Adequacy of Infant Formula With Protein Content of 1.6 g/100 kcal for Infants Between 3 and 12 Months.

OBJECTIVES: Infant formulas provide more protein than breast milk. High protein intakes may place infants at risk of later obesity. The present study tested whether a formula with protein content below the regulatory level supports normal growth from age 3 months. METHODS: Randomized double-blind trial enrolled healthy infants less than age 3 months. At 3 months, formula-fed infants were assigned to experimental (EXPL, 1.61 g protein/100 kcal; modified bovine whey proteins with caseinoglycomacropeptide removed) or control (CTRL 2.15 g protein/100 kcal; unmodified bovine milk protein with a whey/casein ratio of 60/40) formula; breast-fed (BF) infants were enrolled in a reference group. Complementary foods were allowed in small amounts from 4 to 6 months and unrestricted after 6 months. RESULTS: Weight gain (g/day) from 3 to 6 months was similar in the EXPL and CTRL groups (EXPL-CTRL -0.84 g/day; 95% confidence interval -2.25 to 0.57) and faster in the EXPL and CTRL groups than in the BF group. Weight analyzed longitudinally from 4 to 12 months was lower in the EXPL group than in the CTRL group (P = 0.031) but higher than in the BF group (P < 0.0001). Longitudinal analysis of odds ratios from 4 to 12 months indicated fewer infants with weight >85th percentile in the EXPL group than in the CTRL group (P = 0.015). Length z scores were lower than, and body mass index z scores were similar to, World Health Organization Standards in all of the groups. Serum biochemical parameters in the EXPL group reflected lower protein intake and were closer to parameters in the BF infants than in the CTRL group. CONCLUSIONS: A formula with 1.61 g of protein/100 kcal supports normal growth of infants after age 3 months. This protein content is adequate if provided from a high-quality source.

Vitamin D supplementation of breastfed infants: a randomized dose-response trial.

BACKGROUND: Breastfed infants require supplementation with vitamin D (vD), but little is known about the necessary dose. This double blind trial evaluated four different doses of vD. METHODS: Exclusively breastfed infants (N = 213) were randomized at 1 mo to one of four doses, which they received through 9 mo while receiving no formula. The supplements provided daily 200 IU, 400 IU, 600 IU, or 800 IU of vD. The primary endpoint was plasma 25(OH)D level, and secondary outcomes were plasma parathyroid hormone and calcium, and illness incidence. The study was conducted during winter at 41° N. RESULTS: Most infants had low (<50 nmol/l) 25(OH)D levels at 1 mo, but with supplementation levels rose. Overall, levels of 25(OH)D differed significantly in proportion to vD dose. There were no effects of vD on illness incidence or growth. Low levels were common, with 7.8% of levels being <50 nmol/l and 15 infants having 2 to 4 low levels. CONCLUSION: The four doses of vD produced different plasma levels of 25(OH)D. The higher doses were somewhat more efficacious in maintaining vD sufficiency in breastfed infants. The findings support the recommended dose of 400 IU/d, and stress the need to start supplementation at birth.

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.

Lack of Effect of Graded Doses of Vitamin D on Bone Metabolism of Breastfed Infants.

OBJECTIVE: A range of doses of supplemental vitamin D has been shown to be effective in preventing rickets in breastfed infants, but the effect of different doses of vitamin D on bone metabolism and mineral content has not been delineated. METHODS: In a randomized trial, breastfed infants received from 2 to 9 months daily supplements of vitamin D in doses of 200 IU/d, 400 IU/d, 600 IU/d or 800 IU/d. Measures of bone metabolism (plasma) were determined periodically and bone mineral content (DXA) was determined at study entry and at the end of winter when infants were 5.5 to 9 months old. The main findings have been reported; here we report findings related to bone metabolism. RESULTS: There were no consistent meaningful effects of vitamin D dose on markers of bone metabolism. Some markers showed changes with age. Bone mineral content increased with age but showed no effect of vitamin D dose. CONCLUSION: Vitamin D in daily doses from 200 IU/d to 800 IU/d had no measurable effect on bone mineral content or bone metabolism of breastfed infants.

Iron stores of breastfed infants during the first year of life.

The birth iron endowment provides iron for growth in the first months of life. We describe the iron endowment under conditions of low dietary iron supply. Subjects were infants participating in a trial of Vitamin D supplementation from 1 to 9 months. Infants were exclusively breastfed at enrollment but could receive complementary foods from 4 months but not formula. Plasma ferritin (PF) and transferrin receptor (TfR) were determined at 1, 2, 4, 5.5, 7.5, 9 and 12 months. At 1 month PF ranged from 38 to 752 µg/L and was only weakly related to maternal PF. PF declined subsequently and flattened out at 5.5 months. PF of females was significantly higher than PF of males except at 12 months. TfR increased with age and was inversely correlated with PF. PF and TfR tracked strongly until 9 months. Iron deficiency (PF < 10 µg/L) began to appear at 4 months and increased in frequency until 9 months. Infants with ID were born with low iron endowment. We concluded that the birth iron endowment is highly variable in size and a small endowment places infants at risk of iron deficiency before 6 months. Boys have smaller iron endowments and are at greater risk of iron deficiency than girls.

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 supplementation of breastfed infants from an early age.

BACKGROUND: In breastfed infants, iron deficiency at <6 mo of life, although uncommon, is observed in industrialized countries. Iron supplementation starting at an early age may prevent iron deficiency. OBJECTIVE: The study assessed the effect of early iron supplementation of breastfed infants and tested the hypothesis that iron supplementation enhances iron status. Potential adverse effects (tolerance and growth) were monitored. DESIGN: The prospective, placebo-controlled study involved exclusively breastfed infants who were randomly assigned at 1 mo of age to iron (n = 37) or placebo (n = 38). Iron (7 mg/d as multivitamin preparation with ferrous sulfate) or placebo (multivitamin preparation without iron) was given from 1 to 5.5 mo of age. Complementary foods were allowed at >4 mo. Infants were followed to 18 mo. Blood concentrations of ferritin, transferrin receptor, hemoglobin, and red cell indexes were determined at bimonthly intervals. Stool consistency and color and feeding behavior were recorded. RESULTS: Iron supplementation caused modest augmentation of iron status during the intervention at 4 and 5.5 mo but not thereafter. Iron supplements were well tolerated and had no measurable effect on growth. One infant developed iron deficiency anemia by 5.5 mo of age. Plasma ferritin and hemoglobin tracked over time. CONCLUSION: Early iron supplementation of breastfed infants is feasible and transiently increases iron status but not hematologic status. Iron is tolerated by most infants. The prevalence of iron deficiency anemia is low (3%) among unsupplemented breastfed infants in the first 6 mo of life.

Iron status of breastfed infants is improved equally by medicinal iron and iron-fortified cereal.

BACKGROUND: Although uncommon, iron deficiency (ID) occurs in breastfed infants. The regular provision of iron may prevent ID. OBJECTIVE: The objective was to test the feasibility and effectiveness of 2 modalities of providing iron (medicinal iron or iron-fortified cereal) to breastfed infants. The study tested the hypothesis that regular provision of iron improves iron status of breastfed infants without adverse effects. DESIGN: In this prospective, randomized, open-label trial, breastfed infants received on a regular basis either medicinal iron (n = 48) or an iron-fortified fruit-cereal combination (n = 45) from 4 to 9 mo or no intervention (control group; n = 59). The interventions provided 7.0-7.5 mg ferrous sulfate/d. Infants were enrolled at 1 mo and were followed to 2 y. Iron-status indicators were determined periodically, stool characteristics were recorded, and growth was monitored. RESULTS: The regular provision of iron led to improved iron status during and for some months after the intervention. Both sources of iron were about equally effective. Iron affected stool color but had no effect on feeding-related behavior. However, medicinal iron was associated with a small but significant reduction in length gain and a trend toward reduced weight gain. ID anemia was observed in 4 infants (2.3%), most of whom had a low birth iron endowment. Mild ID was common in the second year of life. CONCLUSIONS: Regular provision of medicinal iron or iron-fortified cereal improves the iron status of breastfed infants and may prevent ID. Both modalities are equally effective, but medicinal iron leads to somewhat reduced growth. This trial was registered at ClinicalTrials.gov as NCT00760890.

Vitamin D deficiency in breastfed infants in Iowa.

OBJECTIVE: The purpose of this work was to assess the vitamin D status of breastfed infants living in Iowa (latitude: 41 degrees N). METHODS: Blood samples and dietary records from 84 breastfed infants participating in another study were used for a survey of vitamin D status at 280 days of age. The vitamin D status of those (35 infants) who did not receive preformed vitamin D at 280 days of age (unsupplemented infants) was assessed longitudinally between 112 days and 15 months of age. Plasma 25-hydroxyvitamin D and, in most cases, parathyroid hormone and alkaline phosphatase were determined. RESULTS: At 280 days of age, 10% of breastfed infants were vitamin D deficient (25-hydroxyvitamin D < 11 ng/mL). Deficiency was significantly more prevalent among dark-skinned infants and during winter and occurred exclusively in unsupplemented infants. During winter, 78% of unsupplemented infants were vitamin D deficient. During summer, only 1 infant who had dark skin pigmentation was vitamin D deficient. Longitudinal assessment of unsupplemented infants similarly showed that the majority of breastfed infants were vitamin D deficient during winter. Severe deficiency (25-hydroxyvitamin D < 5 ng/mL) was common and was accompanied by elevation of parathyroid hormone and alkaline phosphatase. The prevalence of vitamin D deficiency decreased with age but was still 12% at 15 months of age if no preformed vitamin D was received. CONCLUSIONS: Vitamin D deficiency, including severe deficiency, was common among breastfed infants in Iowa who did not receive preformed vitamin D. Deficiency occurred mostly during winter but was not completely absent during summer. It affected infants with light as well as dark skin pigmentation. Consumption of preformed vitamin D from vitamin supplements or formula is effective in preventing vitamin D deficiency. Vitamin D supplementation should be provided to all breastfed infants.