![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Nutritional Intervention Research Unit and * Biostatistics Unit, MRC, Parow, South Africa, and ** UNICEF, New York, NY
3To whom correspondence should be addressed. E-mail: marius.smuts{at}mrc.ac.za.
 |
ABSTRACT |
|---|
 TOP ABSTRACT SUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
KEY WORDS: • iron • zinc • multiple micronutrient supplementation • infant’s growth • anemia
In the developing world, many vulnerable population groups suffer from multiple micronutrient deficiencies, and iron, vitamin A, and iodine are the ones most commonly reported. Infants are likely to have multiple, concurrent deficiencies, because the same causative factors are responsible for deficiency of different micronutrients. The cereal-based diets commonly consumed in developing countries are rich in phytate and low in animal products, predisposing people to insufficient absorption of both iron and zinc (1), and low intakes of several vitamins.
In South Africa, a national survey in 1994 showed that, for children aged 6–71 mo, the prevalence of marginal vitamin A deficiency (serum retinol < 0.7 µmol/L) and anemia [hemoglobin (Hb)4 < 110 g/L] was 33% and 20%, respectively. However, in the age category 6–11 mo, the prevalence of anemia was 48%; 25% of the children were stunted, whereas 10% were underweight. Interprovincial differences were observed, and children living in rural areas, whose mothers had low educational levels, were affected the most (2). A national food consumption survey showed that the great majority of children in South Africa consumed a diet of poor nutrient density, with the nutrient intake of those living in rural areas being considerably poorer than that of children living in urban areas (3).
Adequate intakes of iron, vitamin A, zinc, iodine, and other micronutrients are essential for growth, as well as mental and motor development, and for the prevention of disease. Children with micronutrient deficiencies often present with linear growth retardation, higher morbidity and mortality, and reduced psychomotor development, such that those who survive have less possibility of developing to their full potential (4,5). Exclusive breast-feeding is considered sufficient to provide adequate nutrition for infants during the first 6 mo of life (6). However, the transition to complementary foods in the process of weaning children to household diets is associated with greatly increased risks of nutrient deficiencies (7), due to the low density and/or poor bioavailability of certain nutrients in some household diets. It is well known that anemia is common in infants even in industrialized nations (8,9) and that obtaining sufficient zinc from dietary sources is a challenge in most settings (7). The consequence may be widespread prevalence of deficiencies of iron, zinc, and other micronutrients from 7 mo of age onward, especially in low-income societies (10,11). Providing for optimal nutrition status of infants born under the least favorable socioeconomic and climatic conditions would require exclusive breast-feeding during the first 6 mo of life, with the possible application of routine dietary enrichment and/or supplementation with selected micronutrients during the period of weaning transition (12).
Combining multiple micronutrients in a single delivery mechanism has been suggested as a cost-effective way to achieve multiple benefits (13,14). Some studies have questioned the effectiveness of nutrients combined within a supplement because of possible interactions among the nutrients and interference in their absorption (15,16). The aim of the study was to investigate the efficacy of multiple micronutrient supplementation (daily and weekly) on the micronutrient, anthropometric, and morbidity status of infants. A weekly supplement compared with a daily supplement was included because of data showing that intermittent (e.g., weekly) micronutrient supplementation could be less expensive and easier for participants to follow (17). Finally, a daily iron-only treatment group was added to identify any effects of other vitamins and minerals on iron absorption and metabolism.
|
SUBJECTS AND METHODS |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
The study was carried out in the Valley of a Thousand Hills, situated 
40 km northwest of the coastal city of Durban in the KwaZulu-Natal Province, South Africa. This is a rural area with an estimated population of 200,000 people. The population density is low, because the families are scattered over a large mountainous area. The study was done through the Community Based Health Programme of The Valley Trust, a nongovernmental organization that operates through 12 health posts and that has >100 community health workers.
Subject selection and study design
Infants aged 6–12 mo were recruited through the health posts. The sample size was calculated based on the comparison of a fall in standardized weight for age from –0.65 to –0.95 for the daily multiple micronutrient supplement (DMM) group compared with a fall from –0.65 to –1.20 in the placebo (P) group. For a two-group repeated measures ANOVA with 7 levels (mo 0 to 6) a sample size of 256 per group will provide the analysis with 80% power when the significance level is 5%. The aim was to include at least 70 infants per group (65 + 5 dropouts). We enrolled 290 infants into the study. Exclusion criteria included premature birth (<37 wk gestation), low birth weight (<2500 g), severe wasting [<–3 weight-for-height Z-score (WHZ)], Hb < 80 g/L, and fever (>39°C) on the day of blood sampling, as described in further detail by Smuts et al. (18).
The study had a randomized, double-blind, placebo-controlled design. Children were randomly assigned to 1 of 4 intervention groups using a simple computer program provided to all participating countries. Group 1 (DMM) received a daily supplement containing 1 daily allowance of multiple micronutrients for young children. Group 2 (P) received a daily placebo supplement containing no micronutrients. Group 3 (WMM) received a weekly supplement containing 2 daily allowances of multiple micronutrients for young children and a placebo supplement on the other days of the week. Group 4 (DI) was given a daily supplement containing 10 mg of elemental iron.
Supplements
Roche Laboratories was responsible for the final blend of the product, and a private laboratory in Peru (Hersil SA) for the production and quality control of the supplements. The supplements were manufactured as large chewable tablets or foodlets, which were easy to break and dissolve. A week’s supply of foodlets was wrapped in identical coded blister packs, and all foodlets had the same taste, color, and flavor. Three of the groups (P, DI, and DMM) had blisters with 7 foodlets, and, within each group, all foodlets had the same composition; the 4th group (WMM) had blisters that included 6 placebo foodlets and one 2-daily-allowance foodlet always placed in the same position within the blister arrangement. Codes were kept by UNICEF (United Nations Children’s Fund), New York, and were revealed at the end of the study, during the final statistical analyses at the Medical Research Council in South Africa.
Consumption of foodlets
Blister packs and working materials were color coded to facilitate and simplify the identification of groups. Because the houses were scattered over a large mountainous area, it was impossible for the community health workers to visit each household every day. Therefore mothers were provided with a 1 mo foodlet supply. Each mother received a color-coded container to store the foodlets. The mothers and/or caregivers were given demonstrations on how to crumble and mix the foodlet with porridge. Mothers were trained to mix foodlets with a small quantity of porridge (predominantly maize meal), because it was important that the child should eat the entire portion mixed. The community health workers monitored compliance using a short questionnaire and observation during weekly visits. The number of foodlets removed from the previous week’s blister pack was counted and recorded. This recorded compliance was verified retrospectively by means of a questionnaire to both the caretakers and community health workers at the end of the study.
Measurements
Questionnaire. The questionnaire was developed according to the recommendations of Gross and Schultink (19) and comprised 4 different sections: 1) the household questionnaire, which was used at baseline only; 2) the monthly weight and height recording form, which also included the date of measurement; 3) the weekly health visit recording form; and 4) the weekly health and infant feeding information questionnaire.
Anthropometry. Infants’ anthropometric measurements were measured on a monthly basis. With subjects in light clothing, weight was recorded to the nearest 50 g on a load-cell-operated digital scale (UC-300 Precision Health Scale; A and D Instruments). Recumbent body length was measured to the nearest 0.1 cm on a horizontally placed measuring board. To exclude individual variation, all anthropometric measurements were taken by the same field worker. The anthropometric data and the age of the child were used to yield 3 measures of nutritional status: height-for-age, weight-for-age, and weight-for-height, which were expressed as Z-scores using the United States National Center for Health Statistics median as reference (20). Children with height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and WHZ Z-score <–2 SD of this reference median were classified as stunted, underweight, and wasted, respectively. WHZ > 2 SD was classified as overweight for height.
Blood sampling and biochemical analyses.
Blood (3 mL) was collected in heparinized tubes via antecubital venipuncture. Hb concentrations were determined in the field with the cyanomethemoglobin method using a portable photometer. The rest of the blood was immediately centrifuged, and the plasma was stored at –20°C for the duration of the fieldwork (±10 d). Care was taken to limit the exposure of the samples to direct light. After completion of the fieldwork, the samples were stored at –80°C until shipped to Germany on dry ice, where they were analyzed in the Micronutrient Laboratory of the Institute of Biological Chemistry and Nutrition at the University of Hohenheim. Plasma ferritin was measured by a standard sandwich ELISA procedure from the provider of the antibodies (DAKO). Plasma zinc concentrations were analyzed by flame atomic absorption spectrophotometry, according to the description of the manufacturer (Perkin Elmer). Plasma retinol and tocopherol levels were analyzed according to Erhardt et al. (21). Plasma homocysteine levels were measured by HPLC (22), and riboflavin status was assessed by calculating the activation coefficient of the erythrocyte glutathione reductase (EGRAC) with and without added riboflavin (23). C-reactive protein (CRP) and 
-1-acid glycoprotein (AGP) were measured as indicators of short- and long-term infection, respectively, by means of a Sandwich ELISA (DAKO). More detail is given elsewhere (18).
Morbidity. Morbidity data were collected on a weekly basis during the 6-mo intervention period. Indicators recorded were whether the child suffered from diarrhea (more than 4 runny stools) or acute respiratory infection (cough, runny nose, fever, earache, or sore throat) during the week of visit, and if the child had fever on the day of the visit. The data were used to calculate the percentage of child contacts positive for each of the 3 morbidity indicators.
Ethical considerations
The Ethics Committee of the South African Medical Research Council approved the study, and permission was obtained from local community leaders. Written informed consent was obtained from the mother or the guardian of all participating infants, after a detailed explanation of the purpose of the study.
Statistical analysis
Descriptive statistics on the change from baseline to postintervention were obtained. All biochemical variables had a normal distribution, except plasma ferritin. Analysis of variance was done on variables with normal distributions to test whether there were significant group differences (F-test) and the Dunnett’s t test to specifically test whether each of the 3 supplementation groups differed significantly from the P group. Anthropometric data were treated similarly, except that height and weight gains were calculated per week. For the P, WMM, and DMM groups, tests for linear or quadratic dose effects were also done. Coefficients were specified to take into account either a linear increase or a quadratic increase in supplementation over the 7-d period.
Because infection can affect blood concentrations of micronutrients, cases with elevated plasma C-reactive protein at baseline (CRP > 12 mg/L) were excluded from the statistical analysis for plasma ferritin, retinol, and zinc (DMM group, n = 4; P group, n = 6; WMM group, n = 11, and DI group, n = 13). The logarithmic transformation was used for ferritin and this transformed scale was used for all analyses with this variable.
|
RESULTS |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
|
|
|
|
|
|
|
DISCUSSION |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
The DMM intervention was the most efficacious treatment for improving anemia during infancy in this South African setting. This study supports the conclusion made by Beaton and McCabe (29) that daily supplements containing iron are more efficacious than intermittent supplementation for treating anemia. Although there was some improvement in Hb status in all 3 nonplacebo groups and there was a significant decrease in the prevalence of anemia in both the DMM and DI treatment groups, the treatment effect was only significant for the DMM supplement. The adequate vitamin A status possibly enabled the Hb response to both multiple micronutrient and iron treatments of iron deficient infants (30,31). van Stuijvenberg et al. (32) noted that responses to iron fortification are limited in children with marginal vitamin A status. The improved effect of the multiple micronutrient supplement on reducing anemia compared with iron alone could also be due to other micronutrients in the supplement, including riboflavin, B-12, and folic acid, which have been shown to have an enhancing effect on the metabolism of iron or synthesis of Hb (33–36).
The DMM supplement was the best treatment for improving both zinc and iron status of the infants. Although plasma ferritin, which is an indicator of iron stores, showed no improvement in any of the treatment groups, there was a significant deterioration in the P group, which resulted in a significant treatment effect being detected in both the daily multiple micronutrient and iron only groups. These supplements thus prevented the deterioration in iron stores as the infant grew older. The treatment effect for ferritin was slightly but nonsignificantly larger in the iron only group, possibly suggesting lack of interference from other micronutrients that may compete with iron for absorption, e.g., zinc (37). However, it could also have been that the presence of vitamin A in the multiple micronutrient supplement mobilized more of the storage iron for hematopoiesis (38), based on the slightly (but not significantly) greater change in the multiple micronutrient supplementation group. DMMs significantly increased the plasma zinc concentration from baseline to the end of the study and compared with the P group. This indicates that the DMMs more effectively improved zinc status compared with the other treatment groups. In general, there was a significant dose response effect observed for zinc when the DMM, WMM, and P treatments were compared.
The DMM supplement was the best intervention tested for improving both the fat-soluble and the water-soluble vitamin status of the infants. Plasma retinol only showed an increase in the DMM group, although this was not significant. With an overall plasma retinol concentration of 0.99 µmol/L at baseline and only 16% of infants being vitamin A deficient, a greater effect could not be expected. It is likely that this relatively adequate vitamin A status is a reflection of breast-feeding practices, with 60% of mothers still giving more than 3 breast-milk feedings a day at baseline. Tocopherol concentrations fell in all groups over the 6 mo of the trial, with the greatest protection in the group receiving multiple micronutrients daily. These falling vitamin E levels are of concern and suggest that the tocopherol status of the mothers and the amounts passing to the infants in breast milk are suboptimal.
Whereas, riboflavin status of the infants receiving multiple micronutrients improved, the status of the DI and P groups got worse during the course of the study. Similarly homocysteine concentrations were lowest in the infants that received multiple micronutrient supplements daily, and the decrease over time was significantly less in the P group than in the DMM group. Homocysteine concentrations depend largely on folate, vitamin B-6, vitamin B-12, and riboflavin status, and are elevated if any one of these is limiting. A study on adults in West Africa has shown that their high levels of circulating homocysteine were related to limited folate rather than B-12 status (39). The amounts of folic acid and B-12 provided by the DMM supplements seem sufficient to ensure adequate folate and B-12 status, although we cannot be sure which were limiting in the other groups.
The issues of compliance and dropout rates are unlikely to have introduced any bias in the results of the study, and the supplements were generally well received. Although designed to be a true efficacy study, because the households were scattered over a large mountainous area, the health workers could not visit each house and observe the foodlets consumption on a daily basis. The information collected weekly from the mothers by the health workers was largely confirmed by the retrospective data collected at the end of the study by the research team. The positive effect on plasma micronutrient status and the dose–response effects observed are also supportive of the reported compliance rate of >90%. The dropout rate in the IRIS study in South Africa over the 6-mo intervention period was unexpectedly high, mainly because the study ran through the festive season. The dropout rate tripled from 9% to 27% over this period, but the infants who dropped out were not significantly different in terms of baseline characteristics from the rest of their groups (results not shown). In the beginning, there were some complaints that infants were nauseous after taking the supplements, but these complaints disappeared after the community health workers provided encouragement and encouraged mothers to mix the supplement in the porridge.
Diarrhea was the most prevalent morbidity indicator noted, with an average prevalence of >20% for the entire 6-mo intervention period. In previous studies done by our group, the prevalence of diarrhea was 16% for 4- to 12-mo-old babies in a neighboring rural village (40) and 28% in an urban setting near Cape Town (41). The high rate of infections was also confirmed by the prevalence of increased acute-phase proteins, namely, CRP and AGP. The lack of effect of multiple micronutrient or iron-only supplementation on morbidity differs from results of other studies where micronutrient supplementation reduced morbidity (27,42,43).
In conclusion, although the multiple micronutrient supplements did not prevent growth faltering during infancy, they were successful at improving micronutrient status in this South African infant population. The DMM supplement was the most efficacious for preventing anemia and improving status of iron, zinc, riboflavin, and tocopherol.
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
2 Supported by UNICEF as part of a multicenter International Research study on Infant Supplementation.
4 Abbreviations used: AGP, -1-acid glycoprotein; CRP, C-reactive protein; DI, daily iron supplement; DMM, daily multiple micronutrient supplement; EGRAC, erythrocyte glutathione reductase activation coefficient; HAZ, height-for-age Z-score; Hb, hemoglobin; IRIS, International Research on Infant Supplementation; P, Placebo; UNICEF, United Nations Childrens’ Fund; WAZ, weight-for-age Z-score; WHZ, weight-for-height Z-score; WMM, weekly multiple micronutrient supplement.
|
LITERATURE CITED |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
1. Ferguson, E. L., Gibson, R. S., Opare-Obisaw, C., Ounpuu, S., Thomson, L. U. & Lehrfeld, J. (1993) The zinc nutriture of preschool children living in two African countries. J. Nutr. 123:1487-1496.
2. South African Vitamin A Consultative Group (SAVACG) (1996) Anthropometry, vitamin A, iron and immunization coverage status in children aged 6–71 months in South Africa, 1994. S. Afr. Med. J. 86:354-357.[Medline]
3. Labadarios, D., Steyn, N., Maunder, E., MacIntyre, U., Swart, R., Gericke, G., Huskisson, J., Dannhauser, A., Voster, H. H. & Nesamvuni, A. E. (2001) The National Food Consumption Survey (NFCS): Children Aged 1–9 Years, South Africa, 1999 2001 Stellenbosch University Cape Town, South Africa.
4. Kikafunda, J. K., Walker, A. F., Collett, D. & Tumwine, J. K. (1998) Risk factors for early childhood malnutrition in Uganda. Pediatrics 102:E45.[Medline]
5. Vazir, S., Naidu, A. N. & Vidyasagar, P. (1998) Nutritional status, psychosocial development and the home environment of Indian rural children. Indian Pediatr. 35:959-966.[Medline]
6. Baumslag, N. & Favin, M. (1992) Do Infants Under Six Months of Age Need Extra Iron? A Probe. Working Paper #12 1992 MotherCare, John Snow Inc. Arlington, VA.
7. Brown, K. H., Dewey, K. G. & Allen, L. H. (1998) Complementary Feeding of Young Children in Developing Countries 1998 WHO Geneva, Switzerland.
8. Dallman, P. & Siimes, M. (1979) Iron Deficiency in Infancy and Childhood 1979 The International Nutritional Anemia Consultancy Group Washington, DC.
9. Yip, R. (1994) Iron deficiency: contemporary scientific issues and nutritional programmatic approaches. J. Nutr. 124:1479S-1490S.
10. Ramakrishnan, U. (2002) Prevalence of micronutrient malnutrition worldwide. Nutr. Rev. 60:S46-S52.[Medline]
11. Chakravarty, I. & Sinha, R. K. (2002) Prevalence of micronutrient deficiency based on results obtained from the National Pilot Program on Control of Micronutrient Malnutrition. Nutr. Rev. 60:S53-S58.[Medline]
12. Gross, R. (2001) Micronutrient Supplementation Through the Life Cycle 2001 UNICEF New York, NY.
13. Briend, A. (2001) Highly nutrient-dense spreads: a new approach to delivering multiple micronutrient to high-risk groups. Br. J. Nutr. 85(suppl. 2):S175-S179.
14. Alnwick, D. (1998) Weekly iodine supplements work. Am. J. Clin. Nutr. 67:1103-1104.[Medline]
15. Argiratos, V. & Samman, S. (1994) The effect of calcium carbonate and calcium citrate on the absorption of zinc in health female subjects. Eur. J. Clin. Nutr. 45:198-204.
16. Allen, L. H. (1998) Iron-Ascorbic Acid and Iron-Calcium Interactions and Their Relevance in Complementary Feeding: Micronutrient Fortification of Complementary Foods 1998 International Life Sciences Institute Washington, DC.
17. Gross, R., Angeles-Agdeppa, I., Schultink, W., Dillon, D. & Sastromanidjojo, S. (1997) Daily versus weekly iron supplementation: programmatic and economic implications for Indonesia. Food Nutr. Bull. 18:64-70.
18. Smuts, C. M., Benadé, A.J.S., Berger, J., Hop, L. T., López de Romaña, G., Untoro, J., Karyadi, E., Erhardt, J. & Gross, R. (2003) IRIS I: a foodlet-based multiple-micronutrient intervention in 6- to 12-month-old infants at high risk of micronutrient malnutrition in four contrasting populations. Description of a multicenter trial. Food Nutr. Bull. 24:S27-S33.
19. Gross, R. & Schultink, W. (1997) Micronutrient deficiency in urban Indonesia. Arch. Latinoam Nutr. 47:50-53.
20. Hamill, P.V.V., Drizd, T. A., Johnson, C. L., Reed, R. B., Toche, A. F. & Moore, W. M. (1979) Physical growth; National Center for Health Statistics percentiles. Am. J. Clin. Nutr. 32:607-629.
21. Erhardt, J. G., Mack, H., Sobeck, U. & Biesalski, H. K. (2002) ß-Carotene and -tocopherol concentration and antioxidant status in buccal mucosal cells and plasma after oral supplementation. Br. J. Nutr. 87:471-475.[Medline]
22. Pfeiffer, C. M., Huff, D. L. & Gunter, E. W. (1999) Rapid and accurate HPLC assay for plasma total homocysteine and cysteine in a clinical laboratory setting. Clin. Chem. 45:290-292.
23. Bayoumi, R. A. & Rosalki, S. B. (1976) Evaluation of methods of coenzyme activation of erythrocyte enzymes for detection of deficiency of vitamins B1, B2, and B6. Clin. Chem. 22:327-335.
24. Faber, M., Jogessar, V. B. & Benade, A.J.S. (2001) Nutritional status and dietary intakes of children aged 2–5 years and their caregivers in a rural South African community. Int. J. Food Sci. Nutr. 52:401-411.[Medline]
25. Hautvast, J.L.A., Tolboom, J.J.M., Kafwembe, E. M., Musonda, R. M., Mwanakasale, V., van Staveren, W. A., van’t Hof, M. A., Sauerwein, R. W., Willems, J. L. & Monnens, L.A.H. (2000) Severe linear growth retardation in rural Zambian children: the influence of biological variables. Am. J. Clin. Nutr. 71:550-559.
26. Oelofse, A., van Raaij, J.M.A., Benadé, A.J.S., Dhansay, M. A., Tolboom, J.J.M. & Hautvast, J.G.A.J. (2003) The effect of a micronutrient-fortified complementary food on micronutrient status, growth and development of 6- to 12-month-old disadvantaged urban South African infants. Int. J. Food Sci. Nutr. 54:399-407.[Medline]
27. Rosado, J. L., López, P., Muñoz, E., Martinez, H. & Allen, L. H. (1997) Zinc supplementation reduced morbidity, but neither zinc nor iron supplementation affected growth or body composition of Mexican preschoolers. Am. J. Clin. Nutr. 65:13-19.
28. Rivera, J. A., González-Cossío, T., Flores, M., Romero, M., Rivera, M., Téllez-Rojo, M. M., Rosado, J. L. & Brown, K. H. (2001) Multiple micronutrient supplementation increases the growth of Mexican infants. Am. J. Clin. Nutr. 74:657-663.
29. Beaton, G. H. & McCabe, G. P. (1999) Efficacy of Intermittent Iron Supplementation in the Control of Iron Deficiency Anemia in Developing Countries: An Analysis of Experience 1999 The Micronutrient Initiative Ottawa, Canada.
30. West, C. E. & Roodenburg, A.J.C. (1992) Role of vitamin A in iron metabolism. Voeding 53:201-205.
31. Ahmed, F., Khan, M. R. & Jackson, L.A.A. (2001) Concomitant supplemental vitamin A enhances the response to weekly supplemental iron and folic acid in anemic teenagers in urban Bangladesh. Am. J. Clin. Nutr. 74:108-115.
32. van Stuijvenberg, M. E., Kruger, M., Badenhorst, C. J., Mansvelt, E.P.G. & Laubscher, J. A. (1997) Response to an iron fortification programme in relation to vitamin status in 6–12-year-old school children. Int. J. Food Sci. Nutr. 48:41-49.[Medline]
33. Meijia, L. A. & Chew, F. (1988) Hematological effect of supplementing anemic children with vitamin A alone and in combination with iron. Am. J. Clin. Nutr. 48:595-600.
34. Alfrey, C. P. & Lane, M. (1970) The effect of riboflavin deficiency on erythropoiesis. Semin. Hematol. 7:49-54.[Medline]
35. Worthington-White, D. A., Behnke, M. & Gross, S. (1994) Premature infants require additional folate and vitamin B12 to reduce severity of anemia of prematurity. Am. J. Clin. Nutr. 60:930-935.
36. Gallagher, P. G. & Ehrenkranz, R. A. (1995) Nutritional anemias in infancy. Clin. Perinatol. 22:671-692.[Medline]
37. Solomons, N. W. & Jacob, R. A. (1981) Studies on the bioavailability of zinc in humans: effect of heme and nonheme iron on the absorption of zinc. Am. J. Clin. Nutr. 34:475-482.
38. Bloem, M. W. (1995) Interdependence of vitamin A and iron: an important association for programmes of anaemia control. Proc. Nutr. Soc. 54:501-508.[Medline]
39. Amazou, K. A., Chabi, N. W., Adjalla, C. E., Rodriguez-Gueant, R. M., Feillet, F., Villaume, C., Sanni, A. & Geant, J.-L. (2004) High prevalence of hyperhomocysteinemia related to folate deficiency and the 677C to T mutation of the gene encoding methylenetetrahydrofolate reductase in coastal West Africa. Am. J. Clin. Nutr. 79:619-624.
40. Faber, M. & Benadé, A.J.S. (1999) Nutritional status and dietary practices of 4–24-month-old children from a rural South African community. Public Health Nutr. 2:179-185.[Medline]
41. Oelofse, A., van Raaij, J.M.A., Benadé, A.J.S., Dhansay, M. A., Tolboom, J.J.M. & Hautvast, J.G.A.J. (2001) Disadvantaged black and coloured infants in two urban communities in the Western Cape, South Africa differ in micronutrient status. Public Health Nutr. 5:289-294.
42. Berger, J., Dyck, J. L., Aplogan, A., Schneider, D., Traissac, P. & Hercberg, H. (2000) Effect of daily iron supplementation on iron status, cell-mediated immunity, and incidence of infections in 6–36-month-old Togolese children. Eur. J. Clin. Nutr. 54:29-35.[Medline]
43. Osendarp, S.J.M., Raaij, M. A., Darmstadt, G. L., Baqui, A., Hautvast, J.G.A.J. & Fuchs, G. J. (2001) Zinc supplementation during pregnancy and effects on growth and morbidity in low birthweight infants: a randomised placebo control trial. Lancet 357:1080-1085.[Medline]
This article has been cited by other articles:
|
|
 |
|
  S. Adu-Afarwuah, A. Lartey, K. H Brown, S. Zlotkin, A. Briend, and K. G Dewey Home fortification of complementary foods with micronutrient supplements is well accepted and has positive effects on infant iron status in Ghana Am. J. Clinical Nutrition, April 1, 2008; 87(4): 929 - 938. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Adu-Afarwuah, A. Lartey, K. H Brown, S. Zlotkin, A. Briend, and K. G Dewey Randomized comparison of 3 types of micronutrient supplements for home fortification of complementary foods in Ghana: effects on growth and motor development Am. J. Clinical Nutrition, August 1, 2007; 86(2): 412 - 420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. F. Walker, K. Kordas, R. J Stoltzfus, and R. E Black Interactive effects of iron and zinc on biochemical and functional outcomes in supplementation trials Am. J. Clinical Nutrition, July 1, 2005; 82(1): 5 - 12. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
