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Iron and zinc in infancy: results from experimental trials in Sweden and Indonesiaa
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
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.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 887
Keyword [en]
Public health
Keyword [sv]
Folkhälsomedicin
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Epidemiology
Identifiers
URN: urn:nbn:se:umu:diva-277ISBN: 91-7305-631-6 (print)OAI: oai:DiVA.org:umu-277DiVA: diva2:142926
Public defence
2004-05-28, Sal B, by 1D, Norrlands universitetssjukhus, Umeå, 09:00 (English)
Opponent
Available from: 2004-05-12 Created: 2004-05-12 Last updated: 2011-04-08Bibliographically approved
List of papers
1. Effects of weaning cereals with different phytate contents on hemoglobin, iron stores, and serum zinc: a randomized intervention in infants from 6 to 12 mo of age
Open this publication in new window or tab >>Effects of weaning cereals with different phytate contents on hemoglobin, iron stores, and serum zinc: a randomized intervention in infants from 6 to 12 mo of age
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2003 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 78, no 1, 168-175 p.Article in journal (Refereed) Published
Abstract [en]

Background: Weaning foods frequently contain phytate, an inhibitor of iron and zinc absorption, which may contribute to the high prevalence of iron and zinc deficiency seen in infancy.

Objective: The objective was to investigate whether either an extensive reduction in the phytate content of infant cereals or the use of milk-based, iron-fortified infant formula would improve iron and zinc status in infants.

Design: In a double-blind design, infants (n = 300) were randomly assigned to 3 cereal groups from 6 to 12 mo of age: commercial milk-based cereal drink (MCD) and porridge (CC group), phytate-reduced MCD and phytate-reduced porridge (PR group), or milk-based infant formula and porridge with the usual phytate content (IF group). Venous blood samples were collected at 6 and 12 mo. Dietary intake was recorded monthly. After the intervention, 267 infants remained in the analysis.

Results: Hemoglobin concentrations of < 110 g/L, serum ferritin concentrations of < 12 µg/L, and serum zinc concentrations of < 10.7 µmol/L had overall prevalences at baseline and 12 mo of 28% and 15%, 9% and 18%, and 22% and 27%, respectively. After the intervention, there were no significant differences in any measure of iron or zinc status between the CC and the PR groups. However, hemoglobin was significantly higher (120 g/L compared with 117 g/L; P = 0.012) and the prevalence of anemia was lower (13% compared with 23%; P = 0.06) in the PR group than in the IF group, which could be explained by differences in daily iron intake between the 2 groups.

Conclusion: Extensive reduction in the phytate content of weaning cereals had little long-term effect on the iron and zinc status of Swedish infants.

Keyword
Infants, cereals, iron, zinc, phytate, randomized controlled trial, weaning, Sweden
Identifiers
urn:nbn:se:umu:diva-30976 (URN)
Available from: 2010-01-25 Created: 2010-01-25 Last updated: 2017-12-12
2. Effects of weaning cereals with different phytate content on growth, development and morbidity: a randomized intervention trial in infants from 6 to 12 months of age.
Open this publication in new window or tab >>Effects of weaning cereals with different phytate content on growth, development and morbidity: a randomized intervention trial in infants from 6 to 12 months of age.
Show others...
2004 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 93, no 12, 1575-1582 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Phytate decreases iron and zinc bioavailability and contributes to deficiencies of iron and zinc, potentially causing anaemia, poor psychomotor development, impaired growth and increased risk of diarrhoea and respiratory infections. AIM: To investigate whether a reduced dietary intake of phytate, either via extensively phytate-reduced infant cereals [milk cereal drinks (MCDs) and porridge] or a milk-based infant formula, would improve growth and development and reduce morbidity in infants. DESIGN: Infants (n = 300) were, in a double-blind design, randomized to three diet intervention groups from 6 to 12 mo of age-commercial MCD and porridge (CC group), phytate-reduced MCD and phytate-reduced porridge (PR group), or milkbased infant formula and porridge with regular phytate content (IF group)-then followed until 18 mo. Dietary intake, anthropometry, development (Bayley Scales of Infant Development) and episodes of infectious diseases were registered. Results: There were no significant differences between study groups in growth, development or morbidity until 12 mo of age. The IF group had a 77% higher risk (95% CI: 1.05-2.97) of diarrhoea compared to the PR group during the 12-17-mo period. Infants with haemoglobin concentration (Hb) < 110 g/l at 12 mo had lower attained weight at 18 mo (11.14 kg vs 11.73 kg, p = 0.012). Infants with serum zinc (S-Zn) <10.7 pmol/l at 12 mo had higher risk of respiratory infections (RR = 1.74, 95% CI: 1.19-2.56) compared to controls. CONCLUSION: Phytate reduction had no effect on growth, development or incidence of diarrhoeal or respiratory infections. Infants with low Hb or low S-Zn may be at higher risk of poor growth and respiratory infections, even in this high-income population.

Keyword
Anthropometry, Cereals/*chemistry, Child Development/*drug effects, Diarrhea/blood/*epidemiology, Double-Blind Method, Energy Intake, Energy Metabolism, Food; Fortified, Growth Disorders/blood/*epidemiology, Hemoglobins/metabolism, Humans, Infant, Infant Nutrition Physiology, Infant; Low Birth Weight, Infant; Newborn, Phytic Acid/*analysis/*pharmacology, Prevalence, Respiratory Tract Infections/blood/*epidemiology, Weaning, Zinc/blood
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-13729 (URN)10.1111/j.1651-2227.2004.tb00846.x (DOI)15841764 (PubMedID)
Available from: 2008-06-24 Created: 2008-06-24 Last updated: 2017-12-14Bibliographically approved
3. Dietary iron intake is positively associated with hemoglobin concentration during infancy but not during the second year of life.
Open this publication in new window or tab >>Dietary iron intake is positively associated with hemoglobin concentration during infancy but not during the second year of life.
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2004 (English)In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 134, no 5, 1064-1070 p.Article in journal (Refereed) Published
Abstract [en]

Iron status during infancy and early childhood reflects highly dynamic processes, which are affected by both internal and external factors. The regulation of iron metabolism seems to be subjected to developmental changes during infancy, although the exact nature of these changes and their implications are not fully understood. We wanted to explore the association between dietary iron intake and indicators of iron status, and to assess temporal changes in these variables. This was done by secondary analysis of data from a recently conducted dietary intervention trial in which healthy, term, well-nourished infants were randomly assigned to consume iron-fortified infant cereals with regular or low phytate content, or iron-fortified infant formula. Dietary iron intake from 6 to 8 mo and from 9 to 11 mo was associated with hemoglobin (Hb) concentration at 9 mo (r = 0.27, P < 0.001) and 12 mo (r = 0.21, P = 0.001), respectively, but iron intake from 12 to 18 mo was not associated with Hb at 18 mo. In contrast, iron intake from 6 to 11 mo was not associated with serum ferritin (S-Ft) at 9 or 12 mo, whereas iron intake from 12 to 17 mo was positively associated with S-Ft at 18 mo (r = 0.14, P = 0.032). These shifts in associations between dietary iron intake, and Hb and S-Ft, respectively, may be due to developmental changes in the channeling of dietary iron to erythropoiesis relative to storage, in the absence of iron deficiency anemia. These observations should be taken into consideration when evaluating iron nutritional status during infancy and early childhood.

Keyword
Iron, infancy, cerals
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-16360 (URN)15113946 (PubMedID)
Available from: 2008-01-10 Created: 2008-01-10 Last updated: 2017-12-14Bibliographically approved
4. A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: interactions between iron and zinc
Open this publication in new window or tab >>A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: interactions between iron and zinc
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2003 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 77, no 4, 883-890 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Combined supplementation with iron and zinc during infancy may be effective in preventing deficiencies of these micronutrients, but knowledge of their potential interactions when given together is insufficient. OBJECTIVE: The goal was to compare the effect in infants of combined supplementation with iron and zinc and of supplementation with single micronutrients on iron and zinc status. 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 + 10 mg Zn (Fe+Zn group), or placebo from 6 to 12 mo of age. Venous blood samples were collected at the start and end of the study. Five hundred forty-nine infants completed the supplementation and had both baseline and follow-up blood samples available for analysis. RESULTS: Baseline prevalences of anemia, iron deficiency anemia (anemia and low serum ferritin), and low serum zinc (< 10.7 micromol/L) were 41%, 8%, and 78%, respectively. After supplementation, the Fe group had higher hemoglobin (119.4 compared with 115.3 g/L; P < 0.05) and serum ferritin (46.5 compared with 32.3 microg/L; P < 0.05) values than did the Fe+Zn group, indicating an effect of zinc on iron absorption. The Zn group had higher serum zinc (11.58 compared with 9.06 micromol/L; P < 0.05) than did the placebo group. There was a dose effect on serum ferritin in the Fe and Fe+Zn groups, but at different levels. There was a significant dose effect on serum zinc in the Zn group, whereas no dose effect was found in the Fe+Zn group beyond 7 mg Zn/d. CONCLUSION: Supplementation with iron and zinc was less efficacious than were single supplements in improving iron and zinc status, with evidence of an interaction between iron and zinc when the combined supplement was given.

Keyword
Iron, zinc, infants, randomized controlled trial, anemia, Indonesia, micronutrient supplementation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-3994 (URN)12663287 (PubMedID)
Available from: 2004-05-12 Created: 2004-05-12 Last updated: 2017-12-14Bibliographically approved
5. A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: effects on growth and development.
Open this publication in new window or tab >>A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: effects on growth and development.
Show others...
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.

Keyword
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
Identifiers
urn:nbn:se:umu:diva-13730 (URN)15321815 (PubMedID)
Available from: 2007-09-05 Created: 2007-09-05 Last updated: 2017-12-14Bibliographically approved

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