title: Chorioamnionitis and increased neonatal lung lavage fluid matrix metalloproteinase-9 levels: implications for antenatal origins of chronic lung disease.
abstract: OBJECTIVE
  Matrix metalloproteinase-9 (MMP-9) degrades type IV collagen, the major constituent of lung basement membrane. We studied the effects of chorioamnionitis and antenatal corticosteroids on bronchoalveolar lavage (BAL) fluid levels of MMP-9, and its inhibitor, TIMP-1 in preterm infants.
  
  
  METHODS
  A prospective study was performed on serial BAL samples from 79 ventilated preterm infants at less than 33 weeks' gestation, 18 of whom were from pregnancies complicated by chorioamnionitis. MMP-9 levels were measured by gelatin zymography and TIMP-1 by enzyme-linked immunosorbent assay, and the median value for each infant was calculated. The presence and severity of chorioamnionitis were defined histologically.
  
  
  RESULTS
  BAL fluid MMP-9 levels were higher in preterm infants in the chorioamnionitis group (86 [29-518] vs 13 [3-43] ng/mL, P =.001), and levels increased stepwise with the increasing severity of chorioamnionitis. Antenatal corticosteroids had no effect on median MMP-9 levels. Infants in the chorioamnionitis group were more likely to have chronic lung disease (CLD) develop (55% vs 28%, P <.05). TIMP-1 levels were no different between groups.
  
  
  CONCLUSIONS
  Chorioamnionitis is associated with increased lung type IV collagenase levels in the ventilated preterm infant. Antenatal lung inflammation with up-regulation of MMP-9 may be important in the pathogenesis of CLD.
authors.affiliation: Department of Child Health, Queen's University of Belfast, Institute of Clinical Science, Belfast, Northern Ireland.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Curley
authors.forename: David G
authors.initials: DG
authors.lastname: Sweet
authors.forename: Claire M
authors.initials: CM
authors.lastname: Thornton
authors.forename: M Denis
authors.initials: MD
authors.lastname: O'Hara
authors.forename: Emily
authors.initials: E
authors.lastname: Chesshyre
authors.forename: Jessica
authors.initials: J
authors.lastname: Pizzotti
authors.forename: Mark S
authors.initials: MS
authors.lastname: Wilbourn
authors.forename: Henry L
authors.initials: HL
authors.lastname: Halliday
authors.forename: Jane A
authors.initials: JA
authors.lastname: Warner
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002821:Chorioamnionitis / Q000150:complications / Q000503:physiopathology*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007231:Infant, Newborn / Q000378:metabolism*; D007232:Infant, Newborn, Diseases / Q000196:embryology / Q000201:enzymology / Q000209:etiology; D008168:Lung / Q000201:enzymology*; D008171:Lung Diseases / Q000196:embryology / Q000201:enzymology / Q000209:etiology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D011247:Pregnancy; D011446:Prospective Studies
chemical_list: D020780:Matrix Metalloproteinase 9