Chapter 2: Micronutrients

Iodine Deficiency Disorders
Vitamin A Deficiency
Iron Deficiency Anaemia
Folic Acid
Zinc
Calcium: an emerging issue for developing countries?
References

INTRODUCTION

This chapter presents new information on trends in micronutrient deficiencies. Since the publication of the Second Report on the World Nutrition Situation in 1992, great strides have been taken globally to implement a strategy of universal salt iodization, resulting in significant reductions in iodine deficiency disorders in all regions. One of the most dramatic effects of this global programme is protection from mental impairment for millions of new-borns who now have access to effectively iodized salt. Clinical vitamin A deficiency, resulting in blindness, is also on the decline, a most welcome trend. Iron deficiency anaemia, a problem in almost all countries, including industrialized countries, is finally receiving increased attention. Iron fortification programmes are getting off the ground in many countries, and preventive iron supplementation is receiving increased policy attention. Short sections on folic acid and zinc deficiency are included. Zinc deficiency may be an important determinant of maternal mortality in African women, and of childhood stunting. The chapter concludes with information on calcium and its purported relationship to osteoporosis.

Iodine Deficiency Disorders

Introduction

Iodine is required for the synthesis of thyroid hormones which in turn are needed for the regulation of metabolic activities of all cells throughout the life cycle. They are also required to ensure normal growth, especially of the brain, which occurs from foetal life to the end of the third postnatal year. Consequently, if severe enough, iodine deficiency will impair thyroid function, resulting in a lower metabolic rate, growth retardation and brain damage. The long-term consequence is irreversible mental retardation.

Iodine deficiency is the most prevalent cause of preventable mental retardation in the world (reviewed by Delange, 1994).

Reconceptualizing the Problem

Up to the early 1980s, goitre was considered the single and almost exclusively cosmetic consequence of iodine deficiency. Endemic goitre was seen as an exotic disorder affecting populations in developing countries especially those living in isolated subsistence economies. The concept was then developed by Dr Basil Hetzel and others that goitre was only the tip of the iceberg and that the consequences of iodine deficiency were much broader, including physical and mental retardation, increased perinatal mortality and other defects. From about 1983, these various effects have been grouped and referred to as iodine deficiency disorders or IDD (Hetzel, 1983). To date, IDD is still poorly recognized by the medical profession in many countries and is given short shrift in some of the major textbooks on paediatric nutrition.

Due to the coordinated efforts of a series of international organizations, including the International Council for Control of Iodine Deficiency Disorders (ICCIDD), the importance of IDD is now better recognized internationally. The sustainable elimination of IDD by the year 2000 was accepted as one of the priorities in the field of nutrition by the WHO and UNICEF in 1990, and was further endorsed by the World Summit for Children the same year.

Knowledge of the impact of iodine deficiency on intellectual development and the resulting costs to societies, including delayed socio-economic development, has played a significant role in mobilizing scientists, public health administrations and political leaders the world over to deal effectively with IDD (Pandav, 1996).

Changes in approach

Up to the early 1960s, the correction of IDD was almost exclusively focused on the administration of iodine in the form of solutions of potassium iodide or Lugol's solution. In spite of several effective salt iodization programmes in the United States and in Switzerland in the early 1920s, large preventive programmes were virtually untried in the developing world. Pilot studies using iodized oil as a source of long-lasting iodine supplementation at a population level were implemented in New Guinea in the early 1950s (McCullagh, 1963).

These were followed by campaigns offering iodized oil by the intramuscular route in several countries, including Ecuador, India, Nepal, Peru and the former Zaire. These campaigns resulted in a spectacular regression of goitre for periods up to ten years after one single injection. This approach also prevented the occurrence of endemic cretinism and endemic mental retardation (Dunn, 1987, p. 127). The efficacy and safety of iodized oil used during pregnancy in the prevention of endemic goitre and cretinism have been established (Delange, 1996).

In the late 1970s, concern emerged about disease transmission through the use of syringes for intramuscular injection of iodized oil. This was mostly in connection with the AIDS epidemic. Oral iodized oil was tried and its efficacy established, but, the period of protection was observed to be much shorter. At the same time, it was felt that the use of iodized oil (by either route) was not ideal for the long term because it required use of medical personnel and depended on access to individuals and communities.

The long-term solution for the sustainable elimination of iodine deficiency would more likely take place through increasing the iodine content of the general food supply. Although there had been iodization trials using drinking water, bread and sweets, the most promising vehicle was clearly common table salt. By 1991 universal salt iodization, i.e., all salt for human and animal consumption, was identified as the preferred means of reaching populations, including those consuming salt produced by small-scale artisanal saltworks. Thus the focus shifted from treatment of cases to working with the salt industry to upgrade technologies and management. The application of salt iodization technology to developing country settings has progressed enormously during the past five years. Comprehensive technical guides are available (Sullivan et al., 1995; Mannar and Dunn, 1995).

Iodine dietary requirements

Current recommendations made by WHO for dietary intake of iodine are shown in Table 5. These are slightly higher for three vulnerable groups (young infants, pregnant and breastfeeding women) than previous recommendations made by the National Academy of Sciences in the USA (NAS, 1989). This change was based on new information from iodine balance studies in infants. Delange (1993) has since recommended intakes of 90 mg iodine per day from birth to six years of age. This recommendation has now entered paediatric practice in a number of countries in both western and eastern Europe. This recommended level covers the needs of all infants, including pre-term infants.

Indicators

The indicators recommended by the involved agencies for assessing iodine deficiency and for defining degrees of severity are shown in Table 6. The selection of these criteria, made by an expert group convened in late 1992, was based on technical feasibility, cost and performance. They are purposely oriented towards public health action in the field and are not intended to cover the needs of an individual clinically affected by IDD.

The prevalence of goitre gives an idea of the past history of iodine nutrition at the population level. Palpation is the simplest method for measuring thyroid size. However, palpation becomes imprecise as the majority of goitres in a population diminish in size, i.e., following implementation of a national salt iodization scheme. In this case measurement of thyroid volume is more accurately performed by ultrasound. Portable ultrasound machines are available. Much of the recent IDD assessment work done in Europe was accomplished by ultrasonography transported across countries and borders by van (Delange et al., 1997). New normative values for thyroid volume in school-age children for assessment of IDD in populations were derived from this work. They were recently endorsed by WHO and ICCIDD (Table 7). These new norms are based on pooled samples of iodine-replete schoolchildren living in Europe and are applicable the world over.

Table 5: Recommended Dietary Intakes of Iodine for Populations

Age range/state	Intake mg/d (WHO, 1996)	RDA mg/d (NAS, 1989)
0-12 months	50	0-6 mths 40 6-12 mths 50
1-6 years	90	1-6 yr 70-90
7-12 years	120	7-10 yr 120
12 years to (and through) adulthood	150	150
Pregnancy	200	175
Lactation	200	200

Source: WHO (1996b, p.62) and NAS (1969, p.213)

Variable	Normal	Mild IDD	Moderate IDD	Severe IDD
Prevalence of goitre In school-age children (SAC) (%)	< 5	5-19.9	20-29.9	³ 30
Frequency of thyroid volume In SAC >97th centile by ultrasound (%)	< 5	5-19.9	20-29.9	³ 30
Median urinary Iodine In SAC and adults (mg/L)	100-200	50-99	20-49	< 20
Frequency of neonatal TSH >5 mU/L whole blood (%)	< 3	3-19.9	20-39.9	³ 40

Source: WHO/UNICEF/ICCIDD (1994, p. 28)

Age (years)	Thyroid volume - Upper limit of normal (ml)
	Boys	Girls
6	5.4	5.0
7	5.7	5.9
8	6.1	6.9
9	6.8	8.0
10	7.8	9.2
11	9.0	10.4
12	10.4	11.7
13	12.0	13.1
14	13.9	14.6
15	16.0	16.1

Source: Delange, F. et al. (1997) and WHO/ICCIDD (1997)

Neonatal thyroid stimulating hormone (TSH) assesses saturation of brain cell receptors and consequently measures the supply of thyroid hormones to the developing brain. Elevated neonatal TSH is therefore the only indicator which allows prediction of possible impairment of mental development. National screening programmes for congenital hypothyroidism, most usually based on the detection of elevated TSH, are in place in all industrialized countries. Evidence of elevated neonatal TSH has also been used to generate information on the extent of IDD in crowded urban slums in developing countries for advocacy purposes (Nordenberg et al., 1993).

Magnitude

The first evaluation of the magnitude of goitre on a world scale was published by WHO in 1960 (Kelly and Snedden, 1960, p 28). The total was reported to be "not far short of 200 million". This figure is an obvious underestimation because a number of countries were not surveyed. Also, the only indicator used was goitre by palpation which can underestimate both the true prevalence of goitre and the importance of iodine deficiency.

Estimates of populations affected by IDD about the time of the World Summit for Children were around 600 million people (WHO, 1990). It was not until 1994 that IDD, and not only goitre, was assessed country by country and for all regions. This new work applied the concept of risk of IDD, defined as 'living in areas with iodine deficiency and a total goitre rate above five per cent'.

By applying this criterion (and lowering the goitre rate cutoff from ten to five per cent), IDD was found to be a significant public health problem in 118 countries, affecting 1572 million people worldwide. This was higher than all previous estimates. In addition, some 655 million were affected by goitre, that is, 12% of the global population. This survey also yielded key information which provided the main motivation to eliminate IDD as a public health problem: some 11.2 million humans were affected by overt endemic cretinism and another 43 million people were affected by some degree of mental impairment (WHO/UNICEF/ICCIDD, 1993, p. 5).

Trends in Salt Iodization Rates since 1992

Rates of salt iodization in all regions have increased significantly since publication of the Second Report in 1992. These trends have been documented by the series of Progress of Nations reports put out by UNICEF, as well as periodic reports by WHO. In 1994, UNICEF helped to draw considerable media attention to the reporting of salt iodization rates by ranking countries according to efforts made to iodize salt. At that time 12 of the most seriously affected countries had household rates ranging from zero to 95% (UNICEF, 1994, p. 9).

In 1996, WHO reported on salt iodization rates for those countries with a population over one million and where IDD was recognized to be a public health problem, or where IDD would be a public health problem if salt iodization programmes ceased (WHO, 1996a).

Nineteen countries for which information was available were iodizing more than 90% of all salt produced for human consumption. A further 15 countries were iodizing more than 70% of their salt. Thus more than one half (57%) of the population of surveyed countries (some 2500 million) were obtaining iodine through consumption of iodized salt. In many of the remaining countries surveyed, the infrastructure to produce iodized salt had already been established and the proportion of salt iodized was judged likely to reach or exceed 90% by the year 2000. For this to occur, awareness of the importance of the problem and its cost-effective solution, as well as appropriate national and international political choice, would need to be maintained.

Some countries with an IDD public health problem which were unable to fully implement universal salt iodization (USI) were using iodized oil as a temporary measure.

Thirty-eight countries reported using iodized oil supplements, up from 21 countries in 1992. WHO stated however that 'no country has yet been identified in which universal salt iodization has been demonstrated to be impossible or less cost-effective than any feasible alternative' (WHO, 1996a).

During 1995 and 1996, UNICEF conducted household surveys on the use of iodized salt as part of their cluster surveys designed to evaluate progress towards the Summit goals. UNICEF reported towards the end of 1996 that 27 countries had reached the goal of 90% iodization (UNICEF, 1996, p. 20). A further 15 countries reported between 75% and 90% of household salt was iodized. Forty-eight developing countries with IDD which had no significant salt iodization programmes in 1994 now iodized more than half of their salt. Nigeria, with the largest population in Africa, reported reaching 97% salt iodization. The Democratic Republic of the Congo (formerly Zaire), where severe iodine deficiency has been documented for many decades, was reported to have access to iodized salt.

An updated report on salt iodization produced by UNICEF in 1997 summarized further impressive progress (UNICEF, 1997). This report provided more examples of very poor countries with historically severe IDD reaching significant national objectives. For example, Laos and Nepal reported iodization rates of more than 75%. All countries in South Asia and South-East Asia, including China, have national iodization schemes in place. Progress has also been impressive in Sub-Saharan Africa where all but four countries have implemented salt iodization programmes. While iodization rates tend to be lower in Sub-Saharan African, with only 11 of the 40 countries in this region reporting more than 75% of salt adequately iodized, progress continues to be made and momentum is high.

Progress has been dramatic in Central and South America, which have historically had very high prevalences of IDD. Half of the countries in this region iodize more than 90% of their salt. This can be attributed in part to longstanding and effective legislation. In 20 countries in this region, more than 90% of salt is iodized and in an additional 14 countries the rate is between 75% and 90%. There are still some countries in other regions where special efforts need to be made, including Afghanistan, Azerbaijan, Estonia, Kyrgyzstan, Latvia and Lithuania, where special efforts need to be exerted to set up effective programmes.

In summary, the implementation of universal salt iodization on a worldwide basis is a remarkable achievement that will have lasting effects on the lives of many millions of people. IDD elimination could, in due course, be named the most spectacular public health success of this century. It bears repeating, however, that the management systems put in place so far are fragile. They are extremely vulnerable to a range of both national or international factors that could easily interupt the supply of adequately iodized salt to families and communities. Vigilance, care and good monitoring (discussed below) are needed well into the future.

Table 8: Proportion of total population at risk of IDD by region in 1994 and 1997

WHO Region	% Population at risk of IDD
	1994	1997
Africa	32.8	23.4
Americas	23.1	6.6
Eastern Mediterranean	42.6	30.3
Europe	16.7	10.7
South-East Asia	35.9	14.4
Western Pacific	27.2	9.8
Total	28.9	13.7

Source: WHO/UNICEF/ICCIDD (1994) and WHO (1997a)

The decline in the proportion of the global population at risk of IDD following implementation of universal salt iodization is shown in Table 8. Between 1994 and 1997 this figure decreased from 28.9% to 13.7%, a reduction of over one half. Further progress may be especially challenging because of limited access to populations not yet reached.

Table 9: Impact of Salt Iodization on Goitre Prevalence and Urinary Iodine over a Nine-Year Period in Peru

Variables			1986	1995
Iodized salt
	Production (30-40 ppm) (% needs)		56	112
	Consumption at household (%)		20	81
	Iodine level at household (%)
		0 ppm	32	3.2
		> 20 ppm	36	75
Follow up of clusters of SAC
	(Sierra + Silva)
	Population at risk (M)		6	1.2
	Urinary Iodine (mg/L)		70	139
	TGR (median %)		47.7	10.8

Source: ICCIDD (1996a)

Variables			1990	1991	1992	1993	1994	May 1995	November 1995
Iodized Salt
	Iodine level at household (%)			USI
		0 ppm			33.5	21.2	13.7	8.5	9.6
		> 50 ppm			13.8	49.3	71.5	85.2	60.8
Follow up of a cluster of SAC
	Urinary Iodine (mg/L)		67			68			104
	TGR (%)		64.2			38.9		16.8	21.1

Source: From Lantum and Delange (unpublished)

Variables			1985	1996
Iodized Salt
	Production (60 ppm) % needs		0	> 100
	Iodine level at household (%)
		0 ppm	100	0
		> 15-20 ppm	0	82
Follow up of clusters of SAC
	Urinary Iodine		62% < 50 mg/L	76% > 100 mg/L
	TGR (%)		64.5	14

Source: Adapted from: Royal Government of Bhutan (1996)

A number of country case studies are now available; three sets of results are presented in Tables 9 to 11. In each of these studies, longitudinal follow-up was organized in sentinel sites by national authorities. An evaluation was then carried out by nationals in partnership with an international team, including senior members of ICCIDD.

In Bhutan, Cameroon and Peru, the increase in availability and consumption of adequately iodized salt at the household level was accompanied by an almost complete normalization of urinary iodine levels and a dramatic reduction in the prevalence of goitre. In Peru, within a period of nine years, the population at risk of IDD decreased from 6 to 1.2 million (ICCIDD, 1996a).

Peru did not have endemic cretinism in the past, but its neighbour, Ecuador, had both endemic cretinism and mental retardation. Both these conditions are now prevented by the salt iodization programme. Both Cameroon and Bhutan had endemic cretinism in the past, up to ten per cent in Bhutan. These dramatic consequences of iodine deficiency are now also prevented in Bhutan.

Trends in the Prevention of Mental Retardation

The main effect of dietary iodine deficiency is on the developing brain. The prevalence of the most severe form of brain damage, i.e. endemic cretinism, can be as high as one to ten per cent of the total population. This was seen in the past in parts of Bhutan, Democratic Republic of the Congo and Ecuador before the introduction of control programmes (Delange, 1994). The incidence of neonatal hypothyroidism, one of the mechanisms involved in the pathogenesis of endemic cretinism, can be as high as ten per cent of neonates. This rate is around 1/4000 (0.025 per cent) in iodine replete populations. Endemic cretinism is prevented by the correction of iodine deficiency in populations especially before and during pregnancy.

Cretinism is an extreme form of brain damage resulting from iodine deficiency. Even in populations known to be at risk of IDD where there is no evident cretinism, there is a downward shift in the frequency distribution of IQ in schoolchildren. This has been documented in Italy and Spain (Stanbury, 1993). The Ministry of Health of Indonesia estimated that before its current preventive campaign, 140 million IQ points were lost each year due to iodine deficiency (ICCIDD, 1996). A meta-analysis has indicated that iodine deficiency reduced the average population cognitive capacity by 10% to 15% (Bleichrodt and Born, 1993).

It was estimated that, up to 1990, about 40 million infants - one-third of all babies born each year in the world - were at some risk of mental impairment due to inadequate iodine in the maternal diet. In 1997, because of the worldwide increase in the use of iodized salt, 12 million children were expected to be spared that risk. In addition, the number of babies born as cretins was expected to have dropped by more than half, from around 120,000 in 1990 to under 55,000 worldwide (UNICEF, 1997a, p. 54).

Further research into the impact of iodine deficiency on intellectual development in conditions of mild deficiency (such as exist in Europe) would be beneficial.

Programme Monitoring

The massive implementation of salt iodization described in this Report is a spectacular achievement, but is not sufficient to ensure the sustainable elimination of IDD. Once set up, a salt iodization scheme needs constant monitoring so that corrective actions can take place without delay. Quality control of iodized salt production and consumption as well as surveys of representative groups are the main tools of monitoring (Dunn, 1996). Clinical and biochemical evidence of adequate iodine intake, regression of goitre and prevention of mental retardation are also important aspects of programme monitoring. Indeed in a Resolution made during the 49^th World Health Assembly in 1996, WHO urged Member States to

'increase efforts for the sustainability of the elimination of IDD by continuing monitoring, training and technical support, including advice on appropriate health legislation, and social communication...'

Criteria for monitoring progress towards the goal of IDD elimination as a public health problem have been established by WHO/UNICEF/ICCIDD (1994, p.36). These criteria include both process and impact indicators: i.e., the proportion of households consuming effectively iodized salt should be above 90%, less than 20% of the population should have urinary iodine <50 mg/L and the prevalence of enlarged thyroids by palpation or ultrasound should be below five percent. A cut-off for neonatal TSH was also presented: 97% of newborns should be < 5 mU/L of whole blood.

Iodized salt The goal is to ensure that 90% of household salt is adequately iodized. The level of iodization required to provide 150 mg of iodine per day via iodized salt is influenced by several factors. These include average salt intake, degree of iodine deficiency in the region, and estimated iodine loss from producer to consumer. Consequently the level of iodization at the production site will vary from one country to another and has varied from five to 100 ppm. Current recommendations are contained in WHO/UNICEF/ICCIDD (1996). They are 20 to 40 ppm at the site of production in order to ensure a median concentration of iodine of 100 to 200 mg/L in the urine.

Regular quality control of iodine concentration in salt at the production site can be done by titration methods or, in the case of imported salt, at the border by using rapid test kits. Periodic monitoring of salt iodine levels in retail shops, schools and households should also be performed using rapid test kits. Recent survey work conducted in Africa has indicated a need to continually improve available test kits, even for qualitative assessment which determines simply the presence or absence of iodine.

The second criteria is urinary iodine. The value 100 mg/L, recommended as the minimal desirable population median, was chosen because 100 mg corresponds to the requirements for daily synthesis of thyroid hormones. It also corresponds to the level below which iodine stores in the thyroid start to decrease. Monitoring urinary iodine is the best way to assess current access of populations to iodine. Unfortunately, at the moment, this still requires the transfer of samples collected in the field to well-equipped laboratories. There is an urgent need for rapid field test kits for urinary iodine and some applied research is being undertaken.

The third criteria is thyroid size. The cut-off of five per cent was proposed considering that in iodine replete populations up to five per cent of the population may have abnormal thyroid enlargement due to factors other than iodine deficiency.

Neonatal TSH The cut-off of not more than three per cent of values >5 mU/L was selected because it corresponds to the frequency found in iodine replete areas, such as Australia where this has been extensively documented (reviewed by Delange 1997). One good example of the use of neonatal thyroid screening to monitor an IDD programme is in Poland. Before salt iodization in Poland, the frequency of neonatal TSH above the cut-off point was about 40%. The normal value is below three per cent. Implementation of salt iodization was followed by a rapid shift of neonatal TSH to tower values. Four years later, the frequency of abnormal neonatal TSH was only about ten per cent and continues to decline (Delange, 1997). Neonatal thyroid screening implies technology and cost. However, because of the extreme sensitivity of this indicator we are likely to see more developing countries implementing neonatal TSH to monitor IDD control programmes in the near future.

Iodine-Induced Hyperthyroidism The critical importance of monitoring was recently illustrated by cases of iodine-induced hyperthyroidism (IIH) in Zimbabwe and possibly the former Zaire (Todd et al., 1995; and Bourdoux et al., 1996). IIH is included in the spectrum of abnormalities which can result from iodine deficiency and its correction. It is a severe condition and can be fatal. In these two countries, IIH resulted from the sudden introduction of uncontrolled and excessively iodized salt. In Zimbabwe 14 deaths occurred. IIH is fortunately extremely rare and measures can be put in place to identify and appropriately treat cases. Furthermore, the occurrence of new cases spontaneously decreases after a couple of years. It classically affects old individuals with large nodular goitres. The conditions of maximum risk are long-standing severe iodine deficiency and massive and rapid introduction of excessively iodized salt.

Other Control Measures

Iodized oil As indicated earlier, this procedure was initially used in emergency in severely affected areas where salt iodization was not feasible. About 12 million closes of iodized oil have been administered worldwide since 1955. Spectacular results have been achieved in terms of prevention and correction of goitre and prevention of endemic goitre and endemic cretinism, especially when the iodine supplementation was administered before or during early gestation. There are anecdotal reports from women participating in these programmes of feeling better and stronger after receiving capsules of iodized oil. This is conceivable considering the extremely low values of serum levels of thyroid hormones before the introduction of an iodized oil programme in severely affected populations. Extremely rare side-effects have been noted (Stanbury, in press) and the cost is low, some five US cents per individual per year of protection.

Iodized oil will remain an important technology well into the future for some parts of some countries. Iodized oil may also be of great value in emergency settings when dramatic political events disrupt the supply of iodized salt. It will be of use, as well, in circumstances of severe relapse of IDD due to rapid socio-economic decline, for example in the former USSR.

Iodized water Drinking water can be iodized by release of iodine from elastomers or by dropping iodine into the community water supply. This method has been tried on a pilot basis in a number of countries including: Burkina Faso, Cambodia, Central African Republic, Chile, China, Malaysia, Mali, Mexico, Sudan and Thailand, as well as Sicily in Europe and the US. An evaluation of these trials was carried out by the ICCIDD in 1996 (ICCIDD, 1997). Results showed that, when properly monitored, water iodization is efficacious in controlling iodine deficiency. Side-effects such as IIH are rare, and are probably similar in frequency to other methods. It is generally more expensive than iodized salt in large-scale national programmes. Its main use will be for targeted populations where special circumstances make iodized water more cost-effective and quicker to implement. One limitation is that water iodization is unlikely to be sustainable in poor rural communities and thus may require continual external funding. Water iodization can frequently compare favourably with iodized oil in terms of cost.

Iodized bread Pilot studies in the iodization of bread were conducted, especially in Russia, and these appeared efficious (Gerasimov et al., 1997). However, iodization of bread is probably not effective on a large scale in many countries because of marked regional differences in bread intake.

Vitamin A Deficiency

Introduction

Global progress is being made in combating ocular consequences of vitamin A deficiency (VAD), but efforts need to be intensified if the mortality-risk consequences associated with subclinical deficiency are to be fully controlled. Because VAD is caused by habitually low intake of vitamin A in relation to requirement, sustainable solutions lie in improving intake and controlling preventable factors that elevate requirement. The underlying cause of inadequate consumption and high need is related to poverty. Economic, social and environmental deprivation limits accessibility to, and consumption of, vitamin A-containing foods. This is particularly the case when physiological needs are greatest, namely during periods of rapid growth and development, i.e., infancy, early childhood and pregnancy, and during lactation when breastmilk carries the vitamin in a highly absorbable form from mother to infant. The major non-physiological factor that increases need is frequency of infections, including diarrhoea and other febrile illnesses such as measles. Strategies for sustained elimination of VAD, therefore, will have to consider both improving vitamin A consumption and limiting the risk of infection.

Indicators

Vitamin A status is best assessed by the total body content of vitamin A, which can be viewed as a continuum from deficiency to excess, with obvious health consequences at either extreme (Figure 5). The extremes are marked by specific indicators, for example in the case of severe depletion, by ocular signs (xerophthalmia, including night blindness) and very low serum retinol levels (<0.35 mmol/L). Physiological functions, however, are impaired before tissues are depleted. It is this stage of subclinical depletion of body stores that defines VAD and is thought to be the beginning of an increased occurrence in the severity of infectious illness and risk of death. Monitoring the prevalence of disease severity and deaths is too non-specific for attribution to a single nutrient, and, unfortunately, currently available biological indicators lack specificity and sensitivity for identifying subclinically depleted body stores. This has necessitated using prevalence values below arbitrary cut-offs specific for different vitamin A indicators. Blood retinol levels are the most commonly measured indicator of vitamin A status in surveys and, using a cut-off of 0.7 mmol/L, a prevalence > 10% has been set as defining a public health problem (WHO, 1996, p. 7).

Figure 5: Vitamin A Status

Consequences

The most obvious health consequences of severe VAD involve the visual system, affecting vision in low light or darkness, and dryness (xerosis) and disruption in the integrity of the surface of the conjunctiva and cornea (Bitot's spot, corneal clouding, ulceration). Occurrence of these signs is associated with elevated risk of blindness and death. Hidden consequences that occur even before eye signs are detectable include changes in surface linings of the gastrointestinal, respiratory, excretory and reproductive systems. In addition, the integrity of the immune system is impaired. Risk for severe disease and death is increased by these hidden changes. Only in the last decade have the mortality-associated risks of sub-clinical VAD been appreciated. A recent study from Nepal found that mortality risk is not limited to children. During pregnancy, even relatively mild night blindness was associated with greatly increased mortality risk (West et al., 1997). VAD also contributes to impaired growth and development, and to inefficient utilization of iron for haemoglobin production (Underwood and Arthur, 1996).

Goals

In 1990, the end of decade goal set for vitamin A was the virtual elimination of VAD and all its consequences, including blindness. Global progress in achieving this goal is tracked in this report by trends both in reduction of prevalence of xerophthalmia and low serum levels of vitamin A. The expectation is that as deficient populations progressively ascend on the continuum toward adequate vitamin A status (Figure 5), clinical signs will virtually disappear and the tower portion of population-based blood vitamin A distribution curves will shift toward adequacy. The risk of health consequences from VAD will remain, however, until serum retinol levels reach adequacy, which for relatively healthy vitamin A-sufficient populations means above 1.05 mmol/L (Flores et al., 1991).

To achieve and maintain adequate serum retinol levels among deprived populations, attention will need to be given not only to an increased dietary intake of vitamin A but also to infectious disease control, including protecting, promoting and supporting breastfeeding, immunizations and parasite control programmes. Acute and chronic infections independent of vitamin A status suppress serum retinol levels (Filteau et al., 1993). Hence, tracking serum retinol levels of vitamin A may in part serve as a proxy for progress in achieving other health-related goals even after clinical eye signs have been eliminated. This is the rationale WHO used in establishing two cut-off prevalences marking ascension toward adequacy on the vitamin A status continuum, e.g., less than 10% prevalence of serum levels under 0.7 mmol/L as a public health problem specific to VAD, but less than 5% for elimination of risk of all consequences of VAD (WHO, 1996). This section of the paper reports current prevalence of VAD, trends in progress toward the goal and progress in implementing control strategies.

Table 12: Trends in Prevalences of Clinical Signs of VAD Calculated from Instances where Multiple Surveys have been Reported

Country	Year	Indicator	Prevalence (%)	Percent Change per 10 years	Trend (percentage points/10 yrs)
India	1976	X1B	1.40
	1979		0.90
	1988-90		0.70	-42.0%	-0.58
Nepal	1979-80	X1B	0.60
	1981		0.64
	1996		0.50*	-10.0%	-0.06
Sri Lanka	1975-76	X1B	1.10
	1987		0.33	-60.0%	-0.64
Indonesia	1977-78	X1B	1.01
	1992		0.30	-48.5%	-0.49
Aceh (Regional)	1977	X1B	2.42
	1982-83		1.23
	1989		1.28	-40.0%	-0.95
Philippines	1982	Total	3.20
	1993		0.50	-78.0%	-2.50
Ethiopia	1980-81	X1B	1.00
	1996		0.50*	-32.3%	-0.32
Niger	1988	XN	2.01
	1992		2.47	+57.2%	+1.15
Bhutan	1976	Total	1.30
	1989		0.70	-35.6%	-0.46

Source: WHO (1995) and UNICEF et al. (1997b, p.20)

* Estimated X1B, actual data was XN only. See Annex 5 for explanation of X1B and XN.

Note: In cases where there are three different surveys, the difference between the earliest and the latest years is taken.

Clinical VAD Early in the 1980s, xerophthalmia was estimated to afflict 4-8 million pre-school age children and to cause half million cases of childhood blindness, two-thirds of whom died (Sommer et al., 1981). A large amount of data has been compiled since these estimates were made (WHO, 1995), and additional information obtained from UNICEF field offices and country reports at recent meetings (IVACG, 1997). In the last decade, the degree of increased activity related to VAD is reflected by the fact that 72 countries have conducted nationally representative surveys, 32 of which included assessment of ocular signs and symptoms and 40 of which included serum retinol. An additional 16 countries have surveys planned² (UNICEF et al., 1997b). Xerophthalmia rates in most surveys were based on night blindness (XN) and Bitot's spot (X1B) as the two most commonly reported clinical signs, and prevalence of serum retinol levels under 0.7 mmol/L as the most common expression of subclinical VAD. To date, only a few of these surveys were re-assessment surveys that could be used to document trends, particularly following implementation of control programmes.

² The survey in Eritrea was reported at the IVACG XVIII in Cairo in September 1997.

Region	Percent Clinical Prevalence		Numbers of Children Affected (millions)		Percent change per 10 years	Rate of Prevalence Change, 1985-95, percentage points/10 yrs
	1985	1995	1985	1995
South Asia	1.79	0.95	2.67	1.58	-47%	-0.84
East Asia/Pacific	0.43	0.25	0.66	0.40	-42%	-0.18
Latin America & the Caribbean	0.35	0.24	0.17	0.12	-31%	-0.11
East/South Africa	1.80	1.06	0.69	0.53	-41%	-0.74
West/Central Africa	1.40	0.87	0.53	0.45	-38%	-0.53
Middle East/North Africa	0.63	0.27	0.24	0.12	-57%	-0.36
Total	1.06	0.63	5.00	3.30	-41%	-0.43

Source: UNICEF et al., (1997b, p.21)

Data from 35 surveys of clinical VAD prevalence, judged to be sufficiently comparable for estimating regional prevalence at different time points, were used to develop a model from which the situation in 1985 could be more precisely interpolated. These 35 surveys are listed in Annex 4. This established a baseline against which to evaluate progress. Annex 5 provides a description of the method used.

Table 13 presents the clinical VAD prevalence and trend estimates by region for 1985 and 1995. The model estimates that five million children were clinically afflicted in 1985 in comparison to 3.3 million in 1995. The model estimate for 1995 is somewhat higher than the 2.8 million estimated by WHO using a different methodology (WHO, 1995, p. 4).

Regional variations in prevalence reductions are evident. Their meaning in terms of achieving elimination goals is clear when calculated in terms of percentage points per 10 years (pp/10 yrs). Global reduction in prevalence was occurring at a rate of 0.43 pp/10 yrs, with region-specific variations from a low of 0.11 in Latin America and the Caribbean to a high of 0.84 in South Asia. The end-of-decade global goal of elimination of the risk of VAD-related blindness will not be achieved at these rates.

Table 14: Year when Elimination of Clinical VAD will Occur at Current Reduction Rates, by region

Region	Percentage points/10 yr	Percent Clinical Prevalence (%)		Expected Years of Elimination of Clinical VAD
		1990 (year of the World Summit for Children)	2000
South Asia	-0.84	1.37	0.53	2006
East Asia/Pacific	-0.18	0.34	0.16	2008
Latin America/Caribbean	-0.11	0.29	0.18	2014
East/South Africa	-0.74	1.43	0.69	2009
West/Central Africa	-0.53	1.34	0.81	2015
Middle East/North Africa	0.36	0.35	-	-
Total	-0.43	0.84	0.41	2009

Table 14 shows the year when the risk of blindness - part of the decade goal - would be achieved, predicted by the model and barring circumstances that could disrupt current progress, e.g., civil unrest and disasters. Only the Middle East and North Africa region would achieve the year 2000 goal. Latin America and the Caribbean, with the lowest prevalence (0.29%) in 1990 would not reach the goal until 2014 and a similar time is needed by Western and Central Africa, where the prevalence in 1990 was four times higher (1.34%). Hence, although trends are encouraging, global reduction rates would have to increase and regional rates will need to be considerably accelerated.

This discussion of prevalence and trends has been based primarily on data available for pre-school-age children. In areas of endemic VAD, there are increasing numbers of reports that prevalences of night blindness in pregnant and breastfeeding women are similar to or exceed those in children (IVACG, 1997a). Due to limited survey information, this vulnerable group is only recently beginning to enter the global estimates of those with VAD. In view of recent reports from Nepal showing a reduction in maternal mortality brought about by weekly supplements of beta-carotene or vitamin A equivalent to 23,000 IU vitamin A (West et al., 1997), priority should be given to assessing populations of VAD pregnant women and including them in programmes.

Subclinical VAD The results of 42 surveys of sub-clinical VAD, assessed biochemically on the basis of low serum retinol in children under five years old, were compiled from WHO (1995) and UNICEF field office reports (UNICEF et al., 1997b). These are listed in Annex 6. Some of these surveys are subnational and extrapolation to a national basis has limitations. The cut-off of serum retinol less than 0.7 mmol/L although not usually associated with ocular signs, carries mortality-related risk. The prevalence of children under five who are subclinically deficient is much higher than for clinical VAD. Reported ranges exceed 70% in Burkina Faso and Mali, and are more than 40% in Côte D'Ivoire, Honduras and Mauritania. The prevalence rate in Indonesia is about 58%, according to a 1991 survey.

Global trends in sub-clinical prevalence estimates are less easily tracked than clinical deficiency. Confounding disease-related factors that vary in intensity from country to country, making cross-country and regional comparisons difficult to evaluate, influence serum retinol levels. Few data are available from representative repeat serum retinol surveys, particularly at a national level; in fact repeat survey data are currently available from only four countries, all of them in Latin America. These limited data are insufficient to develop a reliable predictive model from which to interpolate global or regional prevalence at different time points. Presumably global progress in reducing clinical VAD is being reflected by progress in reducing subclinical VAD, but it is not possible to substantiate this until sufficient data from repeat surveys become available.

Figure 6: Prevalence of Low Serum Retinol Levels in Countries in which Nationally Representative Surveys have been Undertaken since 1990

Source: Adapted from UNICEF et al., 1997b, p. 31

³ There is virtually no recent data for minority children in Canada.

Of the 78 countries where VAD is known to be a public health problem, 61 (78%) have policies supporting regular vitamin A supplementation of children (UNICEF et al., 1997b, p. 8). The majority of countries implementing vitamin A supplementation programmes have adopted the policy recommended by WHO/UNICEF/IVACG (1997). This calls for children aged 6-12 months to receive a 100,000 IU dose, and for children aged 12 months and over to receive a 200,000 IU dose of vitamin A once every four to six months. Fifteen countries use alternative supplementation regimens in which a lower dose, usually 50,000 IU, is provided. Coverage has been increased in recent years by providing supplements during National Immunization Days (NIDs) or other mass campaigns such as periodic anti-helminth campaigns. Thirty-four of 78 countries which have used NIDs for delivery increased coverage rates of children under five (UNICEF et al., 1997b, p. 22 and p. 32). While NIDs typically take place on a yearly basis, several countries have organized additional periods, such as Vitamin A week' or Vitamin A month', to achieve extensive biannual distribution.

It should be noted that in many countries NIDs are organized to eradicate polio and may be discontinued after the year 2000. In the long term, it is critical to integrate vitamin A supplementation into ongoing routine child immunization programmes or to develop other more sustainable ways to ensure that children receive supplements regularly until adequate intake from food sources is achieved. In many countries, vitamin A supplementation of young children has been successfully integrated into routine maternal child health visits, or is often linked to community-based nutrition improvement programmes.

Where VAD is a public health problem, WHO/UNICEF/IVACG (1997) recommend that all breastfeeding mothers receive a high dose supplement within eight weeks of delivery to improve her own status and raise the level of vitamin A in her breastmilk. Of 78 countries with recognized VAD, 46 have adopted this policy although coverage is highly variable (UNICEF et al., 1997b, p. 11).

Food-based approaches to increase the quantity and quality of micronutrients in diets, particularly to improve vitamin A intake, include home-based horticulture promotion and fortification of processed foods. Fortification of commonly consumed foods, such as sugar, cereals, flours, margarine and oils, is being pursued by governments in over half of the countries with a recognized VAD problem. In South East Asia, instant noodle fortification is occurring and other vehicles are being explored elsewhere. Although supplements continue to be routinely provided to address the immediate situation found in some of these countries, it is anticipated that a phase-in of fortified foods will sustain the progress achieved and allow supplementation to be phased-out. In other countries, such as Guatemala where xerophthalmia is rare but subclinical deficiency is still prominent, mandatory fortification of sugar has moved the country toward adequate vitamin A status. This has occurred in the absence of supplementation, and it is expected that the progress will continue and be sustained as long as fortification continues.

Lessons learned from the Guatemala fortification experience are valuable guidance for other Central American countries that have fortified sugar or have sugar fortification under preparation - Colombia, Ecuador, El Salvador, and Nicaragua - and for several countries in Asia, Africa and South America where feasibility is being explored. Reliance on a single fortification approach to control micronutrient deficiencies is a fragile strategy, even though it may not require changes in food-habits or knowledge. This was illustrated in Guatemala when the vitamin A fortification programme temporarily stopped in the 1980s and evidence of VAD reappeared. Similarly, in Venezuela when national economic adversity temporarily stopped flour fortification with iron, anaemia prevalence increased (Institute of Medicine, 1997). In the past, identification of a single widely consumed food vehicle to fortify has dominated efforts, but the potential to fortify different products to take advantage of more localized food availability and consumption patterns is increasingly clear. In addition, social marketing of fortified products is advised so as to inform consumers of the benefit of making wise food choices, both from natural food sources and what is likely to become a variety of fortified foods available in the future.

Another lesson learned from fortification experiences is the need for early government-private sector alliances, as well as alliances with other stake-holders (Ending Hidden Hunger, 1991). This is important to create among the private sector a sense of social responsibility for control of micronutrient deficiencies, and, in turn, elicit government recognition of private-sector economic risk concerns. Where possible, accommodating some private sector needs has provided incentives for voluntary private sector involvement. For example, in the Philippines where margarine is fortified, a government endorsement visible on the product as an 'acceptance seal' and for cost-recovery of initial capital investments was found to be an appropriate incentive. Now in the Philippines, the private-sector on its own initiative is considering a variety of food products for fortification. Multiple nutrient fortification is also being explored. In Venezuela, for example, wheat and maize flour are fortified with both iron and vitamin A.

Horticulture approaches are increasingly recognized for their effectiveness and potential sustainability in improving not only vitamin A status, but also micronutrient status generally. Recent evaluation of the large-scale horticultural intervention in Bangladesh has shown effectiveness in improving vitamin A status of those households that have home gardens, including increased consumption by children of vitamin A-rich garden produce (UNICEF, 1997a). Moreover, homestead gardening lends itself to adapting traditional preservation and preparation practices to improve nutrient retention, for example the indirect rather than direct sun solar drying of mangoes in Haiti and West Africa. Since several food sources of provitamin A also are rich sources of vitamin C, and contain iron, increased consumption of these foods addresses multiple nutrient needs. The importance of combining increased vitamin A levels in the food supply with nutrition education and appropriate social marketing that promotes consumption by the vulnerable groups is increasingly recognized (IVACG, 1997).

Socio-economic progress itself in many countries, including direct poverty-reduction programmes, probably accounts for part of the notable improvement in reducing prevalence of VAD. Specific interventions, however, have undoubtedly made an important contribution to VAD control, both through provision of vitamin A itself and through other health promotion and social measures. For example, during the early years of life, promotion of breastfeeding and supplementation of breastfeeding mothers immediately post-partum (breast milk being the infant's primary source of vitamin A), broad immunization coverage and oral rehydration therapy (ORT) use in diarrhoeal disease control are likely to have contributed significantly. Measles immunization may account for another part of the improvement, as higher measles immunization coverage can be shown to be associated with lower clinical VAD prevalence, taking account of economic status. And programmes that enhance the social status of women and empower them have been linked to family nutrition improvements.

Attention is given to the importance for sustainability of embedding VAD control programmes into community programmes. Supplementation programmes for the 6- to 72-month population accelerated around 1994, and using the measles immunization contact for delivery around nine months of age expanded. Thus supplementation and measles immunization may account for part of the global improvement in the last few years, particularly in the reduced prevalence of xerophthalmia.

It is crucial to take advantage of the present opportunity to firm up the evaluation experience from various health promotion programmes and to determine the relative impact of large-scale supplementation programmes. It is noteworthy, for example, that Indonesia, where supplementation has been a national programme since 1974, declared the country xerophthalmia-free at a public health level in 1994. However, Figure 6 shows that subclinical VAD persists in Indonesia at over 50% prevalence. Recently the Indonesian government has expanded its efforts to control VAD through supplementation of mothers and promotion of consumption of foods rich in vitamin A (UNICEF, 1997a), while private sector involvement in providing fortified foods, e.g., instant noodles, is being pursued.

With the continuation of present trends, clinical VAD may be eliminated in many parts of the world on average in the next 15 to 20 years. But many, especially children, will remain affected by sub-clinical deficiency, unless intervention programmes that include sustainable solutions are actively implemented and/or given increased emphasis. This is necessary to underpin the trend toward decreased prevalence of VAD. Therefore, it will be necessary to sustain major efforts to deal with both clinical and sub-clinical VAD for at least the next two decades.

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

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)

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.

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.

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

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