Balancing Benefits and Risks of Iron Fortification in Resource-Rich Countries

Abstract

or the last 25 years, the American Academy of Pediatrics (AAP) has endorsed the use of iron-fortified infant formulas, noting "no role for the use of low-iron formulas." The rationale for these policies was the recognition that the increase in the use of iron-fortified formulas, accounting for 80% of all formula sold in 1985, was responsible for the declining prevalence of iron-deficiency anemia in US infants. 1 These recommendations were also based on the absence of evidence of discernible adverse effects. Controlled trials had reported no differences in gastrointestinal symptoms, such as colic, constipation, diarrhea, regurgitation, and fussiness, among infants receiving low-iron vs iron-fortified formulas. 2,3 Likewise, evidence was lacking to support another theoretical concern of clinically significant interactions with other micronutrients, specifically zinc and copper. In 1999, the AAP took an even stronger stand and recommended that low iron formulas be removed from the market entirely, 4 for reasons similar to those of the 1989 policy. Further, it was recommended that the minimum iron content for all term infant formulas be at least 4 mg/L. 4 Currently, standard, term infant formulas on the market are all ironfortified and contain 4-12 mg/L of iron, even though there are some regional differences. In the US, the AAP recommends that infant formulas have an iron content of 10-12 mg/L 5 ; in Europe, the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommends 4-8 mg/L. 6 In the recommendations, the contrast in the iron exposure of formula-fed infants vs breastfed infants has primarily focused on the better bioavailability of the iron in breast milk. Although an absorption efficiency of approximately 50% is often quoted, some studies have actually reported absorption in the range of 12%-16%, 7,8 making that bioavailability distinction much less potent. This also suggests that absorption of substantial amounts of dietary iron simply is not critical during the early months of life in healthy infants of normal birth weight. Among all the compositional differences between human milk and formula, the differences in iron content are the most extreme. Virtually all mammalian milks are low in iron, with the exception of rodents, in which postnatal growth is extremely rapid. It seems implausible that this conserved biological pattern is without purpose. It is also clear that iron deficiency occurs in breastfed infants only after the very early months of life. The practical challenge is to identify when the birth iron endowment is exhausted, at which point the infant needs a source of iron from the diet. This article will discuss the potential advantages of a low iron intake for the infant and the potential adverse effects of drastically altering this, especially in the first 6 months of life. From the outset, two realities must be acknowledged. First, iron deficiency (especially without anemia) in infants remains common, particularly in high-risk groups, including older normal breastfed i...

The Benefits and Risks of Iron Supplementation in Pregnancy and Childhood

“…Bacteria species have variable iron needs, and some of the most siderophilic species include Escherichia coli and Salmonella, both potential pathogens (99). Bifidobacteria, in contrast, have low iron requirements (70). In addition, pathogenic organisms dwelling within the body (e.g., the malaria protozoa) also proliferate more aggressively in iron-rich environments compared with iron-poor environments (49).…”

Maternal Diet and Nutrient Requirements in Pregnancy and Breastfeeding. An Italian Consensus Document

“…On the other hand, an excessively high iron intake may expose women to oxidative stress, lipid peroxidation, impaired glucose metabolism, and gestational hypertension [40]. International recommendations in terms of intake levels range from the 27 mg per day for all pregnant women as advised by the Center for Disease Control and Prevention and the WHO to the 30–60 mg as advised by the Italian RDA (Table 2).…”

Approaches for Reducing the Risk of Early-Life Iron Deficiency-Induced Brain Dysfunction in Children

“…The main theoretical risks of iron supplementation in general, but particularly of iron-sufficient populations are the generation of reactive oxygen species, alteration of the intestinal microbiome toward a more “pathogenic” profile with or without an increase in diarrheal diseases, and an increased risk of non-gastrointestinal infections [ 83 , 84 ]. In contrast to the large preclinical and clinical research literature on the negative effects of early-life iron deficiency, the literature on the potential negative effects of iron supplementation of iron-sufficient populations is relatively limited.…”