Published online February 29, 2008
PEDIATRICS Vol. 121 No. 3 March 2008, pp. 555-561 (doi:10.1542/peds.2007-2479)
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ARTICLE

Plasma Biomarkers of Oxidative Stress: Relationship to Lung Disease and Inhaled Nitric Oxide Therapy in Premature Infants

Philip L. Ballard, MD, PhDa, William E. Truog, MDb, Jeffrey D. Merrill, MDc, Andrew Gow, PhDe, Michael Posencheg, MDc, Sergio G. Golombek, MD, MPHd, Lance A. Parton, MDd, Xianqun Luan, MSc, Avital Cnaan, PhDc and Roberta A. Ballard, MDa

a Department of Pediatrics, University of California, San Francisco, California
b Department of Pediatrics, Children's Mercy Hospitals and Clinics/University of Missouri-Kansas City School of Medicine, Kansas City, Missouri
c Department of Pediatrics and Biostatistics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania
d Department of Pediatrics, New York Medical College/Maria Fareri Children's Hospital at Westchester Medical Center, Valhalla, New York
e Department of Pharmacology and Toxicology, Rutgers University, New Brunswick, New Jersey

OBJECTIVES. Inhaled nitric oxide treatment for ventilated premature infants improves survival without bronchopulmonary dysplasia. However, there has been no information regarding possible effects of this therapy on oxidative stress. We hypothesized that inhaled nitric oxide therapy would not influence concentrations of plasma biomarkers of oxidative stress.

PATIENTS AND METHODS. As part of the Nitric Oxide Chronic Lung Disease Trial, we collected blood samples at specified intervals from a subpopulation of 100 infants of <1250 g birth weight who received inhaled nitric oxide (20 ppm, weaned to 2 ppm) or placebo gas for 24 days. Plasma was assayed for total protein and for 3-nitrotyrosine and carbonylation by using immunoassays.

RESULTS. The demographic characteristics and primary outcome for the infants were representative of the entire group of infants who were in the Nitric Oxide Chronic Lung Disease Trial. For all infants at baseline, before receiving study gas, the concentration of total protein was inversely correlated with the respiratory severity score, and plasma carbonyl was positively correlated with severity score, supporting an association between oxidative stress and severity of lung disease. Infants who survived without bronchopulmonary dysplasia had 30% lower protein carbonylation concentrations at study entry than those who had an adverse outcome. At each of 3 time points (1–10 days) during exposure to study gas, there were no significant differences between control and treated infants for concentrations of plasma protein, 3-nitrotyrosine, and carbonylation.

CONCLUSIONS. Inhaled nitric oxide treatment for premature infants who are at risk for bronchopulmonary dysplasia does not alter plasma biomarkers of oxidative stress, which supports the safety of this therapy.

Key Words: nitric oxide • premature infant • 3-nitrotyrosine • carbonyl • bronchopulmonary dysplasia

Abbreviations: NO—nitric oxide • iNO—inhaled nitric oxide • BPD—bronchopulmonary dysplasia • NO-CLD—Nitric Oxide Chronic Lung Disease • RSS—respiratory severity score • PMA—postmenstrual age • FIO2—fraction of inspired oxygen

Accepted Oct 9, 2007.