title: Plasma Concentrations of Hepcidin in Anemic Zimbabwean Infants.
abstract: OBJECTIVE
  Anemia in infancy is a global public health problem. We evaluated the relative contributions of iron deficiency and inflammation to infant anemia.
  
  
  METHODS
  We measured plasma hepcidin, ferritin, soluble transferrin receptor (sTfR), alpha-1-acid glycoprotein and C-reactive protein (CRP) by ELISA on archived plasma from 289 HIV-unexposed anemic or non-anemic Zimbabwean infants at ages 3 mo, 6 mo and 12 mo. Among anemic infants, we determined the proportion with iron-deficiency anemia (IDA) and anemia of inflammation (AI). We undertook regression analyses of plasma hepcidin and anemia status, adjusting for sex, age and birthweight.
  
  
  RESULTS
  Anemic infants at 3 mo were more stunted and had higher CRP (median 0.45 vs 0.21 mg/L; P = 0.037) and hepcidin (median 14.7 vs 9.7 ng/mL; P = 0.022) than non-anemic infants, but similar levels of ferritin and sTfR; 11% infants had IDA and 15% had AI. Anemic infants at 6 mo had higher hepcidin (median 7.9 vs 4.5 ng/mL; P = 0.016) and CRP (median 2.33 vs 0.32 mg/L; P<0.001), but lower ferritin (median 13.2 vs 25.1 μg/L; P<0.001) than non-anemic infants; 56% infants had IDA and 12% had AI. Anemic infants at 12 mo had lower ferritin (median 3.2 vs 22.2 μg/L; P<0.001) and hepcidin (median 0.9 vs 1.9 ng/mL; P = 0.019), but similar CRP levels; 48% infants had IDA and 8% had AI. Comparing anemic with non-anemic infants, plasma hepcidin was 568% higher, 405% higher and 64% lower at 3 mo, 6 mo and 12 mo, respectively, after adjusting for sex and birthweight (all p<0.01). Plasma hepcidin declined significantly with age among anemic but not non-anemic infants. Girls had 61% higher hepcidin than boys, after adjusting for age, anemia and birthweight (p<0.001).
  
  
  CONCLUSIONS
  Anemia is driven partly by inflammation early in infancy, and by iron deficiency later in infancy, with plasma hepcidin concentrations reflecting the relative contribution of each. However, there is need to better characterize the drivers of hepcidin during infancy in developing countries.
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.
authors.forename: Tatenda G
authors.initials: TG
authors.lastname: Mupfudze
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States of America.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Stoltzfus
authors.affiliation: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rukobo
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Moulton
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.
authors.forename: Jean H
authors.initials: JH
authors.lastname: Humphrey
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe; Blizard Institute, Queen Mary University of London, London, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Prendergast
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Jones
authors.forename: Amee
authors.initials: A
authors.lastname: Manges
authors.forename: Goldberg
authors.initials: G
authors.lastname: Mangwadu
authors.forename: John A
authors.initials: JA
authors.lastname: Maluccio
authors.forename: Mduduzi N N
authors.initials: MN
authors.lastname: Mbuya
authors.forename: Robert
authors.initials: R
authors.lastname: Ntozini
authors.forename: James M
authors.initials: JM
authors.lastname: Tielsch
mesh_terms: D000740:Anemia / Q000097:blood*; D018798:Anemia, Iron-Deficiency / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001724:Birth Weight; D002097:C-Reactive Protein / Q000378:metabolism; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005293:Ferritins / Q000097:blood; D015658:HIV Infections; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000097:blood; D007501:Iron / Q000097:blood; D008297:Male; D009961:Orosomucoid / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D011990:Receptors, Transferrin / Q000097:blood; D012044:Regression Analysis; D014801:Vitamin A / Q000627:therapeutic use; D015030:Zimbabwe
chemical_list: D015415:Biomarkers; D064451:Hepcidins; D009961:Orosomucoid; D011990:Receptors, Transferrin; D014801:Vitamin A; D002097:C-Reactive Protein; D005293:Ferritins; D007501:Iron