Perspective: Integration to Implementation (I-to-I) and the Micronutrient Forum-Addressing the Safety and Effectiveness of Vitamin A Supplementation.

An ongoing challenge to our ability to address the role of food and nutrition in health promotion and disease prevention is how to design and implement context-specific interventions and guidance that are safe, efficacious, and avoid unintended consequences. The integration to effective implementation (I-to-I) concept is intended to address the complexities of the global health context through engagement of the continuum of stakeholders involved in the generation, translation, and implementation of evidence to public health guidance/programs. The I-to-I approach was developed under the auspices of the Micronutrient Forum and has been previously applied to the question of safety and effectiveness of interventions to prevent and treat nutritional iron deficiency. The present article applies the I-to-I approach to questions regarding the safety and utility of large-dose vitamin A supplementation programs, and presents the authors' perspective on key aspects of the topic, including coverage of the basic and applied biology of vitamin A nutrition and assessment, clinical implications, and an overview of the extant data with regard to both the justification for and utility of available intervention strategies. The article includes some practical considerations based on specific country experiences regarding the challenges of implementing vitamin A-related programs. This is followed by an overview of some challenges associated with engagement of the enabling communities that play a critical role in the implementation of these types of public health interventions. The article concludes with suggestions for potential approaches to move this important agenda forward.

Public Health Aspects in the Prevention and Control of Vitamin Deficiencies.

Vitamin deficiencies remain major etiological factors in the global burden of disease, especially in low- and middle-income countries. The purpose of this state-of-the-art review was to update current information on deficiencies of vitamins and public health approaches to addressing them. Some stages of life present a higher risk of deficiency than others: risks are higher in pregnant women, children (from conception to young childhood), adolescents, the elderly, and all of the over 800 million people globally who are undernourished. At risk are approximately 125 million preschool children with vitamin A deficiency, as well as sub-populations at risk of deficiencies of folate, thiamin, vitamin B12, niacin, riboflavin, other B vitamins. and vitamin D. Addressing micronutrient deficiencies requires identifying those at risk and then working to prevent and manage that risk. Public health approaches include improved, diversified diets; supplementation; fortification and biofortification; and other supportive public health measures. Historically, as with pellagra and beriberi and, in the last 3 decades, with vitamin A and folic acid, there has been encouraging progress, but much remains to be done.

Large-Scale Food Fortification and Biofortification in Low- and Middle-Income Countries: A Review of Programs, Trends, Challenges, and Evidence Gaps.

BACKGROUND: Food fortification and biofortification are well-established strategies to address micronutrient deficiencies in vulnerable populations. However, the effectiveness of fortification programs is not only determined by the biological efficacy of the fortified foods but also by effective and sustainable implementation, which requires continual monitoring, quality assurance and control, and corrective measures to ensure high compliance. OBJECTIVE: To provide an overview of efficacy, effectiveness, economics of food fortification and biofortification, and status of and challenges faced by large-scale food fortification programs in low- and middle-income countries (LMIC). METHODS: A literature review of PubMed publications in English from 2000 to 2017, as well as gray literature, targeting nongovernmental organizations whose work focuses on this topic, complemented by national reports and a "snowball" process of citation searching. The article describes remaining technical challenges, barriers, and evidence gap and prioritizes recommendations and next steps to further accelerate progress and potential of impact. RESULTS: The review identifies and highlights essential components of successful programs. It also points out issues that determine poor program performance, including lack of adequate monitoring and enforcement and poor compliance with standards by industry. CONCLUSIONS: In the last 17 years, large-scale food fortification initiatives have been reaching increasingly larger segments of populations in LMIC. Large-scale food fortification and biofortification should be part of other nutrition-specific and nutrition-sensitive efforts to prevent and control micronutrient deficiencies. There are remaining technical and food system challenges, especially in relation to improving coverage and quality of delivery and measuring progress of national programs.

Integration to Implementation and the Micronutrient Forum: A Coordinated Approach for Global Nutrition. Case Study Application: Safety and Effectiveness of Iron Interventions.

Paramount among the challenges to our ability to address the role of food and nutrition in health promotion and disease prevention is how to design and implement context-specific interventions and guidance. The Integration to Effective Implementation (I-to-I) concept is intended to address the complexities of the global health context through engagement of the continuum of stakeholders involved in the food and nutrition enterprise. The 2014 Micronutrient Forum (MNF) Global Conference held in Addis Ababa, Ethiopia, in June 2014 offered the opportunity to apply the I-to-I approach with the use of current concerns about the safety and effectiveness of interventions to prevent and treat iron deficiency (ID) as a case study. ID is associated with a range of adverse outcomes, especially in pregnant and nonpregnant women, infants, and primary school-age children. Strategies to combat ID include iron supplementation, multiple micronutrient powders, and food-based interventions to enhance dietary iron intake. Recent reports indicate potential increased adverse risks when iron is provided in areas with high infection burdens (e.g., malaria). This paradox has weakened iron intervention programs. Furthermore, the selection and interpretation of available biomarkers for assessing iron nutrition have been found to be compromised by the inflammatory process. These issues highlight the need for a comprehensive approach that considers basic biology, assessment, interventions, and how these can be translated into appropriate programs and policies. The application of the I-to-I with the use of the MNF offered an opportunity to explore how that might be achieved.

Micronutrients in pregnancy in low- and middle-income countries.

Pregnancy is one of the more important periods in life when increased micronutrients, and macronutrients are most needed by the body; both for the health and well-being of the mother and for the growing foetus and newborn child. This brief review aims to identify the micronutrients (vitamins and minerals) likely to be deficient in women of reproductive age in Low- and Middle-Income Countries (LMIC), especially during pregnancy, and the impact of such deficiencies. A global prevalence of some two billion people at risk of micronutrient deficiencies, and multiple micronutrient deficiencies of many pregnant women in LMIC underline the urgency to establishing the optimal recommendations, including for delivery. It has long been recognized that adequate iron is important for best reproductive outcomes, including gestational cognitive development. Similarly, iodine and calcium have been recognized for their roles in development of the foetus/neonate. Less clear effects of deficiencies of zinc, copper, magnesium and selenium have been reported. Folate sufficiency periconceptionally is recognized both by the practice of providing folic acid in antenatal iron/folic acid supplementation and by increasing numbers of countries fortifying flours with folic acid. Other vitamins likely to be important include vitamins B12, D and A with the water-soluble vitamins generally less likely to be a problem. Epigenetic influences and the likely influence of micronutrient deficiencies on foetal origins of adult chronic diseases are currently being clarified. Micronutrients may have other more subtle, unrecognized effects. The necessity for improved diets and health and sanitation are consistently recommended, although these are not always available to many of the world's pregnant women. Consequently, supplementation programmes, fortification of staples and condiments, and nutrition and health support need to be scaled-up, supported by social and cultural measures. Because of the life-long influences on reproductive outcomes, including inter-generational ones, both clinical and public health measures need to ensure adequate micronutrient intakes during pregnancy, but also during adolescence, the first few years of life, and during lactation. Many antenatal programmes are not currently achieving this. We aim to address the need for micronutrients during pregnancy, the importance of micronutrient deficiencies during gestation and before, and propose the scaling-up of clinical and public health approaches that achieve healthier pregnancies and improved pregnancy outcomes.

Effect of long-term intermittent supplementation with multiple micronutrients compared with iron-and-folic acid supplementation on Hb and micronutrient status of non-anaemic adolescent schoolgirls in rural Bangladesh.

The present study examined whether long-term supplementation with once- and twice-weekly multiple micronutrients (MMN-1 and MMN-2) can improve Hb and micronutrient status more than twice-weekly Fe-folic acid (IFA-2) supplementation in non-anaemic adolescent girls in Bangladesh. An equal number of 324 rural schoolgirls aged 11-17 years were given MMN-1 or MMN-2 or IFA-2 supplements for 52 weeks in a randomised, double-blind trial. Blood samples were collected at baseline, and at 26 and 52 weeks of supplementation. The girls receiving IFA-2 supplements were more likely to be anaemic than the girls receiving MMN-2 supplements for 26 weeks (OR 5·1, 95% CI 1·3, 19·5; P = 0·018). All three supplements reduced Fe deficiency effectively. Both the MMN-1 and MMN-2 groups showed significantly greater improvements in vitamins A, B(2) and C status than the girls in the IFA-2 group, as might be expected. Receiving a MMN-1 supplement was found to be less effective than MMN-2 supplement in improving Fe, vitamins A, B(2) and folic acid status. Receiving micronutrient supplements beyond 26 weeks showed little additional benefit in improving micronutrient status. In conclusion, given twice-weekly for 26 weeks, MMN supplements can improve micronutrient status effectively with no significant increase in Hb concentration compared with IFA supplements in non-anaemic Bangladeshi adolescent girls. However, it significantly reduces the risk of anaemia. Before any recommendations can be made, further research, including into cost-effectiveness, is needed to see whether MMN supplementation has any additional longer-term health benefits over that of IFA supplementation in this population.

Global burden and significance of multiple micronutrient deficiencies in pregnancy.

Maternal mortality, low birthweight infants and childhood stunting continue to be major global public health problems, part of a recurring cycle of disadvantage. Maternal undernutrition in particular is one of the most neglected aspects of nutrition in public health. One possible low-cost public health intervention that might help address these problems is the antenatal provision of multiple micronutrient supplements. If the evidence base could be established, cost-effectiveness found to be acceptable and safety ensured, supplementation could ameliorate the impact of poor nutrition and diets, high disease burdens and the sociocultural factors contributing to these problems. There have been good studies in over a dozen countries addressing some of these issues but with conflicting results. Consequently, at least three meta-analyses have been undertaken to establish significant findings that could help guide policies and programs. They concluded that multimicronutrient supplementation improves birthweight and likely reduces the number of infants born low birthweight. Supplementation with iron-folic acid or multimicronutrients also appears to have positive longer-term impacts on the health and development of the offspring. There remain concerns about possible increased infant mortality in some populations. Given the results of the meta-analyses, cautious scaling-up of country effectiveness trials appears justified with careful monitoring and evaluation.

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.

Long-term intermittent multiple micronutrient supplementation enhances hemoglobin and micronutrient status more than iron + folic acid supplementation in Bangladeshi rural adolescent girls with nutritional anemia.

Previous short-term supplementation studies showed no additional hematologic benefit of multiple micronutrients (MMN) compared with iron + folic acid (IFA) in adolescent girls. This study examines whether long-term once- or twice-weekly supplementation of MMN can improve hemoglobin (Hb) and micronutrient status more than twice-weekly IFA supplementation in anemic adolescent girls in Bangladesh. Anemic girls (n = 324) aged 11-17 y attending rural schools were given once- or twice-weekly MMN or twice-weekly IFA, containing 60 mg iron/dose in both supplements, for 52 wk in a randomized double-blind trial. Blood samples were collected at baseline and 26 and 52 wk. Intent to treat analysis showed no significant difference in the Hb concentration between treatments at either 26 or 52 wk. However, after excluding girls with hemoglobinopathy and adjustment for baseline Hb, a greater increase in Hb was observed with twice-weekly MMN at 26 wk (P = 0.045). Although all 3 treatments effectively reduced iron deficiency, once-weekly MMN produced significantly lower serum ferritin concentrations than the other treatments at both 26 and 52 wk. Both once- and twice-weekly MMN significantly improved riboflavin, vitamin A, and vitamin C status compared with IFA. Overall, once-weekly MMN was less efficacious than twice-weekly MMN in improving iron, riboflavin, RBC folic acid, and vitamin A levels. Micronutrient supplementation beyond 26 wk was likely important in sustaining improved micronutrient status. These findings highlight the potential usefulness of MMN intervention in this population and have implications for programming.

Addressing tuberculosis in the context of malnutrition and HIV coinfection.

BACKGROUND: Tuberculosis is the second leading cause of infectious disease mortality (1.8 million/year), after HIV/AIDS. There are more than 9 million new cases each year. One-third of the world's population, and 50% of adults in sub-Saharan Africa, South Asia, and SouthEast Asia, are infected, representing an enormous pool of individuals at risk for developing the disease. The situation is complicated by the HIV/AIDS pandemic, widespread undernutrition, smoking, diabetes, increased mobility, and emergence of multi- and extensively drug-resistant tuberculosis. OBJECTIVE: To review the scientific evidence about the interactions among tuberculosis, nutrition, and HIV coinfection. RESULTS: HIV infection and malnutrition lower immunity, increasing the risk of reactivation tuberculosis and primary progressive disease. Having either tuberculosis or HIV infection causes weight loss. Malnutrition markedly increases mortality among both tuberculosis and HIV/AIDS patients and should be treated concurrently with treatment of the infections. Tuberculosis treatment is a prerequisite for nutritional recovery, in addition to intake of nutrients required for rebuilding tissues, which is constrained in food-insecure households. Additional pharmaceutical treatment to reduce the catabolic impact of inflammation or promote growth may be needed. Specific nutrients can contribute to faster sputum smear clearance, which is important for reducing transmission, as well as faster weight gain when combined with an adequate diet. Adequate nutrition and weight gain in undernourished populations might reduce the incidence of tuberculosis. CONCLUSIONS: The many risk factors for the development of tuberculosis need to be addressed simultaneously, especially HIV/AIDS and food insecurity and undernutrition. For stronger evidence-based guidelines, existing recommendations and clinical applications need to be more widely applied and evaluated.

Addressing tuberculosis in the context of malnutrition and HIV coinfection.

BACKGROUND: Tuberculosis is the second leading cause of infectious disease mortality (1.8 million/year), after HIV/AIDS. There are more than 9 million new cases each year. One-third of the world's population, and 50% of adults in sub-Saharan Africa, South Asia, and South-East Asia, are infected, representing an enormous pool of individuals at risk for developing the disease. The situation is complicated by the HIV/AIDS pandemic, widespread undernutrition, smoking, diabetes, increased mobility, and emergence of multi- and extensively drug-resistant tuberculosis. OBJECTIVE: To review the scientific evidence about the interactions among tuberculosis, nutrition, and HIV coinfection. RESULTS: HIV infection and malnutrition lower immunity, increasing the risk of reactivation tuberculosis and primary progressive disease. Having either tuberculosis or HIV infection causes weight loss. Malnutrition markedly increases mortality among both tuberculosis and HIV/AIDS patients and should be treated concurrently with treatment of the infections. Tuberculosis treatment is a prerequisite for nutritional recovery, in addition to intake of nutrients required for rebuilding tissues, which is constrained in food-insecure households. Additional pharmaceutical treatment to reduce the catabolic impact of inflammation or promote growth may be needed. Specific nutrients can contribute to faster sputum smear clearance, which is important for reducing transmission, as well as faster weight gain when combined with an adequate diet. Adequate nutrition and weight gain in undernourished populations might reduce the incidence of tuberculosis. CONCLUSIONS; The many risk factors for the development of tuberculosis need to be addressed simultaneously, especially HIV/AIDS and food insecurity and undernutrition. For stronger evidence-based guidelines, existing recommendations and clinical applications need to be more widely applied and evaluated.

How to ensure nutrition security in the global economic crisis to protect and enhance development of young children and our common future.

The global economic crisis, commodity price hikes, and climate change have worsened the position of the poorest and most vulnerable people. These crises are compromising the diet and health of up to 80% of the population in most developing countries and threaten the development of almost an entire generation of children ( approximately 250 million), because the period from conception until 24 mo of age irreversibly shapes people's health and intellectual ability. High food prices reduce diversity and nutritional quality of the diet and for many also reduce food quantity. Poor households are hit hardest, because they already spend 50-80% of expenditures on food, little on medicines, education, transport, or cooking fuel, and cannot afford to pay more. Reduced public spending, declining incomes, increased food and fuel prices, and reduced remittance thus impede and reverse progress made toward Millenium Development Goals 1, 4, and 5. Investments in nutrition are among the most cost-effective development interventions because of very high benefit:cost ratios, for individuals and for sustainable growth of countries, because they protect health, prevent disability, boost economic productivity, and save lives. To bridge the gap between nutrient requirements, particularly for groups with high needs, and the realistic dietary intake under the prevailing circumstances, the use of complementary food supplements to increase a meal's nutrient content is recommended. This can be in the form of, e.g., micronutrient powder or low-dose lipid-based nutrient supplements, which can be provided for free, in return for vouchers, at subsidized, or at commercial prices.

Multiple micronutrient supplementation during pregnancy in developing-country settings: policy and program implications of the results of a meta-analysis.

BACKGROUND: An independent Systematic Review Team performed a meta-analysis of 12 randomized, controlled trials comparing multiple micronutrients with daily iron-folic acid supplementation during pregnancy. OBJECTIVE: To provide an independent interpretation of the policy and program implications of the results of the meta-analysis. METHODS: A group of policy and program experts performed an independent review of the meta-analysis results, analyzing internal and external validity and drawing conclusions on the program implications. RESULTS: Although iron content was often lower in the multiple micronutrient supplement than in the iron-folic acid supplement, both supplements were equally effective in tackling anemia. Community-based supplementation ensured high adherence, but some mothers still remained anemic, indicating the need to concomitantly treat infections. The small, significant increase in mean birthweight among infants of mothers receiving multiple micronutrients compared with infants of mothers receiving iron-folic acid is of similar magnitude to that produced by food supplementation during pregnancy. Larger micronutrient doses seem to produce greater impact. Meaningful improvements have also been observed in height and cognitive development of the children by 2 years of age. There were no significant differences in the rates of stillbirth, early neonatal death, or neonatal death between the supplemented groups. The nonsignificant trend toward increased early neonatal mortality observed in the groups receiving multiple micronutrients may be related to differences across trials in the rate of adolescent pregnancies, continuing iron deficiency, and/or adequacy of postpartum health care and merits further investigation. CONCLUSIONS: Replacing iron-folic acid supplements with multiple micronutrient supplements in the package of health and nutrition interventions delivered to mothers during pregnancy will improve the impact of supplementation on birthweight and on child growth and development.

Maternal and child undernutrition: effective action at national level.

80% of the world's undernourished children live in just 20 countries. Intensified nutrition action in these countries can lead to achievement of the first Millennium Development Goal (MDG) and greatly increase the chances of achieving goals for child and maternal mortality (MDGs 4 and 5). Despite isolated successes in specific countries or for interventions--eg, iodised salt and vitamin A supplementation--most countries with high rates of undernutrition are failing to reach undernourished mothers and children with effective interventions supported by appropriate policies. This paper reports on an assessment of actions addressing undernutrition in the countries with the highest burden of undernutrition, drawing on systematic reviews and best-practice reports. Seven key challenges for addressing undernutrition at national level are defined and reported on: getting nutrition on the list of priorities, and keeping it there; doing the right things; not doing the wrong things; acting at scale; reaching those in need; data-based decisionmaking; and building strategic and operational capacity. Interventions with proven effectiveness that are selected by countries should be rapidly implemented at scale. The period from pregnancy to 24 months of age is a crucial window of opportunity for reducing undernutrition and its adverse effects. Programme efforts, as well as monitoring and assessment, should focus on this segment of the continuum of care. Nutrition resources should not be used to support actions unlikely to be effective in the context of country or local realities. Nutrition resources should not be used to support actions that have not been proven to have a direct effect on undernutrition, such as stand-alone growth monitoring or school feeding programmes. In addition to health and nutrition interventions, economic and social policies addressing poverty, trade, and agriculture that have been associated with rapid improvements in nutritional status should be implemented. There is a reservoir of important experience and expertise in individual countries about how to build commitment, develop and monitor nutrition programmes, move toward acting at scale, reform or phase-out ineffective programmes, and other challenges. This resource needs to be formalised, shared, and used as the basis for setting priorities in problem-solving research for nutrition.

Conclusions of the Joint WHO/UNICEF/IAEA/IZiNCG Interagency Meeting on Zinc Status Indicators.

Zinc deficiency is an important cause of morbidity in developing countries, particularly among young children, yet little information is available on the global prevalence of zinc deficiency. A working group meeting was convened by the World Health Organization (WHO), the United Nations Children's Fund (UNICEF), the International Atomic Energy Agency (IAEA), and the International Zinc Nutrition Consultative Group (IZiNCG) to review methods of assessing population zinc status and provide standard recommendations for the use of specific biochemical, dietary, and functional indicators of zinc status in populations. The recommended biochemical indicator is the prevalence of serum zinc concentration less than the age/sex/time of day-specific cutoffs; when the prevalence is greater than 20%, intervention to improve zinc status is recommended. For dietary indicators, the prevalence (or probability) of zinc intakes below the appropriate estimated average requirement (EAR) should be used, as determined from quantitative dietary intake assessments. Where the prevalence of inadequate intakes of zinc is greater than 25%, the risk of zinc deficiency is considered to be elevated. Previous studies indicate that stunted children respond to zinc supplementation with increased growth. When the prevalence of low height-for-age is 20% or more, the prevalence of zinc deficiency may also be elevated. Ideally, all three types of indicators would be used together to obtain the best estimate of the risk of zinc deficiency in a population and to identify specific subgroups with elevated risk. These recommended indicators should be applied for national assessment of zinc status and to indicate the need for zinc interventions. The prevalence of low serum zinc and inadequate zinc intakes may be used to evaluate their impact on the target population's zinc status.

Home fortification in emergency response and transition programming: experiences in Aceh and Nias, Indonesia.

BACKGROUND: Improving the nutritional status of an emergency-affected population is essential, because undernutrition increases infection risk and is linked to more than 50% of childhood deaths in developing countries. Emergency food aid addresses nutritional needs, including micronutrient deficiencies, but is provided only for a limited time and uses few items, so the needs of specific target groups are often not fully met. OBJECTIVE: To describe the post-tsunami experience with distribution of Vitalita Sprinkles in Aceh and Nias and to analyze the monitoring data gathered for the emergency response. METHODS: International agencies such as Helen Keller International and partners provided micronutrients in response to the tsunami emergency in Aceh and Nias and to analyze the monitoring data gathered for the emergency response. RESULTS: In March and April 2006, the percentage of children aged 6 months to 59 months who had consumed Vitalita in the previous month was more than 70% in 5 of 11 districts evaluated, 40% to 70% in another five districts, and 32% in one district. An independent survey found 25% less anemia among recipients. Almost all mothers interviewed during March to April 2006 (96.3%) had heard about Vitalita and recognized its packaging, 69% said that Vitalita contained vitamins for under-fives, 86% knew the appropriate target group for Vitalita, and 83% said it had to be mixed with solid food. Of the 26% that reported not having given Vitalita to their child in the last month, 90.5% said that their child did not like it. CONCLUSIONS AND LESSONS LEARNED: Because the product, including its concept, was new, appropriate information and training was required as well as a thorough introduction to the beneficiaries, particularly on proper use, to ensure acceptance. This experience demonstrates that providing micronutrients as part of emergency relief and transition programming, as recently recommended by the World Health Organization/UNICEF/World Food Program, is feasible.