title: Antenatal inflammation and lung injury: prenatal origin of neonatal disease.
abstract: BACKGROUND
  Antenatal inflammation in utero may be associated with lung injury and subsequent aberrant lung development resulting in bronchopulmonary dysplasia (BPD). BPD has become a developmental disease with a uniform arrest in lung development.
  
  
  METHODS
  The role of antenatal inflammation in the induction of lung injury was explored in a sheep model suitable for the study of lung development with respect to human development. Chorioamnionitis was induced by a single injection of endotoxin into the amniotic cavity under ultrasound guidance.
  
  
  RESULTS
  Endotoxin-induced chorioamnionitis caused a cascade of lung injury, pulmonary inflammation and remodeling in the fetal lung similar to lung injury previously described in adult animal models. The structural changes in the fetal lung after chorioamnionitis showed little to no fibrosis and alveolar/microvascular simplification similar to new BPD. The identified cytokine networks and regulators may explain the absence of fibrosis and lung simplification after strictly intra-uterine inflammation.
  
  
  CONCLUSIONS
  The mechanisms of antenatal inflammation in the fetal lung were multifactorial and could be antenatally modulated. Fetal pulmonary inflammation was temporarily suppressed by maternal glucocorticoid therapy. However, pulmonary inflammation could be augmented postnatally by resuscitation, oxygen toxicity, mechanical ventilation and pulmonary and systemic infection, which opens a broad window of clinical options.
authors.affiliation: Department of Pediatrics, Academisch ziekenhuis Maastricht, Maastricht, The Netherlands. bkra@paed.azm.nl
authors.forename: B W
authors.initials: BW
authors.lastname: Kramer
mesh_terms: D000818:Animals; D001997:Bronchopulmonary Dysplasia / Q000209:etiology / Q000503:physiopathology; D002821:Chorioamnionitis / Q000209:etiology* / Q000503:physiopathology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000150:complications* / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005325:Fetal Organ Maturity / Q000502:physiology; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000097:blood; D008168:Lung / Q000196:embryology / Q000503:physiopathology; D011247:Pregnancy; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000209:etiology* / Q000503:physiopathology; D012151:Resuscitation; D012307:Risk Factors; D012756:Sheep; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology* / Q000503:physiopathology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators