Iron Deficiency Anaemia

Introduction

Iron deficiency anaemia (IDA) is the most prevalent nutritional deficiency worldwide. It is a major public health problem with adverse consequences especially for women of reproductive age and for young children. Over 90% of affected individuals live in developing countries. The consequences of IDA are numerous as iron plays a central role in the mechanism for oxygen transport, and is essential in many enzyme systems. Of greatest concern is that IDA in infants and children is associated with impaired physical and cognitive development. In adults, IDA is associated with weakness and fatigue which reduce capacity for physical work and productivity. In pregnant women, it contributes to maternal morbidity and mortality, and increases the risk of foetal morbidity, mortality and low birth weight (reviewed by Viteri, 1997).

Table 15: Haemoglobin Levels Indicative of Anaemia

Age/sex group	Haemoglobin level (g/dl)
Children 6m-5y	<11
Children 6y-14y	<12
Adult males	<13
Adult females (non pregnant)	<12
Adult females (pregnant)	<11

Source: WHO, 1968

Severe anaemia may be a contributory factor in up to 50% of maternal deaths, and is the main cause of up to 20% of maternal deaths in developing countries (ACC/SCN, 1991).

At the World Summit for Children in 1990, there was political commitment to reduce IDA in women of reproductive age to one-third of 1990 levels by the end of the decade. At the International Conference on Nutrition in 1992, this goal was expanded to include young children, with specific reference to the impact of IDA on cognitive development.

Iron deficiency and anaemia

Iron deficiency occurs when an insufficient amount of iron is absorbed to meet the body's requirements. This may result from inadequate iron intake, reduced bioavailability of dietary iron, increased need for iron (e.g., during growth or pregnancy) or chronic blood toss.

Iron deficiency encompasses a range of iron depletion states. The least severe is diminished iron stores, diagnosed by decreased serum ferritin levels. Decreased iron stores are not usually associated with adverse physiological consequences, but do represent a vulnerable state. Iron deficiency without anaemia occurs when iron depletion is severe enough to affect normal production of haemoglobin, but without haemoglobin levels falling below the clinical criteria defining IDA. This is characterized by decreased transferrin saturation levels and increased erythocyte protoporphyrin.

The major clinical manifestation of iron deficiency is IDA, which occurs when haemoglobin production is compromised by lack of iron to such an extent that the haemoglobin concentration falls below defined age- and sex-specific cut-off values (Table 15). Epidemiological criteria can be used to define severe (>40%), moderate (10-39.9%) or mild (<10%) prevalence of anaemia within populations (WHO, 1996, p. 8 and elsewhere).

'...In Sub-Saharan Africa, bioavailability of dietary iron was the most important determinant of anaemia...'

Intestinal helminths, especially hookworm infections, cause gastrointestinal blood toss and are one of the major causes of iron deficiency anaemia. There are a number of causes of anaemia other than iron deficiency, including malaria (Weatherall, 1988), congenital haemolytic diseases such as thalassaemia, and other micronutrient deficiencies (e.g., vitamin A deficiency, Suharno and Muhilal, 1996). The relative importance of anaemia determinants has recently been assessed by different geographical region from a life-cycle perspective (Micronutrient Initiative, in preparation). In Sub-Saharan Africa, bioavailability of dietary iron was considered the most important determinant of anaemia in every age group except pregnant women (Figure 7). In pregnant women, malaria is a more important determinant of anaemia than iron deficiency in primagravidae. For multigravidae, iron deficiency appears to be a more important determinant. The importance of helminth and other infections (e.g., AIDS), genetic disorders and other factors as determinants of anaemia was also ranked for different age groups. Worldwide, at least half of anaemia is due to nutritional iron deficiency, and subclinical iron deficiency is as widespread as IDA. In areas with high anaemia prevalence (above 50%), it can be assumed that almost all the population is iron deficient (WHO/UNICEF/UNU, in preparation).

Table 16: Prevalence of Anaemia among Different Populations, Based on National Data

Regions1	Children				Women (15-59y)				Men(15-59y)
	0-4y		5-14y		Pregnant		All
	%	Pop (million)	%	Pop (million)	%	Pop (million)	%	Pop (million)	%	Pop (million)
Africa	33.1	35.5	52.0	85.2	46.9	9.6	37.9	57.6	28.0	41.9
Non-industrialized Americas	22.9	13.0	36.9	39.5	39.0	3.8	31.0	44.9	11.0	15.8
South East Asia	52.7	93.8	63.9	207.8	79.6	22.2	60.0	218.6	42.4	184.8
Eastern Mediterranean	38.3	28.1	30.8	37.9	63.9	8.8	51.1	60.6	32.7	41.5
Non-industrialized West Pacific	14.7	19.7	56.9	156	38.5	9.4	33.8	152.9	36	172.5
Total	34	190	53	526	56	54	43	535	34	456.5

1. WHO regions as defined in WHO'S World Health Report, 1997 (Note: South Asian countries are included in the South East Asia region) Source: WHO (in preparation)

Table 17: Life-Cycle Anaemia Risk Matrix for Sub-Saharan Africa (The numbers in each box represent the priority attached to the determinant at each life cycle stage, with 1 being the most important).

Determinants	Infant (0-1y)	Preschool (1-5y)	School-aged (5-15y)	Adolescent (12-19y)	Reproductive-age women (15-45y)	Pregnant women	Adult men (20y+)
Diet	- iron content of complementary foods - composition/bioavailability of dietary iron - lack of exclusive breastfeeding (1 or 2)	- iron content and bioavailability of complementary foods. - continuity of breastfeeding (within 2nd year) - content and bioavailability of family diet - vitamin A? (1)	- bioavailability of dietary iron (1)	- bioavailability of dietary iron - high iron requirements - iron density of diet - seasonality (1)	- bioavailability of dietary iron (1) - increased iron demand - folate deficiency (3) - lactation may increase iron absorption?	- primagravidae (2) * low iron stores * high demand * folate deficiency - multigravidae (1) * inadequate intake and bioavailability of dietary iron (need for supplements)	N/A
Malaria	- biggest cause of anaemia (1 or 2)	- diminishing with age as immunity acquired - dependent on local transmission (2, but main cause of life-threatening anaemia)	(4)	(4)	(5)	- primagravidae (1) - multigravidae (2) - cause of low birth weight and low iron stores in newborns - seasonality	- some resistance
Helminths		- increasing problem, unknown scale in Africa (3)	- hookworm (2) - schistosomiasis increasing (3)	- helminths and schistosomiasis (2) but little data on schistosomiasis related to anaemia	- hookworm (3) local transmission variation	- hookworm (4) regional differences	- high risk occupations, especially farmers, miners (1)
Genetic	- sickle cell disease (4) (1-2% newborns)	- surviving sickle cell disease (4)	- sickle cell disease diminishing (5)			- sickle cell disease (5)
Other infections	- poor appetite, catabolic losses, raised requirements, AIDS	poor appetite, catabolic losses, raised requirements		- AIDS, TB (3) especially girls	- AIDS, TB and related infections (2) - HIV and malaria interaction	- AIDS (3)	- AIDS, TB, trauma, chronic infections (2)
Other factors	- low birth weight - maternal nutrition			- excess blood loss

Source: Micronutrient Initiative. Expert Consultation on Determinants of Anaemia, MI, Ottawa, September 1997.

Magnitude of the problem

Calculations using the most recent estimates of anaemia prevalence from WHO suggest that 43% of all women and 34% of all men are anaemic in developing regions (Table 16). South East Asian countries have the highest prevalence of anaemia, with almost 80% of pregnant women in this region being anaemic. In all regions, the prevalence of anaemia is higher in pregnant women than in non-pregnant women. These updated estimates are based on available national prevalence data starting from the 1970s, up to and including data from 1997, and using population data from 1995 (DeMaeyer and Adiels-Tegman, 1985; WHO, 1992; AbouZahr, Ahman and Bailey, in preparation; WHO, in preparation).

Estimating trends in anaemia prevalence over time remains problematic. This would require representative longitudinal data. Comparing summary data from one database with summary data from the same, updated database can be difficult to interpret without detailed information concerning which components have been updated. Further analysis is required, both to compare data from representative surveys over time in specific countries, and to combine the existing data in more meaningful ways.

Control and Prevention of IDA - Current Status of Programmes

Strategies to improve IDA include supplementation, fortification, dietary modification and parasitic disease control. It is generally acknowledged that progress in addressing IDA has lagged behind progress for iodine and vitamin A deficiencies. However, there are many programmes currently implemented, including widespread adoption of iron/folate supplementation in pregnancy, and growing support for fortification of staple foods. Many control programs are currently implemented, including widespread adoption of iron/folate supplementation in pregnancy, and growing support for fortification of staple foods with iron.

There is still lack of agreement on dosage and optimal duration of supplementation for certain target groups. The most recently published statement from WHO (DeMaeyer et al., 1989) recommended universal iron supplementation for pregnant women (60 mg of elemental iron + 250 mg of folic acid, once or twice daily) to be taken throughout the second half of pregnancy. In 1995, the UNICEF/WHO Joint Committee on Health Policy (JCHP) endorsed iron/folate supplementation as the strategy of choice and recommended that where the prevalence of IDA in pregnant women exceeds 30%, countries should implement universal supplementation through antenatal clinics, regardless of women's individual haemoglobin status (UNICEF/WHO, 1995). The International Nutritional Anaemia Consultative Group (INACG) recently drafted guidelines for iron/folate supplementation, which make a similar recommendation but where anaemia prevalence in pregnant women is greater than 40% (Stoltzfus and Dreyfuss, 1997).

To update the current status and progress of programmes to control and prevent iron deficiency anaemia, UNICEF recently conducted a survey. Questionnaires were sent to all UNICEF field offices in August 1997. Specific objectives of this exercise were:

à to review the global situation of IDA assessments conducted and planned;

à to report on the status of policies adopted by countries to support antenatal supplementation of pregnant women;

à to report on the procurement, utilization and cost of iron/folate supplements;

à to summarize the composition and dosages adopted by countries supporting antenatal supplementation;

à to review the status of related policies to supplement young children with iron and to support regular de-worming of women and young children.

Completed questionnaires were received from 57 (35%) of the 163 countries where UNICEF has programmes.

Table 18: Type of Supplements used by Countries Supporting Iron/folate Supplementation Programmes

Supplements used	Number of countries
Ferrous sulphate 200 mg (60 mg elemental iron) + 250 mg folic acid. One tablet daily.	43
Ferrous sulphate only (60 mg elemental Iron). One tablet dally. (No folate supplementation)	8
Folic acid 1 mg. One tablet dally In addition to the Standard ferrous salt/folic acid preparation.	2
Ferrous salt (60 mg), one tablet dally in addition to the Standard ferrous salt/folic acid preparation.	2

Source: UNICEF

Additional information was obtained from annual reports of UNICEF country offices for 1995 and 1996, USAID-funded Demographic and Health Surveys from 1987 to 1996, and UNICEF's Supply Division in Copenhagen. Of the 163 countries, fewer than half (43%) have conducted at least one nationally representative survey to assess IDA prevalence. Eleven countries are planning to conduct surveys in the near future but very few countries have completed repeat surveys.

Status of Supplementation Policy and Programmes for Pregnant Women

According to the UNICEF survey, 49 countries have adopted a universal preventive supplementation policy for pregnant women. Eleven countries have policies whereby only those pregnant women found to be anaemic (determined by blood test or by clinical judgement) are given supplements. Six countries do not have a clear targeting policy.

Of the countries supporting supplementation programmes for pregnant women, 43 use the previously recommended iron/folate combination, 60 mg iron + 250 mg folic acid. In December 1997 the Essential Drugs Committee of WHO approved increasing the folic acid content of the iron/folate tablet used in the programme to 400 mg. The survey showed that eight countries give iron supplementation without folic acid. In two countries, folic acid tablets are given in addition to the iron/folate preparation, and in two others, iron tablets are given in addition to the iron/folate preparation (Table 18). National anaemia control programs in Bangladesh, Bhutan, Oman and Pakistan include iron/folate supplementation through the post-partum period. In other countries, such as Madagascar and India, the current policy requires that pregnant women receive supplements for at least 100 days.

Eight countries [in the survey] give iron supplementation [to pregnant women] without folic acid. This practice must be corrected.'

Even though the evidence supporting the effectiveness of weekly iron supplementation is limited (Ridwan et al., 1996), eight countries are introducing such a policy for supplementation during pregnancy. Chad alone has a policy of monthly supplementation of pregnant women.

The survey showed that there are 29 countries where at least 50% of pregnant women receive iron/folate supplements during routine ante-natal care. In 11 of these 29 countries, more than 80% of pregnant women presenting for antenatal care receive iron supplements. The percentage of women using antenatal services may be a proxy for potential supplement coverage through these facilities.

Regular supplies are obviously important for programme effectiveness, but so is compliance. It has long been argued that gastro-intestinal side effects, with associated nausea, reduce compliance. More recent work has shown that few women stop taking iron pills if they are counselled that side effects may occur and that they are not serious (as reviewed by Galloway and McGuire, 1996). In one unsupervised supplementation trial in India, it was found that counselling and reassurance, especially in the first ten days after starting supplementation, played a crucial role. Side effects also reduced with time. Only 11% of women receiving 180 mg/d reported side effects at 32-36 weeks gestation (Seshadri et al., 1994).

Status of Supplementation Policy and Programmes for Children

Full-term healthy infants who are exclusively breastfed until about six months of age are not at high risk of developing anaemia. From six months onward, the infant's iron needs must be met by the family diet. Rapid growth during this period increases the need for iron, and in older children, high prevalences of intestinal helminth infections, especially hookworms, increase the risk of iron deficiency. The JCHP called for preventive iron supplementation for all infants and young children in situations where the prevalence of IDA in pregnant women exceeds 30% (UNICEF/WHO, 1995). More recently, a USAID/UNICEF consultation on anaemia in young children recommended supplementation of children aged 6-9m with 12.5 mg oral iron per day unless there is strong evidence that children's diets contain adequate available iron (Nestel and Alnwick, 1996; Stoltzfus and Dreyfuss, 1997). In older children, supplementation dosage depends on the child's age and weight: the INACG draft guidelines recommend 20-30 mg elemental iron daily for children aged 2-5y; 30-60 mg for children aged 6-11y; and 60 mg for adolescents (Stoltzfus and Dreyfuss, 1997). Periodic cycles of daily iron supplements and treatment of those already anaemic, plus periodic de-worming, are recommended by WHO (WHO/UNICEF/UNU, in preparation).

The UNICEF survey showed that 23 countries have adopted supplementation of pre-school or school-aged children as a policy. In six countries (Ecuador, El Salvador, Honduras, Mongolia, Niger and Thailand) over 10% of preschool and/or school-aged children routinely received supplements in 1996, with over 50% of children receiving supplements in Ecuador and El Salvador.

Status of Food Fortification Programmes

Fortification of foods with iron is a preventive measure that aims to improve and sustain iron nutrition on a long-term basis. One of the recommended actions of the JCHP was for countries to study the feasibility of food fortification as a means to reducing iron deficiency anaemia (UNICEF/WHO, 1995). Fortification with iron has been practised for many years in industrialized countries such as Canada, UK and USA. Although it is generally held that fortification has contributed to a reduction in anaemia prevalence in developed countries, there are almost no studies confirming its effectiveness. In developing countries, five large studies have demonstrated the effectiveness of iron fortification (in Guatemala, India, South Africa, Thailand and Venezuela), but only when based on careful planning and well-established guidelines (reviewed by Viteri, 1997). These include an evaluation of the national food fortification programme in Venezuela, which was shown to be effective in reducing anaemia prevalence in school-age children (Layrisse et al, 1996).

The availability of iron fortificants with increased bioavailable iron and greater stability, together with the potential for multiple nutrient fortification, suggest that fortification is an attractive solution in countries where a significant proportion of vulnerable groups consume centrally processed foods. In Latin America and the Middle East, wheat flour is widely consumed by all population groups and most wheat flour is centrally milled, making the fortification of flour with iron an attractive intervention. The UNICEF survey showed that 42 countries are implementing or strongly considering fortification of flour (wheat or other types) and/or infant cereals with iron. The majority of countries in Latin America and the Caribbean (81%) have already planned or implemented flour fortification programmes, and laws mandating the fortification of flour with iron have been introduced in Chile, Guatemala, Peru, Trinidad and Tobago and Venezuela. Iron fortification of flour is being pursued by well over half of countries in the Middle East and North Africa region (WHO/UNICEF/MI/PAMM, 1996), and the countries of Central Asia have also developed an area-based programme to fortify all wheat flour.

Dietary Diversification

Improvement in supply, consumption and bioavailability of iron in food is an important strategy to improve the iron status of populations. There are two types of dietary iron; haem (present in meat, fish and blood products), and non-haem (present to varying degrees in all plant foods). Non-haem iron is the most important source of dietary iron, especially in many parts of the developing world, where a vegetarian diet is an economic necessity. Leguminous seeds are an important source of iron in many regions, however food supply data indicate that the per capita availability of leguminous seeds is declining, especially in south Asia (FAO, 1992). In general, the availability of iron-rich foods has lagged behind that of energy and protein. This gives cause for concern.

The bioavailability of iron in foods is influenced by other food components and food preparation methods. Vitamin C, meat, fish and an acidic pH all enhance iron absorption. There are many vegetables that are good sources of iron and vitamin C, and the promotion of their use in combinations that favour iron absorption should be undertaken (see Viteri, 1997, p. 17). Phytates, polyphenols and tannins inhibit iron absorption, and decreasing the consumption of foods such as tea, coffee, chocolate and soy products reduces the intake of these inhibitors. There are no programmatic experiences thus far to show that dietary diversification can effectively reduce iron deficiency anaemia.

Status of Other Anaemia Control Programmes

Malaria and intestinal parasites (especially hookworm) are important contributors to anaemia in endemic areas. A number of countries have explicitly included malaria and intestinal helminth control as part of their anaemia control programmes. The UNICEF survey showed that 20 countries have policies of regular de-worming or distribution of anthelmintics to school-aged children (e.g., Cuba, El Salvador, Indonesia, Niger, Sri Lanka, Thailand and Viet Nam). In many countries, de-worming activities are carried out via the school system, but several countries have special bi-annual mass campaigns to de-worm women and children.

In populations where hookworm is prevalent, effective treatment of this helminth infection has been shown to reduce the prevalence of iron deficiency and anaemia in school-aged children (Stolzfus et al., 1997). The role of anthelmintics and micronutrient supplements in the control of iron deficiency anaemia for this age group is also being addressed within the framework of the Partnership for Child Development - an international programme established in 1992 to improve the health, nutrition and education of children through school-based services. Currently, six countries are involved in this programme; Colombia, Ghana, India, Indonesia, Tanzania and Viet Nam. Although each country participating in the Partnership has different priorities for health intervention, all have a core package of interventions - anthelmintics, micronutrient supplements and participatory health education. These address the most common causes of ill-health in schoolchildren and offer greatest benefit at least cost (PCD, 1996).

Until recently, the use of benzimidazole anthelmintics during pregnancy and breastfeeding has been contra-indicated. A recent WHO consultation however concluded that, given the safety of anthelmintics, 'single dose, oral anthelmintic treatment can also be given to pregnant and lactating women' (WHO, 1995a). However, as a general rule, no drug should be given in the first trimester.

Vitamin A deficiency also contributes to anaemia. National policies ensuring vitamin A supplementation of children (reviewed in the previous section of this chapter), are in place in at least 61 countries. In 46 countries, women are routinely provided with a high-dose vitamin A supplement soon after delivery. In many countries, AIDS is also a major contributor to anaemia, particularly severe anaemia, and AIDS control programmes may be expected to play a part in anaemia reduction.