Zinc deficiency: what are the most appropriate interventions?
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《英国医生杂志》
1 Centre for International Child Health, Institute of Child Health, London WC1N 1EH, 2 Nutrition Section, Programme Division, Unicef, New York, USA, 3 Health Section, Programme Division, Unicef
Correspondence to: R Shrimpton Roger.Shrimpton@ich.ucl.ac.uk
Introduction
Strong evidence exists that zinc supplements improve the prognosis of children being treated for diarrhoeal disease. A pooled analysis of randomised controlled trials of therapeutic zinc in children with diarrhoea showed that children with acute diarrhoea given zinc supplements had a 15% lower probability of continuing diarrhoea on a given day compared with those in the control group; children with persistent diarrhoea had a 24% lower probability of continuing diarrhoea. In addition, children with persistent diarrhoea had a 42% lower rate of treatment failure or death if given zinc supplements.9
Summary points
Zinc deficiency is common in developing countries with high mortality
Regular zinc supplements can greatly reduce common infant morbidities in developing countries
Zinc is also an effective adjunct treatment for diarrhoeal disease
Zinc deficiency commonly coexists with other micronutrient deficiencies including iron, making single supplements inappropriate
Until the results of trials of multiple micronutrient interventions are available, zinc supplements should be given to children with infections
The most effective way to deliver zinc supplements in diarrhoeal disease control programmes is not yet clear. Since zinc supplementation reduces the duration and severity of diarrhoeal episodes it might be beneficial to add zinc to oral rehydration solution; one of the shortcomings of oral rehydration therapy is that the frequency and volume of stools is not reduced. However, studies of the efficacy of including zinc in oral rehydration solutions are not conclusive.10 In addition, many countries promote the use of home made fluids.
WHO and Unicef propose to distribute blister packs of 10 dispersible tablets of 20 mg zinc for daily consumption as the part of the treatment of diarrhoea. The use of zinc as an adjunct therapy significantly improves the cost effectiveness of standard management of diarrhoea.11 Achieving and maintaining high levels of coverage of current interventions for diarrhoeal disease, such as oral rehydration therapy, are already proving difficult.12 The challenge of promoting zinc supplements to treat diarrhoea is therefore considerable.
Preventive action
Regular zinc supplements have been shown to prevent disease. Supplementation seems to be most beneficial in children with lower birth weights and those with stunted growth or zinc deficiency. The supplementation of low birthweight infants in Brazil from birth for 8 weeks reduced both diarrhoea and coughs by a third in the first six months of life.w2 Pooled analysis of randomised control trials found that zinc supplements reduced diarrhoeal diseases by 18% and pneumonia by 41% in preschool children.13 The results for pneumonia are remarkable considering the challenge that pneumonia presents from a child health perspective.14 Zinc supplementation has also been shown to reduce cases of falciparum malaria presenting at health centres in Africa and Papua New Guinea.w3 w4 Zinc supplementation of babies with low birth weight in India reduced mortality during infancy by a third.15 Maternal zinc supplementation during pregnancy improves neonatal immune status, early neonatal morbidity, and infant infections but not birth weight.w1
Zinc supplementation may also prevent failure of child growth, although the evidence is weaker than for prevention of disease. A meta-analysis of randomised controlled trials of the effects of supplemental zinc on growth of prepubertal children found that height and weight growth were only moderately improved, and the greatest responses were shown by children who were initially underweight or stunted.16 Zinc supplementation trials in infants with birth weights > 2.5 kg have shown little effect on preventing growth faltering in the second half of infancy in Indonesia.w5 w6 In Ethiopia, zinc supplements increased length growth of stunted infants, but these infants were not selected on birthweight criteria.w7 Trials in infants from birth to 6 months in Bangladesh showed growth effects only in those with initial low zinc status.w8
Adding zinc to treatment for diarrhoeal disease is the first step to tackle deficiency
Credit: CAROLINE PENN/PANOS
Administering supplements
Consensus is growing that zinc should not be promoted as a single nutrient supplement for preventing zinc deficiency in young children and their mothers. This is because many people have multiple micronutrient deficiencies. Anaemia is a marker for both iron and zinc deficiency. The use of iron and folate supplements to treat and prevent anaemia during pregnancy and lactation has been recommended for three decades,w9 and iron for the treatment of anaemia in young children for almost a decade.w10 Progress in reducing anaemia in developing countries has, however, been disappointing,w11 largely because of poor execution of programmes, especially the inadequate preparation of health staff and systems to deliver the supplements.17 w12 In addition, only a half of anaemia is thought to be solely due to iron deficiency; other micronutrients, such as vitamin A and vitamin C, are implicated as well as infection and blood loss.w13 The diets of anaemic women in developing countries are more often deficient in micronutrients than they are deficient in energy.18 w14 w15 Infant diets also commonly have inadequacies in zinc and iron as well as B vitamins.19
Zinc, iron, vitamin A, and copper all potentially interact and interfere with each other's absorption and metabolism when used as single nutrient supplements.20 21 w16 Trials are ongoing of a multiple micronutrient supplement formulated by WHO, Unicef, and United Nations University for mothers during pregnancy and lactationw17 w18; this supplement could eventually replace iron and folate if proved effective. Various trials of multiple micronutrients as preventive supplements during infancy and childhood have been carried out or are under way.w19 w20 w21 w22 The results of this research need to be brought together to determine whether to promote multiple micronutrient supplementation programmes during pregnancy, lactation, and infancy.
Zinc fortification
Increased consumption of foods with a high content of absorbable zinc is the long term sustainable solution to problems of zinc deficiency. Strategies are being developed that target agricultural and food production, household food processing, and dietary modification.5 Zinc is highly correlated with the protein content of foods, but the availability of zinc in protein rich plant foods is much less than that in animal protein foods. Plant breeding efforts aim to produce new cereal varieties with higher zinc concentrations that are more available by reducing concentrations of inhibitors such a phytate and increasing enhancers of absorption such as the sulphurous amino acids. At the household level, food processing methods for increasing the availability of zinc in cereal grains and legumes include sprouting, fermenting, and soaking. These programme interventions are complex and require considerable investment in behaviour change, which takes time. As yet no evidence exists of their effectiveness for preventing zinc deficiency, especially in mothers and young children.
Conclusions
World Health Organization. The World Health Report 2002: reducing risks, promoting healthy life. Geneva: WHO, 2002.
Prasad AS. Zinc deficiency has been known for 40 years but ignored by global health organizations. BMJ 2003;326: 409-10.
Black R. Micronutrient deficiency—an underlying cause of morbidity and mortality. Bull World Health Organ 2003;81: 79.
Jones G, Steketee RW, Black RE, Bhutta ZA, Morris SS, Bellagio Child Survival Study Group. How many child deaths can we prevent this year? Lancet 2003;362: 65-71.
International Zinc Nutrition Consultative Group. Assessment of the risk of zinc deficiency in populations and options for its control. Food Nutr Bull 2004;25: S91-204.
World Health Organization. Complementary feeding of young children in developing countries: a review of current scientific knowledge. Geneva: WHO, 1998 (WHO/NUT/98.1).
Gibson RS, Yeudall F, Drost N, Mtitimuni B, Cullinan T. Dietary interventions to prevent zinc deficiency. Am J Clin Nutr 1998;68(suppl): 484-7S.
World Health Organization, Unicef. Joint statement on the management of acute diarrhoea. Geneva: WHO, 2004.
Zinc Investigators Collaborative Group. Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomised controlled trials. Am J Clin Nutr 2000;72: 1516-22.
Bahl R, Bhandari N, Saksena M, Strand T, Kumar GT, Bhan MK, et al. Efficacy of zinc-fortified oral rehydration solution in 6-35 month old children with acute diarrhea. J Pediatr 2002;141: 677-82.
Robberstad B, Strand T, Black RE, Somerfelt H. Cost effectiveness of zinc as an adjunct therapy for acute childhood diarrhoea in developing countries. Bull World Health Organ 2004;82: 523-31.
Bryce J, el Arifeen S, Parlyo G, Lanata CF, Gwatkin D, Habicht J-P, et al. Reducing child mortality: can public health deliver? Lancet 2003;362: 159-64.
Zinc Investigators Collaborative Group. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: Pooled analysis of randomised controlled trials. J Pediatr 1999;135: 689-97.
Black RE, Morris SS, Bryce J. Where and why are 10 million children dying every year? Lancet 2003;361: 226-34.
Sazawal S, Black RE, Menon VP, Dinghra P, Caulfield LE, Dhingra U, et al. Zinc supplementation in infants born small for gestational age reduces mortality: a prospective, randomised controlled trial. Pediatrics 2001;108: 1280-6.
Brown KH, Peerson JM, Rivera J, Allen LH. Effect of supplemental zinc on the growth and serum zinc concentrations of prepubertal children: a meta-analysis of randomised controlled trials. Am J Clin Nutr 2002;75: 1062-71.
Yip R. Iron supplementation: Country level experiences and lessons learned. J Nutr 2002;132: 859-61S.
Dijkhuizen MA, Wieringa FT, West CE, Muherdiyantiningsih, Muhilal. Concurrent micronutrient deficiencies in lactating mothers and their infants in Indonesia. Am J Clin Nutr 2001;73: 786-91.
Dewey KG, Brown KH. Update on technical issues concerning complementary feeding of young children in developing countries and implications for intervention programs. Food Nutr Bull 2003;24: 5-28.
Donangelo CM, Woodhouse LR, King SM, Viteri FE, King JC. Supplemental zinc lowers measures of iron status in young women with low iron reserves. J Nutr 2002;132: 1860-4.
O'Brien KO, Zavaleta N, Caulfield LE, Wen J, Abrams SA. Prenatal iron supplements impair zinc absorption in pregnant Peruvian women. J Nutr 2000;130: 2251-5.
Salgueiro MJ, Zubigalla M, Lysioek A, Caro R, Weill R, Boccio J. Fortification strategies to combat zinc and iron deficiency. Nutr Rev 2002;60: 52-8.
Herman S, Griffin IJ, Suwarti S, Ernawati F, Permaesih D, Pambudi, et al. Cofortification of iron-fortified flour with zinc sulphate but not zinc oxide, decreases iron absorption in Indonesian children. Am J Clin Nutr 2002;76: 813-7.(Roger Shrimpton, honorary senior researc)
Correspondence to: R Shrimpton Roger.Shrimpton@ich.ucl.ac.uk
Introduction
Strong evidence exists that zinc supplements improve the prognosis of children being treated for diarrhoeal disease. A pooled analysis of randomised controlled trials of therapeutic zinc in children with diarrhoea showed that children with acute diarrhoea given zinc supplements had a 15% lower probability of continuing diarrhoea on a given day compared with those in the control group; children with persistent diarrhoea had a 24% lower probability of continuing diarrhoea. In addition, children with persistent diarrhoea had a 42% lower rate of treatment failure or death if given zinc supplements.9
Summary points
Zinc deficiency is common in developing countries with high mortality
Regular zinc supplements can greatly reduce common infant morbidities in developing countries
Zinc is also an effective adjunct treatment for diarrhoeal disease
Zinc deficiency commonly coexists with other micronutrient deficiencies including iron, making single supplements inappropriate
Until the results of trials of multiple micronutrient interventions are available, zinc supplements should be given to children with infections
The most effective way to deliver zinc supplements in diarrhoeal disease control programmes is not yet clear. Since zinc supplementation reduces the duration and severity of diarrhoeal episodes it might be beneficial to add zinc to oral rehydration solution; one of the shortcomings of oral rehydration therapy is that the frequency and volume of stools is not reduced. However, studies of the efficacy of including zinc in oral rehydration solutions are not conclusive.10 In addition, many countries promote the use of home made fluids.
WHO and Unicef propose to distribute blister packs of 10 dispersible tablets of 20 mg zinc for daily consumption as the part of the treatment of diarrhoea. The use of zinc as an adjunct therapy significantly improves the cost effectiveness of standard management of diarrhoea.11 Achieving and maintaining high levels of coverage of current interventions for diarrhoeal disease, such as oral rehydration therapy, are already proving difficult.12 The challenge of promoting zinc supplements to treat diarrhoea is therefore considerable.
Preventive action
Regular zinc supplements have been shown to prevent disease. Supplementation seems to be most beneficial in children with lower birth weights and those with stunted growth or zinc deficiency. The supplementation of low birthweight infants in Brazil from birth for 8 weeks reduced both diarrhoea and coughs by a third in the first six months of life.w2 Pooled analysis of randomised control trials found that zinc supplements reduced diarrhoeal diseases by 18% and pneumonia by 41% in preschool children.13 The results for pneumonia are remarkable considering the challenge that pneumonia presents from a child health perspective.14 Zinc supplementation has also been shown to reduce cases of falciparum malaria presenting at health centres in Africa and Papua New Guinea.w3 w4 Zinc supplementation of babies with low birth weight in India reduced mortality during infancy by a third.15 Maternal zinc supplementation during pregnancy improves neonatal immune status, early neonatal morbidity, and infant infections but not birth weight.w1
Zinc supplementation may also prevent failure of child growth, although the evidence is weaker than for prevention of disease. A meta-analysis of randomised controlled trials of the effects of supplemental zinc on growth of prepubertal children found that height and weight growth were only moderately improved, and the greatest responses were shown by children who were initially underweight or stunted.16 Zinc supplementation trials in infants with birth weights > 2.5 kg have shown little effect on preventing growth faltering in the second half of infancy in Indonesia.w5 w6 In Ethiopia, zinc supplements increased length growth of stunted infants, but these infants were not selected on birthweight criteria.w7 Trials in infants from birth to 6 months in Bangladesh showed growth effects only in those with initial low zinc status.w8
Adding zinc to treatment for diarrhoeal disease is the first step to tackle deficiency
Credit: CAROLINE PENN/PANOS
Administering supplements
Consensus is growing that zinc should not be promoted as a single nutrient supplement for preventing zinc deficiency in young children and their mothers. This is because many people have multiple micronutrient deficiencies. Anaemia is a marker for both iron and zinc deficiency. The use of iron and folate supplements to treat and prevent anaemia during pregnancy and lactation has been recommended for three decades,w9 and iron for the treatment of anaemia in young children for almost a decade.w10 Progress in reducing anaemia in developing countries has, however, been disappointing,w11 largely because of poor execution of programmes, especially the inadequate preparation of health staff and systems to deliver the supplements.17 w12 In addition, only a half of anaemia is thought to be solely due to iron deficiency; other micronutrients, such as vitamin A and vitamin C, are implicated as well as infection and blood loss.w13 The diets of anaemic women in developing countries are more often deficient in micronutrients than they are deficient in energy.18 w14 w15 Infant diets also commonly have inadequacies in zinc and iron as well as B vitamins.19
Zinc, iron, vitamin A, and copper all potentially interact and interfere with each other's absorption and metabolism when used as single nutrient supplements.20 21 w16 Trials are ongoing of a multiple micronutrient supplement formulated by WHO, Unicef, and United Nations University for mothers during pregnancy and lactationw17 w18; this supplement could eventually replace iron and folate if proved effective. Various trials of multiple micronutrients as preventive supplements during infancy and childhood have been carried out or are under way.w19 w20 w21 w22 The results of this research need to be brought together to determine whether to promote multiple micronutrient supplementation programmes during pregnancy, lactation, and infancy.
Zinc fortification
Increased consumption of foods with a high content of absorbable zinc is the long term sustainable solution to problems of zinc deficiency. Strategies are being developed that target agricultural and food production, household food processing, and dietary modification.5 Zinc is highly correlated with the protein content of foods, but the availability of zinc in protein rich plant foods is much less than that in animal protein foods. Plant breeding efforts aim to produce new cereal varieties with higher zinc concentrations that are more available by reducing concentrations of inhibitors such a phytate and increasing enhancers of absorption such as the sulphurous amino acids. At the household level, food processing methods for increasing the availability of zinc in cereal grains and legumes include sprouting, fermenting, and soaking. These programme interventions are complex and require considerable investment in behaviour change, which takes time. As yet no evidence exists of their effectiveness for preventing zinc deficiency, especially in mothers and young children.
Conclusions
World Health Organization. The World Health Report 2002: reducing risks, promoting healthy life. Geneva: WHO, 2002.
Prasad AS. Zinc deficiency has been known for 40 years but ignored by global health organizations. BMJ 2003;326: 409-10.
Black R. Micronutrient deficiency—an underlying cause of morbidity and mortality. Bull World Health Organ 2003;81: 79.
Jones G, Steketee RW, Black RE, Bhutta ZA, Morris SS, Bellagio Child Survival Study Group. How many child deaths can we prevent this year? Lancet 2003;362: 65-71.
International Zinc Nutrition Consultative Group. Assessment of the risk of zinc deficiency in populations and options for its control. Food Nutr Bull 2004;25: S91-204.
World Health Organization. Complementary feeding of young children in developing countries: a review of current scientific knowledge. Geneva: WHO, 1998 (WHO/NUT/98.1).
Gibson RS, Yeudall F, Drost N, Mtitimuni B, Cullinan T. Dietary interventions to prevent zinc deficiency. Am J Clin Nutr 1998;68(suppl): 484-7S.
World Health Organization, Unicef. Joint statement on the management of acute diarrhoea. Geneva: WHO, 2004.
Zinc Investigators Collaborative Group. Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomised controlled trials. Am J Clin Nutr 2000;72: 1516-22.
Bahl R, Bhandari N, Saksena M, Strand T, Kumar GT, Bhan MK, et al. Efficacy of zinc-fortified oral rehydration solution in 6-35 month old children with acute diarrhea. J Pediatr 2002;141: 677-82.
Robberstad B, Strand T, Black RE, Somerfelt H. Cost effectiveness of zinc as an adjunct therapy for acute childhood diarrhoea in developing countries. Bull World Health Organ 2004;82: 523-31.
Bryce J, el Arifeen S, Parlyo G, Lanata CF, Gwatkin D, Habicht J-P, et al. Reducing child mortality: can public health deliver? Lancet 2003;362: 159-64.
Zinc Investigators Collaborative Group. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: Pooled analysis of randomised controlled trials. J Pediatr 1999;135: 689-97.
Black RE, Morris SS, Bryce J. Where and why are 10 million children dying every year? Lancet 2003;361: 226-34.
Sazawal S, Black RE, Menon VP, Dinghra P, Caulfield LE, Dhingra U, et al. Zinc supplementation in infants born small for gestational age reduces mortality: a prospective, randomised controlled trial. Pediatrics 2001;108: 1280-6.
Brown KH, Peerson JM, Rivera J, Allen LH. Effect of supplemental zinc on the growth and serum zinc concentrations of prepubertal children: a meta-analysis of randomised controlled trials. Am J Clin Nutr 2002;75: 1062-71.
Yip R. Iron supplementation: Country level experiences and lessons learned. J Nutr 2002;132: 859-61S.
Dijkhuizen MA, Wieringa FT, West CE, Muherdiyantiningsih, Muhilal. Concurrent micronutrient deficiencies in lactating mothers and their infants in Indonesia. Am J Clin Nutr 2001;73: 786-91.
Dewey KG, Brown KH. Update on technical issues concerning complementary feeding of young children in developing countries and implications for intervention programs. Food Nutr Bull 2003;24: 5-28.
Donangelo CM, Woodhouse LR, King SM, Viteri FE, King JC. Supplemental zinc lowers measures of iron status in young women with low iron reserves. J Nutr 2002;132: 1860-4.
O'Brien KO, Zavaleta N, Caulfield LE, Wen J, Abrams SA. Prenatal iron supplements impair zinc absorption in pregnant Peruvian women. J Nutr 2000;130: 2251-5.
Salgueiro MJ, Zubigalla M, Lysioek A, Caro R, Weill R, Boccio J. Fortification strategies to combat zinc and iron deficiency. Nutr Rev 2002;60: 52-8.
Herman S, Griffin IJ, Suwarti S, Ernawati F, Permaesih D, Pambudi, et al. Cofortification of iron-fortified flour with zinc sulphate but not zinc oxide, decreases iron absorption in Indonesian children. Am J Clin Nutr 2002;76: 813-7.(Roger Shrimpton, honorary senior researc)