title: Systemic inflammation associated with mechanical ventilation among extremely preterm infants.
abstract: Little evidence is available to document that mechanical ventilation is an antecedent of systemic inflammation in preterm humans. We obtained blood on postnatal day 14 from 726 infants born before the 28th week of gestation and measured the concentrations of 25 inflammation-related proteins. We created multivariable models to assess the relationship between duration of ventilation and protein concentrations in the top quartile. Compared to newborns ventilated for fewer than 7 days (N=247), those ventilated for 14 days (N=330) were more likely to have elevated blood concentrations of pro-inflammatory cytokines (IL-1β, TNF-α), chemokines (IL-8, MCP-1), an adhesion molecule (ICAM-1), and a matrix metalloprotease (MMP-9), and less likely to have elevated blood concentrations of two chemokines (RANTES, MIP-1β), a matrix metalloproteinase (MMP-1), and a growth factor (VEGF). Newborns ventilated for 7-13 days (N=149) had systemic inflammation that approximated the pattern of newborns ventilated for 14 days. These relationships were not confounded by chorioamnionitis or antenatal corticosteroid exposure, and were not altered appreciably among infants with and without bacteremia. These findings suggest that 2 weeks of ventilation are more likely than shorter durations of ventilation to be accompanied by high blood concentrations of pro-inflammatory proteins indicative of systemic inflammation, and by low concentrations of proteins that might protect from inflammation-mediated organ injury.
authors.affiliation: Department of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA. cbose@med.unc.edu
authors.forename: Carl L
authors.initials: CL
authors.lastname: Bose
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Laughon
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: Allred
authors.forename: T Michael
authors.initials: TM
authors.lastname: O'Shea
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Van Marter
authors.forename: Richard A
authors.initials: RA
authors.lastname: Ehrenkranz
authors.forename: Raina N
authors.initials: RN
authors.lastname: Fichorova
authors.forename: Alan
authors.initials: A
authors.lastname: Leviton
mesh_terms: D018932:Chemokine CCL2 / Q000097:blood; D054407:Chemokine CCL4 / Q000097:blood; D018946:Chemokine CCL5 / Q000097:blood; D018925:Chemokines / Q000097:blood; D002821:Chorioamnionitis / Q000097:blood; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases; D007249:Inflammation / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D011247:Pregnancy; D012121:Respiration, Artificial / Q000009:adverse effects*; D018746:Systemic Inflammatory Response Syndrome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: C111835:CCL2 protein, human; C483024:CCL5 protein, human; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D016207:Cytokines; D053583:Interleukin-1beta; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9