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.

Figure 1

Derivation of the study population, beginning with the original cohort of infants from then ELGAN Study

Figure 2

Blood concentrations of 9 inflammation-associated proteins on day 14 among newborns classified by the cumulative number of days they were ventilated during the first 2 postnatal weeks. Concentrations of proteins have been log transformed for illustrative purposes. The median is the line close to the middle of each box, and the 25^th and 75^th centiles are indicated by the top and bottom of the box. The length of the vertical lines above and below the box indicates the limits of the range of values, exclusive of outliers, identified by black dots.