Decreased serum level of macrophage inflammatory chemokine-3beta/CCL19 in preterm labor and delivery

OBJECTIVE: Chemokines are small soluble molecules which mediate leukocyte migration and may be involved in the pathophysiology of preterm labor. We aimed to determine if serum concentrations of selected chemokines are changed in preterm labor and delivery. STUDY DESIGN: A novel array-based enzyme-linked immunosorbent assay was used to quantitate serum levels of nine chemokines from a single sample: MDC/CCL22, TARC/CCL17, ITAC/CXCL11, I-309/CCL1, IP-10/CXCL10, MIP-1alpha/CCL3, -1beta/CCL4, -3alpha/CCL20 and -3beta/CCL19. Women in preterm labor who delivered (n = 17), women at preterm pregnancy not in labor (n = 13) and women in labor at term (n = 8) participated. RESULTS: In the preterm delivery group of patients, the MIP-3beta/CCL19 concentration was in mean (+/-S.D.) 70.4+/-31.7 pg/mL, which was significantly lower than that in preterm gravidas not in labor of 123+/-34 pg/mL (p < 0.001) and those in labor at term of 118+/-25.6 pg/mL (p < 0.01). The other measured chemokines did not differ significantly. CONCLUSIONS: Of a small number of examined chemokines, we were able to show that one of them, MIP-3beta/CCL19 was significantly lower in women with preterm labor and delivery. Whether or not this chemokine has a potential as biochemical marker of preterm delivery remains to be determined.     

Maternal Serum Interleukin-6 Concentration as a Marker for Impending Preterm Delivery

Objective: To determine whether serum interleukin-6 concentrations predict impending preterm delivery.Methods: Blood samples were collected from 130 gravidas at 22–34 weeks’ gestation. The study group consisted of 89 women evaluated for preterm contractions or premature rupture of membranes, and these women were compared with 41 outpatient controls without evidence of labor or infection, chosen by clinicians at the time of routine prenatal visits. Serum interleukin-6 concentrations were measured using a specific enzyme-linked immunosorbent assay kit. Analyses were by the Mann-Whitney U and the Kruskal-Wallis tests.Results: All 41 control subjects had serum interleukin-6 concentrations less than 8 pg/mL. Sixteen of the 89 study patients had serum interleukin-6 concentrations greater than or equal to 8 pg/mL and 73 had values less than 8 pg/mL. When the serum interleukin-6 concentration was at least 8 pg/mL, the median interval from collection to delivery was significantly shorter than that among study and control subjects with serum interleukin-6 less than 8 pg/mL (5.5 versus 240 and 1801 hours, respectively; P < .001). The median gestational age at delivery was significantly lower when the serum interleukin-6 concentration was at least 8 pg/mL, compared with study and control subjects with serum interleukin-6 concentrations less than 8 pg/mL (29.6 versus 33.4 and 39.0 weeks, respectively; P < .001). In patients with preterm contractions, the interval from collection to delivery was significantly shorter when the serum interleukin-6 concentration was at least 8 pg/mL than when it was less than 8 pg/mL (3 versus 600 hours, P < .001). Similarly, the median gestational age at delivery was significantly lower when serum interleukin-6 was at least 8 pg/mL (29.0 versus 36.1 weeks, P < .001).Conclusion: Maternal serum interleukin-6 concentrations appear to be elevated in women destined to deliver prematurely. Measurement of this cytokine may prove useful in treating patients at high risk for preterm delivery.     

孕产妇血清中MMP-3、TNF-α、IL-10的表达与早产和早产胎膜早破的关系

目的探讨基质金属蛋白酶-3（MMP-3）、肿瘤坏死因子-α（TNF-α）、白细胞介素-10（lL-10）在孕产妇血清中的表达与早产、胎膜早破的关系。方法选择单胎头位初产妇80例作为研究对象,按孕周、胎膜是否破裂和产妇是否临产分为早产临产组（sPTD）、早产胎膜早破组（PPROM）、先兆早产组（TPL）和妊娠28～36＋6周无产兆组（对照组）,每组各20例。用ELISA法检测孕妇血清中MMP-3及TNF-α、lL-10的水平。结果①早产临产组、早产胎膜早破组、先兆早产组和对照组血清中MMP-3的浓度分别为（242.25±72.40）ng/ml、（225.95±85.43）ng/ml、（197.85±57.08）ng/ml、（186.80±54.33）ng/ml;TNF-α的浓度分别为（1332.35±346.65）pg/ml、（1365.00±211.80）pg/ml、（1188.15±269.43）pg/ml、（1061.85±210.02）pg/ml;IL-10的浓度分别为（563.65±116.50）pg/ml、（566.80±123.03）pg/ml、（521.00±105.14）pg/ml、（483.50±119.17）pg/ml;②早产组血清中MMP-3,TNF-α浓度高于对照组,以TNF-α升高更明显（P〈0.01）;而IL-10在前两组中有增高趋势,但与后两组相比差异无统计学意义（P〉0.05）;③血清中MMP-3、TNF-α、IL-10浓度呈两两正相关。结论①孕产妇血清中MMP-3及TNF-α浓度与早产、胎膜早破密切相关;②孕产妇血清中MMP-3、TNF-α及IL-10在临产、胎膜早破中可能起协同作用。     

Tissue concentrations of cytokines in the lower uterine segment during preterm parturition.

AIMS: To determine the concentrations of tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, and interleukin-8 in the lower uterine segment during preterm parturition. METHODS: In 71 patients who delivered prematurely by non-elective cesarean tissue specimens were obtained from the lower uterine segment. The patients were grouped in relation to the stage of cervical dilatation (< 2 cm, 2- < 4 cm, > or = 4 cm), duration of labor (< or = 6 h, > 6-12 h; > 12 h), and parity (1 versus > 1). Cytokine concentrations in protein extracts of the tissue samples were measured using enzyme-linked immunosorbent assays. RESULTS: Median concentration of tumor necrosis factor alpha did not change, but that of interleukin-1 beta, interleukin-6, and interleukin-8 were significantly higher at 2- < 4 cm than at < 2 cm cervical dilatation (6.6, 67.7, and 125.8 versus 1.1, 17.6, and 22.2 pg/mg protein, respectively). The concentrations of interleukin-6 and interleukin-8 showed a further increase at > or = 4 cm (297.2 and 468.6 pg/mg, respectively), but for interleukin-1 beta a decrease was observed (0.6 pg/mg). Cytokine concentrations were not related to duration of labor or parity. CONCLUSIONS: Local inflammation-associated changes that are mainly related to the stage of cervical dilatation and to only a minor degree to uterine activity may play a crucial role in preterm parturition.     

Quantitation of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 in the effusions of ovarian epithelial neoplasms.

OBJECTIVE: Our objective was to determine the presence and quantities of multifunctional cytokines in cyst and ascites fluids obtained from patients with ovarian cancer. STUDY DESIGN: Cyst and ascites fluids obtained from 35 patients with ovarian epithelial neoplasms were analyzed for the multifunctional cytokines tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6. The fluids were classified on the basis of the pathologic diagnosis of the tumor tissue. Data were evaluated by analysis of variance. RESULTS: The fluids from patients with papillary forms of adenocarcinoma had high levels of all three cytokines when compared with all other pathologic groups. Interleukin-6 was significantly higher than tumor necrosis factor-alpha or interleukin-1 beta in fluids from all diagnostic categories (p < 0.01). Interleukin-6 levels were significantly higher in fluids from patients with papillary serous cystadenocarcinoma (817 +/- 137 pg/ml) and papillary adenocarcinoma (838 +/- 171 pg/ml) (p < 0.01). Interleukin-1 beta was significantly elevated (p < 0.01) in neoplastic effusions from papillary serous cystadenocarcinomas (53 +/- 8 pg/ml), mucinous cystadenomas (51 +/- 12 pg/ml), and endometrioid carcinomas (54 +/- 18 pg/ml). Tumor necrosis factor-alpha was highest in fluids from patients with papillary adenocarcinoma (46.2 +/- 22.8 pg/ml); however, these levels were not significantly different from the mean quantities of tumor necrosis factor-alpha in other fluids. CONCLUSIONS: The detection of interleukin-1 beta and interleukin-6 in neoplastic effusions provides possible evidence for a host immune response to ovarian cancer. These multifunctional cytokines have been implicated in growth stimulation and cytotoxicity of ovarian tumor cells.     

Tumor necrosis factor in preterm and term labor.

OBJECTIVE: Our objective was to determine if labor (term and preterm) and microbial invasion of the amniotic cavity were associated with changes in amniotic fluid concentrations of tumor necrosis factor. STUDY DESIGN: Amniotic fluid was retrieved by transabdominal amniocentesis from 269 women in the following groups: midtrimester (n = 38), preterm labor with intact membranes (n = 52), preterm premature rupture of membranes (n = 74), term in active labor (n = 84), and term not in labor (n = 21). Fluid was cultured for aerobic and anaerobic bacteria and for Mycoplasma species. Tumor necrosis factor was measured with a commercially available enzyme-linked immunosorbent assay validated for amniotic fluid (sensitivity 60 pg/ml). RESULTS: Amniotic fluid from pregnant women in the second and third trimesters who were not in labor did not contain tumor necrosis factor. Among women in preterm labor, 92.3% (12/13) of patients with a positive amniotic fluid culture had detectable tumor necrosis factor in the amniotic fluid (median 820 pg/ml, range less than 60 to 2340 pg/ml). In contrast, only 10.2% (4/39) of women with a negative amniotic fluid culture had detectable tumor necrosis factor. Histopathologic chorioamnionitis was found in all patients who had a positive amniotic fluid culture, and tumor necrosis factor was detectable in the amniotic fluid of all but one of these patients. Among women in active labor at term, 25% (21/84) had detectable tumor necrosis factor in the amniotic fluid. Tumor necrosis factor was detected more frequently in the amniotic fluid of patients with a positive amniotic fluid culture than in patients with a negative culture (46.6% [7/15] vs 20.2% [14/69], p = 0.047). Amniotic fluid concentrations of tumor necrosis factor were significantly higher in patients with preterm premature rupture of membranes, labor, and a positive amniotic fluid culture than in the other subgroups of patients with preterm premature rupture of membranes. CONCLUSION: Parturition in the setting of microbial invasion of the amniotic cavity is associated with activation of the cytokine network as demonstrated by the detection of tumor necrosis factor in human amniotic fluid.     

Cytokine abundance in placental tissues: evidence of inflammatory activation in gestational membranes with term and preterm parturition

OBJECTIVES: This study of the changes in cytokine concentrations in gestational tissues from women with term and preterm labor was undertaken to assess the extent of inflammatory activation associated with spontaneous labor and delivery. STUDY DESIGN: Extracts of amniotic, chorionic-decidual, and placental tissues from women delivered at term before labor (n = 15), at term after labor (n = 15), and preterm (n = 31) were assayed for interleukin 1beta, interleukin 6, and interleukin 8. RESULTS: In amniotic tissues of women delivered by spontaneous labor at term the median interleukin-6, interleukin-8, and interleukin-1beta concentrations were 3.8 to 5.4 times those of tissues from women delivered at term without labor (P <.05, Mann-Whitney U test). Interleukin-6 and interleukin-8 concentrations were also significantly increased (3. 3-4 times) in chorionic-decidual tissues. Marked increases (approximately 3-6 times) in the concentrations of all 3 cytokines were observed in both amniotic and chorionic-decidual tissues from women with preterm deliveries with respect to those from women with term deliveries after labor. Cytokine concentrations were significantly correlated within amniotic tissues from both women with term delivery after labor and women with preterm delivery and also in preterm chorionic-decidual tissues but not preterm placental tissues. Concentrations of cytokines in the tissues of women delivered preterm were not significantly affected by mode of delivery, treatment with antibiotics, or twin birth. In preterm tissues with evidence of intrauterine infection only amniotic interleukin-1beta concentrations were significantly elevated (P <. 05). Little or no labor-related change in cytokine concentrations was seen within placental tissues. CONCLUSIONS: Increased cytokine abundance in gestational membranes associated with labor supports the view that an inflammatory process is involved in both term and preterm labor. This process does not, however, appear to be evident in the villous placenta.     

Maternal serum tumor necrosis factor-alpha in patients with preterm labor

OBJECTIVE: To evaluate maternal serum tumor necrosis factor-alpha (TNF alpha) levels in patients with preterm labor without clinical signs of chorioamnionitis and to compare these with levels in nonlaboring controls. STUDY DESIGN: The study group consisted of 44 patients with a singleton pregnancy admitted to our department with the diagnosis of preterm labor between 26 and 36 weeks' gestation. The control group consisted of 25 healthy consecutive patients with a singleton pregnancy without preterm contractions who were seen for routine antenatal visits. Maternal serum TNF alpha was measured using a solid-phase, two-site chemiluminescent enzyme immunometric assay method, and levels were compared in patients with preterm labor and nonlaboring controls. RESULTS: The median maternal serum TNF alpha level for patients with preterm labor was 29.4 pg/mL (range, 12.3-173) as compared with 23 pg/mL (range, 11.9-62.7) in the control group (P = .031). Among 44 patients with preterm labor, 14 (32%) delivered within one week of admission. The median maternal serum TNF alpha level was significantly higher in patients who delivered within one week than in those who delivered after one week and controls (71.3 pg/mL [range, 28-173]) versus 22 pg/mL (range, 12.3-86) versus 23 pg/mL (range, 11.9-62.7) (P < .0001). CONCLUSION: TNF alpha was elevated in patients with preterm labor, suggesting a role for maternal serum TNF alpha in its initiation.     

Fetal plasma MMP-9 concentrations are elevated in preterm premature rupture of the membranes

OBJECTIVE: The objective of this study was to determine whether the concentrations of matrix metalloproteinase-9 (MMP-9) in the fetal (fetal plasma and amniotic fluid) and maternal compartments (plasma) are different in patients presenting with preterm premature rupture of membranes (PROM) than in those with preterm labor and intact membranes. STUDY DESIGN: Fetal plasma MMP-9, interleukin-1beta (IL-1beta), IL-6, soluble tumor necrosis factor receptors 1 (sTNF-R1) and 2 (sTNF-R2) were measured in fetuses with preterm labor and intact membranes (n = 96) and preterm PROM (n = 43). The concentrations of analytes were determined with sensitive and specific immunoassays. A P value <.05 was considered significant. RESULTS: (1) The median fetal plasma MMP-9 concentration was significantly higher in fetuses with preterm PROM than in those with preterm labor (P =.035). (2) In contrast, fetal plasma IL-1beta, sTNF-R1, and sTNF-R2 were significantly higher in patients with preterm labor than in those with preterm PROM (IL-1beta, P =.01; sTNF-R1, P =.003; and sTNF-R2, P =.02). (3) The median amniotic fluid concentration of MMP-9 was higher in patients with preterm PROM than in those with preterm labor (P <.001). CONCLUSION: Fetuses with preterm PROM have increased concentrations of an enzyme (MMP-9) implicated in the mechanism of membrane rupture but lower concentrations of IL-1beta, sTNF-R1, and sTNF-R2 than fetuses with preterm labor and intact membranes. A role for the fetus in the genesis of preterm PROM deserves consideration.     

Maternal plasma interleukin-6, interleukin-1beta and C-reactive protein as indicators of tocolysis failure and neonatal outcome after preterm delivery.

OBJECTIVE: To investigate whether maternal serum interleukin-6 (IL-6), interleukin-1beta (IL-1beta) and high sensitive C-reactive protein (CRP) could be used as markers of tocolysis failure and adverse neonatal outcome in pregnancies with preterm labor (PL). METHODS: Forty-seven maternal blood samples taken because of PL at admission and delivery were analyzed. Control samples were taken from 20 gravidas with normal pregnancies. Differences in interleukins and CRP levels with or without chorioamnionitis, connatal infection or periventricular leukomalacia (PVL) were analyzed. Cut-off values were estimated for prediction of tocolysis failure and adverse neonatal outcome. RESULTS: All three parameters were significantly higher in patients delivering prematurely than in patients delivering at term. All three parameters were significantly higher with than without histologic chorioamnionitis (p < 0.001), with than without connatal infection (p < 0.01), with than without PVL (p < 0.01 for IL-6 and IL-1beta, p < 0.05 for CRP), and in pregnancies with preterm premature rupture of membranes (PPROM) delivered within 48 hours compared to those more prolonged (p < 0.01). Choosing 50.9 pg/mL of IL-6 and a CRP of 19.7 as cut-offs in maternal blood admission concentrations for neonatal PVL, resulted in sensitivity of 81% and specificity of 91% and sensitivity of 91% and specificity of 81%, respectively. At respective maternal blood admission cut-off levels of 27.8 pg/mL of IL-6 and 8.9 of CRP, both parameters were effective predictors of connatal infection. CONCLUSIONS: Maternal blood IL-6 and CRP could become useful in predicting tocolysis failure and intrauterine treat for the fetus.     

Maternal serum cytokines in labor, pregnancy and chorioamnionitis

The purpose of our study was to compare maternal serum levels of interleukin-6, interleukin-8, tumor necrosis factor-alpha and interferon-gamma in gravidities, during spontaneous term and preterm labor and their relation to histologic chorioamnionitis. METHODS: We investigated 61 women: 10 in preterm labor, 36 in term labor and 15 healthy pregnant nonlabouring controls. Venous bloods for cytokines determinations were obtained during the first stage of labor and during routine screening tests. Titers of cytokines were measured by means of ELISA technique. All births after preterm deliveries were examined to establish histologic chorioamnionitis. RESULTS: Serum levels of IL-6 and IL-8 were significantly elevated both in term (mean: IL-6: 17.5 +/- 58 pg/ml; IL-8: 148 +/- 215 pg/ml) and preterm labor (IL-6: 23 +/- 44 pg/ml; IL-8: 332 +/- 389 pg/ml) when compared to nonlabouring gravidities (IL-6: 5 +/- 7 pg/ml; IL-8: 14 +/- 11 pg/ml). IL-6 and IL-8 titers were statistically similar in term and preterm labors and in patients with and without histologic chorioamnionitis. TNF-alpha and IFN-gamma were not statistically analyzed because only a few patients had detectable serum levels of these cytokines. CONCLUSION: Serum levels of IL-6 and IL-8 in both: term and preterm labor are elevated in comparison to nonlabouring gravidities. The elevated levels of these cytokines are not connected with coexisting chorioamnionitis.     

Unconjugated serum estriol in the prediction of preterm delivery

OBJECTIVE: The objective was to analyze the serum estriol levels among patients with sings and symptoms of preterm labor and/or preterm rupture of membranes. STUDY DESIGN: A prospective study included pregnant women with sings and symptoms of preterm labor. The main end point of the study was the delivery <28 days from testing. RESULTS: 196 patients were included. 116 patients were included in group I (idiopathic preterm labor), 37 patients in group II (PROM) and the control group (group III) consisted of 43 patients. The incidence of preterm delivery was 31% in group I; in the PROM group all the patients delivered preterm. The mean serum estriol levels in all groups were compared regarding delivery <28 days from testing. In group I patients that delivered <28 days had statistically higher serum level of E3 (14.5 ng/ml vs. 11.1 ng/ml, p = 0.03); in group II the mean E3 serum level did not differ significantly (12.5 ng/ml, p = 0.168). The detailed analysis revealed that significant difference was observed in patients tested after completed 30 wk of gestation (15.4 ng/ml vs 12,8 ng/ml, p = 0.043), but not in patients <30 wk of gestation (9,5 ng/ml vs. 10.0 ng/ml, p = 0.842). CONCLUSIONS: The serum level of E3 seems to have prognostic value in the diagnosis of preterm delivery among symptomatic patients after 30 week of gestation.     

Microbial invasion and cytokine response in amniotic fluid in a Swedish population of women in preterm labor

BACKGROUND: Previous studies indicate an association between intra-amniotic microbial invasion and/or inflammation and spontaneous preterm birth, but there is a limited amount of data available from Europe. The aim of this study was to investigate the occurrence of intra-amniotic microorganisms and cytokines (interleukin-6 and interleukin-8) in a Swedish population of women in preterm labor and their correlation with preterm birth. METHODS: Amniotic fluid was retrieved transabdominally from 61 patients in preterm labor before 34 weeks of gestation. Polymerase chain reaction analyses for Ureaplasma urealyticum and Mycoplasma hominis and culture for aerobic and anaerobic bacteria were performed. Interleukin-6 and interleukin-8 were analyzed with enzyme-linked immunosorbent assay. RESULTS: Microorganisms in amniotic fluid were detected in 10 patients (16%). Patients with detected bacteria in the amniotic fluid had significantly higher levels of interleukin-6 and interleukin-8. There was also an association between interleukin-6/-8, the amniocentesis-delivery interval (or= 1.5 ng/mL or interleukin-8 >or= 1.3 ng/mL was associated with an increased risk of delivery within 7 days (interleukin-6: relative risk 7.3; 95% confidence interval: 2.8-19; sensitivity 83%, specificity 87%; interleukin-8: relative risk 14, 95% confidence interval: 3.6-55, sensitivity 91%, specificity 87%). CONCLUSIONS: The occurrence of intra-amniotic microbial invasion and inflammation in this population of Swedish women in preterm labor was similar to data reported from populations with a higher incidence of preterm delivery. Amniotic interleukin-6 and interleukin-8 correlated with the presence of microorganisms and with preterm birth.     

Maternal serum interleukin-6, interleukin-8, tumor necrosis factor-alpha and interferon-gamma in preterm labor

BACKGROUND: To find out whether preterm labor is associated with raised maternal serum concentrations of interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) and whether the measurement of these cytokines can be used to detect early intrauterine infection in preterm labor. METHODS: Cross-sectional study: 77 women in preterm labor, 47 controls of healthy preterm women not in labor and 19 women in term labor. The serum cytokines levels were measured by enzyme-linked immunosorbent assay (ELISA). The newborns of women who were in labor were followed up for evidence of infection. Differences between groups were tested using analysis of variance, Student's t-test and chi2-test. RESULTS: There was no significant difference in the concentration of all the cytokines measured between the different groups. No statistical difference was found in the concentration of the cytokines between women in preterm labor with ruptured membranes and those with intact membranes. There was also no difference found in the concentration of cytokines between women whose newborns had positive bacterial culture and those with negative culture. There was a positive correlation between the concentrations of IL-6, IL-8 and TNF-alpha. CONCLUSION: Serum levels of interleukin-6, interleukin-8 and tumor necrosis factor-alpha were not increased in preterm labor compared to normal control women. There is doubt regarding the usefulness of maternal serum measurement of these cytokines for the detection of early fetal infection in preterm labor, but this needs further evaluation.     

Evaluation of amniotic fluid cytokines in preterm labor and intact membranes.

OBJECTIVE: To compare the amniotic fluid (AF) concentration of pro-inflammatory cytokines between women with preterm labor and intact membranes that delivered within 7 days, with those that delivered after 7 days of the amniocentesis according to the result of the AF culture. METHODS: Fifty-two women with preterm labor and intact membranes between 21 and 35 weeks of gestation were included in the study. Transabdominal amniocentesis was performed to rule out intra-amniotic infection, and AF concentrations of interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor (TNF) were determined with sensitive and specific enzyme-linked immunosorbent assays. Amniotic fluid was cultured for aerobic and anaerobic bacteria, Ureaplasma urealyticum, and Mycoplasma hominis. Exclusion criteria included preterm premature rupture of membranes, vaginal bleeding, multiple gestations, uterine anomalies, fetal congenital anomalies, ominous fetal heart rate tracings and fetal deaths. Proportions were compared using chi2 or Fisher's exact test. Receiver operator characteristic (ROC) curve analysis was performed for each cytokine for the prediction of delivery within 7 days. RESULTS: Sixty-two percent (32/52) of women delivered within 7 days and 38% (20/52) delivered after 7 days of amniocentesis. All women that delivered after 7 days of the procedure had negative AF cultures. In contrast, 28% (9/32) of women that delivered within 7 days had positive AF cultures and 72% (23/32) had negative AF cultures. Women that delivered within 7 days regardless of AF cultures had a lower birth weight and a shorter amniocentesis-to-delivery interval than those that delivered after 7 days of amniocentesis. Among women that delivered within 7 days, those with positive AF cultures had a lower gestational age at delivery and a higher frequency of histologic chorioamnionitis than those with negative AF cultures. The AF concentrations of all cytokines were significantly higher in women that delivered within 7 days with positive AF cultures than in those with negative AF cultures. Similarly, the AF concentrations of IL-1alpha, IL-6, and IL-8 were significantly higher in women that delivered within 7 days than those that delivered after 7 days of the amniocentesis, regardless of the AF culture results. Diagnostic indexes were calculated for all cytokines using critical values derived from ROC curve analysis for the prediction of delivery within 7 days. CONCLUSIONS: Women with preterm labor and intact membranes that delivered within 7 days had higher AF concentrations of pro-inflammatory cytokines than those who delivered after 7 days of the amniocentesis regardless of the AF culture results.     

Distinct molecular events suggest different pathways for preterm labor and premature rupture of membranes

OBJECTIVE: On a clinical level, the etiologies associated with premature rupture of the membranes and preterm labor are virtually identical, though these conditions end in distinctly different events. This study was designed to determine differences between preterm labor and preterm premature rupture of membranes by using molecular markers of extracellular matrix degradation and apoptosis. STUDY DESIGN: Amniochorion and amniotic fluid samples were collected from gestational age-matched groups of women undergoing cesarean delivery before term. Samples were collected from 2 groups of women, women with premature rupture of membranes and women with preterm labor with no rupture of membranes. Changes in the expression pattern of messenger ribonucleic acid for matrix metalloproteinases (MMP), tissue inhibitor of metalloproteinases (TIMP), and pro-apoptotic (p53 and Bax) and anti-apoptotic (Bcl-2) proteins were identified by quantitative polymerase chain reaction. Enzyme-linked immunosorbent assay was used to determine the levels of these proteins in the amniotic fluid. Multiplex polymerase chain reaction was performed to study the expression of Fas-Fas ligand-associated pro-apoptotic genes. Unpaired nonparametric, 2-tailed Mann-Whitney U test was used to determine statistical significance of quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (P <.05 was considered significant). RESULTS: Quantitative polymerase chain reaction results demonstrated an increased mRNA expression for MMP2, MMP9, and MT1-MMP and a decreased expression for TIMP2 in prematurely ruptured membranes compared with preterm labor membranes. Enzyme-linked immunosorbent assay documented increases in the amniotic fluid concentrations of immunoreactive and bioactive MMP2 and MMP9 and immunoreactive MMP3 and a decreased TIMP2 concentration in fluids obtained from the premature rupture of membranes group compared with the preterm labor group. The pro-apoptotic genes p53 and bax were up-regulated in premature rupture of membranes when compared with preterm labor. Anti-apoptotic gene (Bcl-2 ) expression was increased in preterm labor membranes compared with prematurely ruptured membranes. Interleukin-18 (a pro-apoptotic cytokine) was increased in the amniotic fluid during premature rupture of membranes compared with preterm labor. Prematurely ruptured membranes also demonstrated fragmented deoxyribonucleic acid and expression of Fas and caspase 8 (apoptosis initiator), which were all absent in preterm labor membranes. CONCLUSIONS: We have begun to delineate 2 divergent molecular pathways for premature rupture of membranes and preterm labor. Most likely, this is the beginning of the identification of differences that will become evident with the use of molecular biology.     

The effects of intrapartum magnesium sulfate therapy on fetal serum interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha at delivery: a randomized, placebo-controlled trial.

OBJECTIVE: Elevated levels of inflammatory cytokines in the fetus have been linked to neurologic morbidities in preterm neonates. Magnesium sulfate is currently being studied in clinical trials as a potential fetal neuroprotective agent. The purpose of this study was to determine whether intrapartum magnesium sulfate therapy has an effect on the umbilical venous concentrations of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha at delivery. STUDY DESIGN: Women with singleton gestations >32 weeks with no clinical indications for magnesium sulfate therapy (preeclampsia or tocolysis) and either clinical chorioamnionitis or prolonged rupture of membranes were recruited for the study. Consenting patients were randomly assigned, in a double-blinded fashion, to receive either magnesium sulfate (6-g load then 2 g/hr) or matched volumes of lactated Ringer's solution until delivery. Fetal blood specimens were obtained by aspiration of the umbilical vein after cord clamping but before placental separation. Umbilical cytokine levels were measured with a sensitive and specific immunoassay. RESULTS: Twenty-two patients were randomly assigned to groups and received either magnesium sulfate (n = 11) or placebo (n = 11). There were no differences in the demographic or clinical characteristics between groups. The umbilical venous ionized magnesium concentration was significantly higher in the magnesium sulfate group (2.32 +/- 0.27 mg/dL vs 1.23 +/- 0.15 mg/dL; P <.001). There were no statistically significant differences between groups with respect to umbilical levels of interleukin-1beta (1.5 pg/mL [1.5-58] vs 1.5 pg/mL [1.5-10]; P =.5); interleukin-6 (8.5 pg/mL [1-1000] vs 11.2 pg/mL [1-113]; P =.9); or tumor necrosis factor-alpha (16 pg/mL [7.6-20.3] vs 16.6 pg/mL [8.3-22.2]; P =.5). CONCLUSION: In this pilot study the intrapartum administration of magnesium sulfate does not appear to affect the concentration of inflammatory cytokines in fetal blood at delivery.     

早产和足月产母体龈沟液及血清IL-1β水平的比较

目的 通过比较早产与足月产孕妇龈沟液及血清中自细胞介素-1β(interleukin-1β,IL-1β)水平,探讨牙周感染与早产之间的关系. 方法 以28例先兆早产孕妇和22例足月先兆临产孕妇为研究对象,在临产前采集龈沟液样本,分别随机抽取12份血清样本,采用酶联免疫吸附法(enzyme-linked immunoabsorbent assay,ELISA)检测龈沟液和血清的IL-1β水平. 结果 早产组龈沟液IL-1β水平明显高于足月组[(66.66±4.50)pg/ml和(38.77±8.14)pg/ml,P<0.01];早产组血清IL-1β水平与足月组比较无统计学差异[(3.26±0.25)pg/ml和(2.78士0.13)pg/ml,P>0.05)].早产组龈沟液IL-1β水平与出现先兆早产孕周呈负相关(r=-0.555,P<0.05). 结论 牙周感染可能和早产相关.     

Amniotic fluid tumor necrosis factor-alpha is a marker for the prediction of early-onset neonatal sepsis in preterm labor

BACKGROUND: Our purpose was to determine whether amniotic fluid concentrations of tumor necrosis factor-alpha are of value in the prediction of early-onset neonatal sepsis (proven or suspected) in patients with preterm labor and intact membranes. METHODS: The relationship between amniotic fluid tumor necrosis factor-alpha concentrations and early-onset neonatal sepsis was examined in 59 consecutive patients with preterm labor and intact membranes who delivered preterm neonates within 72 h after transabdominal amniocentesis. Early-onset neonatal sepsis was defined either as the presence of a positive blood culture or as suspected sepsis within 72 h of delivery. Tumor necrosis factor-alpha was determined by enzyme-linked immunosorbent assays. RESULTS: Patients delivering neonates with early-onset neonatal sepsis had significantly higher median amniotic fluid TNF-alpha concentrations than patients delivering neonates without early-onset neonatal sepsis (p < 0.0005). An amniotic fluid tumor necrosis factor-alpha concentration > or =41 pg/ml had a sensitivity of 82% (23/29) and specificity of 79% (38/48) in the prediction of early-onset neonatal sepsis. Multiple logistic regression indicated that elevated amniotic fluid tumor necrosis factor-alpha (> or =41 pg/ml) was the only independent predictor of early-onset neonatal sepsis (odds ratio 12.9, 95% confidence interval 1.3-125.3, p=0.01) after correction for known confounding variables. CONCLUSIONS: (1) Amniotic fluid tumor necrosis factor-alpha is a marker for the prediction of early-onset neonatal sepsis in patients with preterm labor and intact membranes. (2) Amniotic fluid tumor necrosis factor-alpha is a better independent predictor of early-onset neonatal sepsis than placental histologic finding or amniotic fluid culture.