Amniotic fluid matrix metalloproteinase-8 indicates intra-amniotic infection.

OBJECTIVE: This study was undertaken to determine whether matrix metalloproteinase-8, which is produced by neutrophils, is a useful marker for the detection of intra-amniotic infection. STUDY DESIGN: We performed a case-control study using enzyme-linked immunosorbent assays to detect matrix metalloproteinase-8 in 77 amniotic fluid specimens that were obtained by amniocentesis from women with preterm contractions or preterm labor and intact fetal membranes (n = 66) and from women with preterm premature rupture of membranes (n = 11). RESULTS: Thirty women had culture-proven intra-amniotic infection (cases), 21 of whom had intact membranes. After constructing receiver operating characteristic curves to establish the optimal threshold concentration of matrix metalloproteinase-8 for a positive test result, we detected matrix metalloproteinase-8 in 27 of 30 women with intra-amniotic infection; only 10 of 47 control specimens contained matrix metalloproteinase-8 (P <.001; odds ratio, 33.3; 95% CI, 8.4, 132.7). Matrix metalloproteinase-8 was present in 20 of 21 women with intact membranes and intra-amniotic infection and in only 10 of 45 control subjects (P <.001; odds ratio, 70.0; 95% CI, 8.3, 587.6). Among women with intact membranes, the sensitivity of the assay was 0.95 and the specificity was 0.78. CONCLUSION: Our results indicate that matrix metalloproteinase-8 is highly correlated with intra-amniotic infection and that enzyme-linked immunosorbent assay for matrix metalloproteinase-8 may be a clinically useful test for the diagnosis of intra-amniotic infection in women with preterm contractions and preterm labor.     

Amniotic fluid matrix metalloproteinase-9 levels in women with preterm labor and suspected intra-amniotic infection.

OBJECTIVE: To determine the accuracy of amniotic fluid (AF) matrix metalloproteinase-9 measurements for diagnosing intra-amniotic infection in women with preterm labor. METHODS: We performed amniocenteses in 44 women between 22 and 35 weeks' gestation who presented to our center with preterm labor and clinical suspicion of intra-amniotic infection. Each sample was analyzed by glucose measurement, Gram stain, and culture for aerobes, anaerobes, and mycoplasmas. We tested the AF for matrix metalloproteinase-9 using gelatin zymography and a commercial enzyme-linked immunosorbent assay (ELISA) system. We calculated accuracy and confidence intervals (CIs) for AF matrix metalloproteinase-9, glucose, and Gram stain for diagnosing intra-amniotic infection, using culture as the criterion standard. RESULTS: All patients who had matrix metalloproteinase-9 detectable by ELISA also demonstrated matrix metalloproteinase-9 by zymography. Six cases of intra-amniotic infection were confirmed by culture (prevalence 14%). The performance statistics of AF matrix metalloproteinase-9 for diagnosing intra-amniotic infection were: sensitivity 83% (95% CI 53, 99), specificity 95% (95% CI 88, 99), positive predictive value 71% (95% CI 37, 99), and negative predictive value 97% (95% CI 92, 99). Two women had false-positive results; one had gram-negative rods on the AF Gram stain and developed clinical signs and symptoms of chorioamnionitis several hours after amniocentesis and the other had a purulent vaginal discharge and an AF glucose level less than 15 mg/dL. Both delivered within 24 hours of amniocentesis. CONCLUSION: Measuring matrix metalloproteinase-9 in the AF appeared to be reliable for diagnosing intra-amniotic infection. An elevated matrix metalloproteinase-9 concentration in the AF at a preterm gestational age may portend imminent delivery regardless of microbiologic confirmation of intra-amniotic infection.     

Amniotic fluid soluble fas levels in intra-amniotic infection

OBJECTIVE: Membrane Fas can induce apoptosis in sensitive cells. It has been reported that soluble Fas (sFas) is elevated in septicemia. We examined amniotic fluid (AF) sFas levels in patients with and without intra-amniotic infection. METHODS: Forty-two AF specimens were studied. Intra-amniotic infection was defined as the presence of a positive AF culture. Twenty-one specimens were from patients with intra-amniotic infection and 21 were from patients without intra-ammotic infection. Amniotic fluid sFas was determined by an enzyme immunoassay and normalized by AF creatinine levels. The Mann-Whitney U test, contingency table method, and Spearman's rank correlation test were used for statistical analyses. Data were expressed as median with ranges. RESULTS: There were no significant differences in maternal age, gestational age, parity, and race between the groups. The median AF sFas was significantly higher with intra-amniotic infection than without it (5.07 U/mL, range 0.32-13. 25 compared with 1.95 U/mL, range 0.01-5.35; P =.004). After normalizing to AF creatinine, infected fluids also had significantly higher median sFas/creatinine than uninfected amniotic fluids (289.1 U/mg creatinine, range 16.6-920.5 compared with 126.8 U/mg creatinine, range 0.5-546.2; P =.01). Amniotic fluid sFas and sFas/creatinine were positively correlated with AF leukocytes and negatively correlated with AF glucose. CONCLUSION: Elevated AF sFas is associated with intra-amniotic infection. High production of AF sFas in intra-amniotic infection may play a role in the inhibition of apoptosis of AF leukocytes, leading to the persistence of inflammation.     

Amniotic fluid concentrations of fibronectin and intra-amniotic infection

A cohort study with four groups of pregnant women was designed to evaluate if a decrease in the concentration of fibronectin (FN) in amniotic fluid plays a role in the genesis of premature rupture of the membranes (PROM) and/or intra-amniotic infection: group 1, 15 patients with PROM and intra-amniotic infection; group 2, 15 patients with PROM but without intra-amniotic infection; group 3, 15 patients with preterm labor without PROM or intra-amniotic infection; and group 4, 15 patients who underwent elective amniocentesis for fetal lung maturity studies. No significant differences in amniotic fluid concentrations of FN among any of the four groups was observed (F = 0.146; P = 0.931). These results suggest that a deficiency of FN in amniotic fluid is not a critical factor in determining which patients may be affected by PROM or which of them will develop an intra-amniotic infection.     

Amniotic fluid concentration of surfactant proteins in intra-amniotic infection

Objective. Pulmonary surfactant is a complex molecule of lipids and proteins synthesized and secreted by type II alveolar cells into the alveolar epithelial lining. Both lipid and protein components are essential for lung function in postnatal life. Infection is a well-established cause of preterm delivery, and several inflammatory cytokines play a role in the mechanisms of preterm parturition. An increased concentration of inflammatory cytokines in amniotic fluid or fetal plasma has been linked to the onset of preterm parturition and fetal/neonatal injury, including cerebral palsy and chronic lung disease. Experimental evidence indicates that inflammatory mediators also regulate surfactant protein synthesis, and histologic chorioamnionitis is associated with a decreased incidence of hyaline membrane disease in neonates. This study was conducted to determine if amniotic fluid concentrations of surfactant protein (SP)-A, SP-B, and SP-D change in patients with and without intra-amniotic infection (IAI).

Materials and methods. A case–control study was conducted to determine amniotic fluid concentrations of SP-A, SP-B, SP-D, and total protein in patients who had an amniocentesis performed between 18 and 34 weeks of gestation for the detection of IAI in patients with spontaneous preterm labor with intact membranes (n = 42) and cervical insufficiency prior to the application of cerclage (n = 6). Amniotic fluid samples were selected from a bank of biological specimens and included patients with (n = 16) and without (n = 32) IAI matched for gestational age at amniocentesis. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms. Each group was further subdivided according to a history of corticosteroid administration within 7 days prior to amniocentesis into the following subgroups: (1) patients without IAI who had received antenatal corticosteroids (n = 21), (2) patients with IAI who had received antenatal corticosteroids (n = 9), (3) patients without IAI who had not received antenatal corticosteroids (n = 11), and (4) patients with IAI who had not received antenatal corticosteroids (n = 7). Amniotic fluid was obtained by transabdominal amniocentesis. SP-A, SP-B, and SP-D concentrations in amniotic fluid were determined by enzyme-linked immunosorbent assay (ELISA). Non-parametric statistics were used for analysis.

Results. Women with IAI had a higher median amniotic fluid concentration of SP-B and of SP-B/total protein, but not other SPs, than those without IAI (both p = 0.03). Among patients who had received antenatal corticosteroids, the median amniotic fluid concentration of SP-B and of SP-B/total protein was significantly higher in patients with IAI than in those without IAI (SP-B, IAI: median 148 ng/mL, range 37.3–809 ng/mL vs. without IAI: median 7.2 ng/mL, range 0–1035 ng/mL; p = 0.005 and SP-B/total protein, IAI: median 14.1 ng/mg, range 4.3–237.5 ng/mg vs. without IAI: median 1.45 ng/mg, range 0–79.5 ng/mg; p = 0.003). Among women who had not received antenatal corticosteroids, the median amniotic fluid concentrations of SP-B and of SP-B/total protein were not significantly different between patients with and without IAI (SP-B, IAI: median 4 ng/mL, range 0–31.4 ng/mL vs. without IAI: median 3.4 ng/mL, range 0–37 ng/mL; p = 0.8 and SP-B/total protein, IAI: median 0.55 ng/mg, range 0–6.96 ng/mg vs. without IAI: median 0.59 ng/mg, range 0–3.28 ng/mg; p = 0.9). The median amniotic fluid concentrations of SP-A, SP-A/total protein, SP-D, and SP-D/total protein were not significantly different between patients with and without IAI whether they received antenatal corticosteroids or not (all p > 0.05).

Conclusions. IAI was associated with an increased amniotic fluid concentration of SP-B in patients who received antenatal corticosteroids within 7 days prior to amniocentesis.     

Amniotic fluid glucose concentration as a marker for intra-amniotic infection

This study evaluated the use of amniotic fluid (AF) glucose concentration as a rapid indicator of intra-amniotic infection. Amniotic fluid glucose concentrations were measured in 86 pregnancies and compared with AF cultures. There were 14 positive cultures with a mean AF glucose of 7.1 mg/dL (range 1-24) and 72 negative cultures with a mean AF glucose of 30.4 mg/dL (range 5-66), a significant difference (P less than .001). An AF glucose of less than or equal to 5 mg/dL had a positive predictive value of 90%; an AF glucose of greater than 20 mg/dL had a 98% negative predictive value. Amniotic fluid glucose can be obtained rapidly and inexpensively, and may be of use in the diagnosis of intra-amniotic infection.     

Amniotic fluid matrix metalloproteinase-8 in preterm labor with intact membranes.

OBJECTIVE: Intra-amniotic inflammation is a major determinant of maternal and neonatal outcome in patients with preterm labor. Matrix metalloproteinase-8 is a sensitive marker of inflammation in body fluids. This study was conducted to examine the value of amniotic fluid matrix metalloproteinase-8 determinations in patients with preterm labor and intact membranes. STUDY DESIGN: Amniotic fluid was obtained by transabdominal amniocentesis from 371 patients with preterm labor. Fluid was cultured for aerobic and anaerobic bacteria and Mycoplasmas. Amniotic fluid analysis included Gram stain examination, white blood cell count, and matrix metalloproteinase-8 (enzyme-linked immunosorbent assay) determination. Nonparametric statistics were used for analysis. RESULTS: The rate of preterm delivery was 54% (200/371) and that of intra-amniotic infection was 9.2% (34/371). The median amniotic fluid matrix metalloproteinase-8 concentration was more than 50-fold higher in patients with intra-amniotic infection than in patients with no intra-amniotic infection (median, 605.6 ng/mL; range, 0.65-15,000 ng/mL vs median, 10.6 ng/mL; range, <0.06-16,600 ng/mL, respectively; P <.0001). The matrix metalloproteinase-8 amniotic fluid concentrations were significantly higher in patients who delivered preterm than in patients who delivered at term (median, 19.5 ng/mL; range, <0.06-16,600 ng/mL vs median, 2.1 ng/mL; range, <0.06-500 ng/mL, respectively; P <.001). After exclusion of patients with intra-amniotic infection, patients who delivered preterm had a significantly higher median amniotic fluid matrix metalloproteinase-8 than patients who delivered at term (P <.05). An amniotic fluid matrix metalloproteinase-8 level of >30 ng/mL was an independent predictor for the occurrence of neonatal morbidity (odds ratio, 3.4; 95% CI, 1.9-5.8; P <.01). CONCLUSION: Increased amniotic fluid matrix metalloproteinase-8 concentrations identify patients at risk for intra-amniotic infection, impending preterm delivery, and adverse neonatal outcome.     

Amniotic fluid analysis. Part I: Rapid markers in the prediction of intra-amniotic infection

Intraamniotic infection has been recognized as a major etiologic factor for preterm delivery. Several groups have proposed that amniocentesis be used to identify the patient at risk for infectious morbidity. The number of techniques have been studied for rapid identification of bacterial colonization of amniotic cavity. Diagnostic index value of Gram stain, white blood cell count, glucose level and LDH (lactate dehydrogenase) activity for prediction of positive amniotic fluid culture, preterm delivery, clinical infection and neonatal sepsis were shown in the study. Investigators continue attempts to establish a rapid, more useful tests to predict preterm delivery.     

Amniotic fluid matrix metalloproteinase-8 and the development of cerebral palsy

AIMS: To examine if increased concentrations of matrix metalloproteinase-8 (MMP-8) in amniotic fluid are associated with the development of cerebral palsy at the age of three years. METHODS: The relationship between amniotic fluid concentrations of MMP-8 and the development of cerebral palsy was examined in 116 preterm singleton newborns (gestational age at birth < 35 weeks) born to mothers who underwent amniocentesis and were followed for at least 3 years. Amniotic fluid was cultured for aerobic and anaerobic bacteria and mycoplasmas. MMP-8 concentrations were measured by specific immunoassays. Cerebral palsy was diagnosed by neuro developmental assessment at the age of three years. RESULTS: Median amniotic fluid concentration of MMP-8 was significantly higher in mothers whose newborns developed cerebral palsy than in mothers whose newborns did not develop cerebral palsy (median 153.9 [range < 0.3-1535.9] ng/ml vs median 6.4 [range < 0.3-3836.8] ng/ml; p < 0.01). Neonates who developed cerebral palsy were delivered at earlier gestational age than those without cerebral palsy. After adjustment for the gestational age at birth and the results of amniotic fluid culture, elevated concentrations of amniotic fluid MMP-8 significantly increased the odds of development of cerebral palsy (odds ratio, 6.0; 95% confidence interval, 1.1-33.0; p < 0.05). CONCLUSION: Increased concentrations of amniotic fluid MMP-8 are associated with the subsequent development of cerebral palsy at the age of 3 years.     

Amniotic fluid soluble human leukocyte antigen-G in term and preterm parturition,and intra-amniotic infection/inflammation

Objective.?Circulating soluble human leukocyte antigen-G (sHLA-G) has been associated with pregnancy complications, and determination of sHLA-G concentrations in amniotic fluid (AF) has been reported in normal pregnancies. Our aim was to determine if the AF concentrations of sHLA-G change with advancing gestation, spontaneous labor at term, and in patients with spontaneous preterm labor (PTL) with intact membranes, as well as in those with preterm prelabor rupture of membranes (PROM), in the presence or absence of intra-amniotic infection/inflammation (IAI).

Study design.?This cross-sectional study included the following groups: (1) mid-trimester (n?=?55); (2) normal pregnancy at term with (n?=?50) and without (n?=?50) labor; (3) spontaneous PTL with intact membranes divided into: (a) PTL who delivered at term (n?=?153); (b) PTL who delivered preterm without IAI (n?=?108); and (c) PTL with IAI (n?=?84); and (4) preterm PROM with (n?=?46) and without (n?=?44) IAI. sHLA-G concentrations were determined by ELISA. Non-parametric statistics were used for analysis.

Results.?(1) Among patients with PTL, the median AF sHLA-G concentration was higher in patients with IAI than in those without IAI or women that delivered at term (p?<?0.001 for both comparisons); (2) Similarly, patients with preterm PROM and IAI had higher median AF sHLA-G concentrations than those without IAI (p?=?0.004); (3) Among patients with PTL and delivery, those with histologic chorioamnionitis and/or funisitis had a higher median AF sHLA-G concentration than those without histologic inflammation (p?<?0.001); and (4) The median AF sHLA-G concentration did not change with advancing gestational age.

Conclusions.?AF sHLA-G concentrations are elevated in preterm parturition associated to IAI as well as in histologic chorioamnionitis. We propose that sHLA-G may participate in the regulation of the host immune response against intra-amniotic infection.     

Identification of matrix metalloproteinase-9 in amniotic fluid and amniochorion in spontaneous labor and after experimental intrauterine infection or interleukin-1 beta infusion in pregnant rhesus monkeys.

OBJECTIVE: The purpose of this study was to examine the roles of intrauterine infection, inflammation, and spontaneous labor on the expression of matrix metalloproteinase-9 in fetal membranes and amniotic fluid of late pregnant rhesus monkeys. STUDY DESIGN: Pregnant rhesus monkeys with timed gestations were chronically catheterized to allow serial sampling of amniotic fluid before and during experimentally induced intrauterine inflammation. Six animals received group B streptococci into the chorionic-decidual space, and 4 animals received intra-amniotic interleukin-1 beta infusions (10 microg). Three additional animals were serially sampled by amniocentesis through late pregnancy until spontaneous term labor. Amniotic fluid samples were examined by zymography for matrix metalloproteinase-9 and -2 and Western immunoblot for matrix metalloproteinase-9 and -2 and tissue inhibitors of metalloproteinase-1 and -2. Fetal membranes were obtained at cesarean delivery during labor (before rupture), formalin fixed, and embedded in paraffin for immunocytochemistry of matrix metalloproteinase-9 and in situ hybridization of matrix metalloproteinase-9 messenger RNA. Tissues from 2 additional animals were collected as age-matched non-labor controls. RESULTS: In amniotic fluid, the 92-kd latent matrix metalloproteinase-9 was detectable in late pregnancy and increased dramatically, followed by the appearance of the 83-kd active form before spontaneous term delivery. Amniotic fluid matrix metalloproteinase-2 levels (both latent and active forms) remained relatively constant throughout pregnancy and in labor. Both bacteria and interleukin-1 beta rapidly increased the signal of latent matrix metalloproteinase-9 without a consistent increase in the active form before the onset of labor. Chorionic-decidual inoculation of group B streptococci was followed by the expression of latent matrix metalloproteinase-9 before the appearance of group B streptococci in amniotic fluid or the onset of labor. Matrix metalloproteinase-2 increased to a new steady-state level or remained unchanged after group B streptococci inoculation or interleukin-1 beta infusion, respectively. Amniotic fluid tissue inhibitors of metalloproteinase-1 declined and tissue inhibitors of metalloproteinase-2 remained unchanged during early group B streptococci infection, after interleukin-1 beta infusion and on the day of spontaneous term labor. However, both tissue inhibitors of metalloproteinase-1 and -2 levels increased after preterm labor that was induced by group B streptococci. Immunocytochemistry localized matrix metalloproteinase-9 protein to amnion and chorion epithelial and mesenchymal cells and decidual stromal cells. Granular matrix metalloproteinase-9 staining was observed in the connective tissue layer of inflamed fetal membranes. In situ hybridization for messenger RNA confirmed the production of matrix metalloproteinase-9 by amnion and chorion. CONCLUSION: Bacterial- and interleukin-1 beta-induced preterm labor and spontaneous term labor are preceded and accompanied by progressive increases in amniotic fluid matrix metalloproteinase-9 (92 kd) in rhesus monkeys. Amniotic fluid matrix metalloproteinase-9 may serve as a clinical marker for the onset of both preterm and term labor.     

Amniotic fluid interleukin-6 and neutrophil gelatinase-associated lipocalin for predicting fetal inflammatory response syndrome based on histological chorioamnionitis and funisitis

ObjectiveWe aimed to analyze the predictive efficacy of amniotic fluid interleukin-6 (IL-6) and neutrophil gelatinase-associated lipocalin (NGAL) for fetal inflammatory response syndrome (FIRS)-related infection.Materials and methodsWe included singleton pregnancies classified into FIRS and non-FIRS groups. FIRS was defined as histologic chorioamnionitis and funisitis. Amniotic fluid samples were collected during vaginal delivery (VD) or cesarean section (CS). We compared amniotic fluid IL-6 and NGAL levels between the groups.ResultsForty-six pregnancies were analyzed and classified into 20 (43.5%) FIRS and 26 (56.5%) non-FIRS pregnancies. We observed significant differences in amniotic fluid IL-6 and NGAL. Amniotic fluid collection significantly influenced NGAL levels (p < 0.001). The area under the concentration–time curve (AUC), with optimal cutoff values, for amniotic fluid IL-6 and NGAL (VD and CS) levels was 0.948 (11,344 pg/mL), 0.800 (1180 ng/mL), and 0.946 (708 ng/mL), respectively.ConclusionAmniotic fluid IL-6 and NGAL levels showed equivalent predictive ability for FIRS-related infection.     

Amniotic fluid lactoferrin in intrauterine infection

Lactoferrin (LF) has been found in most biological fluids including amniotic fluid and cervical mucus in pregnant women and is released from neutrophils in response to inflammation. It is an important component of the host defence against microbial infections due to its antimicrobial properties. Premature labour is caused by amniotic infection and high concentrations of inflammatory cytokines in amniotic fluid with infection are well established. In the present study, LF levels of intrauterine infection in amniotic fluid were measured and the biological significance of LF was investigated. The effects of LF on IL-6 production in cultured amnion cells were also investigated. The concentrations of LF and IL-6 in amniotic fluid with chorioamnionitis (CAM) were 8.76+/-0.65 microg/ml and 6.92+/-4.88 ng/ml (n = 28), respectively, and both were significantly higher (P<0.01) than those without CAM (0.86+/-0.81 microg/ml and 0.34+/-0.25 ng/ml; n = 31). LF and IL-6 levels were significantly higher (P<0.01) with CAM. A significant positive correlation between LF and IL-6 levels in amniotic fluid was found (r = 0.91, P<0.01). To our knowledge, this was the first study of its kind, which shows that IL-6 production induced by lipopolysaccharide in cultured cells was significantly inhibited below physiological concentration of LF in the amnion. In addition, the immunohistochemical localization of LF in fetal membranes was investigated. In the fetal membranes with CAM, strong positive staining was observed in amniotic and chorionic membranes, with leucocyte migration, while weak staining was observed in membranes without CAM. These results show conclusively that LF suppresses amniotic IL-6 production under the conditions of intrauterine infection.     

Amniotic fluid glucose and intraamniotic infection

Thirty-nine patients with either premature labor and/or preterm premature ruptured membranes underwent transabdominal amniocentesis to enable the following amniotic fluid analyses to be performed: culture and sensitivity, Gram's stain, and glucose determination. All nine patients with intraamniotic infection had amniotic fluid glucose values less than 10 mg/dl. Three patients with amniotic fluid glucose levels less than 10 mg/dl but without chorioamnionitis were delivered of infants within 72 hours of admission. The mean amniotic fluid glucose level of patients with intraamniotic infection (5 +/- 2.4 mg/dl) was significantly lower than in those without intraamniotic infection (39.8 +/- 18.42 mg/dl). All patients with amniotic fluid glucose values less than 10 mg/dl had either bacteria and/or white blood cells on Gram's stain. Two patients without chorioamnionitis had white cells on Gram's stain and amniotic fluid glucose values greater than 10 mg/dl. It appears that amniotic fluid glucose is more sensitive and more specific than Gram's stain in the diagnosis of intraamniotic infection. All 12 patients with low amniotic fluid glucose values were delivered of infants within 72 hours as the result of either the presence of infection or the progression of labor.     

Elevated concentrations of interleukin-6 in intra-amniotic infection with Ureaplasma urealyticum in asymptomatic women during genetic amniocentesis.

BACKGROUND: Intra-amniotic infection is an important cause of preterm delivery and interleukin-6 (IL-6) determination was recently applied for identification of microbial invasion of the amniotic cavity. Our aim was to determine the levels of IL-6 in culture-positive amniotic fluids at genetic amniocentesis and to evaluate their significance in relation to pregnancy outcome. METHODS: Seven culture-positive and 23 culture-negative amniotic fluids, obtained at 17-19 weeks of gestation, were analyzed for IL-6 levels by an immunoassay (ELISA). Pregnancy outcomes of all 30 women were obtained from the medical charts. RESULTS: The mean level of IL-6 in the culture-negative amniotic fluids was 78+/-206 pg/ml. Among the seven culture-positive, high levels of IL-6 were found only in three amniotic fluids that were culture-positive for Ureaplasma urealyticum (1834, 1342 and 2832 pg/ml). Low levels of IL-6, ranging from zero to 60 pg/ml, were found in four AFs that were culture-positive for Staphylococcus epidermidis (n=3) and Bacillus Gram-positive (n= 1). Adverse pregnancy outcome occurred in the three women who had intra-amniotic infection with U. urealyticum accompanied by high levels of IL-6 (two fetal loss and one preterm delivery at 28 weeks of gestation). The four women with culture-positive but IL-6 negative amniotic fluids, had normal pregnancy outcome and term delivery. Two of the 23 women with culture-negative had preterm delivery, one with high (1000 pg/ml) and one with low (80 pg/ml) levels of IL-6. CONCLUSION: High levels of IL-6 are suggestive of a genuine intra-amniotic infection with urea-plasmas resulting in adverse pregnancy outcome, while culture-positive amniotic fluids with normal IL-6 levels, may suggest a state of contamination.     

Amniotic fluid analysis. Its role in maternal neonatal infection

Indirect evidence suggests that amnionitis, in the absence of maternal symptoms, contributes to neonatal morbidity. The incidence is unknown because diagnostic techniques are not available. A quantitative amniotic fluid analysis of bacteria, white blood cells, and lactic dehydrogenase levels was performed during labor among 28 patients considered to be a risk for infection. Thirteen of 16 patients with bacterial colony counts greater than 10(3)/ml subsequently developed maternal infection had a premature delivery, neonatal sepsis, or a combination of these factors. Maternal fever was a late sign in clinical infection and was frequently absent in cases of premature delivery associated with microbiologic evidence of amnionitis. Amniotic fluid analysis may be of value in diagnosing unrecognized amnionitis among patients delivering prematurely and those requiring nonelective cesarean section.     

Amniotic fluid interleukin-1 in spontaneous labor at term

The regulatory signals responsible for the increased biosynthesis of prostaglandins during parturition have not been established. Interleukin-1 (IL-1) is capable of stimulating prostaglandin production by intrauterine tissues and is an inflammation mediator. It has been postulated as a signal for the onset of labor in the setting of intrauterine infection. A study was designed to determine if spontaneous labor at term was associated with changes in IL-1 activity in amniotic fluid. Such fluid was retrieved from 41 women in labor and from 39 women who were not in labor at term. Immunodetectable IL-1 beta was present in 22 of the 41 women in labor but in only 8 of the 39 women without labor. IL-1-like bioactivity was not different between the two groups at a dilution of 1:4, but at dilutions of 1:12, 1:36 and 1:108, amniotic fluid from women in labor had significantly higher bioactivity than that from women not in labor. A significant correlation was found between the bioassay and immunoassay results. Our data show that inhibitors of IL-1 bioactivity are present in amniotic fluid and suggest that in a subset of laboring women at term, an inflammatory reaction may play a role in triggering the onset of parturition.