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Because of the production of nutrient-deficient infant formulas (IFs), the United States Congress passed regulations on the composition and production of IF, referred to as the Infant Formula Act (IFA), in 1980, which was amended in 1986. More detailed FDA rules have been created since then, specifying the ranges or minimum intakes of nutrients and providing details for the safe production and evaluation of infant formulas. Although generally effective in ensuring safe IF, recent events have made it clear that a re-evaluation of aspects of all the nutrient composition regulations for IF is needed, including consideration of adding requirements related to bioactive nutrients not mentioned in the IFA. We propose that, as principal examples, the requirement for iron content needs to be re-evaluated and that DHA and AA should be considered for addition to the nutrient requirements after scientific review by a panel such as those established by the National Academies of Sciences, Engineering, and Medicine. Additionally, there is no specific requirement in current FDA regulations for the energy density of IF, and this should be added alongside potential revisions of the protein requirement. It would also be ideal to have specific FDA rules on nutrient intakes for premature infants as these are exempted from the specific nutrient regulations of the amended IFA., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Iron is an essential nutrient for normal growth and neurodevelopment of infants. Iron deficiency (ID) remains the most common micronutrient deficiency worldwide. There are convincing data that ID is associated with negative effects on neurological and psychomotor development. Objectives: In this review, we provide an overview of current knowledge of the importance of iron in normal term breast-fed infants with a focus on recommendations, metabolism, and iron requirements. Conclusions: Health organizations around the world recommend the introduction of iron-rich foods or iron supplements for growing infants to prevent ID. However, there is no routine screening for ID in infancy. Multicenter trials with long-term follow-up are needed to investigate the association between iron fortification/supplementation and various health outcomes. [ABSTRACT FROM AUTHOR]

Iron requirements were estimated from the results of the National Health and Nutrition Surveys of Japan 2003–2007 using the numerical analysis of requirements based on an integral equation. The numerical analysis used population-based data on iron nutriture, the prevalence of inadequate iron status, and the distribution of iron intakes. The cutoff value for inadequate iron status was defined as a serum ferritin concentration <30 ng/mL. Iron intakes and menstrual blood losses followed a log-normal distribution and published values were corrected accordingly to calculate usual values. For women aged 18–29 years old, the median of the estimated median iron requirement (corresponding to the estimated average requirement by using the terminology of the dietary reference intakes) was 7.59 mg (range, 6.86–8.11). The median of the estimated usual iron intake covering the needs of women with 80 mL per cycle of menstrual blood loss was 11.27 mg (range, 10.16–12.00), and the median of the usual iron intake covering the needs of 97.7% of women was 13.93 mg (range, 12.55–14.81). For women aged 30–49 years old, the corresponding figures were 8.13 mg (range, 7.96–8.69), 11.95 mg (range, 11.72–12.77), and 14.71 mg (range, 14.44–15.72). [ABSTRACT FROM AUTHOR]

Currently, a factorial approach is used to derive reference values for iron. Calculations include the use of a bioavailability factor to convert the physiological requirement, derived from obligatory losses and requirements for growth and development, into a dietary intake value. A series of systematic reviews undertaken by the EURRECA Network of Excellence aimed to identify data that may increase the accuracy of factorial calculations across all population groups. The selection of robust data was guided by the use of standardized review methodology and the evidence-based selection of status biomarkers and dietary intake assessment techniques. Results corroborated the dearth of relevant factorial data, including whole-diet bioavailability data, and confirmed the need to continue extrapolating physiological requirements across population groups. Data were also unavailable that would allow reference values to be based on selected health outcomes associated with iron intake or status. Ideally, a series of observational and randomized controlled trial (RCT) studies need to be undertaken across all population groups and life stages to generate robust data for setting dietary reference values for iron. It will also be essential to include information on polymorphisms that potentially influence iron absorption and status in the derivation process. [ABSTRACT FROM PUBLISHER]

Abstract: The ability of four Clostridium difficile strains to utilize various exogenous organic and inorganic iron sources for growth under iron-depleted (250 μM DPP) and iron-limited (75 μM DPP) conditions was analyzed in liquid broth cultures grown in tubes and in microtiter plates, and data compared with results from a bioassay developed on solid media. The growth profile of C. difficile varied depending on the iron source and availability. Addition of FeSO4, FeCl3, Fe citrate and ferritin allowed growth in an iron-depleted environment whereas glycoproteins (iron-saturated and low-iron lactoferrin, apo- and holo-transferrin) and heme proteins (hemoglobin, hematin and hemin) did not. All iron sources, except lactoferrin, were able to restore bacterial growth under iron-limited conditions to varying extents. The results demonstrated that the broth microtiter assay developed here was reproducible, reliable and convenient for high-throughput analysis of the growth of C. difficile compared to alternative traditional methods. [Copyright &y& Elsevier]

A systematic review was conducted to summarize the evidence currently available from randomized controlled trials (RCTs) concerning the effect of iron intake of infants, children and adolescents on measures of cognitive development and function. The Cochrane Library, MEDLINE and Embase were searched up to and including February 2010. Studies were also identified by checking the bibliographies of the articles retrieved. All RCTs with an adequate control group in which iron supply was provided by natural food sources, fortified foods, formula or supplements to infants, children or adolescents until the age of 18 years were considered for inclusion. No language restrictions were applied. Fourteen studies met the selection criteria. Twelve out of these 14 studies had a high or moderate risk of bias. A large degree of heterogeneity of study populations, iron dosages and outcome measures precluded performing a quantitative meta-analysis. Overall, the studies suggest a modest positive effect of iron supplementation on cognition and psychomotor outcomes in anemic infants and children after supplementation periods of at least 2 months of duration. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Iron deficiency anemia is the most common micronutrient deficiency worldwide and infants constitute a risk group due to their high iron requirements. Iron is critical for brain development, and case control studies have shown a consistent association between iron deficiency anemia in infancy and poor neurodevelopment, suggesting that it is important to prevent iron deficiency anemia in infants. However, it is also important to avoid excessive iron intakes which may have adverse effects on growth. Due to redistribution of iron from hemoglobin to iron stores, healthy, term, normal birth weight infants are virtually self-sufficient with regard to iron during the first 6 months of life. After that age, iron becomes a critical nutrient. The estimated daily iron requirements at the age of 6-12 months (0.9-1.3 mg/kg body weight) are higher than during any other period of life. Exclusively breast-fed infants normally do not need additional iron until 6 months of life. Formula-fed infants should receive iron-fortified formula. Low birth weight infants should receive additional iron supplements from an early age. From 6 months of age, all infants should receive a sufficient intake of iron-rich (complementary) foods, which may be meat products or iron-fortified foods. The estimations of iron requirements in infants have a weak evidence base and current European and American recommendations for infants differ significantly. To further clarify iron requirements in infants, there is clearly a need for randomized, controlled trials assessing the effects of different iron intake on anemia, neurodevelopment, and other health outcomes. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Meeting the iron requirements of infants and children is difficult, and supplementation or fortification of food with iron is often recommended. Although iron supplementation of infants and children with iron deficiency and iron-deficiency anemia may be beneficial, recent studies suggest that this may not be the case for those with adequate iron status, and adverse effects have been noted. The recent discoveries of proteins and peptides regulating iron absorption have enhanced our knowledge of iron metabolism in infants and children. Iron is taken up in the small intestine by divalent metal transporter-1 and is either stored by ferritin inside the mucosal cell or transported to the systemic circulation by ferroportin, while being oxidized by hephaestin to be incorporated into transferrin. Hepcidin, a small peptide synthesized by the liver, can sense iron stores and regulates iron transport by inhibition of ferroportin. However, regulation of iron transporters is immature in infants, possibly explaining the adverse effects of iron supplementation. Interactions among iron, vitamin A, zinc, and copper need to be considered when evaluating the effects of iron supplementation on infants and children. [ABSTRACT FROM AUTHOR]

Background: Adaptation of iron absorption in response to dietary iron bioavailability is less likely in premenopausal women, who generally have lower iron stores, than in men. Objective: The objective of the study was to ascertain whether iron absorption in women adapts to dietary iron bioavailability and whether adaptation reflects altered absorptive efficiency or adjustment to specific inhibitors or enhancers of absorption. Design: Heme- and nonheme-iron absorption from either high- or low-bioavailability diets was measured at 0 and 10 wk in premenopausal women as they consumed one of the diets for 12 wk (randomized 2 x 2 factorial design). The high- and low-bioavailability diets contained similar amounts of total iron, as 13.1 and 14.8 mg/d nonheme and 2.0 and 0.3 mg/d heme iron, respectively, and they differed in contents of meat, ascorbate, whole grains, legumes, and tea. Results: In premenopausal women, the efficiency of nonhemeiron absorption (P = 0.06, two-tailed test), but not of heme-iron absorption, tended to adapt in response to a 12-wk difference in dietary iron bioavailability, whether absorption was tested with high- or low-bioavailability menus. Bioavailability, but not adaptation, substantially influenced total iron absorption (≈ 6-fold). In contrast with iron absorption from the low-bioavailability diet, that from the high-bioavailability diet consistently was inversely associated with serum ferritin. Conclusion: Only the high-bioavailability diet enabled women to absorb more iron in relation to their low iron stores. Women consuming the high-bioavailability diet absorbed up to 4.5 mg (30-35%) dietary iron with minimal influence of the diet consumed during the previous 10 wk. [ABSTRACT FROM AUTHOR]

Plants having the C4 photosynthetic pathway required higher concentrations of iron in the nutrient solution for maximum growth when grown in sand culture than those with the C3 pathway. There were only small differences among species in the concentration of iron required in the leaves to achieve near maximum dry matter yield. This suggests that C3 and C4 plants differ in their ability to absorb iron from the root zone. Higher concentrations of iron were required in the nutrient solution for maximum growth of both the C3 and C4 plants when nitrate, rather than ammonium nitrate, was the sole source of nitrogen. It seems likely that when nitrate was used,, there was a decrease in availability of iron to the plant as a result of the increased alkalinity in the root zone. By contrast, the root zone was acidified when ammonium nitrate was. applied. Iron concentrations greater than 2 to 5 µg Fe ml-1 in the nutrient solution reduced the dry matter yields of a number of plants grown with ammonium nitrate as the nitrogen source, probably because of a decrease in the absorption of phosphorus by the roots. [ABSTRACT FROM AUTHOR]

Absorbed iron (Fe) requirements are partly recalculated based on new figures for Fe requirements in menstruating women. The new higher figures were obtained by including in the calculation of the total requirements the effect of variations in hemoglobin concentration, which influences the variation in menstrual Fe losses and the variation in basal Fe losses. Higher figures were also found for menstruating teenage girls. Dietary iron requirements were also recalculated based on a critical examination of data available allowing estimations of bioavailability of the dietary iron in Western-type diets. In borderline Fe-deficient subjects, with optimal hemoglobin levels but no iron stores, the 95th percentile range for the bioavailability was estimated to 14-16% of the fraction of the dietary Fe that is potentially available for absorption (correction for partially available fortification Fe). [ABSTRACT FROM AUTHOR]

Background: Prevention of iron deficiency in African children is a public health priority. Current WHO/FAO estimations of iron requirements are derived from factorial estimates based on healthy, iron-sufficient "model" children using data derived mainly from adults., Objectives: In this study, we aimed to quantify iron absorption, loss, and balance in apparently healthy 5- to 7-y-old children living in rural Africa., Methods: We directly measured long-term iron absorption and iron loss in a 2-y observational study in Malawian children (n = 48) using a novel stable iron isotope method., Results: Of the 36 children with height-for-age and weight-for-age z scores ≥-2, 13 (36%) were iron deficient (soluble transferrin receptor >8.3 mg/L) and 23 were iron sufficient. Iron-deficient children weighed more than iron-sufficient children [mean difference (95% CI): +2.1 (1.4, 2.7) kg; P = 0.01]. Mean iron losses did not differ significantly between iron-deficient and iron-sufficient children and were comparable to WHO/FAO median estimates of 19 µg/(d × kg). In iron-sufficient children, median (95% CI) dietary iron absorption was 32 (28, 34) µg/(d × kg), comparable to WHO/FAO-estimated median requirements of 32 µg/(d × kg). In iron-deficient children, absorption of 28 (25, 30) µg/(d × kg) was not increased to correct their iron deficit, likely because of a lack of bioavailable dietary iron. Twelve children (25%) were undernourished (underweight, stunted, or both)., Conclusions: Our results suggest that WHO/FAO iron requirements are adequate for healthy iron-sufficient children in this rural area of Malawi, but iron-deficient children require additional bioavailable iron to correct their iron deficit., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Estimation of nutritional requirements is a difficult task, especially for nutrients whose requirements have skewed distribution like iron in menstruating women. To mathematically develop a simplified population data analysis using gamma distribution for the estimation of nutritional requirements, not depending on extensive numerical calculation. The required equations for the estimation of requirements were devised and solved. Existing data of iron intakes and iron losses in literature were fitted to cumulative distribution curves including gamma distribution. The proposed method was applied to the estimation of iron requirements in women using the National Health and Nutrition Survey data from 2003 to 2007 in Japan. The type 2 equation of nutritional state is first introduced: prevalence of inadequate nutritional state = Σ(individuals with intake/requirement <1)/(total number of individuals). The prevalence of inadequate nutritional status is determined by F -distribution with positive real number parameters, if the intake and the requirement have independent gamma distributions. The sum of basal and menstrual iron losses is well approximated by gamma distribution, if the basal and menstrual iron losses have independent gamma distributions. Using these relationships, an approximate estimate of iron requirements was determined. Iron intakes and losses were found to be well approximated by gamma distribution. The median of the coefficient of variation (CV) of basal iron loss was 34 %. A new correction method for intra-individual variation in gamma distribution under constant CV is presented also. The median of the estimated median iron requirement was 8.12 mg, 8.15 mg and 8.18 mg for women aged 18−29 years, respectively, as the exact numerical estimate, the approximate estimate using BETA.INV in Excel and the approximate estimate using F.INV in Excel. For women aged 30−49 years, it was 9.15 mg, 9.17 mg and 9.14 mg. The intake covering the needs of 97.7 % women was 14.55 mg, 14.44 mg and 14.49 mg for women aged 18−29 years, and 15.70 mg, 15.77 mg and 15.60 mg for women aged 30−49 years. The approximate estimates of iron requirements agreed well with the exact numerical estimate. The proposed method is useful for the estimation of iron requirements in menstruating women that usually requires extensive numerical calculations. [ABSTRACT FROM AUTHOR]

Le fer est un micronutriment essentiel à la synthèse de l'hémoglobine, au développement du système nerveux central et à la protection contre les infections. La petite enfance est une période de vulnérabilité au cours de laquelle la carence en fer est liée à une perturbation du développement neurologique. Une situation socioéconomique défavorisée, une naissance prématurée et un régime alimentaire sous-optimal sont des facteurs de risque de carence en fer. Une surcharge de fer attribuable à une insuffisance du mécanisme d'excrétion du fer peut également se manifester. Il est capital d'offrir un apport en fer suffisant aux nourrissons jusqu'à l'âge de deux ans. [ABSTRACT FROM AUTHOR]

Iron is an essential micronutrient required for hemoglobin synthesis, central nervous system development, and protection from infection. Early childhood is a time of vulnerability as iron deficiency in this period is associated with impaired neurodevelopment. Low socioeconomic status, preterm birth, and suboptimal diet are risk factors for iron deficiency. Due to a lack of iron excretory mechanism, the possibility of iron excess also exists. Appropriate iron intake in the first 2 years of life is critical. [ABSTRACT FROM AUTHOR]