Early inflammation in the absence of overt infection in preterm neonates exposed to intensive care

Abstract

Background: Systemic inflammation, typically attributed to sepsis, has been repeatedly linked to adverse long-term outcomes in infants born prematurely. However, it is unclear whether other factors can contribute to potentially harmful systemic inflammatory responses.

Objective: To determine the timing and extent of systemic inflammation occurring in absence of infection in preterm infants exposed to intensive care.

Methods: First, we screened for inflammation biomarkers most strongly linked to infection in a large prospective cohort of 425 newborns (gestational age 24-42 weeks). Second, we longitudinally measured levels of infection-related inflammation biomarkers up to 42 days of post-natal life in a series of 58 infants born ≤30 weeks of gestation exposed to intensive care. Ante- or post-natal infections were excluded using stringent definitions including rigorous histological placental examination. Spearman correlations were used to identify putative clinical factors potentially linked to inflammation.

Results: Three biomarkers were most strongly associated with neonatal sepsis (IL-6, IL-8 and G-CSF) in the first cohort. Using these markers, we found a predominant early high intensity systemic inflammation period within the first 72 h of preterm infants' extra-uterine life. Remarkably, this systemic inflammatory response was of magnitude comparable to that observed during sepsis in absence of ante- or post-natal signs of infection, and correlated with the amount of supplemental oxygen exposure (r=0.51-0.60).

Conclusions: Non-infectious sources of systemic inflammation are significant in preterm infants exposed to intensive care and may contribute to intensive care-related organ injury.