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Single additional dose postpartum therapy for women with chorioamnionitis.

OBJECTIVE: To determine whether a short course of antibiotics provides adequate treatment for chorioamnionitis. METHODS: Women received intravenous ampicillin, 2 g every 6 hours, and gentamicin, 1.5 mg/kg every 8 hours, when clinical chorioamnionitis was diagnosed. After delivery, subjects were randomized to continue this regimen until afebrile and asymptomatic for 24 hours (control group) or to receive only the next scheduled dose of each drug (study group). If delivered via cesarean, patients received clindamycin, 900 mg intravenously, at umbilical cord clamping. The control group continued receiving clindamycin every 8 hours until antibiotics were discontinued. The primary outcome was treatment failure, defined as a single temperature after the first postpartum dose of antibiotics of 39.0C or more, or two temperatures 38.4C or more at least 4 hours apart. To detect a 150% increase in rate of treatment failures from 8% in the control group to 20% in the study group, 292 subjects were needed (alpha = .05; 1 - beta = .80). RESULTS: From December 26, 1999, to March 18, 2003, a total of 292 women were enrolled in the study. In the intent-to-treat analysis, treatment failure rate did not differ between the control (n = 141) and study (n = 151) groups (3.5% versus 4.6%; P = .639). CONCLUSION: If treated promptly intrapartum, one additional dose of a broad-spectrum combination of antibiotics is sufficient postpartum therapy for immune-competent women with chorioamnionitis.

Adult↗

Cytokine production in chorioamnionitis.

Lymphohematopoietic cytokines play a significant role in many biological mechanisms including a number of reproductive processes such as ovulation, implantation, placentation, cervical dilation and parturition. Recent experiments have suggested that cytokines play a crucial role in the mechanisms of preterm labor and delivery, which are the leading causes of perinatal morbidity and mortality. Growing evidence suggests that infection is deeply concerned in the pathogenesis of preterm labor and delivery. Chorioamnionitis, a subset of intrauterine infection, has been identified in 20-33% of women with preterm delivery, and the inflammatory and related cytokines, interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8), showed substantial increases in the amniotic fluid at women with intrauterine infection. Although the precise mechanism for chorioamnionitis-driven preterm labor mediated via cytokines is still unknown, both IL-1 and TNF-alpha along with IL-6 enhance prostaglandin production by human amnion cells, chorionic cells and decidual cells. Analysis of the regulatory sequences in the 5' upstream regions of receptor gene for human oxytocin, a potent uterotonic agent, suggests a close relationship between preterm labor and inflammatory cytokines through induction at the oxytocin receptor. Prompt identification of the patients with intra-amniotic infection may be useful in clinical practice. At present, the measurement of IL-8 in maternal serum or the measurement of IL-6 in cervical secretion may be helpful as a non-invasive screening for chorioamnionitis.

Cervix Uteri↗

Maternal serum granulocyte-colony stimulating factor in preterm birth with subclinical chorioamnionitis.

Preterm birth has been linked with intrauterine infection and inflammation. Serum and amniotic fluid markers of inflammation, such as interleukin-1 (IL-1), IL-6, and granulocyte-colony stimulating factor (G-CSF), have been associated with clinical chorioamnionitis and preterm delivery. As G-CSF regulates the production and maturation of neutrophils, we sought to determine if maternal serum G-CSF levels are elevated in patients with preterm birth with subclinical histologic chorioamnionitis. Maternal serum G-CSF levels were significantly different among five groups of women studied (P < .001, Kruskall-Wallis test), and were highest in subjects with preterm labor who delivered preterm (P < .05, Mann-Whitney U test). Among women with preterm labor who delivered preterm, maternal serum G-CSF levels were significantly higher if histologic chorioamnionitis was present than when histologic evidence of infection was not present (P = 0.04, Mann-Whitney U test). Intrauterine infection may cause a local inflammatory process and initiate preterm labor. This inflammatory response may include production of G-CSF, which would enter the circulation and stimulate the migration of neutrophils to the site of infection. Our data support this concept, as maternal serum G-CSF is elevated with subclinical infection in association with preterm birth.

Chorioamnionitis↗

Induction of hepatic granulopoiesis due to chorioamnionitis during the second trimester of development.

OBJECTIVE: To detect post mortem changes in fetal hematopoiesis consistent with infection from liver examination alone. STUDY DESIGN: We investigated the immunohistochemical expression of Glycophorin C, Neutrophilic elastase, and CD34, in the hepatic parenchyma from fetuses miscarried as a result of chorioamnionitis (caused by Chlamydia trachomatis) and correlated them with the equivalent from fetuses after voluntary abortion (gestational age: 16th, 20th, and 24th weeks). RESULTS: A statistically significant difference was found in the Neutrophilic elastase positive cells to the advantage of cases with chorioamnionitis over voluntary abortions (24th week: P=0.0001, t-test) and also at the level of total hematopoiesis (20th and 24th week: P=0.041 and 0.004, respectively, t-test). There was no quantitative difference between the two settings at the level of erythropoiesis in the three examined periods. CONCLUSIONS: Fetal infection can be diagnosed from the liver alone. After detection of changes in fetal hematopoiesis indicative of infection, examination of additional specimens of placenta and membranes will document the diagnosis of chorioamnionitis.

Abortion, Spontaneous↗

Chorioamnionitis is associated with placental transmission of human immunodeficiency virus-1 subtype E in the early gestational period.

The frequency and the cellular basis for HIV-1 transmission from mother to child in the early gestational period are poorly understood. We compared the placentas of 24 women seropositive for HIV-1 subtype E and who had not received any antiretroviral drugs, to placentas of 25 seronegative women. All placentas were obtained during therapeutic abortion at 6-23 weeks gestation. Placentas and fetal organs were examined by routine light microscopy, immunostaining for p24 capsid protein, and in situ PCR to localize which cells were infected with HIV-1 subtype E. The number of previous abortions was not a factor in placental HIV infection since this number was higher in seronegative women (P < 0.01). There were no significant differences between the placentas of the two groups with respect to presence of chorioamnionitis, villitis, villous stromal fibrosis, infarction, abnormal villous maturation, deciduitis or decidual necrosis. HIV-1 subtype E was detected in up to 83% of placentas, either by immunostaining or in situ PCR, in trophoblast, villous stromal cells, Hofbauer cells, decidual and decidual glandular epithelium. Fetal organs were positive for HIV in 30% (6/20) of cases. There was a significant association between transmission of HIV to the fetus and the histologic findings of chorioamnionitis, plasmacellular deciduitis and decidual cell necrosis. This is the first report showing an association of chorioamnionitis with early in utero transmission of HIV-1 subtype E. This may help explain the cases of in utero transmission that persist despite antiretroviral prophylaxis, given that therapy is started in the late gestational period.

Chorioamnionitis↗

Meconium-stained amniotic fluid and neonatal morbidity in near-term and term deliveries with acute histologic chorioamnionitis and/or funisitis.

OBJECTIVE: To determine the incidence of meconium-stained amniotic fluid (MSAF) and neonatal morbidity in near-term and term deliveries with histologic acute chorioamnionitis and/or funisitis compared to those with normal placental histology. STUDY DESIGN: In a retrospective case-control design, we compared the incidence of MSAF and neonatal outcome in 45 cases of acute histologic chorioamnionitis and/or funisitis with 89 cases of normal placental histology. We reviewed the obstetric and neonatal records for perinatal complications and neonatal morbidity. RESULTS: Mean birthweights (3372+/-473 vs 3287+/-518 g) were similar in infants born to mothers with histologic chorioamnionitis and/or funisitis compared to infants born to mothers with normal placental histology. The incidence of MSAF was significantly higher in the group with acute chorioamnionitis/funisitis (p<0.05). Similarly, the incidence of admissions to newborn intensive care unit, respiratory distress, meconium aspiration syndrome, and presumed sepsis was also significantly higher (p<0.05) in this group. CONCLUSION: The incidence of MSAF and neonatal morbidity is higher in the presence of acute inflammation of placental membranes. The presence of meconium in the amniotic fluid should alert the physician to the potential for infection and increased neonatal morbidity.

Acute Disease↗

What explains away the increased risk of histological chorioamnionitis in African-American mothers of very-low-birthweight infants? Developmental Epidemiology Network Investigators.

We sought explanations for African-American mothers' increased risk of chorioamnionitis by sequentially adjusting for confounder variables both individually and in groups. We searched for a subset of covariates that had the most influence on the chorioamnionitis odds ratio (OR) of these women. The sample consisted of 305 African-American and 520 White mothers who gave birth to a very-low-birthweight (< or = 1500 g) infant between 1991 and 1993, whose placenta was examined according to protocol and whose hospital chart was reviewed. Histologically proven chorioamnionitis was present in 43% of the placentas from African-American women and in 27% of those from Whites (crude OR 2.1, 95% confidence interval 1.5, 2.8). Singleton status appeared to be the most important effect modifier, with significant crude ORs of 1.5 among singletons and 3.4 among non-singletons. Using logistic regression models in the whole sample and in subgroups, we sought to 'explain away' this increased risk. Indeed, addition of information about confounder variables resulted in considerable reduction in the ORs to 1.1 among singletons and 1.9 among non-singletons. Particularly important among the confounders were singleton birth, Medicaid insurance, duration of ruptured membranes and gestational age. We discuss the possibility that this set of confounding variables conveys, in part, the same information as the variable African-American, and also perhaps information about the availability and/or utilisation of prenatal health care.

Black or African American↗

Successful outcome after antibiotic treatment of postamniocentesis membrane rupture and chorioamnionitis in multiple pregnancy.

Postamniocentesis chorioamnionitis is usually managed with induction of labor to prevent maternal sepsis and related morbidity and mortality. We report a case of chorioamnionitis in a triplet pregnancy after midtrimester genetic amniocentesis, in which multiple antibiotic treatment (ampicillin 2 g i.v. loading dose followed by 1 g i.v. every 6 hr; clindamycin 900 mg i.v. every 8 hr; gentamicin 120 mg i.v. loading dose followed by 100 mg i.v. every 8 hrs; and erythromycin 500 mg i.v. every 6 hr) for 7 days and delivery of the presumably infected triplet A successfully reversed the clinical symptomatology, allowing prolongation of pregnancy until 26 weeks and survival of the remaining fetuses. At age 2 years, both infants are doing well and are meeting their developmental milestones. The viable outcome of this management strategy suggests that antibiotic treatment and expectancy may be an option in selected cases of postamniocentesis chorioamnionitis in multiple pregnancies.

Adult↗

Candida chorioamnionitis diagnosed by amniocentesis with subsequent fetal infection.

Isolation of Candida albicans from the vaginal secretions of pregnant women occurs with an incidence of 5-23%. Intrauterine infection caused by Candida during pregnancy is relatively rare; only 81 cases, all diagnosed after delivery, have been reported. We report six cases of candidal chorioamnionitis diagnosed by amniocentesis and confirmed by histologic studies, associated with preterm labor and delivery of five viable infants. Three of the six maternal patients had intrauterine contraceptive devices in situ. Three infants had a diagnosis of congenital cutaneous candidiasis and two had congenital systemic candidiasis, one with monilial pneumonia, and one with meningitis and septicemia. All viable neonates were treated successfully. The sixth, a very immature infant, died soon after delivery. Torulopsis (Candida) glabrata was isolated from this amniotic fluid. C. Albicans is a pathogen that potentially may cause chorioamnionitis and has been associated with high mortality (94%) in infants weighing less than 1500 gm. Use of amniocentesis in patients with preterm labor may allow early detection of subclinical candidal chorioamnionitis, thus guiding appropriate perinatal management.

Adolescent↗

Interleukin-8 release from human gestational tissue explants: effects of gestation, labor, and chorioamnionitis.

Interleukin-8 (IL-8) is a chemotactic cytokine that has been implicated in the process of human parturition, including the processes of cervical ripening and rupture of fetal membranes. In this study, the in vitro release of IL-8 from human amnion, choriodecidua, and placenta tissues obtained before and after spontaneous labor onset both at term and preterm, was assessed. The effect of chorioamnionitis on IL-8 release was also established. All tissue explants examined released IL-8; however, IL-8 release from choriodecidual explants was significantly (p < 0.02) greater than that observed from amnion and placenta. Furthermore, choriodecidual IL-8 release was significantly (p < 0.001) greater from term tissues (850 +/- 134.4 ng/mg DNA, n = 18) than from preterm tissues (458 +/- 68.8 ng/mg DNA, n = 17). Spontaneous onset of labor, irrespective of the eventual mode of delivery, was not associated with any significant changes in IL-8 release from human gestational tissues compared to not-in-labor tissues, both at term and preterm. IL-8 release from gestational tissues was not significantly different in the absence or presence of chorioamnionitis. These data are in contrast to the previously reported stimulatory effects of bacterial endotoxin on IL-8 release from human gestational tissues. The data are consistent, however, with the suggestion that IL-8 release is an early event in chorioamnionitis that precedes the appearance of clinically overt symptoms.

Amnion↗

Sequelae of chorioamnionitis.

Chorioamnionitis correlates to preterm delivery prior to 30 weeks of gestation. In most studies, proxies of intrauterine infection (clinical chorioamnionitis, histological chorioamnionitis, intra-amniotic increase in cytokines) are associated with acute neonatal morbidity and mortality and, at least to some degree, with neurological impairments (periventricular leukomalacia, intraventricular hemorrhage, cerebral palsy, polymicrogyria), chronic lung disease, and involution of the thymus in the preterm infant. The connection to visual impairment and cognitive deficits is uncertain or unknown. Full-term babies exposed to intrauterine infection often present with depressed Apgar scores and neonatal encephalopathy, and are at markedly increased risk of developing cerebral palsy. The infectious/inflammatory mechanisms involved are incompletely understood, and the types of microbes, as well as the genetic characteristics of the host adaptive and innate immune response, need to be better characterized.

Central Nervous System Diseases↗

Low incidence of positive amnionic fluid cultures in preterm labor at 27-32 weeks in the absence of clinical evidence of chorioamnionitis.

In order to determine the utility of amniocentesis for detecting subclinical chorioamnionitis in asymptomatic afebrile women in preterm labor with intact membranes, we enrolled 47 women between 27-32 weeks' gestation in a prospective study. After enrollment, 38 women fulfilled all clinical and laboratory criteria for the study; nine women were excluded because they had a leukocyte count exceeding 15,000/microL. None of the 38 asymptomatic afebrile women had a positive culture from the amnionic fluid for bacteria, fungi, Mycoplasma hominis, Ureaplasma urealyticum, Chlamydia trachomatis, or any viruses. Sepsis was not proved in any of the 38 infants delivered to these patients. There was a clear relationship between histologic evidence of chorioamnionitis and failure of tocolytic therapy. Fetal lung profiles were mature in 29% of the amnionic fluid samples from 30-32 weeks' gestation, but in none of the amnionic fluid samples before 30 weeks. Amniocentesis does not seem useful to detect chorioamnionitis in asymptomatic afebrile women with preterm labor and intact membranes at 27-32 weeks' gestation, and should be reserved for those cases in which information about fetal lung maturity would be helpful.

Adolescent↗

Active-phase labor arrest: a randomized trial of chorioamnion management.

OBJECTIVE: To determine whether leaving the membranes intact in active-phase arrest would affect the cesarean delivery rate or the incidence of maternal morbidity secondary to infection. METHODS: We conducted a randomized trial of healthy, spontaneously laboring women at term with an intact chorioamnion and active-phase arrest (defined as 1 cm or less of cervical change over 2 hours in the active phase of labor). Patients were assigned to either oxytocin augmentation with intact chorioamnion or oxytocin augmentation with amniotomy and internal monitoring of the fetal heart rate and uterine contractions. RESULTS: The intact group (n = 58) and the amniotomy group (n = 60) were similar with respect to maternal age, race, parity, labor epidural usage, gestational age, cervical dilatation at randomization, number of vaginal examinations, and infant birth weight. Four patients in the intact group and five in the amniotomy group underwent cesarean delivery (P = 1.0). No patient in the intact group and three in the amniotomy group were diagnosed with chorioamnionitis (P = .24). Endometritis did not occur in the intact group, whereas four cases occurred in the amniotomy group (P = .12). There were no cases of maternal infection in the intact group, versus seven in the amniotomy group (P = .01). The interval between randomization and vaginal delivery was 44 minutes longer in the intact group than in the amniotomy group (P = .11). CONCLUSION: In women with active-phase arrest of labor and intact membranes, oxytocin augmentation with elective amniotomy and internal monitoring increases maternal infectious morbidity.

Adult↗

Prostaglandin E production by the fetal membranes in unexplained preterm labour and preterm labour associated with chorioamnionitis.

The production of prostaglandin E (PGE) by amnion, choriodecidua and placenta was measured in 45 women delivered after spontaneous preterm labour, in 10 women delivered electively preterm, in 30 women at elective caesarean section at term, and in 28 women after spontaneous labour at term. In the preterm labour group 24 women had normal placental histology, and gestational age was 34 (31-36) weeks (median and range); 18 women had evidence of chorioamnionitis and gestational age was significantly shorter, 30 (24-36) weeks; three other patients had placental abruption. In the absence of inflammatory infiltration of these tissues the highest PGE output (fmol/mg dry weight/2 h) was found after labour at term and the lowest after uncomplicated preterm labour: 2640 (360-15,580) (median and range) compared with 1414 (164-11,045) in amnion, 677 (100-3245) compared with 308 (39-1086) in choriodecidua, and 1200 (520-3022) compared with 578 (150-1859) in placenta, respectively. Tissues showing chorioamnionitis produced much higher outputs of PGE from amnion (12,278, 1799-82,617) and from choriodecidua (1018, 216-11,768), but not from placenta (616, 89-4131). Chorioamnionitis seems to cause very early preterm labour by increasing PG production in the amnion and choriodecidua.

Amnion↗

Amniotic fluid concentrations of interleukin-1beta, interleukin-6 and TNF-alpha in chorioamnionitis before 32 weeks of gestation: histological associations and neonatal outcome.

OBJECTIVES: To test the association between cytokine levels in the amniotic fluid and (i) the vascular invasion phase of intrauterine infection, (ii) the occurrence of periventricular leukomalacia; to assess the correlation between C-reactive protein levels, a recognised biological marker of inflammation in maternal serum and cytokine levels in the amniotic fluid. DESIGN: Prospective clinical study. SETTING: Fetal medicine unit and neonatal intensive care unit, Antoine Beclere Hospital, Clamart, France. SAMPLE: Thirty-one pregnancies complicated by chorioamnionitis leading to birth before 32 weeks of gestation. METHODS: Interleukin 1-beta, Interleukin 6 and TNF-alpha prospectively measured in the amniotic fluid. Histological examination of the placenta. Ultrasound examination and magnetic resonance imaging of the brains of the newborn infants performed within the first week of life. MAIN OUTCOME MEASURES: The occurrence of periventricular leukomalacia was assessed by transfontanellar ultrasound and magnetic resonance imaging. RESULTS: There was a significant positive correlation between the occurrence of histological chorioamnionitis, vascular extension of infection of the membranes, maternal inflammatory syndrome and neonatal sepsis. A strong association was found between maternal serum C-reactive protein concentrations and cytokine levels in the amniotic fluid. Interleukin-1beta was the best predictor of vascular extension of chorioamnionitis, and TNF-alpha was the best predictor of the development of severe early neonatal infection. There was no association between the amniotic fluid levels of cytokines and the development of periventricular leukomalacia. CONCLUSIONS: These data suggest that IL-1beta, IL-6 and TNF-alpha are produced in relation to intrauterine inflammation and infection, but cannot be directly implicated in the development of fetal cerebral white matter lesions.

Amniotic Fluid↗

Ureaplasma urealyticum chorioamnionitis.

Controversy reigns over the role of Ureaplasma urealyticum in determining pregnancy outcome. U. urealyticum infection of the chorioamnion is strongly associated with chorioamnionitis (1-3), premature birth (2-4), and perinatal morbidity (4-6). We present 4 cases of U. urealyticum chorioamnionitis and associated morbidity and mortality.

Adult↗

Does amniotomy influence the prognosis of babies in cases with severe chorioamnionitis? Report of a twin pregnancy with varying outcome.

We report our experience in a woman with a twin pregnancy. The patient suffered severe Escherichia coli chorioamnionitis and the outcomes were different between the two babies after birth. The first baby had only a mild infection, but the second suffered sepsis and subsequent perinatal death. These differences in outcome appeared to be due to amniotomy performed for the first baby after late labor stage I to augment uterus contractions. Removal of infectious amniotic fluid from the amniotic cavity might thus have prevented the spread of the chorioamnionitis. E. coli sometimes causes severe infection during pregnancy and the perinatal period. In this case, a large number of enteropathogenic E. coli (serotype O-6) was cultured from blood, stool, pharyngeal swab, gastric juice and puncture fluid from the thoracic cavity of the second baby. O-6 is classified an enterotoxigenic strain mainly causing diarrhea because of endotoxin released from bacteria. O-6 has not hitherto been reported as a cause of severe infection in chorioamnionitis and perinatal sepsis.

Adult↗

TNF, IL-1, IL-6, IL-8 and soluble TNF receptors in relation to chorioamnionitis and premature labor.

Inflammatory cytokines seem to play a key role in mechanisms initiating labor. Since cytokine levels are higher in preterm than in term labor, it has been hypothesized that labor-inducing effects of cytokines are inhibited by an upregulated production of cytokine antagonists, such as soluble cytokine receptors, at early stages of gestation. In this study, TNF, IL-1, IL-6, IL-8 and soluble TNF receptors (sTNFRs) were measured in amniotic fluid samples from a) 39 women in premature labor, b) 25 women who where not in labor but delivered prematurely, and c) 33 women in term labor. Fifty-four of the placentas from premature deliveries were evaluated for presence of histological chorioamnionitis. Chorioamnionitis was associated with increased levels of TNF, IL-1 and IL-6, whereas elevated IL-1, IL-6 and IL-8 concentrations were found in premature parturition with no signs of infection. Concentrations of sTNFR were lower in preterm than in term deliveries. The present study confirms the participation of inflammatory cytokines in parturition. Multivariate analysis suggests a dominant, role of IL-1 in the presence of chorioamnionitis, whereas IL-6 seems to be more important during idiopathic premature labor. TNFR data do not support the hypothesis that production of cytokine antagonists is upregulated prematurely to prevent partirution.

Amniotic Fluid↗