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Outcome of term gestation neonates whose mothers received intrapartum antibiotics for suspected chorioamnionitis.

Intrapartum antibiotics are commonly given to women suspected of having chorioamnionitis. However, there is no consensus regarding management of their babies. To date, there are no data concerning the clinical courses and outcomes of term gestation, "pretreated" neonates. We performed a retrospective review to assess the clinical courses of such infants. From 1987 to 1989, chorioamnionitis was diagnosed in 123 women, 102 of whom received intrapartum antibiotics. Of the 86 term gestation infants born to women in the latter group, 63 were completely asymptomatic. When compared with these neonates, the 23 symptomatic infants were more likely to have lower median 1 and 5 minute Apgar scores (3 vs 8 and 7 vs 9, respectively; p < 0.0001), higher immature:mature neutrophil ratios on their initial complete blood counts (0.48 vs 0.24; p = 0.0003), and positive urine antigen studies for group B Streptococcus in the presence of negative blood cultures (4 vs 2; p = 0.042). The intrapartum courses of those infants destined to be symptomatic were more likely to be complicated by fetal tachycardia (p = 0.049) and malodorous amniotic fluid (p = 0.005). Since more than 95% of asymptomatic, pretreated, term gestation neonates have a benign clinical course, aggressive evaluation and management of these infants may not be necessary.

Anti-Bacterial Agents↗

Prenatal diagnosis of Candida albicans chorioamnionitis.

The use of diagnostic amniocentesis has been proposed for the evaluation of patients with clinical suspicion of chorioamnionitis, such as those with premature rupture of membranes and premature labor. We describe a patient in whom the diagnosis of Candida chorioamnionitis was made after diagnostic amniocentesis with the assistance of a simple and rapidly performed potassium hydroxide smear.

Adult↗

Preterm premature rupture of membranes: vascular endothelial growth factor and its association with histologic chorioamnionitis.

OBJECTIVE: We hypothesize that vascular endothelial growth factor, a known angiogenic and permeability factor that is locally expressed in fetal membranes and decidua, may be the primary regulator in the pathway that eventually leads to preterm premature rupture of membranes. Our objective was to test the hypothesis that, both in the presence and in the absence of histologic chorioamnionitis, there is an increased expression of the vascular endothelial growth factor gene and its receptor Flt-1 in the human fetal membranes. STUDY DESIGN: Membranes were sampled from a region that was distinct as the rupture site from three groups of patients with preterm premature rupture of membranes. Groups 1 and 2 differed only in the length of the latency period from rupture of the membranes to delivery. Group 3 included preterm patients with intact membranes, who acted as control subjects. All patients who were selected for the study lacked clinical signs of chorioamnionitis and were delivered by cesarean delivery. Tissue samples were analyzed for interleukin-6 gene expression by Northern blot analysis and for the presence of interleukin-6 protein by immunocytochemistry. The expression of vascular endothelial growth factor and Flt-1 genes was analyzed by in situ hybridization. RESULTS: All tissue samples from group 1 and five tissue samples from group 2 (designated as group 2A) showed expression of the interleukin-6 gene and the presence of interleukin-6 protein in the fetal membranes (P <.001) and were therefore identified as inflamed. Five tissue samples from the patients in group 2 (designated as group 2B) and all control tissue samples showed neither evidence of interleukin-6 gene expression nor the presence of its protein and therefore were identified as not inflamed. Vascular endothelial growth factor and Flt-1 gene expression were increased significantly in the fetal membrane and decidua samples that were obtained from the noninflamed tissues from group 2B (P <.005) yet showed further enhancement in expression in the inflamed tissues. CONCLUSION: The expression patterns of vascular endothelial growth factor and Flt-1 genes are indicative of a molecular pathologic condition of fetal membranes, regardless of their inflammatory status, which suggests their role as a primary regulator of preterm premature rupture of membranes.

Adolescent↗

Early neonatal brain injury in histologic chorioamnionitis.

The relation between clinical or histologic chorioamnionitis and early neonatal adverse neurologic outcome was investigated (n = 483). Histologic, but not clinical, evidence of chorioamnionitis was found to be a significant predictor of periventricular echodensity (odds ratio, 2.4; 95% CI, 1.8-3.2), echolucency (3.3; 1.9-5.6), ventriculomegaly (2.7; 1.8-4.2), intraventricular hemorrhage > or =3 (3.5; 2.4-5.2), and seizures (2.3; 1.4-3.7).

Age Factors↗

Chorioamnionitis, mechanical ventilation, and postnatal sepsis as modulators of chronic lung disease in preterm infants.

OBJECTIVE: This case-control study of chronic lung disease (CLD) evaluated the hypothesis that chorioamnionitis promotes CLD and interacts with other risk factors for CLD, including mechanical ventilation and postnatal infection. STUDY DESIGN: We identified a population of 193 infants who met our case criteria for CLD whose birth weights were 7 days and culture-documented sepsis. In multivariable analyses, infants were at greatest risk for CLD when they had exposure to both chorioamnionitis and either mechanical ventilation >7 days (odds ratio, 3.2; 95% confidence interval, 0.9-11) or postnatal infection (odds ratio, 2.9; 95% confidence interval, 1.1-7.4). CONCLUSIONS: We conclude that prolonged mechanical ventilation or postnatal infection increases the risk of CLD among surviving preterm infants and that these 2 factors interact with antenatal infection to further increase the risk of CLD.

Case-Control Studies↗

Maternal signs of chorioamnionitis: persistent cognitive impairment in low-birthweight children.

AIM: To examine whether chorioamnionitis (CA) is associated with long-term cognitive impairment in low-birthweight (LBW) children without major handicaps such as cerebral palsy. METHODS: Population-based long-term follow-up study at 11 y of age of 130 LBW children with birthweight less than 2,000 g, without major handicaps. Thirteen children with maternal signs of clinical CA were compared with the 117 LBW children without. Main outcome measure was psychometric intelligence, assessed using four subscales from the Norwegian version of the Wechsler Intelligence Scale for Children -- Revised. RESULTS: Mean performance IQ for the LBW children with maternal signs of CA (89, SD 13) was significantly lower compared to the other LBW children (98, SD 16) at 11 y of age (difference of mean 10, 95% CI of difference 0.4 to 19, p=0.04). CONCLUSION: Maternal chorioamnionitis, known to be associated with an increased frequency of cerebral palsy, may have lasting negative consequences for fetal brain development, resulting in long-term cognitive impairments, even when major handicaps such as cerebral palsy are absent.

Adult↗

Cesarean section is not protective against adverse neurological outcome in survivors of preterm delivery due to overt chorioamnionitis.

OBJECTIVE: To determine whether the mode of delivery has a protective value on the immediate adverse neonatal neurological outcome of infants born from pregnancies complicated by preterm chorioamnionitis. METHODS: A comparison of the immediate and long-term neurological outcome of preterm neonates (24-34 weeks' gestation) of pregnancies complicated by chorioamnionitis, was made between those born by Cesarean section and by vaginal delivery. RESULTS: Of the 73 newborns, 54 (74%) survived the neonatal period; two (2.7%) had incomplete records, leaving 71 for analysis. Thirty (42.2%) were delivered by Cesarean section and 41 (57.7%) vaginally. The obstetric and neonatal characteristics were comparable. Twenty-four (80%) survived in the Cesarean group and 30 (73.2%) in the vaginal delivery group (NS). There was no significant difference in the immediate adverse neonatal neurological outcome between Cesarean and vaginal deliveries. CONCLUSIONS: The mode of delivery did not significantly affect the immediate neurological status of preterm infants exposed to antenatal intrauterine infection.

Cesarean Section↗

Interleukin-1beta in the bronchoalveolar lavage fluid of premature neonates: a marker for maternal chorioamnionitis and predictor of adverse neonatal outcome.

OBJECTIVE: To determine whether the presence of the proinflammatory cytokine interleukin (IL)-1beta in the lungs of preterm infants immediately after birth was associated with maternal inflammation and could predict adverse neonatal outcome. STUDY DESIGN: Prospective evaluation of serially obtained tracheal aspirates for the presence of IL-1beta in 25 preterm infants (birth weight 595-1700 g; gestational age 24-32 weeks) with respiratory distress syndrome. The initial tracheal aspirate was obtained within 1 h after delivery. RESULTS: An initial tracheal aspirate positive for IL-1beta had a highly significant correlation with documented maternal chorioamnionitis for the given patient. In addition, the presence of IL-1beta correlated significantly with elevated total cell count (2.62 vs. 0.96 x 10(6)/ml, p = 0.0097), granulocyte count (2.12 vs. 0.22 x 10(6)/ml, p = 0.001), macrophage count (0.28 vs. 0.01 x 10(6)/ml, p = 0.02) and the presence of proinflammatory cytokines IL-6, IL-8 and tumor necrosis factor (TNF)-alpha. Preterm neonates positive for IL-1beta in their initial sample were on prolonged assisted ventilation (38 vs. 16 days, p = 0.013) and oxygen supplementation (62 vs. 40.5 days, p = 0.0462) and required prolonged hospitalization (69 vs. 46 days, p = 0.0165). CONCLUSIONS: The concentration of IL-1beta in the initial tracheal aspirate obtained from the lungs of preterm infants within the first hour of life may serve as a marker of antenatal/perinatal inflammation, probably due to maternal chorioamnionitis, and could predict an adverse clinical course and short-term outcome.

Biomarkers↗

Chorioamnionitis caused by Capnocytophaga: case report and review.

We report a case of pathologically demonstrated chorioamnionitis due to Capnocytophaga species. The mother had high fever and marked uterine tenderness, and the infant had poor Apgar scores, fever, and pulmonary infiltrates. Both recovered after receiving specific antibiotics. Pathological examination of the placenta revealed acute chorioamnionitis, subchorionitis, and vasculitis of the umbilical vein. The dramatic clinical and pathological features of this case are compared with those of the nine previously reported cases of infection due to Capnocytophaga species occurring in pregnancy.

Adult↗

NAD(P)H oxidase in human fetal membrane chorion laeve trophoblasts with or without chorioamnionitis: ultrastructural enzyme histochemical study.

We examined the subcellular localizations of NAD(P)H oxidase, a reactive oxygen species (ROS)-producing enzyme, in fetal membrane chorion laeve trophoblasts from preterm or term pregnant women with or without chorioamnionitis (CAM). Ultrastructural enzyme histochemistry for NAD(P)H oxidase was used. In fetal membranes without CAM, approximately one quarter of the chorion laeve trophoblasts (25.6%) showed NAD(P)H oxidase activity on their surface plasma membranes and microvillous membranes. In mild CAM, the proportion of these NAD(P)H oxidase-positive cells significantly increased, reaching about half (51.0%). Enzyme activity appeared on the plasma and microvillous membranes and also on both phagosomal membranes and intracellular vesico-tubular structures. Appearance of NAD(P)H oxidase on surface plasma membranes, phagosomal membranes, and vesico-tubular structures is strong cytochemical evidence of phagocytic cell activation. These observations indicate that chorion laeve trophoblasts possess NAD(P)H oxidase activity, and therefore that fetal membranes themselves have ROS-generating capacity. Further, in fetal membrane inflammation, chorion laeve trophoblasts exhibited enzyme distribution characteristic of activated professional phagocytes. Similar to phagocytes infiltrating to the intrauterine environment, chorion laeve trophoblast NAD(P)H oxidase may play a role both in the defence of chorioamnion against infection and in the pathogenesis or pathophysiology of CAM-related preterm delivery.

Chorioamnionitis↗

Cerebral palsy and chorioamnionitis: the inflammatory cytokine link.

Cerebral palsy remains a significant cause of perinatal morbidity in medically developed countries. Human epidemiologic data suggest a relationship between cerebral palsy and chorioamnionitis mediated by proinflammatory cytokines. This association has been confirmed by experimental data from human and animal research that demonstrate an increase in cytokine levels in the amniotic fluid of cases of white matter damage. Recent evidence suggests this damage is the result of a fetal inflammatory response initiated in response to placental inflammation. The strong association between cerebral palsy and chorioamnionitis warrants additional investigation into the mechanisms by which white matter damage is initiated and into possible neuroprotective treatments to prevent the development of cerebral palsy.

Adult↗

High compared with standard gentamicin dosing for chorioamnionitis: a comparison of maternal and fetal serum drug levels.

OBJECTIVE: To compare umbilical cord and maternal serum peak gentamicin concentration, gentamicin elimination, and clinical outcomes between women who received once-daily compared with standard, thrice-daily dosing for clinical chorioamnionitis. METHODS: We randomly assigned 38 laboring women, at least 34 weeks gestation, with clinical chorioamnionitis, into 1 of 2 gentamicin dosing groups: 5.1 mg/kg every 24 hours (once-daily; n = 18), or 120 mg followed by 80 mg every 8 hours (standard; n = 20). We measured maternal serum peak and delivery gentamicin concentrations and cord serum levels at delivery. Polynomial curve fitting was used to summarize gentamicin elimination. We also compared maternal and neonatal outcomes. RESULTS: Demographic characteristics of the 2 groups were similar. Median maternal peak gentamicin levels were higher with once-daily (18.2 microg/mL) compared with standard dosing (7.1 microg/mL) (P < .001). Maternal serum levels decreased below 2 microg/mL by 10 hours in the once-daily group and by 5 hours in the standard dosing group. Extrapolated peak cord serum levels were 6.9 microg/mL in the once-daily and 2.9 microg/mL in the standard dosing arm. Cord levels decreased below 2 microg/mL by 10 hours in the once-daily and by 5 hours in the standard dosing group. We found no differences in maternal or neonatal outcomes. CONCLUSION: Peak maternal serum gentamicin levels ranged from 13 to 25 microg/mL after a dose of 5.1 mg/kg. Single-dose gentamicin resulted in fetal serum peak levels that were closer to optimal neonatal values. Gentamicin clearance in the term fetus was similar to published values for the newborn infant. No adverse effects of high-dose therapy were noted.

Adolescent↗

Presence of IgE cells in human placenta is independent of malaria infection or chorioamnionitis.

We have shown previously that numerous IgE(+) macrophage-like cells are present in the villous stroma of full term placenta and that there was no difference in the amount of IgE(+) cells between allergic and non-allergic mothers. The presence of such an abundant number of IgE(+) cells in the placenta in allergic as well as non-allergic women suggests that the IgE is of some importance for a successful pregnancy outcome. Here we have investigated the IgE-pattern in 59 placentas from second and third trimesters from Sweden with different degrees of chorioamnionitis and 27 full term placentas from Ghana with and without malaria parasites. The immunohistochemical staining pattern for IgE looked similar to our previous study, with the IgE located on Hofbauer-like cells. We could not find any difference in the amount or distribution of IgE(+) cells between malaria-infected and non-infected placentas, nor between different degrees of chorioamnionitis. The IgE score in the placenta did not correlate with the levels of IgE in maternal serum or plasma. However, the IgE score was significantly higher in second- compared to third-trimester placentas (P = 0.03). This might reflect a maturation time-point in the fetus and in the intrauterine environment during the second trimester, or it might be associated with the increased number of intrauterine fetal deaths in the second trimester.

Acute Disease↗

Amniotic fluid granulocyte colony stimulating factor levels: a rapid marker for diagnosing chorioamnionitis.

PROBLEM: To assess the usefulness of amniotic fluid (AF) granulocyte colony stimulating factor (G-CSF) levels as a rapid marker for diagnosing chorioamnionitis. METHOD OF STUDY: AF levels were obtained from term and preterm patients with and without chorioamnionitis (CAM). Patients with urinary tract, respiratory tract, and other infections were excluded. Results obtained from the AF G-CSF assays were compared with those from other parameters used for diagnosing CAM: maternal fever, leukocytosis, tachycardia, fetal tachycardia, AF glucose levels, white blood cell count, Gram stain, and aerobic and anaerobic cultures. The sensitivity, specificity, and predictive values were calculated. RESULTS: In the uninfected AF samples, G-CSF levels were present but low, ranging from 400 to 1600 pg/ml. Levels in the infected samples, however, were markedly increased, ranging from 1600 to 14,000 pg/ml; P < 0.05. When a cutoff of 2000 pg/ml was used as a clear marker for CAM, the sensitivity was 67%, the specificity was 100%, and the positive and negative predictive values were 100% and 86%, respectively. The comparison of the other AF G-CSF laboratory parameters also revealed high sensitivity, specificity, and predictive values for detecting CAM. CONCLUSION: (i) AF G-CSF levels are elevated in CAM. (ii) An AF G-CSF level > 2000 pg/ ml is a strong positive predictor of CAM. (iii) Elevated AF G-CSF levels appear to be more reliable in predicting CAM than any other single test currently used in clinical practice.

Amniotic Fluid↗

Chorioamnionitis and serum IgM in Wilson-Mikity syndrome.

A total of 753 infants weighing less than 1800 g at birth were studied prospectively and their serum IgM concentrations measured within 72 hours of age. Placentas from 584 of these infants were examined histologically for chorioamnionitis. The results were correlated with chronic respiratory insufficiency. Altogether 101 infants developed chronic respiratory insufficiency of which 22 had bronchopulmonary dysplasia and 35 Wilson-Mikity syndrome. The remaining 44 infants were classified as 'unexplained chronic lung disease'. Mean serum IgM concentration for Wilson-Mikity syndrome was 1.02 g/l whereas it was 0.14 g/l for bronchopulmonary dysplasia and 0.32 g/l for unexplained chronic lung disease. The incidence of chorioamnionitis was significantly higher in Wilson-Mikity syndrome (30/35) compared with bronchopulmonary dysplasia (4/16) and with infants without chronic respiratory insufficiency (145/490). Wilson-Mikity syndrome was shown to be significantly correlated with the evidences of intrauterine inflammation.

Chorioamnionitis↗

Performance characteristics of putative tests for subclinical chorioamnionitis.

OBJECTIVE: To evaluate amniotic fluid glucose, matrix metalloproteinase (MMP)-9, interleukin (IL)-6, and IL-12 for diagnosing subclinical chorioamnionitis in women with preterm labor. METHODS: Forty-four women in preterm labor at 22-35 weeks gestation with suspected subclinical chorioamnionitis underwent amniocentesis. Amniotic fluid analysis included Gram stain, culture, and determination of glucose, MMP-9, IL-6, and IL-12 concentrations. Median values of these analytes were compared using the Mann-Whitney U test. Sensitivity, specificity, and positive and negative predictive values were calculated for tests using a positive amniotic fluid culture or delivery within 24 hours as the key outcome variables. RESULTS: Amniotic fluid concentrations of glucose, MMP-9, and IL-6 correlated closely with positive culture or delivery within 24 hours. IL- 12 concentrations did not correlate with either a positive culture or delivery within 24 hours. CONCLUSIONS: Amniotic fluid glucose, MMP-9, and IL-6 reliably predict microbial invasion of the amniotic cavity or imminent delivery. IL- 12 values did not correlate with amniotic fluid culture results or imminent delivery.

Amniocentesis↗

Chorioamnionitis: a risk factor for fetal and neonatal morbidity.

Despite widespread use of drugs to arrest preterm labor, there has been no decrease in the numbers of low-birth-weight or preterm infants in the last 20 years. Evidence from many sources links preterm birth to symptomatic and subclinical infections. Recently, an increasing body of evidence has suggested that not only is subclinical infection responsible for preterm birth but also for many serious neonatal sequelae, including periventricular leukomalacia, cerebral palsy, respiratory distress and even bronchopulmonary dysplasia and necrotizing enterocolitis. Proxies of intrauterine infection include clinical chorioamnionitis, histological chorioamnionitis and intraamniotic increase in cytokines, which have been found to be associated with acute neonatal morbidity and mortality and, at least to some degree, with neurological impairment, chronic lung disease and thymus involution in the preterm infant. The infectious/inflammatory mechanisms involved are not fully understood, and the types of microbes and genetic features of host adaptive and innate immune responses need to be better characterized.

Animals↗

Chorioamnionitis is associated with increased CD40L expression on cord blood platelets.

Chorioamnionitis (CA) is a severe infection responsible not only for premature birth but also for many severe neonatal diseases. The aim of the present study was to investigate the expression of CD40L and P-selectin on platelets and the plasma levels of their soluble forms in the umbilical cord blood in infants with documented chorioamnionitis. Umbilical cord blood samples were obtained from 10 healthy term newborns, 10 non-infected preterm infants, 10 preterm infants with premature rupture of membranes and 9 preterm infants with clinical and histological CA. The expression of CD40L and P-selectin on platelets was analyzed by flow cytometry. Soluble P-selectin (sCD62P), soluble CD40L (sCD40L) and interleukine-6 (IL-6) were measured in plasma by ELISA assays. Neonates with CA had significantly higher percentages of platelets expressing CD40L in basal conditions (5.3 +/- 2.9% vs. 1.6 +/- 0.7% and in non-infected preterm infants p < 0.05), while the percentages of P-selectin positive platelets were similar among all groups. In contrast, the level of sP-selectin was higher in infants with CA (222 +/- 128 ng/ml vs. 104 +/- 71 ng/ml in non-infected preterm infants, p < 0.05) but no differences were found in the levels of sCD40L. As expected, the levels of IL-6, a pro-inflammatory cytokine were significantly higher in samples obtained from preterm neonates whose mothers had also elevated inflammatory parameters. Our observations suggest that platelets are involved in the complex inflammatory pathogenesis of CA. Neither P-selectin expression on cord blood platelets nor plasma sP-selectin or sCD40L were suitable platelet markers in CA, whereas CD40L was significantly elevated in histologically proven CA.

Blood Platelets↗