Chorioamnionitis and increased neonatal lung lavage fluid matrix metalloproteinase-9 levels: implications for antenatal origins of chronic lung disease

Am J Obstet Gynecol. 2003 Apr;188(4):871-5. doi: 10.1067/mob.2003.215.


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.

Study design: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchoalveolar Lavage Fluid / chemistry*
  • Chorioamnionitis / complications
  • Chorioamnionitis / physiopathology*
  • Chronic Disease
  • Female
  • Humans
  • Infant, Newborn / metabolism*
  • Infant, Newborn, Diseases / embryology
  • Infant, Newborn, Diseases / enzymology
  • Infant, Newborn, Diseases / etiology
  • Lung / enzymology*
  • Lung Diseases / embryology
  • Lung Diseases / enzymology
  • Lung Diseases / etiology
  • Matrix Metalloproteinase 9 / metabolism*
  • Pregnancy
  • Prospective Studies


  • Matrix Metalloproteinase 9