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Clinical chorioamnionitis, elevated cytokines, and brain injury in term infants.

OBJECTIVES: To determine the initial inflammatory cytokine response in term infants born to mothers with clinical chorioamnionitis and to assess whether the cytokine response is associated with birth depression, abnormal neurologic examination, and hypoxic-ischemic encephalopathy (HIE). METHODS: Infants who were exposed to chorioamnionitis and admitted to the neonatal intensive care unit (n = 61) were studied prospectively. Cytokine concentrations were measured from umbilical cord blood and at 6 and 30 hours after birth. Control values (n = 50) were determined from cord blood of healthy term infants. Enzyme-linked immunosorbent assays were performed for interleukin (IL)-1beta; IL-6; IL-8; regulated on activation, normal T-cell expressed and secreted (RANTES); macrophage inflammatory protein-1alpha; and tumor necrosis factor-alpha. Serial blinded neurologic examinations using a modified Dubowitz score were performed simultaneously at 6 and 30 hours. RESULTS: Cord IL-6 (1071 +/- 1517 vs 65 +/- 46 pg/mL), IL-8 (2580 +/- 9834 vs 66 +/- 57 pg/mL), and RANTES (95 917 +/- 16 518 vs 54 000 +/- 14 306 pg/mL) concentrations only were higher in infants with chorioamnionitis versus control infants. IL-6 increased at 6 hours to 1451 +/- 214 pg/mL, followed by a 5-fold decline at 30 hours in contrast to progressive decreases over time in IL-8 and RANTES. There was no relationship between cytokines and birth depression. Modified Dubowitz score correlated with IL-6 at 6 hours (r = 0.5). Infants with HIE/seizures (n = 5) had significantly higher cytokine concentrations at 6 hours versus infants without either (n = 56): IL-6 (3130 vs 1219 pg/mL), IL-8 (5433 vs 780 pg/mL), and RANTES (97 396 vs 46 914 pg/mL). CONCLUSIONS: There was a significant association between abnormalities in the neurologic examination and cytokine concentrations, with the highest cytokines concentrations observed in infants who developed HIE/seizures.

Apgar Score↗

Investigation of the fetal pulmonary inflammatory reaction in chorioamnionitis, using an in situ Y chromosome marker.

Chorioamnionitis is a frequent finding in the placenta in second-trimester premature labor. Seventy-six archival perinatal and fetal autopsies between 15 and 28 weeks of gestation with a morphologic diagnosis of chorioamnionitis were reviewed. Of the 76 cases, 52 (68%) had inflammatory cells in the lungs, which is higher than the reported incidence of clinical infection in neonates with chorioamnionitis. In 23 cases there were peribronchial lymphocytic hyperplasia and neutrophils in the airspaces, in 8 there was a lesser degree of interstitial inflammation as well as luminal neutrophils, and in 21 (40%) there were neutrophils in the airspaces only. To determine whether the neutrophils in the airspaces in the latter were maternal or fetal in origin, the lung sections of seven male fetuses in the group were examined by in situ hybridization for the Y repeat probe pHY 2.1, together with appropriate controls. Two of the tests were technical failures. The remaining five, and the positive controls, showed positivity for pHY 2.1 in 70-86% of luminal neutrophils. We conclude that luminal neutrophils in fetal lungs in this situation are fetal in origin.

Chorioamnionitis↗

Candida albicans chorioamnionitis associated with preterm labor and sudden intrauterine demise of one twin. A case report.

BACKGROUND: Although cervicovaginal Candida infections occur in 20-25% of pregnancies, the incidence of ascending infection in these cases is only 0.8%, and such infection rarely causes chorioamnionitis. CASE: Sudden intrauterine fetal demise (IUFD) of twin A occurred in a diabetic primigravida presenting with a twin pregnancy and preterm labor at 33 weeks of gestation. Placental pathology and autopsy of the stillborn twin revealed extensive chorioamnionitis and fetal sepsis in the presence of Candida albicans. Twin B was unaffected. CONCLUSION: In this case, C albicans chorioamnionitis seemed to be associated with sudden IUFD.

Adult↗

Placental abruption in the preterm gestation: an association with chorioamnionitis.

Thirty-seven women with acute severe preterm placental abruption were compared with a control group of 51 women requiring preterm delivery for a medical complication of pregnancy. Histologic chorioamnionitis and funisitis were present significantly more often in patients with abruption than in control patients (41 versus 4%; P less than .0001). No patient in either group had clinical evidence of chorioamnionitis. We conclude that a significant association exists between preterm placental abruption and histologic chorioamnionitis.

Abruptio Placentae↗

Total complement activity in maternal sera, amniotic fluids and cord sera in women with premature labor, premature rupture of membranes or chorioamnionitis.

Total hemolytic complement activity (CH50) was determined in maternal sera, amniotic fluids or cord sera, or all, from 119 patients with preterm uterine contractions, premature rupture of membranes or chorioamnionitis, or all, at 24 to 40 weeks of gestation. The mean CH50 of maternal sera exceeded the mean CH50 of both amniotic fluids and cord sera. The mean CH50 of amniotic fluids exceeded that of cord sera and increased significantly at 32 weeks. This rise preceded that of the mean CH50 of cord sera, which occurred at a fetal weight of approximately 2,500 grams. The mean CH50 of amniotic fluids varied significantly and inversely with that of cord sera. The levels of CH50 in these three fluids did not distinguish between patients with preterm uterine contractions who delivered prematurely and those who delivered at term. The CH50 in patients with premature rupture of membranes did not differ from a control population of women with uncomplicated pregnancies. The mean CH50 of maternal sera was increased in patients with chorioamnionitis but was not predictive of chorioamnionitis. The mean CH50 of maternal sera was decreased in patients who smoked cigarettes and in patients who received intravenous ritodrine.

Amniotic Fluid↗

Chorioamnionitis: a study of organisms isolated in perinatal autopsies.

The purpose of this study was to determine the validity of postmortem cultures in perinatal autopsies; in particular, those cases where there is gross or histologic evidence of chorioamnionitis. Lung, liver, blood, and placental cultures were obtained from 159 neonatal autopsies with histologic evidence of chorioamnionitis at Magee-Women's Hospital between January 1980 and July 1985. The criterion for chorioamnionitis was a polymorphonuclear leukocytic infiltrate in the placental membranes. The neonates studied were 63 percent white and 36 percent black; the male to female ratio was 83 to 76. Intrauterine fetal death occurred in 43 percent of the cases. The mean gestational age was 24 weeks. Premature labor occurred in 64 percent of the cases, and 70 percent of the cases presented with premature rupture of fetal membranes. Congenital pneumonia (defined by the presence of polymorphonuclear leukocytes in the alveolar spaces) was present in 45 percent of cases. The lung was the most frequent site cultured; the four most frequently isolated organisms were: Staphylococcus epidermidis--18 percent; Beta Streptococcus Group B--13 percent; E. coli--nine percent; Ureaplasma urealyticum--nine percent. Negative cultures from multiple sites occurred in seven percent of cases. The results of this investigation indicate that multi-organ cultures help in defining the role of a particular bacteria as a pathogen, and that Staphylococcus epidermidis may be a true fetal pathogen under certain conditions. It is recommended that cultures for Chlamydia trachomatis not be done on fetal tissues.

Bacteria↗

Term maternal and neonatal complications of acute chorioamnionitis.

One hundred and three women who developed acute chorioamnionitis at 37 weeks' gestation or beyond were studied retrospectively. Clinical findings included fever (99.2%), fetal (82%) and maternal (19.4%) tachycardia, uterine tenderness (16.5%), and foul-smelling amniotic fluid (8.7%). Three of the 46 women who underwent cesarean section subsequently required addition of a second or third antibiotic for serious pelvic infection, whereas two had a subcutaneous wound infection requiring open drainage. Importantly, between zero and ten hours of the diagnosis of chorioamnionitis, a critical time interval where delivery impacted on neonatal infectious morbidity was not identified. Additionally, in the initial 24 hours after rupture of the fetal membranes there was no association between fetal, neonatal, or maternal complications versus duration of membrane rupture. These data suggest that immediate operative delivery of term gestations complicated by acute chorioamnionitis will not reduce neonatal morbidity.

Acute Disease↗

Cytokine expression in the placenta. The role of interleukin 1 and interleukin 1 receptor antagonist expression in chorioamnionitis and parturition.

Interleukin 1 (IL-1) is known to be present in placental tissue and is implicated as an endogenous mediator of inflammation and parturition. This study was undertaken to assess the role of IL-1 receptor antagonist (IL-1ra) in the placenta. Placentas with acute chorioamnionitis, with meconium staining, and without significant inflammation were examined for immunohistochemical expression of IL-1 and IL-1ra. Interleukin 1 and IL-1ra immunoreactivity was variably noted in the amnion, trophoblast, vascular smooth muscle, stromal cells, fibrinoid, and decidua in all placentas. Interleukin 1 immunoreactivity was less intense than IL-1ra immunoreactivity, and both were generally more intense in acute chorioamnionitis. Interleukin 1 receptor antagonist was detected (approximately 5 to 6 ng/mL) in the amniotic fluid of pregnant women at term. Colocalization of IL-1 and IL-1ra in normal and inflamed placentas suggests that the balance between these proinflammatory and anti-inflammatory mediators plays a role in parturition as well as in the pathogenesis of acute inflammation. An increase and/or imbalance in the IL-1 and IL-1ra expression associated with chorioamnionitis may precipitate preterm labor.

Adolescent↗

[Premature rupture of fetal membranes and chorioamnionitis].

The article presents a survey of preterm rupture of the amniotic membranes at term (more than 1 hour prior to uterine contractions) and preterm (< 37 weeks). The diagnosis of rupture can be suspected from the history alone in 90% of the cases, and confirmed by inspection. In doubtful cases the pH in fluid from the posterior fornix of the vagina is determined and microscopy is performed. Amniotic fluid is alkaline. Microscopy of a dried specimen shows "ferning" when amniotic fluid is present (crystallization test). Staining with Nil blue will reveal orange foetal cells in fresh specimens, usually only late in pregnancy (after the 38 week). The crystallization test is useful, however, in all three trimesters. The cause of membrane rupture and of chorioamnionitis may be infection. Chorioamnionitis is a serious clinical condition, but can be subclinical and may occur with intact membranes. It can lead to preterm delivery. It is important that chorioamnionitis be diagnosed (maternal fever, tachycardia, uterine contractions, abdominal pain, foul smelling vaginal discharge and elevated C-reactive protein). The condition is treated with antibiotics and labour must be induced.

Chorioamnionitis↗

[Clinical evaluation of flomoxef in the treatment of chorioamnionitis and changes in the fetal fibronectin level in vaginal secretion].

Flomoxef (FMOX) was administered as an initial treatment for chorioamnionitis complicating possible spontaneous abortion or premature delivery and preterm PROM (premature rupture of the membranes), and the clinical effectiveness of the drug, and the usefulness of fetal fibronectin (FFN) as a diagnostic marker of premature delivery were evaluated. 1. Clinical effects of drip infusion of FMOX (2-4 g/day) with and without tocolysis for the treatment of chorioamnionitis were evaluated in 43 patients with possible spontaneous abortion or premature delivery and those with preterm PROM (n = 43). Changes in the FFN level in the vaginal secretion were also studied in 11 patients. 2. It was possible to prevent premature delivery in 7 (26.9%) of 26 patients, and the latent period of preterm PROM was longer than 8 days in 6 (46.2%) of 13 patients. 3. The FFN level decreased slightly in patients for whom FMOX was effective, and the outcome was satisfactory in those whose FFN levels were less than 200 ng/ml. However, the outcome was poor in those whose FFN levels were higher than 1,000 ng/ml. These findings suggest that changes in the FFN level in the vaginal secretion reflect the clinical course of chorioamnionitis as do changes in CRP.

Adult↗

[Histology of chorioamnionitis: relations to maternal and fetal infection parameters].

With regard to clinical diagnosis and prognosis, intrauterine infection continues to pose major problems for obstetricians. In recent years serum assay of CRP, an acute phase protein, has become firmly established in the obstetric management of premature rupture. We investigated the relationship between histologically confirmed chorioamnionitis and maternal and fetal inflammation parameters in 69 patients on the basis of inflammation of the membranes, placenta and cord occurring in histomorphologic stages. Our results show the C-reactive protein to be a sensitive and specific indicator of chorioamnionitis and closely correlated with both the histologic stage and the severity of the chorioamnionitis. We therefore advocate adoption of the histologic result as the "gold standard" for evaluating subclinical and clinically manifest forms of intrauterine infection.

Adult↗

Safety of spinal and epidural anesthesia in parturients with chorioamnionitis.

BACKGROUND AND OBJECTIVES: The safety of spinal and epidural anesthesia in patients with chorioamnionitis was explored. METHODS: A retrospective study was made of the charts of 517 parturients who had received epidural anesthesia and 14 who had received spinal anesthesia before delivery and whose placentas had subsequently been found to be positive for chorioamnionitis. RESULTS: Of the 146 blood culture results that were reported, 13 were positive. Of these 13 blood cultures, 5 had been drawn within 6 hours after placement of the epidural block, and four of the five bacteremic patients did not receive antibiotics until after the regional anesthetic was administered. One quarter (11/45) of the patients who were febrile and three quarters (174/229) of those who had leukocytosis before their block received no antibiotics before the block was placed. After the epidural block was performed, the catheter was left in place for over 24 hours in 18% (46/260) of the women who spiked a fever and in 14% (18/130) of those who exhibited leukocytosis during that period. There was no report of an epidural or spinal abscess or of meningitis in any of the women in the study. CONCLUSION: Conduction anesthesia may be safe in parturients with chorioamnionitis without prior antibiotic therapy.

Anesthesia, Epidural↗

Elevated concentrations of prorenin and renin in amniotic fluid of women with chorioamnionitis.

OBJECTIVE: The objective of this study was to determine the concentrations of prorenin and renin in amniotic fluid of women under various physiologic and pathologic conditions. METHODS: Amniotic fluid was collected from women with chorioamnionitis treated in the Labor and Delivery Unit, University of Utah Medical Center, and from gestation-matched control women with preterm labor who were delivered within 1 week and later than 1 week and at term in labor or not in labor. Prorenin and renin concentrations were measured in these fluids by a direct immunoradiometric assay. RESULTS: Large amounts of prorenin and renin were detected in all samples with 85% to 95% in the form of prorenin. Concentrations of both prorenin and renin were significantly higher in the amniotic fluid of women with chorioamnionitis than in the amniotic fluid of control women. There were no other significant differences between the groups. CONCLUSIONS: Our data indicate that amniotic fluid concentrations of renin and prorenin are elevated in women with clinically evident chorioamnionitis. We suggest that these elevations reflect a possible role for renin and prorenin in the pathophysiologic process of intrauterine infection-associated preterm labor.

Amniotic Fluid↗

[Perinatal morbidity and mortality related to gestational infection. The histological identification of chorioamnionitis and its incidence in the population studied].

Infection of the embryo and foetus remains a major public health problem. It has been widely accepted as a major cause of spontaneous abortion, premature birth and morbidity and mortality of the newborn. Furthermore, many studies stress the role of chorioamnionitis in the onset of premature labor. We have found a significant incidence of chorioamnionitis in placentas examined in our laboratory, but we do not know the real prevalence of intra amniotic infection and the magnitude of its consequences. Furthermore, there is no data concerning the micro-organisms that can act as pathogens in our patients. The aim of this study was to better define the role of infection in pregnancy in our hospital. As a first approach we studied all the placentas that were sent to the Histopathology Department during 1993, trying to correlate histological findings with clinical data. We found that 38% of 280 placentas had histological criteria for chorioamnionitis, 33% of which were associated with fetal death. Only 13% of these cases had clinical signs of infection. These facts stress the need for a sensitive and selective method of identifying organisms that act as pathogens in intrauterine infection. It may be possible to prevent some of its complications if an earlier diagnosis and identification of the agent are done.

Chorioamnionitis↗

Silent chorioamnionitis as a cause of preterm labor refractory to tocolytic therapy.

Thirty-seven consecutive patients with singleton pregnancies in "uncomplicated" preterm labor with intact membranes suitable for tocolysis were evaluated for evidence of silent chorioamnionitis by means of maternal serum C-reactive protein and amniotic fluid white blood cell count, Gram stain, and cultures. Abnormalities in these markers of infection were found to be significantly more common in cases that were refractory to tocolysis. These cases also showed both pathologic evidence of chorioamnionitis and a significantly greater neonatal early infectious morbidity. We conclude that silent chorioamnionitis is a significant cause of "uncomplicated" preterm labor refractory to conventional methods of tocolysis.

Amnion↗

Comparative study of the human amnion, chorion and chorioamnion permeability to monovalent cations.

Amnion, chorion and chorioamnion from human term placenta were mounted between two Ussing chambers. The monovalent cation transfer was estimated by potentials (dilution, bi-ionic) and conductance measurements. This study revealed that amnion and chorioamnion discriminate the monovalent cations (the sequence is: Rb = Cs = K greater than Na greater than Li), while the chorion does not discriminate these cations. This discrimination relies on the size of the sites on the cell membrane and in intercellular spaces. The monovalent cation conductance for the three layers is gA greater than gC = gCA, and reveals that the chorioamnion properties derive in part from the properties of the isolated amnion (cationic discrimination) and those of the isolated amnion + chorion (size of sites and hydration pathways). The transfer is dependent on the three membranes' orientation and corresponds to fetal needs; the conductance ratio (g mother-fetus/g fetus-mother) is always superior to 1 when the two sides are bathed by the same medium.

Amnion↗

Management of chorioamnionitis.

Chorioamnionitis presents as a serious threat to both mother and fetus. We have evaluated the diagnostic criteria and method of management by means of a retrospective analysis. Ninety-nine per cent of mothers had two of three major risk factors: 1, rupture of membranes; 2, leukocytosis of greater than 15,000, and 3, temperature greater than 100.4 degrees F. All three risk factors were present in 82.7 per cent. The method of management included culturing the endocervix when premature rupture of the membranes was present, administering parenteral antibiotics once the diagnosis of chorioamnionitis was made and performing cesarean sections for obstetric indications only. This management protocol resulted in a perinatal survival rate of 94.9 per cent in infants weighing more than 1,000 grams compared with 98.3 per cent in the general population and no perinatal deaths in infants weighing more than 1,500 grams. There were no maternal deaths. Our data support the recommendations that endocervical cultures be obtained for all patients with premature rupture of membranes, mothers with ROM and normal temperature and white blood cell count be managed without antibiotics, mothers with a diagnosis of chorioamnionitis have induction of labor and cesarean section be performed for obstetric indications only.

Adolescent↗

Chorioamnionitis in the preterm gestation.

Two hundred fifty-one patients with premature rupture of membranes between 28 and 34 weeks' gestation were followed prospectively to evaluate the maternal and neonatal effects of chorioamnionitis. Forty-seven (19%) developed intrauterine infection prior to delivery. Fetal tachycardia, maternal leukocytosis, and uterine contractions were not predictive of intrauterine infection in afebrile patients. In afebrile patients, however, amniocenteses positive for bacteria on Gram stains and/or with subsequent positive culture correlated with subsequent development of antenatal maternal fever. Other than an increased rate of postpartum endometritis no serious maternal complications were seen in patients with chorioamnionitis. Neonatal outcome, however, was significantly adversely affected with respect to increase in perinatal mortality, overall neonatal infection rate, and respiratory distress syndrome (RDS) in patients with maternal infection. Neither trial of labor nor duration of labor in patients with chorioamnionitis correlated with adverse neonatal outcome. However, the appearance of maternal fever prior to the onset of labor correlated more significantly with neonatal death and RDS in the newborn that did the development of maternal fever in the intrapartum period.

Amniotic Fluid↗