Realistic Food-Based Approaches Alone May Not Ensure Dietary Adequacy for Women and Young Children in South-East Asia.

Objectives Micronutrient deficiencies, in southeast Asia (SE Asia), remain a public health challenge. We evaluated whether promoting the consumption of locally available nutritious foods, which is a low-risk micronutrient intervention, alone can ensure dietary adequacy, for women of reproductive age and 6-23 m old children. Methods Representative dietary data from Cambodia, Indonesia, Lao PDR, Thailand and Vietnam were analysed using linear programming analysis to identify nutrients that are likely low in personal food environments (problem nutrients), and to formulate food-based recommendations (FBRs) for three to six target populations per country. Results The number of problem nutrients ranged from zero for 12-23 m olds in Indonesia, Thailand and Vietnam to six for pregnant women in Cambodia. The FBRs selected for each target population, if adopted, would ensure a low percentage of the population was at risk of inadequate intakes for five to ten micronutrients, depending on the country and target population. Of the 11 micronutrients modelled, requirements for iron, calcium and folate were most difficult to meet (≥ 10 of the 24 target populations), using FBRs alone. The number of individual FBRs selected per set, for each target population, ranged from three to eight; and often included meat, fish or eggs, liver/organ meats, vegetables and fruits. Conclusions for practice Intervention strategies need to increase access to nutritious foods, including products fortified with micronutrients, in SE Asia, when aiming to ensure dietary adequacy for most individuals in the population.

Triple-fortified rice containing vitamin A reduced marginal vitamin A deficiency and increased vitamin A liver stores in school-aged Thai children.

Vitamin A (VA)-fortified rice is a potential intervention strategy to prevent VA deficiency in at-risk populations. Hot-extruded, triple-fortified rice grains with added VA, zinc, and iron were produced by hot extrusion technology and their ability to improve VA status was tested in Thai schoolchildren. The fortification levels were 10 mg of iron, 9 mg of zinc, and 1.05 mg of VA/g extruded rice. A paired stable isotope dilution technique with labeled ¹³C2-retinyl acetate (¹³C-RID) was used to quantify VA pool size at the beginning and end of the feeding period. Fifty healthy schoolchildren with a serum retinol (SR) concentration of >0.7 µmol/L were randomly assigned to 2 groups to receive either triple-fortified rice (n = 25) or natural rice (n = 25) for 2 mo as part of the daily school meal. The fortified grains, mixed 1:50 with regular rice, were estimated to provide an extra 890 µg of VA/d, 5 d/wk. ¹³C2-retinyl acetate (1.0 µmol) was administered orally to each child before and at the end of the feeding period to estimate total body reserves (TBRs) of VA, which increased significantly (P < 0.05) in the intervention group from 153 ± 66 µmol retinol at baseline to 269 ± 148 µmol retinol after 2 mo of feeding. There was no change in the TBRs of VA in the control group (108 ± 67 vs. 124 ± 89 µmol retinol) (P = 0.22). Serum retinol remained unchanged in both groups. We conclude that VA-fortified, hot-extruded rice is an efficacious vehicle to provide additional VA to at-risk populations, and that the efficacy of VA-fortified foods can be usefully monitored by the ¹³C-RID measurement of TBRs of VA but not by changes in SR concentration.

International experiences in assessing vitamin A status and applying the vitamin A-labeled isotope dilution method.

Inadequate vitamin A (VA) nutrition continues to be a major problem worldwide, and many interventions being implemented to improve VA status in various populations need to be evaluated. The interpretation of results after an intervention depends greatly on the method selected to assess VA status. To evaluate the effect of an intervention on VA status, researchers in Cameroon, India, Indonesia, Mexico, Senegal and Zambia have used serum retinol as an indicator, and have not always found improvement in response to supplementation. One problem is that homeostatic control of serum retinol may mask positive effects of treatment in that changes in concentration are observed only when status is either moderately to severely depleted or excessive. Because VA is stored mainly in the liver, measurements of hepatic VA stores are the “gold standard” for assessing VA status. Dose response tests such as the relative dose response (RDR) and the modified relative dose response (MRDR), allow a qualitative assessment of VA liver stores. On the other hand, the use of the vitamin A-labeled isotope dilution (VALID) technique, (using 13C or 2H-labeled retinyl acetate) serves as an indirect method to quantitatively estimate total body and liver VA stores. Countries including Cameroon, China, Ghana, Mexico, Thailand and Zambia are now applying the VALID method to sensitively assess changes in VA status during interventions, or to estimate a population’s dietary requirement for VA. Transition to the use of more sensitive biochemical indicators of VA status such as the VALID technique is needed to effectively assess interventions in populations where mild to moderate VA deficiency is more prevalent than severe deficiency.

Key strategies to further reduce stunting in Southeast Asia: lessons from the ASEAN countries workshop.

BACKGROUND: To further reduce stunting in Southeast Asia, a rapidly changing region, its main causes need to be identified. OBJECTIVE: Assess the relationship between different causes of stunting and stunting prevalence over time in Southeast Asia. METHODS: Review trends in mortality, stunting, economic development, and access to nutritious foods over time and among different subgroups in Southeast Asian countries. RESULTS: Between 1990-2011, mortality among under-five children declined from 69/1,000 to 29/1,000 live births. Although disease reduction, one of two direct causes of stunting, has played an important role which should be maintained, improvement in meeting nutrient requirements, the other direct cause, is necessary to reduce stunting further. This requires dietary diversity, which is affected by rapidly changing factors: economic development; urbanization, giving greater access to larger variety of foods, including processed and fortified foods; parental education; and modernizing food systems, with increased distance between food producers and consumers. Wealthier consumers are increasingly able to access a more nutritious diet, while poorer consumers need support to improve access, and may also still need better hygiene and sanitation. CONCLUSIONS: In order to accelerate stunting reduction in Southeast Asia, availability and access to nutritious foods should be increased by collaboration between private and public sectors, and the Association of Southeast Asian Nations (ASEAN) can play a facilitating role. The private sector can produce and market nutritious foods, while the public sector sets standards, promotes healthy food choices, and ensures access to nutritious foods for the poorest, e.g, through social safety net programs.

The SMILING project: a North-South-South collaborative action to prevent micronutrient deficiencies in women and young children in Southeast Asia.

BACKGROUND: The "Sustainable Micronutrient Interventions to Control Deficiencies and Improve Nutritional Status and General Health in Asia" project (SMILING), funded by the European Commission, is a transnational collaboration of research institutions and implementation agencies in five Southeast Asian countries--Cambodia, Indonesia, Laos PDR, Thailand, and Vietnam--with European partners, to support the application of state-of-the art knowledge to alleviate micronutrient malnutrition in Southeast Asia. OBJECTIVE: The major expected outcomes are to improve micronutrient status on a large scale, to identify priority interventions in each Southeast Asian country, and to develop a road map for decision makers and donors for inclusion of these priority interventions into the national policy. METHODS: SMILING has been built around a strong project consortium that works on a constant and proactive exchange of data and analyses between partners and allows for the differences in contexts and development stages of the countries, as well as a strong North-South-South collaboration and colearning. RESULTS: The selection of Southeast Asian countries considered the range of social and economic development, the extent of micronutrient malnutrition, and capacity and past success in nutrition improvement efforts. SMILING is applying innovative tools that support nutrition policy-making and programming. The mathematical modeling technique combined with linear programming will provide insight into which food-based strategies have the potential to provide essential (micro) nutrients for women and young children. Multicriteria mapping will offer a flexible decision-aiding tool taking into account the variability and uncertainty of opinions from key stakeholders. The lessons learned throughout the project will be widely disseminated.

Use of nutritional biomarkers in program evaluation in the context of developing countries.

The Lancet series on maternal and child undernutrition emphasized the need for accurate and reliable biomarkers that reflect nutrient status and measure the impact of interventions. An initiative called Biomarkers of Nutrition for Development (BOND) by the Eunice Kennedy Shriver National Institute of Child Health and Human Development aims to provide guidance for the selection and interpretation of biomarkers that meet a range of interests, including research, clinical policy, and program development. This article summarizes the activities of the program working group of the BOND initiative. The working group specified biomarkers according to program objectives such as assessing the nutritional situation or status of target populations/areas; monitoring progress of intervention; and evaluating program impact. In addition, the biomarkers developed were required to be feasible in the field settings. Based on these considerations, population-based biomarkers for programs are proposed for case examples of vitamin A, folate, vitamin B-12, iron, and zinc. Biomarkers of underlying infection/inflammation, anthropometric measures of growth, and dietary intake are recommended to be included. A program manager guide and future research to develop biomarkers for program context are recommended.

Moving towards evidence-based policy and program planning in multiple micronutrient interventions for children: symposium summary.

This article provides a summary of the symposium "Multiple Micronutrient Interventions during Early Childhood: Moving toward Evidence-Based Policy and Program Planning." The symposium reviewed the strength of evidence of multiple micronutrient interventions on child health, growth, and development, case examples demonstrating how information from program evaluations and the local context can be used to improve program design and performance, and the process by which evidence evolves, resulting in guidelines for policy-makers and program managers. The presentations highlighted the importance of an interactive platform at the country level where the scientific community and country stakeholders exchange ideas, develop a priority implementation research agenda, and clarify key issues to generate and modify policy and programs based on the best evidence available and the ability to deliver results in real time.

Multi-micronutrient-fortified biscuits decreased prevalence of anemia and improved micronutrient status and effectiveness of deworming in rural Vietnamese school children.

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.

Zinc supplementation improved length growth only in anemic infants in a multi-country trial of iron and zinc supplementation in South-East Asia.

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 (P < 0.01). Baseline factors modified the effect of supplementation, with infants anemic at baseline (hemoglobin < 105 g/L) benefiting from zinc supplementation, with an estimated increase in height-for-age Z-score (HAZ) score of 0.17 (P < 0.01), 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 of >3500 g (estimated effect size, -0. 14 HAZ score; P < 0.01), 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.

Only a small proportion of anemia in northeast Thai schoolchildren is associated with iron deficiency.

BACKGROUND: Iron deficiency is assumed to be the major cause of anemia in northeast Thailand, but other factors may be involved. OBJECTIVE: We determined the prevalence of anemia among schoolchildren in northeast Thailand and the role of hemoglobinopathies, selected micronutrient deficiencies, and other factors in hemoglobin status. DESIGN: Blood samples were collected from 567 children aged 6-12.9 y attending 10 primary schools for the determination of a complete blood count and hemoglobin type [Hb AA (normal hemoglobin), Hb AE (heterozygous for Hb type E), and Hb EE (homozygous for Hb type E)] and the measurement of serum ferritin, transferrin receptor, retinol, vitamin B-12, and plasma and erythrocyte folate concentrations. Children with a C-reactive protein concentration > or = 10 mg/L (n = 12), which indicated infection, were excluded. RESULTS: The prevalence of anemia was 31%. Age, hemoglobin type, and serum retinol were the major predictors of hemoglobin concentration. Hb AA and Hb AE children with anemia had lower (P < 0.01) hematocrit, mean cell volume, and serum retinol values than did their nonanemic counterparts; no significant differences in serum ferritin were found by hemoglobin type. Only 16% (n = 22) of the anemic Hb AA and Hb AE children were iron deficient. Hb AA and Hb AE children with a serum retinol concentration <0.70 micromol/L (n = 14) had a significantly higher geometric mean serum ferritin concentration than did those with a retinol concentration > or = 0.70 micromol/L (P = 0.009); no significant difference in transferrin receptor concentrations was found between these 2 groups. CONCLUSIONS: Hemoglobinopathies, suboptimal vitamin A status, and age were the major predictors of hemoglobin concentration. The contribution of iron deficiency to anemia was low, and its detection was complicated by coexisting suboptimal vitamin A status.

Application of isotope dilution technique in vitamin A nutrition.

The isotope dilution technique involving deuterated retinol has been developed to quantitatively estimate total body reserves of vitamin A in humans. The technique provided good estimates in comparison to hepatic vitamin A concentrations in Bangladeshi surgical patients. Kinetic studies in the United States, Bangladesh, and Guatemala indicated the mean equilibration time of 17 to 20 days irrespective of the size of hepatic reserves. Due to the controversy surrounding the efficacy of a carotene-rich diet on improvement of vitamin A status, the isotope dilution technique was proposed to pursue this research question further (IAEA's coordinated research program). In the Philippines, schoolchildren with low serum retinol concentrations showed significant improvement in total body vitamin A stores following intake of carotene-rich foods (orange fruits and vegetables), using a three-day deuterated-retinol-dilution procedure. When Chinese kindergarten children were fed green and yellow vegetables during the winter, their total body vitamin A stores were sustained as compared to a steady decline of vitamin A stores in the control children. Likewise, daily consumption of purified beta-carotene or diet rich in provitamin A carotenoids were shown to prevent a loss in total body vitamin A stores among Thai lactating women during the rice-planting season. These studies demonstrate potentials of the isotope dilution technique to evaluate the impact of provitamin A carotenoid intervention programs.

Executive summary--Biomarkers of Nutrition for Development: Building a Consensus.

The ability to develop evidence-based clinical guidance and effective programs and policies to achieve global health promotion and disease prevention goals depends on the availability of valid and reliable data. With specific regard to the role of food and nutrition in achieving those goals, relevant data are developed with the use of biomarkers that reflect nutrient exposure, status, and functional effect. A need exists to promote the discovery, development, and use of biomarkers across a range of applications. In addition, a process is needed to harmonize the global health community's decision making about what biomarkers are best suited for a given use under specific conditions and settings. To address these needs, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, organized a conference entitled "Biomarkers of Nutrition for Development: Building a Consensus," which was hosted by the International Atomic Energy Agency. Partners included key multilateral, US agencies and public and private organizations. The assembly endorsed the utility of this initiative and the need for the BOND (Biomarkers of Nutrition for Development) project to continue. A consensus was reached on the requirement to develop a process to inform the community about the relative strengths or weaknesses and specific applications of various biomarkers under defined conditions. The articles in this supplement summarize the deliberations of the 4 working groups: research, clinical, policy, and programmatic. Also described are content presentations on the harmonization processes, the evidence base for biomarkers for 5 case-study micronutrients, and new frontiers in science and technology.

Performance of the CRAFTi portable fluorometer comparing with the HPLC method for determining serum retinol.

OBJECTIVE: To determine the performance of a portable fluorometer for measuring serum retinol (SR) concentration. DESIGN AND METHODS: Serum samples were obtained from 75 factory worker women and 143 school children. SR concentration was quantified using a portable fluorometer ('CRAFTi') and HPLC analysis. RESULTS: SR by HPLC (1.23 ± 0.43 µmol/L) and CRAFTi (1.16 ± 0.46 µmol/L) was significantly correlated. Sensitivity and specificity were 85.3% and 78.0% (cutoff of 1.05 µmol/L). Kappa statistics showed moderate agreement. CONCLUSIONS: CRAFTi portable fluorometer is a promising field-friendly tool for screening vitamin A deficiency.

Decreased parasite load and improved cognitive outcomes caused by deworming and consumption of multi-micronutrient fortified biscuits in rural Vietnamese schoolchildren.

Micronutrient deficiencies are associated with impaired growth and cognitive function. A school-based fortification program might benefit schoolchildren but a high prevalence of parasite infestation might affect effectiveness. A randomized, double-blind, placebo-controlled 2 × 2 factorial trial was conducted to assess the efficacy of multi-micronutrient fortified biscuits with or without de-worming on growth, cognitive function, and parasite load in Vietnamese schoolchildren. Schoolchildren (n = 510), 6-8 years of age were randomly allocated to receive albendazole or placebo at baseline and four months of multi-micronutrient fortified biscuits (FB) or non-fortified biscuits. Children receiving FB for four months scored higher on two cognitive tests: Raven's Colored Progressive Matrices and the Digit Span Forward test. Children receiving albendazole plus FB had the lowest parasite load after four months. In children receiving FB, mid-upper arm circumference was slightly improved (+0.082 cm) but there were no differences in other indexes of anthropometry. Combining multi-micronutrient fortified biscuits with de-worming is an effective strategy.

A micronutrient-fortified seasoning powder reduces morbidity and improves short-term cognitive function, but has no effect on anthropometric measures in primary school children in northeast Thailand: a randomized controlled trial.

BACKGROUND: Reductions in iodine and zinc deficiencies and improvements in hemoglobin were achieved from a micronutrient-fortified seasoning powder consumed in school lunches by children in northeast Thailand. OBJECTIVE: The objective was to determine whether fortification with 4 micronutrients in a school lunch results in changes in children's growth, morbidity, and cognitive function compared with no fortification. DESIGN: In a randomized controlled trial of 569 children aged 5.5-13.4 y from 10 schools, we compared the efficacy of a seasoning powder fortified with or without 5 mg Fe, 5 mg Zn, 50 mug I, and 270 mug vitamin A per serving consumed with a school lunch 5 d/wk. Here we report on results of the secondary functional outcomes. RESULTS: The groups were comparable concerning compliance and loss to follow-up. The intervention had no statistically significant effect on anthropometric measures over 31 wk, but reduced the incidence of respiratory-related illnesses [rate ratio (RR): 0.83; 95% CI: 0.73, 0.94], symptoms of runny nose (RR: 0.80; 95% CI: 0.70, 0.92), cough (RR: 0.80; 95% CI: 0.66, 0.96), and diarrhea (RR: 0.38; 95% CI: 0.16, 0.90). For the visual recall test, those in the fortified group recalled 0.5 more items (95% CI: 0.1, 0.9) than did the controls. There were no statistically significant differences between groups in the results of the digits forward and backward tests or in school grades at the conclusion of the 2 semesters. CONCLUSION: The beneficial effects on morbidity and visual recall over a short period, in addition to some biochemical improvements, highlight the potential of this micronutrient-fortified seasoning powder supplied in a school lunch. This trial was registered at clinical trials.gov as ACTRN12605000341628.

Sex differences in prevalence of anaemia and iron deficiency in infancy in a large multi-country trial in South-East Asia.

To evaluate effects of Fe supplementation and sex on the prevalence of anaemia and Fe status in infants in South-East Asia, biochemical data from four parallel, randomized, double-blind trials with Fe and/or Zn supplementation in infants (n 2452) in Indonesia, Thailand and Vietnam was pooled. At recruitment (5 months of age), Hb concentrations were slightly but significantly lower in boy infants compared with girl infants (108.7 g/l v. 111.4 g/l, P = 0.04). At 11 months of age, boy infants not receiving Fe had significantly lower Hb (106.2 g/l v. 111.0 g/l, P < 0.001) and lower serum ferritin concentrations (14.3 microg/l v. 21.1 g/l, P < 0.001) than girl infants not receiving Fe. Consequently, boy infants had a relative risk of 1.6 (95% CI 1.3, 2.1) to be anaemic, and of 3.3 (95% CI 2.1, 5.0) for having Fe deficiency anaemia compared with girl infants. Fe supplementation significantly increased Hb concentrations in both boys and girls. There was no sex difference in Fe status in infants receiving Fe for 6 months. This study shows that the markedly higher risk for anaemia and Fe deficiency indicates higher Fe requirements in boy than in girl infants. In South-East Asia, standard infant feeding practices do not provide sufficient Fe to meet requirements of infants, especially boys. Current daily recommended intake for Fe in infancy is the same for boy and girl infants however. Our findings suggest that in especially the second half of infancy, Fe requirements for boy infants are approximately 0.9 mg/d higher than for girl infants.

Combined iron and zinc supplementation in infants improved iron and zinc status, but interactions reduced efficacy in a multicountry trial in southeast Asia.

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% (P<0.01) and zinc deficiency by 10% (P<0.05) but was less effective (P<0.05) 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 P<0.01), but had no separate effect on zinc status, whereas zinc supplementation had a negative effect on hemoglobin concentrations (-2.5 g/L, P<0.001), 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.