2.1 Iron Deficiency Update
Iron is essential for the production of haemoglobin, which helps deliver oxygen from the lungs to body tissues, transport electrons in cells, and synthesize iron enzymes that are required to utilize oxygen for the production of cellular energy.2, 3 Iron balance is determined by the body’s iron stores, iron absorption, and iron loss. At least two-thirds of body iron is functional iron, mostly haemoglobin within circulating red blood cells, with some as myoglobin in muscle cells and parts of iron-containing enzymes. Most of the remaining body iron is storage iron (existing as ferritin and haemosiderin), which serves as a deposit to be mobilized when needed.
The reduction of body iron has three main stages: (1) iron depletion, which refers to a decrease of iron stores, measured by a reduction in serum ferritin concentration; (2) iron deficient erythropoeisis, when storage iron is depleted and there is insufficient iron absorption to counteract normal body losses (at this time, haemoglobin synthesis starts to become impaired and haemoglobin concentrations fall); and (3) iron deficiency anaemia, the most severe degree of iron deficiency, which ensues if the haemoglobin concentration falls below a statistically defined threshold lying at two standard deviations below the median of a healthy population of the same age, sex, and stage of pregnancy.4 For every case of iron deficiency anaemia found in a population, there are thought to be at least two cases of iron deficiency.5 A recent report has questioned the current criteria for diagnosis of anaemia and suggested that these be reviewed and revised to link them explicitly to functional outcomes of public health significance.6
Knowledge continues to grow of the very serious functional consequences of iron deficiency anaemia. A recent analysis of the economic consequences of iron deficiency has estimated the median value of productivity losses due to iron deficiency to be about US$4 per capita, or 0.9% of GDP, for a range of developing countries.7 The dominant effect is the loss associated with cognitive deficits in children. This estimate does not include the burden of maternal death associated with severe anaemia, nor the lowered effectiveness of funds spent on education.
Comparing Prevalences and Numbers
Iron deficiency and its anaemia affect more than 3.5 billion people in the developing world.8 While accurate prevalence estimates are difficult to obtain and periodically revised, all public health and nutrition experts agree that this is a huge problem.
To estimate iron deficiency at the global, regional, or national level, anaemia prevalences are used as a proxy indicator. This assumption - namely that iron deficiency is the main cause of anaemia - is likely to hold true in industrialized countries but is less certain in some regions of the developing world where other factors play an important role. These other factors include, for example, malaria and some other parasitic infections, current infectious disease, and other pathologies as well as other nutrient inadequacies that may limit haemoglobin formation. Any estimate of iron deficiency based on anaemia data can thus only be an approximation.
The level of haemoglobin concentration in the blood is used as an indicator to estimate the prevalence of anaemia. Other criteria have been recommended by the Centers for Disease Control and Prevention (CDC) for pregnant women, but these have not yet been adopted and applied on a broad basis. Table 2.1 presents the cut-off points recommended by UNICEF, UNU, and WHO.
Table 2.1: Cut-off points for blood haemoglobin concentration to define anaemia by age group
When global anaemia prevalence is examined for each physiological group, using the WHO Global Database on Anaemia, the most affected groups are pregnant women (48%) and 5 - to 14-year-old children (46%). Preschool children (39%) are also a high-risk group. However, the preschool data should be interpreted cautiously as the prevalence estimates are based on a limited number of surveys, mostly carried out in North and Latin America. Small-scale studies in Africa and Asia have shown higher prevalences for this age group.
Predictably, the prevalence of anaemia in developing countries is three to four times higher than in industrialized countries. The most highly affected population groups in developing countries are pregnant women (56%), school-age children (53%), nonpregnant women (44%), and preschool children (42%). But another group demands attention as well: older adults, half of whom are anaemic (51%).
In industrialized countries, the most-affected groups are pregnant women (18%) and preschool children (17%), followed by nonpregnant women and older adults, both at 12%. The prevalence of anaemia is low for adult males in industrialized countries (5%), but no less than one-third of adult males are anaemic in developing countries (see Figure 2.1). Prevalence estimates are not disaggregated by severity, although such distinctions are increasingly being made in field programmes where the priority is usually to prevent severe anaemia and its high functional costs.
Figure 2.2 presents prevalences by WHO region. (A list of countries in each WHO region appears in Appendix 9.) With regard to preschool children, anaemia prevalence is the highest in Africa and Asia. In Africa the middle part of the continent from the west to the east is the most affected, with anaemia prevalences ranging from 42% to 53%. In Asia the most affected sub-region is South Central Asia. In the Americas the Caribbean is most affected, with a prevalence of 39%, while anaemia prevalences in South and Central America are similar to those observed in the remaining parts of Africa and Asia. Among industrialized countries, anaemia prevalences are lowest in Northern Europe (2%) and around 5% in Western Europe and North America.
The geographical pattern of anaemia in pregnant women follows that observed for preschool children, with the most affected regions being Africa and Asia (Figure 2.3). In Asia anaemia prevalences are as high as 75% in South Central Asia; in - Africa they range from 47% in Eastern Africa to 56% in Western Africa. In the Americas the prevalence is highest in the Caribbean. In industrialized countries the prevalences range from 14% in Oceania (Australia and New Zealand) to 20% in Eastern Europe.
Finally, although the data for 5 - to 14-year-olds are limited, some estimates can be made. The prevalence of anaemia is highest in South-East Asia (63%) and Africa (52%), followed by the Eastern Mediterranean (45%), the Americas (23%) and the Western Pacific (21%). In industrialized countries, regional prevalences range from 5% in North America to 22% in Europe, including high prevalences in Eastern Europe.
Data on adolescents are scarce. In a multicountry study on adolescent nutritional status carried out by the International Center for Research on Women (ICRW), anaemia was found to be the most widespread nutritional problem and highly prevalent in four of the six country studies in which it was assessed. Prevalences ranged from 32 to 55%; there was no significant gender difference.10 Before the ICRW study, little research had been done on anaemia during adolescence. While girls lose more iron through menses, boys may need more per kilogram weight gained, as relatively more muscle is built during male than female adolescent growth.
With regard to older adults, some data are available from the LSHTM study described in section 1.6. In India, the prevalence of anaemia among people over age 60 was found to be high, using WHO criteria: 38% among men (< 130g/L) and 52% among women (< 120g/L). Among women over 70 years, the prevalence rose to 70%. In both men and women, the prevalence of anaemia was highest among those with severe undernutrition (BMI < 16 kg/m2).
These are only rough estimates of the global prevalence of anaemia, which need to be refined. Few countries have reported data on anaemia prevalences at the national or sub-national level, so some sub-regions, such as Oceania and Eastern Europe, are poorly covered by the database. Trends could not be assessed anywhere, owing to the lack of repeated, comparable national surveys of anaemia. Moreover, different methods for sampling, assessment, and classification often render data difficult to use. One thing is clear, however: anaemia remains a major problem with serious consequences.
Prevention and Control
A recent joint technical workshop concluded that interventions to control iron deficiency are available, affordable, and sustainable.8 Advances have been made in iron fortification of food staples or condiments and in fortification of complementary foods. A recent review has concluded that iron fortification does not significantly increase the prevalence of iron overload in susceptible individuals, nor the rate at which it develops. These concerns should not constrain the development of iron fortification programmes.11 The use of iron/folate supplements to prevent iron deficiency in malaria-endemic regions has also been endorsed by expert groups.
Nonetheless, in contrast to vitamin A and iodine deficiency control, there remains a significant gap between the efficacy (potential effect) and the effectiveness (actual effect under expected conditions) of programmes aimed at controlling iron deficiency anaemia among highly vulnerable sub-groups such as pregnant women and older infants. Oral iron supplementation programmes are blighted by problems ranging from an inadequate supply of supplements (itself often related to the low priority attached to control of iron deficiency) to poor compliance with their consumption. The UNU/UNICEF/WHO/MI technical consultation recommended better monitoring, evaluation, and research to improve effectiveness.
An authoritative meta-analysis of the efficacy of intermittent iron supplementation was completed in 1999.6 The major findings were that (1) both daily and weekly iron supplementation are efficacious, but weekly supplementation is likely to be less effective than daily administration, except in situations where weekly but not daily supervision is feasible; (2) weekly supplementation may be particularly disadvantageous during pregnancy and in situations where the baseline prevalence of anaemia is high; (3) unless ways are found to greatly improve compliance, neither daily nor weekly supplementation is likely to be an effective approach to preventing and controlling anaemia in developing countries, and (4) regardless of the degree of supervision that can be arranged, weekly iron administration instead of daily is not recommended for pregnancy.
This analysis concludes with a call for applied research to develop other strategies for effectively improving utilizable iron intakes (by altered food usage or food fortification where this is feasible) or for greatly improving compliance in daily or weekly direct supplementation programmes.
One other approach gaining momentum is “self-fortification” through plant breeding, which holds great promise for making a significant, low-cost, and sustainable contribution to reducing micronutrient deficiencies. In this approach, plant breeders seek to take advantage of existing consumption behaviours by developing staple food crops that, in some sense, fortify themselves by loading high amounts of minerals and vitamins into their seeds. One promising variety being tested at the International Rice Research Institute (IRRI) has double the iron (after milling) of standard IRRI releases and is also early maturing, high yielding, and disease resistant. Bioavailability tests using human subjects are planned for 2000. Pending the results of these and other agronomic tests, the new variety may be ready for release to farmers in the Philippines in a few years.12
The development of strategies to control iron deficiency is further hampered by uncertainties concerning its etiology in different situations - particularly in Africa where the non-iron deficiency causes of anaemia may be significant. Working criteria to distinguish the different types of anaemia are needed in order to better define the target groups as well as the most appropriate action. A recently developed tool - the life cycle anaemia risk matrix - may help in organizing etiological assessments, with a view to better determining and prioritizing appropriate control strategies.4
Our understanding of the consequences of iron deficiency has advanced significantly, as has our knowledge of what to do, but our understanding of how to implement appropriate interventions effectively on a large scale is still limited. Research in this area remains an absolute priority. Allied to this, more effective advocacy and communication on the national importance of iron deficiency prevention and control are urgently required.
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