Zinc supplementation and stunted infants in Ethiopia: a randomised controlled trial

doi:10.1016/S0140-6736(00)02348-5

The Lancet

Volume 355, Issue 9220, 10 June 2000, Pages 2021-2026

https://doi.org/10.1016/S0140-6736(00)02348-5 Get rights and content

Summary

Background

Stunting is highly prevalent in Ethiopia and many other developing countries but the reason for it is poorly understood. Zinc is essential for growth but diets in such countries often do not contain zinc in sufficient quantity or of sufficient bioavailability. Thus zinc deficiency may play a major role in stunting. The aim of the study was to investigate whether the low rate of linear growth of apparently healthy breastfed infants in a rural village in Ethiopia could be improved by zinc supplementation.

Methods

A randomised, double-blind, placebo-controlled trial was done on apparently healthy breastfed infants aged 6–12 months. 100 non-stunted (length-for-age, Z score <−2) were matched for age and sex with 100 randomly selected stunted (>−2) infants. Infants, both stunted and non stunted, were matched by sex, age (within 2 months) and recumbent length (within 3 cm) for random assignment, to receive a zinc supplement (10 mg zinc per day, as zinc sulphate) or placebo, 6 days a week for 6 months. Anthropometric measurements were taken monthly, data on illness and appetite were collected daily, and samples of serum and hair were taken at the end of the intervention for the analysis of zinc.

Findings

The length of stunted infants increased significantly more (p<0·001) when supplemented with zinc (7·0 cm [SE 1·1]) than with placebo (2·8 cm [0·9]); and the effect was greater (p<0·01) than in non-stunted infants (6·6 [0·9] vs 5·0 [0·8] cm for the zinc and placebo groups respectively, p<0·01). Zinc supplementation also increased the weight of stunted children (1·73 [0·39] vs 0·95 [0·39] kg for the corresponding placebo group, p<0·001) and of non-stunted children (1·19 [0·39] vs 1·02 [0·32] kg for the corresponding placebo group, p<0·05). Zinc supplementation resulted in a markedly lower incidence of anorexia and morbidity from cough, diarrhoea, fever, and vomiting in the stunted children. The total number of these conditions per child was 1·56 and 1·11 in the stunted and non-stunted zinc supplemented children versus 3·38 and 1·64 in the stunted and non-stunted placebo-treated children, respectively. At the end of the intervention period, the concentrations of zinc in serum and hair of stunted infants, who had not been supplemented with zinc, were lower than the respective concentrations of zinc in serum and hair of their non-stunted counterparts.

Interpretation

Combating zinc deficiency can increase the growth rate of stunted children to that of non-stunted infants in rural Ethiopia. This would appear to be due, at least in part, to reduction in morbidity from infection and increased appetite.

Introduction

Zinc has long been recognised as an essential micronutrient for health and normal growth, but only in the past 20 years has the manifestation of mild zinc deficiency been documented in man.¹ Zinc is a constituent of a number of enzymes and as such is involved in a large number of metabolic processes. Mild-to-severe zinc deficiency disturbs several biological functions such as gene expression, protein synthesis, immunity, skeletal growth and maturation, gonad development and pregnancy outcomes, and taste perception and appetite.² It has been suggested that zinc deficiency may have a role in stunting, especially in developing countries.³ The assessment of zinc status is hampered by the lack of a single sensitive and specific biochemical factor. At present, the most reliable method to assess zinc status in children would appear to be to measure increase in growth velocity in response to zinc supplementation in physiological amounts.

The early studies in which adolescents with nutritional dwarfism in Egypt⁴ and Iran⁵ were supplemented with zinc did not show any consistent effect of zinc on linear growth. However, increased growth with zinc supplementation was found in malnourished infants and children.6, 7, 8 Controlled studies in apparently healthy infants and children from developing and affluent countries have shown a positive effect of zinc supplementation on linear growth,9, 10 and also on lean body mass.11, 12

57% of infants aged 6–11 months in Ethiopia are stunted.¹³ Moreover, the dietary pattern is largely cereal and tubers and is low in animal products. Thus suboptimal zinc status is likely to exist in the population. Three earlier studies in subSaharan Africa found no effect of zinc supplementation in linear growth in infants and young children.12, 14, 15 Therefore, we decided to test whether zinc deficiency is responsible for the low rate of growth of stunted children in Ethiopia. We did a randomised, double-blind, placebo-controlled study in which stunted and non-stunted infants aged 6–12 months were supplemented with zinc (10 mg/day) or a placebo, 6 days a week) for 6 months. Length and other anthropometric factors were measured monthly and the concentrations of zinc in serum and hair was measured at the end of the intervention. Because their incidence has been reported to be reduced by zinc supplementation, information was collected on anorexia¹⁶ and morbidity six days each week.17, 20

Before deciding on the design of this study, it was important to address the question of whether or not it would be ethical to include a placebo group. Stunting is a serious problem in Ethiopia but its cause is poorly understood. We regarded zinc deficiency as a possible major contributing factor but there were no data on the extent of severity of the problem in the country when the study was being conceived in 1994 and 1995. As stated above, other studies in Africa, both before and after the present study was done, have not shown any effect on growth12, 14, 15 although evidence was building up for a role of zinc in growth⁹ that was later confirmed.¹⁰ In Ethiopia, no programmes have ever provided zinc supplements to infants or to any other group of the population. The double-blind placebo-controlled trial is probably the most powerful tool we have to examine whether or not a nutrient deficiency is present that is affecting the health or nutritional status of a group of individuals. It is generally agreed that it is ethical to use a design including a placebo group when there is insufficient evidence to accept or reject the proposed hypothesis and when the individuals enrolled in the study are not being deprived of prophylaxis or treatment.Thus, we regarded the proposed study as ethical and the ethical committee was of the same opinion.

Section snippets

Study individuals

The study area was in the Dodota Sire district, Arsi zone, central Ethiopia, which is about 150 km east of the capital, Addis Ababa. In this district two working centres, Dheera and Hamude, about 40 km apart with available health facilities and access to all-weather road, were selected. The area lies in the Great Rift Valley of Africa with hot weather and a short rainy season. The staple crops are wheat, maize, sorghum, barley, and tef, which are grown for subsistence not profit. Traditional

Results

The number of children recruited in the census was 305 and, of the 50 individuals in each group, complete results over the 6-month period were obtained from 45–47 individuals per group (figure 1). All children in the study were exclusively breastfed for the first 4 months of life. When the intervention commenced, some mothers had begun to provide traditional cereal-based weaning foods. The practice was observed throughout the study period and, among those children who completed the study, 11

Discussion

This study clearly shows that zinc supplementation can halt the stunting process in stunted infants in rural Ethiopia (table 2, figure 2). This would appear to be due, at least in part, to improved appetite, as judged by recording episodes of anorexia, and reduced morbidity from gastrointestinal and respiratory disease (table 4).

During the 6-month intervention period, the LAZ score increased 0·14 thus suggesting that the catch-up growth during this period was 7% of the 2·04 LAZ deficit at

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Previous studies stated that zinc supplements affected appetite positively in individuals having a poor appetite and problems gaining weight [21,22]. Umeta et al. found that a zinc supplement decreased the cases of coughing, diarrhea, fever, anorexia resulting from vomiting, and morbidity in children, and that it helped gain weight [23]. In the present study, the blood zinc level was found to be significantly higher among children defined as having a good appetite by their mothers (p < .05; Table 4).
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ArticlesZinc supplementation and stunted infants in Ethiopia: a randomised controlled trial

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Study individuals

Results

Discussion

Am J Clin Nutr

Am J Clin Nutr

Am J Clin Nutr

Am J Clin Nutr

Am J Clin Nutr

Am J Clin Nutr

Am J Clin Nutr

Am J Clin Nutr

Clin Chem Acta

Am J Clin Nutr

Am J Clin Nutr

Clinical and biochemical spectrum of zinc deficiency in human subjects

Severe zinc deficiency

The worldwide magnitude of protein-energy malnutrition: an overview from the WHO Global Database on Child Growth

Bull World Health Organ

Effect of zinc on lean tissue synthesis during recovery from malnutrition

Eur J Clin Nutr

Articles
Zinc supplementation and stunted infants in Ethiopia: a randomised controlled trial