Iron supplementation of breastfed infants

Reported here are three studies performed with the objective of finding ways to improve the iron status of breastfed infants and to prevent iron deficiency (ID). Participating infants were exclusively breastfed until 4 months of age; thereafter, they could receive complementary foods and, in some studies, supplemental formula. In the first study, infants were given medicinal iron between the ages of 1 and 5.5 months. During this period, iron status improved and ID was prevented; however, these benefits did not continue after the intervention ceased. In the second study, infants received medicinal iron or an equivalent amount of iron from an iron-fortified cereal between the ages of 4 and 9 months. Again, iron supplementation largely prevented ID from occurring, while non-anemic ID and ID anemia occurred in the control group as well as in the intervention groups before the intervention began. In the third study, infants received dry cereals fortified with electrolytic iron or with ferrous fumarate between the ages of 4 and 9 months. The cereals were equally effective in providing relative protection from ID. The results of these three studies indicate it is possible to protect breastfed infants from ID and IDA.     

Iron bioavailability in infants from an infant cereal fortified with ferric pyrophosphate or ferrous fumarate

BACKGROUND: Infant cereals are commonly fortified with insoluble iron compounds with low relative bioavailability, such as ferric pyrophosphate, because of organoleptic changes that occur after addition of water-soluble iron sources. OBJECTIVE: Our objective was to compare iron bioavailability from ferric pyrophosphate with an alternative iron source that is soluble in dilute acid, ferrous fumarate, and to evaluate the influence of ascorbic acid on iron bioavailability from ferrous fumarate in infants. DESIGN: Iron bioavailability was measured as the incorporation of stable iron isotopes into erythrocytes 14 d after administration of labeled test meals (25 g dry wheat and soy infant cereal, 100 g water, and 2.5 mg Fe as [57Fe]ferric pyrophosphate or [57Fe]ferrous fumarate). Ascorbic acid was added to all test meals (25 mg in study 1 or 25 or 50 mg in study 2). Infants were fed each test meal on 4 consecutive days under standardized conditions. The 2 different test meals within each study were administered 2 wk apart in a crossover design. RESULTS: Geometric mean iron bioavailability was significantly higher from [57Fe]ferrous fumarate than from [57Fe]ferric pyrophosphate [4.1% (range: 1.7-14.7%) compared with 1.3% (range: 0. 7-2.7%); n = 8, P = 0.008]. In this study, doubling the ascorbic acid content did not further enhance iron bioavailability; the geometric means (range) were 3.4% (1.9-6.6%) and 4.2% (1.2-18.7%) for the test meals with 25 and 50 mg ascorbic acid added, respectively (n = 9). CONCLUSION: Iron bioavailability from iron-fortified infant cereals can be improved by using an iron compound with high relative bioavailability and by ensuring adequate ascorbic acid content of the product.     

α-Lactalbumin and casein-glycomacropeptide do not affect iron absorption from formula in healthy term infants

Iron absorption from infant formula is relatively low. α-Lactalbumin and casein-glycomacropeptide have been suggested to enhance mineral absorption. We therefore assessed the effect of α-lactalbumin and casein-glycomacropeptide on iron absorption from infant formula in healthy term infants. Thirty-one infants were randomly assigned to receive 1 of 3 formulas (4 mg iron/L, 13.1 g protein/L) from 4-8 wk to 6 mo of age: commercially available whey-predominant standard infant formula (standard formula), α-lactalbumin-enriched infant formula (α-LAC), or α-lactalbumin-enriched/casein-glycomacropeptide-reduced infant formula (α-LAC/RGMP). Nine breast-fed infants served as a reference. At 5.5 mo of age, (58)Fe was administered to all infants in a meal. Blood samples were collected 14 d later for iron absorption and iron status indices. Iron deficiency was defined as depleted iron stores, iron-deficient erythropoiesis, or iron deficiency anemia. Iron absorption (mean ± SD) was 10.3 ± 7.0% from standard formula, 8.6 ± 3.8% from α-LAC, 9.2 ± 6.5% from α-LAC/RGMP, and 12.9 ± 6.5% from breast milk, with no difference between the formula groups (P = 0.79) or all groups (P = 0.44). In the formula-fed infants only, iron absorption was negatively correlated with serum ferritin (r = -0.49; P = 0.005) and was higher (P = 0.023) in iron-deficient infants (16.4 ± 12.4%) compared with those with adequate iron status (8.6 ± 4.4%). Our findings indicate that α-lactalbumin and casein-glycomacropeptide do not affect iron absorption from infant formula in infants. Low serum ferritin concentrations are correlated with increased iron absorption from infant formula.     

An evaluation of EDTA compounds for iron fortification of cereal-based foods

Fe absorption was measured in adult human subjects consuming different cereal foods fortified with radiolabelled FeSO4, ferrous fumarate or NaFeEDTA, or with radiolabelled FeSO4 or ferric pyrophosphate in combination with different concentrations of Na2EDTA. Mean Fe absorption from wheat, wheat-soyabean and quinoa (Chenopodium quinoa) infant cereals fortified with FeSO4 or ferrous fumarate ranged from 0.6 to 2.2%. For each infant cereal, mean Fe absorption from ferrous fumarate was similar to that from FeSO4 (absorption ratio 0.91-1.28). Mean Fe absorption from FeSO4-fortified bread rolls was 1.0% when made from high-extraction wheat flour and 5.7% when made from low-extraction wheat flour. Fe absorption from infant cereals and bread rolls fortified with NaFeEDTA was 1.9-3.9 times greater than when the same product was fortified with FeSO4. Both high phytate content and consumption of tea decreased Fe absorption from the NaFeEDTA-fortified rolls. When Na2EDTA up to a 1:1 molar ratio (EDTA:Fe) was added to FeSO4-fortified wheat cereal and wheat-soyabean cereal mean Fe absorption from the wheat cereal increased from 1.0% to a maximum of 5.7% at a molar ratio of 0.67:1, and from the wheat-soyabean cereal from 0.7% to a maximum of 2.9% at a molar ratio of 1:1. Adding Na2EDTA to ferric pyrophosphate-fortified wheat cereal did not significantly increase absorption (P > 0.05). We conclude that Fe absorption is higher from cereal foods fortified with NaFeEDTA than when fortified with FeSO4 or ferrous fumarate, and that Na2EDTA can be added to cereal foods to enhance absorption of soluble Fe-fortification compounds such as FeSO4.     

Haemoglobin fortified cereal: a source of available iron to breast-fed infants

We tested in the field an extruded rice flour, fortified with a bovine haemoglobin concentrate (Fe:14 mg/100 g of powder). This cereal has a high iron bioavailability, good protein quality and amino acid score. Healthy, term breast-fed infants were prospectively studied. One group (n = 92) received the fortified cereal (from 4 to 12 months of age). As control, 96 infants received regular solid foods (cooked vegetables and meat) from age 4 months. At the end of the field trial, a subsample of infants in both groups was supplemented with 45 mg Fe during 90 d. Iron nutrition status was determined at 9, 12 and 15 months. At 12 months, iron deficiency anaemia was present in 17 per cent of controls, in 10 per cent of fortified infants as a whole, but only in 6 per cent of the babies who consumed over 30 g of cereal/d. In addition, this latter group did not show any significant changes in iron nutrition status after the supplementation trial. Results demonstrate that the consumption of a haemoglobin fortified cereal is effective in markedly reducing the incidence of iron deficiency in breast-fed infants.     

Ferrous sulfate is more bioavailable among preschoolers than other forms of iron in a milk-based weaning food distributed by PROGRESA, a national program in Mexico

After 1 y of distributing a milk-based fortified weaning food provided by the Mexican social program PROGRESA, positive effects on physical growth, prevalence of anemia, and several vitamin deficiencies were observed. There was no effect on iron status, which we hypothesized was related to the poor bioavailability of the reduced iron used as a fortificant in PROGRESA. The objective of this study was to compare the iron bioavailability from different iron sources added as fortificants to the weaning food. Children (n = 54) aged 2-4 y were randomly assigned to receive 44 g of the weaning food fortified with ferrous sulfate, ferrous fumarate, or reduced iron + Na(2)EDTA. Iron absorption was measured using an established double-tracer isotopic methodology. Iron absorption from ferrous sulfate (7.9 +/- 9.8%) was greater than from either ferrous fumarate (2.43 +/- 2.3%) or reduced iron + Na(2)EDTA (1.4 +/- 1.3%) (P < 0.01). The absorption of log-(58)Fe sulfate given with the iron source correlated with serum ferritin (s-ferritin) concentration (n = 13, r = 0.63, P = 0.01) and log-(57)Fe absorption (reference dose) (n = 14, r = -0.52, P = 0.02). Absorption from ferrous fumarate and reduced iron + Na2EDTA did not correlate with s-ferritin or absorption of (57)Fe. The recommended daily portion of the fortified complementary food provides an average of 0.256, 0.096, 0.046 mmol (1.44, 0.54, and 0.26 mg) of absorbed iron, if fortified with sulfate, fumarate and reduced iron + Na(2)EDTA, respectively. Ferrous sulfate was more bioavailable than either ferrous fumarate or reduced iron + Na(2)EDTA when added to the milk-based fortified food and more readily met the average daily iron requirements for children 2-3 y of age.     

Reducing Iron Content in Infant Formula from 8 to 2 mg/L Does Not Increase the Risk of Iron Deficiency at 4 or 6 Months of Age: A Randomized Controlled Trial

Many infant formulas are fortified with iron at 8–14 mg/L whereas breast milk contains about 0.3 mg/L. Another major difference between breast milk and infant formula is its high concentration of lactoferrin, a bioactive iron-binding protein. The aim of the present study was to investigate how reducing the iron content and adding bovine lactoferrin to infant formula affects iron status, health and development. Swedish healthy full-term formula-fed infants (n = 180) were randomized in a double-blind controlled trial. From 6 weeks to 6 months of age, 72 infants received low-iron formula (2 mg/L) fortified with bovine lactoferrin (1.0 g/L) (Lf+), 72 received low-iron formula un-fortified with lactoferrin (Lf−) and 36 received standard formula with 8 mg of iron/L and no lactoferrin fortification as controls (CF). Iron status and prevalence of iron deficiency (ID) were assessed at 4 and 6 months. All iron status indicators were unaffected by lactoferrin. At 4 and 6 months, the geometric means of ferritin for the combined low-iron groups compared to the CF-group were 67.7 vs. 88.7 and 39.5 vs. 50.9 µg/L, respectively (p = 0.054 and p = 0.056). No significant differences were found for other iron status indicators. In the low-iron group only one infant (0.7%) at 4 months and none at 6 months developed ID. Conclusion: Iron fortification of 2 mg/L is an adequate level during the first half of infancy for healthy term infants in a well-nourished population. Adding lactoferrin does not affect iron status.     

Iron fortification of infant cereals: a proposal for the use of ferrous fumarate or ferrous succinate

Hemoglobin-repletion tests in rats, organoleptic studies, and iron-absorption studies in humans were used to search for Fe sources with high bioavailability that could be added to infant cereals as alternatives to the Fe compounds currently used for fortification. From rat and organoleptic studies on 11 alternative Fe sources, ferrous fumarate, ferrous succinate, and ferric saccharate were selected as the most suitable for infant-cereal fortification and, by use of radioactive labels, absorption of those compounds from fortified cereal was measured in adult human volunteers. There was no difference in absorption between ferrous fumarate and ferrous sulfate whereas the values for ferrous succinate, ferrous saccharate (10% Fe), and ferric pyrophosphate were 92%, 74%, and 39% of the ferrous sulfate values, respectively. We conclude that ferrous fumarate and ferrous succinate are highly available Fe sources in man that can be used to fortify infant cereals without causing fat oxidation or discoloration.     

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.     

Predominant breast-feeding from birth to six months is associated with fewer gastrointestinal infections and increased risk for iron deficiency among infants

Iron deficiency (ID) is prevalent among infants world-wide and may be more likely among infants born to women living in disadvantaged environments. A strategy to address ID in this context is to feed iron-fortified formula, but this may create risk for gastrointestinal (GI) infection. Our objective was to investigate the relationship between infant feeding practices, iron status, and likelihood of a GI infection in the first 6 mo of life. We conducted a prospective study at a public hospital in Guadalajara, Mexico. Healthy women who gave birth to a healthy term infant were eligible to participate. Each month, mothers (n = 154) provided information on infant feeding methods and symptoms of GI infection. At 6 mo of age, infants' iron status was assessed [hemoglobin (Hb) and serum ferritin concentration]. When compared with nonpredominantly breast-fed [partially breast-feeding (PBF) and formula feeding (FF) combined], predominantly breast-fed (PRBF) infants to 6 mo had a lower incidence of GI infection from 0-6 mo [18 vs. 33%; P = 0.04; adjusted odds ratio (OR) = 0.4; 95% CI = 0.2, 1.0] but a higher risk for ID (serum ferritin < 12 microg/L) at 6 mo (22 vs. 4%; P = 0.001; adjusted OR = 9.2; 95% CI = 2.3, 37.0). Anemia (Hb < 110 g/L) prevalence did not differ among feeding groups (13% for PRBF, 19% for PBF, and 4% for FF; P = 0.09). In this low-income population, our results suggest that PRBF should be promoted and the risk for ID managed using public health and nutrition strategies.     

Effects of weaning cereals with different phytate contents on hemoglobin,iron stores,and serum zinc: a randomized intervention in infants from 6 to 12 mo of age

BACKGROUND: Weaning foods frequently contain phytate, an inhibitor of iron and zinc absorption, which may contribute to the high prevalence of iron and zinc deficiency seen in infancy. OBJECTIVE: The objective was to investigate whether either an extensive reduction in the phytate content of infant cereals or the use of milk-based, iron-fortified infant formula would improve iron and zinc status in infants. DESIGN: In a double-blind design, infants (n = 300) were randomly assigned to 3 cereal groups from 6 to 12 mo of age: commercial milk-based cereal drink (MCD) and porridge (CC group), phytate-reduced MCD and phytate-reduced porridge (PR group), or milk-based infant formula and porridge with the usual phytate content (IF group). Venous blood samples were collected at 6 and 12 mo. Dietary intake was recorded monthly. After the intervention, 267 infants remained in the analysis. RESULTS: Hemoglobin concentrations of < 110 g/L, serum ferritin concentrations of < 12 microg/L, and serum zinc concentrations of < 10.7 micromol/L had overall prevalences at baseline and 12 mo of 28% and 15%, 9% and 18%, and 22% and 27%, respectively. After the intervention, there were no significant differences in any measure of iron or zinc status between the CC and the PR groups. However, hemoglobin was significantly higher (120 g/L compared with 117 g/L; P = 0.012) and the prevalence of anemia was lower (13% compared with 23%; P = 0.06) in the PR group than in the IF group, which could be explained by differences in daily iron intake between the 2 groups. CONCLUSION: Extensive reduction in the phytate content of weaning cereals had little long-term effect on the iron and zinc status of Swedish infants.     

Iron availability of a fortified processed wheat cereal: a comparison of fourteen iron forms using an in vitro digestion/human colonic adenocarcinoma (CaCo-2) cell model

In this three-phase study we first compared the availability of fourteen Fe forms in a wheat-based ready-to-eat breakfast cereal using an in vitro digestion/human colonic adenocarcinoma (CaCo-2) cell model. We then investigated the effect of milk and/or coffee on those fortified cereals found in phase 1 to show promising increases in Fe availability. The Fe forms assessed in phase 1 were reduced (control), carbonyl, electrolytic, FePO(4), FeSO(4), FeCO(3), Na(2)FeEDTA, Ferrochel (Albion Laboratories, Clearfield, UT, USA; ferrous bis-glycinate), encapsulated ferrous fumarate, FeSO(4), ferrous lactate and Biofer (LipoTech, Britwell Salome, Oxfordshire; FeSO(4)), SQM (Sea-Questra-Min Iron; Quali Tech, Chaska, MN, USA; polysaccharide-complexed FeSO(4)) and Sun Active (Taiyo Kagaku, Yokkaichi, Japan). All these forms increased Fe uptake compared with the unfortified cereal. Relative to the control, the following increases in Fe availability were observed: electrolytic, 52 %; ferrous fumarate, 30-35 %; Sun Active, 78 %; Ferrochel, 125 %; Na(2)FeEDTA, 291 %. Recent human studies have shown similar data with regard to Ferrochel, FeSO4 and Na(2)FeEDTA, with the latter being more bioavailable. Our phase-2 studies indicated that the addition of milk to FeSO(4)-fortified cereal increased Fe availability, but this availability was markedly decreased by the addition of coffee to the digest. Conversely, a loss in availability from Na(2)FeEDTA was observed with the addition of milk; however, the addition of coffee did not markedly affect Fe availability from this form. In phase-3 studies we observed increased Fe availability upon the addition of milk to cereals containing Ferrochel, FeSO(4), Sun Active, a mixture of reduced Fe and Na(2)FeEDTA or reduced Fe. For these forms we did not assess the behaviour after the addition of coffee. In conclusion, when considering possible fortificants for optimizing Fe bioavailability within a foodstuff, it is of paramount importance to consider the interaction between the fortified foodstuffs and other components of the meal (such as milk and coffee with a breakfast).     

Effect of iron fortification of nursery complementary food on iron status of infants in the DPRKorea

The aim of this study was to determine the iron status of infants who consumed porridge cooked in water with added ferrous sulphate. A total of 234 infants, aged 6-12 months, were recruited from 36 nurseries in the Democratic Peoples Republic of Korea (DPRK North Korea) and randomly divided into iron (Fe) and placebo groups. At baseline, almost half the children had Hb<110 g/L and no significant differences between the two groups were found with regard to hemoglobin concentration and anemia prevalence. The Fe group received rice porridge fortified with 10 mg of iron (as ferrous sulfate) per day, added to the water in which the rice was cooked and the placebo group non-fortified cereal for 6 months. After which, the hemoglobin (Hb), serum ferritin (SF) and packed cell volume (PCV) were measured and it was found that the proportion of children with anemia (Hb<110 g/L) was lower (24.3% v 48.1% p<0.01), the Hb levels (117.6 g/L v 109.8 g/L p<0.001) and serum ferritin were higher (40.7 v 26.8 mcg/L p<0.001); and iron deficiency anemia (Hb<110 g/L, SF<12 mcg/L) was lower in the Fe group (3% v 22% p<0.001) when compared to the placebo group. Ferrous sulphate, added to the water in which rice was cooked, lowered the prevalence of iron deficiency anemia of infants in the DPRK with no adverse reactions. This simple fortification would be suitable as a nationwide program in the DPRK and other countries with large infant nurseries.     

Treatment of anemia with microencapsulated ferrous fumarate plus ascorbic acid supplied as sprinkles to complementary (weaning) foods.

BACKGROUND: Standard therapy for anemia in infants is ferrous sulfate drops administered 3 times/d. Adherence to treatment, however, is often poor. One likely reason for poor adherence is the unpleasant side effects associated with drops. OBJECTIVE: The objective was to evaluate the use of a new form of iron and a delivery system to treat anemia in infants that is likely to produce better adherence to treatment. DESIGN: Using a prospective, randomized, controlled design, we studied 557 anemic children aged 6-18 mo (hemoglobin: 70-99 g/L) in rural Ghana. One group received a daily sachet of microencapsulated ferrous fumarate (80 mg elemental Fe) in powder form plus ascorbic acid to be sprinkled onto any complementary food eaten (sprinkles group); a control group received ferrous sulfate drops 3 times/d for 2 mo (total dose: 40 mg elemental Fe). Hemoglobin and serum ferritin concentrations were measured at baseline and at the end of treatment. RESULTS: Successful treatment of anemia (hemoglobin > 100 g/L) occurred in 58% of the sprinkles group and in 56% of the drops group, with minimal side effects in both groups. Geometric mean ferritin concentrations increased significantly in each group from baseline to the end of treatment (P < 0.001). CONCLUSION: Use of ferrous sulfate drops or a single daily dose of microencapsulated ferrous fumarate sprinkles plus ascorbic acid resulted in a similar rate of successful treatment of anemia without side effects. To our knowledge, this is the first demonstration of the use of microencapsulated iron sprinkles to treat anemia. Improved ease of use may favor the use of sprinkles to deliver iron.     

The diagnostic criteria for iron deficiency in infants should be reevaluated

Diagnostic criteria for iron deficiency (ID) and iron deficiency anemia (IDA) in infants are poorly defined. Our aim was to establish appropriate cut-off values for hemoglobin (Hb), plasma ferritin, erythrocyte mean cell volume (MCV), zinc protoporphyrin (ZPP) and soluble transferrin receptors (TfR) in infancy. Exclusively breast-fed infants (n = 263) in Honduras and Sweden were randomly assigned to receive iron supplementation or placebo, and blood samples were obtained at 4, 6 and 9 mo of age. Reference ranges were determined using three different approaches for defining iron-replete infants. The usefulness of several variables for predicting the Hb response to iron was evaluated. We found the following 2 SD cut-off values in iron-replete infants: Hb <105 g/L at 4-6 mo and <100 g/L at 9 mo; ZPP >75 micro mol/mol heme at 4-6 mo and >90 micro mol/mol heme at 9 mo; ferritin <20 micro g/L at 4 mo, <9 micro g/L at 6 mo and <5 micro g/L at 9 mo; and TfR >11 mg/L at 4-9 mo. The Hb response to iron was not a useful definition of IDA at 4 mo of age. Hb, MCV and ZPP at 6 mo as well as growth variables predicted the Hb response at 6-9 mo, but ferritin and TfR at 6 mo did not. We conclude that there is need for a reevaluation of the definitions of ID and IDA in infants.     

Iron status of infants fed low-iron formula: no effect of added bovine lactoferrin or nucleotides

BACKGROUND: The appropriate level of iron fortification in infant formula remains undetermined. OBJECTIVES: We compared hematologic indexes and iron-status indicators in infants who were either breast-fed or fed formula with concentrations of 2 or 4 mg Fe/L and evaluated the effects of providing part of the iron as bovine lactoferrin and of adding nucleotides. DESIGN: Healthy term infants were exclusively breast-fed (n = 16) or fed formula (n = 10-12) from age 4 +/- 2 wk to 6 mo. Anthropometric measures were taken monthly, and blood samples were taken at 1, 4, and 6 mo. Hematologic indexes; indicators of iron, zinc, and copper status; and erythrocyte fatty acids were assessed. RESULTS: No significant differences in hematology or iron status were observed between groups at 4 and 6 mo of age. Although 34% of all infants had a hemoglobin concentration <110 g/L at 6 mo, the absence of iron deficiency or defective erythropoiesis suggests that this hemoglobin cutoff is too high for this age group. Neither the source or the concentration of iron in formula nor fortification with nucleotides had any significant effect on serum zinc or copper, and nucleotide fortification did not affect erythrocyte fatty acids. CONCLUSIONS: A concentration of 1.6 mg Fe/L formula meets the iron requirement of healthy term infants aged 相似文献   

Complementary foods fortified with micronutrients prevent iron deficiency and anemia in Vietnamese infants

To investigate whether an intervention including micronutrient-fortified complementary foods can improve iron status, we conducted a randomized controlled trial in 5-mo-old Vietnamese infants (n = 246). Villages (n = 29) were randomly divided into those receiving instant flour (FF) or a food complement (FC) both fortified with micronutrients or nothing [control (C)]. FF and FC infants received daily for 6 mo at least 2 meals of fortified complementary foods. Micronutrient status was assessed by measurement of hemoglobin (Hb) and plasma ferritin (PF), transferrin receptor, zinc, and retinol. Final Hb (mean ± SD) was higher in the FF (112.5 ± 8.0 g/L) and FC (114.0 ± 7.0 g/L) groups compared with C (109.0 ± 8.0 g/L; P = 0.006). PF (geometric mean [95% CI]) was also higher in FF (19.8 μg/L [17.5-22.3]) and FC (20.8 μg/L [18.3-23.6]) compared with C (11.1 μg/L [9.8-12.5]; P < 0.0001). Anemia prevalence decreased more in the FC group (-43.6%) compared with C (-10.3%; P = 0.006). The change in prevalence of PF < 12 μg/L was different in the FF (-16.4%) and FC (-6.7%) groups compared with C (+30.4%; P < 0.01). Endpoint prevalence of iron deficiency (ID) and ID anemia (IDA) were lower in the FF (13.4 and 6.7%, respectively) and FC (15.2 and 3.8%) groups compared with C (57.5 and 37.5%) (P < 0.0001). Retinol and zinc concentrations did not differ among groups, but endpoint prevalence of zinc deficiency was lower in FF infants (36.1%) than in C infants (52.9%; P = 0.04). Micronutrient-fortified complementary foods significantly improved iron status and decreased the prevalence of anemia, ID, and IDA in Vietnamese infants and can be an important tool to reduce ID in infancy in developing countries.     

The usefulness of elemental iron for cereal flour fortification: a SUSTAIN Task Force report. Sharing United States Technology to Aid in the Improvement of Nutrition

Fortification of cereal flours may be a useful public health strategy to combat iron deficiency. Cereal flours that are used shortly after production (e.g., baking flour) can be fortified with soluble iron compounds, such as ferrous sulfate, whereas the majority of flours stored for longer periods is usually fortified with elemental iron powders to avoid unacceptable sensory changes. Elemental iron powders are less well absorbed than soluble iron compounds and they vary widely in their absorption depending on manufacturing method and physicochemical characteristics. Costs vary with powder type, but elemental iron powders are generally less expensive than ferrous sulfate. This review evaluates the usefulness of the different elemental iron powders based on results from in vitro studies, rat assays, human bioavailability studies, and efficacy studies monitoring iron status in human subjects. It concludes that, at the present time, only electrolytic iron powder can be recommended as an iron fortificant. Because it is only approximately half as well absorbed as ferrous sulfate, it should be added to provide double the amount of iron.     

Iron and ascorbic Acid: proposed fortification levels and recommended iron compounds

An adequate supply of dietary iron during the 1st 24 mo of life is essential for preventing iron deficiency with its attendant negative effects on mental, motor and emotional development as well as later cognitive performance. Iron reserves and the small amount of highly bioavailable iron in human milk are adequate to satisfy the iron requirements of breast-fed infants of adequate birth weight for the 1st 6 mo of life. Thereafter, complementary foods, iron supplements or both are needed to meet this requirement. Complementary foods should not displace the consumption of human milk. The quantities eaten, particularly by younger infants, may therefore be quite small. As a consequence it is essential that the iron be supplied in a highly bioavailable form. This can be achieved by fortifying complementary foods with ferrous sulfate and ascorbic acid provided that the ascorbic acid is not lost during storage or meal preparation. Suggested fortification levels for ferrous sulfate and ascorbic acid for some types of complementary foods are given. The use of ferrous fumarate or an elemental iron powder instead of ferrous sulfate has not been evaluated adequately. There is a need to develop alternative strategies for improving iron bioavailability in complementary foods because it may not be possible to preserve ascorbic acid activity in many of them.     

Iron supplementation affects growth and morbidity of breast-fed infants: results of a randomized trial in Sweden and Honduras

Iron supplements are often prescribed during infancy but their benefits and risks have not been well documented. We examined whether iron supplements affect growth or morbidity of breast-fed infants. Full-term infants in Sweden (n = 101) and Honduras (n = 131) were randomly assigned to three groups at 4 mo of age: 1) placebo from 4 to 9 mo; 2) placebo from 4 to 6 mo and iron supplements [1 mg/(kg. d)] from 6 to 9 mo; or 3) iron supplements from 4 to 9 mo. All infants were exclusively or nearly exclusively breast-fed to 6 mo and continued to be breast-fed to at least 9 mo. Growth was measured monthly and morbidity data were collected every 2 wk. Among the Swedish infants, gains in length and head circumference were significantly lower in those who received iron than in those given placebo from 4 to 9 mo. The same effect on length was seen in Honduras, but only at 4-6 mo among those with initial hemoglobin (Hb) > or =110 g/L. There was no significant main effect of iron supplementation on morbidity, nor any significant interaction between iron supplementation and site, but for diarrhea (with both sites combined), there was an interaction between iron supplementation and initial Hb. Among infants with Hb < 110 g/L at 4 mo, diarrhea was less common among those given iron than in those given placebo from 4-9 mo, whereas the opposite was true among those with Hb > or = 110 g/L (P < 0.05). We conclude that routine iron supplementation of breast-fed infants may benefit those with low Hb but may present risks for those with normal Hb.