Growth retardation is highly prevalent in developing countries and is associated with several adverse outcomes throughout life. Inadequate intakes of dietary energy and protein and frequent infections are well-known causes of growth retardation. However, the role of specific micronutrient deficiencies in the etiology of growth retardation has gained attention more recently. Micronutrient deficiencies are highly prevalent in low-income countries, and the most probable causes are low content in the diet and poor bioavailability. More than half of preschool children are anemic, and an estimated 75 million and 140 million preschool children have clinical and subclinical vitamin A deficiencies, respectively. Less information is available on the prevalence of zinc deficiency, although it has been estimated recently that about half of the world’s population is at risk of inadequate intake of absorbable zinc.
Attained height is the result of the interaction between genetic endowment and both macro- and micronutrient availability during the growth period. Longitudinal growth occurs through a process of cell proliferation, the addition of new cells to the growth plate of the bone and hypertrophy, resulting in the expansion of the growth plate . Although the control of bone growth in its different phases is not entirely understood, the key roles of growth hormone (GH)3 and insulin-like growth factor I (IGF-I) have been identified. IGF-I receptors are found predominantly in proliferating bone chondrocytes, and IGF-I itself stimulates synthesis of collagen and proteoglycans. These physiological functions explain the role of IGF-I in linear growth. Furthermore, GH itself and its effect on IGF-I synthesis exert a direct effect on growth.
Nutrition plays a key role in the control of linear growth through a variety of mechanisms. Evidence from animal models indicates that energy and protein restriction reduces IGF-I plasma concentration, which returns to normal after replenishment. The impact of reduced protein intake appears to be larger than that observed with energy restriction. The association between nutritional status and the IGF-I system also has been observed in humans: IGF-I is reduced during acute protein deficiency (kwashiorkor) and protein-energy malnutrition in children. Some micronutrients also affect the IGF-I system. For example, it is well documented that zinc deficiency in rats causes not only growth retardation but also a decrease in both IGF-I plasma concentration and GH receptors, which return to normal after zinc repletion. Additionally, through its influence on the GH/IGF-I system, zinc deficiency has been observed to affect bone metabolism. The role of zinc in growth also may be explained in part through its participation in DNA synthesis.
Studies on rats also have shown similar decreases in plasma IGF-I concentrations with depletion of potassium, magnesium or thiamine, which return to normal after repletion of these nutrients. Copper also is involved in growth through its role in cross-linking collagen fibers, and manganese deficiency is associated with skeletal abnormalities, including retarded growth, which may be mediated through defects in proteoglycan physiology in the growth plate. Vitamin D and calcium deficiencies also affect bone development, as manifested through the condition known as rickets.
Vitamin A was first identified as the growth-promoting factor “A.” Studies in the 1920s–1930s demonstrated arrested growth, especially of weight in rats, after acute vitamin A depletion . However, even today effects of vitamin A on linear growth, bone formation and body composition in animals are less clear Judisch et al. found that anemic children were small for their age and that their growth rates accelerated when treated with iron. Since then, however, evidence for the effect of iron deficiency on growth has been equivocal.
Deficiencies of some micronutrients, such as iron, magnesium and zinc, result in anorexia . Therefore, these nutrient deficiencies also may contribute to growth retardation indirectly by reducing the intake of other growth-limiting factors, such as energy and protein. Also, several micronutrients, including zinc, iron and vitamin A, are associated with immune function and risk of morbidity, which in turn affect growth . Therefore, micronutrient deficiencies may have an indirect effect on growth by increasing the prevalence or severity of morbidity and anorexia.