Effects of iron supplementation on serum hepcidin and serum erythropoietin in low-birth-weight infants

Background: The iron-regulatory hormone hepcidin has not been studied in infants, who experience large physiologic changes in iron status. Objective: The objective was to study hepcidin and erythropoietin and their correlation with iron status in iron-replete and irondeficient low-birth-weight (LBW) infants-a group at particular risk of iron deficiency (ID). Design: We randomly assigned 285 otherwise healthy LBW infants to receive, from 6 wk to 6 mo of age, 3 doses of iron supplements: 0 (placebo), 1, or 2 mg/kg daily. Hepcidin, erythropoietin, hemoglobin, and variables of iron status were analyzed. Results: Serum hepcidin did not change over time in the placebo group, despite a rapid decrease in serum ferritin. In iron-supplemented infants, hepcidin increased significantly, reaching a mean (+/- SD) concentration of 19.2 +/- 2.5 ng/mL in the 2-mg/kg group compared with 13.0 +/- 2.6 ng/mL in the placebo group at age 6 mo (P < 0.001). The difference was even larger between irondeficient and iron-replete infants. Hepcidin was independently positively correlated with ferritin at all ages and was negatively correlated with the transferrin receptor concentration at age 6 wk and with transferrin at age 6 mo. Erythropoietin was initially similar between groups but decreased significantly in iron-supplemented infants. In addition to being negatively correlated with hemoglobin, it was also independently negatively correlated with indicators of iron status. Conclusions: Hepcidin is closely associated with iron status and may be a useful indicator of iron stores and ID in infants. Erythropoietin is negatively correlated with iron status, which suggests a feedback mechanism that needs further study. This trial is registered at clinicaltrials. gov as NCT00558454. Am J Clin Nutr 2011; 94: 1553-61.