Journal of Nutrition LabDiet, Your World of Nutritional Answers

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gross, R.
Right arrow Articles by Lopez, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gross, R.
Right arrow Articles by Lopez, G.
© 2005 The American Society for Nutritional Sciences J. Nutr. 135:628S-630S, March 2005

International Research on Infant Supplementation: Randomized Controlled Trials of Micronutrient Supplementation During Infancy

The International Research on Infant Supplementation Initiative1,2

Rainer Gross3, Spinnler Benade* and Guillermo Lopez{dagger}

UNICEF, New York; * Nutrition Intervention Research Unit, Medical Research Council, Cape Town, South Africa; and {dagger} Instituto de Investigaçión Nutricional, Universidad La Molina, Lima, Peru

3To whom correspondence should be addressed. E-mail: rgross{at}unicef.org.


   ABSTRACT
TOP
 ABSTRACT
LITERATURE CITED
 
The International Research on Infant Supplementation trials emerged as an attempt to develop a credible evidence base to guide policy decision making in this area. The fact that infant diets in developing country settings are more often deficient in multiple micronutrients rather than in single nutrients and/or energy was increasingly recognized during the 1990s. The concept of a "foodlet," a crushable hybrid between a tablet and a food that is water dispersible, was developed at the first IRIS meeting in Rio de Janeiro in 1999. Trials were performed in 4 countries: Indonesia, Peru, South Africa, and Vietnam. Four different formulations of foodlets were tested: a daily placebo supplement, a daily iron supplement, a daily multiple micronutrient supplement, and a weekly multiple micronutrient supplement with a placebo on the other 6 d. The multiple micronutrient foodlets contained adequate daily intakes of 13 micronutrients considered most likely to be inadequate in infant diets. The foodlets were produced in Peru and distributed to all 4 of the country study sites. The methods used in the efficacy trials were standardized across countries, and the trials were carried out in infants 6–11 mo of age for 6 mo. Anthropometry was measured monthly and morbidity checked daily. Blood samples were collected at baseline and at the end of the trial. The data and the biological samples collected in each country were analyzed centrally. The results of this remarkable international collaboration are encouraging and, hopefully, will spur the development of programs in this area of nutrition interventions.

KEY WORDS: • multiple micronutrients • infant supplementation • anemia • UNICEF • IRIS

Introduction and background

The International Research on Infant Supplementation (IRIS) initiative, the concepts behind it, and its objectives evolved during the second half of the 1990s. The concept of "hidden hunger" first brought to worldwide attention at a conference held by WHO and UNICEF (United Nations Children’s Fund) in Montreal in 1991, led to a large collaborative effort during the 1990s for the elimination of vitamin A in young children and iodine deficiencies in whole populations (1–2). The fact that infant diets in developing country settings are more often deficient in multiple micronutrients rather than single nutrients and/or energy was increasingly recognized during the 1990s, and the lack of policy guidance on how to resolve these issues led to the creation of IRIS. A global strategy exists for infant and young child feeding (3), but the global-level program recommendations for nutrient supplementation during infancy are restricted to just 2 nutrients: iron (4) and vitamin A (5). The development of policy guidelines increasingly requires an adequate evidence base, which, even for the majority of single micronutrients, is recognized to be poor (6). Although the potential benefit of multiple micronutrient supplement interventions is hypothetically strong, there is no concrete evidence of this in practice. The notion of developing a multiple micronutrient supplement for use during infancy and of testing its efficacy in randomized controlled trials thus emerged from these realizations as an attempt to develop a credible evidence base to guide policy decision making.

The steps leading to IRIS

The IRIS initiative originated at a workshop in Rio de Janeiro in 1999, where 3 key theoretical convictions were identified: 1) micronutrient deficiencies rarely occur as single nutrient problems but rather as deficiencies of multiple micronutrients concurrently and therefore should be addressed concurrently, 2) the combination of micronutrients to provide an average of one recommended dietary allowance or less is inherently safe, and 3) a convenient, novel, and perhaps intrinsically sustainable approach to public health delivery of multiple micronutrients to an infant population would be in the form of an edible food substance. The term "foodlet" was coined during the meeting, the specifications of such a product were defined, and the outline of a protocol for randomized controlled trials of their efficacy was developed (7). Subsequent to this, multiple micronutrient supplement product development was initiated and preliminary field testing was realized. The process of product development and the description of the common protocol were further communicated at a meeting in Peru in 2001, together with the sharing of baseline data from the 4 countries that had agreed to realize the IRIS trials and some preliminary findings of the centralized data analysis (8).

The IRIS concept

The efficacy trials of the foodlet multiple micronutrient supplements were carried out in 6- to 12-mo-old infants in Indonesia, Peru, South Africa, and Vietnam during 2000. Central to the IRIS concept was the development of a new multiple micronutrient supplement for young children. The aim was to find a product that could not be easily swallowed, because of the dangers of accidental overdose if infants ate a month’s supply of iron in one go. The foodlet is a crumbly hybrid between a food and a tablet, which is a chewable, flavored, reasonably soluble, water dispersible, and affordable product, with a good shelf life (9). The product was formulated by an international supplier of micronutrients (Roche Laboratories) and was manufactured by a local pharmaceutical company in Peru (Hersil, SA) and was distributed from the central production facility to all 4 of the country study sites.

The nutrient levels used in the foodlets for the IRIS studies are shown in Table 1. The IRIS protocol included 4 treatment groups, for each of which the families received identical-looking blister packs with 7 foodlets, one for each day of the week. The blister pack of the daily multiple micronutrient supplement group had multiple micronutrient in all 7 foodlets. The blister pack of the weekly multiple micronutrient group had multiple micronutrient supplements in only one foodlet, and a placebo the other 6 d. The blister pack of the daily iron group had iron in all 7 foodlets. A fourth placebo group had no nutrients in the foodlets. The daily multiple micronutrient supplement foodlet contained 13 nutrients at the level of one adequate intake, which, in the absence of adequate data, are used as a surrogate for the recommended dietary allowance in infants or for the average daily intake that is considered sufficient to meet the requirements of 97% to 98% of the population (6). The weekly multiple micronutrient foodlets contained the same 13 micronutrients but at double the dose, taken one day of the week, with 6 placebo foodlets in the blister pack to be taken on the other 6 d. The daily iron foodlets contained 10 mg of iron for consumption each day.


View this table:
[in this window]
[in a new window]
  		TABLE 1 Nutrients doses used in the IRIS trials foodlets, by treatment group1

 
The methods used in the efficacy trials were standardized across countries, and the data and biological samples collected were analyzed centrally. A common protocol was developed for carrying out the study, including the development of the baseline surveys (10). For the methods for measuring the morbidity, growth, and clinical biochemical indicators to be common across sites, the questionnaire was developed according to the recommendations of Gross et al. (11), and comprised 4 different sections: the household questionnaire, which was used at baseline only; the monthly weight and height recording form; the weekly health visit recording form; and the weekly health and infant feeding information questionnaire. All equipment used to collect the blood samples was purchased centrally, and the biological samples collected were sent on dry ice to Germany, where they were analyzed at the Micronutrient Laboratory of the Institute of Biological Chemistry and Nutrition at the University of Hohenheim. At the end of the trials in the 4 countries, the data were sent to the Medical Research Council in South Africa, where statistical analysis was carried out. A report containing the pooled data analysis was shared with, and was discussed by, the participants of the 4 countries at a meeting held in New York in December 2002 (12).

Conclusions and follow-up

The results of the 4 country trials and the combined pooled data analysis as reported in this supplement all contribute to the growing evidence base, indicating the extra benefits to be derived from multiple micronutrient supplements compared with single nutrient supplements of iron, for example, for preventing the development of anemia during infancy. The next steps required are for effectiveness studies to be carried out to learn how to implement the foodlet intervention at the program scale in the field. There have been numerous recommendations on how and why such steps should be taken (13). Hopefully, the publication of the results of the IRIS trials will give impetus to the development of policy guidance and the apportioning of funds necessary for rolling out programs for improving the nutrient status of infants through multiple micronutrient interventions such as the foodlet.


   FOOTNOTES
 
1 Published in a supplement to The Journal of Nutrition. The research and supplement publication were supported by UNICEF. The contents are the sole responsibility of the authors and do not represent the official views of UNICEF. Guest Editors were Roger Shrimpton, Institute of Child Health in London, United Kingdom, and Lindsay Allen, University of California, Davis, California. Back

2 Funded by UNICEF. Back


   LITERATURE CITED
TOP
 ABSTRACT
 LITERATURE CITED
 

1. Shrimpton, R. & Schultink, W. (2002) Can supplements help meet the micronutrient needs of the developing world?. Proc. Nutr. Soc. 61:223-229.[Medline]

2. Hetzel, B. S. (2002) Elimination of iodine deficiency disorders—the role of the International Council in the global partnership. Bull. WHO 80:410-417.[Medline]

3. WHO/UNICEF (2003) Global Strategy for Infant and Young Child Feeding 2003 World Health Organization Geneva, Switzerland.

4. UNICEF/UNU/WHO (2001) Iron deficiency Anaemia: Assessment, Prevention and Control. A Guide for Programme Managers 2001 World Health Organization Geneva, Switzerland.

5. WHO/UNICEF/IVACG (1997) Vitamin A Supplements: A Guide to Their Use in the Treatment and Prevention of Vitamin A Deficiency and Xerophthalmia 2nd ed. 1997 World Health Organization Geneva, Switzerland.

6. Institute of Medicine (2002) Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc 2002 National Academy Press Washington, DC.

7. Gross, R. (2001) Micronutrient Supplementation Throughout the Lifecycle 2001 UNICEF New York, NY.

8. Gross, R., Dwivedi, A. & Solomons, N. W. (2003) Introduction to the Proceedings of the International Research on Infant Supplementation (IRIS) Initiative. Food Nutr. Bull. 24:S3-S6.[Medline]

9. Lock, G. (2003) The foodlet vehicle designed for and used in the IRIS I intervention. Food Nutr. Bull. 24:S16-S19.[Medline]

10. Smuts, C. M., Spinnler Benade, A. J., Berger, J., Hop, L. T., Lopez de Romano, G., Untoro, J., Karyadi, E., Erhardt, J. & Gross, R. (2002) IRIS I: a foodlet-based multiple micronutrient intervention in four contrasting populations: description of a multicenter field trial. Food Nutr. Bull. 24:S27-S33.

11. Gross, R., Kielmann, A., Korte, R., Schoeneberger, H. & Schultink, W. (1997) Nutritional baseline surveys in communities. Erhardt, J. Gross, R. eds. Nutrition Surveys and Calculations: Guidelines, Software and Additional Information 1997 (online). http://www.nutrisurvey.de [accessed August 8, 2004].

12. Schultink, W., Gross, R., Smuts, C. M., Benade, A.J.S., Lombard, C. J. & Swanevelder, S. A. (2002) International Research on Infant Supplementation (IRIS): Analysis of the Multi-Centre Study on the Efficacy of Multi-Micronutrient Supplementation in Small Children 2002 MRC South Africa Cape Town, South Africa.

13. Institute of Medicine (1998) Prevention of Micronutrient Deficiencies: Tools for Policy Makers and Public Health Workers 1998 National Academy Press Washington, DC.




This article has been cited by other articles:


Home page
 J Trop PediatrHome page
A. Chatterjee, R. J. Bosch, D. J. Hunter, K. Manji, G. I. Msamanga, and W. W. Fawzi
Vitamin A and Vitamin B-12 Concentrations in Relation to Mortality and Morbidity among Children Born to HIV-Infected Women
J Trop Pediatr, June 5, 2009; (2009) fmp045v1.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
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]

Home page
 Am. J. Clin. Nutr.Home page
M. Wijaya-Erhardt, J. Untoro, E. Karyadi, L. Wibowo, and R. Gross
Efficacy of daily and weekly multiple micronutrient food-like tablets for the correction of iodine deficiency in Indonesian males aged 6-12 mo
Am. J. Clinical Nutrition, January 1, 2007; 85(1): 137 - 143.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gross, R.
Right arrow Articles by Lopez, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gross, R.
Right arrow Articles by Lopez, G.

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Copyright © 2005 by American Society for Nutrition