Amniotic Fluid Interleukin-6 Concentrations Research Articles

Microbial invasion of the amniotic cavity with Ureaplasma urealyticum is associated with a robust host response in fetal, amniotic, and maternal compartments

Objective: Ureaplasma urealyticum is the microorganism most frequently isolated from the amniotic fluid of women with preterm labor and preterm premature rupture of the membranes, yet the significance of amniotic fluid infection exclusively caused by this microorganism is unclear. This study was conducted to examine the presence and intensity of the inflammatory response in the fetal, amniotic, and maternal compartments in patients with preterm premature rupture of membranes and amniotic fluid infection with U urealyticum . Study Design: One hundred twenty patients with preterm premature rupture of the membranes who delivered preterm neonates (gestational age ≤36 weeks) within 5 days of amniocentesis were included. Amniotic fluid was cultured for aerobic and anaerobic bacterias and mycoplasmas. The intensity of the inflammatory response was evaluated by amniotic fluid concentrations of interleukin-6, tumor necrosis factor-α, interleukin-1β, amniotic fluid white blood cell count, histologic chorioamnionitis, and interleukin-6 concentrations of umbilical cord plasma at birth. Cytokines were measured by sensitive and specific immunoassays. Results: The prevalence of a positive amniotic fluid culture in which the only microbial isolate was U urealyticum was 21% (25/120) and that of positive cultures with other or mixed microorganisms was 9% (11/120). Intrauterine inflammatory response was significantly more intense in patients with positive amniotic fluid cultures limited to U urealyticum than in those with a negative culture (median and range of amniotic fluid interleukin-6, 13.4 [0.7-115.2] ng/mL vs 0.9 [0.001-137.2] ng/mL; median and range of amniotic fluid tumor necrosis factor-α, 85.5 [0.9-1600] pg/mL vs 2.4 [0-1142] pg/mL; median and range of amniotic fluid interleukin-1β, 274.0 [0.3->80,000] pg/mL vs 3.4 [0-1449] pg/mL; median and range of amniotic fluid white blood cell count, 306 [0-19,764] cells/mm 3 vs 3 [0-7956] cells/mm 3 ; median and range of cord interleukin-6, 20.0 [2.3-1199.6] pg/mL vs 6.7 [0-5550] pg/mL; histologic chorioamnionitis, 100% [22/22] vs 42% [30/72]; P < .01 for each) but was similar to values of patients with a positive amniotic fluid culture for other bacteria or mixed microorganisms. Conclusion: Patients with preterm premature rupture of membranes and microbial invasion of the amniotic cavity with U urealyticum are associated with a robust host inflammatory response in the fetal, amniotic, and maternal compartments. (Am J Obstet Gynecol 1998;179:1254-60.)

The fetal inflammatory response syndrome

OBJECTIVE: The objective of this study was to determine the frequency and clinical significance of a systemic inflammatory response as defined by an elevated plasma interleukin-6 concentration in fetuses with preterm labor or preterm premature rupture of membranes. STUDY DESIGN: Amniocenteses and cordocenteses were performed in 157 patients with preterm labor and preterm premature rupture of membranes. Written informed consent and multi-institutional review board approvals were obtained. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as mycoplasmas. Amniotic fluid and fetal plasma interleukin-6 concentrations were measured with a sensitive and specific immunoassay. Statistical analyses included contingency tables, receiver operating characteristic curve analysis, and multiple logistic regression. RESULTS: One hundred five patients with preterm labor and 52 patients with preterm premature rupture of membranes were included in this study. The overall prevalence of severe neonatal morbidity (defined as the presence of respiratory distress syndrome, suspected or proved neonatal sepsis, pneumonia, bronchopulmonary dysplasia. intraventricular hemorrhage, periventricular leukomalacia, or necrotizing enterocolitis) among survivors was 34.8% (54/155). Neonates in whom severe neonatal morbidity developed had higher concentrations of fetal plasma interleukin-6 than fetuses without development of severe neonatal morbidity (median 14.0 pg/mL, range 0.5 to 900 vs median 5.2 pg/mL, range 0.3 to 900, respectively; P < .005). Multivariate analysis was performed to explore the relationship between the presence of a systemic fetal inflammatory response and subsequent neonatal outcome. To preserve a meaningful temporal relationship between the results of fetal plasma interleukin-6 concentrations and the occurrence of severe neonatal morbidity, the analysis was restricted to 73 fetuses delivered within 7 days of cordocentesis who survived. The prevalence of severe neonatal morbidity in this subset of patients was 53.4% (39/73). A fetal plasma interleukin-6 cutoff value of 11 pg/mL was used to define the presence of a systemic inflammatory response. The prevalence of a fetal plasma interleukin-6 level >11 pg/mL was 49.3% (36/73). Fetuses with fetal plasma interleukin-6 concentrations >11 pg/mL had a higher rate of severe neonatal morbidity than did those with fetal plasma interleukin-6 levels ≤11 pg/mL (77.8% [28/36] vs 29.7% [11/37], respectively; P < .001). Stepwise logistic regression analysis demonstrated that the fetal plasma interleukin-6 concentration was an independent predictor of the occurrence of severe neonatal morbidity (odds ratio 4.3, 95% confidence interval 1 to 18.5) when adjusted for gestational age at delivery, the cause of preterm delivery (preterm labor or preterm premature rupture of membranes), clinical chorioamnionitis, the cordocentesis-to-delivery interval, amniotic fluid culture, and anmiotic fluid interleukin-6 results. CONCLUSION: A systemic fetal inflammatory response, as determined by an elevated fetal plasma interleukin-6 value, is an independent risk factor for the occurrence of severe neonatal morbidity. (Am J Obstet Gynecol 1998;179:194-202.)

The relationship between amniotic fluid interleukin-6 concentration and histologic evidence of chorioamnionitis

The relationship between amniotic fluid interleukin-6 concentration and histologic evidence of chorioamnionitis

Amniotic fluid cytokines (interleukin-6, tumor necrosis factor-α, interleukin-1β, and interleukin-8) and the risk for the development of bronchopulmonary dysplasia

OBJECTIVE: Our purpose was to test the hypothesis that neonates who develop bronchopulmonary dysplasia have higher amniotic fluid concentrations of proinflammatory cytokines than those who do not develop bronchopulmonary dysplasia. STUDY DESIGN: The relationship between amniotic fluid concentrations of interleukin-6, tumor necrosis factor-α, interleukin-1β, and interleukin-8 and the occurrence of bronchopulmonary dysplasia in the neonate was examined in 69 patients who were delivered of preterm neonates (≤33 weeks) within 5 days of amniocentesis. Cytokines were measured by specific immunoassays. RESULTS: Bronchopulmonary dysplasia was diagnosed in 19% (13/69) of newborns. Median amniotic fluid concentrations of interleukin-6, tumor necrosis factor-α, interleukin-1β, and interleukin-8 concentrations were significantly higher in mothers whose infants had bronchopulmonary dysplasia than in mothers whose infants did not have bronchopulmonary dysplasia ( p < 0.05 for each). Neonates who had bronchopulmonary dysplasia were delivered at earlier gestational ages and had lower birth weights than those without bronchopulmonary dysplasia. The differences in median amniotic fluid interleukin-6, interleukin-1β, and interleukin-8 between these two groups remained significant after we adjusted for the effect of gestational age at birth ( p < 0.05 for each). CONCLUSIONS: (1) Antenatal exposure to proinflammatory cytokines is a risk factor for the development of bronchopulmonary dysplasia; (2) the injury responsible for bronchopulmonary dysplasia in a subset of neonates may begin before birth. (Am J Obstet Gynecol 1997;177:825-30.)

Polymorphonuclear Elastase and Interleukin-6 in Amniotic Fluid in Preterm Labor

Microbial invasion of the amniotic cavity has been demonstrated in 16.1% of women with preterm labor and intact membranes (1). This situation is frequently difficult to diagnose because its clinical manifestations occur late in pregnancy and because biochemical and microbiological studies are required for accurate diagnosis (2). Saito et al. (3) implicated cytokines in the pathophysiology of preterm labor, and high concentrations of interleukin-6 (IL-6) have been detected in amniotic fluid of women with amniotic infection (4). Moreover, we thought that a proteinase, e.g., elastase, located in the polymorphonuclear neutrophils (PMN) might be involved in infection-associated preterm labor. We therefore undertook a study of IL-6, elastase-PMN (which has not been studied before), leukocytes, and glucose concentrations in amniotic fluid in women in preterm …

Measurement of amniotic fluid interleukin-6 using commercial kits

Objective The association between increased amniotic fluid interleukin-6 (IL-6) concentrations and preterm labor has received increasing attention. Several research groups have evaluated this association using commercial IL-6 kits, which principally use the sandwich-enzyme-immunoassay method, and were originally created to measure IL-6 in plasma, serum, or culture media. We evaluated commercial kits for the determination of IL-6 in amniotic fluid. Methods Seven commercial kits were used to determine IL-6 concentrations in three amniotic fluid samples which were obtained from patients with clinical chorioamnionitis during labor and five from normal pregnancies at mid-trimester. Results Amniotic fluid IL-6 values differed significantly with some having over a 50-fold discrepancy and the recovery of known IL-6 added to amniotic fluid ranged from 12 to 123%. However, by all kits we were able to identify that amniotic fluid from patients with chorioamnionitis contained significantly higher IL-6 concentrations than those from normal mid-trimester pregnancies. Conclusion Our data indicate that standardization of the method for measuring IL-6 in amniotic fluid is desirable for the comparison of values from various laboratories. Infect. Dis. Obstet. Gynecol. 5:222–225, 1997. © 1997 Wiley-Liss, Inc.

Measurement of Amniotic Fluid Interleukin-6 Using Commercial Kits

Objective: The association between increased amniotic fluid interleukin-6 (IL-6) concentrations and preterm labor has received increasing attention. Several research groups have evaluated this association using commercial IL-6 kits, which principally use the sandwich-enzyme-immunoassay method, and were originally created to measure IL-6 in plasma, serum, or culture media. We evaluated commercial kits for the determination of IL-6 in amniotic fluid. Methods: Seven commercial kits were used to determine IL-6 concentrations in three amniotic fluid samples which were obtained from patients with clinical chorioamnionitis during labor and five from normal pregnancies at mid-trimester. Results: Amniotic fluid IL-6 values differed significantly with some having over a 50-fold discrepancy and the recovery of known IL-6 added to amniotic fluid ranged from 12 to 123%. However, by all kits we were able to identify that amniotic fluid from patients with chorioamnionitis contained significantly higher IL-6 concentrations than those from normal mid-trimester pregnancies. Conclusion: Our data indicate that standardization of the method for measuring IL-6 in amniotic fluid is desirable for the comparison of values from various laboratories.

Soluble tumor necrosis factor receptors and interleukin-6 levels in patients with severe preeclampsia

To investigate whether serum and amniotic fluid (AF) levels of soluble tumor necrosis factor receptors and interleukin-6, markers of immune activation and endothelial dysfunction, are altered in patients with severe preeclampsia. Plasma was collected before induction of labor, at delivery, and postpartum from 19 patients with severe preeclampsia. Amniotic fluid was also obtained in early labor from these patients. Similar samples were obtained from an antepartum control group matched for gestational age and a term control group without preeclampsia. All plasma and AF samples were assayed for p55 and p75 soluble tumor necrosis factor receptors and for interleukin-6 by specific enzyme-linked immunoassays. Levels in preeclamptic patients and the control groups were compared. Levels of both receptors were significantly elevated in AF and all maternal plasma samples except those collected 24 hours postpartum for patients with preeclampsia relative to levels in controls. Interleukin-6 was detected more frequently and in higher concentrations in the plasma collected before labor for preeclamptic patients compared with controls, but no difference was noted in interleukin-6 detection rates or plasma concentrations at delivery. Conversely, AF concentrations of interleukin-6 were significantly reduced in patients with preeclampsia. The increased levels of soluble tumor necrosis factor receptors found in patients with severe preeclampsia may represent a protective response to increased tumor necrosis factor activity and be a marker for immune activation. Increased interleukin-6 concentrations in maternal plasma before labor suggest the involvement of this cytokine as well in the altered immune response and its contribution to endothelial cell dysfunction.

Differential release of interleukin-6 from human gestational tissues in association with labour and in vitro endotoxin treatment.

In this study, we quantified interleukin-6 (IL-6) concentrations in amniotic fluid at term and preterm labour, and determined the gestational tissue source of IL-6. In addition, aspects of the regulatory mechanisms involved in IL-6 release at the time of term labour and in response to bacterial endotoxin, lipopolysaccharide (LPS), have been established. IL-6 concentrations were 2-fold higher in amniotic fluid collected at term compared with preterm gestation, with an additional 2-fold increase in association with term labour. IL-6 was released from all choriodecidual and placental explants but was detected in only 33% of amniotic explant cultures of tissues obtained before labour onset. In contrast, IL-6 was detected in all amniotic, choriodecidual and placental cultures of tissues obtained after term labour onset and delivery, and the mean IL-6 release was significantly higher than that measured in explant cultures of both amniotic (80-fold increase, P < 0.0001) and choriodecidual (3-fold increase, P < 0.02) but not placental explants taken at the time of elective Caesarean section at term before labour onset. LPS significantly (P < 0.05) increased the release of IL-6 from human choriodecidual and placental explants but not amniotic explants, in a time- and dose-dependent manner. IL-6 is a physiological constituent of amniotic fluid and its production by gestational tissues is differentially regulated by LPS and spontaneous labour onset and delivery.

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 fludi 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.

The Value of Amniotic Fluid Interleukin‐6, White Blood Cell Count, and Gram Stain in the Diagnosis of Microbial Invasion of the Amniotic Cavity in Patients at Term

Subclinical microbial invasion of the amniotic cavity occurs in 18.8% of women with term labor and intact membranes and in 34% of patients with term PROM and is a risk factor for the development of puerperal infection related morbidity. Although amniotic fluid white blood cell count, interleukin-6 determination, and Gram stain examination have been used for the diagnosis of intrauterine infection in patients with preterm labor and preterm premature rupture of membranes, no information is available about the accuracy and specific cut-off values for these tests in patients at term. The purpose of this study was to compare the performance of the amniotic fluid Gram stain examination, white blood cell count, and interleukin-6 determination in the identification of microbial invasion of the amniotic cavity in patients at term with and without PROM. Amniotic fluid was retrieved from 148 patients with term gestations (90 patients with spontaneous labor and intact membranes and 58 patients with PROM). Samples were cultured for bacteria and Mycoplasma species. Amniotic fluid Gram stain, white blood cell count, and interleukin-6 determinations (ELISA, sensitivity: 43 pg/ml) were performed in all samples. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture for microorganisms. Analysis was conducted using Mann-Whitney U test, Fisher's exact test, receiver operating characteristic curves and logistic regression. Patients with spontaneous labor and intact membranes: The prevalence of microbial invasion of amniotic cavity in this group was 15.6% (14/90). The most sensitive test for the detection of microbial invasion of the amniotic cavity was amniotic fluid interleukin-6 determination (sensitivity for: interleukin-6 > or = 5.7 ng/ml = 86%, white blood cell count > or = 20 cells/mm3 = 64%, Gram stain = 28%). The most specific test was the Gram stain of the amniotic fluid (specificity for: Gram stain = 84%, interleukin-6 = 79% and white blood cell count = 63%). Multiple logistic regression demonstrated that amniotic fluid interleukin-6 concentration was the only covariate that retained statistical significance when intrauterine infection was used as outcome variable. Patients with PROM: The prevalence of a positive amniotic fluid culture in this group was 39.7% (23/58). Logistic regression demonstrated that only interleukin-6 retained a significant relationship with the results of amniotic culture when all variables were entered simultaneously into a model to predict amniotic fluid culture results. The most sensitive tests for the detection of intrauterine infection were interleukin-6 determination and white blood cell count (sensitivity for interleukin-6 > or = 3.4 ng/ml and white blood cell count > or = 20 cells/mm3 = 69.6% for both). The most specific test was Gram stain (97.1%). Amniotic fluid interleukin-6 determination is the best rapid test for the detection of microbial invasion of the amniotic cavity in patients at term with and without PROM. When this test is not available, amniotic fluid Gram stain and white blood cell count represent valid diagnostic tools to assess the microbial state of amniotic cavity.

Clinical value of amniotic fluid interleukin‐6 determinations in the management of preterm labour

To ascertain whether the determination of amniotic fluid interleukin-6 (IL-6) concentrations would be a useful clinical test in the management of women with preterm contractions. The labour and delivery unit and the Fetal Diagnostic Centre at the University of Utah. Pregnant women at various stages of gestation in the third trimester. Amniotic fluid samples were collected from women experiencing one of four clinical scenarios: 1. term pregnancy, not in labour with no evidence of intrauterine infection; 2. normal term labour with no evidence of infection; 3. preterm labour with no evidence of infection and undelivered within one week of sampling; and 4. preterm labour and delivered within seven days of sample collection. Amniotic fluid was obtained by amniocentesis or at the time of amniotomy or hysterotomy. IL-6 in each specimen was determined by a specific rapid ELISA. Amniotic fluid IL-6 levels, given as mean (SEM) in the four groups of women listed were: 1. term pregnancy, not in labour: 20.9 (7.2) pg/ml (n = 60); 2. normal term labour with no infection: 554 (90.7) pg/ml (n = 46); 3. preterm labour with no evidence of infection, undelivered: 47.0 (17.2) pg/ml (n = 35); and 4. preterm labour, delivered: 456.7 (101.7) pg/ml (n = 40). There was no significant difference in the means of amniotic fluid IL-6 for the term labour and preterm labour delivered groups. In general, amniotic fluid IL-6 levels during term labour increased with advancing cervical dilation. There was no correlation of cervical dilation and amniotic fluid IL-6 levels in women having preterm delivery. Receiver-operator curves revealed optimal IL-6 levels for discrimination of labour at term to be 50 pg/ml and for preterm delivery to be 200 pg/ml. IL-6 can readily be detected in the amniotic fluid of most women who are in active labour, regardless of gestational age. Our data suggest that amniotic fluid IL-6 determinations may be clinically useful in the management of preterm labour.

Systemic and local cytokine profiles in endotoxin-induced preterm parturition in mice

OBJECTIVE: Our purpose was to determine whether endotoxin-induced preterm parturition is preceded by a change in the maternal serum and amniotic fluid concentrations of tumor necrosis factor-α, interleukin-6, and interleukin-1α. STUDY DESIGN: C3H/HeN pregnant mice at 15 days of gestation (70% gestation) were randomized to receive an intraperitoneal injection of phosphate-buffered saline solution or lipopolysaccharide (50 μg/mouse). Blood (n = 93) and amniotic fluid (n = 58) were collected at 1, 4, and 10 hours after lipopolysaccharide injection. Tumor necrosis factor-α, interleukin-6, and interleukin-1α were determined with sensitive and specific enzyme-linked immunoassays. RESULTS: The injection-to-delivery interval was shorter in mice injected intraperitoneally with 50 μg lipopolysaccharide than in phosphate-buffered saline solution–treated mice (median 15.5 hours, range: 10 to 105 hours vs median 88.5 hours, range: 53 to 105 hours; p < 0.001). In comparison with phosphate-buffered saline solution–treated mice, a distinct serum cytokine pattern was observed in lipopolysaccharide–treated mice. Concentrations of tumor necrosis factor-α were detectable 1 and 4 hours after lipopolysaccharide injection (median 874 pg/ml, range: <100 to 8000 pg/ml, p < 0.001; and median 263 pg/ml, range: <100 to 927 pg/ml, p < 0.001, respectively). Concentrations of interleukin-6 were elevated at 1, 4, and 10 hours (median 11.8 ng/ml, range: 6 to 500 ng/ml, p < 0.001; median 27.1 ng/ml, range: 4.5 to 192 ng/ml, p < 0.001; median 1.95 ng/ml, range: < 0.05 to 35 ng/ml, p < 0.015, respectively). Concentrations of interleukin-1a were significantly increased 4 hours after lipopolysaccharide injection (median 102 pg/ml, range: <15 to 306 pg/ml, p < 0.001). A cytokine pattern distinct from serum was observed in amniotic fluid of lipopolysaccharide-treated mice. In comparison with controls, concentrations of interleukin-6 were significantly elevated 4 and 10 hours after treatment with lipopolysaccharide (median 0.88 ng/ml, range: 0.40 to 2.7 ng/ml, p < 0.025; and median 4 ng/ml, range: 1.9 to 33.6 ng/ml, p < 0.001, respectively). Interleukin-1a was elevated 10 hours after lipopolysaccharide treatment (median 185.3 pg/ml, range: 38 to 511 pg/ml, p < 0.015). Tumor necrosis factor-a was not significantly increased in amniotic fluid. CONCLUSION: Preterm delivery after lipopolysaccharide administration is preceded by the appearance of dramatic increases in maternal serum concentrations of tumor necrosis factor-α, interleukin-6, and interleukin-1α and in amniotic fluid concentrations of interleukin-6 and interleukin-1α. (AM J OBSTET GYNECOL 1994;170:1467-75.)

A comparative study of the diagnostic performance of amniotic fluid glucose, white blood cell count, interleukin-6, and Gram stain in the detection of microbial invasion in patients with preterm premature rupture of membranes

Our aim was to compare the value of amniotic fluid tests for the detection of microbial invasion of the amniotic cavity and in the prediction of the amniocentesis-to-delivery interval and neonatal complications in patients with preterm premature rupture of membranes. Amniotic fluid was obtained by transabdominal amniocentesis from 110 consecutive patients with preterm premature rupture of membranes. Fluid was cultured for aerobic and anaerobic bacteria, as well as mycoplasmas. Amniotic fluid analysis included a Gram stain examination, white blood cell count, and glucose and interleukin-6 determinations. Logistic regression and survival techniques (proportional hazards model) were used for statistical analysis. (1) The prevalence of positive amniotic fluid cultures in patients with preterm premature rupture of membranes was 38% (42/110); (2) patients with microbial invasion had a shorter amniocentesis-to-delivery interval and a higher neonatal complication rate than patients with negative cultures; (3) the most sensitive test for the detection of microbial invasion of the amniotic cavity was amniotic fluid interleukin-6 determinations (cutoff 7.9 ng/ml) (sensitivity: for IL-6 80.9%; for white blood cell count 57.1%; for glucose 57.1%; for Gram stain 23.8%; p < 0.05 for all comparisons); (4) the most specific test for the detection of microbial invasion was the Gram stain of amniotic fluid (specificity: for Gram stain 98.5%; for white blood cell count 77.9%; for interleukin-6 75%; for glucose 73.5%; p < 0.01 for all); (5) of all amniotic fluid tests, interleukin-6 determination was the only test that had significant clinical value in the prediction of the amniocentesis-to-delivery interval and neonatal complications. Interleukin-6 concentrations in amniotic fluid are a better predictor of microbial invasion of the amniotic cavity, amniocentesis-to-delivery interval and neonatal complications than the amniotic fluid Gram stain, glucose, or white blood cell count in patients with preterm premature rupture of membranes.

The diagnostic and prognostic value of amniotic fluid white blood cell count, glucose, interleukin-6, and Gram stain in patients with preterm labor and intact membranes

Our goal was to compare the value of amniotic fluid tests in the detection of microbial invasion of the amniotic cavity and in the relationship with the amniocentesis-to-delivery interval and neonatal complications in patients with preterm labor and intact membranes. Amniotic fluid was retrieved by transabdominal amniocentesis from 120 patients with preterm labor and intact membranes. Fluid was cultured for aerobic and anaerobic bacteria and for mycoplasmas. Amniotic fluid analysis included a Gram stain, white blood cell count, glucose and interleukin-6 determinations. Logistic regression and Cox's proportional hazards model were used for analysis. (1) The prevalence of positive amniotic fluid cultures was 9.2% (11/120); (2) patients with microbial invasion had a shorter amniocentesis-to-delivery interval and a higher neonatal complications rate than patients with a negative culture; (3) the most sensitive test for the detection of microbial invasion of the amniotic cavity was amniotic fluid interleukin-6 determinations (cutoff 11.3 ng/ml) (sensitivity; for interleukin-6 100%, for glucose 81.8%, for white blood cell count 63.6%, and for Gram stain 63.6%; p < 0.05 for all comparisons); (4) the most specific test was the Gram stain of amniotic fluid (specificity: for Gram stain 99.1%, for white blood cell count 94.5%, for interleukin-6 82.6%, and for glucose 81.6%; p < 0.01 for all); (5) of all amniotic fluid tests, interleukin-6 determinations were the only ones that had significant relationship with the amniocentesis-to-delivery interval and neonatal complications. Interleukin-6 concentrations in amniotic fluid are better indicators of microbial invasion of the amniotic cavity, amniocentesis-to-delivery interval, and neonatal complications than the amniotic fluid Gram stain, glucose concentration, or white blood cell count.

Amniotic fluid interleukin-6 determinations are of diagnostic and prognostic value in preterm labor.

The purpose of this study was to determine if amniotic fluid concentrations of the interleukin-6 (IL-6) are of value in diagnosis of microbial invasion of the amniotic cavity and in the prediction of failure of tocolysis, preterm delivery and perinatal morbidity and mortality. Amniotic fluid was obtained by transabdominal amniocentesis from 146 consecutive patients admitted with the diagnosis of preterm labor and intact membranes. Fluid was cultured for aerobic and anaerobic bacteria as well as for mycoplasmas. Amniotic fluid IL-6 levels were measured using a monoclonal antibody-based enzyme-linked immunosorbent assay with a sensitivity of 0.03 ng/ml. Logistic regression and Cox's proportional hazards model were used to examine the effect of several variables on dichotomous outcomes or interval to delivery. Patients with a positive amniotic fluid culture had a significantly higher amniotic fluid IL-6 concentrations than patients with a negative culture (median 91.2 ng/ml, range 0.9 to 437 ng/ml versus median 0.4 ng/ml, range < 0.3 to 195 ng/ml, respectively; P < .0001). An amniotic fluid IL-6 concentration of greater than or equal to 11.3 ng/ml had a sensitivity of 93.3% (14 of 15) and a specificity of 91.6% (120 of 131). All patients with an amniotic fluid IL-6 concentration above 11.3 ng/ml and a negative amniotic fluid culture (N = 11) delivered preterm and all placenta available for examination (N = 7) had histologic evidence of chorioamnionitis. Amniotic fluid concentrations of IL-6 were an independent predictor of preterm delivery, amniocentesis-to-delivery interval and neonatal morbidity and mortality. Moreover, IL-6 concentrations added significant information to the prediction of these outcomes to that provided only by clinical information such as cervical dilatation, gestational age at admission or at delivery. IL-6 is a sensitive and rapid test for the detection of microbial invasion of the amniotic cavity and for identifying women at risk for spontaneous preterm delivery and neonates at risk for morbidity and mortality.

242 Evidence of Topographic Differences in Amniotic Fluid Interleukin-6 Concentrations During Spontaneous Active Labor at Term

242 Evidence of Topographic Differences in Amniotic Fluid Interleukin-6 Concentrations During Spontaneous Active Labor at Term

Cytokines in normal and abnormal parturition: Elevated amniotic fluid interleukin-6 levels in women with premature rupture of membranes associated with intrauterine infection

The participation of interleukin-6 (IL-6) in the pathophysiology of normal and abnormal human parturition was evaluated by determining IL-6 concentrations in amniotic fluid (AF). Biologically active IL-6 was determined (in U/ml) using the B9 hybridoma growth factor assay, while the concentrations of immunoreactive IL-6 species (in pg/ml) were assessed using a monoclonal antibody (moAb)-based ELISA. Two hundred and twenty-seven AF samples from women in normal labor and from those presenting with a clinical diagnosis of premature rupture of membranes (PROM) were assayed. In selected instances, IL-6 levels were evaluated simultaneously in AF and in maternal and fetal plasma. Women with a normal pregnancy had low titers of biologically active IL-6 in AF both at midtrimester (group 1, n = 27; median IL-6 concentration = 16 U/ml) and at term (group 2, n = 33; median = 15 U/ml). There was an increase in the IL-6 bioactivity in AF from women in normal labor at term (group 3, n = 40; median = 74 U/ml; p less than 0.001). In order to distinguish between the relative contributions of parturition per se and of intrauterine infection to the elevation of biologically active IL-6 levels in AF, IL-6 titers were compared in four different groups of women with PROM.(ABSTRACT TRUNCATED AT 250 WORDS)