Randomized controlled trial of the effect of daily supplementation with zinc or multiple micronutrients on the morbidity, growth, and micronutrient status of young Peruvian children. Zinc supplementation and psychosocial stimulation: effects on the development of undernourished Jamaican children. Dose-response trial of prophylactic zinc supplements, with or without copper, in young Ecuadorian children at risk of zinc deficiency. Effect of zinc supplementation on incidence of infections and hospital admissions in sickle cell disease (SCD). Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomised double-blind placebo-controlled trial. Effect of zinc supplementation on malaria and other causes of morbidity in west African children: randomised double blind placebo controlled trial. Zinc supplementation does not affect growth, morbidity, or motor development of US term breastfed infants at 4-10 mo of age. Effect of a zinc-fortified formula on immunocompetence and growth of malnourished infants. Effect of weekly zinc supplements on incidence of pneumonia and diarrhoea in children younger than 2 years in an urban, low-income population in Bangladesh: randomised controlled trial. Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: randomised controlled trial in an urban slum. A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: effects on growth and development.
Zinc supplements reduce childhood morbidity in populations in whom zinc deficiency is common. In such populations, deficiencies in other micronutrients may also occur.
                The objective was to determine whether the administration of other micronutrients with zinc modifies the effect of zinc supplementation on children's morbidity and physical growth.
                Two hundred forty-six children aged 6-35 mo with persistent diarrhea were randomly assigned to 1 of 3 groups to receive a daily supplement of 10 mg Zn alone (Zn; n = 81), zinc plus vitamins and other minerals at 1-2 times recommended daily intakes (Zn+VM; n = 82), or placebo (n = 83) for approximately 6 mo after the diarrhea episode ended. Morbidity information was collected on weekdays. Weight, length, and other anthropometric indicators were measured monthly, and plasma zinc and other indicators of micronutrient status were measured at baseline and 6 mo.
                Supplement consumption was high ( approximately 90%) in all groups, although slightly more vomiting was reported in the Zn+VM group (P < 0.0001, analysis of variance). The change in plasma zinc from baseline to 6 mo was greater in the 2 zinc groups (6.1, 27.3, and 16.2 micro g/dL in the placebo, Zn, and Zn+VM groups, respectively; P < 0.0001, analysis of variance). The Zn group had fewer episodes of diarrhea, dysentery, and respiratory illness and a lower prevalence of fever and cough than did the Zn+VM group and a lower prevalence of cough than did the placebo group (P = 0.05). No significant effects of supplementation on growth were observed.
                Morbidity was greater after supplementation with zinc plus multivitamins and minerals than it was after supplementation with zinc alone. Undernourished children have poor levels of development that benefit from stimulation. Zinc deficiency is prevalent in undernourished children and may contribute to their poor development.
                We assessed the effects of zinc supplementation and psychosocial stimulation given together or separately on the psychomotor development of undernourished children.
                This was a randomized controlled trial with 4 groups: stimulation alone, zinc supplementation alone, both interventions, and control (routine care only). Subjects were 114 children aged 9-30 mo and below -1.5 z scores of the National Center for Health Statistics weight-for-age references who were recruited from 18 health clinics. Clinics were randomly assigned to receive stimulation or not; individual children were randomly assigned to receive zinc or placebo. The stimulation program comprised weekly home visits during which play was demonstrated and maternal-child interactions were encouraged. The supplementation was 10 mg Zn as sulfate daily or placebo. Development (assessed by use of the Griffiths Mental Development Scales), length, and weight were measured at baseline and 6 mo later. Weekly morbidity histories were taken.
                Significant interactions were found between zinc supplementation and stimulation. Zinc benefited the developmental quotient only in children who received stimulation, and benefits from zinc to hand and eye coordination were greater in stimulated children. Zinc supplementation alone improved hand and eye coordination, and stimulation alone benefited the developmental quotient, hearing and speech, and performance. Zinc supplementation also reduced diarrheal morbidity but did not significantly improve growth.
                Zinc supplementation benefits development in undernourished children, and the benefits are enhanced if stimulation is also provided. Multiple studies have shown the benefits of zinc supplementation among young children in high-risk populations. However, the optimal dose and safe upper level of zinc have not been determined.
                The objectives of this study were to measure the effects of different doses of supplemental zinc on the plasma zinc concentration, morbidity, and growth of young children; to detect any adverse effects of 10 mg supplemental Zn on markers of copper or iron status; and to determine whether any adverse effects are alleviated by providing copper with zinc.
                This randomized, double-masked, community-based intervention trial was conducted in 631 Ecuadorian children who were 12-30 mo old at baseline and who had initial length-for-age z scores <-1.3. Children received 1 of 5 daily supplements for 6 mo: 3, 7, or 10 mg Zn as zinc sulfate, 10 mg Zn + 0.5 mg Cu as copper sulfate, or placebo.
                The change in plasma zinc concentration from baseline was positively related to the zinc dose (P < 0.001). Zinc supplementation, including doses as low as 3 mg/d, reduced the incidence of diarrhea by 21-42% (P < 0.01). There were no other significant group-wise differences.
                Zinc supplementation with a dose as low as 3 mg/d increased plasma zinc concentrations and reduced diarrhea incidence in the study population. There were no observed adverse effects of 10 mg Zn/d on indicators of copper or iron status. The current tolerable upper level of zinc recommended by the Institute of Medicine should be reassessed for young children. Zinc deficiency is a common nutritional problem in adult sickle-cell disease (SCD) patients. Hyperzincuria and increased requirement of zinc due to continued hemolysis in SCD are probable bases for zinc deficiency in these patients. Zinc deficiency affects adversely T-helper1 (TH1) functions and cell mediated immunity and interleukin (IL)-2 production is decreased in zinc deficient subjects. We hypothesized that zinc supplementation will improve T-helper1 function and decrease incidence of infections in patients with SCD. We tested this hypothesis in 32 SCD subjects who were divided in three groups (Grs A, B, and C). Grs A (n = 11) and B (n = 10) were zinc deficient based on cellular zinc criteria and Gr C (n = 11) were zinc sufficient. Gr A subjects were observed for 1 year (baseline), following which they received zinc acetate (50 to 75 mg of elemental zinc orally daily) for 3 years. Gr B subjects were observed for 1 year (baseline), following which they received placebo for 1 year and then switched to zinc supplementation (50 to 75 mg of elemental zinc orally daily) for 2 years. Gr C subjects did not receive any intervention inasmuch as they were zinc sufficient. Prolonged zinc supplementation resulted in an increase in lymphocyte and granulocyte zinc (P = 0.0001), and an increase in interleukin-2 production (P = 0.0001), decreased incidence of documented bacteriologically positive infections (P = 0.0026), decreased number of hospitalizations and decreased number of vaso-occlusive pain crisis (P = 0.0001). The predominant pathogens isolated were staphylococci and streptococci involving the respiratory tract and aerobic gram-negative bacteria, particularly Escherichia coli, involving the urinary tract. Further confirmation of our observations will require prospective studies of zinc supplementation in a larger number of SCD patients.
                Copyright 1999 Wiley-Liss, Inc. Zinc deficiency is associated with impaired immune function and an increased risk of infection. Supplementation can decrease the incidence of diarrhoea and pneumonia in children in resource-poor countries. However, in children with HIV-1 infection, the safety of zinc supplementation is uncertain. We aimed to assess the role of zinc in HIV-1 replication before mass zinc supplementation is recommended in regions of high HIV-1 prevalence.
                We did a randomised double-blind placebo-controlled equivalence trial of zinc supplementation at Grey's Hospital in Pietermaritzburg, South Africa. 96 children with HIV-1 infection were randomly assigned to receive 10 mg of elemental zinc as sulphate or placebo daily for 6 months. Baseline measurements of plasma HIV-1 viral load and the percentage of CD4+ T lymphocytes were established at two study visits before randomisation, and measurements were repeated 3, 6, and 9 months after the start of supplementation. The primary outcome measure was plasma HIV-1 viral load. Analysis was per protocol.
                The mean log(10) HIV-1 viral load was 5.4 (SD 0.61) for the placebo group and 5.4 (SD 0.66) for the zinc-supplemented group 6 months after supplementation began (difference 0.0002, 95% CI -0.27 to 0.27). 3 months after supplementation ended, the corresponding values were 5.5 (SD 0.77) and 5.4 (SD 0.61), a difference of 0.05 (-0.24 to 0.35). The mean percentage of CD4+ T lymphocytes and median haemoglobin concentrations were also similar between the two groups after zinc supplementation. Two deaths occurred in the zinc supplementation group and seven in the placebo group (p=0.1). Children given zinc supplementation were less likely to get watery diarrhoea than those given placebo. Watery diarrhoea was diagnosed at 30 (7.4%) of 407 clinic visits in the zinc-supplemented group versus 65 (14.5%) of 447 visits in the placebo group (p=0.001).
                Zinc supplementation of HIV-1-infected children does not result in an increase in plasma HIV-1 viral load and could reduce morbidity caused by diarrhoea.
                Programmes to enhance zinc intake in deficient populations with a high prevalence of HIV-1 infection can be implemented without concern for adverse effects on HIV-1 replication. In view of the reductions in diarrhoea and pneumonia morbidity, zinc supplementation should be used as adjunct therapy for children with HIV-1 infection. To study the effects of zinc supplementation on malaria and other causes of morbidity in young children living in an area holoendemic for malaria in west Africa.
                Randomised, double blind, placebo controlled efficacy trial.
                18 villages in rural northwestern Burkina Faso.
                709 children were enrolled; 685 completed the trial.
                Supplementation with zinc (12.5 mg zinc sulphate) or placebo daily for six days a week for six months.
                The primary outcome was the incidence of symptomatic falciparum malaria. Secondary outcomes were the severity of malaria episodes, prevalence of malaria parasite, mean parasite densities, mean packed cell volume, prevalence of other morbidity, and all cause mortality.
                The mean number of malaria episodes per child (defined as a temperature >/=37.5 degrees C with >/=5000 parasites/microliter) was 1.7, 99.7% due to infection with Plasmodium falciparum. No difference was found between the zinc and placebo groups in the incidence of falciparum malaria (relative risk 0.98, 95% confidence interval 0.86 to 1.11), mean temperature, and mean parasite densities during malaria episodes, nor in malaria parasite rates, mean parasite densities, and mean packed cell volume during cross sectional surveys. Zinc supplementation was significantly associated with a reduced prevalence of diarrhoea (0.87, 0.79 to 0.95). All cause mortality was non-significantly lower in children given zinc compared with those given placebo (5 v 12, P=0.1).
                Zinc supplementation has no effect on morbidity from falciparum malaria in children in rural west Africa, but it does reduce morbidity associated with diarrhoea. It has been documented that growth patterns differ between breastfed and formula-fed infants. Some investigators have suggested that these differences may be related to differences in zinc nutriture.
                The objective of this study was to examine the effect of zinc supplementation on growth, morbidity, and motor development in healthy, term, breastfed infants.
                We conducted a randomized double-blind intervention comparing zinc supplementation (5 mg/d as zinc sulfate) with placebo in breastfed infants aged 4-10 mo. Growth and indexes of body composition and gross motor development were measured monthly from 3 to 10 mo. Morbidity data were collected weekly.
                Eighty-five infants were enrolled, and 70 completed the study. The baseline characteristics, attained weight or length at 10 mo, growth velocity, gross motor development, and morbidity did not differ significantly between groups, even after control for potentially confounding variables.
                The dietary zinc intake of these breastfed infants appeared to be adequate, given that zinc supplementation did not affect growth, development, or risk of infection (although sample size for detection of differences in development or infection was limited). Previously described differences in growth between breastfed and formula-fed infants in such populations do not appear to be due to differences in zinc nutriture. This study attempted to define the possible contribution of zinc nutrition to immunocompetence and growth in severely malnourished infants. The effect of zinc supplementation was evaluated in marasmic infants during nutritional rehabilitation by using a controlled double-blind design in which 19 infants fed a zinc-fortified formula were compared with 20 infants fed the same non-supplemented formula. Evaluation of immunocompetence, growth, and zinc, copper, and iron status was performed on admission and at 30, 60, and 105 d of nutritional rehabilitation. Although energy intake was similar in both groups, the zinc-supplemented infants had significantly higher linear growth gain, and their immune function improved as demonstrated by conversion of their delayed hypersensitivity skin reactions, enhanced lymphoproliferative response to PHA, and increased salivary IgA concentrations. Thus, the use of a zinc-fortified formula during nutritional rehabilitation can prevent the development of zinc deficiency and improve growth and immune function. Pneumonia and diarrhoea cause much morbidity and mortality in children younger than 5 years. Most deaths occur during infancy and in developing countries. Daily regimens of zinc have been reported to prevent acute lower respiratory tract infection and diarrhoea, and to reduce child mortality. We aimed to examine whether giving zinc weekly could prevent clinical pneumonia and diarrhoea in children younger than 2 years.
                1665 poor, urban children aged 60 days to 12 months were randomly assigned zinc (70 mg) or placebo orally once weekly for 12 months. Children were assessed every week by field research assistants. Our primary outcomes were the rate of pneumonia and diarrhoea. The rates of other respiratory tract infections were the secondary outcomes. Growth, final serum copper, and final haemoglobin were also measured. Analysis was by intention to treat.
                34 children were excluded before random assignment to treatment group because they had tuberculosis. 809 children were assigned zinc, and 812 placebo. After treatment assignment, 103 children in the treatment group and 44 in the control group withdrew. There were significantly fewer incidents of pneumonia in the zinc group than the control group (199 vs 286; relative risk 0.83, 95% CI 0.73-0.95), and a small but significant effect on incidence of diarrhoea (1881 cases vs 2407; 0.94, 0.88-0.99). There were two deaths in the zinc group and 14 in the placebo group (p=0.013). There were no pneumonia-related deaths in the zinc group, but ten in the placebo group (p=0.013). The zinc group had a small gain in height, but not weight at 10 months compared with the placebo group. Serum copper and haemoglobin concentrations were not adversely affected after 10 months of zinc supplementation.
                70 mg of zinc weekly reduces pneumonia and mortality in young children. However, compliance with weekly intake might be problematic outside a research programme. To evaluate the effect of daily zinc supplementation in children on the incidence of acute lower respiratory tract infections and pneumonia.
                Double masked, randomised placebo controlled trial.
                A slum community in New Delhi, India.
                2482 children aged 6 to 30 months.
                Daily elemental zinc, 10 mg to infants and 20 mg to older children or placebo for four months. Both groups received single massive dose of vitamin A (100 000 IU for infants and 200 000 IU for older children) at enrollment.
                All households were visited weekly. Any children with cough and lower chest indrawing or respiratory rate 5 breaths per minute less than the World Health Organization criteria for fast breathing were brought to study physicians.
                At four months the mean plasma zinc concentration was higher in the zinc group (19.8 (SD 10.1) v 9.3 (2.1) micromol/l, P<0.001). The proportion of children who had acute lower respiratory tract infection during follow up was no different in the two groups (absolute risk reduction -0.2%, 95% confidence interval -3.9% to 3.6%). Zinc supplementation resulted in a lower incidence of pneumonia than placebo (absolute risk reduction 2.5%, 95% confidence interval 0.4% to 4.6%). After correction for multiple episodes in the same child by generalised estimating equations analysis the odds ratio was 0.74, 95% confidence interval 0.56 to 0.99.
                Zinc supplementation substantially reduced the incidence of pneumonia in children who had received vitamin A. 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.
                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.
                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.
                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.
                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.