Principal Investigator: Logan G. Spector, Ph.D.
Funding Agency: Gerber Foundation

Several epidemiological studies have indicated that prolonged neonatal oxygen supplementation (O2) may increase the risk of childhood cancer. An objection to these findings is that O2 is frequently a brief exposure and thus seems inconsequential. However, reactive oxygen species (from many sources) are known to cause DNA damage. Moreover, one study found that biomarkers of oxidative stress were significantly elevated four weeks after birth in infants who received O2 compared to those who did not. The study we propose will attempt to confirm these findings and to extend them by: 1) testing for a dose-response relationship between length of O2 and biomarkers of oxidative stress, 2) including a biomarker of actual oxidative DNA damage, and 3) examining biomarkers at four as well as at eight weeks of life. Our primary purpose is to describe the biological plausibility of an association between O2 and childhood cancer. The results of this study will also be of great interest to obstetricians and neonatologists, who are currently engaged in a vigorous debate about the benefits of administering O2, as opposed to pressurized room air, to asphyxiated newborns given that oxygen toxicity is known to cause a number of non-cancer conditions. In this observational study we will follow 80 infants born at Fairview Riverside Medical Center (FRMC) whose birth is attended by a Neonatal Nurse Practitioner (NNP). NNPs on the study staff will collect infant cord blood at birth from 40 healthy, term infants who receive O2 at birth and 40 otherwise comparable infants who do not. They will also record details of exposure to O2 for infants that receive it. Mothers will bring their infants to the General Clinical Research Center at the University of Minnesota at four and eight weeks of life to have blood drawn. The levels of biomarkers of oxidative stress [reduced-to-oxidized glutathione ratio; glutathione peroxidase, catalase, and superoxide dismutase enzymes] and oxidative DNA damage [8-hydroxy2'-deoxyguanosine (8-OhdG)] in blood samples will be analyzed in Dr. Ross' lab using off-the-shelf enzyme linked immunosorbent assay (ELISA) kits. The total oxygen radical absorptive capacity (ORAC) of each sample will be determined using ELISA performed at a contract laboratory. The distribution of these measures will then be compared between O2 exposed and unexposed groups using the appropriate statistical tests. HYPOTHESES: 1) Levels of biomarkers of oxidative stress and oxidative DNA damage will be higher at 4 and 8 weeks of life in infants exposed to 100% oxygen supplementation than in unexposed infants. 2) Levels of these biomarkers at 4 and 8 weeks will increase with increasing duration of 100% oxygen supplementation.