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Human Nutrition and Metabolism

Dietary Iron Intake Is Positively Associated with Hemoglobin Concentration During Infancy but Not During the Second Year of Life¹

Torbjörn Lind^*,,2, Olle Hernell^*, Bo Lönnerdal^**, Hans Stenlund, Magnus Domellöf^* and Lars-Åke Persson

^* Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden; Department of Public Health and Clinical Medicine, Epidemiology, Umeå University, Umeå, Sweden; ^** Department of Nutrition, University of California, Davis, CA; and International Maternal and Child Health, Uppsala University, Uppsala, Sweden

²To whom correspondence should be addressed. E-mail: Torbjorn.Lind{at}epiph.umu.se.

	ABSTRACT

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Iron status during infancy and early childhood reflects highly dynamic processes, which are affected by both internal and external factors. The regulation of iron metabolism seems to be subjected to developmental changes during infancy, although the exact nature of these changes and their implications are not fully understood. We wanted to explore the association between dietary iron intake and indicators of iron status, and to assess temporal changes in these variables. This was done by secondary analysis of data from a recently conducted dietary intervention trial in which healthy, term, well-nourished infants were randomly assigned to consume iron-fortified infant cereals with regular or low phytate content, or iron-fortified infant formula. Dietary iron intake from 6 to 8 mo and from 9 to 11 mo was associated with hemoglobin (Hb) concentration at 9 mo (r = 0.27, P < 0.001) and 12 mo (r = 0.21, P = 0.001), respectively, but iron intake from 12 to 18 mo was not associated with Hb at 18 mo. In contrast, iron intake from 6 to 11 mo was not associated with serum ferritin (S-Ft) at 9 or 12 mo, whereas iron intake from 12 to 17 mo was positively associated with S-Ft at 18 mo (r = 0.14, P = 0.032). These shifts in associations between dietary iron intake, and Hb and S-Ft, respectively, may be due to developmental changes in the channeling of dietary iron to erythropoiesis relative to storage, in the absence of iron deficiency anemia. These observations should be taken into consideration when evaluating iron nutritional status during infancy and early childhood.

KEY WORDS: • infants • hemoglobin • ferritin • iron intake • transferrin receptor

During the second half of infancy, considerable amounts of iron must be provided by the diet as endogenous iron stores become depleted and the term infant is no longer self-reliant for iron to meet the needs for erythropoiesis and growth (1). However, a recent study showed that iron supplementation from as early as 1 mo of age to exclusively breast-fed infants increased the hemoglobin concentration (Hb)³ and mean corpuscular volume (MCV) (2). The variables commonly used to assess iron status in infants include Hb (defining anemia), MCV (reflecting the mean size of the RBC), serum ferritin (S-Ft; representing body iron stores), serum iron (S-Fe; measuring transferrin-bound iron, i.e., iron being transported in plasma), and serum transferrin receptors (S-TfR; indicating cellular iron needs) (3–6). These factors are subject to considerable physiologic variation during y 1 of life, making their use in evaluating iron status in this age group difficult. For example, the mean Hb at birth of 180 g/L decreases to 120 g/L at 6 mo and then increases toward the end of y 1 of life. In addition, S-Ft is 100–200 µg/L at birth, but typically increases to 200–400 µg/L during the first weeks of life, after which it decreases to 30 µg/L towards the end of y 1 as storage iron is utilized for growth and blood volume expansion (7,8). In addition, S-Fe decreases from an initial high of 22 µmol/L during the first weeks of life to a median of 14 µmol/L at 6 mo (9).

We reported recently that iron supplementation had different effects on Hb if given before and after 6 mo of age (10). We also reported that when surplus iron was given as part of the normal diet, Hb increased up to 12 mo of age irrespective of iron status (11), suggesting that the regulation of iron metabolism is subjected to developmental changes during infancy.

To optimize iron nutrition during infancy, avoiding deficiency as well as excess, issues regarding the dynamics of iron status in response to dietary iron intake must be disentangled. We recently conducted a large dietary intervention trial on healthy, well-nourished Swedish infants. The infants were randomly assigned to receive iron-fortified infant cereals with regular [commercially available milk cereal drink (MCD) and porridge] or low phytate content (phytate-reduced MCD and porridge), or iron-fortified infant formula and regular porridge. All infants were born at term, and had a low prevalence of iron deficiency anemia (IDA) at baseline. The intervention began at 6 mo and ended at 12 mo of age. At 12 mo, there were no significant differences between study groups for MCV or serum ferritin, and no difference in Hb between the two groups consuming MCD and porridge. However, Hb at 12 mo was significantly lower in the infant formula group compared with the phytate-reduced infant cereal group (117 vs. 120 g/L, P = 0.015). This difference was not significant after adjusting for mean daily iron intake, which was lower in the infant formula group than in the phytate-reduced infant cereal group. Thus, we found few differences in iron status indicators between the study groups, and those found were related to iron intake and not to the phytate intervention as such (11). Study data included extensive information on dietary intake over time, as well as hematological and other indicators of iron status at 6, 9, 12, and 18 mo of age, growth, and morbidity. In this paper, we perform a secondary data analysis, assessing possible associations between dietary iron intake during infancy and early childhood and subsequent hematological and iron status. Extrapolating from other studies (4,12,13), our hypothesis was that in this population of well-nourished, non-IDA, healthy infants, increased dietary iron intake would result in increased storage iron, i.e., S-Ft, but would have little effect on other iron status variables, e.g., Hb, MCV, S-Fe, or S-TfR.

	SUBJECTS AND METHODS

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Characteristics of the participants as well as detailed description of the randomization and intervention procedures of this study were reported previously (11). In short, healthy, term infants (n = 300) <6 mo of age were recruited from 6 well-baby clinics in Umeå, a university town with a population of 105,000, after obtaining written informed consent from the parents. Infants with manifest IDA (Hb < 100 g/L, S-Ft < 12 µg/L, and MCV < 70 fL; researchers’ definition) or chronic illnesses were excluded from this analysis. The study subjects were randomly assigned to one of three dietary intervention groups from 6 to 12 mo of age; regular infant cereals (MCD and porridge; CC group), low-phytate infant cereals (phytate-reduced MCD and porridge; PR group) or cow’s milk-based, iron-fortified, infant formula and porridge (IF group).⁴ The MCD and porridges were composed of precooked cereals, skim milk powder, and vegetable fat, and were fortified with minerals, i.e., iron and calcium, and vitamins, i.e., vitamin A, D, E, C, thiamine, niacin, B-6, folic acid, B-12, and pantothenic acid. The MCD and infant formula were consumed in bottles, whereas the porridge was served on a plate. The two products were not served together. Both breast-fed and nonbreast-fed infants were recruited. The participating mothers were recommended to breast-feed as long as they wished. At the parents’ own discretion, the study products were introduced into the infants’ diets from 6 mo of age, with no other interventions being done. The research nurse, investigators, and families were all unaware of the feeding group assignment of individual infants. At 12 mo, the intervention ceased, the remaining study products were collected, and the children were then followed until 18 mo of age. The Research Ethics Committee, Faculty of Medicine and Odontology, Umeå University, Sweden, approved the study.

    Biochemical assays. Venous blood was collected from the participating infants at inclusion (6 mo) and again at 9, 12, and 18 mo of age, using a zinc-free vacuum system (Vacutainer, Becton Dickinson). Hematological indices and iron status were analyzed at the Department of Clinical Chemistry, Umeå University Hospital by use of a Sysmex SE 9000 Autoanalyzer (Tillqvist). Hb was analyzed using Sysmex Sulfolyser automated hemoglobin reagent (Toa Medical Electronics), and MCV was automatically calculated from erythrocyte particle concentration and hematocrit. S-Fe was analyzed by the ferrozine method (Iron kit 1553712 and UIBC kit 1030600, Boehringer Mannheim, Scandinavia AB). S-Ft was analyzed by an immunoturbidometric technique (BM/Hitachi 704/717/911, Boehringer Mannheim) calibrated against WHO standard 80–602. S-TfR was analyzed by ELISA (Ramco).

    Dietary intake. Each month, starting from baseline until 18 mo, parents or caregivers recorded the type and amount of each food item consumed by the infant for 5 consecutive days, for a total of 12 recordings. Household measures were used for quantities, and the participating child was encouraged to eat all meals from a standardized plate. Breast-feeding was recorded as "meal," equivalent to a full meal, or "snack," i.e., a short feed mainly for comfort or other nonnutritive purposes, according to the mother’s own perception. Intakes of breast milk were assumed to be 134 g/meal up to 8 mo of age, 102 g/meal beyond 8 mo, and 25 g/snack at all ages (14). Nutrient intake from breast milk was calculated from Jensen (15) and Tsang et al. (16). Daily energy and nutrient intake were calculated using the MATs software (Rudans Lättdata), using the food composition tables of the Swedish National Food Administration (17). This database was complemented with commercial baby foods, formulas, and other recipes not originally included according to information from the participating families and the manufacturers.

    Statistical analyses. For statistical computations, SPSS, version 10.0 was used. Results are reported for those participants who completed the trial (n = 245), separately for each age, i.e., 6, 9, 12, and 18 mo of age, and each gender. However, in the multivariate regression analyses, we included all participants with complete data sets up to the time period analyzed, i.e., at 9 mo, n = 266; at 12 mo, n = 269; and at 18 mo, n = 245. Main outcomes were the measures of iron status, i.e., Hb, MCV, S-Ft, S-TfR, and S-Fe at 9, 12, and 18 mo of age. In the present analysis we combined the data from all 3 groups in the original intervention study. The rationale behind this was that although the three groups, i.e., CC, PR, and IF differed in which study products they consumed, the group allocation had little effect on the main outcomes. For Hb, there was a significant difference between PR and IF, but this was not significant when adjusted for mean daily iron intake, indicating that it was iron intake and not group allocation that had an effect.

Variables with skewed distribution, i.e., S-Ft and S-TfR, were ln-transformed. Outcomes are shown as means and SD, geometric means, when applicable, and proportions. The dietary data are shown as mean, daily intakes during the 6–8, 9–11, and 12–17 mo periods, respectively. Breast milk was included in the calculations of daily energy and nutrient intake during the 6–8 and 9–11 mo periods. Differences in means were tested with t test or ANOVA. When comparing proportions, the ²-test or Fisher’s exact test were used. Statistical significance was set at P < 0.05. Lowess smoothed plots, which use an iterative locally weighted least-squares method to fit a curve to a set of points, were used to visualize the dose-effect relation between daily iron intake and the main outcomes (18). Pearson’s correlation coefficients are shown with 2-tailed significance. The associations between dietary iron intake, iron status variables, and background variables were analyzed with linear regressions. Multivariate regression models were constructed, using variables with biologically known or plausible relevance to the main outcomes and dietary iron intake and those with a univariate P-value < 0.20, i.e., gender, birth weight, growth (i.e., relative weight change since birth), intake of cow’s milk and breast milk, baseline values of main outcomes, study group and intakes of energy, protein, calcium, ascorbic acid and phytate, testing for interaction, and confounding.

	RESULTS

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Of the 300 infants originally recruited for the intervention study, 245 (82%) had baseline, 9-, 12-, and 18-mo blood samples, at least 3 dietary registrations during the 6–11 mo period and a minimum of 2 registrations during the 12–17 mo period (Table 1). No infant was excluded due to the preset criteria for IDA at baseline. Of the 55 infants excluded from analysis, 24 left the study before 12 mo of age (5 moved from the area, 16 refused participation, and 3 developed an allergy to cow’s milk), 18 left the study after 12 but before 18 mo of age (16 refusing participation, 2 for other reasons), and 13 had missing dietary information or missing blood samples. There were no significant differences between the children who completed the study and those who did not in baseline Hb, MCV, S-Fe, S-Ft, S-TfR, prevalence of Hb < 110 g/L, or S-Ft < 12 µg/L, gender distribution, birth weight, birth length, weight or length increase from birth until baseline, parental education, breastfeeding status, or study group allocation (data not shown).

    Dietary iron intake and iron status. Mean daily iron intake from 6 to 8 mo was correlated with Hb at 9 mo (r = 0.27, P < 0.001), and iron intake from 9 to 11 mo was associated with Hb at 12 mo (r = 0.21, P = 0.001). However, iron intake from 12 to 17 mo was not correlated with Hb at 18 mo (r = 0.082, P = 0.22) (Fig. 1). Daily iron intake from 6 to 8 mo or 9 to 11 mo was not associated with S-Ft at 9 or 12 mo, respectively. However, iron intake from 12 to 17 mo was correlated with S-Ft at 18 mo (r = 0.14, P = 0.032) (Fig. 2). Iron intake from 6 to 8 mo was positively correlated with S-Fe at 9 mo (r = 0.16, P = 0.011) and intake from 9 to 11 mo was correlated with S-Fe at 12 mo (r = 0.20, P = 0.001). However, iron intake from 12 to 17 mo was not associated with S-Fe at 18 mo (r = –0.03, P = 0.65). Dietary iron intake was not associated with MCV or S-TfR at any time point.

View larger version (16K): [in this window] [in a new window]   FIGURE 1 Lowess curves of the effects of infants’ iron intake at age 6–8, 9–11, and 12–18 mo on Hb at 9, 12, and 18 mo. At 9 mo, there was a linear dose-response relation between iron intake at 6–8 mo and Hb (regression coefficient ß = 3.3, P = 0.005), without evident difference in slope below or above a daily intake of 0.8 mg/(kg body weight · d) [<0.8 mg/(kg body weight · d): ß = 7.2, P = 0.024; >0.8 mg/(kg body weight · d): ß = 6.5, P = 0.030]. At 12 mo, the Hb-slope was significant up to an iron intake from 9 to 11 mo of 1.2 mg/(kg body weight · d) (ß = 8.8, P < 0.001); thereafter, it was not significant (ß = 0.37, P = 0.93). At 18 mo, Hb was not significantly associated with iron intake from 12–18 mo (ß = 1.8, P = 0.41).

View larger version (14K): [in this window] [in a new window]   FIGURE 2 Lowess curves of the effects of iron intake at age 6–8, 9–11, and 12–18 mo on S-Ft at 9, 12, and 18 mo of age. At 9 and 12 mo, ln S- Ft was not significantly associated with iron intake (iron intake 6–8 mo: ß = –0.1, P = 0.36 and iron intake 9–11 mo: ß = –0.06, P = 0.59). At 18 mo, ln S-Ft was significantly associated with iron intake from 12 to 18 mo (ß = 0.38, P = 0.034), but without evident difference for intakes < or >1.0 mg/(kg body weight · d).

We tested the association between dietary intake and S-Ft in a multivariate model. We found no association between ln S-Ft at 9 or 12 mo and dietary iron intake from 6 to 8 mo or 9 to 11 mo, respectively. However, ln S-Ft at 18 mo was associated with dietary iron intake from 12 to 17 mo (ß = 0.44, P = 0.010), adjusting for ln S-Ft at 12 mo and relative weight increase from 12 to 18 mo This model explained 16% of the variation of ln S-Ft at 18 mo of age.

We assessed the relation between total amounts of iron consumed from 6 to 8 mo, from 6 to 11 mo, and from 6 to 17 mo and Hb and ln S-Ft at 9, 12, and 18 mo of age, respectively. These analyses confirmed the significant associations between total iron intake from 6 to 8 mo and Hb at 9 mo (P < 0.001) and the total iron intake from 6 to 11 mo and Hb at 12 mo (P < 0.001). However, there was no association between total iron intake from 6 to 8, 6 to 11, or 6 to 17 mo, and subsequent ln S-Ft, whereas total iron intake from 12 to 18 mo was associated with ln S-Ft at 18 mo (P = 0.015).

We also stratified the multiple linear regressions of Hb and ln S-Ft for initial iron status, i.e., those infants with S-Ft in the lowest (S-Ft < 23 µg/L) and highest quartiles (S-Ft > 80 µg/L). This did not significantly change the results, nor were they affected by inclusion or exclusion of the 6 infants who at 6 mo fulfilled the WHO criteria for IDA (Hb < 110 g/L, S-Ft < 12 µg/L and MCV < 73 fL).

	DISCUSSION

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
In this study, we recruited well-nourished infants with a low prevalence of IDA. These infants were participants in a diet intervention, randomized to foods with different levels of phytate, which is known to decrease the bioavailability of iron (21). However, there were small differences in iron status between the study groups, and the differences found in major outcomes, i.e., Hb, were the result of differences in iron intake rather than the intervention per se (11). Iron intake was carefully monitored throughout the follow-up period with monthly 5-d dietary registrations. This method has high internal validity in estimating the variation of energy and nutrients in infants and children (22). We could therefore assess the effect of iron intake on iron status over a large variation in consumption. We expected to find little effect on variables such as Hb because all infants were well-nourished and IDA was uncommon, and infants with manifest IDA (Hb < 100 g/L, S-Ft < 12 µg/L and MCV < 70 fL) were excluded, but we did expect to find an increase in S-Ft, the storage form of iron. Instead we found the opposite, i.e., in infants < 12 mo old, there was a significant increase in Hb with increasing iron intake, but no effect on S-Ft. Only at 18 mo did we find an association between iron intake and S-Ft, whereas the correlation between iron intake and Hb had disappeared by that time. From 6 to 8 mo, the relation between dietary iron intake and Hb was linear and there was no significant interaction between other nutrients and iron intake. Later, from 9 to 11 mo, there was still a significant, but now nonlinear relation between daily iron intake and Hb.

Gender differences in iron status parameters were shown in several studies. Domellöf et al. (23) found higher Hb, MCV, and S-Ft, and lower zinc protoporphyrin and S-TfR in girls than boys at 4, 6, and 9 mo of age. Emond et al. (24) reported no gender difference in Hb at 8 mo, whereas Hb was significantly higher in girls at 18 mo, and S-Ft was higher in girls at 12 mo (19). Further, Thorsdottir et al. (25) found higher S-Ft and MCV in girls at 12 mo, whereas Male et al. (26) in a large multicenter study found no significant gender differences in Hb or iron status per se, but a higher prevalence of severe anemia (Hb <100 g/L) in boys at 12 mo. Wharf et al. (27) found no gender difference in Hb or iron status variables from 4 to 18 mo. In the present study, we found generally higher MCV and higher S-Ft at 6 and 9 mo in girls. As was suggested (23), in this infant population without IDA, these differences may indicate physiologic differences between girls and boys.

The data presented indicate that the regulation of iron metabolism during the first years of life is highly dynamic. We speculate that dietary iron is to a high degree channeled to erythropoiesis and incorporated into Hb during infancy, as indicated by the almost linear relation between iron intake and Hb concentration in this population of infants without IDA. Interestingly, S-TfR was positively associated with Hb at both 9 and 12 mo. Transferrin receptors are bound to the cell surface and transport iron into the cell. A soluble form of the receptors can be measured in serum and is thought to reflect intracellular iron needs (28–30), mirroring the expression of transferrin receptors on iron-requiring cells. These receptors are found most abundantly on cells involved in erythropoiesis (30). A positive association between Hb and S-TfR may thus indicate increased erythropoiesis. Virtanen et al. (31) described higher S-TfR in infants than in prepubertal boys and men, and increased erythropoiesis is one of several possible explanations. Little of the dietary derived iron seems to be directed to storage, i.e., to ferritin, because there was no correlation between iron intake and S-Ft before 18 mo of age. Fuchs et al. (12) reported no correlation between daily iron intake and S-Ft at 12 mo, whereas Cowin et al. (32) found a positive relation between iron intake and S-Ft at 18 mo, but no correlation between iron intake and Hb. Walter et al. (33) reported a very modest increase in S-Ft at 12 mo in infants consuming a high-iron (12.7 mg/L) vs. low-iron (2.3 mg/L) formula from 6 to 12 mo of age, despite an increase in Hb. In addition, Hb was higher in those consuming more of the high-iron formula.

In the present study, gradually less of the dietary derived iron was incorporated into Hb from 9 to 11 mo, which is seen as a plateau in the iron intake-Hb curve at 12 mo of age (Fig. 1). Thereafter, dietary iron seems to be channeled toward storage to an increasing extent, seen in Figure 2 as an increase in S-Ft at 18 mo with increasing iron intake from 12 to 17 mo. A shift in the channeling at 1 y of age is also indicated by the finding that not even the total iron dose given up to 11 or 17 mo of age affected S-Ft, but only the amount of iron given after 12 mo of age. These findings support those of Domellöf et al. (10), who found that supplemental iron given during the 4 to 6 mo period was incorporated into Hb, regardless of iron status. Friel et al. (2), supplementing exclusively breast-fed infants from 1 to 6 mo of age, found significant effects of the supplementation on Hb and MCV, but no effect on S-Ft at 6 mo of age. Fomon et al. (34) showed that the incorporation of orally administered ⁵⁸Fe into erythrocytes was higher in infants at 5.5 mo than at 2 mo of age, which may indicate that the erythron requires more iron later in infancy.

An alternative interpretation to the differences in iron dynamics seen before and after 12 mo may be the discontinuation of the dietary intervention. The intervention provided the infants with large amounts of highly available iron from the study products. This iron may then have supported a continuous, very robust, and possibly imbalanced erythropoiesis without reliance on stores. The withdrawal of the iron-rich intervention may then have produced a different situation in which iron was partially partitioned to storage, possibly to guard against future deficiency. However, mean iron intake did not change significantly during the time periods before and after the intervention, which would dispute this, although we have no information on the amount of absorbed iron before and after the intervention.

The way iron is provided, i.e., as a food constituent or through supplementation, may modify the effects on hematologic variables. In studies from Indonesia, we and other groups reported that iron supplementation from 6 to 12 mo increased both Hb and S-Ft (35,36), with a significant, positive correlation between the amount of supplement consumed and S-Ft (35). In addition, Domellöf et al. (10) found effects on both Hb and S-Ft when giving iron supplements to infants from 4 to 9 mo of age, whereas Friel et al. (2) found increased Hb and MCV, but no effect on S-Ft when supplementing infants from 1 mo of age. However, iron supplementation of children 6–59 mo of age in Zanzibar improved S-Ft, but had no effect on Hb (37). Nevertheless, any changes in effect over age would be difficult to identify in this broad age range. Several indicators, e.g., Hb, MCV, S-Ft, and S-TfR are used in the evaluation of iron status in infants and young children. The data presented indicate that when evaluating the effects of dietary iron interventions in infancy, Hb is more closely correlated with dietary iron intake than are S-Ft and S-TfR, whereas the opposite may be true in y 2 of life. Further studies are needed to sort out the different effects of supplemental and dietary iron on Hb and S-Ft, respectively, and which indicators are best suited to reflect various aspects of iron status and effects of iron interventions.

In the present study, we found no relation between Hb and S-Ft at any age. Similarly, Emond et al. (24) found no correlation between Hb and S-Ft at 8 mo, whereas Freeman et al. (38) showed a positive correlation between Hb and S-Ft at both 12 and 24 mo of age in Irish children and Friel et al. (2) found significant correlation between Hb and S-Ft in 3.5- and 6-mo-old infants. The relation between Hb and S-Ft in different populations may depend on their underlying iron status.

Several regulators of iron homeostasis have been proposed (39). Among these, an erythropoietic regulator was suggested, in which an imbalance between the bone marrow iron supply and its rate of erythropoiesis is thought to regulate iron absorption (40). We speculate that the erythropoietic regulator, which does not respond to intestinal iron levels or total body iron, but rather to erythropoiesis requirements, is prominent during the latter half of infancy. The higher levels of S-TfR in infants (31), the positive association between Hb and S-TfR, and the absent association between iron intake and S-TfR would point to this. Further, early studies showed a significant inverse relation between age and iron absorption during infancy and early childhood (41,42). As hemoglobin levels reach their nadir during infancy and iron requirements remain high for growth and blood expansion, iron must be supplied from external sources, i.e., the diet. Given this situation, it seems plausible that dietary iron would be channeled toward erythropoiesis rather than to storage at this age, increasing Hb rather than ferritin. During infancy, serum erythropoietin concentrations are inversely correlated with Hb (43); thus, when Hb levels decrease, circulating levels of erythropoietin increase. It is possible that the channeling of iron toward erythropoiesis is mediated by erythropoietin and hepcidin, a recently discovered iron regulatory peptide (44). Although little is known about hepcidin during infancy, animal studies showed that erythropoietin acts both to stimulate erythropoiesis and to inhibit hepcidin, resulting in increased iron absorption (44). Thus, more iron would be absorbed and incorporated into Hb. However, further studies on iron homeostasis in infancy and childhood are warranted.

Iron status during infancy and early childhood reflects highly dynamic processes, affected by both internal and external factors. From 6 to 11 mo, Hb, but not S-Ft was positively associated with dietary iron intake. In contrast, from 12 to 17 mo, S-Ft, but not Hb was positively associated with iron intake. This could be due to developmental changes in the channeling of dietary iron to erythropoiesis vs. storage, in the absence of IDA. The development of these processes with age must be considered when evaluating iron nutritional status during the critical transition from exclusive breast-feeding to sole dependency on family foods.

	FOOTNOTES

 
¹ Supported by grants from the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (formerly the Swedish Council for Forestry and Agricultural Research), the Swedish Nutrition Foundation, the Sven Jerring Foundation, the Samariten Foundation, the Oskar Foundation, the Swedish Medical Research Council, and Semper AB.

³ Abbreviations used: CC, commercial milk cereal drink and porridge; IDA, iron deficiency anemia; IF, infant formula and porridge; Hb, hemoglobin concentration; MCD, milk cereal drink; MCV, mean corpuscular volume; PR, phytate-reduced milk cereal drink and porridge; S-Fe, serum iron; S-Ft, serum ferritin; S-TfR, serum transferrin receptor.

⁴ Compositions are available as supplemental data with the online posting of this paper at www.nutrition.org.

Manuscript received 5 December 2003. Initial review completed 13 January 2004. Revision accepted 10 February 2004.

	LITERATURE CITED

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 

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