7. Iron, Minerals and Trace Elements

Iron is not routinely provided in parenteral nutrition mixtures and is often not a component of commercially available trace element preparations. Currently there are no well-defined recommendations regarding the optimum content of iron in parenteral feeds, and intravenous administration of iron remains problematic. One major concern is that of iron overload. Parenteral administration of iron bypasses the homeostatic control of gastrointestinal iron absorption, causing loss of protection from iron overload if excessive quantities are provided. An accumulation of excess iron has been reported in children receiving prolonged parenteral nutrition. In a study of 30 children aged 1–18 years receiving ferrous sulphate 100 mg/kg per day for an average period of 43 months, 12 children showed evidence of plasma and hepatic iron overload. Ferritin concentrations were . 800 ng/ml in eight children (.1100 ng/ml in five) and correlated with duration of PN. The degree of iron deposition in either hepatocytes or Kupffer cells was most pronounced in children with the higher ferritin concentrations ((1) (LOE 2+)). Thus, iron status of children receiving long-term PN should be monitored by regular measurement of serum ferritin, and supplementation decreased if ferritin concentration is raised. Although Ben-Hariz et al suggested halving iron intake at ferritin concentrations of 500 ng/ml and stopping completely at 1000 ng/ml, these concentrations probably leave only a small margin of safety. There is, therefore, an argument for curtailing iron supplementation at lower plasma ferritin concentration. A further concern over parenteral iron administration is that it may impair immune function and stimulate bacterial growth thus increasing the risk of infection by iron-requiring pathogens (2). Iron availability correlates with bacterial growth and virulence, facilitates viral replication and reverses the bactericidal effect of lactoferrin and lysozyme (3,4). Furthermore, the antibacterial effect of cytokines is mediated by intracellular iron depletion. Interferon, IL-1, and tumour necrosis factor enhance ferritin synthesis resulting in a shift of cellular iron into a storage compartment and downregulate transferrin receptor production decreasing cellular iron uptake and, thereby, iron availability for intracellular pathogens (5). Iron therapy has also been implicated in decreased phagocytosis and inhibition of CD4 and CD8 helper T cell proliferation while enhancing the function of suppressor T cells (6). Yet, several components of the immune response are depressed in iron deficiency. An impaired capacity for the generation of the oxidative burst has been observed in phagocytes from iron deficient children (7). McFarlane et al studied 40 children with kwashiorkor and low serum transferrin given nutritional support including iron supplements. Many of the children who received iron therapy died shortly after supplements were begun suggesting that provision of iron in a setting of low transferrin may have resulted in higher circulating free iron that could have contributed to the development of overwhelming infection and death (8). Septicaemia with Yersinia enterocolitica has been reported in healthy children overdosed with oral iron (9). Nevertheless, there is little clinical evidence that iron supplementation in parenterally fed children increases the risk of sepsis (10). Adverse drug reactions associated with parenteral iron therapy are common, although side effects are mild and self limiting ((11,12) (LOE 2+)). In various series 2–5% of patients experience significant side effects. The processes leading to iron dextran induced symptoms are unclear, but include a type I (IgE-mediated) anaphylactic reaction which is caused by preformed dextran antibodies. Additional mechanisms include a type I anaphylactoid reaction that may be caused by transient overload of the transferrin molecule resulting in small amounts of free iron in the circulation (which appears to be dose related) and immune complex activation by specific IgG antibody. Symptoms include dyspnoea, wheezing, hypotension, nausea, vomiting, abdominal pain, arthralgia and myalgia. Most side-effects are mild and self-limiting with severe reactions occurring in a minority of patients and in conjunction with infusion of larger iron doses. An increased incidence of adverse effects has been reported in patients with collagen diseases. Despite previous Journal of Pediatric Gastroenterology and Nutrition 41:S39–S46 November 2005 ESPGHAN. Reprinted with permission.