Effect of provision of daily zinc and iron with several micronutrients on growth and morbidity among young children in Pakistan: a cluster-randomised trial

doi:10.1016/S0140-6736(13)60437-7

The Lancet

Volume 382, Issue 9886, 6–12 July 2013, Pages 29-40

https://doi.org/10.1016/S0140-6736(13)60437-7 Get rights and content

Summary

Background

Powders containing iron and other micronutrients are recommended as a strategy to prevent nutritional anaemia and other micronutrient deficiencies in children. We assessed the effects of provision of two micronutrient powder formulations, with or without zinc, to children in Pakistan.

Methods

We did a cluster randomised trial in urban and rural sites in Sindh, Pakistan. A baseline survey identified 256 clusters, which were randomly assigned (within urban and rural strata, by computer-generated random numbers) to one of three groups: non-supplemented control (group A), micronutrient powder without zinc (group B), or micronutrient powder with 10 mg zinc (group C). Children in the clusters aged 6 months were eligible for inclusion in the study. Powders were to be given daily between 6 and 18 months of age; follow-up was to age 2 years. Micronutrient powder sachets for groups B and C were identical except for colour; investigators and field and supervisory staff were masked to composition of the micronutrient powders until trial completion. Parents knew whether their child was receiving supplementation, but did not know whether the powder contained zinc. Primary outcomes were growth, episodes of diarrhoea, acute lower respiratory tract infection, fever, and incidence of admission to hospital. This trial is registered with ClinicalTrials.gov, number NCT00705445.

Results

The trial was done between Nov 1, 2008, and Dec 31, 2011. 947 children were enrolled in group A clusters, 910 in group B clusters, and 889 in group C clusters. Micronutrient powder administration was associated with lower risk of iron-deficiency anaemia at 18 months compared with the control group (odds ratio [OR] for micronutrient powder without zinc=0·20, 95% CI 0·11–0·36; OR for micronutrient powder with zinc=0·25, 95% CI 0·14–0·44). Compared with the control group, children in the group receiving micronutrient powder without zinc gained an extra 0·31 cm (95% CI 0·03–0·59) between 6 and 18 months of age and children receiving micronutrient powder with zinc an extra 0·56 cm (0·29–0·84). We recorded strong evidence of an increased proportion of days with diarrhoea (p=0·001) and increased incidence of bloody diarrhoea (p=0·003) between 6 and 18 months in the two micronutrient powder groups, and reported chest indrawing (p=0·03). Incidence of febrile episodes or admission to hospital for diarrhoea, respiratory problems, or febrile episodes did not differ between the three groups.

Interpretation

Use of micronutrient powders reduces iron-deficiency anaemia in young children. However, the excess burden of diarrhoea and respiratory morbidities associated with micronutrient powder use and the very small effect on growth recorded suggest that a careful assessment of risks and benefits must be done in populations with malnourished children and high diarrhoea burdens.

Funding

Bill & Melinda Gates Foundation.

Introduction

Worldwide, about 165 million children younger than 5 years were stunted in 2011.¹ Nearly half of all children aged 0–59 months are estimated to be anaemic² and 17% of the world's population is estimated to be at risk of zinc deficiency because of low dietary intake of zinc.³ Zinc supplementation has been identified as an effective intervention to reduce morbidity⁴ and improve growth.⁵ However, there is no consensus on suitable delivery strategies or vehicles for daily zinc supplementation, and hence no preventive zinc supplementation programmes. The development of micronutrient powders containing microencapsulated iron administered on a daily or regular basis offers a way to provide a regular dose of key micronutrients, particularly iron, to children at risk of deficiency and has been recommended by WHO as a delivery strategy for prevention of iron-deficiency anaemia in at-risk populations.⁶ However, most of the evidence relating to micronutrient powders derives from small studies⁷ and there is little evidence of the benefit of inclusion of zinc within micronutrient powders. In a cluster-randomised trial⁸ of daily administration of micronutrient powders containing 10 mg zinc gluconate among children aged 6–12 months in Cambodia, despite slightly higher serum zinc concentrations at 12 months of age in children who received the powder compared with those who did not, the investigators noted no evidence of improved growth. Although micronutrient powders containing iron are generally regarded as safe⁹ and without the concerns associated with the use of iron supplements in malaria-endemic areas,¹⁰ micronutrient powders have not been assessed in large scale trials with prospective morbidity assessment.¹¹

We assessed the effects of provision of two micronutrient powder formulations, with or without zinc, to children aged between 6 and 18 months in urban and rural Pakistan on their growth, micronutrient status, and morbidity.

Section snippets

Study design and participants

We did a cluster randomised trial with three groups in a cohort of children from urban and rural populations in Sindh. Bilal colony is an urban squatter settlement in Karachi with a population of 75 000. Matiari district, the location of the rural study site, is about 200 km from Karachi with an estimated population of 500 000. Both sites have functional health centres and research infrastructure, and are broadly representative of urban and rural Pakistan.

A baseline census was done in the

Results

The study was done between Nov 1, 2008, and Dec 31, 2011. 2786 children in 256 clusters were eligible for the study and after informed consent 2746 entered the study at 6 months of age (figure 1). The appendix shows characteristics of the three groups of children at 6 months of age and initiation of micronutrient powders. Of the 2746 children, 2395 (87%) remained under follow-up at age 12 months, 2271 (83%) at age 18 months, and 1976 (72%) at age 24 months. No clusters were lost.

The three

Discussion

Provision of micronutrient powder from age 6 months was associated with lower risk of iron-deficiency anaemia at 18 months compared with no supplementation. Compared with the control group, children in the group receiving micronutrient powder without zinc gained about an extra 3 mm in height and children receiving micronutrient powder with zinc an extra 6 mm between 6 and 18 months of age. However, we recorded strong evidence of an increased proportion of days with diarrhoea, increased

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ArticlesEffect of provision of daily zinc and iron with several micronutrients on growth and morbidity among young children in Pakistan: a cluster-randomised trial

Summary

Background

Methods

Results

Interpretation

Funding

Introduction

Section snippets

Study design and participants

Results

Discussion

Adv Nutr

Am J Clin Nutr

Lancet

J Nutr

Am J Clin Nutr

J Nutr

J Nutr

Am J Clin Nutr

Lancet

Am J Clin Nutr

J Nutr

J Nutr

Am J Clin Nutr

Estimating the global prevalence of zinc deficiency: results based on zinc availability in national food supplies and the prevalence of stunting

PLoS One

Preventive zinc supplementation in developing countries: impact on mortality and morbidity due to diarrhoea, pneumonia and malaria

BMC Public Health

Effect of preventive zinc supplementation on linear growth in children under 5 years of age in developing countries: a meta-analysis of studies for input to the lives saved tool

BMC Public Health

Guideline: use of multiple micronutrient powders for home fortification of foods consumed by infants and children 6–23 months of age

Home fortification of foods with multiple micronutrient powders for health and nutrition in children under two years of age

Cochrane Database Syst Rev

Effect of micronutrient sprinkles on reducing anemia: a cluster-randomized effectiveness trial

Arch Pediatr Adolesc Med

UNICEF and the global strategy on infant and young child feeding. Understanding the past, planning the future

Micronutrients (including zinc) reduce diarrhoea in children: the Pakistan sprinkles diarrhoea study

Arch Dis Child

Measurement and standardization protocols for anthropometry used in the construction of a new international growth reference

Food Nutr Bull

Articles
Effect of provision of daily zinc and iron with several micronutrients on growth and morbidity among young children in Pakistan: a cluster-randomised trial