Published online March 30, 2009
PEDIATRICS Vol. 123 No. 4 April 2009, pp. 1132-1141 (doi:10.1542/peds.2008-0526)
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ARTICLE

Cytokines Associated With Bronchopulmonary Dysplasia or Death in Extremely Low Birth Weight Infants

Namasivayam Ambalavanan, MDa, Waldemar A. Carlo, MDa, Carl T. D'Angio, MDb, Scott A. McDonald, BSc, Abhik Das, PhDc, Diana Schendel, PhDd, Poul Thorsen, MDe, Rosemary D. Higgins, MDf for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network

a Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
b Department of Pediatrics, University of Rochester Medical Center, Rochester, New York
c Statistics and Epidemiology Unit RTI International, Research Triangle Park, North Carolina
d National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia
e NANEA Department of Epidemiology Institute of Public Health, University of Aarhus, Aarhus, Denmark; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
f Neonatal Research Network, Pregnancy and Perinatology Branch, Center for Developmental Biology and Perinatal Medicine, Bethesda, Maryland

OBJECTIVE. The goal was to develop multivariate logistic regression models for the outcome of bronchopulmonary dysplasia and/or death at postmenstrual age of 36 weeks by using clinical and cytokine data from the first 28 days.

METHODS. For 1067 extremely low birth weight infants in the Neonatal Research Network of the National Institute of Child Health and Human Development, levels of 25 cytokines were measured in blood collected within 4 hours after birth and on days 3, 7, 14, and 21. Stepwise regression analyses using peak levels of the 25 cytokines and 15 clinical variables identified variables associated with bronchopulmonary dysplasia/death. Multivariate logistic regression analysis was performed for bronchopulmonary dysplasia/death by using variables selected through stepwise regression. Similar analyses were performed by using average cytokine values from days 0 to 21, days 0 to 3, and days 14 to 21.

RESULTS. Of 1062 infants with available data, 606 infants developed bronchopulmonary dysplasia or died. On the basis of results from all models combined, bronchopulmonary dysplasia/death was associated with higher concentrations of interleukin 1β, 6, 8, and 10 and interferon {gamma} and lower concentrations of interleukin 17, regulated on activation, normal T cell expressed and secreted, and tumor necrosis factor β. Compared with models with only clinical variables, the addition of cytokine data improved predictive ability by a statistically significant but clinically modest magnitude.

CONCLUSIONS. The overall cytokine pattern suggests that bronchopulmonary dysplasia/death may be associated with impairment in the transition from the innate immune response mediated by neutrophils to the adaptive immune response mediated by T lymphocytes.

Key Words: logistic models • infant • premature • predictive value of tests

Abbreviations: BPD—bronchopulmonary dysplasia • ELBW—extremely low birth weight • IL—interleukin • IFN—interferon • RANTES—regulated on activation, normal T cell expressed and secreted • TNF—tumor necrosis factor • IMV—intermittent mandatory ventilation • CRP—C-reactive protein • BDNF—brain-derived neurotrophic factor • MCP—monocyte chemoattractant protein • Th—T helper • TGF—transforming growth factor • TREM1—triggering receptor expressed on myeloid cells 1

Accepted Aug 21, 2008.


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