Follow-on formula in the prevention of iron deficiency: a multicentre study

Abstract Six-month-old infants were recruited at 21 centres in the UK and Ireland and randomly assigned to receive matching iron-fortified (12.3 mg/l iron) or non-fortified (1.4 mg/l iron) formula for 9 months. Infants already receiving cow's milk continued this feed. Haematological indices and iron status were evaluated at age 6 months, 9–10 months and 15 months. Four hundred and six infants entered and 302 completed the study. There were no differences between the groups for increases in weight, head circumference or length. Significant differences between the groups were observed at 15 months for haemoglobin, serum ferritin, serum iron and total iron binding capacity. Haemoglobin levels were < 110 g/l in 33% of infants fed cow's milk compared with 13% and 11% in those receiving non-iron-fortified and iron-fortified formula respectively. The corresponding figures for serum ferritin < 10 µg/l were 43%, 22% and 6%. Follow-on formula provides an acceptable vehicle for preventing iron deficiency in this vulnerable group.     

Milk versus medicine for the treatment of iron deficiency anaemia in hospitalised infants.

AIMS: To compare iron fortified follow-on milk (iron follow-on), iron fortified partially modified cows' milk (iron milk), and iron medicine for the treatment of iron deficiency anaemia (IDA) in hospitalised infants. METHODS: In a randomised controlled trial, infants aged 9-23 months with IDA and who were hospitalised with an acute illness received iron follow-on (12 mg/l ferrous iron), iron milk (12.9 mg/l ferrous iron), or iron medicine (ferrous gluconate at 3 mg/kg of elemental iron once daily). All interventions were given for three months. Changes in measures of iron status three months after hospital discharge were determined. RESULTS: A total of 234 infants were randomised. Iron status was measured at follow up in 59 (70%) iron medicine, 49 (66%) iron follow-on, and 54 (70%) iron milk treated infants. There was a significant (mean, 95% CI) increase in haemoglobin (15 g/l, 13 to 16) and iron saturation (9%, 8 to 10) and decrease in ferritin (-53 microg/l, -74 to -31) in all three groups. Mean cell volume increased in iron follow-on (2 fl, 1 to 3) and iron milk (1 fl, 0.1 to 3) treated infants, but not in the iron medicine group (1 fl, -1 to 2). The proportion with IDA decreased in all three groups: iron medicine 93% to 7%, iron follow-on 83% to 8%, and iron milk 96% to 30%. Adverse effects, primarily gastrointestinal, occurred in 23% of the iron medicine, 14% of the iron follow-on, and 13% of the iron milk group. CONCLUSIONS: Iron fortified follow-on milk, iron fortified partially modified cows' milk, and iron medicine all effectively treat IDA in infancy.     

Milk versus medicine for the treatment of iron deficiency anaemia in hospitalised infants

Aims: To compare iron fortified follow-on milk (iron follow-on), iron fortified partially modified cows'' milk (iron milk), and iron medicine for the treatment of iron deficiency anaemia (IDA) in hospitalised infants. Methods: In a randomised controlled trial, infants aged 9–23 months with IDA and who were hospitalised with an acute illness received iron follow-on (12 mg/l ferrous iron), iron milk (12.9 mg/l ferrous iron), or iron medicine (ferrous gluconate at 3 mg/kg of elemental iron once daily). All interventions were given for three months. Changes in measures of iron status three months after hospital discharge were determined. Results: A total of 234 infants were randomised. Iron status was measured at follow up in 59 (70%) iron medicine, 49 (66%) iron follow-on, and 54 (70%) iron milk treated infants. There was a significant (mean, 95% CI) increase in haemoglobin (15 g/l, 13 to 16) and iron saturation (9%, 8 to 10) and decrease in ferritin (–53 µg/l, –74 to –31) in all three groups. Mean cell volume increased in iron follow-on (2 fl, 1 to 3) and iron milk (1 fl, 0.1 to 3) treated infants, but not in the iron medicine group (1 fl, –1 to 2). The proportion with IDA decreased in all three groups: iron medicine 93% to 7%, iron follow-on 83% to 8%, and iron milk 96% to 30%. Adverse effects, primarily gastrointestinal, occurred in 23% of the iron medicine, 14% of the iron follow-on, and 13% of the iron milk group. Conclusions: Iron fortified follow-on milk, iron fortified partially modified cows'' milk, and iron medicine all effectively treat IDA in infancy.     

Iron-fortified and unfortified cow's milk: effects on iron intakes and iron status in young children

Iron intakes and iron status were evaluated in 36 young Swedish children given either iron-fortified or unfortified cow's milk. All children had good iron status and had received breast milk or ironfortified formulae during infancy. Twenty 1-y-old children were randomized to a diet with ironfortified milk (7.0 or 14.9 mg Fe l^-1     

Iron balance and iron nutrition in infancy

At birth, the total body iron content is approximately 75 mg/kg, twice that of an adult man in relation to weight. During the first 6 mo of life, total iron body content increases slightly and exclusive breastfeeding is sufficient to maintain an optimal iron balance. Thereafter, iron body content substantially increases and the infant becomes critically dependent on dietary iron, provided by complementary foods. Numerous factors may contribute to nutritional iron deficiency in infancy, the most important being low body iron content at birth, blood loss, high postnatal growth rate, and a low amount and/or bioavailability of dietary iron. We have documented that the prevalence of iron deficiency declined in Italy as iron nutrition improved and that early feeding on fresh cow's milk is the single most important determinant of iron deficiency in infancy. Healthy full-term infants should maintain optimal iron balance by consuming a good diet, which can be summarized as follows: breastfeeding should be continued exclusively for at least 5 mo and then together with complementary foods containing highly bioavailable iron; infants who are not breastfed or are partially breastfed should receive an iron-fortified formula, containing between 4.0 and 8.0mg/L iron, from birth to 12 mo of age; fresh cow's milk should be avoided before 12 mo of age.     

Iron balance and iron nutrition in infancy

At birth, the total body iron content is approximately 75 mg/kg, twice that of an adult man in relation to weight. During the first 6 mo of life, total iron body content increases slightly and exclusive breastfeeding is sufficient to maintain an optimal iron balance. Thereafter, iron body content substantially increases and the infant becomes critically dependent on dietary iron, provided by complementary foods. Numerous factors may contribute to nutritional iron deficiency in infancy, the most important being low body iron content at birth, blood loss, high postnatal growth rate, and a low amount and/or bioavailability of dietary iron. We have documented that the prevalence of iron deficiency declined in Italy as iron nutrition improved and that early feeding on fresh cow's milk is the single most important determinant of iron deficiency in infancy. Healthy full-term infants should maintain optimal iron balance by consuming a good diet, which can be summarized as follows: breastfeeding should be continued exclusively for at least 5 mo and then together with complementary foods containing highly bioavailable iron; infants who are not breastfed or are partially breastfed should receive an iron-fortified formula, containing between 4.0 and 8.0 mg/L iron, from birth to 12 mo of age; fresh cow's milk should be avoided before 12 mo of age.     

Iron, zinc, copper and selenium status of breast-fed infants and infants fed trace element fortified milk-based infant formula

Infants were fed cow's milk-based formulas containing 4 mg of iron/I from 1.5 to 6 months of age and their hematological status was compared to infants receiving the same formula but with 7 mg of iron/l and with breast-fed infants. One formula with 4 mg of iron/l contained iron as ferrous sulfate, in another, part of the iron was provided as bovine lactoferrin. We also studied the effect of selenium (10 μg/l) and copper (0.4 mg/l) supplementation on selenium and copper status. There were no significant differences in hematological indices among the groups at 6 months of age; all infants had satisfactory iron status. Serum transferrin receptor levels, a potential novel indicator of iron status, were highest in breast-fed infants, suggesting a cellular need for iron, and lowest in infants receiving formula with 7 mg of iron/l. Selenium status, as assessed by serum glutathione peroxidase activity, was similar at 6 months of age in breast-fed infants and infants fed formula fortified with selenium but lower in infants fed unfortified formula. The lowest levels of glutathione peroxidase activity were found in infants fed the highest concentration of iron (7 mg/l). Serum copper concentrations were similar in all groups, but the lowest levels were found in infants fed the highest concentration of iron. These results suggest that 4 mg of iron/l is adequate for infants up to 6 months of age and that higher levels may have some negative effects.     

Progress in the Prevention of Iron Deficiency in Infants

ABSTRACT. Our present success in preventing iron deficiency in infants is based on a gradual growth in our understanding of iron nutrition. It became recognized that full term infants only become vulnerable to iron deficiency after about 5 months of age, and to a lesser degree if they are breast-fed. The specific foods in which iron is provided during infancy were found to be more important in determining iron absorption than the actual amount of iron in the diet. Experience has also shown that fortification of infant foods is more reliable and cost effective than providing iron medication. Our current approaches to preventing iron deficiency in infants include: 1) maintaining breast feeding for at least 6 months, if possible; 2) using an iron-fortified infant formula if a formula is used and using formula in preference to cow's milk; 3) using iron-fortified infant cereal as one of the first solid foods; and 4) providing supplemental iron for low birth weight infants.     

Iron status with different infant feeding regimens: relevance to screening and prevention of iron deficiency

The objective of this study was to evaluate the benefit of screening for anemia in infants in relation to their previous diet. The iron status of 854 nine-month-old infants on three different feeding regimens and on a regimen including iron dextran injection was determined by analysis of hemoglobin, serum ferritin, and erythrocyte protoporphyrin levels and of serum transferrin saturation. Infants were categorized as having iron deficiency if two or three of the three biochemical test results were abnormal and as having iron deficiency anemia if, in addition, the hemoglobin level was less than 110 gm/L. The prevalence of iron deficiency was highest in infants fed cow milk formula without added iron (37.5%), intermediate in the group fed human milk (26.5%), much lower in those fed cow milk formula with added iron (8.0%), and virtually absent in those injected with iron dextran (1.3%). The corresponding values for iron deficiency anemia were 20.2%, 14.7%, 0.6%, and 0%, respectively. The use of iron supplements is therefore justified in infants fed cow milk formula without added iron, even when there is no biochemical evidence of iron deficiency. The low prevalence of iron deficiency in the group fed iron-fortified formula appears to make it unnecessary to screen routinely for anemia in such infants. These results also support the recommendation that infants who are exclusively fed human milk for 9 months need an additional source of iron after about 6 months of age.     

Nutrient intakes of American infants and children fed cow's milk or infant formula

Between April 1984 and August 1984, a national survey, the Ross Laboratories Infant Nutrition Survey, was undertaken to assess patterns of food consumption of American infants ranging in age from 6.5 months to 13.4 months. Nutrient intakes of 865 infants were evaluated according to different foods (milk and milk products, non-iron-fortified formula, iron-fortified formula, infant cereal, commercial baby foods, and home-prepared table foods). Results indicated that most American infants consumed nutrients in appropriate amounts. However, a large proportion of infants who were fed a diet that included cow's milk received amounts of sodium, potassium, and chloride that exceeded the recommended safe and adequate ranges. The median intake of iron of infants fed either cow's milk or a non-iron-fortified formula was below the recommended dietary allowance; a low percentage of these infants received medicinal iron supplementation. The results also indicated that the median estimated renal solute load of the diet of infants fed cow's milk was approximately twice the amount of that of infants fed formula. These data may be useful in the development of nutritional programs for older infants.     

Iron status in low birth weight infants on breast and formula feeding

Iron status in 15 low birth weight infants, 1000–2499 g, on breast feeding was studied longitudinally for the first 6 months of age, and the findings compared to those of 30 low birth weight infants receiving a proprietary iron-fortified formula. The two groups received no iron supplement until they developed iron deficiency. The incidence of iron deficiency at 6 months was significantly greater in the breast-fed group than in the formula-fed group (86% v 33%). The breast-fed group had significantly lower serum ferritin and hemoglobin values after 4 months of age. The findings indicate that breast-fed low birth weight infants have a higher risk of developing iron deficiency and should receive iron supplementation from 2 months of age.Abbreviations TIBC total iron-binding capacity - MCV mean corpuscular volume     

Iron nutritional status in preterm infants fed formulas fortified with iron.

AIMS: To prospectively evaluate the iron nutritional status of preterm infants fed either a term (0.5 mg/dl iron) or preterm (0.9 mg/dl) formulas fortified with iron after hospital discharge. METHODS: Healthy low birthweight preterm infants were randomly assigned into three groups at the time of hospital discharge. Group A were fed an iron fortified preterm formula (0.9 mg/dl iron) until 6 months corrected age; group B, a fortified term formula (0.5 mg/l iron) until 6 months corrected age group C, the preterm formula between hospital discharge and term, then the term formula until 6 months corrected age. RESULTS: Seventy eight infants were followed up to 6 months corrected age. Iron intake from formula differed significantly between the groups (A, 1.17 mg/kg/day (SD 0.32) > C, 0. 86 mg/kg/day (SD 0.40) = B, 0.81 mg/kg/day (SD 0.23); p < 0.0001). Haemoglobin concentrations were similar to those of iron sufficient preterm infants of the same postnatal age, and term infants of the same postmenstrual age (after 3 months of age). There were no significant differences in haemoglobin concentration (p = 0.391), plasma ferritin (A vs B, p = 0.322), or in the incidence of iron deficiency (A vs B, p = 0.534). CONCLUSIONS: Iron fortified formulas containing between 0.5 and 0.9 mg/dl iron seem to meet the iron nutritional needs of preterm infants after hospital discharge.     

Iron fortification of infant milk formula: the effect on iron status and immune function.

We conducted a randomized double-blind trial of a cow's milk infant formula with increased iron fortification in order to confirm its safety and to measure its effects on iron status and immune function. A group of full-term, well nourished and healthy infants was followed from the age of 3 months to 1 year. A control group of 74 infants was given a commercially available infant formula containing 8.3 mg Fe/100g. The test group of 75 infants received a similar formula with 40 mg Fe/100 g. The formula with the extra iron proved to be safe and, when compared with the control group, the children in the test group had significantly improved iron status as reflected by the proportion of children classed as normal (25 of 61 cf. 44 of 65; p less than 0.003), and by the mean values of the haemoglobin concentration (11.5 cf. 11.9 g/dl; p = 0.04), red cell distribution width (15.5% cf. 14.4%; p = 0.0005), red cell zinc protoporphyrin (3.4 cf. 4.0 micrograms/g Hb; p = 0.04) and ferritin (29 cf. 17.3 micrograms/l; p = 0.004). The extra iron fortification depressed zinc concentration in plasma (90.6 cf. 83.5 micrograms/l; p = 0.05). There was no significant difference between the two groups for laboratory measures of immune function or for incidence of infection. No adverse effects such as infection could be attributed to the increased iron. We conclude that iron fortification of cow's milk infant formula may be safely increased to 40 mg/100 g (i.e. by a factor of 4.8 over the common concentration of 8.3 mg/100 g), but that this has less than the expected effect on iron status. Further studies are required to define (a) the long-term role of facilitators of iron absorption such as ascorbic acid, (b) the interaction of iron with absorption of divalent trace elements such as zinc, and (c) the effect of iron status on immune function and susceptibility to infection.     

Food Intake and Growth of Infants between Six and Twenty-six Weeks of Age on Breast Milk, Cow's Milk Formula, or Soy Formula

ABSTRACT. In 59 normal infants attending well-baby clinics, food consumption was registered until 26 and growth until 52 weeks of age. They were either breast-fed or formula-fed with a cow's milk product or a soy protein product. The average consumption of breastmilk was 746, 796, 722 and 689 g/day at 6, 14, 22 and 26 weeks respectively. Bottle-fed infants received larger volumes, and at 6 and 14 weeks were the calculated total energy intakes significantly higher than in breast-fed infants. No differences were seen between the feeding groups with respect to length and the sum of four skin folds. The soy formula-fed children, who happened to be 200 g heavier at birth, had lower weight gains during the first 6 weeks than the other two groups. Thereafter, the average weights of the soy formula group did not differ from the other groups. At 3 months, the soy formula-fed children displayed a slower mineralisation and maturation of bone, but the difference was no longer significant when re-examined at 6 months. Formulas based on soy protein isolates seem to be acceptable as substitutes for cow's milk formulas in feeding normal infants.     

Interactions between Infections, Malnutrition and Ironnutritional Status in Pakistani Infants A Longitudinal Study

The interactions between infections, malnutrition and poor iron nutritional status in infants at weaning ages are poorly defined. Therefore, four groups of infants from an area with a high incidence of malnutrition (Lahore, Pakistan) were enrolled in a prospective, randomized nutritional intervention study. Between 122 and 365 days of age, the infants from one community received either a milk cereal without iron fortification ( n = 29), a milk cereal fortified with ferrous fumarate (7.5 mg/100 g; n = 30), or a milk cereal fortified with ferric-pyrophosphate (7.5 mg/100 g; n = 27). Forty-four infants from a neighbouring community did not receive a nutritional supplement and served as the control group. Calculated mean daily energy- and protein intake with the cereals was between 259–287 kcal, and 9.6–10.6 g at 12 months of age, respectively. Mean daily iron intake with the fortified cereals was between 4.1–5.1 mg at corresponding age. Nutritional supplementation resulted in significantly lower incidence of malnutrition and heigher weight gain. Incidence of acute diarrhoea was significantly ( p <0.05) lower in the supplemented groups. The infants fed the iron-fortified milk cereals had significantly higher hemoglobin (mean 10.4 vs. 9.8 gdl^-1) and serum ferritin (mean 13.3 vs. 8.5 ngml^-1) values than the infants fed the non-fortified milk cereals. However, no differences in the incidence of infections were found between the supplemented groups. It is concluded that poor nutritional intake between 122 and 365 days of age substantially contributed to the high incidence of diarrhoea and malnutrition in Pakistani infants.     

Dietary modifications versus dicyclomine hydrochloride in the treatment of severe infantile colics

This study examined 120 infants, aged 3–12 weeks, with severe colics and compared the results of a specific hypoallergenic diet (group A) with those of pharmacological treatment (group B). Non-breastfed group A infants received soy milk and if unresponsive, hydrolyzed milk formulas; mothers of breast-fed infants received a diet without cow's milk, eggs or fish. Breast-fed and non-breast-fed group B infants received dicyclomine hydrochloride 3 mg/kg/day. Results, based on quantitative measurements of crying. indicated that in breast-fed infants there was no significant improvement between group A (62.5%) and group B (66.6%) infants. Among formula-fed infants, comparison of positive results using soy milk (65.9%) with positive results using dicyclomine (53.3%) was not significant; positive results using soy milk and hydrolyzed milk formulas in non-responders to soy milk, provided an improvement in 95.4% of cases. Pharmacological treatment provided an improvement in 53.3%) of cases. The diffcrence was significant ( p <0.01).     

Manganese absorption from human milk, cow's milk, and infant formulas in humans

Manganese absorption from human milk, cow's milk, and infant formulas was studied in humans by using extrinsic labeling of the diets with manganese 54 or manganese 52 and whole-body retention measurements. The fractional manganese absorption from human milk (8.2% +/- 2.9%) was significantly different when compared with cow's milk (2.4% +/- 1.7%), soy formula (0.7% +/- 0.2%), and whey-preponderant cow's milk formula with 12 mg/L of iron (1.7% +/- 1.0%) and without iron fortification (2 mg/L of iron) (3.1% +/- 2.8%), while no significant difference was observed between a whey-preponderant cow's milk formula with 7 mg/L of iron (5.9% +/- 4.8%) and human milk. The total amount of absorbed manganese was significantly higher from the non--iron-fortified cow's milk formula (2 mg/L of iron) as compared with human milk, while no significant differences were observed for the other milks and formulas.     

Preventing iron deficiency in breast-fed infants by suitable supplementary food. A prospective, controlled study

Iron deficiency may develop in prolonged breast feeding. Introduction of beikost (supplementary nutrition) is recommended in Germany for infants after 4 months of age. In a prospective study 73 exclusively breastfed infants at the age of 16 weeks were assigned to one of two feeding groups: 35 infants received a meat vegetable dinner fortified with iron-2-sulfate (3 mg iron per 100 kcal) as their first supplementary food. At 20 weeks of age a milk based rice cereal (MBRC) without iron fortification was added as a second beikost meal. The other group comprised 38 infants who first received a MBRC fortified with iron-3-pyrophosphate (3 mg iron per 100 kcal). At 20 weeks of age a non iron fortified vegetable potato dinner was introduced. After 6 months of age the iron fortified meat vegetable dinner was offered to all infants once a day. 26 infants who did not receive this dinner but otherwise were consulted and treated identically served as controls at 12 months of age. At 6 months of age values of hemoglobin, MCV, serum iron, ferritin, and transferrin saturation were higher in the meat dinner group compared to the cereal first group. At 12 months of age this was also true for the meat dinner group compared to the controls. However, the differences were minor and statistically not significant. Whereas most of the indicators of iron nutritional status were within the lower normal range, and total iron intake was below the levels recommended by German and American authorities, recommending two iron fortified beikost meals between age 7 and 12 months appears to be justified.     

Cow's milk and intestinal blood loss in late infancy

OBJECTIVES: Young infants commonly show occult intestinal blood loss when fed cow's milk, but in older infants blood loss may be less common. This study examined intestinal blood loss in response to cow's milk feeding in normal 7(1/2)-month-old and 12-month-old infants. STUDY DESIGN: Infants (n = 62) were fed formula for 1 month and then pasteurized cow's milk for 2 months. Stools were collected for quantitative determination of hemoglobin. Iron nutritional status was assessed. RESULTS: Infants fed cow's milk from 7(1/2) months of age showed a significant increase in guaiac-positive stools and in stool hemoglobin concentration. These effects were largely limited to those infants who had been breast fed early in life. Infants fed cow's milk from 12 months of age at baseline had greater stool hemoglobin concentrations than 7(1/2)-month-old infants, but cow's milk produced no significant increase. In neither age group did cow's milk affect iron nutritional status. CONCLUSION: The response to cow's milk is attenuated in infants aged 7(1/2) months compared with younger infants. By 12 months of age, the response has disappeared entirely. We conclude that the gastrointestinal tract of healthy infants gradually loses its responsiveness to cow's milk.     

Type of Milk Feeding and Nutrient Intake during Infancy The Leiden Pre-School Children Study

ABSTRACT. During infancy different types of milk feeding can be used, i.e. breast milk, formula or cow's milk. In the Leiden Pre-School Children Study food intake and anthropometric data of four-, six- and nine-month-old infants were collected to study the influence of the type of milk feeding on the energy and nutrient intake on one hand and on height and weight on the other hand. All three different types of milk feeding were studied in the four-month-old infants. In the six- and nine-month-old infants food intake data of those breast-fed were not collected. No differences in energy intake and in height and weight were found between formula-fed infants and infants fed on cow's milk at the three age-levels. The influence on nutrient intake, on the contrary, was substantial. Compared to formula feeding, cow's milk feeding resulted in a significantly higher intake of protein, sodium, potassium, calcium and phosphorus and a significantly lower intake of linoleic acid, iron and ascorbic acid. Cow's milk feeding at four months was more prevalent among less educated mothers than among mothers with higher education. Breast feeding was strongly positively related to educational level of the mother at all three ages. It can be concluded that more information should be given about the advantages and disadvantages of different types of milk feeding especially to less educated mothers.