Description of the condition

Vitamin and mineral deficiencies affect more than two billion people worldwide (The Micronutrient Initiative 2009). Iron deficiency, which affects over half the world’s population, is the most common preventable nutritional deficiency and, together with vitamin A and zinc deficiencies, has the largest documented disease burden among micronutrients (Black 2008; WHO 2001; WHO 2009). There is a disproportionate burden of vitamin and mineral deficiencies in developing countries. Infants and children are the most vulnerable groups to micronutrient malnutrition, given the high vitamin and mineral intake they need for rapid growth relative to the amount of food they consume (Dewey 2003). Diets of infants and young children that are predominantly plant‐based generally provide insufficient amounts of key micronutrients (particularly vitamin A, zinc and calcium) to meet the recommended nutrient intakes during the age range of six to 23 months and the inclusion of animal‐source foods that could meet the nutrient gap increases the cost and may be not practical for the lowest income groups (PAHO 2001; WHO 2005). There are no global estimates on vitamin and mineral deficiencies specifically for children under two; however, it is calculated that 190 million preschool children are affected by vitamin A deficiency (WHO 2009) and 293 million by anaemia (WHO 2008).

Vitamin A plays a critical role in visual perception and a deficiency is the leading cause of childhood blindness (WHO 2009). Iron is essential to red blood cells and is involved in several metabolic reactions; there is compelling evidence that infants aged six to 24 months with iron‐deficiency anaemia are at risk for poorer cognitive, motor, social‐emotional, and neurophysiologic development in the short and long term (Lozoff 2007). Zinc is important during periods of accelerated growth, and for tissues with rapid cellular differentiation and turnover, such as the immune system and the gastrointestinal tract. Critical functions that are affected by zinc nutriture include physical growth, susceptibility to infection, and neurobehavioral development (Brown 2001).

Multiple vitamin and mineral deficiencies frequently occur simultaneously and their joint effects during the critical period from conception to two years of age can be associated with irreversible physical and cognitive consequences, increased perinatal mortality, and reduced physical work capacity and productivity (WHO 2001; Lozoff 2007; Sanghvi 2007), leading to lifelong detrimental consequences on health, productivity and economic growth. In fact, it has been estimated that nutritional risk factors, including underweight status, sub‐optimal breastfeeding, and vitamin and mineral deficiencies, particularly vitamin A, iron and zinc, are responsible for 3.9 million deaths (35% of total deaths) and 144 million disability‐adjusted life years (DALYs) (33% of total DALYs) in children less than 5 years old (WHO 2009).

Description of the intervention

Interventions to prevent and/or treat micronutrient malnutrition typically include exclusive breastfeeding during the first six months of life; dietary diversification to include foods with highly absorbable vitamins and minerals; fortification of staple and complementary foods, and provision of supplements (Bhutta 2008), with the latter being the most widespread intervention.

It has been reported that vitamin A supplementation of children between six months and five years of age significantly reduces total mortality by about 23% to 30% (Beaton 1993; Fawzi 1993; Glasizou 1993; Imdad 2010) and reduces childhood blindness by 70%. The reduction in mortality is believed to be mediated through improved vitamin A status, which may affect susceptibility to infection by an effect on the immune system (Stephensen 2001). Zinc supplementation leads to a 9% reduction in child mortality and 23% reduction in childhood diarrhoea incidence (WHO 2006; Brown 2009). Since adequate iron status early in life is critical for motor and cognitive development, the World Health Organization (WHO) has recommended blanket supplementation to all infants and children six to 24 months of age in areas where the prevalence of anaemia exceeds 20% to 30% (INACG 1998; WHO 2001).

Micronutrient interventions, particularly vitamin A and zinc supplementation of children, and fortification of foods with iron and iodine, have been shown to be among the most cost‐effective global development efforts (Horton 2008). Despite the well‐recognized benefits of micronutrient interventions, implementation has been hindered by poor adherence to supplementation dosing regimens, inadequate supply, low coverage, and potential dose‐related side effects and safety concerns (Sazawal 2006).

In response to these operational constraints, 'home' or ‘point‐of‐use’ food fortification with micronutrient powders (MNP), for example, Sprinkles^TM was developed as a novel approach for delivering iron and other micronutrients with foods. MNP are single‐dose packets of dry powder containing lipid encapsulated iron and other micronutrients that can be sprinkled onto any semi‐solid food (Zlotkin 2005). The lipid encapsulation coating prevents iron and other nutrients from dissolving into the food and therefore prevents any change in colour, flavour, or taste. Home fortification with MNP are being proposed in complementary feeding based on various advantages: 1) various vitamins and minerals can be added to the formulation in the MNP sachet; 2) the MNP sachets are lightweight, simple to store, transport and distribute; 3) the MNP are easy to produce, with a relatively low production cost; 3) MNP does not affect the maintenance of usual dietary practices that facilitate the transition from exclusive breastfeeding to complementary feeding; 4) MNPs are easy to use even without literacy, and 5) the potential for overdose is unlikely (Slotkin 2004). A drawback mentioned has been the waste disposal challenge with single‐dose sachets. Because MNP products usually have higher acceptability and fewer side effects than iron drops, the approach of home (point‐of‐use) fortification of foods with MNP for treating anaemia is becoming a preferred strategy for interventions in developing countries (World Vision 2005; De Pee 2008; Dewey 2009).

The cost of increasing the number of micronutrients in powders is minimal (the primary cost of the product is in the packaging) (De Pee 2008) and many programs use a standard formulation containing 14 vitamins and minerals (Sprinkles Global Health Initiative 2010), although the formulation and the compound specifications may vary in some other programmes. The efficacy of the standard "multi‐micronutrient" formulation for anaemia has been evaluated in some studies; however, the potential for negative interaction among micronutrients ‐ possibly limiting their absorption and utilization ‐ as well as the effects on other outcomes, warrants further investigation.

Provision of iron containing formulations, either supplements or MNP, in malaria‐endemic areas has been a long‐standing controversy due to concerns that iron therapy may exacerbate infections, in particular malaria, given that the parasite requires iron for growth (Oppenheimer 2001). In 2006, the World Health Organization (WHO) consultative group issued recommendations that no children under two years of age living in malaria‐endemic areas should be provided iron supplementation without appropriate screening for iron deficiency (WHO 2007a; WHO 2007b). However, a recent Cochrane review challenged the body of evidence used by the WHO to make its recommendations. The authors found that iron supplementation to children does not increase the risk of clinical malaria in the presence of regular surveillance of malaria and appropriate treatment (Ojukwu 2009). The impact of this policy is unknown, but because widespread screening for iron deficiency is unlikely to be practical or affordable in developing countries, many iron supplementation programs have come to a halt. This situation has urged experts in nutrition and policy makers worldwide to forthrightly discuss the safety of iron interventions in malaria‐endemic areas in order to promote the use of safe and effective interventions (Suchdev 2009). Due to the way in which iron is absorbed and metabolized, not all forms of iron will necessarily have the same effect on susceptibility to infection. MNP may be less likely to increase the risk of infection because they are mixed with food, and thus are absorbed more slowly, yielding lower peak concentrations of unbound iron in circulation (Liyanage 2002; Dewey 2007).

From the implementation perspective, MNP programs are currently at national scale in several countries, such as Bangladesh, Mongolia, and Haiti, and numerous countries are also planning large‐scale distribution for children (Hyder 2007; Menon 2007). Based on a 2009 UNICEF regional workshop in Asia, 32 programmes of home fortification with MNP have been implemented or are being planned (UNICEF 2009). However, few studies have reported operational and cost considerations, including effective distribution mechanisms (Dewey 2009; Loechl 2009). In addition, there is great variability in the formulation of MNP (for example, the number and dose of the micronutrients), producers that are manufacturing MNP, target age group of children receiving MNP, and settings in which MNP are distributed (De Pee 2008).

Why it is important to do this review

The WHO recommends exclusive breastfeeding until six months of age and continued breastfeeding for at least two years (PAHO 2001; WHO 2005). Intakes of several vitamins and minerals after six months, including iron, zinc, calcium, selected B vitamins and (in some settings) vitamin A, remain problematic because commonly available, low‐cost foods contain inadequate amounts of these nutrients. 

Various Cochrane reviews or protocols have evaluated the effects of supplementation with different vitamins and minerals in children. The effects of iron supplementation with tablets or elixirs alone, or in combination with folic acid or other micronutrients in children less than 18 years of age living in malaria‐endemic areas, is evaluated by Ojukwu 2009. Published reviews have also evaluated the effects of 1) iron supplementation in improving clinical, immunologic, and virologic outcomes in children infected with HIV (Adetifa 2009); 2) micronutrient supplementation in children and adults with HIV infection (Irlam 2005); 3) oral or intramuscular iron therapy for improving psychomotor development and cognitive function in children under the age of three with iron deficiency anaemia (Logan 2001); 4) iodine supplementation for preventing iodine deficiency disorders in children (Angermayr 2004), and 5) vitamin A supplementation for preventing mortality and morbidity in children aged six months to five years (Imdad 2010). A Cochrane protocol for a review to assess the effects of any form of iron supplementation for treating iron deficiency anaemia in children (Zeng 2007) is available and another one assesses the effects of supplementation with two or more micronutrients (iron, vitamin A and/or zinc) versus single micronutrient supplementation (in tablets, syrups, sprinkles) or placebo mainly for preventing acute respiratory infections, other infectious diseases and micronutrient deficiencies in young children (Fraser 2006).

Several countries are at the stage of implementing large‐scale projects with home (point‐of‐use) fortification of foods with MNP, so a systematic review on the effectiveness and safety of this intervention is urgently needed to help guide programs on effectiveness and safety, as well as on the appropriate dose, frequency and duration of this intervention. This review will focus on nutrition, health and developmental outcomes in young children related to micronutrients, particularly iron, zinc and vitamin A. Furthermore, an effort will be made to address the morbidity outcomes of home (point‐of‐use) fortification of foods with MNP in malaria‐endemic areas given the uncertainties and the urgent need for policy decisions on the safe delivery of iron for populations living in these settings.