Urine F2-Isoprostanes and Oxidative Stress in ELGANs and Correlation with Iron Administration
Kendell German, MD
BACKGROUND: Neonatal iron deficiency has been shown to be associated with irreversible neurodevelopmental delays in preclinical models and clinically, however many clinicians are reluctant to give high doses of iron, as free iron is a potential pro-oxidant. It is unknown whether extremely low gestational age neonates (ELGANs) are able to regulate their iron absorption in response to their iron status and thus protect against pro-oxidant injury.
GAP: This study aims to assess the safety of oral supplemental iron administration in neonates by evaluating whether increased iron intake correlates with elevated markers of oxidative injury, as measured by urine F2-isoprostane levels.
HYPOTHESIS: Hypothesis 1: Urine F2-isoprostanes will correlate with iron dose, cumulative iron intake and markers of iron sufficiency as hepcidin response will be inadequate to limit free iron/oxidative stress in ELGANs.
Hypothesis 2: Urine F2-isoprostane level will be lower in children treated with erythropoietin (Epo) vs. placebo, as Epo increases iron uptake for erythropoiesis.
METHODS: This is a retrospective analysis of sequential urine samples collected from 76 subjects at the University of Washington who participated in the Preterm Epo for Neuroprotection Trial (PENUT, U01NS077953). Urine F2 isoprostane concentration, a marker of oxidative injury, will be measured in urine collected at baseline (less than 24 hours), 2, 4, and 12 weeks.
IMPACT: If we show that iron supplementation up to 12 mg/kg/day is not associated with an increase in oxidative injury, this would support an immediate adoption of iron supplementation up to 12 mg/kg/day (the maximum dose received by the study cohort), titrating supplementation to the child’s need, thereby improving the iron status and hopefully neurodevelopment of ELGANs.