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.     

Iron deficiency, but not anemia, upregulates iron absorption in breast-fed peruvian infants

Iron absorption in adults is regulated by homeostatic mechanisms that decrease absorption when iron status is high. There are few data, however, regarding the existence of a similar homeostatic regulation in infants. We studied 2 groups of human milk-fed infants using (57)Fe (given as ferrous sulfate without any milk) and (58)Fe (given at the time of a breast-milk feeding) stable isotopes to determine whether healthy infants at risk for iron deficiency would regulate their iron absorption based on their iron status. We studied 20 Peruvian infants at 5-6 mo of age and 18 infants at 9-10 mo of age. We found no effect of infant hemoglobin concentration on iron absorption with 5-6 mo-old infants absorbing 19.2 +/- 2.1% and 9- to 10-mo-old infants absorbing 25.8 +/- 2.6% of the (57)Fe dose. For (58)Fe, 5- to 6-mo-old infants absorbed 42.6 +/- 5.0% and 9 to 10-mo-old infants absorbed 51.9 +/- 10.3%. Following log transformation, iron absorption from (57)Fe (r = -0.61, P = < 0.001) and (58)Fe (r = -0.61, P = < 0.001) were inversely correlated to serum ferritin (S-Ft). For both the (57)Fe and (58)Fe doses, infants with S-Ft <12 mg/L (n = 11) had significantly higher iron absorption than those with S-Ft >12 mg/L. We concluded that iron absorption in infants is related to iron status as assessed by serum ferritin but not hemoglobin concentration. Infants with low iron status upregulate iron absorption from breast milk at both 5-6 and 9-10 mo of age.     

Dry cereals fortified with electrolytic iron or ferrous fumarate are equally effective in breast-fed infants

Precooked, instant (dry) infant cereals in the US are fortified with electrolytic iron, a source of low reactivity and suspected low bioavailability. Iron from ferrous fumarate is presumed to be more available. In this study, we compared a dry infant rice cereal (Cereal L) fortified with electrolytic iron (54.5 mg iron/100 g cereal) to a similar cereal (Cereal M) fortified with ferrous fumarate (52.2 mg Fe/100 g) for efficacy in maintaining iron status and preventing iron deficiency (ID) in breast-fed infants. Ascorbic acid was included in both cereals. In this prospective, randomized double-blind trial, exclusively breast-fed infants were enrolled at 1 mo and iron status was determined periodically. At 4 mo, 3 infants had ID anemia and were excluded. Ninety-five infants were randomized at 4 mo, and 69 (36 Cereal L, 33 Cereal M) completed the intervention at 9 mo. From 4 to 9 mo, they consumed daily one of the study cereals. With each cereal, 2 infants had mild ID, a prevalence of 4.2%, but no infant developed ID anemia. There were no differences in iron status between study groups. Iron intake from the study cereals was (mean ± SD) 1.21 ± 0.31 mg?kg(-1)?d(-1) from Cereal L and 1.07 ± 0.40 mg?kg(-1)?d(-1) from Cereal M. Eleven infants had low birth iron endowment (plasma ferritin < 55 μg/L at 2 mo) and 54% of these infants had ID with or without anemia by 4 mo. We conclude that electrolytic iron and ferrous fumarate were equally efficacious as fortificants of this infant cereal.     

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.     

Growth patterns of breast-fed infants in affluent (United States) and poor (Peru) communities: implications for timing of complementary feeding.

We compared growth, dietary intake, and morbidity of infants breast-fed for > or = 12 mo from two populations: Davis, CA (n = 46) and Huascar, Peru (n = 52). When compared against WHO reference data (based primarily on formula-fed infants), Huascar infants appeared to falter as early as 3-4 mo, but when compared with Davis breast-fed infants, the curves for weight and length were very similar in girls until 10-12 mo and in boys until 6-9 mo. Thereafter, Huascar infants grew less rapidly than did Davis infants. Breast milk intake was very similar between groups, but in Huascar the amount and nutrient density of complementary foods consumed after 6 mo were lower and morbidity rates were much higher than in Davis. These results indicate that growth faltering of Huascar infants, when judged against breast-fed infants in the United States, occurs primarily after the first 6 mo of life and is not due to poor lactation performance.     

Age of introduction of complementary foods and growth of term, low-birth-weight, breast-fed infants: a randomized intervention study in Honduras

BACKGROUND: The optimal age at which to introduce complementary foods is a topic of considerable debate. OBJECTIVE: This study was designed to evaluate this issue in a nutritionally vulnerable population in Honduras. DESIGN: Mothers of low-birth-weight (1500-2500 g) term (ie, small-for-gestational-age) infants were recruited in the hospital and assisted with exclusive breast-feeding during the first 4 mo. At 4 mo, mothers were randomly assigned to either continue exclusive breast-feeding to 6 mo (EBF; n = 59) or to feed complementary solid foods (jarred rice cereal, chicken, and fruit and vegetables) twice daily from 4 to 6 mo while continuing to breast-feed at their initial frequency (SF; n = 60). At 4 and 6 mo, breast milk and total energy intake were measured for a nonrandom subsample (those who could stay overnight in a central unit: 32 EBF and 31 SF). RESULTS: At 4 mo, breast milk intake in the subsample was not significantly different between groups (EBF: 729 +/- 135 g/d; SF: 683 +/- 151 g/d: P >0.2); from 4 to 6 mo it increased (by 28 g/d) in the EBF group but decreased (by 39 g/d) in the SF group (P < 0.005). Nonetheless, total energy intake (including solid foods) increased more from 4 to 6 mo in the SF than in the EBF group. However, there were no significant differences between groups in weight or length gain during the intervention or subsequently (6-12 mo). CONCLUSION: There was no growth advantage of complementary feeding of small-for-gestational-age, breast-fed infants between 4 and 6 mo of age.     

Iron, zinc, and copper concentrations in breast milk are independent of maternal mineral status

BACKGROUND: Little is known about the regulation of iron, zinc, and copper in breast milk and the transport of these minerals across the mammary gland epithelium. OBJECTIVE: The objective was to study associations between breast-milk concentrations of iron, zinc, and copper and maternal mineral status. DESIGN: Milk samples from 191 Swedish and Honduran mothers were collected at 9 mo postpartum. Iron, zinc, and copper concentrations were measured by atomic absorption spectrometry. Blood samples from mothers were analyzed for plasma zinc and copper and 4 indexes of iron status: hemoglobin, plasma ferritin, soluble transferrin receptors, and zinc protoporphyrin. Complementary food energy (CFE) intake was used as an inverse proxy for breast-milk intake. RESULTS: Mean (+/-SD) breast-milk concentrations of iron were lower in the Honduran than in the Swedish mothers (0.21 +/- 0.25 compared with 0.29 +/- 0.21 mg/L; P < 0.001), and mean breast-milk concentrations of zinc and copper were higher in the Honduran than in the Swedish mothers [0.70 +/- 0.18 compared with 0.46 +/- 0.26 mg/L (P < 0.001) and 0.16 +/- 0.21 compared with 0.12 +/- 0.22 mg/L (P = 0.001), respectively]. Milk iron was positively correlated with CFE intake (r = 0.24, P = 0.001) but was not significantly correlated with any iron-status variable. Milk zinc was negatively correlated with CFE intake (r = -0.24, P = 0.001) but was not significantly correlated with maternal plasma zinc. Milk copper was not significantly correlated with CFE intake or maternal plasma copper. CONCLUSIONS: Milk iron, zinc, and copper concentrations at 9 mo postpartum are not associated with maternal mineral status, which suggests active transport mechanisms in the mammary gland for all 3 minerals. Milk iron concentrations increase and milk zinc concentrations decrease during weaning [corrected]     

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.     

Vitamin B6 status of breast-fed infants in relation to pyridoxine HCl supplementation of mothers

The vitamin B6 nutritue of breast-fed infants was evaluated by vitamin B6 intake, plasma pyridoxal 5'-phosphate (PLP) concentration, and growth patterns during the infants' first 6 mo of age. Vitamin B6 intakes of 47 healthy, term infants were significantly correlated with four levels of maternal vitamin B6 supplements: 2.5, 4.0, 7.5, or 10.0 mg pyridoxine (PN) HCl/d and met the B6 Adequate Intake (AI, 1998) of 0.1 mg/d for infants 0 to 6 mo. Only infants whose mothers received 10.0 mg PN x HCl/d exceeded or met the Recommended Dietary Allowances (RDA, 1989) of 0.3 mg vitamin B6/d from 4 to 6 mo of age. Plasma PLP concentrations of infants, measured at 1, 4, and 6 mo of age paralleled their mother's vitamin B6 intake. Most infants showed normal growth. The findings indicated that a maternal PN x HCl supplement of 2.5 mg/d provided an adequate amount of vitamin B6 in breast milk (0.15 mg/d) for the vitamin B6 status parameters and the growth of breast-fed infants.     

Human milk intake and growth faltering of rural Mesoamerindian infants.

To determine whether growth faltering during early infancy was attributable to inadequate intake of human milk, the nutrient intakes and growth of 30 Otomi infants from Capulhuac, Mexico, were studied at 4 or 6 mo of age. Growth was monitored monthly from 1 through 6 mo of age. The 2H dose-to-the-mother method was used to measure human milk intake. Energy, protein, lactose, and fat concentrations in milk were analyzed by standard techniques. Mean (+/- SD) human milk intakes were 885 +/- 145 and 869 +/- 150 g/d at 4 and 6 mo, respectively. Protein and lactose concentrations in milk were normal but fat and consequently energy concentrations were abnormally low. Energy intakes averaged 81 +/- 14 kcal.kg-1.d-1 at 4 mo and 72 +/- 14 kcal.kg-1.d-1 at 6 mo. Growth faltering by 6 mo was evidenced by the significant decline in growth velocities and National Center for Health Statistics Z scores. Weight gain at 6 mo was 8.1 +/- 3.5 g/d and length gain was 1.0 +/- 0.34 cm/mo. Weight-for-age and length-for-age Z scores were -0.81 +/- 0.94 and -1.51 +/- 0.83, respectively. Growth velocities were not significantly correlated with nutrient intakes. Growth faltering among the Otomi infants despite energy intakes comparable to those of breast-fed infants in more protected environments may have resulted from an increase in the need for nutrients or from a growth-limiting nutrient, other than energy, in their diet.     

Serum leptin concentrations in infants: effects of diet, sex, and adiposity

BACKGROUND: Leptin, the product of the obese (ob) gene, is a regulator of food intake and energy metabolism. Immunoreactive leptin was detected recently in breast milk and it has been hypothesized that leptin may be absorbed and may contribute to differences in body composition between breast-fed and formula-fed infants. OBJECTIVE: The objective was to evaluate whether diet, adiposity, or sex affect plasma leptin in breast-fed and formula-fed infants. DESIGN: Venous blood samples were drawn from healthy, exclusively breast-fed or formula-fed Swedish infants at 1, 4, and 6 mo of age (n = 193) and from 12-mo-old Finnish infants (n = 79). Anthropometric measurements were made and plasma samples were analyzed for leptin, insulin, and glucose. RESULTS: There were no significant differences in plasma leptin between formula-fed and breast-fed infants at 1 and 4 mo of age, whereas formula-fed infants had significantly higher ( approximately 5%) leptin concentrations at 6 mo of age. Similar results were observed after correction for BMI. Plasma leptin was 15-25% higher in female than in male infants at 1, 4, and 12 mo of age (P < 0.05), also after correction for BMI. When all infants were analyzed together, a positive correlation (r = 0.34, P < 0.0001) was found between plasma leptin and BMI. Very low leptin concentrations were found in breast milk after centrifugation and the high concentrations reported previously were likely due to interference in the assay by milk fat. CONCLUSIONS: Plasma leptin concentrations are not higher in breast-fed than in formula-fed infants; however, sex and adiposity affect leptin concentrations even at this early age.     

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.     

Supplemental zinc lowers measures of iron status in young women with low iron reserves

Zinc and iron compete during intestinal absorption, but postabsorptive interactions between these nutrients are less clear. Understanding these interactions is important to determine when supplementation with iron or zinc is proposed. The effect of zinc supplementation (22 mg Zn/d as zinc gluconate) or of iron supplementation (100 mg Fe/d as ferrous sulfate) for 6 wk on iron and zinc metabolism and absorption was evaluated in young women with low iron reserves. Young adult women (ages 20-28 y), nonanemic but with low iron stores (plasma ferritin< 20 microg/L), participated in the 70-d study. The women were divided in two groups (zinc-supplemented, n = 11; iron-supplemented, n = 12). The supplements were taken at bedtime. Iron and zinc biochemical indices and intestinal absorption were measured on d 1 and 56. Radioiron and stable isotopes of zinc were used to measure iron and zinc absorption from a test meal. In the iron-supplemented group, blood hemoglobin, plasma ferritin and the percentage of transferrin saturation increased (P < 0.01). Zinc indices did not change. In the zinc-supplemented group, plasma ferritin and the percentage of transferrin saturation decreased (P < 0.05), whereas the plasma transferrin receptor and erythrocyte zinc protoprophyrin levels increased (P < 0.05). Plasma and urinary zinc also increased (P < 0.01). Iron absorption (%) from the test meal increased (P < 0.01), whereas zinc absorption (%) decreased (P < 0.01) compared with baseline in the Zn-supplemented women. Our results indicate that the use of iron supplements in women with marginal iron status improves iron indices with no effect on zinc status. However, use of a modest zinc supplement improves zinc indices, but also appears to induce a cellular iron deficiency and, possibly, further reduce iron status.     

Proposed vitamin a fortification levels

Fortified complementary foods could be effective in preventing and controlling vitamin A and other common nutritional deficiencies in young children. Milk from well-nourished women is an excellent source of vitamin A. However, in Latin America many children are weaned prematurely and must receive the entire requirement of vitamin A from food. This paper proposes vitamin A fortification levels for foods targeted for children aged 6-23 mo to meet the existing intake gap among both breast-fed and weaned infants and young children. Estimates assume a nonsignificant contribution of common complementary foods and average levels of human milk intake by breast-fed infants and children. The estimated vitamin A gap for breast-fed infants aged 6-11 mo amounts to 63-92 microg RE [16-23% of recommended daily intake (RDI)] and for breast-fed children reaches 125 microg RE (31% of RDI). Weaned infants and children would have to fully meet the RDI (400 microg RE) from complementary foods. A fortified complementary food with 500 mg RE/100 g of dry product provided daily in a single ration of 40 g would meet 50% of the gap for weaned infants aged 6-11 mo and would raise the total intake above RDI for breast-fed infants aged 6-8 mo (125%) and 9-11 mo (127%). The same fortified food given in a daily ration of 60 mg would meet most of the gap (75%) for weaned children aged 12-23 mo and would increase total intake of breast-fed children aged 12-23 mo well above the RDI (144%), with no risk of exceeding established upper tolerable intake levels.     

Low nutrient intakes among infants in rural Bangladesh are attributable to low intake and micronutrient density of complementary foods

We assessed the adequacy of nutrient intakes of 135 rural Bangladeshi breast-fed infants 6-12 mo of age and examined nutritional trade-offs due to possible displacement of breast milk by complementary foods. Observers completed 12-h daytime measurements of breast milk and complementary food intakes; data for the previous 12 h were obtained from maternal recall, yielding estimates of total 24-h intakes. On average, infants were mildly wasted (mean +/- SD weight-for-length Z-score = -0.92 +/- 0.88) and moderately stunted (length-for-age Z-score = -1.49 +/- 0.96). Total energy intakes at 6-8 and 9-12 mo were 88 and 86% of absolute energy requirements (kJ/d), 106 and 105% of requirements per kg body weight, and 97 and 94% of requirements per kg median weight-for-length, respectively. Breast milk contributed 78% of energy intake at 6-8 mo and 75% at 9-12 mo. Mean meal frequency and energy density of complementary foods were generally consistent with recommendations, but only small amounts of food were offered. Nevertheless, only 72% of the food energy offered was consumed. Total energy intake was positively correlated with meal frequency, quantity consumed per meal, and energy intake from breast milk, but not with energy density of complementary foods. Energy intake from complementary foods was inversely related to energy intake from breast milk. The diets fell short of recommended intakes for numerous vitamins and minerals. We conclude that although greater intakes of complementary foods were associated with higher total energy intake, micronutrient intake remained low due to the low micronutrient density of the complementary foods consumed and the partial displacement of breast milk.     

Iron and zinc supplementation improved iron and zinc status, but not physical growth, of apparently healthy, breast-fed infants in rural communities of northeast Thailand

Iron deficiency is prevalent in children and infants worldwide. Zinc deficiency may be prevalent, but data are lacking. Both iron and zinc deficiency negatively affect growth and psychomotor development. Combined iron and zinc supplementation might be beneficial, but the potential interactions need to be verified. In a randomized, placebo-controlled trial using 2 x 2 factorial design, 609 Thai infants aged 4-6 mo were supplemented daily with 10 mg of iron and/or 10 mg of zinc for 6 mo to investigate effects and interactions on micronutrient status and growth. Iron supplementation alone increased hemoglobin and ferritin concentrations more than iron and zinc combined. Anemia prevalence was significantly lower in infants receiving only iron than in infants receiving iron and zinc combined. Baseline iron deficiency was very low, and iron deficiency anemia was almost nil. After supplementation, prevalence of iron deficiency and iron deficiency anemia were significantly higher in infants receiving placebo and zinc than in those receiving iron or iron and zinc. Serum zinc was higher in infants receiving zinc (16.7 +/- 5.2 micromol/L), iron and zinc (12.1 +/- 3.8 micromol/L) or iron alone (11.5 +/- 2.5 micromol/L) than in the placebo group (9.8 +/- 1.9 micromol/L). Iron and zinc interacted to affect iron and zinc status, but not hemoglobin. Iron supplementation had a small but significant effect on ponderal growth, whereas zinc supplementation did not. To conclude, in Thai infants, iron supplementation improved hemoglobin, iron status, and ponderal growth, whereas zinc supplementation improved zinc status. Overall, for infants, combined iron and zinc supplementation is preferable to iron or zinc supplementation alone.     

Efficacy and tolerability of low-dose iron supplements during pregnancy: a randomized controlled trial

BACKGROUND: Iron deficiency anemia (IDA) is common in pregnant women, but previous trials aimed at preventing IDA used high-dose iron supplements that are known to cause gastrointestinal side effects. OBJECTIVE: The objective was to assess the effect on maternal IDA and iron deficiency (ID, without anemia) of supplementing pregnant women with a low dosage (20 mg/d) of iron. Effects on iron status were assessed at the time of delivery and at 6 mo postpartum. Gastrointestinal side effects were assessed at 24 and 36 wk of gestation. DESIGN: This was a randomized, double-blind, placebo-controlled trial of a 20-mg daily iron supplement (ferrous sulfate) given from 20 wk of gestation until delivery. RESULTS: A total of 430 women were enrolled, and 386 (89.7%) completed the follow-up to 6 mo postpartum. At delivery, fewer women from the iron-supplemented group than from the placebo group had IDA [6/198, or 3%, compared with 20/185, or 11%; relative risk (RR): 0.28; 95% CI: 0.12, 0.68; P < 0.005], and fewer women from the iron-supplemented group had ID (65/186, or 35%, compared with 102/176, or 58%; RR: 0.60; 95% CI: 0.48, 0.76; P < 0.001). There was no significant difference in gastrointestinal side effects between groups. At 6 mo postpartum, fewer women from the iron-supplemented group had ID (31/190, or 16%, compared with 51/177, or 29%; RR: 0.57; 95% CI: 0.38, 0.84; P < 0.005). The rate of IDA between the groups did not differ significantly at 6 mo postpartum. CONCLUSION: Supplementing the diet of women with 20 mg Fe/d from week 20 of pregnancy until delivery is an effective strategy for preventing IDA and ID without side effects.     

Exclusive breast-feeding for 6 months, with iron supplementation, maintains adequate micronutrient status among term, low-birthweight, breast-fed infants in Honduras

There is little information on the risk of micronutrient deficiencies during the period of exclusive breast-feeding. We evaluated this among term, low-birthweight (LBW; 1500-2500 g) infants in Honduras. Mother-infant pairs were recruited in the hospital and assisted with exclusive breast-feeding during the first 4 mo. At 4 mo, infants were randomly assigned to either continue exclusive breast-feeding to 6 mo (EBF; n = 59) or be given iron-fortified complementary foods (rice, chicken, fruits, and vegetables) from 4 to 6 mo while continuing to breast-feed (SF, n = 60). Blood samples were collected at 2, 4, and 6 mo and analyzed for hemoglobin (Hb), hematocrit, plasma ferritin, % transferrin saturation, vitamin A, vitamin B-12, folate, zinc, and erythrocyte folate. Infants with Hb < 100 g/L at 2 or 4 mo were given medicinal iron supplements for 2 mo; the proportion administered iron drops did not differ significantly between groups. There was no significant effect of complementary foods on indices of vitamin A, B-12, folate, or zinc status. Among infants not given medicinal iron at 4-6 mo, iron status was higher in the SF group than the EBF group. In those given medicinal iron at 4-6 mo, iron status was higher in the EBF group, suggesting that complementary foods interfered with iron utilization. About half of the infants were anemic by 2 mo, before the age when complementary foods would be recommended. This supports the recommendation that LBW infants should receive iron supplementation in early infancy. Given that infants given iron supplements did not benefit from complementary foods at 4-6 mo, we conclude that exclusive breast-feeding for 6 mo (with iron supplementation) can be recommended for term, LBW infants.     

Redistribution of vitamin A after iron supplementation in Indonesian infants

BACKGROUND: Deficiencies of iron and vitamin A are prevalent worldwide. Single-micronutrient supplementation is widely used to combat these deficiencies. However, micronutrient deficiencies often occur concurrently, and there are many interactions between micronutrients. OBJECTIVE: This study investigated interactions among 3 important micronutrients--iron, vitamin A, and zinc--when they are given as supplements. DESIGN: In a randomized, double-blind, placebo-controlled supplementation trial, 387 Indonesian infants aged 4 mo were supplemented 5 d/wk for 6 mo with 10 mg Fe, 10 mg Zn, 2.4 mg beta-carotene, 10 mg each of Fe and Zn, 10 mg Zn + 2.4 mg beta-carotene, or placebo. Complete data on micronutrient status, including hemoglobin, ferritin, retinol, zinc, and the modified relative dose response (a measure of liver retinol stores), were available from 256 infants at the end of the study. RESULTS: Iron-supplemented infants had significantly lower plasma retinol concentrations and a significantly higher prevalence of vitamin A deficiency, as defined by a plasma retinol concentration <0.70 micromol/L, than did the non-supplemented infants. In contrast, the modified relative dose response of the iron-supplemented infants indicated greater liver stores of vitamin A. Iron supplementation improved iron status, and zinc supplementation improved zinc status, but beta-carotene supplementation did not significantly improve vitamin A status. CONCLUSIONS: In this study, iron supplementation in infants with marginal vitamin A status led to lower plasma vitamin A concentrations and simultaneously to greater vitamin A liver stores. This implies a redistribution of retinol after iron supplementation, which might induce vitamin A deficiency. Therefore, iron supplementation in infants should be accompanied by measures to improve vitamin A status.     

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.