Effect of zinc supplementation between 1 and 6 mo of life on growth and morbidity of Bangladeshi infants in urban slums

BACKGROUND: Evidence for an effect of zinc supplementation on growth and morbidity in very young infants in developing countries is scarce and inconsistent. OBJECTIVE: We assessed the effect of zinc supplementation on growth and morbidity in poor Bangladeshi infants aged 4-24 wk. DESIGN: Infants from Dhaka slums were enrolled at 4 wk of age and randomly assigned to receive 5 mg elemental Zn/d (n = 152) or placebo (n = 149) until 24 wk of age. They were followed weekly for information on compliance and morbidity; anthropometric measurements were performed monthly. Serum zinc was assessed at baseline and at 24 wk of age. RESULTS: At 24 wk of age, serum zinc concentrations were higher in the zinc than in the placebo group (13.3 +/- 3.8 and 10.7 +/- 2.9 micro mol/L, respectively; P < 0.001). Significantly greater weight gains were observed in the zinc than in the placebo group for 43 infants who were zinc deficient (< 9.18 micro mol/L) at baseline (3.15 +/- 0.77 and 2.66 +/- 0.80 kg, respectively; P < 0.04). In the other infants, no significant differences were observed in mean weight and length gains during the study period. Zinc-deficient infants showed a reduced risk of incidence of acute lower respiratory infection after zinc supplementation (relative risk: 0.30; 95% CI: 0.10, 0.92); among the non-zinc-deficient infants there were no significant differences between treatment groups. CONCLUSIONS: Zinc-deficient Bangladeshi infants showed improvements in growth rate and a reduced incidence of acute lower respiratory infection after zinc supplementation. In infants with serum zinc concentrations > 9.18 micro mol/L, supplementation improved only biochemical zinc status.     

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

BACKGROUND: Zinc supplements reduce childhood morbidity in populations in whom zinc deficiency is common. In such populations, deficiencies in other micronutrients may also occur. OBJECTIVE: 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. DESIGN: 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. RESULTS: 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. CONCLUSION: Morbidity was greater after supplementation with zinc plus multivitamins and minerals than it was after supplementation with zinc alone.     

Zinc treatment for 5 or 10 days is equally efficacious in preventing diarrhea in the subsequent 3 months among Bangladeshi children

We conducted a randomized, double-blind placebo controlled, community trial in rural Bangladesh in children 4-59 mo of age to compare the efficacy of a 5- and 10-d course of zinc therapy on the incidence and duration of diarrhea over the subsequent 90-d follow-up after initial treatment for an acute childhood diarrheal (ACD) episode. Children (n = 1622) with ACD were randomly allocated to either 5 or 10 d of zinc treatment. Female field workers visited each child daily, supervised the administration of zinc, recorded the duration of current episode, and the occurrence and duration of diarrhea over the subsequent 3 mo. The incidence of diarrhea over the 90 d of follow-up did not differ between the 5-d (1.08 ± 1.38 episodes) and 10-d (1.02 ± 1.35 episodes) groups (P = 0.35). Children in both groups experienced a comparable duration of diarrheal episodes (3.1 ± 5.6 d vs. 2.9 ± 5.6 d, 5-d vs. 10-d, respectively; P = 0.64) with a mean difference between groups within the defined range of equivalence. Time to onset of the first episode and the proportion children experiencing diarrhea during the 90-d follow-up also did not differ between groups. These findings suggest that among Bangladeshi children, a 5-d zinc treatment for ACD is as efficacious as 10 d in preventing diarrhea in the subsequent 3 mo.     

Short-term supplementation with zinc and vitamin A has no significant effect on the growth of undernourished Bangladeshi children.

BACKGROUND: Several vitamin A supplementation trials have failed to improve the growth rate in children. Addition of zinc to vitamin A might result in enhanced growth. OBJECTIVE: This study evaluated the effect on growth in children of simultaneous supplementation with zinc and vitamin A. DESIGN: This was a randomized, double-blind, placebo-controlled intervention trial. Six hundred fifty-three children aged 12-35 mo were randomly assigned to 1 of 4 intervention groups: 20 mg Zn/d for 14 d (Z group), 60000 retinol equivalents (200000 IU) vitamin A on day 14 (A group), zinc plus vitamin A (ZA group), or placebo syrup and placebo capsule (placebo group). Weight and length were measured at enrollment and again after 3 and 6 mo. RESULTS: Gains in weight and length during the 6-mo follow-up period were not significantly different among the 4 groups by analysis of variance. Catch-up growth also did not differ significantly among the groups. The proportions of children whose weight-for-age z scores did not change or decreased were 57% in the Z group, 46% in the A group, 50% in the ZA group, and 54% in the placebo group (NS). The proportions of children whose length-for-age z scores did not change or decreased were 42% in the Z group, 48% in the A group, 53% in the ZA group, and 46% in the placebo group (NS). CONCLUSION: Combined short-term zinc supplementation and a single dose of vitamin A has no significant effects on weight and length increments in children over a 6-mo period.     

Simultaneous weekly supplementation of iron and zinc is associated with lower morbidity due to diarrhea and acute lower respiratory infection in Bangladeshi infants

Given the high prevalence of micronutrient deficiencies and infectious diseases in infants in developing countries, an evaluation of the efficacy of different micronutrient formulations on infant morbidity is a priority. The efficacy of weekly supplementation of four different micronutrient formulations on diarrhea and acute lower respiratory infection (ALRI) morbidity was evaluated in Bangladeshi infants. In a double-blind, randomized, controlled community trial, 799 infants aged 6 mo were randomly assigned to one of the following 5 groups: 1) 20 mg elemental iron with 1 mg riboflavin, 2) 20 mg elemental zinc with 1 mg riboflavin, 3) 20 mg iron and 20 mg zinc with 1 mg riboflavin, 4) a micronutrient mix (MM) containing 20 mg iron, 20 mg zinc, 1 mg riboflavin along with other minerals and vitamins and 5) a control treatment, 1 mg riboflavin only. Health workers visited each infant weekly until age 12 mo to feed the supplement and to collect data on diarrhea and ALRI morbidity. Hemoglobin, serum ferritin and serum zinc levels of a sample of infants were measured at 6 and 12 mo. Compared with the control group, at 12 mo, serum ferritin levels were higher in the iron + zinc group, and serum zinc levels were higher in the zinc and iron + zinc groups. Simultaneous supplementation with iron + zinc was associated with lower risk of severe diarrhea, 19% lower in all infants and 30% lower in less well-nourished infants with weight-for-age Z-score below -1. Iron + zinc supplementation was also associated with 40% lower risk of severe ALRI in less well-nourished infants. MM supplementation was associated with a 15% higher risk of diarrhea in all infants and 22% higher risk in less well-nourished infants. Intermittent simultaneous supplementation with iron + zinc seems promising; it will be useful to determine whether higher doses would provide greater benefits.     

Growth and metabolism of infants born to women infected with human immunodeficiency virus and fed acidified whey-adapted starter formulas

OBJECTIVE: To compare the effects of a biologically and chemically acidified formula with or without probiotics with a standard formula on growth of infants negative for human immunodeficiency virus (HIV). METHODS: This was a double-masked, randomized, clinical trial. Infants born to consenting HIV-positive women who had decided not to breast-feed before being approached for participating in the study were randomized to receive one of four milk formulas: a chemically acidified formula with or without probiotics (Bifidobacterium lactis), a biologically acidified formula, or a standard whey formula. Infants who subsequently became HIV-positive according to polymerase chain reaction at 6 wk were excluded. Their growth and biochemical status were monitored for 4-6 mo. The z scores at the last visit of infants in each of the four formula groups were compared using analysis of covariance correcting for the z scores at baseline. Blood gases and pH were analyzed using a two-way analysis of variance corrected for center. RESULTS: One hundred thirty-two HIV-negative infants were monitored for growth and biochemical parameters for 4-6 mo. There was an improvement of z scores for all formulas, and there were no differences in weight for age (P = 0.22), length for age (P = 0.56), head circumference for age (P = 0.66), or weight for length (P = 0.13). There were no differences in blood pH and biochemical parameters among the formula groups. CONCLUSION: The growth of infants fed one of the three acidified formulas was not inferior to the standard formula. Growth and metabolism in HIV-negative infants fed the acidified formulas were not affected by the method of milk acidification.     

Multiple micronutrient supplementation increases the growth of Mexican infants.

BACKGROUND: The role of single micronutrient deficiencies in the etiology of growth retardation has recently gained attention. However, because multiple micronutrient deficiencies are common in children in developing countries, it is possible that more than one micronutrient may limit growth and, hence, the correction of a single deficiency may not be enough to improve growth substantially. OBJECTIVE: The objective was to evaluate the effect of multiple micronutrient supplementation on the growth of children aged 8-14 mo whose diets were poor in several micronutrients. DESIGN: Children were randomly assigned to 1 of 2 groups. One group received a multiple micronutrient supplement containing the recommended dietary allowance (RDA) or 1.5 times the RDA of vitamins A, D, E, K, C, B-1, B-6, B-12, riboflavin, niacin, biotin, folic acid, and pantothenic acid, and iron, zinc, iodine, copper, manganese, and selenium. The other group received a placebo. Supplements were administered 6 d/wk for an average of 12.2 mo. Body length was measured at baseline and monthly thereafter until the end of supplementation. RESULTS: Supplemented infants initially aged <12 mo had significantly greater length gains than did the placebo group, with a difference of 8.2 mm (length-for-age z score: 0.3) at the end of supplementation. In contrast, differences in length gains between the supplemented and placebo groups initially aged > or =12 mo were not significant. CONCLUSIONS: Micronutrient deficiencies limited the growth of the Mexican infants studied. Improving micronutrient intakes should be a component of interventions to promote growth in infants living in settings where micronutrient intakes are inadequate.     

A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: effects on growth and development

BACKGROUND: 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. OBJECTIVE: 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. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.     

A randomized, community-based trial of the effects of improved, centrally processed complementary foods on growth and micronutrient status of Ghanaian infants from 6 to 12 mo of age.

BACKGROUND: Koko, a fermented maize porridge used as the primary complementary food in Ghana, has been implicated in the high prevalence of child malnutrition. Weanimix, a cereal-legume blend developed by the United Nations Children's Fund and the Ghanaian government, has been promoted as an alternative. OBJECTIVE: We evaluated the effect of feeding Weanimix and 3 other locally formulated, centrally processed complementary foods on the nutritional status of 208 breast-fed infants. DESIGN: Infants were randomly assigned to receive 1 of 4 foods from 6 to 12 mo of age: Weanimix (W), Weanimix plus vitamins and minerals (WM), Weanimix plus fish powder (WF), and koko plus fish powder (KF). Dietary and anthropometric data were collected regularly. Blood was collected at 6 and 12 mo of age to assess iron, zinc, vitamin A, and riboflavin status. Before and after the intervention, cross-sectional data on the anthropometric status of infants not included in the intervention (NI; n = 464) were collected. RESULTS: There were no significant differences between intervention groups in weight or length gain or in hemoglobin, hematocrit, transferrin saturation, plasma zinc, or erythrocyte riboflavin values between 6 and 12 mo of age. From 9 to 12 mo of age, z scores were lower in NI infants than in the combined intervention groups [at 12 mo: -1.71 +/- 0.90 compared with -1.19 +/- 0.93 for weight and -1.27 +/- 1.02 compared with -0.63 +/- 0.84 for length (P < 0.001 for both), respectively]. The percentage of infants with low ferritin values increased significantly between 6 and 12 mo of age in groups W, WF, and KF but not in group WM. Change in plasma retinol between 6 and 12 mo of age was significantly greater in group WM than in the other 3 groups combined (0.14 +/- 0.3 compared with -0.04 +/- 0.3 micromol/L, P = 0. 003). CONCLUSIONS: All 4 foods improved growth relative to the NI group. Infants fed WM had better iron stores and vitamin A status than those fed nonfortified foods.     

Effects of iron and zinc supplementation in Indonesian infants on micronutrient status and growth.

In this study the effects of supplementation of iron and zinc, alone or combined, on iron status, zinc status and growth in Indonesian infants is investigated. Micronutrient deficiencies are prevalent in infants in developing countries, and deficiencies often coexist; thus, combined supplementation is an attractive strategy. However, little is known about interactions between micronutrients. In a randomized, double-blind, placebo-controlled supplementation trial, 478 infants, 4 mo of age, were supplemented for 6 mo with iron (10 mg/d), zinc (10 mg/d), iron + zinc (10 mg of each/d) or placebo. Anthropometry was assessed monthly, and micronutrient status was assessed at the end of supplementation. Supplementation significantly reduced the prevalence of anemia, iron deficiency anemia and zinc deficiency. Iron supplementation did not negatively affect plasma zinc concentrations, and zinc supplementation did not increase the prevalence of anemia or iron deficiency anemia. However, iron supplementation combined with zinc was less effective than iron supplementation alone in reducing the prevalence of anemia (20% vs. 38% reduction) and in increasing hemoglobin and plasma ferritin concentrations. There were no differences among the groups in growth. The growth of all groups was insufficient to maintain the same Z-scores for height for age and weight for height. There is a high prevalence of deficiencies of iron and zinc in these infants, which can be overcome safely and effectively by supplementation of iron and zinc combined. However, overcoming these deficiencies is not sufficient to improve growth performance in these infants.     

Iron supplementation affects growth and morbidity of breast-fed infants: results of a randomized trial in Sweden and Honduras

Iron supplements are often prescribed during infancy but their benefits and risks have not been well documented. We examined whether iron supplements affect growth or morbidity of breast-fed infants. Full-term infants in Sweden (n = 101) and Honduras (n = 131) were randomly assigned to three groups at 4 mo of age: 1) placebo from 4 to 9 mo; 2) placebo from 4 to 6 mo and iron supplements [1 mg/(kg. d)] from 6 to 9 mo; or 3) iron supplements from 4 to 9 mo. All infants were exclusively or nearly exclusively breast-fed to 6 mo and continued to be breast-fed to at least 9 mo. Growth was measured monthly and morbidity data were collected every 2 wk. Among the Swedish infants, gains in length and head circumference were significantly lower in those who received iron than in those given placebo from 4 to 9 mo. The same effect on length was seen in Honduras, but only at 4-6 mo among those with initial hemoglobin (Hb) > or =110 g/L. There was no significant main effect of iron supplementation on morbidity, nor any significant interaction between iron supplementation and site, but for diarrhea (with both sites combined), there was an interaction between iron supplementation and initial Hb. Among infants with Hb < 110 g/L at 4 mo, diarrhea was less common among those given iron than in those given placebo from 4-9 mo, whereas the opposite was true among those with Hb > or = 110 g/L (P < 0.05). We conclude that routine iron supplementation of breast-fed infants may benefit those with low Hb but may present risks for those with normal Hb.     

Effects of separate delivery of zinc or zinc and vitamin A on hemoglobin response, growth, and diarrhea in young Peruvian children receiving iron therapy for anemia

INTRODUCTION: Anemia is the most prevalent nutritional deficiency in the world. Attempts to improve iron indexes are affected by deficiency of and interaction between other micronutrients. OBJECTIVE: Our goal was to assess whether zinc added to iron treatment alone or with vitamin A improves iron indexes and affects diarrheal episodes. DESIGN: This was a randomized, placebo-controlled, double-blind trial conducted in Peru. Anemic children aged 6-35 mo were assigned to 3 treatment groups: ferrous sulfate (FS; n = 104), ferrous sulfate and zinc sulfate (FSZn; n = 109), and ferrous sulfate, zinc sulfate, and vitamin A (FSZnA; n = 110). Vitamin A or its placebo was supplied only once; iron and zinc were provided under supervision >/=1 h apart 6 d/wk for 18 wk. RESULTS: The prevalence of anemia was 42.97%. The increase in hemoglobin in the FS group (19.5 g/L) was significantly less than that in the other 2 groups (24.0 and 23.8 g/L in the FSZn and FSZnA groups, respectively). The increase in serum ferritin in the FS group (24.5 mug/L) was significantly less than that in the other 2 groups (33.0 and 30.8 mug/L in the FSZn and FSZnA groups, respectively). The median duration of diarrhea and the mean number of stools per day was significantly higher in the FS group than in other 2 groups (P < 0.005). CONCLUSION: Adding zinc to iron treatment increases hemoglobin response, improves iron indexes, and has positive effects on diarrhea. No additional effect of vitamin A was found.     

A double-blind, randomized, clinical trial of the effect of vitamin A and zinc supplementation on diarrheal disease and respiratory tract infections in children in Mexico City, Mexico

BACKGROUND: The efficacy of micronutrient supplementation in improving childhood health and survival in developing countries may be specific to the micronutrient used and health outcome measured. OBJECTIVE: We evaluated the effect of vitamin A and zinc supplementation on overall rates of childhood diarrheal disease and respiratory tract infections and rates stratified by household and personal characteristics. DESIGN: A double-blind, randomized, placebo-controlled trial was carried out in which 736 children aged 6-15 mo living in a periurban area of Mexico City were assigned to receive vitamin A every 2 mo, zinc daily, vitamin A and zinc together, or placebo. Children were followed for 12 mo to determine overall counts of diarrheal episodes and respiratory tract infections. RESULTS: Vitamin A supplementation was associated with a 27% increase in diarrheal disease [risk ratio (RR): 1.27; 95% CI: 1.10, 1.45; P < 0.001] and a 23% increase in cough with fever (RR: 1.23; 95% CI: 1.02, 1.47; P = 0.02), whereas zinc had no effect on these outcomes. Vitamin A supplementation decreased diarrhea in children from households with dirt floors but increased diarrhea in children from households with nondirt floors, piped water, and indoor bathrooms. Zinc supplementation decreased diarrhea in children from households with dirt floors and whose mothers were more educated. Vitamin A supplementation increased cough with fever in children from less-crowded households that lacked indoor bathrooms and in children of less-educated mothers. CONCLUSIONS: Vitamin A increases diarrheal disease and respiratory tract infections in young children in periurban areas of Mexico City. Vitamin A and zinc have more heterogeneous effects in different subgroups of children.     

Oral copper supplementation: effect on copper and zinc balance during acute gastroenteritis in infants

To evaluate the effect of copper supplementation during recovery from acute diarrhea, we randomly assigned 14 hospitalized infants to receive either 80 micrograms copper sulfate.kg body wt-1.d-1 or a placebo. Metabolic balance and plasma copper and zinc concentrations were measured before randomization (period 1) and 6 d after admission (period 2). Fifteen control subjects were studied after respiratory illness. Fecal copper was not affected by supplementation; fecal zinc during period 2 rose significantly only in the copper-supplemented group. Copper retention was significantly higher in the supplemented infants; plasma concentrations increased for period 2 but were similar to those in the placebo group. Zinc concentrations improved over time in both groups but zinc retention was higher in the placebo group for period 2. A significant interference by copper supplementation on zinc absorption was noted. Copper supplementation during the early phase of recovery from diarrhea is not recommended.     

Multiple micronutrient supplements improve micronutrient status and anemia but not growth and morbidity of Indonesian infants: a randomized, double-blind, placebo-controlled trial

Multiple micronutrient deficiencies are highly prevalent in Indonesia, but the interventions are still focused on single micronutrients. This study aimed to investigate the efficacy of multiple micronutrient supplements for improving micronutrient status, anemia, growth, and morbidity of Indonesian infants. In this double-blind, placebo-controlled trial, 284 infants aged 6-12 mo were randomly allocated to 4 treatment groups for 23 wk; 260 (92%) infants completed the study. Group 1 (DMM) received one adequate intake of multiple micronutrient supplements daily (n = 66); group 2 (WMM) received 2 adequate intakes of multiple micronutrient on 1d plus 6 d of placebo (n = 60); group 3 (DI) received 10 mg of iron supplement daily (n = 69); group 4 received a placebo supplement daily (n = 65). Blood samples were collected at baseline and at posttreatment to assess anemia and micronutrient status. Anthropometric measurements were taken monthly, and morbidity was recorded daily. At baseline, 58.1% of infants were anemic, 34.2% were iron deficient, 21.3% were vitamin A deficient, and 11% were zinc deficient. The DMM and DI supplements both corrected iron deficiency, but DMM supplements were more efficacious in improving hemoglobin levels of anemic infants than the other supplements. However, anemia still persisted in one-third of DMM infants posttreatment. The DMM supplement was more efficacious than WMM or DI supplementation in improving infant status of other micronutrients, including zinc, tocopherol, and riboflavin, whereas DI exacerbated zinc deficiency. There were no significant differences in growth and morbidity among treatment groups, and growth faltering was not prevented.     

Zinc supplementation does not affect growth, morbidity, or motor development of US term breastfed infants at 4-10 mo of age

BACKGROUND: 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. OBJECTIVE: The objective of this study was to examine the effect of zinc supplementation on growth, morbidity, and motor development in healthy, term, breastfed infants. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.     

Daily iron alone but not in combination with multimicronutrients increases plasma ferritin concentrations in indonesian infants with inflammation

Iron deficiency is a public health problem in infancy. We assessed the efficacy of iron supplements in infants with inflammation on iron status and subsequent inflammation. This was a prospective, nested, case-control study of 6- to 12-mo-old infants participating in the International Research on Infant Supplementation study, Indonesia. Cases (n = 46) were selected on the basis of their inflammation status at baseline, C-reactive protein (>5 mg/L) or alpha-1 acid glycoprotein (>1 g/L); there were 44 controls without inflammation. Infants received 10 mg/d of elemental iron alone or in combination with multimicronutrients, or placebo. Blood samples were collected at baseline and at 6 mo for determinations of plasma ferritin, zinc, copper, retinol, beta-carotene, alpha-tocopherol, and inflammation status. Data on breast-feeding and acute respiratory infections (ARI) were collected daily. At baseline, 33% of infants had iron deficiency, and those with inflammation had lower retinol, beta-carotene, higher concentrations of copper and higher rates of ARI compared with controls. After 6 mo, compared with infants given placebo, ferritin concentration increased significantly in infants administered iron alone independently of inflammation status at baseline or at the end of the study. In those given multimicronutrients with iron, ferritin increased significantly in infants who did not have inflammation at baseline or at the end of the study compared with those given placebo. Consequently, iron alone resolved iron deficiency, whereas multimicronutrients reduced the deterioration of iron stores compared with placebo (chi(2), P < 0.05), without enhancing inflammation. Iron alone is recommended in populations in which iron deficiency is a public health problem despite the presence of inflammation in infants who are still breast-feeding.     

Dose-response trial of prophylactic zinc supplements, with or without copper, in young Ecuadorian children at risk of zinc deficiency

BACKGROUND: 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. OBJECTIVES: 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. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.     

Oligofructose-supplemented infant cereal: 2 randomized,blinded, community-based trials in Peruvian infants

BACKGROUND: Prebiotics are nondigestible food ingredients that stimulate the growth of Bifidobacterium and other bacteria in the gastrointestinal tract. Improved gastrointestinal and other health effects have been attributed to them. OBJECTIVE: The objective of this study was to evaluate the effects of dietary supplementation with the prebiotic oligofructose with and without zinc on the prevalence of diarrhea in a community with a high burden of gastrointestinal and other infections. DESIGN: Two consecutive randomized, blinded, controlled clinical trials were performed in a shantytown community near Lima, Peru. The first trial compared an infant cereal supplemented with oligofructose (0.55 g/15 g cereal) with nonsupplemented cereal. During the second trial, zinc (1 mg/15 g cereal) was added to both oligofructose-supplemented and control cereals. RESULTS: We enrolled 282 infants in the first trial and 349 in the second. In the first trial, mean (+/- SD) days of diarrhea were 10.3 +/- 9.6 in the nonsupplemented cereal group and 9.8 +/- 11.0 in the prebiotic-supplemented cereal group (P = 0.66). In the second trial, mean days of diarrhea were 10.3 +/- 8.9 in the group consuming cereal fortified only with zinc and 9.5 +/- 8.9 in the group consuming cereal containing both zinc and prebiotics (P = 0.35). Postimmunization titers of antibody to Haemophilus influenzae type B were similar in all groups, as were gains in height, visits to clinic, hospitalizations, and use of antibiotics. CONCLUSIONS: Cereal supplemented with prebiotics was not associated with any change in diarrhea prevalence, use of health care resources, or response to H. influenzae type B immunization. Infants and young children who continue to breast-feed may not benefit from prebiotic supplementation.