nan Muhilal

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 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-γ (IFN-γ), 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-γ, but also significantly higher circulating neopterin concentrations. Production of IFN-γ and IL-12 were strongly correlated, IFN-γ 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).

Maternal micronutrient supplementation with zinc and β-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 newborns immune development. Therefore, this study investigated the effects of maternal zinc and β-carotene supplementation on the infants morbidity and immune function during the first 6 months of life.Subjects/Methods:Mothers were supplemented during pregnancy with β-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 β-carotene supplementation had no effect on infants’ morbidity. Cytokine production in the newborns was affected by maternal zinc and β-carotene supplementation, with zinc supplementation giving higher interleukin-6 production (16% higher), and β-carotene supplementation leading to lower interferon-γ production (36% lower).Conclusions:This study shows that maternal supplementation with zinc and β-carotene affected the newborns 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.

Response of Bitot's Spots in Preschool Children to Vitamin A Treatment

In a double-masked, placebo-controlled, clinical trial in Indonesia, 88 preschool children between the ages of 36 and 72 months with Bitots spots were randomly assigned to 200,000 IU of oral vitamin A or placebo and followed up for five weeks. Baseline and follow-up serum vitamin A levels were obtained. Of the 45 children receiving vitamin A, 33 (73.3%) showed complete cure and disappearance of Bitots spots, six (13.3%) had disappearance of some but not all Bitots spots, and six (13.3%) were unresponsive to treatment. The nonresponsive children were older, all male, and had higher initial mean serum vitamin A levels, 23.0 micrograms/dl, compared to 15.9 micrograms/dl in the cured group (P = .017). These data suggest that normal vitamin A status may be found in approximately 13% of children with Bitots spots before vitamin A intervention and that one fourth of those who had Bitots spots originally will not be cured of all Bitots spots after intervention. These are important factors to consider when using Bitots spots in prevalence surveys as a clinical sign of vitamin A deficiency.

24-Hour History is More Closely Associated with Vitamin a Status and Provides a Better Estimate of Dietary Vitamin a Intake of Deficient Indonesian Preschool Children Than a Food Frequency Method

OBJECTIVES To determine if the Simplified Dietary Assessment to Identify Groups at Risk of Inadequate Intake of Vitamin A developed by the International Vitamin A Consultative Group (IVACG) correctly classified a group of vitamin A-deficient children as being at risk, and to see if a food frequency questionnaire (FFQ) or 24-hour history (24HH) yielded estimated dietary vitamin A intakes most closely associated with vitamin A status. DESIGN Forty-seven foods were identified as contributing most of the vitamin A to the diet of the study population. For each food, usual portion sizes were determined during a pilot study. Intake was calculated from data collected by FFQ and 24HH. Four modifications of the 24HH analysis were made to determine if this method of analysis could be simplified. SUBJECTS/SETTING Subjects were 265 Indonesian children with or at high risk of developing xerophthalmia. RESULTS Mean and median intakes of vitamin A based on the 24HH analysis were 50% and 27% of the US Recommended Dietary Allowance, respectively, which accurately identified the study sample as being at risk. Dietary intake based on the 24HH was significantly associated with serum retinol concentration (P = .01, trend test). Eliciting portion sizes during the 24HH was not necessary once the usual portion sizes consumed by the population were estimated in the pilot study. Mean and median intakes of vitamin A based on the FFQ were 150% and 118% of the Recommended Dietary Allowance, respectively, which suggests that the FFQ overestimated intake. Intake based on the FFQ was not correlated with serum retinol concentration. CONCLUSIONS Our findings do not support the IVACG recommendation that the FFQ be regarded as more reliable than the 24HH when the 2 methods produce different conclusions, nor the recommendation of some users of the method that the 24HH be dropped from the assessment method.

Response of Bitot's spots to a single oral 100,000- or 200,000-IU dose of vitamin A.

PURPOSE A randomized, controlled clinical trial was conducted in Indonesia to study the response of Bitots spots to a 100,000-IU dose of vitamin A, which is known to be associated with fewer acute side effects than the currently recommended 200,000-IU dose. METHODS A total of 114 children (ages 13 to 59 months) with Bitots spots were given an ocular examination; serum retinol concentration was measured, and the relative dose response test carried out. After administering one 100,000- or 200,000-IU oral dose of vitamin A, ocular examinations were repeated weekly for seven weeks and then biweekly for 20 more weeks, or until lesions were healed on two consecutive examinations. RESULTS Either dose of vitamin A was similarly effective in healing Bitots spots. The most important factor in predicting responsiveness to treatment was baseline serum retinol concentration: children with lower pretreatment concentrations were more likely to have responsive lesions. No child had a relapse within the first three months after treatment. However, by six months, children who had received the higher dose were 82% less likely to have a relapse compared with children who had received the lower dose. CONCLUSIONS Although either a 100,000- or 200,000-IU dose of vitamin A is similarly effective in healing Bitots spots, a 200,000-IU dose provides longer protection. This benefit justifies the higher rates of transient mild side effects associated with the 200,000-IU dose. The current 200,000-IU dose of vitamin A recommended by the World Health Organization for prophylactic dosing should not be reduced.

Micronutrient Deficiency and Supplementation in Indonesian Infants

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.