The Importance of Iron Status for Young Children in Low- and Middle-Income Countries: A Narrative Review

Abstract

Early childhood is characterised by high physiological iron demand to support processes including blood volume expansion, brain development and tissue growth. Iron is also required for other essential functions including the generation of effective immune responses. Adequate iron status is therefore a prerequisite for optimal child development, yet nutritional iron deficiency and inflammation-related iron restriction are widespread amongst young children in low- and middle-income countries (LMICs), meaning iron demands are frequently not met. Consequently, therapeutic iron interventions are commonly recommended. However, iron also influences infection pathogenesis: iron deficiency reduces the risk of malaria, while therapeutic iron may increase susceptibility to malaria, respiratory and gastrointestinal infections, besides reshaping the intestinal microbiome. This means caution should be employed in administering iron interventions to young children in LMIC settings with high infection burdens. In this narrative review, we first examine demand and supply of iron during early childhood, in relation to the molecular understanding of systemic iron control. We then evaluate the importance of iron for distinct aspects of physiology and development, particularly focusing on young LMIC children. We finally discuss the implications and potential for interventions aimed at improving iron status whilst minimising infection-related risks in such settings. Optimal iron intervention strategies will likely need to be individually or setting-specifically adapted according to iron deficiency, inflammation status and infection risk, while maximising iron bioavailability and considering the trade-offs between benefits and risks for different aspects of physiology. The effectiveness of alternative approaches not centred around nutritional iron interventions for children should also be thoroughly evaluated: these include direct targeting of common causes of infection/inflammation, and maternal iron administration during pregnancy.

Iron Deficiency Anemia in Children Residing in High and Low-Income Countries: Risk Factors, Prevention, Diagnosis and Therapy

“…Thus, the prevention of IDA in children is feasible by avoiding breastfeeding without the administration of iron supplements beyond the fourth month of life, in addition to using infant formulas high in elemental iron (>6.7mg/L) and consuming meat products. 8 Delayed cord clamping increases the neonate’s body iron stores and may decrease the risk of IDA in the first six months of life. 43 Consumption of large amounts of fresh cow’s milk by infants and toddlers negatively affects their iron stores because of its low iron content, the frequent occurrence of occult gastrointestinal bleeding associated with cow’s milk, and the inhibition of nonheme iron absorption by the casein and calcium of milk.…”

“… 7 On the other hand, up to 40% of preschool children in low- and middle-income countries are estimated to be iron deficient and/or anemic. 8 Special populations at risk for IDA in developed countries include indigenous people, newly arrived immigrants, refugees, regular blood donors, endurance athletes and vegetarians. 9 , 10 …”

Multilevel Impacts of Iron in the Brain: The Cross Talk between Neurophysiological Mechanisms, Cognition, and Social Behavior

“…Among all age populations, infants and young children are the most sensitive to variations in iron levels [20,47]. Presumably, this is associated with their rapid growth, which requires iron to prevent a decline in functions that are mainly exerted by the basal ganglia and that could lead to an impaired psychomotor development, as well as disrupted cognition and behavior [43].…”

“…These supplementations have been successful in the control of anemia and iron deficiency in different age groups. However, the long-term deficits in motor and cognitive functions, as well as the modifications in social behavior, were mostly shown to persist and deserve great attention and debate [8,18,19,20]. Several reasons can account for the absence of (or very small, in a few cases) motor, cognitive, and behavioral effects.…”

Iron as Therapeutic Target in Human Diseases

“…Once the link between malaria and iron deficiency will be formally demonstrated, it would aid readjusting priorities for programs towards prevention and treatment of iron deficiency, which will benefit malaria control. Armitage and Moretti [35] reviewed the demand and supply of iron during early childhood, addressing its importance in aspects that refer to the physiology and development of young children coming from low-and middle-income countries, in particular. Thus, discussing the implications for interventions to improve iron status whilst minimizing infection-related risks is of utmost importance, since strategies should be adapted according to iron deficiency, inflammation status, and infection risk.…”