326 - Longitudinal Gut Barrier Function and Oxidative Stress in Preterm Infants Exposed to Varying Enteral Iron Doses

Publication Number: 3315.326

Madison R. Huszar, University of South Florida, Tampa, FL, United States; Thao Ho, University of South Florida, Tampa, FL, United States; Khanh Linh Hoang, University of South Florida, Tampa, FL, United States

Background: Oral iron increased mucosal inflammation in older children with anemia and was associated with lower antioxidant capacity in term infants. Preterm infants have immature antioxidant capacity; therefore, they are more vulnerable to oxidative injury. However, the clinical evidence of iron-induced oxidative stress and barrier function in preterm infants is not well studied.

Objective: To study the gut barrier function and oxidative stress over time in preterm infants exposed to varying enteral iron doses.

Design/Methods: This is a secondary analysis of a single center, randomized, double-blind clinical trial enrolled preterm infants born < 1500 g, who were assigned to 2 mg/kg/day or 6 mg/kg/day of total enteral iron. The exclusion criteria included intestinal anomalies, intestinal perforation or necrotizing enterocolitis prior to starting iron, or treatment with erythropoietin-stimulating agent. Iron was started when infants were ≥14 postnatal days and when full feeds were reached. Doses were adjusted biweekly based on serum ferritin levels to up to 12 mg/kg/day. For this analysis, we included three time points: before iron, 2 weeks on iron, and 36 weeks corrected gestational age. Oxidative stress was measured by urinary F2-isoprostane-8 and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Barrier function was measured by urinary claudin-3 (CL-3) and intestinal fatty acid binding proteins (IFABP). All urinary biomarkers were normalized to urinary creatinine levels. The associations between oxidative stress and barrier function were examined in relation to average daily iron dose.

Results: Among 162 enrolled infants, 77 received low dose, and 74 received high dose iron initially. Baseline characteristics were similar between groups, except for higher rates of maternal hypertension and pre-eclampsia in the high-dose group. 64 (42%) infants had their initial iron doses adjusted at 2 weeks after iron initiation. At 36 weeks corrected gestational age, infants received an average of 35.9 ± 18.9 days of iron. Urinary 8-OHdG levels were higher in the low-dose group at 36 weeks (Mann-Whitney U Test, p = 0.03, Figure 1). At 36 weeks, urinary 8-OHdG levels positively correlated with both urinary CL-3 (𝝆 = 0.451, p < 0.001, Figure 2) and IFABP levels (𝝆 = 0.377, p < 0.001, Figure 3) and negatively correlated with average daily iron dose (𝝆 = -0.275, p = 0.012).

Conclusion(s): Oxidative stress was associated with gut barrier function in preterm infants. The unexpected inverse relationship between initial iron dose and oxidative stress needs to be further investigated.

Dose Dependent Urinary 8-OHdG Levels
36-week corrected gestational age urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were higher in infants who were initially given the low enteral iron dose (Mann-Whitney U Test, p=0.03).

Urinary 8-OHdG Correlation to Claudin-3
36-week corrected gestational age urinary 8-OHdG levels normalized to urinary creatinine concentration positively correlate to the log of urinary claudin-3 concentration normalized to urinary creatinine concentration (𝝆=0.451, p<0.001).

Urinary 8-OHdG Correlation to Intestinal Fatty Acid Binding Protein
36-week corrected gestational age urinary 8-OHdG levels normalized to urinary creatinine concentration positively correlate to the log of urinary IFABP concentration normalized to urinary creatinine concentration (𝝆=0.451, p<0.001).