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Concurrent micronutrient deficiencies are prevalent among Vietnamese school children. A school-based program providing food fortified with multiple micronutrients could be a cost-effective and sustainable strategy to improve health and cognitive function of school children. However, the efficacy of such an intervention may be compromised by the high prevalence of parasitic infestation. To evaluate the efficacy of school-based intervention using multi-micronutrient-fortified biscuits with or without deworming on anemia and micronutrient status in Vietnamese schoolchildren, a randomized, double-blind, placebo-controlled trial was conducted among 510 primary schoolchildren, aged 6-8 y, in rural Vietnam. Albendazole (Alb) (400 mg) or placebo was given at baseline. Nonfortified or multi-micronutrient-fortified biscuits including iron (6 mg), zinc (5.6 mg), iodine (35 microg), and vitamin A (300 microg retinol equivalents) were given 5 d/wk for 4 mo. Multi-micronutrient fortification significantly improved the concentrations of hemoglobin (+1.87 g/L; 95% CI: 0.78, 2.96), plasma ferritin (+7.5 microg/L; 95% CI: 2.8, 12.6), body iron (+0.56 mg/kg body weight; 95% CI: 0.29, 0.84), plasma zinc (+0.61 micromol/L; 95% CI: 0.26, 0.95), plasma retinol (+0.041 micromol/L; 95% CI: 0.001, 0.08), and urinary iodine (+22.49 micromol/L; 95% CI: 7.68, 37.31). Fortification reduced the risk of anemia and deficiencies of zinc and iodine by >40%. Parasitic infestation did not affect fortification efficacy, whereas fortification significantly enhanced deworming efficacy, with the lowest reinfection rates in children receiving both micronutrients and Alb. Multi-micronutrient fortification of biscuits is an effective strategy to improve the micronutrient status of Vietnamese schoolchildren and enhances effectiveness of deworming.

Data from 4 randomized, placebo-controlled, double-blind trials in Indonesia, Thailand, and Vietnam, the South-East Asian Multicountry Trial on Iron and Zinc supplementation in Infants (SEAMTIZI), were pooled to investigate the effects of iron and zinc supplementation infant growth. Infants (n = 2451) aged 4-6 mo old were supplemented with iron (10 mg/d) and/or zinc (10 mg/d) for 6 mo. Overall, neither iron nor zinc supplementation prevented the progressive growth faltering during infancy, which is common in many developing countries. However, infants who received zinc were less likely to be stunted at the end of the supplementation period (odds ratio 0.80; 95% CI 0.64-1.0). Boys had a 30% higher risk of being stunted at the end of the study than girls (P0.01). Baseline factors modified the effect of supplementation, with infants anemic at baseline (hemoglobin105 g/L) benefiting from zinc supplementation, with an estimated increase in height-for-age Z-score (HAZ) score of 0.17 (P0.01), but with no effect of zinc supplementation on growth in infants not anemic at baseline. Iron supplementation negatively affected linear growth in infants with a birth weight of3500 g (estimated effect size, -0. 14 HAZ score; P0.01), but with no significant effect in infants with a lower birth weight. This study shows that blanket supplementation of infants with iron or zinc will not be beneficial to all recipients and may have adverse effects in some. Hence, interventions such as iron and zinc supplementation for infants should be restricted to subgroups in which there is a clear benefit and baseline factors should be considered and characterized before implementing new policies.

Deficiencies of iron and zinc are prevalent worldwide. Interactions between these micronutrients therefore have important consequences, also for supplementation. To investigate effects on hemoglobin and zinc concentrations and interactions of iron and zinc supplementation in infants, data from 4 parallel, randomized, placebo-controlled, double-blind trials in Indonesia, Thailand, and Vietnam were pooled. Infants (n=2468), aged 4-6 mo, were supplemented daily with iron (10 mg) and/or zinc (10 mg) for 6 mo. At 3 sites, infants were given vitamin A capsules (VAC) at recruitment. Combined supplementation reduced prevalences of anemia by 21% (P0.01) and zinc deficiency by 10% (P0.05) but was less effective (P0.05) than supplementation with either iron (28% reduction in anemia) or zinc alone (18% reduction in zinc deficiency). Iron reduced the effect of zinc supplementation (interaction P0.01), but had no separate effect on zinc status, whereas zinc supplementation had a negative effect on hemoglobin concentrations (-2.5 g/L, P0.001), independent of iron supplementation (Pinteraction=0.25). The effect of iron supplementation on hemoglobin concentrations was almost twice as large in boys than in girls (effect size 12.0 vs. 6.8 g/L, respectively). In infants not receiving iron, VAC administration tended to be associated with lower (3.2%, P=0.07) hemoglobin concentrations. Combined supplementation of iron and zinc was safe and effective in reducing the high prevalences of anemia and iron and zinc deficiencies. Zinc supplementation may negatively affect iron status but iron supplementation does not seem to affect zinc status. Furthermore, VAC administration in the absence of iron supplementation may increase the incidence of anemia.

Objective: To determine effects of vitamin A, zinc and iron deficiency in Indonesian infants on the ability to produce immunoregulatory cytokines. Design, setting and subjects: Immunological asssessment was done in 59 infants participating in a cross-sectional nutritional survey in rural West Java, Indonesia. Production of T-helper cell type-1 (Th1, cell-mediated) cytokines interferon-gamma (IFN-gamma), interleukin-12 (IL-12), interleukin-18 (IL-18) and T-helper cell type-2 (Th2, humoral) cytokine interleukin-6 (IL-6) were measured after stimulation with lipopolysaccharide and phytohemagglutinin in an ex vivo whole blood culture system. Circulating neopterin concentrations were determined as an indicator of in vivo macrophage activity. Results: Of the infants, 48% were vitamin A deficient, 44% were anemic (with 17% having iron deficiency anemia), and 17% were zinc deficient. Vitamin-A deficient infants had significantly reduced ex vivo production of IFN-gamma, but also significantly higher circulating neopterin concentrations. Production of IFN-gamma and IL-12 were strongly correlated, IFN-gamma and IL-18 production were not. Zinc deficiency was accompanied by significantly reduced white blood cell counts and reduced ex vivo production of IL-6. Iron status was not related to cytokine production. Conclusions: This study shows that in vitamin A deficiency there is Th1 dominance in a steady state, combined however with impairment of the Th1 response after stimulation, whereas in zinc deficiency, there is a decreased Th2 response. Overall, vitamin A deficiency and zinc deficiency have marked albeit different effects on the immunocompetence of infants, affecting both cell-mediated and humoral components of the immune system. Sponsorship: Netherlands Foundation for the Advancement of Tropical Research (WOTRO), and Ter Meulen Fund (Royal Netherlands Academy of Arts and Sciences).

Background: Deficiencies of vitamin A, iron, and zinc are prevalent in women and infants in developing countries. Supplementation during pregnancy can benefit mother and infant. Objective: We examined whether supplementation during pregnancy with iron and folic acid plus beta-carotene or zinc or both improves the micronutrient status of mothers and infants postpartum. Design: Pregnant women (n = 170) were supplemented daily only during pregnancy with beta-carotene (4.5 mg), zinc (30 mg), or both or placebo plus iron (30 mg) and folic acid (0.4 mg) in a randomized, double-blind, placebo-controlled trial. Micronutrient status was assessed 1 and 6 mo postpartum. Results: Six months postpartum, plasma retinol concentrations were higher in the women who received zinc during pregnancy than in women who did not. Infants born to mothers supplemented with beta-carotene + zinc had higher plasma retinol concentrations, with the frequency of vitamin A deficiency reduced by >30% compared with the other 3 groups. Breast-milk beta-carotene concentrations were higher in all women supplemented with beta-carotene, but breast-milk retinol concentrations were higher only in women who received beta-carotene + zinc. Zinc concentrations did not differ among groups in mothers and infants. Conclusions: Zinc supplementation during pregnancy improved the vitamin A status of mothers and infants postpartum, which indicates a specific role of zinc in vitamin A metabolism. Addition of both beta-carotene and zinc to iron supplements during pregnancy could be effective in improving the vitamin A status of mothers and infants.

We have constructed two expression vectors based on the pJF118HE vector developed for Escherichia coli by Furste et al. [Gene 48 (1986) 119–131]. The tac promoter (ptac) was exchanged for the trc promoter (ptrc) and an NdeI site was created at the appropriate distance from the ribosome-binding site. The NdeI site permits cloning of a gene at its translation start point without altering the amino-acid sequence of the synthesized protein, while ptrc and the lacIQ gene confer inducible and controlable expression. We have tested these plasmids in E. coli and Salmonella typhimurium.

Item does not contain fulltext BACKGROUND: Deficiencies of iron and vitamin A are prevalent worldwide. Single-micronutrient supplementation is widely used to combat these deficiencies. However, micronutrient deficiencies often occur concurrently, and there are many interactions between micronutrients. OBJECTIVE: This study investigated interactions among 3 important micronutrients--iron, vitamin A, and zinc--when they are given as supplements. DESIGN: In a randomized, double-blind, placebo-controlled supplementation trial, 387 Indonesian infants aged 4 mo were supplemented 5 d/wk for 6 mo with 10 mg Fe, 10 mg Zn, 2.4 mg beta-carotene, 10 mg each of Fe and Zn, 10 mg Zn + 2.4 mg beta-carotene, or placebo. Complete data on micronutrient status, including hemoglobin, ferritin, retinol, zinc, and the modified relative dose response (a measure of liver retinol stores), were available from 256 infants at the end of the study. RESULTS: Iron-supplemented infants had significantly lower plasma retinol concentrations and a significantly higher prevalence of vitamin A deficiency, as defined by a plasma retinol concentration

Health of infants in developing countries is constantly challenged by pathogens. Unfortunately, the immune system of newborn infants is immature, developing during the first year of life to attain adequate immunocompetence at about one year of age. During the first few months of life, maternal antibodies (especially IgG) acquired in utero circulate and protect the newborn. In addition, via breast milk, the infant acquires considerable amounts of immunoglobulins (mostly sIgA) and possibly other humoral and cellular components of the mother’s immune defence. The protective effect of sIgA in breast milk is restricted to the gut. The precise role of the other immunomodulatory components of breast milk, remains unclear.

Many indicators of micronutrient status change during infection because of the acute phase response. In this study, relationships between the acute phase response, assessed by measuring concentrations of C-reactive protein (CRP), alpha(1)-antichymotrypsin (ACT) and alpha(1)-acid glycoprotein (AGP), and indicators of micronutrient status were analyzed in 418 infants who completed a 6-mo randomized, double-blind, placebo-controlled, supplementation trial with iron, zinc and/or beta-carotene. The acute phase response, defined by raised CRP (plasma concentration10 mg/L), raised AGP (1.2 g/L), or both raised CRP and AGP, significantly affected indicators of iron, vitamin A and zinc status, independently of the effects of supplementation. Plasma ferritin concentrations were higher by 15.7 (raised AGP) to 21.2 (raised CRP and AGP) micro g/L in infants with elevated acute phase proteins compared with infants without acute phase response (P0.001). In contrast, plasma concentrations of retinol were lower by 0.07 (P0.05, raised AGP) to 0.12 (P0.01, raised CRP) micro mol/L, and of zinc lower by 1.49 (P0.01, raised AGP) to 1.89 (P0.05, raised CRP and AGP) micro mol/L. Hemoglobin concentrations and the modified relative dose response were not affected. Consequently, the prevalence of iron deficiency anemia was underestimated in infants with raised acute phase proteins by15%, whereas the prevalence of vitamin A deficiency was overestimated by16% compared with infants without acute phase response. Hence, using indicators of micronutrient status without considering the effects of the acute phase response results in a distorted estimate of micronutrient deficiencies, whose extent depends on the prevalence of infection in the population.

Long term follow-up suggests a potential benefit only in children with otitis media For most clinicians, vitamin A is first and foremost associated with eye disease. Vitamin A deficiency causes a range of ocular manifestations including xerophthalmia, night blindness, Bitot’s spots, and keratomalacia. Indeed, vitamin A and the eye provide a well known example of the importance of micronutrients for health, and many children have been told to eat their carrots because it is good for their eyes. In the linked long term follow-up of a randomised controlled trial, Schmitz and colleagues (doi:10.1136/bmj.d7962) assess a different effect of vitamin A—whether vitamin A supplementation in the preschool years can reduce hearing loss.1 Vitamin A has many important functions in the human body and its role in resistance to infectious diseases has been known for almost 100 years.2 However, interest in vitamin A waned with the appearance of antibiotics, to return in the 1980s when a study in Indonesia showed that half yearly high dose vitamin A supplementation dramatically reduced child mortality.3 This brought vitamin A …

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.