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Supplementation strategies to alleviate iron deficiency: Experiences from Indonesia
Nuaition Research, Vol. 18. No. 12, pp. 1943-1952.1998 Copyright Q 1998 Elsevier Science. Inc. Printed in the USA. All rights reserved 0271.5317/98 $19.00 + .OO
PI1 SO271-5317(98)00164-X SUPPLEMENTATION STRATEGIES TO ALLEVIATE IRON DEFICIENCY: EXPERIENCES FROM INDONESIA’ Werner Schultink, PhD ’& Drupadi Dillon, MD 2 ’Deutsche Gesellschaft ftir Technische Zusammenarbeit (GTZ) GmbH, Eschbom, Germany; ’ Regional Southeast Asian Ministers of Education Center for Community Nutrition at the University of Indonesia, Jakarta, Indonesia.
ABSTRACT Anemia, mainly caused by iron deficiency, is common in Indonesia, especially among pregnant women and infants. In pregnancy iron deficiency anemia is associated with undesirable birth outcome, and in infants with reduced mental and motor development. Iron status can be improved through dietary changes, food fortification, antehelminthic treatment, and supplementation. Supplementation offers the best chance for improvement on short term, although reported effectiveness of large scale programs is often limited. In Indonesia supplementation programs exist for pregnant women, female factory workers, and under-five children from poor families. Effectiveness of the programs is limited by tablet supply, program coverage, compliance and a possibly by a low vitamin A status, and the following changes should be considered to improve effectiveness. Tablets should also be distributed through channels other than the health sector, such as through traditional birth attendants. In order to decrease the iron deficiency prevalence during pregnancy young women/adolescent girls should be supplemented before they get pregnant. Infants should also be targeted by programs. Supplementation on a weekly in stead of daily basis should be considered especially under conditions where supplementation can be supervised such as in schools or factories. Since intake of vitamin A and zinc are also frequently deficient, a multi-supplementation should be strived for. Q199s~lsti~sci~~:e Inc. Key words: Anemia, Iron Supplementation Programs, Iron Deficiency
INTRODUCTION
As in many other developing countries, iron deficiency is the most common nutritional disorder in Indonesia (1). The population group most at risk are pregnant women and the prevalence of anemia (defined as hemoglobin < 110 g/L) among them is about 60% in Indonesia (2,3). Although anemia may be caused by other nutritional disorders such as vitamin B- 12 and/or folate deficiency, or by heriditary factors such as thalassemia-minor, iron deficiency is the main cause. In addition to pregnant women, other population categories such as preschool children and fertile age women are also at risk of becoming iron deficient. Although no reliable representative data are available on the nation-wide prevalence of iron deficiency among population categories
‘Corresponding author: Dr W Schultink, P.O. Box 3852, Jakarta 10038, Indonesia; Tel & Fax: +62-21-3907695; E-mail: [email protected] 1943
W. SCHULTINK and D. DILLON
other than pregnant women, scattered surveys indicate that the prevalence among preschoolers and fertile-age women may be as high as 30-50% (3,4). Especially at risk among preschoolers are infants. During the first year of life the growth rate is very high leading to a daily iron requirement which almost equals that of an adult man (5). It can therefore be expected that the prevalence of iron deficiency among infants is even higher than that among children aged 2-5 years. The consequences of iron deficiency are serious. Iron deficiency anemia during the first half of pregnancy is associated with low birth weight babies, premature delivery and even perinatal and fetal death (6,7). Among adults iron deficiency anemia leads to a S- 10% reduction in work output, not only when heavy physical labour is involved (8,9) but also in work requiring concentration and dexterity rather than physical input (10, 11). In infants, iron deficiency leads to a reduced motor and mental development, which if existing at an early stage and left untreated, may be irreversible (12,13). Children who had been iron deficient anemic during early childhood continued to have a lower school performance than their peers who had not been anemic (12). Possibilities to improve iron status include improvement of the diet, food fortification, antehelminthic treatment, and supplementation. The most efficient way to achieve an adequate iron absorption from the natural diet would be through an increased intake of fish and/or meat. In addition it would be important to reduce the intake of iron absorption inhibitors such as phytate, and to increase the intake of absorption enhancers such as vitamin C (14)which would facilitate the absorption of iron from plant sources. Considering the current socio-economic situation and the changes which can be expected in the near future it will probably still take quite some time before desirable changes in the diet would occur in large parts of the population. Fortification of selected foods would not require such a change in food pattern. Encouraging results from food fortification trials were recently published on the fortification of sugar (15), and wheat and maize flour (16). Also in Indonesia some experience exists with the fortification of foods such as instant noodles but it’s impact on iron status of the population is still unknown (3). An impact of antehelminthic treatment can be expected among populations where hookworm infestation is common, and trials among African populations indicate that antehelminthic treatment can significantly improve iron status (17). The efficacy to improve iron status through supplementation has been proven and considering the time and effort involved, and the general applicability, the most effective way to achieve an improvement on a short-term basis would probably be supplementation.
SUPPLEMENTATION
PROGRAMS AND STRATEGIES
TO BE CONSIDERED
In view of the negative consequences of iron deficiency during pregnancy and the demonstrated efficacy in improving iron status (18) an iron supplementation program for pregnant women was initiated more than a decade ago in Indonesia and this program is still running. In the framework of this program iron tablets are distributed free of charge to all pregnant women through the ante-natal health care program. The women should take one tablet a day, throughout the second and third trimester of pregnancy, providing them with 60 mg elemental iron per day (2). More recently the Indonesian Government also addressed the high prevalence of iron deficiency among non-pregnant working women and preschool children through a
IRON SUPPLEMENTATION
STRATEGIES
supplementation program. Considering the demonstrated efficacy of weekly supplementation among non-pregnant women (19) it was decided that female factory workers should be given iron supplements (60 mg Fe) once a week during four months a year. The supplements should be provided by the factory owners, because it is reasoned that they will also protit from the increased production capacity of these female workers after their iron status has been improved. Furthermore, pilot programs in poor villages of 8 provinces were started in 1996 with the aim to provide 20-30 mg iron per day for a period of 3 months to preschool children. This program was organized through the primary health care sector but the impact is still unknown. Although small scale field trials have shown that supplementation may alleviate iron deficiency among target groups (3,18), the effectiveness of large scale supplementation programs was often reported to be limited (2). Unfortunately, the same disappointing experience was made with the Indonesian supplementation program for pregnant women. The prevalence of anemia has not reduced much during the past 10 years. The reasons for this lack of success are the low coverage rate of the program, and the incomplete compliance of the women (20) as can be illustrated by a small cross-sectional study carried out among 107 pregnant women from SouthSulawesi in eastern Indonesia (21). The women in the study were selected by house-to-house visits made in several rural villages. Only a part of the pregnant women made timely use the antenatal care program; 64% of women who were in the second or third trimester of pregnancy had actually been checked by the health staff. Of the women who had visited the health center, only about two-thirds had received iron tablets, and of those who did get the tablets again about twothirds stated that they actually took the tablets. Finally, about 30% of the whole studied group of pregnant women stated that they had taken the iron supplements as prescribed. Another study among urban women from Jakarta confirmed this low compliance with tablet intake (22). Compliance is influenced by the amount, the frequency, and the duration ofprescribed supplement intake and a less frequent dosing schedule may improve compliance while still achieving similar effectiveness (23). Besides problems of health care usage and compliance on the consumer side there is also the factor of tablet availability on the supplier side influencing the effectiveness. The available number of iron tablets was reported to be insufficient to cover the needs of all pregnant women in Indonesia (2). According to 1996 population data, about 3 5 million women are pregnant each year who would need about 472 million tablets (4.5 months 1 tablet/day)(24). The large number of required tablets for pregnant women alone on the one hand, and the necessity to also give attention to other population groups such as infants stress the importance of investigating whether a supplementation less frequent than once-a-day would be possible. Another factor also deserves attention. Iron supplementation may have a limited efficacy when the target population has a low vitamin A status (25). Therefore vitamin A also may need to be supplemented besides iron. In order to alleviate iron deficiency through supplementation the following issues would need to be considered: distribution mechanisms, target groups additional to pregnant women, optimal frequency of supplementation for different target groups and varying circumstances, and important micronutrients other than iron to be supplemented. Distribution
of suonlements
W. SCHULTINK and D. DILLON
Based on the experiences made with the supplementation program for pregnant women it becomes clear that the coverage of tablet distribution and the compliance with the intake should be improved in order to increase the effectiveness of the program. In the existing program for pregnant women tablets are distributed by offtcial health personnel at the community health center and village health posts. It may not be good enough to use health personnel as the only channel for tablet distribution and as the only source of information regarding supplement ingestion, especially since health staff themselves may also be insufficiently informed (26). A study in West-Java compared the coverage and compliance under the existing distribution system with an alternative system in which traditional birth attendants were used to reach and educate the pregnant women (27). Under the alternative system using the traditional birth attendants (TBA) 92% of the targeted women were reported to be reached compared to 53% under the existing health care system. The avarage total number of tablets reported to be taken during pregnancy was 62 under the TBA system, whereas it was reported to be only 24 under the existing health care system. It was concluded that the coverage as well as the compliance with tablet intake was significantly influenced by the distribution system. A study among fertile-age women from the island of Lombok investigated the compliance with once-weekly tablet intake during a period of 8 weeks (28). One group of women received the tablets from village health workers (n=93). Another group received the tablets through religious community leaders (n=94) who have close contact to the population in this muslim community. At the end of the 8 weeks the women were asked how many tablets they had taken which was checked by counting the remaining tablets. The women who were provided by the health workers on average stated to have taken 5.8 tablets whereas the women provided by the religious leaders stated to have taken 6.9 of the tablets. The involvement of health personnel in the distribution of tablets may be a limiting factor in the consideration of expanding supplementation programs to other population groups besides pregnant women. When using once-weekly supplementation, enough iron tablets covering a 2-3 month period may be provided at once to target groups, and therewith reducing the involvement of health personnel. Such an approach would be effective provided that the compliance of the target group would be sufficiently high. In a study among preschool children from West-Java the mothers were instructed to supplement their children once per week (29). After a 9 week period during which health staff did not further intervene the prevalence of anemia had reduced from 37% to 16%, and 72% of a sub-group of children had proven supplement intake at the 6” week of supplementation. Target grouns Considering the high prevalence of iron deficiency among pregnant women and the associated negative consequences it is fully justified to have an iron supplementation program for pregnant women. However, the problem of iron deficiency in pregnancy should not be seen in isolation of other physiological states (30). Prevalence of low iron status (serum ferritin < 1$g/L) among a group of adolescent girls from Jakarta, Indonesia was 30% (3 1) and the prevalence of anemia among non-pregnant women in Indonesia is estimated to be around 30-40% (3). It is clear therefore that many women will already be iron deficient at the start of pregnancy and starting to supplement at the fourth or fifth month of pregnancy will be too late. In order to reduce the prevalence of iron deficiency during pregnancy the iron status of women prior to pregnancy should be improved. A suitable target group of such a supplementation to build iron stores would
IRON SUPPLEMENTATION
STRATEGIES
be adolescent girls. A placebo-controlled study among adolescent girls from Jakarta demonstrated that with a 3 month supplementation providing 60 mg iron and 20000 IU vitamin A once-a-week the prevalence of iron deficiency (ferritin < 15 rig/L)) decreased from 33% to 6%. Six months after ending the supplementation avarage ferritin concentration remained to be significantly erased at 35ug/L which is similar to levels as reported for young European and United States women (32, 33). Weekly supplementation of adolescent girls would therefore be a good strategy to alleviate iron deficiency during pregnancy, especially when the supplementation could be carried out in an environment where some control on supplement intake is possible as in schools. A population category other than pregnant women having a high prevalence of iron deficiency and who may suffer from permanent developmental damage are infants. At birth children should have iron stores as maternal endowment which should last 4-6 months, but between 6-l 2 months of age an infant should absorb daily about 0.1 mg Fe/kg body weight (34). Especially low birth weight babies have high iron requirements during infancy since they are born with smaller iron stores, and their relative growth rate is more rapid than that of term infants (5). The iron requirements at the age of 6- 12 months can not be fulfilled by the usual diets given to infants. These diets typically are home-made and consist of rice, some vegetables, and little or no animal protein source. Furthermore, the frequency of feeding is often less than 3 times a day. It should furthermore be considered that most infants are born from iron deficient mothers, and it is likely that their iron stores ate birth will not last for 6 months but will be depleted at an earlier age. Therefore, population groups who urgently would need attention are infants and young women. Freouencv of suonlementation Under large scale program conditions supplementation has shown to be less effective as expected, due to factors as coverage, sufficiency of tablets and compliance. Weekly supplementation should be considered as an alternative for the daily supplementation because it will reduce cost, has a limited influence on the absorption and balance of other micronutient such as zinc (35,36), reduces the chance on iron overload, may improve compliance when people are properly instructed, and could be used with less involvement of the health sector. Sofar, results on the comparison of weekly compared to daily supplementation were published from studies among Indonesian (29,37) and Chinese preschool children (38), Bolivian school children (39) Indonesian (23) and Chinese pregnant women (40) and Indonesian non-pregnant women (19) and adolescents (3 1). The results from all these studies indicated that the changes in hemoglobin in the weekly supplemented subjects were similar to the changes occurring in the daily supplemented subjects. It has to be considered though that each of the individual studies had only a limited power due to the small sample size. In the study among Chinese preschoolers (38) and among Indonesian adolescents (3 1) the increase in serum ferritin was higher in the daily supplemented subjects compared to those supplemented weekly. For the preschoolers it was argued that the increase in the daily supplemented children was due to a temporary overload. Among the adolescents it was observed that six months after ending the supplementation the remaining difference in ferritin concentration compared to pre-supplementation was 7 ug/L in weekly and 6 pg/L daily supplemented subjects. Therefore weekly iron supplementation was effective in building sustainable iron stores. Most studies which compared weekly and daily supplementation were carried out under supervised conditions and compared therefore the efficacy. Two small scale studies investigated the usage of weekly supplementation under unsupervised conditions,
W. SCHULTINK and D. DILLON one among pregnant women (23) and one among preschoolers (29). Before being applied under program conditions it would be useful to have more information about the effectiveness of weekly supplementation when used on a large scale under conditions where no supervision on tablet intake is possible. However, weekly supplementation may especially be useful when semisupervised tablet intake conditions are possible such as in schools and factories. The Indonesian Ministry of Health is applying this approach for female factory workers. Additional information would furthermore be useful on the usage of weekly supplementation in infants. Preliminary data are available from a study among 6-24 month old children from Vietnam, in whom weekly and daily supplementation of a combination of iron, zinc, and vitamin A was compared. The weekly group received 20 mg iron, 17 mg zinc and 17OOug retinol, and the daily group received 8 mg iron, 5 mg zinc, and 333ug retinol. A placebo group was included who did not receive any supplements. Supplementation lasted 3 months. Both supplemented groups showed the same significant increase in hemoglobin (8 g/L) where as the level in the placebo group remained the same. Addition of other micronutrients Studies among children (41,42) and pregnant women (43) with a sub-optimal vitamin A status showed that a combined iron and vitamin A supplement was more effective in improving iron status than iron supplementation alone, and that only supplementing with vitamin A already improved iron status. Although signs of clinical deficiency have become rare, low serum retinol concentrations are still common in Indonesia (44). It can therefore be expected that the efficacy of iron supplementation is not optimal in large parts of the population. Supplementation with vitamin A would therefore be beneficial, not only for the improvement of vitamin A status but also for iron status. The main reason for the high prevalence of iron deficiency is the fact that the daily diet contains a low amount of bioavailable iron. A diet low in iron is most probably also low in zinc. Although little data are available on the prevalence of zinc deficiency it can be expected that this is also high among many Southeast Asian populations. Several studies have shown that zinc deficiency is associated with growth retardation in children, and with increased morbidity. With respect to iron supplementation it has to be considered that giving daily supplements of iron may have a a negative influence on zinc status, and that when providing iron supplements it might be necessary to include zinc in the supplement. A multi-supplement containing iron-zinc-vitamin A may be more cost-effective to improve micronutrient status than providing iron alone.
CONCLUSION
In a population the degree of iron deficiency and the severity of it’s consequences are most serious among infants and pregnant women. Under the Indonesian circumstances large scale supplementation programs probably offer the fastest possibility for improvement. Infants would need to be supplemented between the age of 6 to 12 months when the requirements are highest. Ideally a supplement for infants should contain iron, zinc, and vitamin A. When given on a daily basis the supplement should contain about 15 mg iron, 15 mg zinc, and 350 ug retinol. However a community based study from Brazil showed that a daily supplementation program for infants was not effective because of a low compliance (45). In this Brazilian program mothers were instructed to give their 4-6 month old children every day a profylactic dose of 6 mg iron. The
IRON SUPPLEMENTATION
STRATEGIES
1949
drop-out rate was reported to be 55%. At the SEAMEO Nutrition Center in Jakarta-preliminary results of a study among infants demonstrated that a weekly dose of 25 mg iron, 20 mg zinc, and 15OOpgretinol proved to have a high efficacy in improving micronutrient status. This amount and mixture might function as a guideline for a weekly dose for infants which may have a better compliance and lower cost. Pregnant women still need to be supplemented with 60 mg iron per day during the second half of pregnancy as is currently practiced in Indonesia. It would need to be further investigated whether a weekly supplementation would be possible under program conditions and whether vitamin A and/or zinc should and could be added to the iron supplement. As already stated iron status during pregnancy should not be considered in isolation. In order to reduce the prevalence programmatic attention should be given to adolescent girls. It is recommended to provide these girls with a weekly supplement of 60 mg iron during at least 3-4 months per year. A large part of these girls can either be reached through schools or factories.
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Gross R, Schultink W, Juliawati. Treatment of anaemiawith weekly iron supplementation. The Lancet 1994; 344:821.
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Schultink W. Iron supplementation: compliance of target groups and frequency of tablet intake. Food and Nutrition Bulletin 1996; 17:22-26.
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Thorand B, Schultink W, Gross R, Sastroamidjojo S, Wentzel S. Efficiency of the iron supplementation program for pregnant women in Jeneponto, South Sulawesi, Indonesia. Asia Pacific Journal of Clinical Nutrition 1994; 3:2 1 l-2 15.
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Fahmida U. Comparison of compliance with iron tablet ingestion among fertile age women when distributed through health workers or religious leaders. Thesis, SEAMEOTROPMED Center Indonesia, Jakarta, 1997.
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Liu XN, Yang W, Zhang J, et al. Weekly iron supplementation pregnant women. FASEB J 1995; 9:A5658 (abstr.)
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Accepted for publication May 25, 1998.
is effective and safe in
PI1 SO271-5317(98)00164-X SUPPLEMENTATION STRATEGIES TO ALLEVIATE IRON DEFICIENCY: EXPERIENCES FROM INDONESIA’ Werner Schultink, PhD ’& Drupadi Dillon, MD 2 ’Deutsche Gesellschaft ftir Technische Zusammenarbeit (GTZ) GmbH, Eschbom, Germany; ’ Regional Southeast Asian Ministers of Education Center for Community Nutrition at the University of Indonesia, Jakarta, Indonesia.
ABSTRACT Anemia, mainly caused by iron deficiency, is common in Indonesia, especially among pregnant women and infants. In pregnancy iron deficiency anemia is associated with undesirable birth outcome, and in infants with reduced mental and motor development. Iron status can be improved through dietary changes, food fortification, antehelminthic treatment, and supplementation. Supplementation offers the best chance for improvement on short term, although reported effectiveness of large scale programs is often limited. In Indonesia supplementation programs exist for pregnant women, female factory workers, and under-five children from poor families. Effectiveness of the programs is limited by tablet supply, program coverage, compliance and a possibly by a low vitamin A status, and the following changes should be considered to improve effectiveness. Tablets should also be distributed through channels other than the health sector, such as through traditional birth attendants. In order to decrease the iron deficiency prevalence during pregnancy young women/adolescent girls should be supplemented before they get pregnant. Infants should also be targeted by programs. Supplementation on a weekly in stead of daily basis should be considered especially under conditions where supplementation can be supervised such as in schools or factories. Since intake of vitamin A and zinc are also frequently deficient, a multi-supplementation should be strived for. Q199s~lsti~sci~~:e Inc. Key words: Anemia, Iron Supplementation Programs, Iron Deficiency
INTRODUCTION
As in many other developing countries, iron deficiency is the most common nutritional disorder in Indonesia (1). The population group most at risk are pregnant women and the prevalence of anemia (defined as hemoglobin < 110 g/L) among them is about 60% in Indonesia (2,3). Although anemia may be caused by other nutritional disorders such as vitamin B- 12 and/or folate deficiency, or by heriditary factors such as thalassemia-minor, iron deficiency is the main cause. In addition to pregnant women, other population categories such as preschool children and fertile age women are also at risk of becoming iron deficient. Although no reliable representative data are available on the nation-wide prevalence of iron deficiency among population categories
‘Corresponding author: Dr W Schultink, P.O. Box 3852, Jakarta 10038, Indonesia; Tel & Fax: +62-21-3907695; E-mail: [email protected] 1943
W. SCHULTINK and D. DILLON
other than pregnant women, scattered surveys indicate that the prevalence among preschoolers and fertile-age women may be as high as 30-50% (3,4). Especially at risk among preschoolers are infants. During the first year of life the growth rate is very high leading to a daily iron requirement which almost equals that of an adult man (5). It can therefore be expected that the prevalence of iron deficiency among infants is even higher than that among children aged 2-5 years. The consequences of iron deficiency are serious. Iron deficiency anemia during the first half of pregnancy is associated with low birth weight babies, premature delivery and even perinatal and fetal death (6,7). Among adults iron deficiency anemia leads to a S- 10% reduction in work output, not only when heavy physical labour is involved (8,9) but also in work requiring concentration and dexterity rather than physical input (10, 11). In infants, iron deficiency leads to a reduced motor and mental development, which if existing at an early stage and left untreated, may be irreversible (12,13). Children who had been iron deficient anemic during early childhood continued to have a lower school performance than their peers who had not been anemic (12). Possibilities to improve iron status include improvement of the diet, food fortification, antehelminthic treatment, and supplementation. The most efficient way to achieve an adequate iron absorption from the natural diet would be through an increased intake of fish and/or meat. In addition it would be important to reduce the intake of iron absorption inhibitors such as phytate, and to increase the intake of absorption enhancers such as vitamin C (14)which would facilitate the absorption of iron from plant sources. Considering the current socio-economic situation and the changes which can be expected in the near future it will probably still take quite some time before desirable changes in the diet would occur in large parts of the population. Fortification of selected foods would not require such a change in food pattern. Encouraging results from food fortification trials were recently published on the fortification of sugar (15), and wheat and maize flour (16). Also in Indonesia some experience exists with the fortification of foods such as instant noodles but it’s impact on iron status of the population is still unknown (3). An impact of antehelminthic treatment can be expected among populations where hookworm infestation is common, and trials among African populations indicate that antehelminthic treatment can significantly improve iron status (17). The efficacy to improve iron status through supplementation has been proven and considering the time and effort involved, and the general applicability, the most effective way to achieve an improvement on a short-term basis would probably be supplementation.
SUPPLEMENTATION
PROGRAMS AND STRATEGIES
TO BE CONSIDERED
In view of the negative consequences of iron deficiency during pregnancy and the demonstrated efficacy in improving iron status (18) an iron supplementation program for pregnant women was initiated more than a decade ago in Indonesia and this program is still running. In the framework of this program iron tablets are distributed free of charge to all pregnant women through the ante-natal health care program. The women should take one tablet a day, throughout the second and third trimester of pregnancy, providing them with 60 mg elemental iron per day (2). More recently the Indonesian Government also addressed the high prevalence of iron deficiency among non-pregnant working women and preschool children through a
IRON SUPPLEMENTATION
STRATEGIES
supplementation program. Considering the demonstrated efficacy of weekly supplementation among non-pregnant women (19) it was decided that female factory workers should be given iron supplements (60 mg Fe) once a week during four months a year. The supplements should be provided by the factory owners, because it is reasoned that they will also protit from the increased production capacity of these female workers after their iron status has been improved. Furthermore, pilot programs in poor villages of 8 provinces were started in 1996 with the aim to provide 20-30 mg iron per day for a period of 3 months to preschool children. This program was organized through the primary health care sector but the impact is still unknown. Although small scale field trials have shown that supplementation may alleviate iron deficiency among target groups (3,18), the effectiveness of large scale supplementation programs was often reported to be limited (2). Unfortunately, the same disappointing experience was made with the Indonesian supplementation program for pregnant women. The prevalence of anemia has not reduced much during the past 10 years. The reasons for this lack of success are the low coverage rate of the program, and the incomplete compliance of the women (20) as can be illustrated by a small cross-sectional study carried out among 107 pregnant women from SouthSulawesi in eastern Indonesia (21). The women in the study were selected by house-to-house visits made in several rural villages. Only a part of the pregnant women made timely use the antenatal care program; 64% of women who were in the second or third trimester of pregnancy had actually been checked by the health staff. Of the women who had visited the health center, only about two-thirds had received iron tablets, and of those who did get the tablets again about twothirds stated that they actually took the tablets. Finally, about 30% of the whole studied group of pregnant women stated that they had taken the iron supplements as prescribed. Another study among urban women from Jakarta confirmed this low compliance with tablet intake (22). Compliance is influenced by the amount, the frequency, and the duration ofprescribed supplement intake and a less frequent dosing schedule may improve compliance while still achieving similar effectiveness (23). Besides problems of health care usage and compliance on the consumer side there is also the factor of tablet availability on the supplier side influencing the effectiveness. The available number of iron tablets was reported to be insufficient to cover the needs of all pregnant women in Indonesia (2). According to 1996 population data, about 3 5 million women are pregnant each year who would need about 472 million tablets (4.5 months 1 tablet/day)(24). The large number of required tablets for pregnant women alone on the one hand, and the necessity to also give attention to other population groups such as infants stress the importance of investigating whether a supplementation less frequent than once-a-day would be possible. Another factor also deserves attention. Iron supplementation may have a limited efficacy when the target population has a low vitamin A status (25). Therefore vitamin A also may need to be supplemented besides iron. In order to alleviate iron deficiency through supplementation the following issues would need to be considered: distribution mechanisms, target groups additional to pregnant women, optimal frequency of supplementation for different target groups and varying circumstances, and important micronutrients other than iron to be supplemented. Distribution
of suonlements
W. SCHULTINK and D. DILLON
Based on the experiences made with the supplementation program for pregnant women it becomes clear that the coverage of tablet distribution and the compliance with the intake should be improved in order to increase the effectiveness of the program. In the existing program for pregnant women tablets are distributed by offtcial health personnel at the community health center and village health posts. It may not be good enough to use health personnel as the only channel for tablet distribution and as the only source of information regarding supplement ingestion, especially since health staff themselves may also be insufficiently informed (26). A study in West-Java compared the coverage and compliance under the existing distribution system with an alternative system in which traditional birth attendants were used to reach and educate the pregnant women (27). Under the alternative system using the traditional birth attendants (TBA) 92% of the targeted women were reported to be reached compared to 53% under the existing health care system. The avarage total number of tablets reported to be taken during pregnancy was 62 under the TBA system, whereas it was reported to be only 24 under the existing health care system. It was concluded that the coverage as well as the compliance with tablet intake was significantly influenced by the distribution system. A study among fertile-age women from the island of Lombok investigated the compliance with once-weekly tablet intake during a period of 8 weeks (28). One group of women received the tablets from village health workers (n=93). Another group received the tablets through religious community leaders (n=94) who have close contact to the population in this muslim community. At the end of the 8 weeks the women were asked how many tablets they had taken which was checked by counting the remaining tablets. The women who were provided by the health workers on average stated to have taken 5.8 tablets whereas the women provided by the religious leaders stated to have taken 6.9 of the tablets. The involvement of health personnel in the distribution of tablets may be a limiting factor in the consideration of expanding supplementation programs to other population groups besides pregnant women. When using once-weekly supplementation, enough iron tablets covering a 2-3 month period may be provided at once to target groups, and therewith reducing the involvement of health personnel. Such an approach would be effective provided that the compliance of the target group would be sufficiently high. In a study among preschool children from West-Java the mothers were instructed to supplement their children once per week (29). After a 9 week period during which health staff did not further intervene the prevalence of anemia had reduced from 37% to 16%, and 72% of a sub-group of children had proven supplement intake at the 6” week of supplementation. Target grouns Considering the high prevalence of iron deficiency among pregnant women and the associated negative consequences it is fully justified to have an iron supplementation program for pregnant women. However, the problem of iron deficiency in pregnancy should not be seen in isolation of other physiological states (30). Prevalence of low iron status (serum ferritin < 1$g/L) among a group of adolescent girls from Jakarta, Indonesia was 30% (3 1) and the prevalence of anemia among non-pregnant women in Indonesia is estimated to be around 30-40% (3). It is clear therefore that many women will already be iron deficient at the start of pregnancy and starting to supplement at the fourth or fifth month of pregnancy will be too late. In order to reduce the prevalence of iron deficiency during pregnancy the iron status of women prior to pregnancy should be improved. A suitable target group of such a supplementation to build iron stores would
IRON SUPPLEMENTATION
STRATEGIES
be adolescent girls. A placebo-controlled study among adolescent girls from Jakarta demonstrated that with a 3 month supplementation providing 60 mg iron and 20000 IU vitamin A once-a-week the prevalence of iron deficiency (ferritin < 15 rig/L)) decreased from 33% to 6%. Six months after ending the supplementation avarage ferritin concentration remained to be significantly erased at 35ug/L which is similar to levels as reported for young European and United States women (32, 33). Weekly supplementation of adolescent girls would therefore be a good strategy to alleviate iron deficiency during pregnancy, especially when the supplementation could be carried out in an environment where some control on supplement intake is possible as in schools. A population category other than pregnant women having a high prevalence of iron deficiency and who may suffer from permanent developmental damage are infants. At birth children should have iron stores as maternal endowment which should last 4-6 months, but between 6-l 2 months of age an infant should absorb daily about 0.1 mg Fe/kg body weight (34). Especially low birth weight babies have high iron requirements during infancy since they are born with smaller iron stores, and their relative growth rate is more rapid than that of term infants (5). The iron requirements at the age of 6- 12 months can not be fulfilled by the usual diets given to infants. These diets typically are home-made and consist of rice, some vegetables, and little or no animal protein source. Furthermore, the frequency of feeding is often less than 3 times a day. It should furthermore be considered that most infants are born from iron deficient mothers, and it is likely that their iron stores ate birth will not last for 6 months but will be depleted at an earlier age. Therefore, population groups who urgently would need attention are infants and young women. Freouencv of suonlementation Under large scale program conditions supplementation has shown to be less effective as expected, due to factors as coverage, sufficiency of tablets and compliance. Weekly supplementation should be considered as an alternative for the daily supplementation because it will reduce cost, has a limited influence on the absorption and balance of other micronutient such as zinc (35,36), reduces the chance on iron overload, may improve compliance when people are properly instructed, and could be used with less involvement of the health sector. Sofar, results on the comparison of weekly compared to daily supplementation were published from studies among Indonesian (29,37) and Chinese preschool children (38), Bolivian school children (39) Indonesian (23) and Chinese pregnant women (40) and Indonesian non-pregnant women (19) and adolescents (3 1). The results from all these studies indicated that the changes in hemoglobin in the weekly supplemented subjects were similar to the changes occurring in the daily supplemented subjects. It has to be considered though that each of the individual studies had only a limited power due to the small sample size. In the study among Chinese preschoolers (38) and among Indonesian adolescents (3 1) the increase in serum ferritin was higher in the daily supplemented subjects compared to those supplemented weekly. For the preschoolers it was argued that the increase in the daily supplemented children was due to a temporary overload. Among the adolescents it was observed that six months after ending the supplementation the remaining difference in ferritin concentration compared to pre-supplementation was 7 ug/L in weekly and 6 pg/L daily supplemented subjects. Therefore weekly iron supplementation was effective in building sustainable iron stores. Most studies which compared weekly and daily supplementation were carried out under supervised conditions and compared therefore the efficacy. Two small scale studies investigated the usage of weekly supplementation under unsupervised conditions,
W. SCHULTINK and D. DILLON one among pregnant women (23) and one among preschoolers (29). Before being applied under program conditions it would be useful to have more information about the effectiveness of weekly supplementation when used on a large scale under conditions where no supervision on tablet intake is possible. However, weekly supplementation may especially be useful when semisupervised tablet intake conditions are possible such as in schools and factories. The Indonesian Ministry of Health is applying this approach for female factory workers. Additional information would furthermore be useful on the usage of weekly supplementation in infants. Preliminary data are available from a study among 6-24 month old children from Vietnam, in whom weekly and daily supplementation of a combination of iron, zinc, and vitamin A was compared. The weekly group received 20 mg iron, 17 mg zinc and 17OOug retinol, and the daily group received 8 mg iron, 5 mg zinc, and 333ug retinol. A placebo group was included who did not receive any supplements. Supplementation lasted 3 months. Both supplemented groups showed the same significant increase in hemoglobin (8 g/L) where as the level in the placebo group remained the same. Addition of other micronutrients Studies among children (41,42) and pregnant women (43) with a sub-optimal vitamin A status showed that a combined iron and vitamin A supplement was more effective in improving iron status than iron supplementation alone, and that only supplementing with vitamin A already improved iron status. Although signs of clinical deficiency have become rare, low serum retinol concentrations are still common in Indonesia (44). It can therefore be expected that the efficacy of iron supplementation is not optimal in large parts of the population. Supplementation with vitamin A would therefore be beneficial, not only for the improvement of vitamin A status but also for iron status. The main reason for the high prevalence of iron deficiency is the fact that the daily diet contains a low amount of bioavailable iron. A diet low in iron is most probably also low in zinc. Although little data are available on the prevalence of zinc deficiency it can be expected that this is also high among many Southeast Asian populations. Several studies have shown that zinc deficiency is associated with growth retardation in children, and with increased morbidity. With respect to iron supplementation it has to be considered that giving daily supplements of iron may have a a negative influence on zinc status, and that when providing iron supplements it might be necessary to include zinc in the supplement. A multi-supplement containing iron-zinc-vitamin A may be more cost-effective to improve micronutrient status than providing iron alone.
CONCLUSION
In a population the degree of iron deficiency and the severity of it’s consequences are most serious among infants and pregnant women. Under the Indonesian circumstances large scale supplementation programs probably offer the fastest possibility for improvement. Infants would need to be supplemented between the age of 6 to 12 months when the requirements are highest. Ideally a supplement for infants should contain iron, zinc, and vitamin A. When given on a daily basis the supplement should contain about 15 mg iron, 15 mg zinc, and 350 ug retinol. However a community based study from Brazil showed that a daily supplementation program for infants was not effective because of a low compliance (45). In this Brazilian program mothers were instructed to give their 4-6 month old children every day a profylactic dose of 6 mg iron. The
IRON SUPPLEMENTATION
STRATEGIES
1949
drop-out rate was reported to be 55%. At the SEAMEO Nutrition Center in Jakarta-preliminary results of a study among infants demonstrated that a weekly dose of 25 mg iron, 20 mg zinc, and 15OOpgretinol proved to have a high efficacy in improving micronutrient status. This amount and mixture might function as a guideline for a weekly dose for infants which may have a better compliance and lower cost. Pregnant women still need to be supplemented with 60 mg iron per day during the second half of pregnancy as is currently practiced in Indonesia. It would need to be further investigated whether a weekly supplementation would be possible under program conditions and whether vitamin A and/or zinc should and could be added to the iron supplement. As already stated iron status during pregnancy should not be considered in isolation. In order to reduce the prevalence programmatic attention should be given to adolescent girls. It is recommended to provide these girls with a weekly supplement of 60 mg iron during at least 3-4 months per year. A large part of these girls can either be reached through schools or factories.
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Accepted for publication May 25, 1998.
is effective and safe in