High concentrations of amniotic fluid proinflammatory cytokines in healthy neonates are associated with low risk of respiratory syncytial virus bronchiolitis

Background: The burden of respiratory syncytial virus (RSV) bronchiolitis in individual children and their families, the medical system and society is considerable. Mechanisms underlying RSV bronchiolitis in healthy term infants are largely unknown. Sterile intraamniotic inflammation and chorioamnionitis have been associated with increased lung volume and compliance. Objective:: The aim of this study was to determine whether high amniotic fluid interleukin-8 (IL-8), and tumor necrosis factor-α protect against RSV bronchiolitis in healthy term infants. Methods: We conducted a prospective birth cohort study of healthy term newborns, born after uncomplicated pregnancy. Amniotic fluid was collected during labor. In case of medical attention for respiratory symptoms during the first year of life, a nose-throat swab was taken to establish the presence of respiratory viruses by polymerase chain reaction. Results: Physician-attended RSV infection was observed in 27 (9.3%) of 292 children at median age 6 months. Amniotic fluid concentrations of IL-8 were higher in children without physician-attended RSV infection than in children with physician-attended RSV infection (11.1 versus 5.5 ng/mL; P = 0.002). Similarly, in children without physician-attended RSV, the proportion of detectable amniotic fluid tumor necrosis factor-α was higher (159/265 [60%] versus 8/27 [30%]; P = 0.002). Among children with physician-attended RSV infection, amniotic fluid IL-8 was inversely correlated to the number of wheezing days during the first year of life (ρ =-0.38; P = 0.048). Conclusions: High concentrations of amniotic fluid IL-8 and tumor necrosis factor-α are associated with low risk of RSV bronchiolitis in healthy term infants. We hypothesize that direct exposure of fetal lungs to proinflammatory signals induces local protection against viral infection during infancy.