Erythrocyte iron incorporation but not absorption is increased by intravenous iron administration in erythropoietin-treated premature infants.

Because critically ill premature infants experience significant iron loss due to phlebotomy and have high iron needs for growth, Fe absorption and incorporation studies are clinically important. A prospective, controlled, randomized, open 21-d study was conducted in infants with birth weight <1300 g and gestational age < 31 wk to assess the efficacy of combining intravenous (IV) sucrose iron (Fe) with erythropoietin (EPO) for increasing Fe absorption, RBC Fe incorporation, and erythropoiesis. Three clinically stable groups were enrolled at 3-4 wk of age: Control, EPO [2100 U EPO/(kg.wk)]; and IV Fe+EPO [2 mg IV sucrose Fe/(kg.d) plus 2100 U EPO/(kg.wk)]. All subjects received 9 mg/(kg.d) of oral Fe polymaltose. Subjects were not allowed RBC transfusions. Indicators of iron status and erythropoiesis were assessed before and 18 d after treatment. On d 4, tracer doses of oral polymaltose (57)Fe and IV sucrose (58)Fe were administered, and stool and blood samples were collected for Fe absorption and incorporation determinations. Compared with the Control group, the EPO group demonstrated greater hemoglobin (Hb) concentration and reticulocyte count, but no difference in Fe incorporation. In contrast, the IV Fe+EPO group demonstrated greater total Fe incorporation, Hb concentration, plasma ferritin, and reticulocyte count compared with the Control and EPO groups. Absorption of (57)Fe and nonisotopic polymaltose Fe did not differ among the groups (range: 48-58%, and 41-47%, respectively). We conclude that IV sucrose Fe administered in combination with EPO to very-low-birth weight premature infants significantly increases RBC Fe incorporation and erythropoiesis more than EPO alone, but without increasing iron absorption.

Demonstrating zinc and iron bioavailability from intrinsically labeled microencapsulated ferrous fumarate and zinc gluconate Sprinkles in young children.

Nutrient-nutrient interactions are an important consideration for any multiple-micronutrient formulation, including Sprinkles, a home-fortification strategy to control anemia. The objectives of this randomized controlled trial were as follows: 1) to compare the absorption of zinc at 2 doses given as Sprinkles; and 2) to examine the effect of zinc and ascorbic acid (AA) on iron absorption from Sprinkles. Seventy-five children aged 12-24 mo were randomly assigned to the following groups: 1) 5 mg of labeled zinc (67Zn) with 50 mg AA (LoZn group); b) 10 mg of labeled zinc (67Zn) with 50 mg AA (HiZn group); or 3) 5 mg zinc with no AA (control). All groups contained 30 mg of labeled iron (57Fe). Intravenous infusions labeled with 70Zn (LoZn and HiZn groups) and 58Fe (control) were administered. Blood was drawn at baseline, 48 h and 14 d later. The percentage of zinc absorbed did not differ between LoZn (geometric mean = 6.4%; min-max: 1.7-14.6) and HiZn (geometric mean = 7.5%; min-max: 3.3-18.0) groups. However, total zinc absorbed was significantly different between the LoZn (geometric mean = 0.31 mg; min-max: 0.08-0.73) and HiZn (geometric mean = 0.82 mg; min-max: 0.33-1.82) groups (P = 0.0004). Geometric mean percentage iron absorption values did not differ between the LoZn (5.9%; min-max: 0.8-21) and HiZn (4.4%; min-max: 0.6-12.3) groups and between the LoZn and control groups (5.0%; min-max: 1.4-24). We conclude that zinc in the form of Sprinkles has a low bioavailability, yet provides adequate amounts of absorbed zinc in young children, and that there is no effect of zinc or AA on iron absorption from the given formulations of Sprinkles.

Iron absorption and oxidant stress during erythropoietin therapy in very low birth weight premature infants: a cohort study.

BACKGROUND: Iron supplementation may be associated with oxidative stress particularly in premature infants. Our purpose was to examine 1) early supplemental iron during treatment with erythropoietin (EPO) and oxidative stress; 2) enhanced iron absorption during EPO in those infants receiving human milk. Therefore, we determined the effect of erythropoietin plus supplemental iron intakes (4 mg/kg/d) on antioxidant status and iron incorporation. METHODS: Ten very-low-birth-weight infants who were enterally fed and receiving either human milk or formula were followed for 4 weeks during erythropoietin therapy; blood and urine were collected at 3 times; baseline, 2 and 4 weeks later. Once oral feeds commenced the study protocol was initiated. After baseline blood collection, a dose of Fe57 was administered. Two weeks later, a dose of Fe58 was administered as ferrous chloride to determine the effect of human-milk or formula on iron incorporation into RBCs. RESULTS: Infants started the study at 35 +/- 13 days. Incorporation of isotope into RBCs did not differ between formula fed for Fe57 (mean incorporation 8 +/- 2.9 n = 3) compared to human-milk fed infants (8.7 +/- 5 n = 7) nor for Fe58 (6 +/- 2.7 n = 3 vs. 8.6 +/- 5 n = 7). Tissue damage measured by malondialdehyde in plasma and F-2--isoprostanes in urine, did not differ by feed or over time. Neither ability to resist oxidative stress/nor RBC superoxide dismutase differed according to feed or over time. CONCLUSION: Data suggest that during erythropoietin therapy antioxidant defence in VLBW infants are capable of dealing with early supplemental iron during treatment with EPO.

Absorption and loss of iron in toddlers are highly correlated.

For estimating the requirements for dietary iron, it is important to know the amount of iron that is lost from the body. Inevitable losses of iron have been determined in adult humans but not in infants or children. We administered (58)Fe, the least abundant stable isotope of iron, to free-living infants at 168 d of age (5.6 mo) and followed them to age 26 mo. There was no dietary restriction after isotope administration. Blood was obtained at regular intervals for determination of isotopic enrichment and indices of iron status. We estimated the quantity of circulating iron, noncirculating active iron, and storage iron at each age. The administered isotope equilibrated with total body iron by 13 mo of age. From 13 to 26 mo of age, we estimated inevitable loss and absorption of iron from the change in tracer abundance in circulating iron. The rate of decrease of tracer abundance was proportional to addition of tracee, i.e., absorption of iron. Conversely, the rate of decrease in quantity of tracer was proportional to removal of tracee, i.e., loss of iron. From 13 to 26 mo of age, iron absorption was (mean +/- SD) 0.49 +/- 0.13 mg/d and inevitable iron loss was 0.25 +/- 0.12 mg/d. Intersubject variability of iron loss and iron absorption was high, and iron loss and absorption were highly correlated (r = 0.789, P < 0.001). Iron stores were low throughout the study and decreased significantly from 13 to 26 mo of age, suggesting that iron absorption from the diet was inadequate to maintain or increase iron nutritional status. The data suggest that, in this cohort, which may be representative, the intake of bioavailable iron from 13 to 26 mo of age was insufficient to maintain iron nutritional status.

Determination of iron absorption from intrinsically labeled microencapsulated ferrous fumarate (sprinkles) in infants with different iron and hematologic status by using a dual-stable-isotope method.

BACKGROUND: The use of microencapsulated ferrous fumarate sprinkles is a new approach for home fortification. Iron and hematologic status may affect the absorption of iron from sprinkles. OBJECTIVE: The objective was to measure the absorption (corrected erythrocyte incorporation of (57)Fe) of 2 different doses of iron from sprinkles added to a maize-based complementary food provided to infants with different iron and hematologic status. DESIGN: Infants aged 6-18 mo were randomly assigned to receive either 30 (n = 45) or 45 (n = 45) mg elemental Fe as (57)Fe-labeled sprinkles added to a maize-based porridge on 3 consecutive days. A (58)Fe tracer (0.2 mg as ferrous citrate) was also infused intravenously (n = 46). Blood was drawn at baseline and 14 d later to determine erythrocyte incorporation of (57)Fe and (58)Fe by using inductively coupled plasma mass spectrometry. On the basis of hemoglobin and soluble transferrin receptor concentrations, subjects were classified as having iron deficiency anemia (IDA), iron deficiency (ID), or sufficient iron status. RESULTS: There was no significant effect of dose on iron absorption (P > 0.05). Geometric mean iron absorption was 8.25% (range: 2.9-17.8%) in infants with IDA (n = 32), 4.48% (range: 1.1-10.6%) in infants with ID (n = 20), and 4.65% (range: 1.5-12.3%) in iron-sufficient infants (n = 20). Geometric mean iron absorption was significantly higher in infants with IDA than in infants with ID or iron-sufficient infants (P = 0.0004); however, there were no significant differences between infants with ID and iron-sufficient infants. CONCLUSION: During infancy, iron absorption from sprinkles in a maize-based porridge meets and surpasses requirements for absorbed iron and is up-regulated in infants with IDA.

Breast milk fractions solubilize Fe(III) and enhance iron flux across Caco-2 cells.

Why breastfed infants absorb extrinsic iron (EFe) exceptionally well is an unexplained phenomenon. Our objective was to identify effects of human milk fractions (HMF) on bioavailability of EFe. HMF were prepared by centrifugation followed by successive ultrafiltration using 10-, 3- and 1-kDa molecular weight cutoff membranes. EFe was added to HMF before and after treatment with digestive enzymes. Solubilization of EFe by HMF was characterized by scintillation counting of radioiron and by size exclusion chromatography/inductively coupled plasma mass spectrometry (SEC/ICPMS) of stable iron. Effects of HMF on EFe uptake and basolateral transfer were assessed by using confluent Caco-2 cells in bicameral chambers. Whey fractions of low molecular weight (MW) derived from 10-kDa filtrate, except the 1-kDa filtrate, were as effective as ascorbate and nitrilotriacetate in solubilizing EFe at intestinal pH. Basolateral radioiron transfer from Caco-2 cell monolayers was greater in the presence of low MW whey fractions than in the presence of ferrous ascorbate. The 3-kDa filtrate and 3-kDa retentate fractions promoted basolateral transfer of cellular radioiron taken up previously. SEC/ICPMS of the 1-kDa retentate fraction revealed a UV-absorbing peak of MW approximately 4.2 kDa that contained iron and that solubilized added ferric iron both before and after in vitro digestion with pepsin, pancreatin and bile extract. Our results suggested that a low MW component of breast milk whey enhances iron bioavailability. Because the iron solubilization activity is resistant to in vitro digestion, it is plausible that the component is active in vivo and may explain the excellent absorption of EFe by breastfed infants [corrected].

Inevitable iron loss by human adolescents, with calculations of the requirement for absorbed iron.

In growing individuals, the requirement for absorbed iron consists of iron needed for growth and iron needed to replace inevitable iron loss. We were able to estimate inevitable iron loss by adolescents because total body iron of the adolescents had been enriched with the stable isotope, (58)Fe, as the result of earlier studies of iron absorption. During an interval beginning at least 1.56 y after isotope administration (a time sufficient for complete mixing of the isotope with total body iron) and extending for no less than 3.29 y, we determined the isotopic enrichment of circulating iron. On the basis of several assumptions, we calculated total body (58)Fe and total body iron at the beginning and end of the interval. Because of complete mixing of the isotope with total body iron, fractional total (58)Fe loss was the same as fractional loss of total iron. In males, the fractional loss of iron was 9.70%/y and the quantitative loss was 256 mg/y or 0.70 mg/d. In females, the fractional loss of iron was 14.60%/y and the quantitative loss was 306 mg/y or 0.84 mg/d. Using several assumptions, we then calculated that the iron requirement for growth during this interval was 0.76 mg/d for males and 0.31 mg/d for females. Adding the iron loss to the iron requirement for growth, the requirement for absorbed iron was estimated to be 1.46 mg/d for males and 1.15 mg/d for females.