Re-Evaluation of Serum Ferritin Cut-Off Values for the Diagnosis of Iron Deficiency in Children Aged 12-36 Months

  • Kawsari Abdullah
    Affiliations
    Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, Canada
    Search for articles by this author
  • Catherine S. Birken
    Affiliations
    Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, Canada

    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada

    Dalla Lana School of Public Health, University of Toronto, Toronto, Canada

    Pediatrics Outcomes Research Team, Division of Pediatric Medicine, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada

    Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, Canada
    Search for articles by this author
  • Jonathon L. Maguire
    Affiliations
    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada

    Dalla Lana School of Public Health, University of Toronto, Toronto, Canada

    Pediatrics Outcomes Research Team, Division of Pediatric Medicine, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada

    Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, Canada

    Applied Health Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Canada

    Department of Pediatrics, St. Michael's Hospital, University of Toronto, Canada
    Search for articles by this author
  • Darcy Fehlings
    Affiliations
    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada

    Dalla Lana School of Public Health, University of Toronto, Toronto, Canada

    Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, Canada

    Division of Developmental Pediatrics, Holland Bloorview Kids Rehabilitation Hospital, Bloorview Research Institute, Toronto, Canada
    Search for articles by this author
  • Anthony J. Hanley
    Affiliations
    Dalla Lana School of Public Health, University of Toronto, Toronto, Canada

    Department of Nutritional Sciences, University of Toronto, Toronto, Canada

    Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, Canada
    Search for articles by this author
  • Kevin E. Thorpe
    Affiliations
    Dalla Lana School of Public Health, University of Toronto, Toronto, Canada

    Applied Health Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Canada
    Search for articles by this author
  • Patricia C. Parkin
    Correspondence
    Reprint requests: Patricia Parkin, MD, FRCPC, The Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning, 686 Bay St, Toronto, ON M5G 0A4, Canada.
    Affiliations
    Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, Canada

    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada

    Dalla Lana School of Public Health, University of Toronto, Toronto, Canada

    Pediatrics Outcomes Research Team, Division of Pediatric Medicine, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada

    Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, Canada
    Search for articles by this author
      An ongoing challenge has been determining clinically relevant serum ferritin cut-offs in the diagnosis of iron deficiency in children aged 1-3 years. We identified 2 potential clinically relevant serum ferritin cut-off values through their association with clinically important cut-off of hemoglobin as the indicator of anemia.

      Keywords

      Abbreviations:

      CRP ( C-reactive protein), Hb ( Hemoglobin), RCS ( Restricted cubic spline)
      To read this article in full you will need to make a payment

      References

        • Centers for Disease Control and Prevention
        Iron deficiency—United States, 1999-2000.
        Morbid Mortal Wkly Rep MMWR. 2002; 51: 897-899
        • Baker R.D.
        • Greer F.R.
        Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age).
        Pediatrics. 2010; 126: 1040-1050
        • World Health Organization
        Iron deficiency anaemia: assessment, prevention and control. A guide for programme managers.
        World Health Organization, Geneva2001 (WHO/NHD/01.32001)
        • Centers for Disease Control and Prevention
        Recommendations to prevent and control iron deficiency in the United States.
        Morbid Mortal Wkly Rep MMWR. 1998; 47: 1-36
        • Idjradinata P.
        • Pollitt E.
        Reversal of developmental delays in iron deficient anaemic infants treated with iron.
        Lancet. 1993; 341: 1-4
        • Lozoff B.
        • Smith J.B.
        • Kaciroti N.
        • Clark K.M.
        • Guevara S.
        • Jimenez E.
        Functional significance of early-life iron deficiency: outcomes at 25 years.
        J Pediatr. 2013; 163: 1260-1266
        • Martins S.
        • Logan S.
        • Gilbert R.E.
        Iron therapy for improving psychomotor development and cognitive function in children under the age of three with iron deficiency anaemia.
        Cochrane Database Syst Rev. 2001; (CD001444)
        • McDonagh M.
        • Blazina I.
        • Dana T.
        • Cantor A.
        • Bougatsos C.
        Routine iron supplementation and screening for iron deficiency anemia in children ages 6 to 24 months: a systematic review to update the U.S. Preventive Services Task Force recommendation.
        (Evidence Synthesis No 122 AHRQ Publication No 13-05187-EF-1) Agency for Healthcare Research and Quality, Rockville (MD)2015
        • Lynch S.
        The rationale for selecting and standardizing iron status indicators. World Health Organization Report: priorities in the assessment of vitamin A and iron status in populations, Panama City, Panama, 15-17 September 2010.
        World Health Organization, Geneva2012
        • Dallman P.R.
        • Siimees M.A.
        • Stekel A.
        Iron deficiency in infancy and childhood.
        Am J Clin Nutr. 1980; 33: 86-118
        • Siimees M.A.
        • Addiego J.E.
        • Dallman P.R.
        Ferritin in serum: diagnosis of iron deficiency and iron overload in infants and children.
        Blood. 1974; 43: 581-590
        • Looker A.C.
        • Dallman P.R.
        • Carroll M.D.
        • Gunter E.W.
        • Johnson C.L.
        Prevalence of iron deficiency in the United States.
        JAMA. 1997; 277: 973-976
        • Sherriff A.
        • Emond A.
        • Hawkins N.
        • Golding J.
        Haemoglobin and ferritin concentrations in children aged 12 and 18 months.
        Arch Dis Child. 1999; 80: 153-157
        • Domellof M.
        • Dewey K.G.
        • Lonnerdal B.
        • Cohen R.J.
        The diagnostic criteria for iron deficiency in infants should be reevaluated.
        J Nutr. 2002; 132: 3680-3686
        • National Institutes of Health
        Iron screening and supplementation of iron-replete pregnant women and young children.
        (Accessed September 11, 2016)
        • Oski F.A.
        • Honig A.S.
        • Helu B.
        • Howanitz P.
        Effect on iron therapy on behavior performance in nonanemic, iron-deficient infants.
        Pediatrics. 1983; 71: 877-880
        • Akman M.
        • Cebeci D.
        • Okur V.
        The effects of iron deficiency on infants' developmental test performance.
        Acta Paediatr. 2004; 93: 1391-1396
        • Abdullah K.
        • Kendzerska T.
        • Shah P.
        • Uleryk E.
        • Parkin P.C.
        Efficacy of oral iron therapy in improving the developmental outcome of pre-school children with non-anemic iron deficiency: a systemic review.
        Public Health Nutr. 2013; 16: 1497-1506
        • TARGet Kids! Collaboration
        About TARGet Kids! Our Team, Our Research, Participant Resource, Publication.
        ([Internet]) (Accessed March 18, 2015)
      1. Roche Diagnostics [internet].
        (Accessed January 2014)
      2. Sysmex [Internet].
        (Accessed January 2014)
        • Harrell F.E.
        Regression modeling strategies: with application to linear models, logistic regression, and survival analysis.
        Springer-Verlag, New York2010
        • Freeman V.E.
        • Mulder J.
        • van Hof M.A.
        • Hoey H.M.V.
        • Gibney M.J.
        A longitudinal study of iron status in children at 12, 24 and 36 months.
        Public Health Nutr. 1998; 1: 93-100
        • Pasricha S.
        • Black J.
        • Muthayya S.
        • Shet A.
        • Bhat V.
        • Nagaraj S.
        • et al.
        Determinants of anemia among young children in rural India.
        Pediatrics. 2010; 126: e140-9
        • Agho K.E.
        • Dibley M.J.
        • D'Este C.
        • Gibberd R.
        Factors associated with haemoglobin concentration among Timor-Leste children aged 6-59 months.
        J Health Popul Nutr. 2008; 26: 200-209
        • Durrleman S.
        • Simon R.
        Flexible regression models with cubic splines.
        Stat Med. 1989; 8: 551-561
        • R Core Team
        R: A language and environment for statistical computing.
        (R Foundation for Statistical Computing, Vienna, Austria) (Accessed March 31, 2017)
        • Abdullah K.
        • Thorpe K.E.
        • Maguire J.L.
        • Birken C.S.
        • Fehlings D.
        • Hanley A.J.
        • et al.
        Risk factors, practice variation and hematological outcomes of children identified with non-anemic iron deficiency (NAID), following screening in primary care setting.
        Paediatr Child Health. 2015; 20: 302-306
        • Munoz M.
        • Garcia-Erce J.A.
        • Remacha A.F.
        Disorders of iron metabolism. Part I: molecular basis of iron homeostasis.
        J Clin Pathol. 2011; 64: 281-286
        • Beaton G.H.
        • Corey P.N.
        • Steele C.
        Conceptual and methodological issues regarding the epidemiology of iron deficiency and their implications for studies of the functional consequences of iron deficiency.
        Am J Clin Nutr. 1989; 50: 575-588
        • Thomas C.
        • Thomas L.
        Biochemical markers and hematological indices in the diagnosis of functional iron deficiency.
        Clin Chem. 2002; 48: 1066-1076
        • Guyatt G.H.
        • Oxman A.D.
        • Ali M.
        • Willan A.
        • McIlroy W.
        Laboratory diagnosis of iron deficiency anemia.
        J Gen Intern Med. 1992; 7: 145-153

      Linked Article

      • Potential for Improved Screening, Diagnosis, and Treatment for Iron Deficiency and Iron Deficiency Anemia in Young Children
        The Journal of PediatricsVol. 188
        • In Brief
          Iron deficiency is the most common cause of anemia worldwide. In developed countries, children aged 12-36 months are at risk for iron deficiency (ID) and progression to frank iron deficiency anemia (IDA), primarily as a result of prolonged breast feeding without iron supplementation and/or excessive cow's milk intake. So-called “cow's milk anemia” became highly prevalent in the 1950s owing to a decline in breastfeeding, in concert with widespread promotion of the benefits of milk.1 From the 1960s through the 1990s, advances in laboratory testing fostered more precise measurement of hemoglobin (Hgb) concentration, red blood cell indices, and iron measurements, thereby facilitating the diagnosis of ID and IDA and the assessment of interventions aimed at treatment.
        • Full-Text
        • PDF