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High Concentrations of Amniotic Fluid Proinflammatory Cytokines in Healthy Neonates Are Associated With Low Risk of Respiratory Syncytial Virus Bronchiolitis

Houben, Michiel L. MD, PhD*; Rovers, Maroeska M. PhD†‡; Wilbrink, Berry PhD§; Belderbos, Mirjam E. MD; Bloemen-Carlier, Eltje M. RN*; Visser, Gerard H. A. MD, PhD; Kimpen, Jan L. L. MD, PhD*; Bont, Louis MD, PhD*

The Pediatric Infectious Disease Journal: September 2012 - Volume 31 - Issue 9 - p 931–934
doi: 10.1097/INF.0b013e31826366e3
Original Studies

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.

Supplemental Digital Content is available in the text.

From the *Department of Pediatrics; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht; Radboud University Nijmegen Medical Centre, Nijmegen; §Laboratory of Infectious Diseases and Perinatal Screening, National Institute of Public Health and the Environment, Bilthoven; University Medical Center Groningen, Groningen; and Department of Obstetrics and Gynaecology, University Medical Center Utrecht, Utrecht, The Netherlands.

Accepted for publication May 01, 2012.

The study was funded by a fellowship award of the European Society for Paediatric Infectious Diseases (ESPID, 2005, to MLH), the Wilhelmina Children’s Hospital Research Fund (grant 2004.02), the Catharijne Stichting, the Dutch Asthma Foundation (grant and the Alexandre Suerman program (University Medical Center Utrecht, to MEB). LB received research funding and speaker’s fees by Abbott International. The authors have no other funding or conflicts of interest to disclose.

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Address for Correspondence: Louis Bont, MD, PhD, Department of Pediatrics, University Medical Center Utrecht, Lundlaan 6, 3584 EA, Utrecht, the Netherlands.

© 2012 Lippincott Williams & Wilkins, Inc.