Persistence after birth of systemic inflammation associated with umbilical cord inflammation

Abstract

Intrauterine inflammation is followed by elevated concentrations of inflammation-related proteins in the newborn's blood. Many of these proteins have short half-lives. The persistence of this postnatal inflammation has not previously been investigated. In a sample of 834 infants born before the 28th week of gestation, 12% (103) had grade 1 or 2, and 17% (142) had grade 3, 4, or 5 umbilical cord inflammation. Concentrations of nine proteins previously shown to be associated with umbilical cord inflammation at birth were measured on the first postnatal day and at two weekly intervals after birth. We evaluated the hypothesis that children who had umbilical cord inflammation were no more likely than others to have elevated concentrations of inflammation-related proteins in postnatal blood. The concentrations of seven of the nine proteins [C-reactive protein (CRP), myeloperoxidase (MPO), IL1β, IL8, TNFα, intercellular adhesion molecule-1 (ICAM3), and matrix metalloproteinase (MMP9)] showed a tendency to be elevated on day 7 among infants with funisitis. Adjusting for gestational age, growth restriction, and three postnatal exposures (ventilation on day 7, presumed and definite early bacteremia, and Bell stage III necrotizing endocolitis) did not diminish the elevated odds ratios of concentrations in the top quartile (for gestational age and day the specimen was obtained) of MPO, IL1β, TNFα, IL8, ICAM3, and MMP9. The persistence of a relationship between umbilical cord inflammation and elevated blood concentrations of inflammation-related proteins on postnatal day 7 suggests the existence of phenomena that contribute to a reinforcement loop and thereby sustained systemic inflammation.