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

Am J Clin Nutr. 2011 Dec;94(6):1553-61. doi: 10.3945/ajcn.111.013938. Epub 2011 Nov 9.

Abstract

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 iron-deficient 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 iron-deficient 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Iron-Deficiency / blood*
  • Anemia, Iron-Deficiency / drug therapy
  • Antimicrobial Cationic Peptides / blood*
  • Dietary Supplements*
  • Erythropoietin / blood*
  • Female
  • Ferritins / blood
  • Hemoglobins / metabolism
  • Hepcidins
  • Humans
  • Infant
  • Infant, Low Birth Weight / blood*
  • Infant, Newborn
  • Iron / pharmacology*
  • Iron / therapeutic use
  • Iron Deficiencies
  • Male
  • Nutritional Status*
  • Receptors, Transferrin / blood
  • Reference Values
  • Trace Elements / deficiency
  • Trace Elements / pharmacology
  • Trace Elements / therapeutic use
  • Transferrin / metabolism

Substances

  • Antimicrobial Cationic Peptides
  • HAMP protein, human
  • Hemoglobins
  • Hepcidins
  • Receptors, Transferrin
  • Trace Elements
  • Transferrin
  • Erythropoietin
  • Ferritins
  • Iron

Associated data

  • ClinicalTrials.gov/NCT00558454