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Center for Human Nutrition, Department of International Health, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore MD
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONWHERE HAVE WE COME...WHERE HAVE WE COME...WHERE DO WE GO...REFERENCES |
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KEY WORDS: • iron deficiency • anemia • public health • history
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONWHERE HAVE WE COME...WHERE HAVE WE COME...WHERE DO WE GO...REFERENCES |
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WHERE HAVE WE COME FROM? TERMS AND CONCEPTS |
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TOPABSTRACTINTRODUCTIONWHERE HAVE WE COME...WHERE HAVE WE COME...WHERE DO WE GO...REFERENCES |
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To determine which nutritional deficiencies were most responsible, WHO
coordinated a series of studies in pregnant women in which anemia,
serum folate, transferrin saturation and serum B-12 were assessed. They
concluded that "Iron deficiency was present in 40–99% of the
pregnant women studied and was undoubtedly responsible for the major
proportion of anemia" (WHO 1968
).
The evidence that led them to that conclusion is shown in
Figure 1
. Certainly the authors were impressed by the prevalence of iron
deficiency, which was 
10 times higher than that of folate deficiency
or vitamin B-12 deficiency based on their indicators. However, the
relation between anemia prevalence and iron deficiency prevalence is
not apparent when the data are compared among populations.
Within-population correlation coefficients with hemoglobin were
published for the study in Vellore, India. There was a strong
correlation between hemoglobin and transferrin saturation (r
= 0.56, P < 0.001), but the correlation with
serum folate was even stronger (r = 0.82, P
< 0.001). There was no significant correlation between serum
vitamin B-12 and hemoglobin (Baker and DeMaeyer 1979
).
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: "The major
factor responsible [for nutritional anemia] is a deficiency of iron,
with folate deficiency also playing a role in some population groups,
especially in pregnant women."
In 1985, DeMaeyer and Adiels-Tegman published a landmark paper
entitled "The Prevalence of Anemia in the World," in which they
compiled global data from reasonably large studies. The data presented
in that paper constitute the core of the database used for global
prevalence estimates of anemia and iron-deficiency anemia. In that
paper, nutritional anemia was considered to be a large component of
global anemia prevalence, and iron deficiency was considered the most
common cause of nutritional anemia. By making the assumption that the
prevalence of anemia in adult men is the amount of anemia not
attributable to iron deficiency, the authors tentatively estimated that
50% of anemia in women and children is attributable to iron
deficiency (DeMaeyer and Adiels-Tegman 1985
).
The next evolution of concepts is the shift from nutritional
anemia (of which iron-deficiency anemia is one important part) to
iron-deficiency anemia as the major public health problem. This is
reflected in the title of the 1989 WHO monograph, Preventing and
Controlling Iron Deficiency Anaemia Through Primary Health Care,
which states (DeMaeyer et al. 1989
), "Iron deficiency
anaemia is the most prevalent nutritional disorder in the world today.
... Iron deficiency is by far the commonest nutritional cause of
anaemia; it may be associated with a folate deficiency, especially
during pregnancy. Other nutrient deficiencies, such as vitamin B-12,
pyridoxine (PN) and copper are of little public health significance
because of their infrequency."
In 1993, a WHO/United Nations International Children’s Emergency Fund (UNICEF)/United Nations University (UNU) consultation made the next shift in thinking, i.e., from iron-deficiency anemia to iron deficiency as the problem. In the report from that meeting, anemia was considered an indicator of iron deficiency rather than iron deficiency being considered a contributing cause of anemia (WHO/UNICEF/UNU, unpublished). The authors state, "Because anaemia is the most common indicator used to screen for iron deficiency, the terms anaemia, iron deficiency, and iron deficiency anaemia are sometimes used interchangeably. There are, however, mild-to-moderate forms of iron deficiency in which, although anaemia is absent, tissues are still functionally impaired."
However, a more recent meeting in Africa brought the thinking full
circle. The lead recommendation from the meeting proceedings reads:
"Beyond iron deficiency—focus on anaemia as the principal problem.
Even though iron deficiency is a major factor contributing to the
anaemia problem in parts of Africa, there are a number of other factors
that coexist and contribute to the burden. They include other nutrient
deficiencies (e.g., folate, vitamin A), malaria, HIV [human
immunodeficiency virus], other infectious diseases, sickle cell
disease and other inherited anemias" [Micronutrients
Initiative (MI)/UNICEF 1997
].
In the past 3 years, there has been a confusing mixture of language, as
illustrated by these three recent expert committee statements:
1) "Iron deficiency is not the only cause of anemia, but
where anemia is prevalent, iron deficiency is usually the most common
cause" (Stoltzfus and Dreyfuss 1998
). 2)
"Anemia has a multifactorial etiology and the contributions of its
determinants vary in many ways. Anemia can be caused by dietary
factors, malaria, intestinal parasites, HIV, or certain genetic
hemoglobinopathies. ... Moreover determinants interact"
(Gillespie and Johnston 1998
). 3) "Although iron
deficiency accounts for most of the anaemia in underprivileged
environments, there are other causes of anaemia. ... As iron
deficiency prevalence decreases, other causes of anaemia may become
proportionately more important, but excepting sickle-cell anaemia
in some populations of Africa, none are at levels requiring a public
health response. Successful iron supplementation results in the
disappearance of anaemia as a public health problem except where
malaria is highly prevalent" (UNICEF/UNU/WHO/MI 1999
).
This confusion has real implications for how we design intervention programs and evaluate their success. It also greatly influences how we estimate the prevalence and distribution of the public health problem, which leads us to our next historical topic.
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WHERE HAVE WE COME FROM? NUMBERS |
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TOPABSTRACTINTRODUCTIONWHERE HAVE WE COME...WHERE HAVE WE COME...WHERE DO WE GO...REFERENCES |
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). It is important to consider the fact that all of the estimates that
follow are derived from measurements of hemoglobin. Prevalence
estimates for iron deficiency or iron-deficiency anemia have been
derived from anemia data and are based on a variety of assumptions.
Thus, the interpretation of hemoglobin values is fundamentally
important. The thinking expressed in a 1972 WHO technical report has
been greatly influential: "It is recognized that there is a
homeostatic mechanism that sets the hemoglobin level in each
individual. Whereas it is not known whether this is the optimum level
for health, it is accepted as ‘normal’ for the individual.
... This distribution of normal values is likely to be the same
throughout the world when allowance is made for such factors as age,
sex, pregnancy, and altitude" (Baker and DeMaeyer 1979
). It is important to remember that the WHO definitions for
anemia were explicitly not designed to indicate optimal human function
nor to be sensitive or specific for iron deficiency as opposed to other
causes. There is also growing opinion that the normative hemoglobin
distribution is not the same throughout the world
(UNICEF/UNU/WHO/MI 1999
).
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). The 1985 anemia estimate and the 50%
attribution of anemia to iron deficiency were cited in two subsequent
documents by WHO (DeMaeyer et al. 1989
) and the United
Nations Subcommittee on Nutrition (Gillespie et al. 1991
). However in 1993, two documents (Levin et al. 1993
, WHO/UNICEF/UNU, unpublished) used De Maeyer and
Adiels-Tiegman’s 1985 anemia number but named it iron-deficiency
anemia. In 1996, the Global Burden of Disease project adjusted these
numbers upward on the basis of a new global population figure but
continued to call this the prevalence of iron-deficiency anemia. In
1997–1998, three expert documents used a higher prevalence number of
2.1 billion people affected; Draper (1997)
used this as
the figure for iron-deficiency anemia, whereas the other documents
(Gillespie and Johnson 1998
, Stoltzfus and Dreyfuss 1998
) stated this to be the number with iron
deficiency. The UNICEF/UNU/WHO/MI (1999)
Technical
Workshop stated that 3.5 billion people suffer from "iron deficiency
and its anemia." Finally, in 1999, a WHO report at an INACG meeting
(INACG 2000
) estimated that 2 billion people were anemic
(applying the 30% prevalence figure of DeMaeyer and Adiels-Tiegman
to a new global population of >6 billion) and tentatively estimated
that the number of iron-deficient people could be as high as 5
billion, or 80% of the world’s population. The latter figure was
obtained by multiplying the number of anemic people by 2.5. This
factor, discussed in the WHO/UNICEF/UNU consultation (unpublished
1993), is based on U.S. national data for women and children, in which
the ratio of iron-deficient people to iron-deficient anemic
people was 2.5 (Yip 1994
). Applying that figure to
global data assumes that this relationship found in the United States
is generalizable to the world—a troubling assumption that was clearly
acknowledged at the INACG meeting. In addition, the factor should
rightly be applied only to the number of iron-deficient anemic
people, not to all anemic people. Thus, in the 15 years since 1985, as our conceptualization of the problem has evolved from iron-deficiency anemia to become iron deficiency with or without anemia, the number of people supposedly affected has grown from 0.6 million to 3.5–5 million. When global population growth is controlled for, prevalence estimates have risen from 15 to 60–80% of the world’s population. I suggest to you that these estimates have become incredible.
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WHERE DO WE GO FROM HERE? |
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TOPABSTRACTINTRODUCTIONWHERE HAVE WE COME...WHERE HAVE WE COME...WHERE DO WE GO...REFERENCES |
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Public health scientists and practitioners working on the problem of iron-deficiency anemia have lamented two challenges, i.e., it is difficult to rally political support for the problem and it is difficult to demonstrate success in controlling it. Our reaction to the first problem has been to hold more meetings and advocate more vociferously. Our reaction to the second problem has been to question our interventions and their efficacy. It is possible that a clearer and more compelling definition of the problem could contribute greatly to meeting both of these challenges. If we define the problem in terms of functional consequences rather than normative indicator distributions, our advocacy to the international health community may be more effective. If we set goals and evaluate programs on the basis of concepts and biological processes that are clear and measurable, we might find that our interventions are more successful than we have documented in the past.
I suggest that at least four steps are key to this process. The first step is to identify the causal factor. What is it that causes functional deficits (i.e., disease, disability or death) in humans? Is it iron deficiency per se? Iron-deficiency anemia? Severe anemia from any cause? The second step is to estimate the magnitude of its effect on important public health outcomes. How large are the relative risks or other measures of effect size? The third step is to estimate the prevalence of the causal factor, and the fourth step is to demonstrate effective ways to reduce the causal factor or to interrupt its link to adverse health consequences. The papers that follow address the first two steps in this process.
John Beard and Lindsay Allen present background papers that describe what we know about the possible causal factors and how they affect human physiology in the relevant outcome domains. Bernard Brabin, Kathleen Rasmussen, Stephen Oppenheimer, Sally Grantham-McGregor and Jere Haas present critical reviews of the causal evidence that links iron deficiency, anemia or both to the six outcome areas. Additional commentaries by Sue Horton and Carol Levin on work productivity and Ernesto Pollitt on child development are included with the respective evidence reviews. The supplement concludes with a summary of how the meeting participants synthesized the evidence.
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FOOTNOTES |
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2 This article was commissioned by the World
Health Organization (WHO). The views expressed are those of the author
alone and do not necessarily reflect those of WHO.
3 Abbreviations: HIV, human immunodeficiency
virus; INACG, International Nutritional Anemia Consultative Group; MI,
Micronutrients Initiative; UNICEF, United National International
Children’s Emergency Fund; UNU, United Nations University.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONWHERE HAVE WE COME...WHERE HAVE WE COME...WHERE DO WE GO...REFERENCES |
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1.
Baker S. J., DeMaeyer E. M. Nutritional anemia: its understanding and control with special reference to the work of the World Health Organization. Am. J. Clin. Nutr. 1979;32:368-417
2. DeMaeyer E. M., Adiels-Tegman M. The prevalence of anaemia in the world. Rapp. Trimest. Stat. Sanit. Mond. 1985;38:302-316
3. DeMaeyer E. M., Dallman P., Gurney J. M., Hallberg L., Sood S. K., Srikantia S. G. Preventing and controlling iron deficiency anaemia through primary health care: a guide for health administrators and programme managers 1989:5-58 WHO Geneva, Switzerland.
4. Draper A. Child development and iron deficiency 1997:1-6 The Oxford Brief, INACG (International Nutritional Anemia Consultative Group) Washington, DC.
5. Gillespie S., Johnston J. L. Expert Consultation on Anemia Determinants and Interventions 1998:1-37 Micronutrient Initiative Ottawa, Canada.
6. Gillespie S., Kevany J., Mason J. Controlling iron deficiency 1991:1-93 United Nations Administrative Committee on Coordination, Sub-Committee on Nutrition Geneva, Switzerland.
7. International Nutritional Anemia Consultative Group (2000) INACG Symposium. 12 March 1999, Durban South Africa, pp. 1–60. ILSI Research Foundation, Washington, DC.
8. Levin H. M., Pollitt E., Galloway R., McGuire J. Micronutrient deficiency disorders. Jamison D. T. Mosley W. H. eds. Disease Control Priorities in Developing Countries 1993 Oxford University Press (World Bank) New York, NY.
9. Micronutrients Initiative/UNICEF Proceedings of the eastern and southern Africa regional consultation on anemia 1997 Micronutrients Initiative Ottawa, Canada.
10. Murray C. J., Lopez A. D. Global Health Statistics 1996:1-906 Harvard University Press Cambridge, MA.
11. Stoltzfus R. J., Dreyfuss M. L. Guidelines for the Use of Iron Supplements to Prevent and Treat Iron Deficiency Anemia 1998:1-39 ILSI Press Washington DC.
12. UNICEF/UNU/WHO/MI Preventing Iron Deficiency in Women and Children, Technical Consensus on Key Issues 1999:1-60 International Nutrition Foundation Boston, MA.
13. World Health Organization Nutritional anaemias: report of a WHO Scientific Group 1968 WHO Geneva, Switzerland.
14. Yip R. Iron deficiency: contemporary scientific issues and international programmatic approaches. J. Nutr. 1994;124:1479S-1490S
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