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Amniotic fluid granulocyte colony stimulating factor levels in chorioamnionitis do not predict neonatal sepsis.

PROBLEM: To assess the usefulness of amniotic fluid (AF) granulocyte colony-stimulating factor levels (G-CSF) in chorioamnionitis (CAM) to predict neonatal sepsis. METHOD OF STUDY: AF samples were obtained from term and preterm patients with (Group I) and without (Group II) CAM and were assayed for G-CSF levels. Patients with other infections were excluded. All AF samples were also tested for gram stain and cultures. The sensitivity, specificity, and predictive values of these parameters for diagnosing neonatal sepsis were assessed. RESULTS: Positive AF cultures were the best predictors of neonatal sepsis in CAM, with a sensitivity of 67% and a positive predictive value (PPV) of 80%. Elevated AF G-CSF levels (> 1,000 pg/ml) were poor predictors of neonatal sepsis with a sensitivity of 29% and PPV of 39%. CONCLUSION: Even though AF G-CSF levels were markedly elevated in patients with CAM, they were poor predictors of subsequent neonatal sepsis.

Amniotic Fluid↗

Early postnatal changes in the perfusion index in term newborns with subclinical chorioamnionitis.

BACKGROUND: Chorioamnionitis (HCA) in term newborns is often subclinical and associated with neonatal morbidity and mortality. OBJECTIVE: To assess the value of the pulse oximetry perfusion index (PI) in the early prediction of subclinical HCA in term newborns. METHODS: PI cut-off values were first identified in 51 term newborns with HCA and 115 matched controls, retrospectively categorised on the basis of placental histology (study phase 1). The PI thresholds obtained were subsequently tested on an unselected case series of 329 prospectively recruited, term newborns (study phase 2). PI was evaluated during the first five minutes after delivery. Initial illness severity and short term clinical outcomes were determined. RESULTS: In study phase 1, newborns with HCA had lower PI one and five minutes (p<0.0001) after delivery, lower one minute Apgar score (p = 0.017), lower cord blood base excess (p = 0.0001), together with higher rates of admission to neonatal intensive care unit (p = 0.0001) and endotracheal intubation (p = 0.017), and higher SNAP-PE (p<0.0001) and NTISS (p<0.0001) scores than those without HCA. In the prospective validation phase of the study, the PI cut-off values generated (one minute < or =1.74, five minutes < or =2.18) showed 100% sensitivity, 99.4% specificity, 93.7% positive predictive value, and 100% negative predictive value in identifying subclinical HCA. Early identification of HCA was associated with a decreased rate of admission to intensive care (p = 0.012), as well as lower initial illness severity (p< or =0.0001) and therapeutic intensity (p = 0.0006) than the newborns with HCA in phase 1. CONCLUSION: These findings suggest that early PI monitoring is helpful in identifying HCA in term newborns.

Apgar Score↗

Chorioamnionitis and fetal/neonatal brain injury.

Chorioamnionitis (CA) is the leading cause of preterm birth and neonatal complications. Even in the absence of a proven infection, fetuses and neonates present a systemic inflammatory response which can be identified by radiological and morphological examination of the thymus. The frequent occurrence of brain injury in neonates with CA is probably linked to systemic, unspecific mechanisms which have not yet been completely clarified. Only by relating placental pathology to clinical evaluation of the newborn will it be possible to achieve a better understanding of these infections and to reduce long-term morbidity and mortality.

Brain Diseases↗

Association of histologic chorioamnionitis, increased levels of cord blood cytokines, and intracerebral hemorrhage in preterm neonates.

The objective of this study was to investigate in a prospective study whether histological chorioamnionitis (ChA) is a risk factor predisposing for intracerebral hemorrhage (ICH), and whether ICH is associated with a systemic fetal inflammation in preterm neonates with a gestational age <32 weeks. 106 neonates were studied; 20 (18.9%) suffered from ICH. ChA occurred significantly more often in neonates with ICH compared to neonates without ICH (70.0 vs. 36.0%, p = 0.006). Neonates with ICH had significantly higher median levels of proinflammatory cytokines (IL-1beta, IL-6 and IL-8) compared to neonates without ICH (p < 0.001 for all comparisons). We conclude that the development of ICH in preterm infants is associated with both ChA and high levels of proinflammatory cytokines at birth.

Cerebral Hemorrhage↗

Reduced nitric oxide in amniotic fluid of patients with chorioamnionitis.

OBJECTIVE: Levels of nitric oxide (NO) and cytokines were assessed in amniotic fluid obtained from patients with severe chorioamnionitis (CAM) and appropriate controls. METHODS: Amniotic fluid was obtained from 12 patients with CAM (17-24 weeks of gestation) and 89 patients undergoing diagnostic amniocentesis (16-18 weeks of gestation). The concentrations of NO, interleukin-6 (IL-6), and leukocyte elastase (LE) in amniotic fluid were then measured and compared. RESULTS: The concentrations of NO, IL-6, and LE were all higher in CAM cases than in normal pregnant women. Furthermore, an inverse correlation between NO and LE was suggested in the CAM group. CONCLUSIONS: These results indicate that in severe CAM, the action of NO might be reduced, not only due to blockage of action but also by degradation, despite increased production.

Amniocentesis↗

Relationship between histologic chorioamnionitis and early inflammatory variables in blood, tracheal aspirates, and endotracheal colonization in preterm infants.

Histologic results of the placenta are usually not available within the first days of life. We identified inflammatory variables in tracheal aspirates and blood that were associated with histologic chorioamnionitis (HC). A derivation cohort consisted of 62 neonates and a validation cohort of 57 neonates with a gestational age < 31 wk and ventilated on d 1. Tracheal aspirates were taken on d 1 and on d 3, if the patient was still ventilated. HC was diagnosed by light microscopy. Logistic regression was used to identify independent factors in the derivation cohort associated with HC at d 1, 2, and 3. Model performance was studied using receiver operating characteristic curve analysis. Independent factors associated with HC were, at d 1, tracheal aspirate IL-8 >or= 917 pg/mL (odds ratio, 60.7; 95% confidence interval, 11-328); at d 2, blood C-reactive protein >or= 14 mg/L (odds ratio, 9.2; 95% confidence interval, 2-38), blood white blood cell count >or= 10400/mm3 (odds ratio, 7.4; 95% confidence interval, 2-28); and at d 3, blood neutrophil count >or= 4968/mm3 (odds ratio, 14; 95% confidence interval, 3-57). The association with HC was less at d 3 (area under receiver operating characteristic curve, 0.77) when compared with the d 1 model (area under the curve, 0.88; p = 0.09). The models performed equally well in the validation cohort (goodness-of-fit test, p > 0.05). We conclude that the d 1 and d 2 models can be used as diagnostic factors for HC. Tracheal aspirate IL-8 taken immediately after birth was equally accurate in the diagnosis of HC as systemic inflammatory response at d 2 and better than on d 3.

Biomarkers↗

Nuclear factor kappaB activation in pulmonary leukocytes from infants with hyaline membrane disease: associations with chorioamnionitis and Ureaplasma urealyticum colonization.

Unresolved pulmonary inflammation in hyaline membrane disease (HMD) may be a precursor to the development of chronic lung disease of early infancy. We investigated whether nuclear factor kappaB (NF-kappaB), a transcription factor that regulates the inflammatory process, is activated in pulmonary leukocytes in tracheal aspirates from premature infants with HMD. A total of 172 samples were obtained from 59 infants, two thirds of whom showed NF-kappaB activation in lung neutrophils and macrophages on at least one occasion. Infants who had activated NF-kappaB showed elevated tumor necrosis factor-alpha concentrations in their tracheal aspirates. These infants also required a longer period of mechanical ventilation support. Almost half of the infants with HMD had antenatal exposure to chorioamnionitis on the basis of placental histopathologic examination. These infants had evidence of activated NF-kappaB and elevated cytokines and were more likely to have Ureaplasma urealyticum colonization in their airways. Together, these observations suggest that NF-kappaB activation in pulmonary leukocytes may be involved in the lung inflammatory process in infants with HMD.

Birth Weight↗

Anti-annexin A2 IgM antibody in preterm infants: its association with chorioamnionitis.

Intrauterine infection is associated with chorioamnionitis (CAM), which can lead to preterm delivery. We previously reported that the levels of IgM and the incidence of CAM were elevated in preterm infants with neonatal pulmonary emphysema. The pathogen and target of this IgM remain unclear. By using Western blot and amino acid sequences, we have determined one of the target proteins: annexin A2. Immunohistochemical analysis showed that annexin A2 was expressed at fetal chorion and amnion membranes. Among very low birth weight (VLBW) infants with hyper-IgM (> or = 30 mg/dL), 58.8% showed a high titer against annexin A2 (more than x 16), which accounted for about 20%-40% of the total IgM. Anti-annexin A2 IgM antibody inhibited plasmin generation. Furthermore, the median of anti-annexin A2 IgM titer from preterm infants who were delivered with high-grade (grade III) CAM was significantly higher than those from preterm infants without CAM (p = 0.011) and with low-grade CAM (grade I and II) (p = 0.010). Here, we indicate the fetal autoimmunoreactivity against the fetomaternal interface in preterm infants.

Amino Acid Sequence↗

The association between early membrane rupture, latency, clinical chorioamnionitis, neonatal infection, and adverse perinatal outcomes in twin pregnancies complicated by preterm prelabour rupture of membranes.

The objective of this study was to evaluate associations between adverse outcomes in twin pregnancies and preterm prelabour rupture of membranes (PPROM). A chart review of 246 consecutive twin pregnancies with confirmed PPROM was conducted. Regression analysis (beta [natural log of the odds ratio] and odds ratio [OR]) was performed to identify independent predictors. Two hundred and forty-six twin pregnancies, 492 liveborns, and 20 neonatal deaths. Mean (SD) PPROM gestational age (GA): 31.3 (3.8) wk; delivery GA: 32.0 (3.3) wk. PPROM < 30 wk was associated with increased parity (OR: 2.66), and log (admission leukocyte count) (OR: 9.99). Shortened latency was associated with PPROM GA (beta = -0.17) and chorioamnionitis (beta = 0.95). Neonatal sepsis was predicted by lower delivery GA (OR: 2.04). Adverse perinatal outcomes were protected against by older GA at PPROM (OR 0.53) and shortened latency (OR 0.73). It was concluded that increased leukocytosis and parity implies an infectious aetiology in earlier PPROM. Increased risk for neonatal sepsis at earlier delivery GA is consistent with gestation-dependent fetal immunocompetence. Early PPROM and long latencies were associated with increased adverse perinatal outcomes.

Adult↗

Transient hypothyroxinemia of prematurity and histological chorioamnionitis.

BACKGROUND: Transient hypothyroxinaemia of prematurity (THOP) is a common condition of preterm infants whose causes remain unclear. We tested the hypothesis that THOP is associated with histological chorioamnionitis (HCA). METHODS: Whole blood T4 and TSH concentrations on day 4 and at 40 weeks' postmenstrual age (rtx-T4 and rtx-TSH), placental histology and illness severity were prospectively evaluated in 155 very low birth weight (VLBW) infants. RESULTS: HCA-positive infants showed significantly decreased blood total T4 concentrations on day 4, as compared to the HCA-negative population (P<0.0001), along with comparable TSH, rtx-T4, and rtx-TSH blood concentrations. None of the infants showed evidence of hypothyroidism during the study. A total T4 < or = 4.4 microg/dL on postnatal day 4 identified HCA-positive newborns with 90.8%, sensitivity, 94.7%, specificity, 96.7% positive predictive and 85.7% negative predictive values. HCA (OR: 32.19; 95% CI: 8.95-115.64), birth weight < or = 880 g (OR: 4.1; 1.15-14.64), and RDS (OR: 3.71, 95% CI: 1.13-12.25) were independently associated with evidence of hypothyroxinaemia on day 4. CONCLUSION: Our findings indicate a previously un-recognized relationship between HCA and THOP, hence suggesting a predominant role for a fetal systemic inflammatory response syndrome in the pathogenesis of THOP.

Age Factors↗

Correlation between cytokine levels of amniotic fluid and histological chorioamnionitis in preterm delivery.

The aim of this study was to investigate the correlation between the cytokine levels in the amniotic fluid (AF) and the histological stage of chorioamnionitis (CAM) in premature labor. AF of 6 cases (7 samples of AF were obtained as one was a twin pregnancy) in whom CAM was diagnosed histologically, and 12 cases without CAM were included in this study. Amniotic fluid was obtained within 24 hours prior to delivery. Cytokine levels (IL-2, -4, -6, TNF-alpha, IFN-gamma) in AF were measured by an ELISA method. Levels of IL-2 and -6 in the CAM-positive group (mean +/-S.E., 52.9 +/- 83.9 pg/ml, and 20,537.9 +/- 8853.7 pg/ml, respectively) were higher than those in the CAM-negative group (i.e. undetectable, and 65.6 +/- 27.5, respectively) with a statistical significance of p < 0.05, p < 0.001, respectively. There was a positive linear relationship between IL-6 levels of AF and the placental histological inflammatory stages of Blanc in the CAM-positive group. From these results it would appear that the IL-6 level in AF is the most sensitive test in the detection of extraamniotic infection or intraamniotic infection in preterm labor with intact membranes and also indicates the severity infection.

Amniocentesis↗

Pasteurella multocida chorioamnionitis from vaginal transmission.

A 21 year old primigravida with a twin pregnancy developed Pasteurella multocida chorioamnionitis. Infection occurred at 27 weeks gestational age after prolonged rupture of membranes. The twin in the separate sac presenting proximal to the cervix suffered infection and died shortly after birth whereas the other twin was not infected. The bacterium is believed to have caused ascending infection from asymptomatic colonization of the vaginal tract.

Adult↗

[Genital condylomatosis and pregnancy associated with chorioamnionitis and premature delivery].

Genital condylomas are produced by the human papilloma virus. On many occasions they are associated with other genital infections (fungi, trichomonas and vaginosis). Pregnancy favours the appearance of condylomas in the anogenital region. On the occasion of a case of genital condylomatosis associated with chorioamnionitis that resulted in a premature delivery, we carry out a review the literature.

Adult↗

Relation between viability of vaginal polymorphonuclear leukocytes and presence of histologic chorioamnionitis.

BACKGROUND: The number and percentage of viable vaginal polymorphonuclear leukocytes (vPMNs) are known to be increased in women who experience preterm labor. Whether those parameters may be associated with the presence of histologic chorioamnionitis (CAM) is not known. METHODS: We investigated prospectively 39 women at 26.3 +/- 6.2 weeks of gestation. The following were determined in vaginal washings: total number of vPMNs and the percent that were viable, the pH, and the concentrations of granulocyte elastase and interleukin-8 (IL-8). In addition, the white blood cell count and the serum level of C-reactive protein were determined in peripheral blood. The placenta and the umbilical cord were examined histologically with special reference to the presence of CAM. The optimal cutoff value for prediction of histologic CAM was obtained for each variable using receiver operating characteristic curves. A multivariate logistic-regression model was used to determine the independent risk factors for this disorder. RESULTS: Histologic CAM was present in ten women (37.1 +/- 3.8 weeks) and absent in 29 women (38.2 +/- 1.5 weeks). The total number of vPMNs, the percent of viable vPMNs, and the IL-8 level were all significantly increased in the women with CAM, in contrast to those without CAM. When the optimal cutoff value for each of seven covariates was entered into the model, only the percent of viable vPMNs, > or = 11%, demonstrated a significant relationship with histologic CAM (odds ratio 26.9; 95% confidence interval 1.3 to 545; p < 0.05). CONCLUSIONS: Women with a % viability of vPMNs of > or = 11% were at a significantly higher risk for histologic CAM. Data suggest that an influx of PMNs into the vagina occurs continuously in patients with histologic CAM.

Adult↗

Influence of chorioamnionitis on survival and morbidity in singletons live-born at < 32 weeks of gestation.

BACKGROUND: Chorioamnionitis (CAM) may accelerate lung maturation in fetuses. It is possible that CAM prevents infant death after live birth. METHODS: A retrospective study of live-born singletons at < 32 weeks of gestation between 1993 and 1997. Perinatal risk factors for adverse outcomes were analyzed using a logistic regression model, with special reference to the presence of histologically confirmed CAM. Adverse outcomes included infant death before 1 year of age, and survival with cerebral palsy and/or mental retardation. RESULTS: A total of 81 infants, weighing 1181 +/- 426 g, were born at 28.1 +/- 2.3 weeks of gestation. Of those, 15 (19%) died before 1 year of age, while 16 (20%) infants developed major handicaps by 1.5 years of age (six with cerebral palsy, eight with mental retardation, and two with both cerebral palsy and mental retardation). CAM, present in 44 women, was significantly associated with a reduced risk of death after live birth, with an odds ratio of 0.11 (p = 0.01). Only the presence of such intracranial lesions as periventricular leukomalacia and intraventricular hemorrhage were significantly associated with an increased risk of major handicaps (odds ratio of 11.0, p = 0.04). Adverse outcomes occurred in a similar proportion of infants in groups without CAM (14/37) and with CAM (17/44). However, among infants with adverse outcomes, the number of deaths was significantly higher in the group without CAM (10/14) vs. with CAM (5/12) (p < 0.05). CONCLUSIONS: The presence of CAM may somehow prevent infant death after live birth. Larger studies are required to confirm this phenomenon.

Adult↗

[Neonatal morbidity and mortality in very low birth weight infants according to exposure to chorioamnionitis].

OBJECTIVES: To study differences in the incidence of neonatal morbidity and mortality among newborns weighing less than 1,500 g according to exposure to chorioamnionitis (CA). PATIENTS AND METHODS: A case-control study of 135 newborns weighing less than 1,500 g at birth and born between 1988 and 1998 was performed. The case group was composed of 45 newborns exposed to clinical or subclinical levels of maternal CA. Each newborn in the case group was matched with two controls, both weighing less than 1,500 g, one of them born immediately before and the other one immediately after. Perinatal records, neonatal morbidity and mortality were analyzed. RESULTS: The mean gestational age was 28.5 weeks (range: 24-38 weeks) with a mean weight of 1,131 g (range: 520-1,500 g). The time of membrane rupture was significantly greater in the case group (176 h vs 57 h; p < 0.001). Forty percent of the cases presented sepsis in the first 72 h of life compared with 10 % of the controls (p < 0.0001). No significant differences in morbidity or mortality were found between the groups, although chronic lung disease (20 % vs 13 %) and intraventricular hemorrhage (24 % vs 17 %) were more frequent in infants exposed to CA. Resuscitation (77.8 % vs 45.6 %; p 0.001) and mechanical ventilation (73 % vs 50 %; p 0.016) were required by a great number of cases than controls. CONCLUSIONS: The presence of CA was associated with a higher risk of early onset infection and the need for neonatal resuscitation and mechanical ventilation. No significant differences were found in morbidity or mortality.

Case-Control Studies↗