic chorioamnionitis. METHODS: Fifty afebrile women with intact membranes in preterm labor at or before 34 weeks' gestation underwent amniocentesis. Cytokine levels were measured in AF, and cultures were performed. Placentas were cultured and examined histologically. RESULTS: Thirty-two (64%) of the 50 patients delivered at or before 34 weeks' gestation. Delivery at or before 34 weeks, compared with delivery after 34 weeks, was related to increased levels of interleukin-6 (IL-6) (88 versus 12%; P < .001), interleukin-1 (IL-1) alpha (50 versus 6%; P = .004), IL-1 beta (42 versus 0%; P = .002), and prostaglandin (PG) E2 (66 versus 22%; P = .008). Bacteria were recovered from the AF of nine (18%) of the 50 patients. All of the cytokines with increased levels, plus tumor necrosis factor (TNF)-alpha, were related to bacteria in the AF. Increased IL-6, IL-1 alpha, IL-1 beta, TNF-alpha, and PGE2 were also associated with histologic chorioamnionitis among women who delivered within 1 week of amniocentesis. Elevated cytokine levels were not related to chorioamnion infection. CONCLUSIONS: Elevated AF cytokines and PGE2 predicted delivery before 34 weeks' gestation and delivery within 7 days of the amniocentesis, as well as AF infection and histologic chorioamnionitis. These findings support the hypothesis that infection is one cause of preterm delivery, operating via a mechanism involving induction of cytokine production.

Adult↗

Re-evaluation of chorioamnionitis and funisitis with a special reference to subacute chorioamnionitis.

Our purpose is to prove that prolonged inflammation of the chorionic plate, which we have termed subacute chorioamnionitis (SCAM), is a distinctive entity and should be differentiated from acute chorioamnionitis (ACAM) because it is an excellent prognostic indicator of chronic lung disease (CLD), including Wilson-Mikity syndrome (WMS). Ninety singleton placentas with stage-3 chorioamnionitis were delivered at 23 to 32 weeks of gestation during 1993 to 1996, and the infants survived more than 28 days. There were 49 placentas with stage 3 SCAM, 33 placentas with stage 3 ACAM, and 8 placentas with subacute necrotizing funisitis (SNF) and without inflammation of the chorionic plate. Fifty-three of gestation- and birthweight-matched placentas without chorioamnionitis were selected as control. To determine the risk factors for CLD, 27 clinical and 6 histological variables were analyzed. Logistic regression analysis showed that amniotic necrosis (AN) (P =.0168) and low birthweight (P =.0341) were the major contributing risk factors for CLD. SNF was not significantly related to CLD. Patients with SCAM (AN+, SNF-) were highly susceptible to CLD. In conclusion, SCAM, especially when associated with AN, seems to be a unique prognostic indicator of CLD.

Amnion↗

Chorioamnionitis with a fetal inflammatory response is associated with higher neonatal mortality, morbidity, and resource use than chorioamnionitis displaying a maternal inflammatory response only.

OBJECTIVE: This study was undertaken to evaluate whether the proximity of infection of the chorion/amnion and fetal vessels affects neonatal outcomes. STUDY DESIGN: We examined all (n=2012) infants admitted to the British Columbia's Children's Hospital Neonatal Intensive Care Unit, from January 1996 to October 1997. We included infants with a placental examination (n=1296), and stratified those with histologic chorioamnionitis into cases displaying a maternal inflammatory response only and cases also displaying a fetal inflammatory response (funisitis and/or fetal surface vessel angiitis). RESULTS: Histologic evidence of chorioamnionitis was present in 31% of placentas. Of those, 38% exhibited maternal inflammation only, whereas 62% also exhibited fetal inflammation. Neonatal mortality (9.2% vs 7.2%), morbidity, and resource use were significantly (P < .05) higher when fetal inflammation was present compared with when only maternal inflammation was present. CONCLUSION: Chorioamnionitis with a fetal inflammatory response is associated with higher neonatal mortality, morbidity, and resource use than when only a maternal inflammatory response is present.

Chorioamnionitis↗

Antenatal steroids may reduce adverse neurological outcome following chorioamnionitis: neurodevelopmental outcome and chorioamnionitis in premature infants.

OBJECTIVE: To examine the effect of antenatal steroid exposure and in utero inflammation on the development of severe intraventricular haemorrhage, periventricular leukomalacia and long-term neurological outcome in infants less than 30 completed weeks gestation. METHOD: Infants less than 30 completed weeks gestation from January 1996 to July 2001 were identified from a prospectively managed database. Placental pathology was reviewed for the presence or absence of chorioamnionitis and funisitis. Infants were divided into three groups depending on the degree of exposure to fetal inflammation (no inflammation, chorioamnionitis only and chorioamnionitis and funisitis). Data relating to gestational age, birthweight, sex, antenatal steroid exposure, surfactant treatment, days of positive pressure ventilation and days of oxygen requirement were collected. Cerebral ultrasound studies were examined for evidence of intraventricular or intraparenchymal echodensity and periventricular leukomalacia. Long-term neurological outcome was assessed by neurological examination for cerebral palsy and by Griffiths Mental Developmental Assessment for general developmental quotient. RESULTS: Two hundred and twenty infants were identified. The mean gestational age was 27.7 weeks and the mean birthweight 1092 g. Seventy-two per cent of mothers had received a complete course of antenatal steroids. The risk of Grade III intraventricular haemorrhage or intraparenchymal echodensity was associated with exposure to in utero inflammation if a complete course of antenatal steroids had not been received (P = 0.002). This association did not exist if a complete course of antenatal steroids was given (P = 0.62). Fourteen infants had cerebral palsy (7%). The presence of cerebral palsy was also associated with in utero inflammation in the absence of complete antenatal steroid cover (P = 0.03) and not in the presence of complete cover (P = 0.59). The mean general developmental quotient on Griffiths Mental Developmental Assessment at 12 months or 3 years was not affected by exposure to in utero inflammation regardless of antenatal steroid exposure. CONCLUSION: Risk of intraventricular haemorrhage or intraparenchymal echodensity and cerebral palsy was associated with in utero inflammation in the absence of a complete course of antenatal steroids. A complete course of antenatal steroids appeared to extinguish any association between in utero inflammation and adverse neurological outcome.

Cerebral Palsy↗

Microbiologic causes and neonatal outcomes associated with chorioamnion infection.

Chorioamnion infection is associated with histologic chorioamnionitis and prematurity, but the specific chorioamnion microorganisms associated with histologic chorioamnionitis, prematurity, and poor neonatal outcome have not been identified. Bacteria were recovered from the chorioamnion cultures of 32% of 112 placentas delivered at less than or equal to 34 weeks' gestation and from 19% of 156 placentas delivered at greater than 34 weeks' gestation (odds ratio 2.1; 95% confidence interval 1.1 to 3.8). Chorioamnion bacteria most highly related to both prematurity and histologic chorioamnionitis were group B Streptococcus and Fusobacterium species. Chorioamnion infection with Peptostreptococcus was significantly related only to preterm delivery, and infection with Escherichia coli, Bacteroides, and Ureaplasma were significantly related to histologic chorioamnionitis. Among preterm infants, isolation of bacteria from the chorioamnion was related to an increased risk of neonatal death (rate ratio 3.8; 95% confidence interval 1.4 to 11.6). Bacterial infection of the chorioamnion is related to preterm birth, histologic chorioamnionitis, and neonatal death.

Adolescent↗

Histologic chorioamnionitis and preterm delivery in different patient populations.

The placentas of 1843 deliveries were examined for the presence of histologic chorioamnionitis, which was classified as mild, moderate, or severe. Chorioamnionitis was present in 7.5% of patients who underwent cesarean before labor and in 18 and 32% of those delivering at term and preterm, respectively. Chorioamnionitis was severe in 74% of preterm but in only 15% of term deliveries. Premature rupture of membranes (PROM) was more frequent with preterm than with term delivery, with chorioamnionitis present in 42 and 15% of patients, respectively. Although chorioamnionitis was equally frequent in women with intact membranes delivering preterm and term, chorioamnionitis was severe in 63% of preterm and 14% of term deliveries (P less than .001). The frequency and severity of chorioamnionitis were related inversely to gestational age at preterm birth. Preterm delivery was more frequent in black than in white patients (19 versus 9%) and in indigent clinic versus private patients (13 versus 7.5%). However, there was no significant difference in frequency and severity of chorioamnionitis between black and white or between indigent clinic and private patients who delivered preterm. Among term births, chorioamnionitis was more often severe in black than in white patients. Chorioamnionitis in term deliveries was more frequent in clinic than in private patients; however, this was not true when only severe chorioamnionitis was considered. There were no differences in PROM between these patient populations. Thus, higher preterm birth rates in black and indigent clinic populations are not due to the more frequent occurrence of chorioamnionitis.

Black People↗

Clinical chorioamnionitis and histologic placental inflammation.

OBJECTIVE: To estimate the rate of histologic chorioamnionitis in the presence of diagnosed clinical chorioamnionitis and determine whether clinical markers of maternal and neonatal infection are associated with histologic chorioamnionitis. METHODS: We identified singleton pregnancies from 1996 in which discharge diagnoses included clinical chorioamnionitis and reviewed maternal and neonatal records for clinical evidence of chorioamnionitis and suspected or confirmed neonatal infections. Placentas were examined for acute histologic chorioamnionitis. RESULTS: One hundred thirty-nine pregnancies with the discharge diagnosis of maternal clinical chorioamnionitis were included. Eighty-six (61.9%) had the clinical diagnosis supported by histologic chorioamnionitis. Histologic chorioamnionitis was associated with an earlier gestational age at delivery (35.7+/-6.5 weeks versus 38.6+/-2.9 weeks, P = .002), lower epidural usage (72.1% versus 92.5%, P = .004), less internal monitoring (47.7% versus 75.5%, P = .001), and possible neonatal sepsis (60.5% versus 35.8%, P = .005). For 19 of 71 (26.8%) infants with possible neonatal sepsis, placentas did not show histologic chorioamnionitis. CONCLUSION: Clinical chorioamnionitis and possible neonatal infection were not supported by histologic evidence for infection in 38.1% and 26.8% of cases, respectively, suggesting other noninflammatory causes of signs and symptoms.

Adult↗

The Maternal-Fetal Medicine Units cesarean registry: chorioamnionitis at term and its duration-relationship to outcomes.

OBJECTIVE: The purpose of this study was to evaluate the relationship between chorioamnionitis and its duration to adverse maternal, fetal, and neonatal outcomes. STUDY DESIGN: This was a 13-university center, prospective observational study. All women at term carrying a singleton gestation who underwent primary cesarean from January 1, 1999 to December 31, 2000 were eligible. Data abstraction was systematic and performed by trained research nurses. Selected adverse outcomes were compared between pregnancies with, and without, clinically diagnosed chorioamnionitis using relative risks (RRs) and 95% CIs. The duration of chorioamnionitis was stratified into 5 intervals ( 3-6 h,>6-9 h,>9-12 h, and>12 h), and respective outcomes compared by Mantel-Haenszel test for trend. Additionally, regression analysis was used to compute odds ratios (ORs) and 95% CIs for chorioamnionitis duration length as a continuous explanatory variable. RESULTS: 16,650 pregnancies were analyzed, 1965 (12%) with chorioamnionitis, which was associated with significantly increased risks of maternal blood transfusion, uterine atony, septic pelvic thrombophlebitis, and pelvic abscess (RR 2.3-3.7), as well as 5-minute Apgar <or=3, neonatal sepsis, and seizures (RR 2.1-2.8). By test of trend, only uterine atony (P <.01), maternal blood transfusion (P=.03), maternal admission to intensive care unit (P=.02), and 5-minute Apgar <or=3 (P <.01) were associated with duration of chorioamnionitis. By logistic analysis, only uterine atony (OR for each hour of chorioamnionitis 1.03, 95% CI 1.00-1.06), 5-minute Apgar <or=3 (OR 1.09, 95% CI 1.00-1.16), and neonatal mechanical ventilation within 24 hours of birth (OR 1.07, 95% CI 1.01-1.12) were significantly associated with chorioamnionitis duration. CONCLUSION: Chorioamnionitis was associated with increased rates of morbidity after cesarean at term. The duration of chorioamnionitis, however, was not related to most measures of adverse maternal or fetal-neonatal outcome.

Adult↗

Maternal and umbilical cord serum interleukin levels in preterm labor with clinical chorioamnionitis.

OBJECTIVE: Our purpose was to determine whether interleukin-1 beta, interleukin-6, and the soluble receptor for interleukin-2 levels in maternal and umbilical cord sera differed among patients with and without clinical chorioamnionitis delivered prematurely. STUDY DESIGN: Between February and November 1992, 32 women who were delivered between 20 and 36 weeks' gestation were enrolled in a prospective study to determine the levels of interleukin-1 beta, soluble interleukin-2 receptor, and interleukin-6 in maternal and umbilical cord serum. Cytokines were measured by enzyme-linked immunosorbent assay. Chorioamnionitis was identified by the presence of clinical markers in 12 patients. RESULTS: Soluble interleukin-2 receptor concentrations in maternal serum were significantly higher in women with clinical chorioamnionitis than in those without chorioamnionitis (median 400 U/ml, range 100 to 2100 U/ml vs median 275 U/ml, range 100 to 1300 U/ml, p < 0.04). Umbilical cord interleukin-6 concentrations were significantly higher in the presence of clinical chorioamnionitis than in the absence of chorioamnionitis (median 12.5 pg/ml, range 0 to 400 pg/ml vs median 0 pg/ml, range 0 to 25 pg/ml; p < 0.02). For patients with clinical chorioamnionitis there was a positive correlation between maternal and umbilical cord IL-2 receptor levels (r = 0.752, p < 0.01). No significant differences in maternal interleukin-1 beta or maternal interleukin-6 determinations were noted. Likewise, the umbilical cord interleukin-1 beta and IL-2 receptor concentrations were unchanged in the presence of clinical chorioamnionitis. CONCLUSIONS: This study demonstrates that for patients with preterm labor and clinical chorioamnionitis, maternal serum levels of IL-2 receptor, and umbilical cord serum levels of interleukin-6 are significantly increased compared with patients without chorioamnionitis.

Adult↗

Apoptosis and proliferation in lungs of human fetuses exposed to chorioamnionitis.

AIMS: To determine whether chorioamnionitis has an impact on the extent of apoptosis and proliferation in fetal lungs. Fetuses exposed to chorioamnionitis have an increased risk of aquiring lung tissue damage in utero. METHODS AND RESULTS: Lung tissue sections from 35 stillborn fetuses were used in this study. Chorioamnionitis-exposed fetuses were subdivided depending on whether pneumonia was diagnosed (n = 13) or not (n = 10); 12 unaffected fetuses served as controls. Apoptotic and proliferating cells were determined by in-situ terminal deoxytransferase-mediated dUTP nick end labelling (TUNEL) assay and by anti-Ki67 immunohistochemistry, and quantified. The median apoptotic index in lungs of chorioamnionitis-exposed fetuses increased 2.4-fold compared with chorioamnionitis-negative stillborn controls (P = 0.043) and rose 21.6-fold when chorioamnionitis-exposed fetuses additionally developed pneumonia (P < 0.001). Compared with the proliferation index of the control group (PI = 2.3), the median percentage of proliferating cells in the lungs of chorioamnionitis-exposed fetuses decreased (PI = 1.4) (P = 0.036), but increased 1.8-fold (P = 0.036) in fetal lungs of the chorioamnionitis/pneumonia group. By double labellings combining the TUNEL assay or the Ki67 antigen with cell marker proteins, we identified distal airway epithelial cells as the cell type undergoing apoptosis in chorioamnionitis-exposed fetal lungs, while epithelial, endothelial and smooth muscle cells proliferated. Immunolabellings of cleaved caspases -8 and -9 revealed that apoptosis is mediated via initiator caspase-8. CONCLUSION: Chorioamnionitis induces apoptosis of distal airway epithelial cells via the caspase-8 pathway and interferes with the normal proliferative activity of epithelial, endothelial, and smooth muscle cells in fetal lungs. Thus, apoptosis and proliferation are an important feature of chorioamnionitis-associated lung injury in utero.

Antigens, CD34↗

Decreased expression of angiogenic factors in placentas with chorioamnionitis after preterm birth.

Chorioamnionitis and funisitis are associated with neonatal morbidity and mortality. We hypothesized that chorioamnionitis may stress fetal endothelium, activate proinflammatory gene transcription. and affect angiogenic homeostasis in fetal capillaries. Placentas from preterm infants were stained for heat-shock protein 70, nuclear factor-kappaB, hypoxia-inducible factor-1alpha, and vascular endothelial growth factor (VEGF). VEGF receptors (VEGF-R) 1 and 2 as well as the receptor tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (TIE-2), which is involved in vascular remodeling, were quantified. Immunohistochemistry was analyzed by counting positive capillaries in placental terminal villi. Staining intensity was quantified by a three-step semiquantitative scale. The samples were divided into three matched groups according to histology: chorioamnionitis with funisitis ("funisitis"), chorioamnionitis without funisitis ("chorioamnionitis"), and control group with no inflammation. In tissues from the funisitis or chorioamnionitis group, heat-shock protein 70 expression was increased over the control group. More nuclear factor-kappaB-positive nuclei of endothelial cells in capillaries were counted in the funisitis and chorioamnionitis groups. Expression of VEGF and VEGF-R1 and -R2 were reduced in cases of funisitis or chorioamnionitis in comparison with controls. Hypoxia-inducible factor-1alpha expression tended to be slightly lower in the funisitis and chorioamnionitis groups but did not reach statistical significance. We speculate that cellular stress and changes in angiogenic homeostasis induced by proinflammatory activation of fetal endothelium in chorioamnionitis may not be limited to the placenta but may also involve other fetal organs.

Angiogenesis Inducing Agents↗

Chorioamnionitis as a risk factor for cerebral palsy: A meta-analysis.

CONTEXT: Chorioamnionitis has been implicated in the pathogenesis of cerebral palsy, but most studies have not reported a significant association. Cystic periventricular leukomalacia (cPVL) is believed to be a precursor of cerebral palsy in preterm infants. OBJECTIVES: To determine whether chorioamnionitis is associated with cerebral palsy or cPVL and to examine factors that may explain differences in study results. DATA SOURCES: Searches of MEDLINE (1966-1999), Index Medicus (1960-1965), Doctoral Dissertation Abstracts On-Line (1861-1999), bibliographies, and online conference proceedings (1999) were performed for English-language studies with titles or abstracts that discussed prenatal risk factors for cerebral palsy or cPVL. STUDY SELECTION: Of 229 initially identified publications, meta-analyses were performed on studies that addressed the association between clinical (n = 19) or histologic (n = 7) chorioamnionitis and cerebral palsy or cPVL in both preterm and full-term infants. Inclusion criteria were: presence of appropriate exposure and outcome measures, case-control or cohort study design, and provision of sufficient data to calculate relative risks (RRs) or odds ratios with 95% confidence intervals (CIs). Studies evaluating risk of cerebral palsy following maternal fever, urinary tract infection, or other maternal infection were collected, but not included in the meta-analysis. DATA EXTRACTION: Information from individual studies was abstracted using standardized forms by 2 independent observers blinded to authors' names, journal titles, and funding sources. DATA SYNTHESIS: Using a random effects model, clinical chorioamnionitis was significantly associated with both cerebral palsy (RR, 1.9; 95% CI, 1.4-2.5) and cPVL (RR, 3.0; 95% CI, 2.2-4.0) in preterm infants. The RR of histologic chorioamnionitis and cerebral palsy was 1.6 (95% CI, 0.9-2.7) in preterm infants, and histologic chorioamnionitis was significantly associated with cPVL (RR, 2.1; 95% CI, 1.5-2.9). Among full-term infants, a positive association was found between clinical chorioamnionitis and cerebral palsy (RR, 4.7; 95% CI, 1.3-16.2). Factors explaining differences in study results included varying definitions of clinical chorioamnionitis, extent of blinding in determining exposure status, and whether individual studies adjusted for potential confounders. CONCLUSION: Our meta-analysis indicates that chorioamnionitis is a risk factor for both cerebral palsy and cPVL. JAMA. 2000;284:1417-1424.

Cerebral Palsy↗

Chorioamnionitis-induced changes of fetal extramedullar hematopoiesis in the second trimester of gestation. Is diagnosis from fetal autopsy possible?

Chorioamnionitis, as the most frequent cause of second trimester abortions, is commonly diagnosed by histomorphological examination of placental tissue. We determined whether chorioamnionitis induces a fetal extramedullary hematopoietic response and estimated whether chorioamnionitis can be diagnosed from fetal liver alone. Clinical data and morphological and histological findings of 39 second trimester abortions, caused by chorioamnionitis, were compared with 32 age-matched control cases. Using hematoxylin and eosin staining, naphtol-ASD-chloracetate esterase and "Berliner Blau" reaction, total hematopoiesis, erythropoiesis, myelopoiesis and intracytoplasmatic iron of fetal liver were examined. In the study group, total hematopoiesis was increased compared with the controls (94.9% versus 84.4%). The same was seen in erythropoiesis (69.2% versus 56.2%, P>0.05). Chorioamnionitis resulted in a significant increase of fetal myelopoiesis with clustering of leukocytes in 56.4% (P=0.001). Neutrophiles were located predominantly intrasinusoidal and periportal (74.4%), while an isolated periportal location was often observed in controls (50.0%). Isolated perivenous iron storing was more often seen with chorioamnionitis (28.3% versus 3.1%) and correlated with the increasing severity of chorioamnionitis. It can be stated that infectious diseases, such as chorioamnionitis, increase fetal intrahepatic myelopoiesis as one defense mechanism. The morphology of fetal intrahepatic hematopoiesis and iron storing might also be helpful in the diagnosis of chorioamnionitis, especially when the placenta is not available for examination.

Abortion, Spontaneous↗

Acute and chronic chorioamnionitis and the risk of perinatal human immunodeficiency virus-1 transmission.

OBJECTIVE: This study was undertaken to examine the prevalence of acute and chronic chorioamnionitis among women infected with human immunodeficiency virus-1 (HIV-1) and to determine the relative contribution of each to perinatal HIV-1 transmission. STUDY DESIGN: In 227 HIV-infected women receiving intrapartum/neonatal nevirapine prophylaxis, we examined associations between fetal membrane histology, cord blood interleukin-6 (IL-6), and perinatal HIV-1 transmission. RESULTS: Acute chorioamnionitis was present in 122 of 227 specimens; chronic chorioamnionitis in 64 of 227. There was a positive correlation between acute chorioamnionitis and labor length (r = 0.208; P = .002), time of ruptured membrane (r = 0.177; P = .008), and cord IL-6 (r = 0.390; P < .001). Chronic chorioamnionitis was associated with high viral load (P = .05) and low cord IL-6 (P < .001). Severe chronic chorioamnionitis was associated with intrauterine HIV-1 transmission (odds ratio [OR] = 7.61; 95% CI = 1.04-85.5), but no correlation was demonstrated between acute chorioamnionitis and vertical transmission. CONCLUSION: In a setting of high perinatal nevirapine use, acute chorioamnionitis was not associated with vertical HIV-1 transmission. Risk for intrauterine transmission increased significantly when chronic chorioamnionitis was present.

Acute Disease↗

Preterm histologic chorioamnionitis: impact on cord gas and pH values and neonatal outcome.

OBJECTIVE: The purpose of this study was to further delineate the impact of preterm chorioamnionitis on a spectrum of neonatal outcomes using a large tertiary hospital population. STUDY DESIGN: The perinatal/neonatal and placental pathology databases of St. Joseph's Health Care, London, Ontario, Canada, were used to obtain the umbilical cord gas and pH values, incidence of adverse neonatal outcomes, patient demographics, and placental pathology reports for all preterm (25 to 34 weeks of gestation), singleton, liveborn infants with no major anomalies who were delivered with spontaneous onset of labor or for suspected chorioamnionitis between November 1, 1995, and October 31, 2003. Patient groupings on the basis of placental inflammation and clinical chorioamnionitis were studied by a comparison of mean values and incidences for those neonatal outcomes that were available from the database with the use of linear and logistic regression analysis and controlling for potentially confounding variables. RESULTS: There were 660 infants who met the inclusion criteria and had placental pathology available of whom 368 (56%) had no placental inflammation, 114 (17%) had placental chorioamnionitis, and 178 (27%) had placental funisitis. Umbilical cord partial pressure oxygen and base excess values were generally higher in the placental inflammation/clinical chorioamnionitis groups, in keeping with enhanced oxygen delivery and an overall decrease in the metabolic contribution to acidosis attributed to altered lactate metabolism in these infants. After adjusting for confounders (primarily differences in gestational age), the incidence of respiratory distress syndrome was significantly decreased in the placental inflammation/clinical chorioamnionitis groups, in keeping with cytokine-induced synthesis of surfactant proteins in these infants. Although the incidence of bronchopulmonary dysplasia, intraventricular hemorrhage, and periventricular leukomalacia was generally unchanged among the groups studied, that for intraventricular hemorrhage and periventricular leukomalacia was lowest in the placental inflammation/no clinical chorioamnionitis patients and highest in the placental inflammation/clinical chorioamnionitis patients, suggesting a differential effect of clinical chorioamnionitis for these outcomes. CONCLUSION: Overall, infants born preterm with intrauterine infection were better oxygenated and showed less metabolic acidosis at birth and had incidences of respiratory distress syndrome and intraventricular hemorrhage, which were variably lower. Although there are likely threshold levels of inflammatory cytokines that do give rise to adverse outcome, a minimal level of cytokines may also be beneficial for the transition at birth from intrauterine to extrauterine existence when preterm pending the circumstances (ie, exposure to antenatal steroids) and emphasizing the complex relationship among preterm birth, infection, and adverse neonatal outcome.

Acidosis↗

Histologic chorioamnionitis, antenatal steroids, and perinatal outcomes.

OBJECTIVE: To determine the perinatal effects of histologic chorioamnionitis on preterm neonates and the effectiveness of antenatal steroids in the presence of histologic chorioamnionitis. METHODS: We studied neonates at our institution who weighed 1750 g or less at birth from January 1990 through December 1997. The population was stratified primarily by presence of histologic chorioamnionitis and secondarily by exposure to antenatal steroids. Subgroups were compared by various perinatal outcomes and confounding variables. Student t test, chi(2), Fisher exact test, and logistic regression were used for analysis. RESULTS: Among 1260 neonates entered, the placentas of 527 had evidence of histologic chorioamnionitis and 733 did not. Those with histologic chorioamnionitis had a lower mean gestational age, lower birth weight, and higher rate of major neonatal morbidities than those without it. After adjusting for confounding variables, histologic chorioamnionitis independently associated with lower gestational age, lower birth weight, and neonatal death. Among neonates exposed to antenatal steroids who had histologic chorioamnionitis, there was a significantly lower incidence of low Apgar scores (18% compared with 33.5%, P <.001), respiratory distress syndrome (RDS) (39.6% compared with 55.9%, P <.001), intraventricular hemorrhage and periventricular leukomalacia (21.9% compared with 36.9%, P <.001), major brain lesions (7.7% compared with 18.4%, P <.001), patent ductus arteriosus (14.8% compared with 23.7%, P =.018), and neonatal death (8.3% compared with 16.2%, P =.02), with no increase in rate of proven neonatal sepsis (18.3% compared with 14%, P =.24). CONCLUSION: Histologic chorioamnionitis increases major perinatal morbidity through its association with preterm birth and is independently associated with neonatal death. In the presence of histologic chorioamnionitis, antenatal steroids significantly decreased the incidence of RDS, intraventricular hemorrhage and periventricular leukomalacia, major brain lesions, and neonatal mortality, without increasing neonatal sepsis.

Anti-Inflammatory Agents↗

Chorioamnionitis and inflammation of the fetal lung.

OBJECTIVE: Fetal intrauterine exposure to proinflammatory cytokines present in amniotic fluid has been associated with an increased risk of chronic lung disease. However, the impact of histologically confirmed chorioamnionitis on the fetal lung has not yet been elucidated. We therefore investigated cellular immune response, cell proliferation, and messenger ribonucleic acid cytokine expression in fetal pulmonary tissue in the presence or absence of chorioamnionitis. STUDY DESIGN: Serial tissue sections were obtained from 27 fetuses at the time of autopsy. Three mothers had received antibiotics for treatment of clinical chorioamnionitis before abortion. Immunohistochemical staining of lung tissue comprised lineage-specific markers (CD68(+), CD3(+), neutrophil elastase). Positively stained cells were evaluated with a graticule, and cells per 5 mm(2) were counted. We undertook in situ hybridization to assess the expression of interleukin 8 messenger ribonucleic acid in the fetal lung. RESULTS: Seven of 27 fetuses had been exposed to chorioamnionitis. Fetal lungs showed a marked increase in the presence of histologically confirmed chorioamnionitis in densities of CD68(+) macrophages (68 vs 9.5 cells/5 mm(2), median group vs control group; P =.02) and lymphocytes (7 vs 2.5 cells/5 mm(2), median chorioamnionitis vs control group; P =.05) and a similar but lesser increase in neutrophil density (16 vs 4 cells/5 mm(2); difference not significant). Interleukin 8 messenger ribonucleic acid was expressed in 4 of 6 tissue specimens investigated in the chorioamnionitis group. Exposure to chorioamnionitis resulted in interleukin 8 messenger ribonucleic acid expression 7-fold higher than in the nonchorioamnionitis group; however, this difference did not achieve statistical significance. CONCLUSION: Chorioamnionitis was associated with an intrauterine inflammatory response of the fetal lung characterized by a severe infiltration of macrophages, neutrophils, and lymphocytes and also by an increased expression of interleukin 8 messenger ribonucleic acid.

Antigens, CD↗