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Strategies for the Prevention and Treatment of Iron Deficiency during Pregnancy

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Abstract

Iron deficiency is the most frequent micronutrient deficiency in humans. It is especially prevalent in certain risk groups, which, because of their elevated requirements, include pregnant women and women of childbearing age. During pregnancy the parameters of iron metabolism are altered, and suitable measures are thus needed to evaluate iron deficiency. Monitoring serum concentrations of ferritin and soluble transferrin receptor is of great use in diagnosing iron deficiency and evaluating the effects of therapy.

Control of iron deficiency during pregnancy encompasses two facets: prophylaxis and therapy. Ideally, iron-deficiency anaemia should be prevented and treatment should be reserved for confirmed iron-deficiency anaemia. However, this situation is not always possible, particularly in the developing world. Therapy of iron-deficiency anaemia during pregnancy is similar to that at any other period in life. Oral iron in the form of ferrous salts is the treatment of choice; its main disadvantages are gastrointestinal adverse effects leading to noncompliance and even discontinuation of therapy. Most of these obstacles can be overcome by using strategies such as preparations with a gastroprotective component, decreasing the dosage, or giving iron with meals.

True malabsorption of iron is rare. Parenteral iron therapy is reserved for very few specific cases, and can be given intramuscularly or intravenously.

Prophylaxis of iron-deficiency anaemia is a health priority everywhere, but is most urgently needed in developing countries, where several strategies, including food fortification and preventive supplementation, should be established for iron alone or with other micronutrients such as folate and zinc. In industrialised countries, targeted prophylaxis is also important for risk groups such as pregnant women. Iron prophylaxis for the general population is a controversial issue in industrialised countries, where the prevalence of haemochromatosis is high. However, adequate reserves of iron are advisable in women of childbearing age, especially when they are planning to become pregnant. Folate is also essential to prevent neural tube defects.

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References

  1. Underwood BA. Perspectives from micronutrient malnutrition elimination/eradication programmes. WHO Bulletin OMS 1998; 76Suppl. 2: 34–7

    Google Scholar 

  2. Picciano MF. Iron and folate supplementation: an effective intervention in adolescent females. Am J Clin Nutr 1999; 69: 1069–70

    PubMed  CAS  Google Scholar 

  3. Yip R. Iron deficiency. WHO Bulletin OMS 1998; 76Suppl. 2: 121–3

    Google Scholar 

  4. Looker AC, Dallman PR, Carroll MD, et al. Prevalence of iron deficiency in the United States. JAMA 1997; 277: 973–6

    Article  PubMed  CAS  Google Scholar 

  5. Galan P, Yoon HC, Preziosi P, et al. Determining factors in iron status of adult women in the SU.VI.MAX study. Eur J Clin Nutr 1998; 52: 383–8

    Article  PubMed  CAS  Google Scholar 

  6. Scholl TO, Hediger ML. Anemia and iron-deficiency anemia: compilation of data on pregnancy outcome. Am J Clin Nutr 1994; 59(Suppl.): 492S–501S

    PubMed  CAS  Google Scholar 

  7. Beard JL. Iron deficiency: assessment during pregnancy and its importance in pregnant adolescents. Am J Clin Nutr 1994; 59(Suppl.): 502S–10S

    PubMed  CAS  Google Scholar 

  8. Rossiter CE, Maternal mortality. Br J Obstet Gynaecol 1985; Suppl. 5: 100-15

    Google Scholar 

  9. World Health Organization (WHO). Special subjects: causes of death. Anaemias. World Health Statistics Quarterly 1977; 26: 594–617

    Google Scholar 

  10. Zhou LM, Yang WW, Hua JZ, et al. Relation of hemoglobin measured at different times in pregnancy to preterm birth and low birth weight in Shanghai, China. Am J Epidemiol 1998; 148: 998–1006

    Article  PubMed  CAS  Google Scholar 

  11. Lozoff B, Jiménez E, Wolf AW. Long-term development outcome of infants with iron-deficiency. N Engl J Med 1991; 325: 687–94

    Article  PubMed  CAS  Google Scholar 

  12. Dallman PR. Iron deficiency: does it matter? J Intern Med 1989; 226: 367–72

    Article  PubMed  CAS  Google Scholar 

  13. Hurtado EK, Claussen AH, Scott KG. Early childhood anemia and mild moderate mental retardation. Am J Clin Nutr 1999; 69: 115–9

    PubMed  CAS  Google Scholar 

  14. Roncagliolo M, Garrido, M, Walter T, et al. Evidence of altered central nervous system development in infants with iron deficiency anaemia at 6 mo: delayed maturation of auditory brainstem responses. Am J Clin Nutr 1998; 68: 683–90

    PubMed  CAS  Google Scholar 

  15. Pollitt E. Early iron deficiency anemia and later mental retardation. Am J Clin Nutr 1999; 69: 4–5

    PubMed  CAS  Google Scholar 

  16. DeMaeyer EM. Dallman PR. Manifestations of iron deficiency. Semin Hematol 1982; 19: 19–30

    Google Scholar 

  17. Mohamed K, Hytten F. Iron and folate supplementation in preg- nancy. In: Chalmers I, editor. Effective care in pregnancy and childbirth. London: Oxford University Press, 1989: 301–17

    Google Scholar 

  18. Hytten FE, Duncan DL. Iron deficiency anaemia in the pregnant woman and its relation to normal physiological changes. Nutr Abstr Rev 1956; 26: 855–68

    CAS  Google Scholar 

  19. DeMaeyer EM. Preventing and controlling iron deficiency anemia through primary health care. Geneva: WHO Press, 1989

    Google Scholar 

  20. Cook JD. Clinical evaluation of iron deficiency. Semin Hematol 1982; 19:6–18

    PubMed  CAS  Google Scholar 

  21. Cook JD, Skikne BS. Iron deficiency: definition and diagnosis. J Intern Med 1989; 226: 349–55

    Article  PubMed  CAS  Google Scholar 

  22. Lipschitz DA, Cook JD, Finch CA. A clinical evaluation of serum ferritin as an index of iron stores. N Engl J Med 1974; 290: 1213–6

    Article  PubMed  CAS  Google Scholar 

  23. Hallberg L, Bengtsson C, Lapidus L, et al. Screening for iron deficiency: an analysis based on bone marrow examinations and serum ferritin determinations in a population sample of women. Br J Haematol 1993; 85: 787–98

    Article  PubMed  CAS  Google Scholar 

  24. Remacha AF, Sarda MP, Parellada M, et al. The role of serum transferrin receptor in the diagnosis of iron deficiency. Haematologica 1998; 83: 960–3

    Google Scholar 

  25. Skikne B, Flowers C, Cook J. Serum transferrin receptor: a quantitative measurement of tissue iron deficiency. Blood 1990; 75: 1870–6

    PubMed  CAS  Google Scholar 

  26. Beguin Y, Lipscei G, Thoumsin H, et al. Blunted erythropoietin production and decreased erythropoiesis in early pregnancy. Blood 1991; 78: 89–93

    PubMed  CAS  Google Scholar 

  27. Akesson A, Bjellerup P, Berglund M, et al. Serum transferrin receptor: a specific marker of iron deficiency in pregnancy. Am J Clin Nutr 1998; 68: 1241–6

    PubMed  CAS  Google Scholar 

  28. O’Brien KO, Zavaleta N, Caulfield LE, et al. Influence of prenatal iron and zinc supplements on supplemental iron absorption, red blood cell iron incorporation, and iron status in pregnant Peruvian women. Am J Clin Nutr 1999; 69: 509–15

    PubMed  Google Scholar 

  29. Carriaga MT, Skikne BC, Finley B, et al. Serum transferrin receptor for the detection of iron deficiency in pregnancy. Am J Clin Nutr 1991; 54: 1077–81

    PubMed  CAS  Google Scholar 

  30. Zhu YI, Haas JD. Response of serum transferrin receptor to iron supplementation in iron-depleted, nonanemic women. Am J Clin Nutr 1998; 67: 271–5

    PubMed  CAS  Google Scholar 

  31. Centers for Disease Control (CDC). CDC criteria for anemia in children and childbearing-aged woman. MMWR Morb Mortal Wkly Rep 1989; 38: 400–4

    Google Scholar 

  32. Food and Nutrition Board, Institute of Medicine. Iron deficiency anemia: recommended guidelines for the prevention, detection, and management among U.S. children and women of childbearing age. Washington DC: National Academy Press, 1993

  33. Viteri FE. Prevention of iron deficiency. In: Howson CP, Kennedy E, Horwitz A, editors. Micronutrient deficiencies: a toolkit for policymakers and public health workers. Institute of Medicine. Washington DC: National Academy Press, 1998: 45–102

    Google Scholar 

  34. Anonymous. Iron supplementation: why are pregnant woman not complying? WHO Bulletin OMS 1991; 69: 130

    Google Scholar 

  35. Fernández-Ballart JD. Iron metabolism during pregnancy. Clin Drug Invest 200; 19 Suppl. 1: 9-19

  36. Hallberg L. Prevention of iron deficiency. Baillière’s Clin Hematol 1994; 7: 805–14

    Article  CAS  Google Scholar 

  37. Olsson KS, Väisänen M, Konar J, et al. The effect of withdrawal of food iron fortification in Sweden as studied with phlebotomy in subjects with genetic hemochromatosis. Eur J Clin Nutr 1997; 51: 782–6

    Article  PubMed  CAS  Google Scholar 

  38. Cogswell ME, McDonnell SM, Khoury MJ, et al. Iron overload, public health, and genetics: evaluating the evidence for hemochromatosis screening. Ann Intern Med 1998; 129: 971–9

    PubMed  CAS  Google Scholar 

  39. Clydesdale FM, Wiemer KL, editors. Iron fortification of foods. New York: Academic Press, 1985

    Google Scholar 

  40. Hurrell RF. Improvement of trace element status through food fortification: technological, biological and health aspects. Bibl Nutr Dieta 1998; 54: 40–57

    PubMed  CAS  Google Scholar 

  41. Hurrell RF. International Nutritional Anemia Consultative Group (INACG). Preventing iron deficiency through food fortification. Nutr Rev 1997; 55: 210–22

    Article  PubMed  CAS  Google Scholar 

  42. INACG. Iron EDTA for food fortification. Washington DC: Nutrition Foundation/TLSI, 1993

    Google Scholar 

  43. Pilch SM, Senti FR. Assessment of the iron nutrition status of the US population based on data collected in the Second National Health and Nutrition Examination Survey, 1976-1980. Bethesda, MD: Life Science Research Office, Federation of American Societies for Experimental Biology, 1984

    Google Scholar 

  44. Andrade AT, Souza JP, Shaw Jr ST, et al. Menstrual blood loss and body iron stores in Brazilian women. Contraception 1991; 42: 241–9

    Article  Google Scholar 

  45. Sood SK, Ramachandran K, Mathur M, et al. WHO sponsored collaborative studies on nutritional anaemia in India. I. The effects of supplemental oral iron administration to pregnant women. Q J Med 1975; 174: 241–58

    Google Scholar 

  46. Charoenlarp P, Dhanamitta S, Kaewvichit R, etal. AWHOcol-laborative study on iron supplementation in Burma and in Thailand. Am J Clin Nutr 1988; 47: 280–97

    PubMed  CAS  Google Scholar 

  47. Chew F, Torun B, Viteri FE. Comparison of weekly and daily iron supplementation to pregnant women in Guatemala (supervised and unsupervised) [abstract]. FASEB J 1996; 10: A4221

    Google Scholar 

  48. Higgins AC, Penchartz PB, Strawbridge JE, et al. Maternal haemoglobin changes and their relationship to infant birth weight in mothers receiving a program of nutritional assessment and rehabilitation. Nutr Res 1982; 2: 641–9

    Article  Google Scholar 

  49. Ekström E-C, Kavishe FP, Habicht JP, et al. Adherence to iron supplementation during pregnancy in Tanzania: determinants and hematological consequences. Am J Clin Nutr 1996; 64: 368–74

    PubMed  Google Scholar 

  50. Sloan NL, Jordan EA, Winikoff B. Does iron supplementation make a difference? Mother Care Project, Working Paper 15. Arlington, VA: 1992: 50pp

  51. Singh K, Fong YF, Arulkumaran S. The role of prophylactic iron supplementation in pregnancy. Int J Food Sci Nutr 1998; 49: 383–9

    Article  PubMed  CAS  Google Scholar 

  52. Kaufer M, Casanueva E. Relation of prepregnancy ferritin levels to hemoglobin levels throughout pregnancy. Eur J Clin Nutr 1990; 44: 709–15

    PubMed  CAS  Google Scholar 

  53. Scholl TO, Hediger ML, Bendich A, et al. Use of multivita-min/mineral prenatal supplements: influence on the outcome of pregnancy. Am J Epidemiol 1997; 146: 134–41

    Article  PubMed  CAS  Google Scholar 

  54. Viteri FE. Effective iron supplementation does not happen in isolation [letter to the editor]. Am J Clin Nutr 1997; 65: 889–92

    PubMed  CAS  Google Scholar 

  55. Viteri FE. Iron supplementation for the control of iron deficiency in populations at risk. Nutr Rev 1997; 55(6): 195–209

    Article  PubMed  CAS  Google Scholar 

  56. Angeles-Agdeppa I, Schultink W, Sastroamidjojo S, et al. Weekly micronutrient supplementation to build iron stores in female Indonesian adolescents. Am J Clin Nutr 1997; 66: 177–83

    PubMed  CAS  Google Scholar 

  57. Viteri FE, Ali F, Tujague J. Long-term weekly iron supplementation improves and sustains non-pregnant women’s iron status as well or better than currently recommended short-term daily supplementation. J Nutr 1999; 129: 2013–20

    PubMed  CAS  Google Scholar 

  58. INACG/WHO/UNICEF. Guidelines for the use of iron supplements to prevent and treat iron deficiency anaemia. Stoltzfus R, Dreyfuss M, editors. The International Nutritional Anaemia Consultative Group, 1998. Washington; ILSI Press, 1998: 1–39

    Google Scholar 

  59. Ridwan E, Schultink W, Dillon D, et al. Effects of weekly iron supplementation on pregnant Indonesian women are similar to those of daily supplementation. Am J Clin Nutr 1996; 63: 884–90

    PubMed  CAS  Google Scholar 

  60. Liu X-N, Liu P-Y. The effectiveness of weekly iron supplementation regimen in improving the iron status of Chinese children and pregnant women. Biomed Environ Sci 1996; 9: 341–7

    PubMed  CAS  Google Scholar 

  61. Liu X-N, Liu P-Y, Viteri FE. Weekly iron supplementation to pregnant women in China is as effective as daily supplementation in controlling ferropenic anemia and iron deficiency. J Nutr In press

  62. Agarwal KN, Agarwal DK, Mishra KP. Impact of anaemia prophylaxis in pregnancy on maternal haemoglobin serum ferritin and birth weight. Indian J Med Res 1991; 94: 277–80

    PubMed  CAS  Google Scholar 

  63. Preziosi P, Prual A, Galan P, et al. Effect of iron supplementation on the iron status of pregnant women: consequences for new-borns. Am J Clin Nutr 1997; 66: 1178–82

    PubMed  CAS  Google Scholar 

  64. Beard JL. Weekly iron intervention: the case for intermittent iron supplementation. Am J Clin Nutr 1998; 68: 209–12

    PubMed  CAS  Google Scholar 

  65. Liu XN, Yang W, Zhang J, et al. Weekly iron supplementation is effective and safe in pregnant women [abstract]. FASEB J 1995; 9: A5658

    Google Scholar 

  66. Hallberg L. Combating iron deficiency: daily administration of iron is far superior to weekly administration. Am J Clin Nutr 1998; 68: 213–7

    PubMed  CAS  Google Scholar 

  67. Hibbard BM. Controversies in therapeutics. Iron and folate supplements during pregnancy: supplementation is valuable only in selected patients. BMJ 1988; 297: 1324–6

    Article  PubMed  CAS  Google Scholar 

  68. Tee E-S, Kandiah M, Awin N, et al. School-administered weekly iron-folate supplements improve hemoglobin and ferritin concentrations in Malaysian adolescent groups. Am J Clin Nutr 1999; 69: 1249–56

    PubMed  CAS  Google Scholar 

  69. Oakley GP. Folic-acid-preventable spina bifida and anencephaly. WHO Bulletin OMS 1998; 76Suppl. 2: 116–7

    Google Scholar 

  70. Caulfield LE, Zavaleta N, Figueroa A. Adding zinc to prenatal iron and folate supplements improves maternal and neonatal zinc status in Peruvian population. Am J Clin Nutr 1999; 69: 1257–63

    PubMed  CAS  Google Scholar 

  71. World Health Organization (WHO). Maternal Health And Safe Motherhood Programme, Nutrition Programme. The prevalence of anaemia in women: a tabulation of available information. Geneva: WHO, 1992: 100pp

  72. Fairbanks, VF, Beutler E. Iron deficiency. In Beutler E, Lichtman Ma, Coller BS, et al., editors. Williams’ hematology. 5th edition. New York; McGraw-Hill 1995: 490–511

    Google Scholar 

  73. Lee GR. Iron deficiency and iron-deficiency anemia. In: Lee GR, Bithell TC, Foerster J, et al., editors. Clinical hematology. 10th ed. Baltimore: Williams &Wilkins, 1999:979–1010

    Google Scholar 

  74. Harju E. Clinical pharmacokinetics of iron preparations. Clin Pharmacokinet 1989; 17: 69–89

    Article  PubMed  CAS  Google Scholar 

  75. Hallberg L, Ryttinger L, Sölvell L. Side effects of oral iron therapy. A double blind study of different iron compounds in tablet form. Acta Med Scand 1966; 180Suppl. 459: 3–10

    Google Scholar 

  76. Cook JD, Carriaga M, Kahn SG, et al. Gastric delivery system for iron supplementation. Lancet 1990; 335: 1136–9

    Article  PubMed  CAS  Google Scholar 

  77. Tinawi M, Martin KJ, Batani B. Oral iron absorption test in patients on CAPD: comparison of ferrous sulfate and polysaccharide ferric complex. Nephron 1996; 74: 291–4

    Article  PubMed  CAS  Google Scholar 

  78. Cook JD. Adaptation in iron metabolism. Am J Clin Nutr 1990; 51:301–8

    PubMed  CAS  Google Scholar 

  79. Cook JD. Iron-deficiency anemia. Baillière’s Clin Hematol 1994; 7: 787–804

    Article  CAS  Google Scholar 

  80. Crosby WH. The rationale for treating iron deficiency anemia. Arch Intern Med 1984; 144: 471–2

    Article  PubMed  Google Scholar 

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Correspondence to Angel F. Remacha.

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Remacha, A.F. Strategies for the Prevention and Treatment of Iron Deficiency during Pregnancy. Clin. Drug Investig. 19 (Suppl 1), 29–43 (2000). https://doi.org/10.2165/00044011-200019001-00004

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