title: Conventional and novel peripheral blood iron markers compared against bone marrow in Malawian children.
abstract: OBJECTIVE
  Iron deficiency is an important child health problem. Its diagnosis in areas of high infection exposure remains complicated as inflammation may interfere with the accuracy of peripheral iron markers. With this study, we aimed to validate the conventional iron markers and two novel iron markers, hepcidin and Red blood cell Size Factor (RSf), against the reference standard of iron status, bone marrow iron, in children living in an infectious setting.
  
  
  METHODS
  We compared ferritin, soluble transferrin receptor, Soluble Transferrin Log-Ferritin Index (sTfR-F), mean cellular volume, mean cellular haemoglobin concentration, hepcidin and RSf, against bone marrow iron in 87 healthy Malawian children (6-66 months) scheduled for elective surgery.
  
  
  RESULTS
  Of all children, 44.8% had depleted bone marrow iron stores. Using optimised cut-offs, ferritin (<18 µg/L) and sTfR-F (>1.85) best predicted depleted iron stores with a sensitivity/specificity of 73.7%/77.1% and 72.5%/75.0%, respectively. Hepcidin (<1.4 nmol/L) was a moderate sensitive marker (73.0%) although specificity was 54.2%; RSf poorly predicted depleted iron stores.
  
  
  CONCLUSIONS
  We provide the first bone marrow-validated data on peripheral iron markers in African children, and showed ferritin and sTfR-F best predicted iron status. Using appropriately defined cut-offs, these indicators can be applied in surveillance and research. As their accuracy is limited for clinical purposes, more reliable iron biomarkers are still required in African children.
authors.affiliation: Global Child Health Group, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Femkje A M
authors.initials: FA
authors.lastname: Jonker
authors.affiliation: Global Child Health Group, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Boele van Hensbroek
authors.affiliation: Department of Infectious Diseases, Division of Internal Medicine, Centre for Tropical Medicine and Travel Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands.
authors.forename: Tjalling
authors.initials: T
authors.lastname: Leenstra
authors.affiliation: Department of Specialized Hematology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Raymond J W M
authors.initials: RJ
authors.lastname: Vet
authors.affiliation: Liverpool School of Tropical Medicine, University of Liverpool, United Kingdom.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Brabin
authors.affiliation: Community Health Department, College of Medicine, Blantyre, Malawi.
authors.forename: Nelson
authors.initials: N
authors.lastname: Maseko
authors.affiliation: Community Health Department, College of Medicine, Blantyre, Malawi.
authors.forename: Montfort B
authors.initials: MB
authors.lastname: Gushu
authors.affiliation: Community Health Department, College of Medicine, Blantyre, Malawi.
authors.forename: Mercy
authors.initials: M
authors.lastname: Emana
authors.affiliation: Laboratory for Clinical Chemistry and Hematology, Meander Medical Centre, Amersfoort, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Kraaijenhagen
authors.affiliation: Hepcidinanalysis.com, Nijmegen, The Netherlands Laboratory of Genetic, Endocrine and Metabolic diseases, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Harold
authors.initials: H
authors.lastname: Tjalsma
authors.affiliation: Hepcidinanalysis.com, Nijmegen, The Netherlands Laboratory of Genetic, Endocrine and Metabolic diseases, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Dorine W
authors.initials: DW
authors.lastname: Swinkels
authors.affiliation: Global Child Health Group, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Job C J
authors.initials: JC
authors.lastname: Calis
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D001853:Bone Marrow / Q000737:chemistry*; D002675:Child, Preschool; D004909:Erythrocyte Indices; D005260:Female; D005293:Ferritins / Q000097:blood; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D007223:Infant; D007501:Iron / Q000032:analysis* / Q000097:blood; D000090463:Iron Deficiencies; D008295:Malawi; D008297:Male; D011990:Receptors, Transferrin / Q000097:blood; D014168:Transferrin
chemical_list: D015415:Biomarkers; D064451:Hepcidins; D011990:Receptors, Transferrin; D014168:Transferrin; D005293:Ferritins; D007501:Iron
keywords: BONE MARROW; DIAGNOSTICS; IRON