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PubMed1996

Amniotic fluid interleukins in Swedish and Mozambican pregnant women.

The aim of the study was to investigate inflammatory cytokines, interleukin-1 beta (IL-1 beta), interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-8 in amniotic fluid, in a cohort of Swedish pregnant women from early to late pregnancy and Mozambican late pregnant women with and without signs of histologic chorioamnionitis. Eleven Swedish women were studied from early pregnancy (week 16-17) to late pregnancy (week 37-38). Amniotic fluid was collected via amniocentesis in early pregnancy and also in late pregnancy during elective Caesarean section. From Mozambican women, amniotic fluid was harvested transmurally through the uterus wall during elective Caesarean section. Half of the group of 30 women showed histological signs of chorioamnionitis and half of the group did not show such signs. A statistical, significant increase in IL-1ra, Il-6 and IL-8 values from early to late pregnancy was seen in the Swedish pregnant women. Among the Mozambican women, no statistically significant increase in the above-mentioned interleukins was observed when comparing women with and without histological signs of chorioamnionitis. Term Swedish and Mozambican women did not show differences in cytokine levels. There were no detectable values of IL-1 beta in either Swedish or Mozambican women. IL-1ra, IL-6 and IL-8 increased in amniotic fluid from the second to the third trimester in the Swedish cohort. No correlation was found between histological chorioamnionitis and elevated cytokine levels of amniotic fluid in term pregnant women not in labour. An equally good cytokine response was found among Swedish and Mozambican third-trimester non-labouring women.

Amniocentesis↗

PubMed2003

Peptide growth factors in tracheal aspirates of mechanically ventilated preterm neonates.

Basic fibroblast growth factor (bFGF or FGF-2), vascular endothelial growth factor (VEGF), and endothelin-1 (ET-1) are peptide growth factors (PGF) mediating normal lung development, maturation, injury, and repair. These PGF may therefore be involved in the pathogenesis of bronchopulmonary dysplasia (BPD). We hypothesized that elevated levels of these PGF in tracheal aspirates would be associated with a) BPD and/or death; b) markers of cell injury and apoptosis; and c) chorioamnionitis, a risk factor for BPD. Tracheal aspirates collected in 29 preterm (<34 wk gestation, 500-2000 g birth weight), mechanically ventilated infants on d 1 of life were assayed for PGF and histone-associated DNA fragments by ELISA and for LDH by enzyme assay. Clinical and pathologic examination was performed for chorioamnionitis. BPD was defined as oxygen requirement/mechanical ventilation at 28 d postnatal age. The birth weight (mean +/- SE) was 1009 +/- 85 g and median gestational age was 26 wk (range, 22-33). Eighteen infants died or developed BPD. bFGF levels were elevated in infants who died or developed BPD [median (25%,75%) level of 36 (23, 44) pg/mL versus 14 (6, 30) in the survivors without BPD, p = 0.01]. bFGF levels correlated with apoptosis (r = 0.73, p < 0.001) and LDH levels (r = 0.59, p < 0.001). VEGF and ET-1 levels were not associated with apoptosis or with BPD/death. PGF levels were not associated with chorioamnionitis. We conclude that elevated bFGF levels in the preterm trachea correlate with BPD/death and markers of cell injury and apoptosis but not with chorioamnionitis. We speculate that bFGF may play a role in the development of BPD.

Bronchopulmonary Dysplasia↗

PubMed2006

IL-1 alpha causes lung inflammation and maturation by direct effects on preterm fetal lamb lungs.

Intra-amniotic endotoxin induces IL-1, causes chorioamnionitis, lung inflammation, lung injury and lung maturation in preterm lambs. Intra-amniotic IL-1alpha also causes chorioamnionitis, lung inflammation and lung maturation. We asked if IL-1alpha effects on the preterm lung are mediated by direct signaling to the lung rather than by indirect effects from the chorioamnionitis. To study IL-1 effects independently of chorioamnionitis, the lungs and the amniotic fluid were surgically separated in fetal sheep by diverting fetal lung fluid via a tracheostomy tube to a sialastic bag. A mini-osmotic pump delivered an intratracheal infusion of recombinant sheep IL-1alpha (10 microg) or saline (control) over 24 h. Preterm lambs were delivered 1d or 7d after the start of the infusion at 124d gestational age (Term = 150d). IL-1alpha recruited inflammatory cells and increased pro-inflammatory cytokine mRNA expression in the fetal lungs. Compared with controls, IL-1alpha did not alter lung antioxidant enzyme activity or alveolar numbers. IL-1alpha had minimal effects on the mRNA or protein expression of proteins essential for vascular development. IL-1alpha induced large increases in alveolar surfactant saturated phosphatidylcholine and increased lung gas volumes. Lung inflammation and maturation result from direct exposure of the fetal lung to a single cytokine - IL-1alpha.

Animals↗

PubMed2000

Placental lesions associated with cerebral palsy and neurologic impairment following term birth.

OBJECTIVE: The aim of this study was to determine the association of placental findings with cerebral palsy and related forms of neurologic impairment (NI) following birth at > or =37 weeks gestation (term). DESIGN: In a retrospective comparison, placentas from 40 term infants with NI ascertained on the basis of clinicopathologic review for medicolegal consultation were compared with placentas from 176 consecutive meconium-stained term infants at low risk for NI. RESULTS: After stratification for severity, 9 lesions were significantly increased in placentas from infants with NI: 5 lesions generally considered to occur within days of the time of labor and delivery (meconium-associated vascular necrosis, severe fetal chorioamnionitis, chorionic vessel thrombi, increased nucleated red blood cells, and findings consistent with abruptio placenta) and 4 lesions generally believed to have their onset long before labor and delivery (diffuse chronic villitis, extensive avascular villi, diffuse chorioamnionic hemosiderosis, and perivillous fibrin). Findings independently associated with NI by logistic regression in this descriptive study were severe fetal chorioamnionitis (odds ratio [OR], 13.2; 95% confidence interval [CI], 1.2-144); extensive avascular villi (OR, 9.0; 95% CI, 1.6-51); and diffuse chorioamnionic hemosiderosis (OR, 74.8; 95% CI, 6.3-894). The risk of NI increased as a function of the number of lesions present (OR, 10.1; 95% CI, 5.1-20 for each additional lesion), particularly when lesions generally considered to occur near the time of labor and those believed to occur well before labor were found in the same placenta (OR, 94.2; 95% CI, 11.9-747). CONCLUSIONS: These findings suggest that placental pathology can contribute to an understanding of the mechanisms that contribute to NI at term.

Birth Injuries↗

PubMed2002

Expression of angiogenic and neurotrophic factors in the human amnion and choriodecidua.

OBJECTIVE: Our objective was to identify the novel or differential expression of growth or development associated genes in the human gestational membranes that might play roles in pregnancy or in term or preterm parturition. STUDY DESIGN: Complementary DNA arrays were probed with [alpha(33)P]dCTP-labeled-complementary DNA that was prepared from the RNA of reflected amnion and choriodecidua that represent term not-in-labor, term spontaneous labor, and preterm labor with and without chorioamnionitis (n = 4 per group). Differential expression (term not-in-labor vs term spontaneous labor or preterm labor with chorioamnionitis vs preterm labor without chorioamnionitis) was evaluated by Wilcoxon tests. RESULTS: All 16 amnion samples expressed angiogenic factors (endothelin-2 and -3, vascular endothelial growth factor, and vascular endothelial growth factor-B) and neurotrophic factors (ephrin-A2, ephrin receptors-A2, -B1, -B3, -B4, and -B5, neuropilin-2, p75/nerve growth factor receptor and semaphorin-F). In both amnion and choriodecidua, the expression of vascular endothelial growth factor and the angiopoietin receptor, Tie-2, were greater with term spontaneous labor than with term not-in-labor (P <.05); increased VEGF receptor-2 (flk-1) expression was observed in term spontaneous labor choriodecidua (P <.05) but not amnion. Ephrin-A1 expression increased with term spontaneous labor in both tissues (P <.05). Semaphorin-F expression decreased with preterm labor with chorioamnionitis in choriodecidua (P <.05), although the trend was not significant in amnion (P =.1). CONCLUSION: Neurotrophic and angiogenic factor genes are expressed in amnion and choriodecidual membranes. Several of the genes exhibit differential expression with labor at term or in association with infection preterm, which suggests roles in or associated with these processes.

Amnion↗

PubMed1999

Prophylactic cefazolin in amnioinfusions administered for meconium-stained amniotic fluid.

OBJECTIVE: To determine if amnioinfusion with an antibiotic solution decreased the rate of clinical chorioamnionitis and puerperal endometritis in patients with meconium-stained amniotic fluid. METHODS: Patients in labor at 36 weeks of gestation or greater with singleton pregnancies and meconium-stained amniotic fluid were randomized to receive either cefazolin, 1 g/1,000 mL, of normal saline (n = 90) or normal saline (n = 93) amnioinfusion. Rates of clinically diagnosed chorioamnionitis and endometritis and of suspected and culture-proven neonatal infection were determined. RESULTS: Between the study and control groups, the incidences of clinical chorioamnionitis (7.8% vs. 8.6%), endometritis (2.4% vs. 3.5%), aggregate intrauterine infection (10.0% vs. 11.8%), suspected neonatal infection (17.8% vs. 21.5%), and proven neonatal infection (0.0% vs. 2.2%) were not significantly different. CONCLUSIONS: Prophylactic use of cefazolin in amnioinfusions did not significantly reduce rates of maternal or neonatal infection in patients with meconium-stained amniotic fluid.

Adult↗

PubMed1988

Leukocyte esterase: a simple bedside test for the detection of bacterial colonization of amniotic fluid.

Chorioamnionitis is a major cause of neonatal mortality, neonatal morbidity, and maternal morbidity. Clinical signs of acute chorioamnionitis occur relatively late, and laboratory tests for acute chorioamnionitis lack the desired sensitivity and specificity. Early antibiotic treatment may have important neonatal implications. The leukocyte esterase test is both rapid and simple. Because of the specificity (100%) and sensitivity (81%) of the test in predicting bacterial colonization of the amniotic fluid, we conclude that it has the potential to become an invaluable tool in assessing the intrauterine environment.

Amniotic Fluid↗

PubMed1995

Early versus late amniotomy for labor induction: a randomized trial.

OBJECTIVE: Our purpose was to determine the impact of early and late amniotomy on labor induction with continuous oxytocin infusion at term. STUDY DESIGN: A total of 209 women admitted for labor induction were randomized to early or late amniotomy. The early amniotomy group (n = 106) had membranes ruptured as soon as it was deemed safe and feasible. The late amniotomy group (n = 103) had membrane rupture performed at > or = 5 cm dilatation. The first 103 women received a continuous oxytocin infusion with incremental adjustments at 60-minute intervals as required. The next 106 women had adjustments every 30 minutes as required. Statistical analysis was confined to concurrent groups. RESULTS: Early amniotomy was associated with shorter labor (13.3 vs 17.8 hours, p = 0.001), chorioamnionitis (22.6% vs 6.8%, p = 0.002), and significant fetal umbilical cord compression (12.3% vs 2.9%, p = 0.017). The benefit regarding shortening of labor was limited to women having oxytocin increments every 30 minutes as required (13.3 vs 17.8 hours, p = 0.001). Alternatively, the increase in chorioamnionitis was confined to the 60-minute group (39% vs 11%, p < 0.001), which also demonstrated a trend toward increased moderate and severe variable decelerations (19.6% vs 6.4%, p = 0.08). CONCLUSIONS: When a protocol of 60-minute increments in oxytocin infusion rate is desired, amniotomy should be performed late in labor to reduce chorioamnionitis and significant umbilical cord compression. Alternatively, if early amniotomy is necessary, oxytocin should be adjusted every 30 minutes as tolerated.

Adolescent↗

PubMed1995

Maternal and perinatal outcome of patients with preterm labor and meconium-stained amniotic fluid.

OBJECTIVE: To determine the clinical significance of meconium-stained amniotic fluid (AF) observed at amniocentesis in patients with preterm labor. METHODS: A nested case-control study was constructed based on the color of AF during amniocentesis. Forty-five women admitted with preterm labor and meconium-stained AF were matched for gestational age at admission and compared with 135 women with preterm labor and clear AF. All AF samples were cultured for aerobic and anaerobic bacteria and mycoplasma. RESULTS: The rates of positive AF cultures for microorganisms, overall preterm birth (before 36 weeks), preterm birth before 32 weeks, and clinical chorioamnionitis were all significantly higher in patients with meconium-stained AF than in those with clear AF (positive AF cultures, 38 versus 11%, P < .001; preterm delivery before 36 weeks, 73 versus 41%, P < .001; preterm delivery before 32 weeks, 51 versus 17%, P < .001; and clinical chorioamnionitis, 22 versus 6%, P = .003). In contrast, no significant differences were observed between groups with respect to maternal age, gravidity, parity, abruptio placentae, placenta previa, fetal distress, cesarean rate, or puerperal morbidity. CONCLUSION: Patients with preterm labor and meconium-stained AF had higher rates of microbial invasion of the amniotic cavity, clinical chorioamnionitis, and premature deliveries than those with clear AF.

Adult↗

PubMed1996

Bacteremia shortly after placental separation during cesarean delivery.

OBJECTIVE: To assess frequency, risk factors, and microbiology of bacteremia within 15 minutes of placental separation during cesarean delivery. METHODS: Ninety-three women undergoing cesarean delivery after a minimum of 4 hours of labor or ruptured membranes were compared with 26 women not in labor undergoing cesarean. Blood cultures for aerobic and anaerobic bacteria were obtained within 15 minutes of delivery of the placenta and before prophylactic antibiotic administration. Chorioamnionic membranes were also cultured. Demographic, labor, delivery, and postpartum characteristics were abstracted from the medical record. RESULTS: Bacteremia was detected in 13 (11%) of 119 women. Bacteremia occurred in 13 (14%) of 93 women after labor or rupture of membranes compared with zero of 26 women not in labor (P = .02). Isolates included group B streptococcus (n = 5), Gardnerella vaginalis (n = 5), Streptococcus pneumoniae (n = 1), Peptostreptococcus sp (n = 1), and mixed flora of Prevotella bivia, G vaginalis, and viridans streptococci (n = 1). Bacteremia was associated with earlier median gestational age, lower median birth weight, and a positive chorioamnionic membrane culture. After adjustment for gestational age, intrauterine monitoring was also significantly associated with bacteremia. CONCLUSION: Bacteremia was common after labor in this population, especially in preterm deliveries and those with positive chorioamnionic-placental culture. Many of the isolates are capable of causing endocarditis. Appraisal of the risk of bacteremia and the risk of bacterial endocarditis should be made in individual patients to assess the need for antibiotic prophylaxis.

Adult↗

PubMed2004

Maternal origin of inflammatory leukocytes in preterm fetal membranes, shown by fluorescence in situ hybridisation.

The aim of this study was to determine the maternal or fetal origin of inflammatory leukocytes in fetal membranes from cases of chorioamnionitis. Fetal membranes were collected from male preterm infants and chorioamnionitis was diagnosed histologically. Fluorescence in situ hybridisation for X and Y chromosomes was used to determine the gender of infiltrating leukocytes in the chorion and amnion. Leukocytes, trophoblast and mesenchymal cells were identified using immunohistochemistry for CD45, cytokeratin-7 and vimentin, respectively. Leukocytes present in the chorion and amnion were labelled XX, indicating maternal origin, and these cells were immunoreactive for the leukocyte marker CD45 but not for vimentin or cytokeratin-7. All other cells in the chorion and amnion were labelled XY and of fetal origin. The results indicated that maternal leukocytes invade the amnion and chorion in chorioamnionitis and we suggest that this is part of the maternal inflammatory response to intrauterine infection.

Adult↗

PubMed1993

Placental interleukin-6 production is enhanced in intrauterine infection but not in labor.

OBJECTIVE: Because interleukin-6 is an important mediator in the host defense mechanism against infection and tissue damage, we studied the capacity of placentas with or without either labor or chorioamnionitis in the third trimester to produce interleukin-6. STUDY DESIGN: The placental blocks were cultured, and their interleukin-6 titers were measured by a bioassay. RESULTS: Placentas with labor produced a similar amount of interleukin-6 to placentas without labor. In contrast, placentas with chorioamnionitis produced much more interleukin-6 than the placentas with or without labor (p < 0.0001). CONCLUSION: Placental interleukin-6 is thus surmised to participate in potentiation of the placental and fetomaternal defense mechanisms together with placental interleukin-1 during chorioamnionitis.

Chorioamnionitis↗

PubMed1998

Concomitant use of glucocorticoids: a comparison of two metaanalyses on antibiotic treatment in preterm premature rupture of membranes.

OBJECTIVE: This study was performed to investigate whether the demonstrated beneficial effects of antibiotics on maternal and neonatal morbidity are altered when glucocorticoids are part of the treatment of preterm premature rupture of membranes. STUDY DESIGN: We performed a metaanalysis of five published, randomized trials of antibiotic treatment in preterm premature rupture of membranes in which glucocorticoids were used as additional treatments and compared the results with those of a previously published metaanalysis of antibiotic treatment in preterm premature rupture of membranes, which excluded studies with concomitant glucocorticoids. Primary outcomes included chorioamnionitis, postpartum endometritis, neonatal sepsis, respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and neonatal mortality. A logistic regression analysis was performed to test whether glucocorticoids significantly influenced the effect of antibiotic treatment. RESULTS: Among the 509 patients from five trials on antibiotic and glucocorticoid treatment published between 1986 and 1993 antibiotic therapy did not show any significant effect on any of the outcomes analyzed. In contrast, antibiotic therapy without concomitant use of glucocorticoids significantly reduced the odds of chorioamnionitis, postpartum endometritis, neonatal sepsis, and intraventricular hemorrhage by 62%, 50%, 68%, and 50%, respectively. The logistic regression analysis showed that glucocorticoids significantly diminished the effect of antibiotic treatment on chorioamnionitis and neonatal sepsis. CONCLUSION: Glucocorticoids appear to diminish the beneficial effects of antibiotics in the treatment of preterm premature rupture of membranes. A careful selection of patients who are likely to benefit from both therapies is therefore recommended.

Anti-Bacterial Agents↗

PubMed1999

Cervical incompetence: elective, emergent, or urgent cerclage.

OBJECTIVE: We define criteria for insertion of cervical cerclage done electively (historical), urgently (in patients without symptoms), or emergently (in patients with symptoms). We compare outcomes as determined by prolongation of pregnancy and survival in each of these groups, and we define whether urgent or emergent cerclage imparted a higher risk of spontaneous rupture of membranes or chorioamnionitis than that associated with elective cerclage. STUDY DESIGN: This is a retrospective analysis of all cervical cerclages placed at Memorial Medical Center between January 1, 1993, and December 31, 1997. Outcomes oberved were as follows: (1) prolongation of pregnancy in weeks after cervical cerclage, (2) presence of spontaneous rupture of membranes or clinical chorioamnionitis necessitating delivery, and (3) neonatal outcome. RESULTS: For prolongation of pregnancy the following results were obtained: emergent cerclage, 8.3 +/- 0.9 weeks; urgent cerclage, 12.2 +/- 1.5 weeks; and elective cerclage, 20.2 +/- 0.9 weeks (elective versus emergent and urgent, P <.05). For average gestational age at delivery, the results were as follows: emergent cerclage, 30.5 +/- 0.9 weeks; urgent cerclage, 33.1 +/- 1.4 weeks; and elective cerclage, 35.5 +/- 0.9 weeks (elective versus emergent and urgent, P <.05). The total neonatal survival was 85.7%. The incidence of spontaneous rupture of membranes was as follows: emergent cerclage, 51%; urgent cerclage, 40%; elective cerclage, 18% (elective versus emergent and urgent, P <.05). The incidence of clinical chorioamnionitis showed similar results. CONCLUSIONS: It is clear that emergency cerclages confer some benefit in patients with evidence of cervical incompetence. From this study it is evident that there is a new group of patients who need cerclage on an urgent basis as shown by subtle ultrasonographic changes in the cervix. Their behavior mirrors that of those belonging to the emergent group, suggesting that if they were left untreated they would need cerclage on an emergency basis.

Adult↗

PubMed2003

Cervical Lactobacillus and leukocyte infiltration in preterm premature rupture of membranes.

OBJECTIVES: To evaluate the possible association between microorganisms present in the cervical secretions and amniotic fluid of pregnant women with preterm premature rupture of membranes (PPROM), and histologic chorioamnionitis. METHODS: Thirty-seven pregnant women with PPROM and 21 healthy pregnant women were studied. Secretions from the cervical canal and amniotic fluid were collected to isolate microorganisms present in the genital tract. Cervical smears were Gram stained and evaluated microscopically. At delivery, chorioamniotic membranes were collected for histopathologic analysis. RESULTS: Microscopic examination of the cervical secretion smears obtained from the PPROM group showed a low rate of Lactobacillus species, large numbers of leukocytes, and a wide diversity of microorganisms compared with the control group. The PPROM group presented an 80% rate of chorioamnionitis. Staphylococcus aureus isolation in cervical secretion was associated with intense inflammatory infiltrate in the membranes and might play a role in the pathogenesis of PPROM. CONCLUSIONS: The low colonization of cervical flora by Lactobacillus species associated with an intense leukocyte infiltrate detected in Gram-stained cervical smears can be considered a rapid method of detecting chorioamnionitis in pregnant women with PPROM.

Amniotic Fluid↗

PubMed1997

Amniotic fluid interleukin-10 (IL-10) concentrations during pregnancy and with labor.

To determine if amniotic fluid interleukin-10 (IL-10) concentrations are elevated in women with labor, either at term or preterm, and in the setting of infection-associated preterm labor, amniotic fluid samples were collected from women: (1) at term, not in labor (n = 42); at term, in labor (n = 56), preterm contractions, undelivered within 1 week (n = 22), and preterm labor, delivered within 1 week (n = 31). IL-10 concentrations were assayed in each sample via ELISA (Pharmingen, San Diego, CA). In a subsequent analysis, 8 women with preterm labor associated with chorioamnionitis were matched for gestational age with women experiencing preterm contractions (undelivered within 7 days) and preterm labor (delivered within 7 days) and amniotic fluid IL-10 concentrations compared. Approximately 40-70% of amniotic fluid samples obtained from women in each group had detectable IL-10. However, there were no significant differences in amniotic fluid IL-10 concentrations among the patients. While 1 of 8 patients with chorioamnionitis had amniotic fluid IL-10 concentrations greater than 300 pg/ml, there were no statistically significant differences among the matched samples. Amniotic fluid IL-10 concentrations were not elevated in women with term labor, preterm labor, or chorioamnionitis. This finding contrasts with the elevated concentrations of pro-inflammatory cytokines and chemokines such as interleukin-1, tumor necrosis factor-alpha, IL-6, IL-8, MIP-1 alpha, and GRO alpha reported in previous studies. Because we did not detect elevations of the key anti-inflammatory cytokine IL-10 in amniotic fluid of women with infection-associated preterm labor, we suggest that anti-inflammatory processes in this setting may be attenuated.

Adult↗

PubMed2003

Antenatal factors and the development of bronchopulmonary dysplasia.

The lung of the preterm fetus is often exposed to antenatal glucocorticoids, and histologic chorioamnionitis is frequent. Clinically and experimentally, antenatal glucocorticoids and/or chorioamnionitis are associated with early lung maturation, but in experimental models, both glucocorticoids and intra-uterine inflammation decrease alveolarization. Experimental chorioamnionitis also can amplify the inflammatory response of the preterm lung to mechanical ventilation. In this article, the hypothesis developed is that bronchopulmonary dysplasia occurs because of repetitive adverse lung exposures, or hits, and that the initial hits may be antenatal glucocorticoid exposure and/or antenatal inflammation.

Animals↗

PubMed2005

Antenatal associations with lung maturation and infection.

Chronic clinically unapparent chorioamnionitis is a common antenatal exposure for very preterm infants, and these infants have variable degrees of lung maturation and a high risk of developing bronchopulmonary dysplasia. Exposure of fetal sheep to intra-amniotic endotoxin or IL-1alpha induces chorioamnionitis and lung injury (decreased alveolarization and microvascular injury), which resolves to a phenotype of striking lung maturation (increased surfactant, improved gas exchange and lung mechanics). The immune responses of the fetus also are suppressed or induced (matured) in time and dose-dependent ways by either chorioamnionitis or antenatal corticosteroids. These experimental observations contribute to explanations of why preterm infants have variable degrees of lung maturation at birth and unpredictably develop bronchopulmonary dysplasia BPD.

Animals↗