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.

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

First, we screened for inflammation biomarkers most strongly linked to infection in a large prospective cohort of 425 newborns (gestational age 24–42weeks). Second, we longitudinally measured levels of infection-related inflammation biomarkers up to 42days of post-natal life in a series of 58 infants born ⩽30weeks 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.

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 72h 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).

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