Maternal micronutrient supplementation with zinc and ß-carotene affects morbidity and immune function of infants during the first 6 months of life.

BACKGROUND/OBJECTIVES: Micronutrient deficiencies are prevalent worldwide, and a major cause of infant death. Supplementation with multiple micronutrients during pregnancy might improve micronutrient status of the newborn, thereby reducing morbidity and death. Moreover, maternal supplementation might affect the newborn's immune development. Therefore, this study investigated the effects of maternal zinc and ß-carotene supplementation on the infant's morbidity and immune function during the first 6 months of life. SUBJECTS/METHODS: Mothers were supplemented during pregnancy with ß-carotene and/or zinc, in addition to iron and folic acid, in a randomized, double-blind controlled trial. Newborn infants (n=136) were followed up for 6 months. RESULTS: Infants born from mothers receiving zinc during pregnancy had significantly fewer episodes of diarrhoea than infants born from mothers not receiving zinc (0.2 and 0.4, respectively), but more episodes of cough (1.3 and 0.9 respectively) during the first 6 months. Maternal ß-carotene supplementation had no effect on infants' morbidity. Cytokine production in the newborns was affected by maternal zinc and ß-carotene supplementation, with zinc supplementation giving higher interleukin-6 production (16% higher), and ß-carotene supplementation leading to lower interferon-γ production (36% lower). CONCLUSIONS: This study shows that maternal supplementation with zinc and ß-carotene affected the newborn's immune development in specific ways, but only maternal zinc supplementation significantly affected morbidity in the infants. Addition of zinc to routine iron and folic acid supplements for pregnant women could be an effective way to reduce diarrhoeal disease during the first 6 months of life, albeit at the expense of more episodes of cough.

Reduced production of immunoregulatory cytokines in vitamin A- and zinc-deficient Indonesian infants.

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 assessment 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.

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.

Concurrent micronutrient deficiencies in lactating mothers and their infants in Indonesia.

BACKGROUND: Deficiencies of vitamin A, iron, and zinc are prevalent worldwide, affecting vulnerable groups such as lactating women and infants. However, the existence of concurrent deficiencies has received little attention. OBJECTIVE: The aim was to investigate the extent to which deficiencies of vitamin A, iron, and zinc coexist and the nutritional relation between lactating mothers and their infants. DESIGN: In a cross-sectional survey in rural West Java, Indonesia, 155 lactating mothers and their healthy infants were assessed anthropometrically and blood, urine, and breast-milk samples were obtained. RESULTS: Marginal vitamin A deficiency was found in 54% of the infants and 18% of the mothers. More than 50% of the mothers and infants were anemic and 17% of the infants and 25% of the mothers were zinc deficient. There was a strong interrelation between the micronutrient status of the mothers and infants and the concentrations of retinol and beta-carotene in breast milk. Vitamin A deficiency in infants led to an increased risk of anemia and zinc deficiency (odds ratios: 2.5 and 2.9, respectively), whereas in mothers the risk of anemia and iron deficiency (odds ratios: 3.8 and 4.8, respectively) increased. In infants, concentrations of insulin-like growth factor I were related to concentrations of plasma retinol and beta-carotene but not to zinc. CONCLUSIONS: Micronutrient deficiencies were prevalent in West Java. The micronutrient status of lactating mothers and that of their infants were closely related; breast milk was a key connecting factor for vitamin A status. Furthermore, concurrent micronutrient deficiencies appeared to be the norm.

A versatile vector for controlled expression of genes in Escherichia coli and Salmonella typhimurium.

We have constructed two expression vectors based on the pJF118HE vector developed for Escherichia coli by Fürste 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.