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      Neonatal Morbidities Associated with Histologic Chorioamnionitis Defined Based on the Site and Extent of Inflammation in Very Low Birth Weight Infants

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          Abstract

          Conflicting results on the influences of histologic chorioamnionitis (HC) on neonatal morbidities might be partly originated from using different definition of HC. The aim of this study was to determine the relationship between HC and neonatal morbidities using definition of HC that reflects the site and extent of inflammation. This was a retrospective cohort study of 261 very low birth weight (VLBW) infants admitted at a tertiary academic center. Based on the site of inflammation, HC was categorized: any HC; amnionitis; funisitis; amnionitis+funisitis. The extent of inflammation in each site was reflected by sub-defining high grade (HG). The incidences of morbidities in infants with and without HC were compared. The bronchopulmonary dysplasia (BPD) rate was significantly higher in infants with amnionitis and the severe retinopathy of prematurity (ROP) rate was significantly higher in infants with any HC and funisitis. After adjustment for both gestational age and birth weight, the respiratory distress syndrome (RDS) rate was significantly lower in infants with all categories of HC except for HG amnionitis and HG funisitis, which are not associated with lower RDS rate. HG amnionitis was significantly associated with increased BPD rate but the association of HC with severe ROP disappeared. In conclusion, HC is significantly associated with decreased RDS and HG amnionitis with increased BPD while lacking association with other neonatal morbidities in VLBW infants. The association with HC and neonatal morbidities differs by the site and extent of chorioamnionitis.

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          Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops.

          The development of bronchopulmonary dysplasia (BPD) often has been attributed to injury from mechanical ventilation and supplemental oxygen. Early lung inflammation in infants with BPD has been thought to be secondary to these factors. The purpose of this study was to evaluate whether preexisting (prenatal) inflammation may be a primary causative factor in the development of BPD. Intubated newborns of less than 2,000 g birth weight were prospectively enrolled. The presence or absence of chorioamnionitis was documented. Lung inflammation was evaluated on days 1, 2, and 4 of intubation by assaying concentrations of interleukin 1 beta (IL-1 beta), thromboxane B2, leukotriene B4, and prostaglandin E2 in tracheal lavages. Infants in whom BPD developed were compared with those in whom it did not using these measures. Fifty-three infants were enrolled; 41 survived. Thirty-eight had respiratory distress syndrome; 15 were intubated for other diagnoses. Infants prenatally exposed to chorioamnionitis were less likely to present with respiratory distress syndrome; however, chorioamnionitis was significantly associated with both the presence of IL-1 beta from the first day of intubation and the development of BPD. Tracheal lavage concentrations of IL-1 beta were higher in infants in whom BPD developed. Thromboxane B2 concentrations were similar on day 1 but were higher on days 2 and 4 in infants in whom BPD developed. In this study, intubated infants weighing less than 2,000 g at birth in whom BPD developed had increased exposure to inflammation prenatally (chorioamnionitis) and evidence of increased lung inflammation from the first postnatal day. We speculate that chorioamnionitis may accelerate lung maturation but that it also causes lung inflammation and subsequent lung injury in intubated infants, fostering the development of BPD.
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            Chorioamnionitis as a risk factor for bronchopulmonary dysplasia: a systematic review and meta-analysis.

            To conduct a systematic review of the association between chorioamnionitis (CA) and bronchopulmonary dysplasia (BPD) in preterm infants. The authors searched Medline, Embase, CINAHL, Science Citation Index and PubMed, reviewed reference lists and contacted the primary authors of relevant studies. Studies were included if they had a comparison group, examined preterm or low birthweight infants, and provided primary data. Two reviewers independently screened the search results, applied inclusion criteria and assessed methodological quality. One reviewer extracted data and a second reviewer checked data extraction. Studies were combined with an OR using a random effects model. Meta-regression was used to explore potential confounders. 3587 studies were identified; 59 studies (15 295 patients) were included. The pooled unadjusted OR showed that CA was significantly associated with BPD (OR 1.89, 95% CI 1.56 to 2.3). Heterogeneity was substantial (I(2)=66.2%) and may be partially explained by the type of CA. Infants exposed to CA were significantly younger and lighter at birth. The pooled adjusted OR was 1.58 (95% CI 1.11 to 2.24); heterogeneity was substantial (I(2)=65.1%) which may be due to different variables being controlled in each study. There was strong evidence of publication bias which suggests potential overestimation of the measure of association between CA and BPD. Unadjusted and adjusted analyses showed that CA was significantly associated with BPD; however, the adjusted results were more conservative in the magnitude of association. The authors found strong evidence of publication bias. Despite a large body of evidence, CA cannot be definitively considered a risk factor for BPD.
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              The relationship among inflammatory lesions of the umbilical cord (funisitis), umbilical cord plasma interleukin 6 concentration, amniotic fluid infection, and neonatal sepsis.

              The purpose of this study was to determine whether funisitis (inflammation of the umbilical cord detected by histologic examination of the placenta) is associated with changes in the umbilical cord plasma concentration of interleukin 6, microbial invasion of the amniotic cavity, and neonatal sepsis. The relationship among the presence of funisitis, interleukin 6 concentrations in umbilical cord plasma at birth, the results of amniotic fluid culture performed within 3 days of birth, and the occurrence of congenital neonatal sepsis was examined in 315 consecutive singleton preterm births (20-35 weeks' gestation). Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton jelly. The interleukin 6 concentration was measured with a specific immunoassay. Amniocentesis was performed in 106 patients within 3 days of birth. Amniotic fluid was cultured for aerobic and anaerobic bacteria and for mycoplasmas. (1) Funisitis was present in 25% of patients (78/315). (2) Patients with funisitis had a significantly higher median cord plasma interleukin 6 and a lower gestational age at birth than did those without funisitis (cord interleukin 6: median, 52.4 pg/mL; range, 0.9-19,230 pg/mL; vs median, 4.6 pg/mL; range, 0-18,108 pg/mL; gestational age: median, 31.1 weeks' gestation; range, 21.0-35.0 weeks' gestation; vs median, 32.9 weeks' gestation; range, 21.4-35.0 weeks' gestation; P or =17.5 pg/mL had a sensitivity of 70% and a specificity of 78% in the identification of funisitis. (4) Microbial invasion of the amniotic cavity and clinical chorioamnionitis were more common among patients with funisitis than among those without funisitis (positive amniotic fluid culture: 53% [20/38]; vs. 12% [8/68]; clinical chorioamnionitis: 18% [14/78]; vs. 4% [9/237]; P<.001 for each comparison). (5) Neonates with funisitis had a significantly higher rate of congenital sepsis than did those without this lesion (12% [8/66] vs. 1% [3/216]; P<.001); this difference remained significant after adjustment for gestational age at birth (odds ratio, 7.2; 95% confidence interval, 1.8-29.0). (1) Umbilical cord plasma interleukin 6 concentrations were higher in neonates born with funisitis than in those without this lesion. (2) Funisitis is associated with amniotic fluid infection, congenital neonatal sepsis, and the fetal inflammatory response syndrome.
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                Author and article information

                Journal
                J Korean Med Sci
                J. Korean Med. Sci
                JKMS
                Journal of Korean Medical Science
                The Korean Academy of Medical Sciences
                1011-8934
                1598-6357
                October 2015
                12 September 2015
                : 30
                : 10
                : 1476-1482
                Affiliations
                [1 ]Department of Pediatrics, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea.
                [2 ]Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea.
                [3 ]Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.
                [4 ]Department of Pediatrics, Asan Medical Center Children's Hospital, Seoul, Korea.
                [5 ]Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
                Author notes
                Address for Correspondence: Chang Won Choi, MD. Division of Neonatology, Department of Pediatrics, Seoul National University Bundang Hospital, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 13620, Korea. Tel: +82.31-787-7286, Fax: +82.31-787-4054, choicw@ 123456snu.ac.kr
                Article
                10.3346/jkms.2015.30.10.1476
                4575938
                97a5c125-e5ad-4e95-9329-8b674472a47f
                © 2015 The Korean Academy of Medical Sciences.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 April 2015
                : 01 July 2015
                Funding
                Funded by: National Research Foundation of Korea
                Award ID: 2010-0021644
                Categories
                Original Article
                Pediatrics

                Medicine
                chorioamnionitis,amnionitis,morbidity,infant, very low birth weight,infant, premature
                Medicine
                chorioamnionitis, amnionitis, morbidity, infant, very low birth weight, infant, premature

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