Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Relationship of vitamin A deficiency, iron deficiency, and inflammation to anemia among preschool children in the Republic of the Marshall Islands


Introduction: Although vitamin A deficiency, iron deficiency, and inflammation may contribute to anemia, their relative contribution to anemia has not been well characterized in preschool children in developing countries.

Objective: To characterize the contributions of vitamin A and iron deficiencies and inflammation to anemia among preschool children in the Republic of the Marshall Islands.

Subjects and methods: A community-based survey, the Republic of the Marshall Islands Vitamin A Deficiency Study, was conducted among 919 preschool children. The relationship of vitamin A and iron status and markers of inflammation, tumor necrosis factor-α, α1-acid glycoprotein, and interleukin-10, to anemia were studied in a subsample of 367 children.

Results: Among the 367 children, the prevalence of anemia was 42.5%. The prevalence of severe vitamin A deficiency (serum vitamin A <0.35 μmol/l) and iron deficiency (serum ferritin <12 μg/dl) were 10.9 and 51.7%, respectively. The respective prevalence of iron deficiency anemia (hemoglobin <110 g/l and iron deficiency), anemia with inflammation (anemia with TNF-α>2 pg/ml and/or AGP >1000 mg/l), and severe vitamin A deficiency combined with anemia was 26.7, 35.6, and 7.6%. In multivariate linear regression models that adjusted for age, sex, and inflammation, both iron deficiency (odds ratio (OR) 1.74, 95% confidence interval (CI) 1.08–2.83, P=0.023) and severe vitamin A deficiency (OR 4.85, 95% CI 2.14–10.9, P<0.0001) were significantly associated with anemia.

Conclusions: Both iron and vitamin A deficiencies were independent risk factors for anemia, but inflammation was not a significant risk factor for anemia among these preschool children.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout


  • Administrative Committee on Coordination/Sub-Committee on Nutrition (ACC/SCN) (2000): Fourth Report on the World Nutrition Situation. Geneva: ACC/SCN.

  • Allen L & Casterline-Sabel J (2001): Prevalence and causes of nutritional anemias. In Nutritional Anemias, ed. U Ramakrishnan, pp 7–21. Boca Raton, FL: CRC Press.

    Google Scholar 

  • Azim T, Ahmad SM, Sefat-E-Khuda, Sarker MS, Unicomb LE, Soma D, Hamadani JD, Salam MA, Wahed MA & Albert MJ (1999): Immune response of children who develop persistent diarrhea following rotavirus infection. Clin. Diag. Lab. Immunol. 6, 690–695.

    CAS  Google Scholar 

  • Bloem MW, Wedel M, van Agtmaal EJ, Speek AJ, Saowakontha S & Schreurs WHP (1990): Vitamin A intervention: short-term effects of a single, oral, massive dose on iron metabolism. Am. J. Clin. Nutr. 51, 76–79.

    Article  CAS  Google Scholar 

  • Flores EG (1991): Report of the National Nutrition Survey of the Republic of the Marshall Islands. New York: UNICEF.

    Google Scholar 

  • Gamble MV, Ramakrishnan R, Palafox NA, Briand K, Berglund L & Blaner WS (2001): Retinol binding protein as a surrogate measure for serum retinol: studies in vitamin A-deficient children from the Republic of the Marshall Islands. Am. J. Clin. Nutr. 73, 594–601.

    Article  CAS  Google Scholar 

  • Lozoff B & Wachs TD (2001): Functional correlates of nutritional anemias in infancy and early childhood – child development and behavior. In Nutritional Anemias, ed. U Ramakrishnan, pp 69–88. Boca Raton, FL: CRC Press.

    Google Scholar 

  • Means Jr RT (2000): The anaemia of infection. Ballière's Clin. Hematol. 13, 151–162.

    Google Scholar 

  • Mejía LA & Chew F (1988): Hematological effect of supplementing anemic children with vitamin A alone and in combination with iron. Am. J. Clin. Nutr. 48, 595–600.

    Article  Google Scholar 

  • Muhilal, Permeisih D, Idjradinata YR, Muherdiyantiningsih & Karyadi D (1988): Vitamin A-fortified monosodium glutamate and health, growth, and survival of children: a controlled field trial. Am. J. Clin. Nutr. 48, 1271–1276.

    Article  CAS  Google Scholar 

  • Murphy M, Perussia B & Trinchieri G (1988): Effects of recombinant tumor necrosis factor, lymphotoxin, and immune interferon on proliferation and differentiation of enriched hematopoietic precursor cells. Exp. Hematol. 16, 131–138.

    CAS  PubMed  Google Scholar 

  • Mwanri L, Worsley A, Ryan P & Masika J (2000): Supplemental vitamin A improves anemia and growth in anemic school children in Tanzania. J. Nutr. 130, 2691–2696.

    Article  CAS  Google Scholar 

  • Nussenblatt V, Mukasa G, Metzger A, Ndeezi G, Garrett E & Semba RD (2001): Anemia and interleukin-10, tumor necrosis factor alpha, and erythropoietin levels among children with acute, uncomplicated Plasmodium falciparum malaria. Clin. Diag. Lab. Immunol. 8, 1164–1170.

    CAS  Google Scholar 

  • Othoro C, Lal AA, Nahlen B, Koech D, Orago ASS & Udhayakumar V (1999): A low interleukin-10 tumor necrosis factor-α ratio is associated with malaria anemia in children residing in a holoendemic malaria region in western Kenya. J. Infect. Dis. 179, 279–282.

    Article  CAS  Google Scholar 

  • Semba RD & Bloem MW (2002): The anemia of vitamin A deficiency: epidemiology and pathogenesis. Eur. J. Clin. Nutr. 56, 271–281.

    Article  CAS  Google Scholar 

  • Semba RD & Palafox NA (2002): Prevention of nutritional blindness in the South Pacific. Asia-Pacific J. Ophthalmol. 14, 6–12.

    Google Scholar 

  • Semba RD, Muhilal, West Jr KP, Winget M, Natadisastra G, Scott A & Sommer A (1992): Impact of vitamin A supplementation on hematological indicators of iron metabolism and protein status in children. Nutr. Res. 12, 469–478.

    Article  CAS  Google Scholar 

  • Su SJ, Yang BC, Wang YW & Yeh TM (1999): Alpha 1-acid glycoprotein-induced tumor necrosis factor secretion of human monocytes is enhanced by serum binding proteins and depends upon protein tyrosine kinase activation. Immunopharmacology 41, 21–29.

    Article  CAS  Google Scholar 

  • Suharno D, West CE, Muhilal, Karyadi D & Hautvast GAJ (1993): Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia. Lancet 342, 1325–1328.

    Article  CAS  Google Scholar 

  • Tilg H, Ulmer H, Kaser A & Weiss G (2002): Role of IL-10 for induction of anemia during inflammation. J. Immunol. 169, 2204–2209.

    Article  CAS  Google Scholar 

  • Wang CQ, Udupa KB & Lipschitz DA (1996): Evidence suggesting a stimulatory role for interleukin-10 in erythropoiesis in vitro. J. Cell. Physiol. 166, 305–310.

    Article  CAS  Google Scholar 

  • Wang CM, Tang RB, Chung RL & Hwang BT (1999): Tumor necrosis factor-alpha and interleukin-6 profiles in children with pneumonia. J. Microbiol. Immunol. Infect. 32, 233–238.

    CAS  PubMed  Google Scholar 

  • West Jr KP & Darnton-Hill I (2001): Vitamin A deficiency. In Nutrition and health in developing countries, eds. RD Semba & MW Bloem, pp 267–306. Totowa, NJ: Humana Press.

    Chapter  Google Scholar 

  • WHO/UNICEF/UNU (1997): Iron Deficiency: Indicators for Assessment and Strategies for Prevention. Geneva, World Health Organization.

Download references


We thank the health care workers in the Republic of the Marshall Islands, especially Laling Riklon, Grace Heine, Kenya Amles, and Ailon Moses, for their diligent assistance, and Dana Totin for her assistance in interpretation of the data. This study was supported in part by the Pacific Health Research Institute, UNICEF, the Fergussen Foundation Hawaii, the Hawaii Community Foundation, Ministry of Health and Environment, Republic of the Marshall Islands, the National Institute of Child Health and Human Development (HD30042), the National Institutes of Health, and the United States Agency for International Development (Cooperative Agreement HRN A-0097-00015-00).

Author information

Authors and Affiliations



Guarantors: MV Gamble, RD Semba.

Corresponding author

Correspondence to R D Semba.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Gamble, M., Palafox, N., Dancheck, B. et al. Relationship of vitamin A deficiency, iron deficiency, and inflammation to anemia among preschool children in the Republic of the Marshall Islands. Eur J Clin Nutr 58, 1396–1401 (2004).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • anemia
  • ferritin
  • hemoglobin
  • inflammation
  • iron deficiency
  • retinol
  • vitamin A deficiency

This article is cited by


Quick links