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A systemic fetal inflammatory response and the development of bronchopulmonary dysplasia

      Abstract

      Objective: The purpose of this study was to test the hypothesis that a systemic fetal inflammatory response is a risk factor for the subsequent development of bronchopulmonary dysplasia in preterm neonates. Study Design: The relationship between interleukin 6 concentrations in umbilical cord plasma at birth and the occurrence of bronchopulmonary dysplasia was examined in 203 preterm births (25-34 weeks). Ninety-six patients underwent transabdominal amniocentesis within 5 days of birth. The relationship between umbilical cord plasma interleukin 6 concentration and bronchopulmonary dysplasia was compared with the relationship between amniotic fluid interleukin 6 concentration and bronchopulmonary dysplasia. Interleukin 6 was measured by specific immunoassay. Logistic regression was used for statistical analysis. Results: Bronchopulmonary dysplasia was diagnosed in 17% (34/203) of the infants. Neonates in whom bronchopulmonary dysplasia developed had a significantly higher median interleukin 6 concentration in umbilical cord plasma at birth than did those in whom bronchopulmonary dysplasia did not develop (median, 68.3 pg/mL and range, 0.3-6150.0 pg/mL vs median, 6.9 pg/mL and range 0-19,230.0 pg/mL; P < .001). This difference remained significant after adjustment for gestational age at birth (odds ratio, 4.2; 95% confidence interval, 1.6-11.2). Logistic regression analysis indicated that an elevated umbilical cord plasma interleukin 6 concentration was a better predictor of the development of bronchopulmonary dysplasia than was an elevated amniotic fluid interleukin 6 concentration (P < .005). Conclusion: An elevated interleukin 6 concentration in umbilical cord plasma at birth is an independent risk factor for the development of bronchopulmonary dysplasia. These data support the concept that the injury responsible for bronchopulmonary dysplasia in a subset of neonates may begin before birth and is associated with the development of a fetal systemic inflammatory response, as determined by plasma concentrations of interleukin 6. (Am J Obstet Gynecol 1999;181:773-9.)

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      References

        • Abman SH
        • Groothius JR.
        Pathophysiology and treatment of bronchopulmonary dysplasia: current issues.
        Pediatr Clin North Am. 1994; 41: 277-315
        • Dusick AM.
        Medical outcomes in preterm infants.
        Semin Perinatol. 1997; 21: 164-177
        • Philip AG.
        Oxygen plus pressure plus time: the etiology of bronchopulmonary dysplasia.
        Pediatrics. 1975; 55: 44-50
        • Rojas MA
        • Gonzalez A
        • Bancalari E
        • Claure N
        • Poole C
        • Silva-Neto G.
        Changing trends in the epidemiology and pathogenesis of neonatal chronic lung disease.
        J Pediatr. 1995; 126: 605-610
        • Watterberg KL
        • Demers LM
        • Scott SM
        • Murphy S.
        Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops.
        Pediatrics. 1996; 97: 210-215
        • Pierce MR
        • Bancalari E.
        The role of inflammation in the pathogenesis of bronchopulmonary dysplasia.
        Pediatr Pulmonol. 1995; 19: 371-378
        • Yoon BH
        • Romero R
        • Jun JK
        • Park KH
        • Park JD
        • Ghezzi F
        • et al.
        Amniotic fluid cytokines (interleukin-6, tumor necrosis factor-α, interleukin-1β, and interleukin-8) and the risk for the development of bronchopulmonary dysplasia.
        Am J Obstet Gynecol. 1997; 177: 825-830
        • Ghezzi F
        • Gomez R
        • Romero R
        • Yoon BH
        • Edwin SS
        • David C
        • et al.
        Elevated interleukin-8 concentrations in amniotic fluid of mothers whose neonates subsequently develop bronchopulmonary dysplasia.
        Eur J Obstet Gynecol Reprod Biol. 1998; 78: 5-10
        • Fujimura M
        • Takeuchi T
        • Kitajima H
        • Nakayama M.
        Chorioamnionitis and serum IgM in Wilson-Mikity syndrome.
        Arch Dis Child. 1989; 64: 1379-1383
        • Yoon BH
        • Romero R
        • Kim CJ
        • Jun JK
        • Gomez R
        • Choi JH
        • et al.
        Amniotic fluid interleukin-6: a sensitive test for antenatal diagnosis of acute inflammatory lesions of preterm placenta and prediction of perinatal morbidity.
        Am J Obstet Gynecol. 1995; 172: 960-970
        • Bancalari E
        • Abdenour GE
        • Feller R
        • Gannon J.
        Bronchopulmonary dysplasia: clinical presentation.
        J Pediatr. 1979; 95: 819-823
        • Erickson AM
        • de la Monte SM
        • Moore GW
        • Hutchins GM.
        The progression of morphologic changes in bronchopulmonary dysplasia.
        Am J Pathol. 1987; 127: 474-484
        • Yoon BH
        • Romero R
        • Yang SH
        • Jun JK
        • Kim IO
        • Choi JH
        • et al.
        Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with white matter lesions associated with periventricular leukomalacia.
        Am J Obstet Gynecol. 1996; 174: 1433-1440
        • Gomez R
        • Romero R
        • Ghezzi F
        • Yoon BH
        • Mazor M
        • Berry SM.
        The fetal inflammatory response syndrome.
        Am J Obstet Gynecol. 1998; 179: 194-202
        • Tomashefski Jr., JF
        Pulmonary pathology of the adult respiratory distress syndrome.
        Clin Chest Med. 1990; 11: 593-619
        • Li XY
        • Donaldson K
        • Brown D
        • MacNee W.
        The role of tumor necrosis factor in increased airspace epithelial permeability in acute lung inflammation.
        Am J Respir Cell Mol Biol. 1995; 13: 185-195
        • Meduri GU
        • Headley S
        • Kohler G
        • Stentz F
        • Tolley E
        • Umberger R
        • et al.
        Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS: plasma IL-1β and IL-6 levels are consistent and efficient predictors of outcome over time.
        Chest. 1995; 107: 1062-1073
        • Laurent T
        • Markert M
        • Von Fliedner V
        • Feihl F
        • Schaller MD
        • Tagan MC
        • et al.
        CD11b/CD18 expression, adherence, and chemotaxis of granulocyte in adult respiratory distress syndrome.
        Am J Respir Crit Care Med. 1994; 149: 1534-1538
        • McCord JM
        • Gao B
        • Leff J
        • Flores SC.
        Neutrophil-generated free radicals: possible mechanisms of injury in adult respiratory distress syndrome.
        Environ Health Perspect. 1994; 102: 57-60
        • Demling RH.
        The modern version of adult respiratory distress syndrome.
        Annu Rev Med. 1995; 46: 193-202
        • Merritt TA
        • Stuard ID
        • Puccia J
        • Wood B
        • Edwards DK
        • Finkelstein J
        • et al.
        Newborn tracheal aspirate cytology: classification during respiratory distress syndrome and bronchopulmonary dysplasia.
        J Pediatr. 1981; 98: 949-956
        • Jonsson B
        • Tullus K
        • Brauner A
        • Lu Y
        • Noack G.
        Early increase of TNF alpha and IL-6 in tracheobronchial aspirate fluid indicator of subsequent chronic lung disease in preterm infants.
        Arch Dis Child Fetal Neonat Ed. 1997; 77: F198-F201
        • Romero R
        • Athayde N
        • Gomez R
        • Mazor M
        • Yoon BH
        • Edwin SS
        • et al.
        The fetal inflammatory response syndrome is characterized by the outpouring of a potent extracellular matrix degrading enzyme into the fetal circulation.
        Am J Obstet Gynecol. 1998; 178 ([abstract 5]): S3
        • Gomez R
        • Berry SM
        • Yoon BH
        • Mazor M
        • Athayde N
        • Ghezzi F
        • et al.
        The hematologic profile of the fetus with the systemic inflammatory response syndrome.
        Am J Obstet Gynecol. 1998; 178 ([abstract 725]): S202
        • Fox RB
        • Hoidal JR
        • Brown DM
        • Repine JE.
        Pulmonary inflammation due to oxygen toxicity: involvement of chemotactic factors and polymorphonuclear leukocytes.
        Am Rev Respir Dis. 1981; 123: 521-523
        • Stenmark KR
        • Eyzaguirre M
        • Westcott JY
        • Henson PM
        • Murphy RC.
        Potential role of eicosanoids and PAF in the pathophysiology of bronchopulmonary dysplasia.
        Am Rev Respir Dis. 1987; 136: 770-772
        • Grigg JM
        • Barber A
        • Silverman M.
        Increased levels of bronchoalveolar lavage fluid interleukin-6 in preterm ventilated infants after prolonged rupture of membranes.
        Am Rev Respir Dis. 1992; 145: 782-786
        • Romero R
        • Gomez R
        • Ghezzi F
        • Yoon BH
        • Mazor M
        • Edwin SS
        • et al.
        A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition.
        Am J Obstet Gynecol. 1998; 179: 186-193
        • Thilaganathan B
        • Meher-Homji N
        • Nicolaides KH.
        Labor: an immunologically beneficial process for the neonate.
        Am J Obstet Gynecol. 1994; 171: 1271-1272