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Clinical chorioamnionitis--analysis of the incubation period in patients with preterm premature rupture of membranes.

Rankit analysis of the incubation periods in 37 patients with preterm premature rupture of membranes and chorioamnionitis was done. The analysis revealed the existence of three distinctive groups: short (6.4 +/- 2.9 hours), medium (40 +/- 24.5), and long (210 +/- 75 hours) incubation period. It is postulated that in the short incubation period group the preterm premature rupture of membranes is a result, rather than the cause, of the infection.

Chorioamnionitis↗

Betamethasone effects on chorioamnionitis induced by intra-amniotic endotoxin in sheep.

OBJECTIVE: Intra-amniotic administration of endotoxin in sheep is a model of subclinical chorioamnionitis. Intrauterine inflammation alters lung development to improve postnatal lung function and may predispose the infant to lung and brain injury. We describe the effects of intra-amniotic endotoxin on cytokines and white cell responses in the membranes and amniotic fluid and investigate the hypothesis that betamethasone treatment suppresses these responses. STUDY DESIGN: Pregnant ewes were allocated at random to receive either intra-amniotic saline solution (control animals), maternal intramuscular betamethasone, intra-amniotic endotoxin by ultrasound guidance (10 mg Escherichia coli 055:B5), or a combination of the betamethasone and endotoxin treatments. Lambs were delivered abdominally at 110 to 125 days of gestation at time points that ranged from 2 hours to 15 days after treatment. RESULTS: When compared with saline solution-injected control animals, the intra-amniotic injection of endotoxin increased white cell counts in amniotic fluid. Levels of interleukin-8, but not interleukin-6, were significantly increased in amniotic fluid from 5 hours to 15 days after intra-amniotic endotoxin injection, and interleukin-8 levels were not decreased by concurrent treatment with betamethasone. After endotoxin treatment, interleukin-1beta and interleukin-8 messenger RNA were expressed in chorion, and interleukin-6 messenger RNA expression was localized to chorionic blood vessel epithelium. The half-life of endotoxin in the amniotic fluid was 1.7 days, and levels remained measurable 15 days after injection. CONCLUSION: These findings confirm that the fetus can survive within amniotic fluid that contains endotoxin, white cells, and cytokines for periods of weeks or more. Betamethasone treatment can suppress the initial inflammation in the amnion-chorion, but interleukin-8 levels and inflammatory cells in amniotic fluid were not suppressed 5 and 15 days after betamethasone treatment, presumably because of the slow clearance of bioactive endotoxin from the amniotic fluid.

Amnion↗

Amniotic fluid neutrophil elastase and lactate dehydrogenase: association with histologic chorioamnionitis.

BACKGROUND: Chorioamnionitis (CAM) is considered to be one of the main causes of preterm labor and has been associated with an adverse perinatal outcome in preterm infants. The diagnosis of acute histologic CAM requires delivery and examination of the placenta. Although numbers of markers have been reported to predict histologic CAM before birth, it is unknown whether the levels of neutrophil elastase and lactate dehydrogenase (LDH) in amniotic fluid are associated with histologic CAM. METHODS: Sixty women at gestational age of 16-35 weeks underwent transabdominal amniocentesis within 48 hr before delivery. Amniotic fluid was analyzed for white blood cell count, glucose level, LDH level, and neutrophil elastase level. The levels of neutrophil elastase were measured by latex immunoassay. Following delivery, tissue samples were obtained from umbilical cord, chorionic plate, and placental membranes. Histologic CAM was diagnosed based on Blanc's criteria. RESULTS: Receiver-operator characteristic curve analysis showed that the amniotic fluid neutrophil elastase had the best screening efficiency in predicting histologic CAM. Using amniotic fluid cut-off levels of 0.15 microg/ml for neutrophil elastase and 250 IU/l for LDH, the sensitivity, specificity, and positive and negative predictive values for predicting histologic CAM were 88.9% versus 84.1%, 73.3% versus 66.7%, 90.9% versus 88.1%, and 68.8% versus 58.8%, respectively. CONCLUSION: Amniotic neutrophil elastase and LDH are useful markers in predicting histologic CAM.

Adolescent↗

Phagocyte activation in preterm infants following premature rupture of the membranes or chorioamnionitis.

Phagocyte activation was studied in 48 preterm infants, gestational age 27.3 +/- 0.3 wk, birthweight 968 +/- 40 g, during the first postnatal week. Human neutrophil lipocalin as a marker of neutrophil activation was measured in plasma and tracheal aspirate fractions; and lysozyme, as a marker of monocyte and macrophage activation, in plasma. The concentration of plasma human neutrophil lipocalin was 69 (46-126) microg/l (median and quartiles), tracheal aspirate fraction fluid 213 (71-433) microg/l and plasma lysozyme 1337 (923-1764) microg/l. Infants born to mothers with premature rupture of the membranes or clinical chorioamnionitis (group A, n = 20) had significantly higher plasma [73 (58-151) vs 53 (38-108) microg/l; p=0.027], and tracheal aspirate fraction human neutrophil lipocalin [319 (129-540) vs 190 (57-324) microg/l; p = 0.019], and plasma lysozyme [1739 (1356-2021) vs 1140 (739-1557)microg/l; p=0.0001] than did infants whose mothers had intact membranes and who had no suspicion of infection (Group B, n = 28). In infants born to mothers receiving corticosteroids ante partum, correlations existed between time from treatment to delivery and plasma (r =0.322, p = 0.0256) and tracheal aspirate fraction human neutrophil lipocalin (r = 0.314, p = 0.0096).

Acute-Phase Proteins↗

Amniocentesis results and novel proteomic analysis in a case of occult candidal chorioamnionitis.

We report a case of subclinical Candida albicans chorioamnionitis with mid-trimester cervical dilation diagnosed by amniotic fluid culture and Gram stain. Proteomic analysis of amniotic fluid demonstrated protein biomarkers previously associated only with bacterial intra-amniotic infections. We hypothesize that since amniotic fluid culture of yeast may take days, novel tests such as proteomic profiling may lead to the development of rapid diagnostic tests for fungal intra-amniotic infections.

Adult↗

Effects of 4-hydroxy-2-nonenal, a marker of oxidative stress, on the cyclooxygenase-2 of human placenta in chorioamnionitis.

Chorioamnionitis (CAM) is one of the causes of preterm labour. A recent study has indicated that NADPH oxidase, a reactive oxygen species (ROS)-producing enzyme, is activated in CAM. CAM is thought to be closely associated with oxidative stress. We have hypothesized that oxidative stress in CAM may induce preterm labour. The purpose of this study is to examine the effect of 4-hydroxy-2-nonenal (HNE), which is a marker of oxidative stress, on human placenta during preterm labour. We initially examined the HNE-modified proteins in human placentas by immunoblotting and immunohistochemistry using anti-HNE antibody. To examine the effect of HNE on human placenta, we stimulated human placental tissue with HNE. The expressions of cyclooxygenase-2 (COX-2) mRNA and protein were observed by RT-PCR and western blot analysis respectively. Furthermore, we measured the peroxidase activity of COX-2 by COX activity assay kit. Prostaglandin E(2) (PGE(2)) in the supernatants of placental tissue was also determined by enzyme-linked immunosorbent assay. Immunoblotting and immunohistochemistry showed that the levels of HNE-modified proteins were increased in the placentas with CAM, compared to the normal placenta. HNE induced the expression of COX-2 mRNA, protein and activity in the placental tissue culture stimulated with HNE. In addition, PGE(2) was also released into the medium in a time-dependent fashion. These findings suggest that HNE-modified proteins, which were increased in the placenta with CAM, play an important role in preterm labour.

Aldehydes↗

Chorioamnionitis and pregnancy outcome in HIV-infected African women. Pregnancy and HIV Study Group.

OBJECTIVE: To assess the role of chorioamnionitis (CAM) on pregnancy outcome in HIV-1-infected (HIV-positive) pregnant women, treated for sexually transmitted diseases (STDs), during the last trimester of pregnancy in Kigali, Rwanda. METHODS: At inclusion in a prospective cohort, from July 1992 to August 1993, 561 pregnant women between 24 and 28 weeks were systematically screened for HIV infection, STDs, anemia, malaria, and hepatitis B infection; a CD4 lymphocyte count was performed. Until delivery, each woman enrolled had a monthly clinical follow-up with STD treatment when needed. The pregnancy outcome was recorded. Diagnosis of CAM was based on histologic examination of the placenta. RESULTS: Among the 275 placentas of HIV-negative women and 286 placentas of HIV-positive women examined, CAM was diagnosed (CAM-positive) in 27 HIV-positive women (9.8%) and in 28 HIV-negative women (9.8%). No statistical association was found between CAM and the following variables, independent of the HIV serostatus: age, parity, hepatitis B, anemia, STDs, and immune deficiency. Among HIV-negative women, CAM was significantly associated with prematurity (relative risk [RR] = 3.0; 95% confidence interval [CI] = 1.5-6.3), stillbirth (RR = 4.2; 95% CI = 1.6-11.0) and premature rupture of membranes (RR = 2.9; 95% CI = 1.4-6.1). Among HIV-positive women, early neonatal mortality was the only adverse outcome associated with CAM (RR = 2.0; 95% CI = 1.6-11.0). CONCLUSIONS: In our study, the prevalence of CAM was low and no risk factor of CAM was identified, a probable consequence of the control factor of STDs. CAM was strongly associated with adverse pregnancy outcomes in HIV-infected women, reflecting a possible deleterious effect of HIV.

Chorioamnionitis↗

A phase III clinical trial of antibiotics to reduce chorioamnionitis-related perinatal HIV-1 transmission.

OBJECTIVE: A multisite study was conducted in Africa to assess the efficacy of antibiotics to reduce mother-to-child transmission (MTCT) of HIV-1. DESIGN: A randomized, double-blinded, placebo-controlled, phase III clinical trial. METHODS: HIV-1-infected women were randomly assigned at 20-24 weeks' gestation to receive either antibiotics (metronidazole plus erythromycin antenatally and metronidazole plus ampicillin intrapartum) or placebo. Maternal study procedures were performed at 20-24, 26-30, and 36 weeks antenatally, and at labor/delivery. Infants were seen at birth, 4-6 weeks, and 3, 6, 9 and 12 months. The primary efficacy endpoints were overall infant HIV-1 infection and HIV-1-free survival at 4-6 weeks. All women and infants received single-dose nevirapine prophylaxis in this study. RESULTS: A total of 1510 live-born infants were included in the primary analysis. The proportions of HIV-1-infected infants at birth were similar (antibiotics 7.1%; placebo 8.3%; P = 0.41). Likewise, there were no statistically significant differences at 4-6 weeks in the overall risk of MTCT of HIV-1 (antibiotics 16.2%; placebo 15.8%; P = 0.89) or HIV-1-free survival (79.4% in each study arm). Post-randomization, the proportion of women with bacterial vaginosis at the second antenatal visit was significantly lower in the antibiotics arm compared with the placebo arm (23.8 versus 39.7%; P < 0.001), but the frequency of histological chorioamnionitis was not different (antibiotics 36.9%; placebo 39.7%; P = 0.30). Adverse events in mothers and their infants did not differ by randomization arm. CONCLUSION: This simple antepartum and peripartum antibiotic regimen did not reduce the risk of MTCT of HIV-1.

Adult↗

Colouterine fistula secondary to endometriosis with associated chorioamnionitis.

BACKGROUND: Intestinal endometriosis may be complicated by bowel obstruction, colonic rupture, sepsis, and rarely, malignant transformation. Fistula formation is extremely rare. CASE: A 26-year-old woman presented at 16 weeks of gestation with an acute abdomen suggestive of ruptured appendicitis. Blood cultures were positive for Bacteroides fragilis. At laparotomy, she was found to have a colouterine fistula with pelvic sepsis. The resected specimens demonstrated extensive uterine adenomyosis and endometriosis of the cecum, with a fistulous tract lined by endometriosis and suppurative inflammation extending from the cecum to the uterine endometrial cavity associated with severe chorioamnionitis and endomyometritis. CONCLUSION: This case illustrates a rare complication of colouterine fistula secondary to intestinal endometriosis.

Adult↗

Histologic chorioamnionitis and severity of illness in very low birth weight newborns.

OBJECTIVE: Estimating the risk of in-hospital mortality in the neonatal intensive care unit provides important information for health care providers, and several neonatal illness severity scores have been developed. Histologic chorioamnionitis (HCA) is a known cause of neonatal morbidity and mortality. To date, the relationship between HCA and neonatal illness severity scores has not been rigorously tested. In this study, the relationships among HCA, initial illness severity, and neonatal outcomes were analyzed in very low birth weight (VLBW) newborns admitted to the neonatal intensive care unit. DESIGN: Prospective. SETTING: Neonatal intensive care unit. PATIENTS: A total of 116 VLBW inborn infants (gestational age, 28.1 +/- 2.82 wks; birth weight, 1009 +/- 312 g) were categorized as HCA-positive (n = 67) and HCA-negative (n = 49). INTERVENTIONS: Placental histology was performed to identify HCA. Illness severity evaluation included several different neonatal illness severity scores-Clinical Risk Index for Babies (CRIB), CRIB-II, Score for Neonatal Acute Physiology-II (SNAP-II), and Score for Neonatal Acute Physiology Perinatal Extension-II (SNAPPE-II)-as well as the recording of severe morbidity and in-hospital mortality. MEASUREMENTS AND MAIN RESULTS: HCA-positive VLBW newborns showed significantly lower gestational age (p < .0001) and birth weight (p = .0010), together with higher CRIB, CRIB-II, SNAP-II, and SNAPPE-II scores at admission to the NICU (p </= .0001) and mortality rate (p = .0018) than HCA-negative infants. After adjustment for gender and gestational age in a multivariable logistic regression analysis, HCA was found to be an independent predictor of high illness severity: CRIB > 5 (odds ratio [OR], 21.37; 95% confidence interval [CI], 6.24-73.21); CRIB-II > 10 (OR, 56.17; 95% CI, 6.75-467.2); SNAP-II > 22 (OR, 43.05; 95% CI, 11.9-155.7), and SNAPPE-II > 42 (OR, 48.95; 95% CI, 10.18-235.4) (all p values <.0001). CONCLUSIONS: Our findings indicate that HCA is a major predictor of morbidity and mortality in VLBW newborns.

Chorioamnionitis↗

Early dynamic changes in pulse oximetry signals in preterm newborns with histologic chorioamnionitis.

OBJECTIVE: No reliable clinical markers of histologic chorioamnionitis (HCA), a major and often subclinical cause of prematurity leading to high neonatal morbidity and mortality, are available to date. Increasing evidence indicates myocardial dysfunctions in affected fetuses and newborns. We sought to assess the value of nonlinear dynamics from pulse oximetry signals in identifying affected newborns. DESIGN: Prospective case-control study. SETTING: Tertiary level neonatal intensive care unit, Brindisi Hospital. PATIENTS AND INTERVENTION: Pulse oximetry-derived signals (pulse rate, oxygen saturation, and perfusion index), recorded within the first 1.5 hrs of life, were analyzed for 110 very low-birth-weight infants, of whom 54 had histopathological evidence of HCA. MEASUREMENTS AND MAIN RESULTS: Four different time series parameters were determined for nonlinear dynamical (NLD) analysis. Significantly decreased Lempel-Ziv, Lyapunov largest exponent, and correlation dimension, with significantly increased Hurst values for heart rate and perfusion index (p < .00001), were observed in newborns with HCA. Heart rate Lempel-Ziv </=0.218 showed 100% sensitivity (95% confidence interval, 98.8-100) and 100% specificity (95% confidence interval, 98.6-100) in distinguishing cases from controls, with positive and negative predictive values of 100% and 95.7%, respectively. CONCLUSIONS: Our findings indicate that early autonomic tone balance abnormalities are present in newborns with HCA and suggest that early dynamic analysis of pulse oximetry signals could be useful in identifying affected infants.

Case-Control Studies↗

Prostaglandins, chorioamnionitis and preterm labour.

The production of prostaglandin E (PGE) and leukotriene B4 (LTB4) by amnion was measured in vitro in 12 women delivered after spontaneous preterm labour and in 15 women delivered after spontaneous labour at term. The placenta and fetal membranes were examined histologically in all cases. PGE output (fmol/mg dry weight/2 h) in the amnions from uncomplicated preterm deliveries was low (median 486, range 232-3203, n = 7) compared with the values obtained after spontaneous labour at term (5529, 1722-14,226, n = 15). In amnions from preterm deliveries complicated by acute chorioamnionitis or round cell infiltration there was massive release of PGE (15,262, 10,905-27,640, n = 5) which was accompanied by an increase in LTB4 production. Inflammatory infiltration of the fetal membranes results in a huge increase in PG production which could cause preterm labour.

Amnion↗

Chorioamnionitis: how useful is the determination of C-reactive protein?

This study was designed to derive the predictive value of C-reactive protein (CRP) in peripheral venous serum of patients admitted to hospital with suspected premature rupture of the membranes (PROM). CRP was assayed by each of 4 separate methods and the results have been compared for accuracy and practical value with respect to clinical outcome and the histopathology of the placenta. Of the 4 techniques used only the latex test had characteristics suitable for a diagnostic screen. While the results were only semiquantitative, when comparisons were made to other techniques no significant change in clinical diagnosis would have been made. The results have confirmed that chorioamnionitis and preterm labour are often associated, but in some instances the extent of inflammatory infiltration was greater than might have been expected from the short time interval between documented membrane rupture and delivery. Thus it may be speculated that some cases of PROM are secondary to, rather than causative of, infection. Finally it is suggested that a controlled therapeutic trial of active intervention in those cases of PROM with elevated CRP in the absence of other clinical parameters suggestive of intrauterine infection should be undertaken.

C-Reactive Protein↗

The incidence of histological chorioamnionitis in IVF/GIFT preterm births.

A retrospective case control study was designed to investigate the role of subclinical infection as a risk factor for the high rate of preterm deliveries in IVF/GIFT pregnancies. The cases and the controls were identified from the records of consecutive livebirths of < 35 weeks' gestational age (GA), at King George V Hospital from 1987-1993. Fifty one singleton and 58 twin IVF/GIFT preterm births were matched for GA, year of birth, plurality, maternal age, parity, preclampsia and antepartum haemorrhage. As a marker of subclinical infection, the incidence of histological chorioamnionitis (HCA) in the 2 groups (as defined by the standardized, semiquantitative method of Benirschke) was compared. The matched variables did not differ significantly between the IVF/GIFT group and the control group. No significant difference in the incidence of HCA was detected between IVF/GIFT and control groups for singletons or twins. Overall 24% of IVF/GIFT and 30% of controls showed evidence of HCA, odds ratio (95% confidence intervals), 0.72 (0.40-1.31). This study showed no evidence that the incidence of HCA, is significantly increased in IVF/GIFT preterm births compared with other matched, preterm births. Therefore, we conclude that subclinical infection/inflammation cannot explain the 4-fold increase in preterm births in the IVF/GIFT population.

Adult↗

Candida glabrata chorioamnionitis following in vitro fertilization and embryo transfer.

Candida glabrata is a yeast which is considered to be a commensal of the vagina with limited pathogenicity in the immunocompetent host. We report 2 cases of severe chorioamnionitis occurring in pregnancies achieved by in vitro fertilization techniques which resulted in preterm delivery and pregnancy loss. Candida glabrata as the causative agent was probably introduced into the uterus by the cannula at the time of embryo transfer. It is recommended that appropriate investigation of the microbial flora of the cervix be undertaken and treatment instituted prior to embryo transfer in order to prevent this complication.

Adult↗