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A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: effects on growth and development.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
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2004 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 80, no 3, 729-736 p.Article in journal (Refereed) Published
Abstract [en]

Background: Deficiencies of iron and zinc are associated with delayed development, growth faltering, and increased infectious-disease morbidity during infancy and childhood. Combined iron and zinc supplementation may therefore be a logical preventive strategy.

Objective: The objective of the study was to compare the effects of combined iron and zinc supplementation in infancy with the effects of iron and zinc as single micronutrients on growth, psychomotor development, and incidence of infectious disease.

Design: Indonesian infants (n = 680) were randomly assigned to daily supplementation with 10 mg Fe (Fe group), 10 mg Zn (Zn group), 10 mg Fe and 10 mg Zn (Fe+Zn group), or placebo from 6 to 12 mo of age. Anthropometric indexes, developmental indexes (Bayley Scales of Infant Development; BSID), and morbidity were recorded.

Results: At 12 mo, two-factor analysis of variance showed a significant interaction between iron and zinc for weight-for-age z score, knee-heel length, and BSID psychomotor development. Weight-for-age z score was higher in the Zn group than in the placebo and Fe+Zn groups, knee-heel length was higher in the Zn and Fe groups than in the placebo group, and the BSID psychomotor development index was higher in the Fe group than in the placebo group. No significant effect on morbidity was found.

Conclusions: Single supplementation with zinc significantly improved growth, and single supplementation with iron significantly improved growth and psychomotor development, but combined supplementation with iron and zinc had no significant effect on growth or development. Combined, simultaneous supplementation with iron and zinc to infants cannot be routinely recommended at the iron-to-zinc ratio used in this study.

Place, publisher, year, edition, pages
2004. Vol. 80, no 3, 729-736 p.
Keyword [en]
Anemia; Iron-Deficiency/complications/*prevention & control, Child Development/*drug effects, Community Health Services, Dietary Supplements, Double-Blind Method, Drug Interactions, Drug Therapy; Combination, Factor Analysis; Statistical, Female, Growth/*drug effects, Humans, Indonesia, Infant, Iron/*administration & dosage/therapeutic use, Male, Placebos, Psychomotor Performance/drug effects, Zinc/*administration & dosage/*deficiency/therapeutic use
National Category
Medical and Health Sciences
URN: urn:nbn:se:umu:diva-13730PubMedID: 15321815OAI: diva2:153401
Available from: 2007-09-05 Created: 2007-09-05 Last updated: 2010-08-04Bibliographically approved
In thesis
1. Iron and zinc in infancy: results from experimental trials in Sweden and Indonesiaa
Open this publication in new window or tab >>Iron and zinc in infancy: results from experimental trials in Sweden and Indonesiaa
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Iron and zinc are difficult to provide in sufficient amounts in complementary foods to infants world-wide, resulting in high prevalence of both iron and zinc deficiency. These deficiency states cause anemia, delayed neurodevelopment, impaired growth, and increased susceptibility to infections such as diarrhea and respiratory infections.

Design: Two different intervention strategies; reduction of a possible inhibitor of iron and zinc absorption, i.e. phytate, or supplementation with iron and zinc, were applied to two different populations in order to improve iron and zinc nutrition:

In a high-income population (Umeå, Sweden), the amount of phytate in commonly consumed infant cereals was reduced. Healthy, term infants (n=300) were at 6 mo of age randomized to phytate-reduced infant cereals, conventional infant cereals, or infant formula and porridge.

In a low income population (Purworejo, Indonesia), daily iron and zinc supplementation was given. Healthy, term infants (n=680) were at 6 mo randomized to supplementation with iron, zinc, a combination of iron and zinc, or placebo.

Blood samples, anthropometrical measurements, and data on infant neurodevelopment and morbidity were collected. Also, in the Swedish study, detailed information on the dietary intake was recorded.

Results: In the Swedish study, the reduction of phytate had little effect on iron and zinc status, growth, development or incidence of diarrhea or respiratory infections, possibly due to the presence of high contents of ascorbic acid, which may counteract the negative effects of phytate. In the Indonesian study, significant negative interaction between iron and zinc was evident for several of the outcomes; Hb and serum ferritin improved more in the iron only group compared to placebo or the combined iron and zinc group. Further, supplementation with iron alone improved infant psychomotor development and knee-heel length, whereas supplementation with zinc alone improved weight and knee-heel length compared to placebo. Combined iron and zinc supplementation did decrease the prevalence of iron deficiency anemia and low serum zinc, but had no other positive effects. Vomiting was more common in the combined group.

Analyses of dietary intake from the Swedish study showed that dietary iron intake in the 6-11 mo period was significantly associated with Hb, but not serum ferritin at 9 and 12 mo, whereas the opposite was true in the 12-17 mo period, i.e. dietary iron intake was significantly associated with serum ferritin, but not Hb at 18 mo.

Conclusions: The phytate content of commercial infant cereals does not seem to contribute to poor iron and zinc status of Swedish infants as feared. However, the current definitions of iron and zinc deficiency in infancy may overestimate the problem, and a change in the recommended cutoffs is suggested. These studies also indicate that dietary iron is preferably channeled towards erythropoiesis during infancy, but to an increasing amount channeled towards storage in early childhood. This suggests that in evaluating dietary programs, Hb may be superior in monitoring response to dietary iron in infancy, whereas S-Ft may respond better later in childhood. However, as shown in this study, increasing Hb may not necessarily be an indicator of iron deficiency, as more dietary iron increased Hb regardless of iron status.

In the low-income setting combined supplementation with iron and zinc resulted in significant negative interaction. Thus, it is not possible to recommend routine iron-zinc supplementation at the molar concentration and mode used in this study. It is imperative that further research efforts are focused at finding cost-effective strategies to prevent iron and zinc deficiency in low-income populations.

Place, publisher, year, edition, pages
Umeå: Umeå university, 2004. 105 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 887
Public health, Folkhälsomedicin
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
urn:nbn:se:umu:diva-277 (URN)91-7305-631-6 (ISBN)
Public defence
2004-05-28, Sal B, by 1D, Norrlands universitetssjukhus, Umeå, 09:00 (English)
Available from: 2004-05-12 Created: 2004-05-12 Last updated: 2011-04-08Bibliographically approved

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