Identifying and measuring the biochemical effects of procedural pain in infants is a continuing challenge for clinicians. To address this issue we evaluated the relationship between procedural pain, ATP utilization (hypoxanthine and uric acid), and oxidative stress (MDA and allantoin) in premature infants. Through these studies we found that 1) a single heel-lance significantly increases plasma uric acid in rabbit kits, 2) tape removal increases MDA and prevents a decrease in uric acid in the plasma of premature infants, and 3) a single dose of oral sucrose before a heel-lance is sufficient to significantly increase plasma markers of ATP utilization and oxidative stress. These studies indicate that, in premature infants, ATP utilization and oxidative stress are altered by procedural pain and that oral sucrose, a common analgesia, may increase ATP breakdown. Next, we examined clinical factors that need to be considered when using the urinary concentrations of hypoxanthine, xanthine, uric acid, and allantoin to evaluate the biochemical effects of procedural pain. Specifically, we determined the effects of gestational age, weight for gestational age, and neonatal morbidity on the urinary concentration of purines and allantoin. We found infants born at earlier gestational ages had significantly higher urinary purine and allantoin concentrations compared to infants born at later gestations, after 31 weeks. Weight for gestational age also altered the urinary concentration of purines with small for gestational age infants having significantly lower urinary hypoxanthine compared to appropriate and large for gestational age infants. In addition, respiratory morbidity significantly increased urinary purines, but not allantoin, within the late preterm population. These data suggest that gestational age, weight for gestational age, and neonatal morbidity alter the urinary concentration of purine metabolites. Allantoin was also found to be significantly altered by gestational age. Based upon these data, we recommend conducting age-matched as well as weight for age-matched studies when using urinary purines and allantoin to evaluate the relationship between procedural pain and hypoxia on ATP utilization and oxidative stress. Lastly, it is important to stratify subjects based on health status or morbidity, due to the significant effects of respiratory diseases on ATP use and oxidative stress.

LLU Discipline



Basic Sciences


School of Medicine

First Advisor

Angeles, Danilyn M.

Second Advisor

Boskovic, Danilo S.

Third Advisor

Deming, Douglas

Fourth Advisor

Duerksen-Hughes, Penelope

Fifth Advisor

Hopper, Andrew O.

Sixth Advisor

Neidigh, Jonathan

Degree Name

Doctor of Philosophy (PhD)

Degree Level


Year Degree Awarded

January 2013

Date (Title Page)




Library of Congress/MESH Subject Headings

Fetal hypoxia; Hypoxia-Ischemia, Brain; Infant, Newborn; Oxidative stress - physiology; Pain

Subject - Local

Procedural pain; Premature Infants; Neonatal hypoxia; Purine metabolites; ATP utilization; oxidative stress



Page Count

186 p.

Digital Format


Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.


Loma Linda University Electronic Theses & Dissertations

Collection Website



Loma Linda University. Del E. Webb Memorial Library. University Archives