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[Transition from the latent to the active enzymatic form as a model of regulation of extracellular matrix degradation in the chorioamnion during human labor].

Matrix metallo proteinases (MMP) are the physiological mediators of collagen degradation and its participation in physiopathogenesis of premature rupture of membranes has been suggested by our group. With the idea of defining if some MMP become active active in a coordinated way with labor in fetal membranes, we analyzed enzymatic activity and immunoreactive protein present in extracts of amnion and chorion. It was possible to identify the presence of MMP-9 in extracts of membranes obtained during cesarean sections, without labor, although its activity/quantity was faintly detectable. Instead, extracts of fetal membranes obtained during active labor showed large activity/quantity of this MMP. With a monoclonal antibody, it was possible to show that the active form of MMP-9 could only be found in samples with labor. MMP-9 and its messenger RNA, were localized by immunohistochemistry and in situ hybridization in amniotic epithelium, in some fibroblasts of the compact layer and in trophoblast-like cells in chorion. It is concluded that: 1. Activity and quantity of MMP-9 increase selectively associated to labor; and 2. That this enzyme is expressed by different cellular populations of fetal membranes.

Amnion↗

Histologic features of chorioamnion membrane rupture: development of methodology.

This study developed a set of histologic features that will allow subclassification of placentas with preterm premature rupture of membranes. Placentas were obtained from patients participating in a multi-institutional NICHD Maternal-Fetal Medicine Unit Network study of antimicrobial therapy after preterm premature rupture of membranes. The rupture site was sampled by inking the open sac margin and rolling a membrane strip in four quadrants from the ink to the placental margin. Independently, four pathologists used a provisional feature list to score the slides from 15 placentas. A concordance analysis was performed on those results. With those results, the slides were reviewed concurrently to discover the source of disagreements and to revise the feature list. The sampling method frequently demonstrated a rupture site with histology distinct from that of the remainder of the membranes. After review of the preliminary scoring results, 29 features of membrane histology present in preterm premature rupture could be objectively described with agreement among four pathologists. The feature list allows both novel and commonly recognized histologic features of fetal membranes to be recorded with objectivity. This list, with the described sampling technique, is presented as a tool for clinical correlation in studies of membrane rupture, especially in preterm, premature rupture.

Amnion↗

Second-trimester pregnancy loss at an urban hospital.

OBJECTIVES: Second-trimester spontaneous pregnancy losses are less common than first-trimester losses, and are often associated with ascending infection and/or acute chorioamnionitis. A Medline search revealed only two large studies published in the recent literature, reporting incidences of chorioamnionitis of 39.3% and 58.2%, respectively. These studies did not address the use of histopathology for the identification of organisms. Since ascending infection is likely to be a significant cause of second-trimester loss in the inner-city population at the University Hospital in Newark, New Jersey, we sought to evaluate the usefulness of stains for microorganisms, which are rarely utilized on these specimens. METHODS: Retrospective review of the medical records and pathologic material for cases of spontaneous abortions seen at the University Hospital in Newark between January 1999 and March 2001 was undertaken. Stains for microorganisms were performed on archival placental tissue for cases with histologic acute chorioamnionitis. RESULTS: A total of 67 cases were available for review, of which 38 cases (56.7%) showed histologic acute chorioamnionitis, similar to the rates in one previous study, but significantly higher than those in the other (p = 0.01). Of 25 cases with histological chorioamnionitis for which appropriate fetal material was available, 13 cases (52%) showed polymorphonuclear leukocytes (PMNs) in the fetal lungs, one case (4%) showed PMNs in the fetal stomach, and seven cases (28%) showed PMNs in both the lung and the stomach. Of the 38 cases with chorioamnionitis, Gram stains showed Gram-positive cocci in six cases, two of which were culture positive for group B streptococcus. Warthin-Starry stains showed filamentous organisms consistent with Fusobacterium sp. in the placenta in three cases. CONCLUSIONS: Acute chorioamnionitis is associated with second-trimester pregnancy loss at this inner-city hospital, and may be related to the high incidence of risk factors in this population. A small proportion of cases can be further characterized by the inclusion of Gram and Warthin-Starry stains in the evaluation. Selection of cases with histologic acute chorioamnionitis for further study with special stains may provide additional information on the causative organism.

Aborted Fetus↗

[Clinical significance of matrix metalloproteinase-9/tissue inhibitors of matrix metalloproteinase -1 imbalance in maternal serum, amniotic fluid, umbilical cord serum in patients with premature rupture of the membranes].

OBJECTIVE: To investigate the roles of matrix metalloproteinase (MMP)-9 and tissue inhibitors of matrix metalloproteinase (TIMP)-1 in maternal serum, amniotic fluid and umbilical cord serum in predicting premature rupture of the membranes (PROM) and chorioamnionitis. METHODS: The levels of MMP-9 and TIMP-1 were detected by enzyme linked immunosorbent assay in maternal serum, amniotic fluid, umbilical cord serum of 58 pregnant women with PROM and 38 women with normal pregnancies. Chorioamnionitis was histopathologically confirmed after delivery. RESULTS: (1) The levels of MMP-9 in maternal serum, umbilical cord serum and amniotic fluid were (141.9 +/- 84.6) ng/L, (138.2 +/- 81.4) ng/L and (85.6 +/- 27.5) ng/L respectively, significantly higher in patients with PROM than those of the control group (P < 0.05, P < 0.05 and P < 0.01 respectively), while the levels of TIMP-1 in maternal serum, amniotic fluid and umbilical cord serum were (378.1 +/- 220.2) ng/L, (44.6 +/- 24.0) ng/L and (257.2 +/- 98.8) ng/L respectively, significantly lower in patients with PROM than those of the control group (P < 0.05, P < 0.05 and P < 0.01 respectively). (2) The longer the duration from rupture of membranes to delivery was, the more serious chorioamnionitis was, and the higher the levels of MMP-9 and the lower the TIMP-1 levels in maternal serum, amniotic fluid, and umbilical cord serum were. (3) The levels of MMP-9 in maternal serum, umbilical cord serum and amniotic fluid were (183.8 +/- 84.7) ng/L, (171.2 +/- 92.9) ng/L and (95.5 +/- 21.1) ng/L respectively, significantly higher in patients with chorioamnionitis than those of non-chorioamnionitis (P < 0.05, P < 0.05 and P < 0.01 respectively), while the levels of TIMP-1 in maternal serum, amniotic fluid and umbilical cord serum were (269.7 +/- 144.4) ng/L, (32.1 +/- 16.6) ng/L and (210.6 +/- 81.9) ng/L respectively, significantly lower in patients with chorioamnionitis than those of non-chorioamnionitis (P < 0.05, P < 0.05 and P < 0.01 respectively). (4) The levels of MMP-9 in maternal serum, umbilical cord serum and amniotic fluid were (234.4 +/- 79.4) ng/L, (222.1 +/- 120.1) ng/L and (108.5 +/- 42.2) ng/L respectively, significantly higher in neonates whose Apgar score < or = 7 than those of neonates whose Apgar score > or = 8 (P < 0.05, P < 0.05 and P < 0.01 respectively), while the levels of TIMP-1 in maternal serum, amniotic fluid and umbilical cord serum were (225.3 +/- 121.7) ng/L, (25.2 +/- 15.8) and (181.7 +/- 135.2) ng/L respectively, significantly lower in neonates whose Apgar score < or = 7 than those of neonates whose Apgar score > or = 8 (P < 0.05, P < 0.05 and P < 0.01 respectively). CONCLUSIONS: It is suggested that preterm PROM is associated with increased MMP-9 and decreased TIMP-1 levels. MMP-9 and TIMP-1 are valuable clinical biological markers for identifying chorioamnionitis and predicting neonates prognosis.

Adult↗

Ultrasonographic assessment of the uterine cervix and interleukin-8 concentrations in cervical secretions predict intrauterine infection in patients with preterm labor and intact membranes.

OBJECTIVE: Interleukin-8 concentrations in cervical secretions have been related to microbial invasion of the amniotic cavity and histological chorioamnionitis. Since a short uterine cervix may be a risk factor for intrauterine infection, we set out to determine the interrelationship between cervical-secretion interleukin-8 concentration, cervical length measured by transvaginal sonography and intrauterine infection in women with preterm labor and intact membranes. DESIGN: The study group comprised 144 pregnant women admitted to hospital for preterm labor and intact membranes. At admission, interleukin-8 in cervical secretions was assayed. The uterine cervix was evaluated by transvaginal sonography and the cervical index (funnel length + 1)/cervical length) was measured. In all cases, amniotic fluid was obtained by amniocentesis immediately after cervical examination and was cultured for aerobic and anaerobic bacteria including Ureaplasma ureolyticum and Mycoplasma hominis. Placentas were analyzed at delivery for the presence of histological chorioamnionitis. RESULTS: Forty-three per cent (62/144) of pregnancies delivered preterm and 12.5% (18/144) of the amniotic fluid cultures were positive. Placentas were available from 54 pregnancies which delivered preterm and histological chorioamnionitis was found in 59.2% (32/54) of the cases. Interleukin-8 concentrations in cervical secretions were significantly higher in the presence of microbial invasion of the amniotic cavity (median 1191.5 ng/ml, range 812-5234 ng/ml vs. median 109 ng/ml, range 12-2231 ng/ml; p < or = 0.0001) and histological chorioamnionitis (median 982.5 ng/ml, range 430-5234 ng/ml vs. median 435 ng/ml, range 40-1750 ng/ml; p < or = 0.0001). Similarly, higher values for cervical index were obtained in the presence of a positive amniotic fluid culture (median 1.23, range 0.35-5.88 vs. median 0.29, range 0.024-4.85; p < or = 0.0001) or histological chorioamnionitis (median 1.18, range 0.043-5.88 vs. median 0.562, range 0.040-2.48; p = 0.011). Multiple logistic regression analysis indicates significant independent associations with a positive amniotic fluid culture and histological chorioamnionitis for the cervical interleukin-8 concentrations (amniotic fluid culture positive > or = 850, histological chorioamnionitis > or = 450) and for the cervical index (amniotic fluid culture positive < or = 0.58, histological chorioamnionitis < or = 0.56). CONCLUSIONS: Intrauterine infection is associated with increased interleukin-8 concentrations in cervical secretions and a short cervix. Their combined analysis may reduce the indications for invasive procedures and improve the selection of women in preterm labor who may benefit from antimicrobial treatment.

Adult↗

Chorioamnionitis/funisitis and the development of bronchopulmonary dysplasia.

OBJECTIVE: To examine the association between chorioamnionitis with or without funisitis and bronchopulmonary dysplasia in infants less than 30 completed weeks gestation given the current standards of antenatal steroid and surfactant use. METHODS: Infants included in the study were those delivered at less than 30 completed weeks gestation from January 1996 to July 2001, 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 degree of exposure to fetal inflammation (no inflammation, chorioamnionitis only and chorioamnionitis and funisitis). Data relating to gestational age, sex, antenatal steroid exposure, surfactant treatment, days of positive pressure ventilation and days of oxygen required were collected. Bronchopulmonary dysplasia was defined as death due to respiratory failure or any oxygen requirement at 36 weeks postmenstrual age. RESULTS: Two hundred and forty-one infants were included in the study. The mean gestational age was 27.7 weeks and mean birthweight 1089 g. One hundred and sixty-one infants were not exposed to any in utero inflammation, 40 showed chorioamnionitis and 40 showed chorioamnionitis and funisitis. There was no significant difference between antenatal steroid and surfactant treatment between the three groups. There was no significant difference between the three groups in the development of bronchopulmonary dysplasia. Low gestational age was the most significant predictor of developing bronchopulmonary dysplasia. CONCLUSION: The risk of developing bronchopulmonary dysplasia is not increased following exposure to chorioamnionitis or funisitis in the context of current antenatal steroid and surfactant use. The most significant predictor for developing bronchopulmonary dysplasia is gestational age at the time of delivery.

Betamethasone↗

The diagnostic value of interleukin-8 and fetal fibronectin concentrations in cervical secretions in patients with preterm labor and intact membranes.

The objectives of this study were 1) to evaluate interleukin-8 concentrations in cervical secretions in predicting preterm delivery, microbial invasion of the amniotic cavity and histologic chorioamnionitis in patients with preterm labor and intact membranes and 2) to compare the diagnostic value of interleukin-8 with fetal fibronectin determinations in predicting preterm delivery, microbial invasion of the amniotic cavity and histologic chorioamnionitis in patients with preterm labor and intact membranes. Interleukin-8 and fetal fibronectin were assayed in cervical secretions in 106 patients with singleton pregnancies and intact membranes admitted for preterm labor. Amniotic fluid obtained by amniocentesis was cultured and placentas (No = 43) analyzed for the presence of chorioamnionitis. The prevalence of pregnancies delivered preterm was 46.2% (49/106) and 15.09% (16/106) of amniotic fluid cultures were positive. Interleukin-8 levels in cervical secretions were significantly increased in patients who delivered preterm (p < or = 0.0001), in presence of positive amniotic fluid culture (p = 0.0016) and histological chorioamnionitis (p = 0.008) than in patients with negative findings. Receiver-operator characteristics curve analysis showed that an interleukin-8 value > 450 pg/ml is comparable to that of a fetal fibronectin value > 50 ng/ml in predicting preterm delivery (p = 0.247). Among patients who delivered preterm interleukin-8 concentrations > 860 pg/ml predicted a positive amniotic fluid culture with a sensitivity of 81.2% and a specificity 66.6%. Further, in patients who delivered preterm and had a negative amniotic fluid culture, IL-8 concentrations > 480 pg/ml predicted histological chorioamnionitis with a sensitivity 78.5% and specificity 61.5%. A positive fetal fibronectin > 50 ng/ml was not predictve of either a positive amniotic fluid culture or the presence of histological chorioamnionitis. In conclusion, increased concentrations of interleukin-8 and fetal fibronectin are associated with impending delivery and their diagnostic value seems comparable. However, interleukin-8 concentrations identify patients at risk of a positive amniotic fluid culture and the presence of histological chorioamnionitis. Measurement of interleukin-8 in cervical secretion is a non-invasive method to identify patients at risk for both preterm delivery and intrauterine infection.

Adult↗

The significance of C-reactive protein levels in women with premature rupture of membranes.

In a prospective study of 100 patients with preterm premature rupture of membranes, clinical chorioamnionitis was present in 18 and histologic chorioamnionitis was present in 63. Patients who were managed conservatively for premature rupture of membranes were monitored by C-reactive protein determination, white blood cell and differential counts, maternal temperature, and fetal heart tone. C-reactive protein was measured nephelometrically (Immuno-chemistry Analyzer II, Beckman). Elevated C-reactive protein levels correlated well with both the pathologic and the clinical diagnosis of chorioamnionitis. Elevated C-reactive protein levels (at least 12 to 24 hours before delivery) were more sensitive than other standard laboratory or clinical tests in predicting chorioamnionitis both by clinical and pathologic criteria. When C-reactive protein values were normal, clinical chorioamnionitis was rarely found, whereas pathologically diagnosed chorioamnionitis was found half of the time. We conclude that although the C-reactive protein level is a very sensitive predictor of infectious morbidity in premature rupture of membranes, its specificity is not high.

Adolescent↗

The preterm prediction study: fetal fibronectin, bacterial vaginosis, and peripartum infection. NICHD Maternal Fetal Medicine Units Network.

OBJECTIVE: To determine the relation between vaginal and upper genital tract infection and cervical-vaginal fetal fibronectin levels. METHODS: We screened 2899 women at ten centers every 2 weeks from 23-24 to 30 weeks' gestation for cervical and vaginal fetal fibronectin. A positive test was defined as a level of at least 50 ng/mL. The relation between a positive test and bacterial vaginosis at 23-24 weeks and clinical or histologic chorioamnionitis at delivery plus neonatal sepsis was determined. RESULTS: Fetal fibronectin was present in 4.0% of cervical and/or vaginal samples at 23-24 weeks and was nearly twice as common in women with bacterial vaginosis. Adjusting for the presence of bacterial vaginosis, race, and parity, women positive for fetal fibronectin were much more likely to have clinical chorioamnionitis (mean +/- standard deviation gestational age 30.6 +/- 4.1 weeks), with an odds ratio of 16.4 and 95% confidence interval of 7.1-37.8, and neonatal sepsis (6.3 and 2.0-20.0, respectively), than those who were fetal fibronectin-negative. A positive cervical fetal fibronectin test was a better predictor of clinical chorioamnionitis and neonatal sepsis than was a vaginal test or a combination of vaginal and cervical tests. Among 40 women who delivered before 32 weeks and had placental histology available for evaluation, ten had a positive cervical and/or vaginal fetal fibronectin test before delivery; all ten had histologic evidence of chorioamnionitis, compared with only 13 of 30 women (43%) who were fetal fibronectin-negative (P = .02). CONCLUSION: Women with bacterial vaginosis were more likely to have a positive fetal fibronectin test than uninfected women. Women with a positive fetal fibronectin test who delivered before 32 weeks' gestation all had evidence of histologic chorioamnionitis. Women positive for fetal fibronectin also had a 16-fold increase in clinical chorioamnionitis and a sixfold increase in neonatal sepsis. There is strong evidence that upper genital tract infection and cervical and/or vaginal fetal fibronectin are closely linked.

Adult↗

Expression of bone morphogenetic protein 2 in normal spontaneous labor at term, preterm labor, and preterm premature rupture of membranes.

OBJECTIVE: Genome-wide screening studies of the chorioamniotic membranes unexpectedly identified an increase in the expression of bone morphogenetic protein 2 in spontaneous labor at term. The objective of this study was to determine whether bone morphogenetic protein 2 messenger RNA and protein expression are altered in the chorioamniotic membranes of patients with term labor, preterm labor, and preterm premature rupture of membranes. STUDY DESIGN: Chorioamniotic membranes were obtained from patients at term (with and without labor), with preterm labor (with and without histologic chorioamnionitis), and with preterm premature rupture of membranes (with and without histologic chorioamnionitis). The expression of bone morphogenetic protein 2 was studied by real-time quantitative reverse transcriptase-polymerase chain reaction (n = 88) and immunohistochemistry (n = 124). Nonparametric statistics were used for analysis. Primary amnion cells obtained from women at term not in labor were treated with bone morphogenetic protein 2 to examine whether there was increased prostaglandin E2 expression. RESULTS: The median bone morphogenetic protein 2 messenger RNA and protein expression were significantly higher in the membranes of patients with spontaneous labor at term than in those of patients not in labor at term (P < .001 for both). Bone morphogenetic protein 2 messenger RNA and protein expression were increased in patients with preterm labor with histologic chorioamnionitis than in those without histologic chorioamnionitis (P < .05 and P < .001, respectively). There was no difference in bone morphogenetic protein 2 messenger RNA and protein expression in patients with preterm premature rupture of membranes, regardless of chorioamnionitis (P = .13 and P = .08, respectively). There was a correlation between bone morphogenetic protein 2 and cyclooxygenase 2 protein expression in chorioamniotic membranes (R = .34; P < .001). CONCLUSION: Bone morphogenetic protein 2 messenger RNA and protein expression are increased in the chorioamniotic membranes of patients with spontaneous labor at term and patients with preterm labor associated with histologic chorioamnionitis. Its expression pattern and biologic effects strongly suggest that bone morphogenetic protein 2 is involved in human parturition.

Amnion↗

Serum C-reactive protein, white blood cell count, and amniotic fluid white blood cell count in women with preterm premature rupture of membranes.

OBJECTIVE: To compare the diagnostic performance of maternal blood C-reactive protein, white blood cell count (WBC), and amniotic fluid (AF) WBC in the identification of positive AF culture, histologic and clinical chorioamnionitis, and neonatal morbidity in women with preterm premature rupture of membranes (PROM). METHODS: Maternal blood was collected for the determination of C-reactive protein and WBC at the time of amniocentesis from 90 women with preterm PROM. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as mycoplasmas. Amniotic fluid WBC was determined for research purposes. Receiver operating characteristic curve and logistic regression were used for statistical analysis. RESULTS: The prevalence of positive AF culture was 28% (25 of 90). Women with positive AF culture and clinical chorioamnionitis had significantly higher median C-reactive protein, WBC, and AF WBC than did women without these conditions (P < .05), whereas women with histologic chorioamnionitis and significant neonatal morbidity had higher median C-reactive protein and AF WBC, but not WBC, than those without the conditions (P < .05). An AF WBC of at least 20 cells per mm3 had a greater sensitivity than C-reactive protein (cutoff, 0.7 mg/dL) and WBC (cutoff, 13,000 cells per mm3) in the detection of positive AF culture and histologic chorioamnionitis. Logistic regression analysis indicated that among AF WBC, C-reactive protein, and WBC, AF WBC was the best predictor of positive AF culture (odds ratio [OR] 24.2, 95% confidence interval [CI] 6.0, 97.5, P < .001), histologic (OR 74.0, 95% CI 7.4, 736.3, P < .001) and clinical chorioamnionitis (OR 8.9, 95% CI 0.9, 85.6, P = .057), and neonatal morbidity (OR 4.3, 95% CI 1.1, 16.6, P < .05). CONCLUSION: Amniotic fluid WBC performs better than C-reactive protein and maternal blood WBC in the diagnosis of positive AF culture, histologic and clinical chorioamnionitis, and neonatal morbidity in women with preterm PROM.

Adult↗

Umbilical vein interleukin-6 levels correlate with the severity of placental inflammation and gestational age.

Interleukin-6 (IL6) and suppurating placental inflammation are markers of neonatal sepsis. The purpose of this study was to define a relationship between IL6 and acute chorioamnionitis and funisitis of the placenta, and to compare IL6 levels in term and preterm neonates. Umbilical venous IL6 was measured in 137 term and 110 preterm neonates. Acute chorioamnionitis was graded as none, mild, moderate, severe, and necrotizing. Funisitis was graded as none, 1 vessel, 2 vessels, 3 vessels, or necrotizing. A 2-way analysis of variance with interaction was used to compare the IL6 levels. There was a stepwise progression of IL6 levels with increasing severity of acute chorioamnionitis and funisitis. Term neonates showed an IL6 elevation with mild acute chorioamnionitis and single-vessel vasculitis, which increased progressively until the inflammation became severe. In contrast, IL6 levels in preterm neonates did not increase significantly until severe acute chorioamnionitis or 3-vessel vasculitis was seen. Statistically significant differences in IL6 levels were seen in term versus preterm infants when the acute chorioamnionitis was mild or moderate or when the funisitis involved either 1 or 2 vessels (P < 0.05). The difference may be related to the relative immaturity of the preterm immune system, as has been demonstrated in vivo and in vitro. However, differences in management could be confounding factors. In conclusion, umbilical venous IL6 levels correlate with the severity of acute placental inflammation, with greater IL6 elevations in term infants compared to preterm infants until the inflammation becomes severe.

Acute Disease↗

Umbilical vein interleukin 6 and tumor necrosis factor alpha plasma concentrations in the very preterm infant.

OBJECTIVE: To examine the relationship between umbilical vein plasma concentrations of interleukin 6 (IL-6) and tumor necrosis factor (TNF)-alpha and early neonatal sepsis in the very preterm infant, and the histopathologic findings of chorioamnionitis in the placentas from these pregnancies. METHODS: A prospective study was conducted in 43 very preterm, singleton infants delivered at or before 32 weeks of gestation. IL-6 and TNF-alpha were measured by enzyme-linked immunoassay. Placentas from these pregnancies were histologically examined for the presence of chorioamnionitis. Infants were prospectively classified as confirmed sepsis group, clinical sepsis group or control group. IL-6 and TNF-alpha plasma concentrations were not normally distributed, so they were transformed to their natural log values for statistical analysis. RESULTS: The enrolled infants had a mean gestational age of 27.2 +/- 2.7 weeks and a mean birth weight of 956 +/- 325 g. Three (7%) infants had confirmed sepsis, 18 (42%) were in the clinical sepsis group and 22 (51%) were in the control group. IL-6 concentrations but not TNF-alpha were significantly higher (P < 0.05) in the confirmed (8.9 +/- 1.7) and clinical sepsis (5.5 +/- 2.4) groups in comparison with the control group (2.1 +/- 1.6). We examined 42 placentas. Twenty-three (55%) had no evidence of chorioamnionitis, 1 (2%) had mild grade, 8 (19%) had a moderate grade and 10 (24%) had a severe grade of chorioamnionitis. IL-6 was significantly elevated in the moderate (5.9 +/- 1.6 vs. 1.9 +/- 1.6) and severe grade (7.2 +/- 2.3 vs. 1.9 +/- 1.6) of chorioamnionitis, in the presence of acute deciduitis (6.0 +/- 2.7 vs. 2.1 +/-1.8), chorionic vasculitis (6.8 +/- 2.1 vs. 2.2 +/- 1.9) and funisitis (7.3 +/- 1.9 vs. 2.7 +/- 2.3) (P < 0.05) TNF-alpha plasma concentrations were not significantly different. CONCLUSION: An elevated umbilical vein IL-6 concentration is a good indicator of sepsis syndrome in the very preterm infant and also correlates with histologic chorioamnionitis in these pregnancies.

Blood Cell Count↗

[Intrauterine infections. I. The role of C-reactive protein, white blood cell count and erythrocyte sedimentation rate in pregnant women in the detection of intrauterine infection after preliminary rupture of membranes].

UNLABELLED: The purpose of our study was to analyze the efficacy of serum C-reactive protein (CRP), white blood cell count (WBC) and erythrocyte sedimentation rate (ESR) serial evaluations in the prediction of chorioamnionitis in cases of premature rupture of membranes (PROM). MATERIALS AND METHODS: A group of 80 patients with PROM before 35 weeks' gestation were evaluated prospectively and managed expectantly. We applied the expectant management with the permanent use of tocolysis, antibiotics, steroids, amnioinfusions of artificial amniotic fluid and intravaginal chemotherapeutics. Patients were monitored with frequent vital signs, fetal heart rate evaluation and everyday blood tests as follows: CRP, WBC and ESR. All afterbirths were examined to establish the presence of histologic chorioamnionitis (gold standard of intrauterine infection). RESULTS: 59 (73.7%) patients had significant chorioamnionitis on histopathology and only 15 of them had clinical chorioamnionitis. Serum CRP serial determinations (definition of abnormal tests: 1) > 1.2 mg/dl; 2) > 2.0 mg/dl; 3) > 1.2 mg/dl and increasing in two consecutive days) were found the most reliable with a sensitivity 1) 91.5%; 2) 85%; 3) 88%, specificity 57%; 76%; 86%, positive predictive value 86%; 90%; 94.5%, negative predictive value 70.5%; 64%; 72% and accuracy 82.5%; 82.5%; 87.5% respectively. The efficacy of WBC (abnormal tests: > 12500/mm3; > 15000/mm3; > 12500/mm3 and increasing in two consecutive days) and ESR (abnormal tests: > 60 mm/h; > 60 mm/h and increasing in two consecutive days) serial evaluations was significantly lower. Moreover, in cases of chorioamnionitis CRP increased above the upper limit of normal 3 days earlier than WBC or ESR. CONCLUSIONS: CRP was found the most reliable indicator of histologic chorioamnionitis and indicated the presence of intrauterine infection earlier than WBC or ESR.

Adult↗

Amniotic fluid interleukin-6: correlation with upper genital tract microbial colonization and gestational age in women delivered after spontaneous labor versus indicated delivery.

OBJECTIVE: Our purpose was to determine whether amniotic fluid interleukin-6 is increased and inversely proportional to gestational age in women with chorioamnion colonization and spontaneous labor versus women delivered for medical or obstetric indications. STUDY DESIGN: The chorioamnion and amniotic fluid were cultured at cesarean delivery for aerobic and anaerobic bacteria, fungi, mycoplasmas, Chlamydia trachomatis and Trichomonas vaginalis in 269 women with singleton gestations with intact membranes. The amniotic fluid interleukin-6 concentration was also determined. RESULTS: Amniotic fluid interleukin-6 levels were (1) higher in women with spontaneous labor versus those with indicated deliveries (15.8 +/- 5.0 vs 2.2 +/- 0.2 ng/ml, p = 0.01), (2) inversely proportional to gestational age in women with spontaneous labor (< 34 weeks: 47.4 +/- 18.0 ng/ml vs > or = 34 weeks: 8.7 +/- 4.1 ng/ml, p = 0.001) but not in women with indicated deliveries (1.5 +/- 0.4 vs 2.4 +/- 0.3 ng/ml), (3) higher in women with a positive versus a negative chorioamnion (15.1 +/- 4.8 vs 3.0 +/- 0.8 ng/ml, p < 0.001) or amniotic fluid (17.4 +/- 7.7 vs 3.8 +/- 0.9 ng/ml, p < 0.001) culture, and (4) higher in women with a negative amniotic fluid but positive chorioamnion culture compared with women in whom both cultures were negative (10.0 +/- 4.4 vs 3.0 +/- 0.9 ng/ml, p = 0.002). CONCLUSIONS: Amniotic fluid interleukin-6 levels are (1) higher and inversely proportional to gestational age in women with intact membranes and spontaneous labor versus indicated deliveries, (2) higher in women with one or more microorganisms in the chorioamnion or amniotic fluid, and (3) reflective of chorioamnion microbial colonization, even when the amniotic fluid culture is negative, and may be a useful clinical marker for infection-mediated preterm labor.

Amnion↗

C-reactive protein in preterm premature rupture of the membranes.

The usefulness of maternal C-reactive protein (CRP) measurements in the diagnosis of chorioamnionitis and puerperal and neonatal infectious morbidity was studied among 147 patients with preterm rupture of the membranes (PROM). Thirty-three patients developed chorioamnionitis, 10 patients developed puerperal endometritis, and 21 newborn infants developed neonatal infections. There was no difference in the highest antepartum CRP between patients with or without chorioamnionitis. The overall test performance for CRP was poor suggesting that elevated antepartum CRP may be misleading in the diagnosis of chorioamnionitis. However, use of serial CRP measurements increases the test performance. The high negative predictive value suggests that CRP is useful in predicting the absence of chorioamnionitis.

Adult↗

Amniotic fluid interleukin-6: a sensitive test for antenatal diagnosis of acute inflammatory lesions of preterm placenta and prediction of perinatal morbidity.

OBJECTIVE: Our purpose was to determine whether amniotic fluid concentrations of interleukin-6 are of value in the antenatal diagnosis of acute inflammatory lesions (histologic chorioamnionitis) of preterm placenta and in the prediction of perinatal morbidity and mortality. STUDY DESIGN: The relation among placental histologic findings, perinatal outcome, and amniotic fluid interleukin-6 concentrations was examined in 50 consecutive patients who delivered preterm neonates within 72 hours after amniocentesis. Interleukin-6 was determined by enzyme-linked immunosorbent assays. Receiver-operator characteristic curve was used for analysis. RESULTS: Patients with acute histologic chorioamnionitis had significantly higher median amniotic fluid interleukin-6 concentrations than patients without histologic chorioamnionitis (median 70.8 ng/ml, range 0.7 to 499.2 ng/ml vs median 2.9 ng/ml, range 0.8 to 16.0 ng/ml, respectively; p < 0.00001). An amniotic fluid interleukin-6 concentration > 17 ng/ml had a sensitivity of 79% (23/29) and a specificity of 100% (21/21) in the diagnosis of acute histologic chorioamnionitis and a sensitivity of 69% (18/26) and a specificity of 79% (19/24) in the prediction of significant neonatal morbidity (defined as neonatal sepsis, respiratory distress syndrome, pneumonia, intraventricular hemorrhage, bronchopulmonary dysplasia, or necrotizing enterocolitis) and mortality. These sensitivities were significantly higher than those of amniotic fluid culture (79% vs 38%, p < 0.005; 69% vs 27%, p < 0.01, respectively). CONCLUSIONS: Amniotic fluid interleukin-6 is a sensitive test for the prospective diagnosis of acute histologic chorioamnionitis and the identification of neonates at risk for significant morbidity and mortality.

Amniotic Fluid↗