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.     

Micronutrient deficiencies and gender: social and economic costs

Vitamin and mineral deficiencies adversely affect a third of the world's people. Consequently, a series of global goals and a serious amount of donor and national resources have been directed at such micronutrient deficiencies. Drawing on the extensive experience of the authors in a variety of institutional settings, the article used a computer search of the published scientific literature of the topic, supplemented by reports and published and unpublished work from the various agencies. In examining the effect of sex on the economic and social costs of micronutrient deficiencies, the paper found that: (1) micronutrient deficiencies affect global health outcomes; (2) micronutrient deficiencies incur substantial economic costs; (3) health and nutrition outcomes are affected by sex; (4) micronutrient deficiencies are affected by sex, but this is often culturally specific; and finally, (5) the social and economic costs of micronutrient deficiencies, with particular reference to women and female adolescents and children, are likely to be considerable but are not well quantified. Given the potential impact on reducing infant and child mortality, reducing maternal mortality, and enhancing neuro-intellectual development and growth, the right of women and children to adequate food and nutrition should more explicitly reflect their special requirements in terms of micronutrients. The positive impact of alleviating micronutrient malnutrition on physical activity, education and productivity, and hence on national economies suggests that there is also an urgent need for increased effort to demonstrate the cost of these deficiencies, as well as the benefits of addressing them, especially compared with other health and nutrition interventions.     

Identifying nutritional need for multiple micronutrient interventions

Micronutrient deficiency remains a major public health problem in many countries worldwide with important consequences for the health of the population and child growth and development. The objective of this article is to review information that should be taken into consideration in identifying the need for and in designing micronutrient programs. We review information that could be used to identify nutritional need, including the prevalence of deficiency and evidence of inadequate dietary intake as well as potential data sources and some strengths and weakness of such data for program decision-making. We also review factors that might modify the potential impact of programs and that should therefore be taken into consideration in their design. For example, such factors may include access to formal and informal health systems, quality of health provider training, and behavior change communication and complementary or overlapping interventions. Nationally representative data on micronutrient deficiencies and dietary intake are most useful for identifying unmet needs. Although the burden of micronutrient deficiencies lies in low-income countries, few have detailed information on specific deficiencies beyond anemia, and nationally representative dietary intake data are scarce. Nationally representative data may still mask considerable within-country variability by geographic, economic, or ethnic group. Some efforts designed to promote coordination in nutrition programming within countries utilizing information on prevalence, intake, and program coverage and utilization are also reviewed. Improving the quality of such data and ensuring continual updates are vital to guide decision making and to ensure that programs can appropriately respond to needs.     

Limitations of current indicators of micronutrient status

Assessment of micronutrient status is a major concern in public health nutrition, yet there are serious limitations to the indicators currently available. This paper presents the merits of these indicators along with their drawbacks, which include cost, lack of congruence between cutoffs denoting deficiency and adverse functional consequences, and inconsistent methods of evaluating the confounding effects of infections on micronutrient status indicators. Methods for assessing the functional consequences of micronutrient deficiencies are even less well developed; their usefulness would be enhanced by a greater focus on outcomes known to be influenced by deficiencies. Although there have been notable breakthroughs, further improvements in methods to assess micronutrient status are urgently needed.     

Micronutrient needs of malnourished children

PURPOSE OF REVIEW: In addition to overt manifestations of undernutrition such as stunting, wasting and underweight, micronutrient deficiencies are also recognized as important components of the spectrum of malnutrition. This review focuses on recent advances in our understanding of undernutrition and micronutrient deficiencies during childhood from a review of the literature over the last 18 months (August 2006-January 2008). RECENT FINDINGS: There is considerable advance in our understanding of the epidemiology and burden of childhood undernutrition and micronutrient deficiencies. Based on recent surveys, an estimated 32% (178 million) of children under 5 years of age were stunted. The corresponding global estimate of wasting is 10% (55 million children), of which 3.5% (19 million children) are severely wasted. It is estimated that nearly 11% of all children under 5 years of age, die due to four micronutrient deficiencies (vitamin A, zinc, iron and iodine). There is evidence from recent reviews of evidence-based interventions that administering single or multiple micronutrients can make a significant difference to health outcomes. However, delivery strategies may differ and recent data suggest that fortification may be a more efficient strategy to deliver multiple micronutrients. SUMMARY: These findings support the scaling up of evidence-based interventions to prevent and treat such deficiencies and to integrate these within health systems.     

Micronutrients and anaemia

Micronutrient deficiencies and anaemia remain as major health concerns for children in Bangladesh. Among the micronutrient interventions, supplementation with vitamin A to children aged less than five years has been the most successful, especially after distribution of vitamin A was combined with National Immunization Days. Although salt sold in Bangladesh is intended to contain iodine, much of the salt does not contain iodine, and iodine deficiency continues to be common. Anaemia similarly is common among all population groups and has shown no sign of improvement even when iron-supplementation programmes have been attempted. It appears that many other causes contribute to anaemia in addition to iron deficiency. Zinc deficiency is a key micronutrient deficiency and is covered in a separate paper because of its importance among new child-health interventions.     

Fortification strategies to meet micronutrient needs: successes and failures

Food fortification is likely to have played an important role in the current nutritional health and well-being of populations in industrialized countries. Starting in the early part of the 20th century, fortification was used to target specific health conditions: goitre with iodized salt; rickets with vitamin D-fortified milk; beriberi, pellagra and anaemia with B-vitamins and Fe-enriched cereals; more recently, in the USA, risk of pregnancy affected by neural-tube defects with folic acid-fortified cereals. A relative lack of appropriate centrally-processed food vehicles, less-developed commercial markets and relatively low consumer awareness and demand, means it has taken about another 50 years for fortification to be seen as a viable option for the less-developed countries. The present paper reviews selected fortification initiatives in developing countries to identify different factors that contributed to their successful implementation, as well as the challenges that continually threaten the future of these programmes. Ultimately, the long-term sustainability of fortification programmes is ensured when consumers are willing and able to bear the additional cost of fortified foods. There has been an enormous increase in fortification programmes over the last couple of decades in developing countries. Considerable progress has been made in reducing vitamin A and I deficiencies, although less so with Fe, even as Zn and folic acid deficiencies are emerging as important public health problems. Food fortification based on sound principles and supported by clear policies and regulations can play an increasingly large role in this progress towards prevention and control of micronutrient malnutrition.     

Consequences of poor maternal micronutrition before and during early pregnancy

In developing countries, micronutrient deficiencies are common and associated with poor pregnancy outcomes, which may in turn have longer-term effects on human health. The peri-conceptional period represents a particularly sensitive window of feto-placental development, during which suboptimal maternal micronutrition may have far-reaching consequences. The effects of targeted interventions during this period have been little studied in humans.     

The principles of disease elimination and eradication

The Dahlem Workshop discussed the hierarchy of possible public health interventions in dealing with infectious diseases, which were defined as control, elimination of disease, elimination of infections, eradication, and extinction. The indicators of eradicability were the availability of effective interventions and practical diagnostic tools and the essential need for humans in the life-cycle of the agent. Since health resources are limited, decisions have to be made as to whether their use for an elimination or eradication programme is preferable to their use elsewhere. The costs and benefits of global eradication programmes concern direct effects on morbidity and mortality and consequent effects on the health care system. The success of any disease eradication initiative depends strongly on the level of societal and political commitment, with a key role for the World Health Assembly. Eradication and ongoing programmes constitute potentially complementary approaches to public health. Elimination and eradication are the ultimate goals of public health, evolving naturally from disease control. The basic question is whether these goals are to be achieved in the present or some future generation.     

The historical evolution of thought regarding multiple micronutrient nutrition

Multiple micronutrient nutrition is an idea that originated in the 1940s and exemplifies the iterative nutritional paradigm. In the first four decades of the 20th century, scientists sought to separate and characterize the vitamins that were responsible for xerophthalmia, rickets, pellagra, scurvy, and beriberi. The dietary requirements of the different micronutrients began to be established in the early 1940s. Surveys showed that multiple micronutrient deficiencies were widespread in industrialized countries, and the problem was addressed by use of cod-liver oil, iodized salt, fortified margarine, and flour fortification with multiple micronutrients, and, with rising living standards, the increased availability and consumption of animal source foods. After World War II, surveys showed that multiple micronutrient deficiencies were widespread in developing countries. Approaches to the elimination of multiple micronutrient deficiencies include periodic vitamin A supplementation, iodized salt, targeted iron/folate supplementation, fortified flour, other fortified foods, home fortification with micronutrient powders, and homestead food production. The prevention of multiple micronutrient malnutrition is a key factor in achieving the Millennium Development Goals, given the important effects of micronutrients on health and survival.     

Meeting the challenges of micronutrient deficiencies in emergency-affected populations

Micronutrient deficiencies occur frequently in refugee and displaced populations. These deficiency diseases include, in addition to the most common Fe and vitamin A deficiencies, scurvy (vitamin C deficiency), pellagra (niacin and/or tryptophan deficiency) and beriberi (thiamin deficiency), which are not seen frequently in non-emergency-affected populations. The main causes of the outbreaks have been inadequate food rations given to populations dependent on food aid. There is no universal solution to the problem of micronutrient deficiencies, and not all interventions to prevent the deficiency diseases are feasible in every emergency setting. The preferred way of preventing these micronutrient deficiencies would be by securing dietary diversification through the provision of vegetables, fruit and pulses, which may not be a feasible strategy, especially in the initial phase of a relief operation. The one basic emergency strategy has been to include a fortified blended cereal in the ration of all food-aid-dependent populations (United Nations High Commissioner for Refugees/World Food Programme, 1997). In situations where the emergency-affected population has access to markets, recommendations have been to increase the general ration to encourage the sale and/or barter of a portion of the ration in exchange for locally-available fruit and vegetables (World Health Organization, 1999a,b, 2000). Promotion of home gardens as well as promotion of local trading are recommended longer-term options aiming at the self-sufficiency of emergency-affected households. The provision of fortified blended foods in the general ration has successfully prevented and controlled micronutrient deficiencies in various emergency settings. However, the strategy of relying only on fortified blended foods to prevent micronutrient deficiencies should be reviewed in the light of recurring evidence that provision of adequate supplies of these foods is often problematic. Donor policies on the bartering or exchange of food aid should also be clarified. Furthermore, the establishment of micronutrient surveillance systems, including standardized micronutrient deficiency diagnostic criteria, are vital for the control of micronutrient deficiency diseases.     

Can multi-micronutrient food fortification improve the micronutrient status, growth, health, and cognition of schoolchildren? A systematic review

Micronutrient deficiencies compromise the health and development of many school-age children worldwide. Previous research suggests that micronutrient interventions might benefit the health and development of school-age children and that multiple micronutrients might be more effective than single micronutrients. Fortification of food is a practical way to provide extra micronutrients to children. Earlier reviews of (multiple) micronutrient interventions in school-age children did not distinguish between supplementation or fortification studies. The present review includes studies that tested the impact of multiple micronutrients provided via fortification on the micronutrient status, growth, health, and cognitive development of schoolchildren. Twelve eligible studies were identified. Eleven of them tested the effects of multiple micronutrients provided via fortified food compared to unfortified food. One study compared fortification with multiple micronutrients to fortification with iodine alone. Multi-micronutrient food fortification consistently improved micronutrient status and reduced anemia prevalence. Some studies reported positive effects on morbidity, growth, and cognitive outcomes, but the overall effects on these outcomes were equivocal.     

Micronutrient status of populations and preventive nutrition interventions in South East Asia

Objectives Since the 1990s, programs for the control of micronutrient deficiencies became a public health priority for many governments, including the countries partnering the project “Sustainable Micronutrient Interventions to Control Deficiencies and Improve Nutritional Status and General Health in Asia” (SMILING): Cambodia, Indonesia, Laos-PDR, Thailand and Vietnam. The aim of this study was to map which micronutrient deficiencies have been addressed and which interventions were in place in the SMILING countries. Methods The mapping covered the period up to 2012. Updated information from relevant surveys after 2012 is included in this paper after the completion of the SMILING project. The mapping of micronutrient status was limited to either national or at least large-scale surveys. Information on nutrition interventions obtained through a systematic mapping of national programs combined with a snowball collection from various sources. Results Among the five SMILING countries, Thailand differed historically by an early implementation of a nationwide community-based nutrition program, contributing to reductions in undernutrition and micronutrient deficiencies. For Cambodia, Indonesia, Laos PDR, and Vietnam, some national programs addressing micronutrients have been implemented following adjusted international recommendations. National surveys on micronutrient status were scattered and inconsistent across the countries in design and frequency. Conclusion for practice In conclusion, some micronutrient deficiencies were addressed in national interventions but the evidence of effects was generally lacking because of limited nationally representative data collected. Improvement of intervention programs to efficiently reduce or eliminate micronutrient deficiencies requires more systematic monitoring and evaluation of effects of interventions in order to identify best practices.

     

Prevalence of Micronutrient Malnutrition Worldwide

Recent estimates indicate that globally over two billion people are at risk for vitamin A, iodine, and/or iron deficiency, in spite of recent efforts in the prevention and control of these deficiencies. The prevalence is especially high in Southeast Asia and sub-Saharan Africa, and pregnant women and young children are at greatest risk. Other micronutrient deficiencies of public health concern include zinc, folate, and the B vitamins. However, there is limited data on the actual prevalence of these deficiencies. Finally, in many settings, more than one micronutrient deficiency exists, suggesting the need for simple approaches that evaluate and address multiple micronutrient malnutrition.     

Control of Micronutrient Deficiencies in India: Obstacles and Strategies

Micronutrient deficiencies of vitamin A, iron, and iodine continue to be of public health significance in India. The government of India initiated national programs to prevent, control and combat these deficiencies and their serious consequences. The interventions involved (1) distribution of iodized salt in the endemic areas, (2) administration of semiannual massive dose of vitamin A to young children, and (3) distribution of iron-folic acid tablets to the vulnerable groups. Evaluations revealed that the biologic impact of these interventions was unsatisfactory. Inadequate allocation of funds (10% of the actual needs) necessary to cover the enormous number of beneficiaries was one of the important obstacles. Consequently, the allocation of supplies to different provinces was far short of the requirements (10–30%). As a result of poor orientation, the functionaries were not adhering to the guidelines, leading to woefully inadequate (1–20%) and irregular coverage. There was no proper monitoring or supervision to make midcourse corrections to improve the functioning. The community was not informed of the purpose and details of each intervention. Hence, it did not utilize the resources completely and remained passive recipients. The community was not aware of the dietary approaches to prevent micronutrient disorders owing to absence of nutrition education. With the adoption of National Nutrition Policy by the government of India, a concerted and focused approach should be adopted. The future strategies should include a mix of short-term supplementation and food-based strategy encompassing food fortification and home gardening. Innovative approaches in information, education, and communication (such as social marketing strategy) for making the interventions sustainable should be adopted.     

Eliminating mother-to-child transmission of human immunodeficiency virus,syphilis and hepatitis B in sub-Saharan Africa

Triple elimination is an initiative supporting the elimination of mother-to-child transmission of three diseases – human immunodeficiency virus (HIV) infection, syphilis and hepatitis B. Significant progress towards triple elimination has been made in some regions, but progress has been slow in sub-Saharan Africa, the region with the highest burden of these diseases. The shared features of the three diseases, including their epidemiology, disease interactions and core interventions for tackling them, enable an integrated health-systems approach for elimination of mother-to-child transmission. Current barriers to triple elimination in sub-Saharan Africa include a lack of policies, strategies and resources to support the uptake of well established preventive and treatment interventions. While much can be achieved with existing tools, the development of new products and models of care, as well as a prioritized research agenda, are needed to accelerate progress on triple elimination in sub-Saharan Africa. In this paper we aim to show that health systems working together with communities in sub-Saharan Africa could deliver rapid and sustainable results towards the elimination of mother-to-child transmission of all three diseases. However, stronger political support, expansion of evidence-based interventions and better use of funding streams are needed to improve efficiency and build on the successes in prevention of mother-to-child transmission of HIV. Triple elimination is a strategic opportunity to reduce the morbidity and mortality from HIV infection, syphilis and hepatitis B for mothers and their infants within the context of universal health coverage.     

Implementing micronutrient fortification programs as a potential practical contribution to achieving sustainable diets

Due to sustainability concerns related to current diets and environmental challenges, it is crucial to have sound policies to protect human and planetary health. It is proposed that sustainable diets will improve public health and food security and decrease the food system's effect on the environment. Micronutrient deficiencies are a well-known major public health concern. One-third to half of the world's population suffers from nutrient deficiencies, which have a negative impact on society in terms of unrealised potential and lost economic productivity. Large-scale fortification with different micronutrients has been found to be a useful strategy to improve public health. As a cost-effective strategy to improve micronutrient deficiency, this review explores the role of micronutrient fortification programmes in ensuring the nutritional quality (and affordability) of diets that are adjusted to help ensure environmental sustainability in the face of climate change, for example by replacing some animal-sourced foods with nutrient-dense, plant-sourced foods fortified with the micronutrients commonly supplied by animal-sourced foods. Additionally, micronutrient fortification considers food preferences based on the dimensions of a culturally sustainable diet. Thus, we conclude that investing in micronutrient fortification could play a significant role in preventing and controlling micronutrient deficiencies, improving diets and being environmentally, culturally and economically sustainable.     

Do multiple micronutrient interventions improve child health, growth, and development?

Micronutrient deficiencies are common and often co-occur in many developing countries. Several studies have examined the benefits of providing multiple micronutrient (MMN) interventions during pregnancy and childhood, but the implications for programs remain unclear. The key objective of this review is to summarize what is known about the efficacy of MMN interventions during early childhood on functional outcomes, namely, child health, survival, growth, and development, to guide policy and identify gaps for future research. We identified review articles including meta-analyses and intervention studies that evaluated the benefits of MMN interventions (3 or more micronutrients) in children (<5 y of age) using Pubmed and EMBASE. Several controlled trials (n = 45) and meta-analyses (n = 6) have evaluated the effects of MMN interventions primarily for child morbidity, anemia, and growth. Two studies found no effects on child mortality. The findings for respiratory illness and diarrhea are mixed, although suggestive of benefit when provided as fortified foods. There is evidence from several controlled trials (>25) and 2 meta-analyses that MMN interventions improve hemoglobin concentrations and reduce anemia, but the effects were small compared to providing only iron or iron with folic acid. Two recent meta-analyses and several intervention trials also indicated that MMN interventions improve linear growth compared to providing a placebo or single nutrients. Much less is known about the effects on MMN interventions during early childhood on motor and mental development. In summary, MMN interventions may result in improved outcomes for children in settings where micronutrient deficiencies are widespread.     

The challenge to eliminate micronutrient malnutrition

OBJECTIVE: This paper takes a public health approach to examine briefly: (i) the global magnitude and consequences of deficiencies of iodine, vitamin A and iron; (ii) the intervention options for addressing the deficiencies and associated critical issues; (iii) roles of the main 'players' involved; (iv) current programs and results. METHOD: Analysis of the literature, especially that coming from the UN agencies; distillation of experience from the recently completed OMNI Project, and involvement in relevant international meetings. RESULTS: More than one in three individuals throughout the world are at risk of the health and development consequences of iron, vitamin A and/or iodine deficiencies. There has been a 40% decline in the prevalence of vitamin A deficiency over the last 10 years. More than 60% of all salt is now fortified with iodine. CONCLUSIONS: Significant progress has been made, particularly with the iodine deficiency disorders and vitamin A deficiency. Little apparent progress has been made with iron deficiency anaemia. IMPLICATIONS: National governments, UN multilateral agencies, international consultative groups, bilateral agencies, global and national non-governmental organisations, and increasingly, the private sector need to work together in looking for innovative approaches, especially for iron, increasing awareness of the broader social and public health nutrition context, and supporting increased international funding.     

Adverse Outcomes of Poor Micronutrient Status in Childhood and Adolescence

The adverse effects of micronutrient deficiencies and excesses in children up to reproductive age are presented. A summary of risks and adverse functional and health outcomes associated with deficient and excessive intakes and nutrition status of iron, iodine, zinc, vitamins A and D, folate, vitamin B₁₂, and riboflavin is presented. Nutrient-nutrient interactions of micronutrients, age, gender, and other host and environmental conditions, such as pregnancy, genetic conditions, overall nutrition, force of infection, and social conditions are considered as covariates in trying to define causation and outcomes due to specific micronutrients. The outcomes analyzed focus on growth and development, mental and neuromotor performance, immunocompetence, physical working capacity, morbidity, and in the case of pregnancy, overall reproductive performance. The results presented include responses to specific and multiple "experimental" interventions. A brief analysis of possible public health programs is presented, with emphasis on prevention.