![[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}
|
|
|
|
|
||
4 Department of Internal Medicine, UMCN, Radboud University, Nijmegen, The Netherlands; 5 Institute for Research and Development, Montpellier, France; 6 Department Public Health, Medical Faculty, Trisakti University, Jakarta, Indonesia; 7 National Institute of Nutrition, Hanoi, Vietnam; 8 Center for Child Survival, University of Indonesia, Jakarta, Indonesia; and 9 Institute of Nutrition, Mahidol University, Bangkok, Thailand
* To whom correspondence should be addressed. E-mail: wieringa{at}tiscali.nl.
 |
ABSTRACT |
|---|
 TOP ABSTRACT IntroductionMethodsResultsDiscussionLITERATURE CITED |
|---|
|
Introduction |
|---|
|
TOPABSTRACTIntroductionMethodsResultsDiscussionLITERATURE CITED |
|---|
The prevalence of zinc deficiency has been estimated at 
20% worldwide (8), but might be much higher in certain populations (9). Zinc deficiency causes reduced growth and stunting (9), reduced immuno-competence (10), and impaired psycho-motor development (11). Several meta-analyses indicate that zinc supplementation reduces the incidence and severity of diarrheal and respiratory diseases (12,13) and improves growth in stunted children (9).
In many developing countries, over half of the infants are anemic at the age of 1 y, and, given the possible detrimental effects of iron deficiency on psycho-motor development, it is not surprising that these countries are considering blanket iron supplementation for infants and children. However, evidence suggests that iron supplementation may increase the morbidity of infectious diseases (2), especially in malarious areas, and may reduce linear growth in iron replete infants (14). Moreover, iron supplementation has been shown to negatively affect zinc status (15), which is especially important as deficiencies of iron and zinc often occur concomitantly (16,17).
The combined supplementation of iron and zinc may be an effective tool for the prevention of both iron and zinc deficiency. However, data on interactions between iron and zinc is confusing and published results are often conflicting (15,18–20).
To evaluate effects and interactions of zinc and iron supplementation, a series of parallel studies were conducted on infants of Southeast Asia between 1996 and 2000 in a collaborative multicountry trial framework [Southeast Asia Multicountry Trial on Iron and Zinc supplementation in Infants (SEAMTIZI) Study Group]. A core protocol for these studies was developed in order to combine the data from separate sites, after completion, for a pooled analysis. The different study sites represented a range of conditions encountered in Southeast Asia. This study reports the results of the pooled analysis of the effects of iron and zinc supplementation in infants on biochemical indicators.
|
Methods |
|---|
|
TOPABSTRACTIntroductionMethodsResultsDiscussionLITERATURE CITED |
|---|
Sites. The pooled analysis data set consisted of data from 4 different research sites: Thailand, Vietnam, and 2 sites in Indonesia. Initially there were 2 additional research sites from Indonesia, but these were not included in the pooled data because one site had a different study design (stepped design with no iron-only group) (25), and one site decided not to participate in the final pooled analysis (26).
Description of sites.
The research in Thailand was conducted by the Institute of Nutrition, Mahidol University (INMU),10 Khon Kaen province of northeast Thailand. Infants were recruited from 106 rural villages. A survey prior to the study showed the prevalence of anemia in infants aged 4–6 mo to be 50% in this area.
The research in Vietnam was conducted by the National Institute of Nutrition, Hanoi (NIN) in the rural Que Vo district, Bac Ninh province of northwest Vietnam. Infants were recruited from 120 villages. A recent study showed that 60% of infants are anemic (27).
The first trial in Indonesia was conducted by the University of Trisakti and University of Indonesia (UT/UI), Indramayu province, West Java. The area is rural and more remote than the second study site in Indonesia described below.
The second Indonesian trial was conducted by the Nutrition Research and Development Center (NRDC) in Bogor district, West Java. Infants were recruited from 6 rural villages. In an earlier study in the same area, 50% of the infants were anemic, and 20% had low plasma zinc concentrations (17).
Subjects and procedures. Mothers of eligible infants were invited to participate in the study, informed of the procedures and purpose of the study, and asked to provide written informed consent. At recruitment, infants were assessed anthropometrically, and a short history was taken. Exclusion before recruitment was determined by the presence of chronic or severe illness, severe clinical malnutrition, anemia (hemoglobin concentration <70 g/L), or congenital anomalies. Recruited infants were randomly assigned to 1 of 4 supplementation groups following a computer-generated block randomized group allocation. Three of 4 study sites administered a high-dose vitamin A capsule prior to the study [INMU 50,000 IU (15 mg); NIN and UT/UI 100,000 IU (30 mg) of all-trans retinol]. These sites also took baseline blood samples in all (NIN) or a subsample of the infants (INMU, UT/UI).
Infants received either iron (10 mg/d), zinc (10 mg/d), iron + zinc (10 mg of each/d), or a placebo as 2 mL/d of syrup (5–7 d/wk, according to site). Supplements for all sites were made by the same pharmaceutical company (PT Kenrose) in cooperation with UNICEF-Jakarta. Supplementation was administered double-blind, and the code was made known only after all analyses were complete.
After 6 mo of supplementation, a blood samples were taken from infants for biochemical assessment of nutritional status. All infants with anemia (<110 g/L) were supplemented with iron at the end of the study.
Ethical consent for the studies were obtained from the Ethical Board of Mahidol University, Bangkok, Thailand; the Ethical Committee of the Ministry of Health, Vietnam; the Ethical Committee of University of Indonesia, Jakarta, Indonesia; the Ethical Committee of Wageningen University, Wageningen, The Netherlands; and the Ethical Committee of Ministry of Health, Indonesia.
Anthropometry and biochemical analyses. Anthropometry was done by trained anthropometrists using standard methods (28). Z-scores (weight-for-age, height-for-age, and weight-for-height) were calculated with EPI-Info 6.02, using WHO recommended growth curves (29).
Blood samples were obtained either by venapuncture (INMU, NIN, NRDC) or heel prick (UT/UI). Hemoglobin concentrations were measured by standard cyanmethemoglobin method (INMU, NIN, NRDC) or Hemocue (UT/UI) (28). Serum (INMU, NIN) or plasma (NRDC) ferritin concentrations were measured with ELISA (30). Serum (INMU, NIN) or plasma (NRDC) zinc concentrations were measured with flame atomic absorption spectrophotometry using trace-element free procedures (31). Anemia was defined as hemoglobin concentration <110 g/L, and iron deficiency anemia was defined as anemia combined with ferritin concentration <12 µg/L. Furthermore, zinc deficiency was defined as zinc concentration <10.7 µmol/L (28).
Statistical analysis. The effect of supplementation on biochemical indicators was investigated using a general linear model (GLM), controlling for site and gender, using a full factorial analysis. Differences among groups were analyzed with ANOVA, again controlling for site and gender. If the overall F-test was significant (P < 0.05), conservative post-hoc comparisons were made (Bonferroni post-hoc comparison for GLM, or Tamhane's post-hoc comparison for ANOVA). The regression equations and residual statistics were checked because the different sites were not homogenous subsets of each other. Effect sizes were calculated from estimated means, using the full factorial model. Data were presented as effect sizes (95% CI) and differences considered significant at P < 0.05. Variance stabilizing transformations were done only when significant improvement of the model was achieved (ferritin and zinc concentrations were transformed to natural logarithms). All significant 2-way interactions (P < 0.1) were further explored, except for interactions with site. Differences in prevalence among groups were analyzed using chi-square statistics. Differences in compliance among study sites were tested with the nonparametric Kruskal Wallis test.
Baseline biochemistry was not available for all subjects. One site (NRDC) did not take baseline blood samples, and 2 sites (INMU, UT/UI) performed baseline biochemistry only on subgroups. Furthermore, 1 site (UT/UI) did not measure zinc concentrations. The subgroup of subjects with baseline blood samples did not differ from other subjects in end-point indicators of micronutrient status and anthropometry.
In addition, an investigation was conducted on the effect of vitamin A capsule distribution, at baseline, as a potential effect modifier of end-point hemoglobin concentrations. Hemoglobin concentrations of supplemented groups from the different sites were standardized to the mean hemoglobin concentration of nonsupplemented infants (placebo group) within each site, and the effect of supplementation was expressed as a proportion of the placebo mean. The effect of vitamin A capsule distribution prior to the study on proportional differences in hemoglobin concentrations, and on the effect of iron and zinc supplementation on hemoglobin concentrations, was investigated using a GLM model, including gender and age at recruitment, with vitamin A distribution coded as a binary variable. Age at entry was categorized by months.
|
Results |
|---|
|
TOPABSTRACTIntroductionMethodsResultsDiscussionLITERATURE CITED |
|---|
|
|
|
|
Gender significantly modified the effect of iron supplementation. The estimated effect size of iron supplementation on end-point hemoglobin concentrations in boys was 12.0 g/L (10.2–13.8), whereas in girls it was 6.8 g/L (4.9–8.7). In the iron supplemented groups, hemoglobin concentrations did not differ between boys [116.9 g/L (115.6–118.2)] and girls 116.5 g/L (115.2–17.9). Furthermore, anemia at baseline significantly modified the effect of iron supplementation on hemoglobin concentrations (Pinteraction = 0.093), with an estimated effect size (95% CI) of iron supplementation of 12.3 g/L (9.1–15.4) in anemic infants compared with 8.5 g/L (5.5–11.6) in infants not anemic at baseline. Anemia at baseline did not modify the effect of zinc supplementation on hemoglobin concentrations. Stunting at recruitment (height-for-age Z-score <–2.0) did not modify the effect of either iron nor zinc supplementation on hemoglobin concentrations.
In line with the higher hemoglobin concentrations after iron supplementation, the prevalence of anemia was lowered in the iron and iron + zinc supplemented groups compared with the placebo group (P < 0.001, Table 3), although the efficacy of the combined iron and zinc supplement was less than that of iron alone in reducing anemia prevalence (P < 0.05).
Similar to its effect on hemoglobin concentrations, iron supplementation also increased ferritin concentrations (P < 0.001) with a mean estimated effect size of 29.5 µg/L (25.3–34.2). Accordingly, zinc supplementation had a negative effect on ferritin concentrations (P = 0.001) with a mean estimated effect size of –4.5 µg/L (–6.8 to –1.8). However, in contrast to hemoglobin, there was a significant interaction between iron and zinc supplementation on ferritin concentrations (P < 0.10), which was also reflected by the higher ferritin concentration in infants receiving iron than in those receiving iron + zinc (P = 0.014, Table 3).
The end-point prevalence of both low ferritin concentrations and iron deficiency anemia was lower in both the iron and iron + zinc groups compared with the placebo and zinc groups (P < 0.001, Table 3).
Zinc supplementation resulted in higher end-point zinc concentrations (P < 0.001, Table 3), with a mean estimated effect size (95% CI) of 4.3 µmol/L (3.7–4.8). In contrast, iron supplementation had a negative effect on plasma zinc concentrations (P = 0.015), with an estimated effect size of –0.6 µmol/L (–1.0 to –0.1). However, there was a significant interaction between iron and zinc supplementation on zinc concentrations (P < 0.001, GLM). The negative effect of iron supplementation on zinc concentrations was apparent only when iron and zinc supplementation was combined, with the zinc concentrations in the zinc group being higher than in the iron + zinc group (P = 0.001); but the iron and placebo groups did not differ (Table 3). The estimated effect size (95%CI) of supplementation with zinc alone [5.8 µmol/L (5.6–6.1)] was higher than that of iron and zinc combined [+ 3.5 µmol/L (3.3–3.7), P < 0.001]. Neither anemia at baseline nor stunting at recruitment modified the effect of zinc or iron supplementation on zinc concentrations.
The prevalence of zinc deficiency was lower in the zinc and iron + zinc groups compared with the placebo group (P < 0.001). Iron supplementation alone did not increase the prevalence of zinc deficiency. In fact, the prevalence of zinc deficiency in the iron group was lower than in the placebo group (P < 0.05, Table 3). The negative effect of iron on the efficacy of zinc supplementation was also confirmed by the higher prevalence of zinc deficiency in infants receiving iron and zinc combined than in infants receiving only zinc (P < 0.05).
VAC distribution prior to the study affected end-point hemoglobin concentrations (P = 0.041, GLM controlling for age at recruitment and gender, and with hemoglobin concentrations standardized at each site). Moreover, VAC distribution modified the effect of iron supplementation on end-point hemoglobin concentrations (Pinteraction = 0.080). Subgroup analysis showed that vitamin A capsule distribution negatively affected hemoglobin concentrations in the infants not receiving iron, with end-point hemoglobin concentrations tending to be 3.2% lower in infants receiving VAC compared with infants not receiving vitamin A (P = 0.066). In infants who received iron supplementation, VAC administration did not modify end-point hemoglobin concentrations (2.1% higher after VAC, P = 0.20).
|
Discussion |
|---|
|
TOPABSTRACTIntroductionMethodsResultsDiscussionLITERATURE CITED |
|---|
Anemia in infancy remains a serious health problem in many countries of Southeast Asia, and the high prevalence of anemia (>50%) in the placebo group at the end of the present study reflects this. The prevalence of zinc deficiency was also high (>20% in the placebo group). Although supplementation with zinc significantly improved zinc status, the addition of iron to the zinc supplement significantly reduced the efficacy. Iron supplementation alone, however, did not negatively affect zinc status. The overall negative effect of iron supplementation on zinc concentrations as reported in this study can therefore be attributed to a negative effect of iron on the efficacy of concomitant zinc supplementation. These findings support several other studies that also reported no independent negative effect of iron supplementation (33,34), or even a small beneficial effect (23,35) on zinc status. Therefore, this study shows that iron alone can be given safely to infants without negatively affecting zinc status. In contrast, supplementation of zinc alone may negatively affect iron status, although the overall negative effect was small in this multicountry study. These findings are similar to the results of the study that decided not to participate in this pooled analysis (26). Hence, we are convinced that the results of this pooled analysis are not biased by the exclusion of the third study from Indonesia.
Despite iron supplementation for 6 mo, at least 25% of the infants remained anemic in the iron-supplemented groups. The prevalence of iron deficiency anemia, however, was <2.5% after iron supplementation alone or combined with zinc. Hence, the anemia remaining after supplementation may be due to unresolved deficiencies of other nutrients or to hereditary hemoglobinopathies. Estimates of, for example, 
-thalassemia prevalence in the region ranges from 3 to 11% (36). However, the cut-off values for anemia that are currently used may not be appropriate for infants and may thus lead to an overestimation of anemia prevalence in this age group. Domellof et al. (37) recently proposed a cut-off for anemia at hemoglobin concentrations <100 g/L in infants 9 mo of age. In the present study, using this cut-off, the prevalence of anemia would be 10–13% in the infants who received iron (Fig. 1), in line with the expected prevalence of anemia from other causes.
The effect of iron supplementation on hemoglobin concentrations was almost twice as large in boys than in girls. Although hemoglobin concentrations differed between genders at recruitment, they were not as large as at the end of the study. One possible explanation for these gender differences may be the higher growth rate of boy infants, leading to increased iron requirements. An important implication is that boy infants are more at risk for anemia, a finding that has been reported before (38). This finding is also evident from the higher anemia prevalence in boys than in girls at the end of the study in the noniron supplemented groups.
Vitamin A supplementation is known to affect hemoglobin concentrations and the efficacy of iron supplementation (39–41), with vitamin A supplementation increasing the utilization of iron. Also, iron supplementation in infants has been shown to affect vitamin A status (42), hence, interactions between iron and vitamin A metabolism can be expected. This multicountry trial was not designed to investigate the effect of vitamin A on hemoglobin concentrations. However, analysis of hemoglobin concentrations standardized per site showed that vitamin A capsule distribution prior to the study significantly contributed toward differences in the efficacy of iron supplementation. The fact that vitamin A capsule distribution is related to relatively lower hemoglobin concentrations in infants not receiving iron is cause for concern. Combined with the slight positive effect of vitamin A capsule distribution on the efficacy of iron supplementation, the finding supports earlier evidence that iron utilization is improved after vitamin A supplementation (43). This also implies that vitamin A supplementation without measures to improve iron status may increase anemia prevalence. Because vitamin A capsule distribution is widely implemented in areas with a high prevalence of nutritional anemia, further research into this interaction is certainly warranted.
In conclusion, this study shows that iron supplementation alone will not negatively affect zinc status in infants. However, as zinc deficiency is also prevalent in this region, concomitant zinc supplementation should be recommended, especially insofar as combined iron and zinc supplementation is effective in improving hemoglobin concentrations and reducing the prevalence of anemia. Supplementation of zinc alone, however, can negatively affect iron status. Vitamin A capsule distribution may potentially be an important factor affecting iron status in infants, and, in the absence of iron supplementation, may increase anemia prevalence.
|
FOOTNOTES |
|---|
2 This article is dedicated to the memory of Steven Esrey, who started the pooled analysis but was unfortunately not able to complete it.
3 Corresponding author is listed first, other authors are listed alphabetically.
10 SEAMTIZI: South-East Asia Multi-country Trial on Iron and Zinc supplementation in Infants Study Group.
10 Abbreviations used: GLM, general linear model; INMU, Institute of Nutrition, Mahidol University, Bangkok; NIN, National Institute of Nutrition, Hanoi, Vietnam; NRDC, Nutrition Research and Development Center, Bogor, Indonesia; UI, University of Indonesia, Jakarta, Indonesia; UMCN, University Medical Center Nijmegen, Radboud University, Netherlands; UT, Trisakti University, Jakarta, Indonesia; VAC, (high dose) Vitamin A capsule.
Manuscript received 23 July 2006. Initial review completed 23 August 2006. Revision accepted 17 November 2006.
|
LITERATURE CITED |
|---|
|
TOPABSTRACTIntroductionMethodsResultsDiscussionLITERATURE CITED |
|---|
1. Standing Committee on Nutrition. 5th Report of the world nutrition situation: nutrition for improved outcomes 2004 June. Available at: www.unsystem.org/scn/.
2. Oppenheimer SJ. Iron and its relation to immunity and infectious disease. J Nutr. 2001;131:616S–35S.
3. Christian P, Khatry SK, Katz J, Pradhan EK, LeClerq SC, Shrestha SR, Adhikari RK, Sommer A, West KP, Jr. Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomised community trial. BMJ. 2003;326:571–7.
4. Bates CJ, Powers HJ, Thurnham DI. Vitamins, iron, and physical work. Lancet. 1989;2:313–4.[Medline]
5. Grantham-McGregor S, Ani C. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr. 2001;131:649S–68S.
6. Black MM. Micronutrient deficiencies and cognitive functioning. J Nutr. 2003;133:3927S–31S.
7. Allen LH. Nutritional influences on linear growth: a general review. Eur J Clin Nutr. 1994;48: Suppl 1:S75–89.
8. International Zinc Nutrition Consultative Group (IZiNCG). Assessment of the risk of zinc deficiency in populations and options for its control. Hotz C and Brown KH, eds. 2004:Food and Nutrition Bulletin 25;S91–S204.
9. Brown KH, Peerson JM, Rivera J, Allen LH. Effect of supplemental zinc on the growth and serum zinc concentrations of prepubertal children: a meta- analysis of randomized controlled trials. Am J Clin Nutr. 2002;75:1062–71.
10. Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998;68: 447S–463S.[Abstract]
11. Caulfield LE, Zavaleta N, Shankar AH, Merialdi M. Potential contribution of maternal zinc supplementation during pregnancy to maternal and child survival. Am J Clin Nutr. 1998;68:499S–508S.[Abstract]
12. Bhutta ZA, Bird SM, Black RE, Brown KH, Meeks Gardner J, Hidayat A, Khatun F, Martorell R, Ninh NX, et al. Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr. 2000;72:1516–22.
13. Sazawal S, Black RE, Jalla S, Mazumdar S, Sinha A, Bhan MK. Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial. Pediatrics. 1998;102:1–5.
14. Dewey KG, Domellof M, Cohen RJ, Landa Rivera L, Hernell O, Lonnerdal B. Iron supplementation affects growth and morbidity of breast-fed infants: results of a randomized trial in Sweden and Honduras. J Nutr. 2002;132:3249–55.
15. Whittaker P. Iron and zinc interactions in humans. Am J Clin Nutr. 1998;68:442S–6S.[Abstract]
16. Gibson RS. Zinc nutrition in developing countries. Nutr Res Rev. 1994;7:151–73.
17. Dijkhuizen MA, Wieringa FT, West CE. Muherdiyantiningsih & Muhilal Concurrent micronutrient deficiencies in lactating mothers and their infants in Indonesia. Am J Clin Nutr. 2001;73:786–91.
18. Sreedhar B. Conflicting evidence of iron and zinc interactions in humans: does iron affect zinc absorption? Am J Clin Nutr. 2003;78:1226–7.
19. Wieringa FT, Dijkhuizen MA, West CE. Iron and zinc interactions. Am J Clin Nutr. 2004;80:787–8.
20. Fischer Walker C, Kordas K, Stoltzfus RJ, Black RE. Interactive effects of iron and zinc on biochemical and functional outcomes in supplementation trials. Am J Clin Nutr. 2005;82:5–12.
21. Berger J, Ninh NX, Khan NC, Nhien NV, Lien DK, Trung NQ, Khoi HH. Efficacy of combined iron and zinc supplementation on micronutrient status and growth in Vietnamese infants. Eur J Clin Nutr. 2006;60:443–54.[Medline]
22. Wieringa FT, Dijkhuizen MA, West CE, van der Ven-Jongekrijg J, van der Meer JW. Reduced production of immunoregulatory cytokines in vitamin A- and zinc-deficient Indonesian infants. Eur J Clin Nutr. 2004;58:1498–504.[Medline]
23. Dijkhuizen MA, Wieringa FT, West CE, Martuti S. Muhilal. Effects of iron and zinc supplementation in Indonesian infants on micronutrient status and growth. J Nutr. 2001;131: 2860–65.
24. Wasantwisut E, Winichagoon P, Chitchumroonchokchai C, Yamborisut U, Boonpraderm A, Pongcharoen T, Sranacharoenpong K, Russameesopaphorn W. Iron and zinc supplementation improved iron and zinc status, but not physical growth, of apparently healthy, breast-fed infants in rural communities of northeast Thailand. J Nutr. 2006;136:2405–11.
25. Fahmida U. Iron, zinc, vitamin A intervention trials in East Lombok, West Nusa Tenggara, Indonesia, pp. 1–25. SEAMEO-TROPMED, University of Indonesia, PhD thesis. 2000.
26. Lind T, Lonnerdal B, Stenlund H, Ismail D, Seswandhana R, Ekstrom EC, Persson LA. A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: interactions between iron and zinc. Am J Clin Nutr. 2003;77:883–90.
27. Nguyen XN, Berger J, Dao TQ, Nguyen CK, Traissac P, Ha HK. [Efficacy of daily and weekly iron supplementation for the control of iron deficiency anaemia in infants in rural Vietnam] Sante. 2002;12:31–7.[Medline]
28. Gibson RS. Principles of nutritional assessment. Oxford: Oxford University Press. 1990.
29. Group WW. Use and interpretation of anthropometric indicators of nutritional status. Bull WHO. 1986;64:929–41.[Medline]
30. Fortier RL, McGrath WP, Twomey SL. Enzyme-labeled immunosorbent assay for serum ferritin: method evaluation and comparison with two radioassays. Clin Chem. 1979;25:1466–9.
31. Cornelis R, Heinzow B, Herber RFM, Molin Christensen J, Poulsen OM, Sabbioni E, Templeton DM, Thomassen Y, Vahter M, Vesterberg O. Sample collection guidelines for trace elements in blood and urine. J Trace Elem Med Biol. 1996;10:103–27.[Medline]
32. Baqui AH, Zaman K, Persson LA, El Arifeen S, Yunus M, Begum N, Black RE. Simultaneous weekly supplementation of iron and zinc is associated with lower morbidity due to diarrhea and acute lower respiratory infection in Bangladeshi infants. J Nutr. 2003;133:4150–7.
33. Yip R, Reeves JD, Lonnerdal B, Keen CL, Dallman PR. Does iron supplementation compromise zinc nutrition in healthy infants? Am J Clin Nutr. 1985;42:683–7.
34. Munoz EC, Rosado JL, Lopez P, Furr HC, Allen LH. Iron and zinc supplementation improves indicators of vitamin A status of Mexican preschoolers. Am J Clin Nutr. 2000;71:789–94.
35. Zlotkin S, Arthur P, Schauer C, Antwi KY, Yeung G, Piekarz A. Home fortification with iron and zinc sprinkles or iron sprinkles alone successfully treats anemia in infants and young children. J Nutr. 2003;133:1075–80.
36. Weatherall DJ, Clegg JB. Inherited haemoglobin disorders: an increasing global health problem. Bulletin WHO. 2001;79:704–12.
37. Domellof M, Dewey KG, Lonnerdal B, Cohen RJ, Hernell O. The diagnostic criteria for iron deficiency in infants should be reevaluated. J Nutr. 2002;132:3680–6.
38. Domellof M, Lonnerdal B, Dewey KG, Cohen RJ, Rivera LL, Hernell O. Sex differences in iron status during infancy. Pediatrics. 2002;110:545–52.
39. Suharno D, West CE. Muhilal, Karyadi, D. & Hautvast, J. G. Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia. Lancet. 1993;342:1325–8.[Medline]
40. Roodenburg AJ, West CE, Hovenier R, Beynen AC. Supplemental vitamin A enhances the recovery from iron deficiency in rats with chronic vitamin A deficiency. Br J Nutr. 1996;75:623–36.[Medline]
41. Bloem MW, Wedel M, Egger RJ, Speek AJ, Schrijver J, Saowakontha S, Schreurs WH. Iron metabolism and vitamin A deficiency in children in northeast Thailand. Am J Clin Nutr. 1989;50:332–8.
42. Wieringa FT, Dijkhuizen MA, West CE, Thurnham DI, Muhilal, van der Meer JWM. Redistribution of vitamin A after iron supplementation in Indonesian infants. Am J Clin Nutr. 2003;77:651–7.
43. Zimmermann MB, Biebinger R, Rohner F, Dib A, Zeder C, Hurrell RF, Chaouki N. Vitamin A supplementation in children with poor vitamin A and iron status increases erythropoietin and hemoglobin concentrations without changing total body iron. Am J Clin Nutr. 2006;84:580–6.
This article has been cited by other articles:
|
|
 |
|
  M. Wijaya-Erhardt, J. G Erhardt, J. Untoro, E. Karyadi, L. Wibowo, and R. Gross Effect of daily or weekly multiple-micronutrient and iron foodlike tablets on body iron stores of Indonesian infants aged 6 12 mo: a double-blind, randomized, placebo-controlled trial Am. J. Clinical Nutrition, December 1, 2007; 86(6): 1680 - 1686. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
