Supplementation of an adapted formula with bovine lactoferrin. 2. Effects on serum iron, ferritin and zinc levels

Breast milk provides an excellent supply of most nutrients for newborn infants. Infant formulae should be nutritionally comparable to breast milk especially with regard to critical nutrients like iron and other trace elements. Infant formulae supplemented with various amounts of bovine lactoferrin were given to two groups of infants. These infants were compared with infants receiving unsupplemented formula and breast-fed infants. The effects of these diets on levels of haemoglobin, haematocrit, serum iron, ferritin and zinc were examined for a study period of 150 days. At birth, concentrations of iron, haemoglobin, haematocrit and zinc were comparable in all four feeding groups. The fact that the serum zinc level was not altered by lactoferrin supplementation appears to rule out an in-vivo effect of lactoferrin on zinc nutrition of infants. Ferritin levels of breast-fed infants were significantly higher than in non-supplemented formula-fed infants at day 30 and day 90. This difference was seen only at day 30, when comparing breast-fed infants to lactoferrin-supplemented formula-fed infants. Comparing the infants receiving formulae, the formula supplemented with the higher amount of bovine lactoferrin induced significantly higher serum ferritin levels compared to the unsupplemented formula at day 90 and day 150. These observations favour the idea that lactoferrin may be involved in iron absorption. Since this effect was pronounced only after 90 days, it has to be discussed as to whether this effect is a convincing argument for supplementing infant formulae with bovine lactoferrin.     

A study of the iron requirement in infants,using changes in total body iron determined by hemoglobin,serum ferritin and bodyweight

The amount of iron absorption in healthy breast-fed infants was estimated in order to assess the iron requirement. This was carried out by monitoring changes in total body iron (TBI). Hemoglobin and serum ferritin were measure to calculate hemoglobin iron, body storage iron and TB1 at the ages of 4–5 months and 10–11 months. The amount of iron absorption was ∼ 0.4 mg/day, calculated as the sum of TBI increment and physiological iron loss. From this study, the dietary iron requirement for the weaning period was estimated as 4 mg/day.     

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 and the exclusively breast-fed infant from birth to six months

This study was designed to determine whether normal, full-term, exclusively breast-fed infants develop iron deficiency anemia, as defined by hemoglobin or red blood cell indices more than two standard deviations below the age-specific mean, or depletion of iron stores, as defined by an abnormally low serum ferritin level. Thirty-three breast-fed infants were followed from birth to 6 months. Maternal blood and cord blood at delivery, and venous blood from the infants at 2, 4, and 6 months were analyzed for anemia as defined above. At 6 months of age, the mean hemoglobin concentration of these infants was slightly higher than the normal mean; four of 33 infants (12%) had a mean corpuscular volume greater than 2 SD below the reported normal mean; and two of 33 infants (6%) had a serum ferritin level less than 12 ng protein/ml. These data suggest that the infant who is exclusively breast-fed for the first 6 months of life is not at high risk for the development of iron deficiency anemia or the depletion of iron stores during that time.     

Serum ferritin in term and preterm infants

Serum ferritin levels were examined in maternal serum, In cord sera and at one, four, eight and twelve weeks in 19 term and 28 preterm infants. There was no correlation between maternal and cord ferritin levels. Mean serum ferritin concentration was lower in preterm infants, and both term and preterm Infants exhibited' an initial rise in serum ferritin concentration followed by a steady fall. Serum ferritin concentration showed a good correlation with calculated iron stores at twelve weeks of age suggesting that serum ferritin estimation is the method of choice for monitoring body iron stores in infants. No correlation was found between serum ferritin concentration and calculated iron intake at any age in either term or preterm infants. It is suggested that iron supplementation additional to that present in modified cow's milk is not necessary for the first twelve weeks of life in either term or preterm infants.     

Does maternal iron supplementation during the lactation period affect iron status of exclusively breast-fed infants?

Iron deficiency anemia (IDA) causes growth and developmental retardation in infants. Iron supplementation from the 4th month of age may prevent IDA, but side effects of oral iron supplementation limit its usage. The aim of this study was to investigate the effect of maternal iron supplementation on the iron status of mothers and their exclusively breast-fed infants. In a prospective, placebo-controlled, double-blinded randomized study, healthy mothers (Hb > or = 11 g/dl) and their 10-20-day-old healthy term infants who were admitted to Hacettepe University for neonatal screening were enrolled. The mothers who were intending to exclusively breast-feed at least up to four months were included. Iron supplementation (n = 82, 80 mg elementary iron) and placebo (n = 86) were given to the mothers randomly for four months. The anthropometrical measurements of infants were recorded monthly. Of all, 69 mothers and their infants in the iron group and 63 in the placebo group completed the study. At the end of the study period, blood samples (complete blood count, serum iron, iron binding capacity and serum ferritin) were drawn from the mothers and their infants. After adjustment for baseline hemoglobin value, the mean levels of hemoglobin, serum iron and ferritin were similar in the two groups at the end of the study; however, serum iron binding capacity was significantly lower in the iron group than in the placebo group. Giving maternal iron supplementation during the first four months of the lactation period had no effect on the serum iron and ferritin levels of mothers and infants. This could be due to the relatively short duration of the follow-up period. A longer follow-up period is recommended to detect the effect of the maternal iron supplementation during lactation.     

Iron status at 9 months of infants with low iron stores at birth

OBJECTIVE: To determine the 9-month follow-up iron status of infants born with abnormally low serum ferritin concentrations.Study design: Ten infants of >34 weeks' gestation with cord serum ferritin concentrations <5th percentile at birth (<70 microg/L) and 12 control infants with cord serum ferritin concentrations >80 microg/L had follow-up serum ferritin concentrations measured at 9 +/- 1 month of age. The mean follow-up ferritins, incidences of iron deficiency and iron-deficiency anemia, and growth rates from 0 to 12 months were compared between the two groups. RESULTS: At follow-up, the low birth ferritin group had a lower mean ferritin than the control group (30 +/- 17 vs 57 +/- 33 microg/L; P =.03), but no infant in either group had iron deficiency (serum ferritin <10 microg/L) or iron-deficiency anemia. Both groups grew equally well, but more rapid growth rates were associated with lower follow-up ferritin concentrations only in the low birth ferritin group (r = -0.52; P =.05). Both groups were predominantly breast-fed without iron supplementation before 6 months. CONCLUSIONS: Infants born with serum ferritin concentrations <5th percentile continue to have significantly lower ferritin concentrations at 9 months of age compared with infants born with normal iron status, potentially conferring a greater risk of later onset iron deficiency in the second postnatal year.     

Efficacy of daily and weekly iron supplementation on iron status in exclusively breast-fed infants

Iron deficiency anemia (IDA) remains the most prevalent nutritional deficiency in infants worldwide. The purpose of this study was to determine the efficacy of daily and weekly iron supplementation for 3 months to improve the iron status in 4-month-old, exclusively breast-fed healthy infants. Infants 4 months of age were eligible for the open, randomized controlled trial if their mothers intended to continue exclusive breast-feeding until the infants were 6 months of age. Infants or mothers with iron deficiency (ID) or IDA on admission were excluded. The infants (n = 79) were randomly assigned to three groups, the first group receiving daily (1 mg/kg daily), the second group weekly (7 mg/kg weekly), and the third group no iron supplementation. Anthropometric measurements were taken on admission and at 6 and 7 months of age. Iron status was analyzed on admission and monthly for 3 months. Both hematologic parameters and anthropometric measurements were found to be similar among the three groups during the study period. Seven infants (31.8%) in the control group, six (26.0%) in the daily group, and three (13.6%) in the weekly group developed ID or IDA (P > 0.05). Infants whose mothers had ID or IDA during the study period were more likely to develop ID or IDA independently from iron supplementation. Serum ferritin levels decreased between 4 and 6 months of age in the control and daily groups; the weekly group showed no such decrease. In all groups, the mean levels of serum ferritin were significantly increased from 6 months to 7 months of age during the weaning period. In this study, which had a limited number of cases, weekly or daily iron supplementation was not found to decrease the likelihood of IDA. In conclusion, exclusively breast-fed infants with maternal IDA appeared to be at increased risk of developing IDA.     

Iron status in breast-fed full-term infants

The aim of this study was to evaluate the iron status of full-term babies breast-fed exclusively for four months and the importance of iron supplementation. One hundred sixteen term infants followed up since the newborn period by a well baby clinic were included in the study. Iron deficient and/or anemic infants were excluded from the study at four months. Some of the infants (51) were later given appropriate complementary food besides breast-feeding (Group A) and some (42) were given ferrous sulfate (1 mg/kg/d) (Group B). Blood count and serum iron and ferritin measurements were done at four and six months of age. At the 4th month, iron deficiency was found in 23 (19.8%) infants, 11 of which had iron deficiency anemia. At the 6th month, 23 (45%) infants in Group A were iron deficient and 11 (21.6%) of them had iron deficiency anemia. In Group B, three (7.1%) infants were iron deficient and one (2.4%) of them also had iron deficiency anemia (p < 0.0001). Significant iron deficiency and iron deficiency anemia have been found in four-month-old exclusively breast-fed full-term infants. It is observed that complementary food alone is insufficient; there is need for iron supplementation.     

SERUM FERRITIN IN ASSESSMENT OF IRON NUTRITION IN HEALTHY INFANTS

ABSTRACT. We followed up 238 infants on 7 occasions during their first year of life. The diets of the infants were systematically either supplemented or not supplemented with iron. Developmental changes in serum ferritin were determined from a group with adequate intake of iron and without evidence of iron deficiency by three laboratory criteria: hemoglobin, mean corpuscular volume and transferrin saturation. The data indicate that the average level of serum ferritin correlates well with iron nutrition within groups of infants since the developmental changes are in accordance with the known changes in storage iron, the level of serum ferritin correlates with iron intake, and low ferritin levels are associated with lower transferrin saturation. The usefulness of serum ferritin as the sole criterion of iron deficiency in individual infants is limited, suggesting the use of more than one indicator to refine the diagnosis of iron deficiency without anemia.     

Iron gain in low-birthweight infants: role of milk feeding

The availability of iron is critical in low-birthweight infants. We followed a group of small preterm infants without iron supplementation who were either exclusively breast-fed or weaned early to industrial infant milk formula or home-prepared cow's milk formula. The gain of iron was compared within the milk groups on the basis of hemoglobin and serum ferritin concentrations at the ages of 3 and 4 mth when only trace amounts of solid foods had been given. Contrary to the reports on term infants we found unsupplemented proprietary infant milk formula and breast milk similar as a source of iron. It is possible that there is no major inhibition of iron absorption from any milk during the time of simultaneously occurring accelerated erythropoiesis and exhaustion of iron stores in preterm infants. The apparent inferiority of cow's milk could be due to increased intestinal loss of blood.     

Plasma ferritin in the assessment of iron status of Indian infants

In order to assess the iron nutritional status of infants, plasma ferritin levels were measured in the infants and children at different time intervals till two years of age from two different socio economic groups. While ferritin levels at 3-4 months age were significantly higher in upper income group infants, levels were almost similar in the subsequent infancy between the two income groups. A close correlation was seen between ferritin levels of mothers and infants at 1-3 months of age (p less than 0.001). Prenatal iron supplements (oral or parenteral) resulted in higher ferritin levels at 4-6 months age as compared to placebo group. While the infants born to mothers receiving parenteral iron did not show any evidence of iron deficiency (serum ferritin levels less than 12 ng/ml), 23.5 and 25.0% of infants in oral iron and placebo group had evidence of iron deficiency between 6-12 months. Thus it would appear that improving the iron status of mothers during pregnancy will have significant impact on the iron status of breast fed infants till 6 months.     

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.     

Prolonged Exclusive Breast-Feeding Results in Low Serum Concentrations of Immunoglobulin G, A and M

ABSTRACT. Serum levels of IgG, IgA and IgM were measured in 198 infants at ages 2, 4, 6, 9 and 12 months. By age 9 months 30 infants were still exclusively breast-fed; their IgG and IgM levels were significantly lower than those of infants weaned early to formula (before age 3.5 months). By 12 months 6 infants were still exclusively breast-fed; their IgA levels were by then also similarly lower. There was no significant difference in the number of infections experienced by these groups of infants. After 2 months on formula feeding, the IgG and IgM levels of the infants who were exclusively breast-fed for 9 months had caught up with the levels of the infants weaned early to formula. Only at 12 months of age prealbumin levels of the exclusively breast-fed infants showed a positive correlation to IgG and IgA levels; no correlation was found between immunoglobulin levels and levels of serum iron and zinc.     

Prolonged exclusive breast-feeding results in low serum concentrations of immunoglobulin G, A and M

Serum levels of IgG, IgA and IgM were measured in 198 infants at ages 2, 4, 6, 9 and 12 months. By age 9 months 30 infants were still exclusively breast-fed; their IgG and IgM levels were significantly lower than those of infants weaned early to formula (before age 3.5 months). By 12 months 6 infants were still exclusively breast-fed; their IgA levels were by then also similarly lower. There was no significant difference in the number of infections experienced by these groups of infants. After 2 months on formula feeding, the IgG and IgM levels of the infants who were exclusively breast-fed for 9 months had caught up with the levels of the infants weaned early to formula. Only at 12 months of age prealbumin levels of the exclusively breast-fed infants showed a positive correlation to IgG and IgA levels; no correlation was found between immunoglobulin levels and levels of serum iron and zinc.     

Blood transfusion and chronic lung disease in preterm infants

Frequent blood transfusions may produce changes in iron status which can give rise to oxygen-derived free-radical (ODFR) generation and oxidative injury. Preterm infants developing chronic lung disease (CLD) receive significantly more transfusions. A total of 73 very preterm infants had weekly estimations of serum iron, transferrin, transferrin saturation, ferritin, caeruloplasmin, bleomycin detectable (‘free’) iron (BDI), and thiobarbituric acid reacting substances (TBARS) made over the first 28 days. Thirty infants remained oxygen dependent at 36 weeks postmenstrual age and were termed as having CLD. They were significantly lighter and less mature at birth and received more than twice as many transfusions during the 1st month. They had significantly lower transferrin levels initially but similar total iron and transferrin saturations as non-CLD infants. Ferritin and caeruloplasmin levels rose to significantly higher levels over the 1st month in CLD infants, and ferritin levels were significantly related to the number of transfusions given. Infants with higher ferritin levels were more likely to show BDI, although this was not associated with increased lipid peroxidation as evidenced by higher TBARS. Conclusion It is unlikely that oxidative injury from ODFRs induced by blood transfusion contributes to the risk of developing CLD in preterm infants.     

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.     

Bioavailability of iron in soy-based formula and its effect on iron nutriture in infancy

Soy products have been reported to inhibit absorption of nonheme food iron and fortification iron. Iron bioavailability from a soy formula (Prosobee-PP 710) (iron added as ferrous sulfate: 12 mg/L; ascorbic acid: 54 mg/L) was examined in 16 adult women using the extrinsic radioactive tag method. The geometric mean absorption from the soy formula was only 1.7%. The effect of this formula on iron nutrition in infants was studied in 47 healthy term infants weaned spontaneously before 2 months of age and who received the formula ad libitum until 9 months of age. For control, 45 infants received a cow's milk formula fortified with ferrous sulfate (iron: 15 mg/L; ascorbic acid: 100 mg/L), which has been shown to be effective in preventing iron deficiency, and 49 additional breast-fed infants were also followed. All babies received solid foods (vegetables and meat) starting at 4 months of age. Iron nutritional status was determined at 9 months. Infants fed soy formula and iron-fortified cow's milk had similar mean values of hemoglobin, mean corpuscular volume, transferrin saturation, free erythrocyte protoporphyrin, and serum ferritin; both formula groups differed significantly (P less than .05) from the breast-fed group in all measurements except free erythrocyte protoporphyrin. Anemia (hemoglobin less than 11 g/dL) was present in only 4.3% and 2.2% of infants receiving the soy and the fortified formulas, respectively, v 27.3% in the breast-fed group. These results indicate that soy formula, in spite of the lower iron bioavailability when measured in adults, is essentially as effective as iron-fortified cow's milk in preventing iron deficiency in infants.     

Blood transfusion and chronic lung disease in preterm infants

Frequent blood transfusions may produce changes in iron status which can give rise to oxygen-derived free-radical (ODFR) generation and oxidative injury. Preterm infants developing chronic lung disease (CLD) receive significantly more transfusions. A total of 73 very preterm infants had weekly estimations of serum iron, transferrin, transferrin saturation, ferritin, caeruloplasmin, bleomycin detectable (‘free’) iron (BDI), and thiobarbituric acid reacting substances (TBARS) made over the first 28 days. Thirty infants remained oxygen dependent at 36 weeks postmenstrual age and were termed as having CLD. They were significantly lighter and less mature at birth and received more than twice as many transfusions during the 1st month. They had significantly lower transferrin levels initially but similar total iron and transferrin saturations as non-CLD infants. Ferritin and caeruloplasmin levels rose to significantly higher levels over the 1st month in CLD infants, and ferritin levels were significantly related to the number of transfusions given. Infants with higher ferritin levels were more likely to show BDI, although this was not associated with increased lipid peroxidation as evidenced by higher TBARS. Conclusion It is unlikely that oxidative injury from ODFRs induced by blood transfusion contributes to the risk of developing CLD in preterm infants. Received: 26 September 1995 / Accepted: 20 April 1996     

极低出生体重儿血清铁蛋白水平及影响因素

目的 分析极低出生体重儿(very low birth weight infants,VLBWI)的铁营养状况及影响其变化的因素.方法 收集2014年1月至12月我院收治的115例VLBWI,检测其基础血清铁蛋白及出院前末次血清铁蛋白水平,并对可能的影响因素如胎龄、出生体重、基础血红蛋白、住院期间累积输血量、累积失血量,孕母糖尿病、高血压及贫血等临床资料进行分析.结果 115例VLBWI的基础血清铁蛋白为100.8 ～210.3 μg/L,平均(140.32±13.21) μg/L;不同胎龄的VLBWI基础血清铁蛋白水平比较差异有统计学意义(F=14.367,P=0.000),胎龄＜32周的LBWI其基础血清铁蛋白最低[(124.5±31.3) g/L].母亲贫血程度越重,婴儿基础血清铁蛋白越低[无贫血:(230.9±68.7) μg/L,轻度贫血:(189.5 ±75.3) μtg/L,中度贫血:(133.5 ±88.1) μg/L,重度贫血:(122.2 ±56.8) μg/L;P ＜0.05].VLBWI基础血红蛋白水平越低,其基础血清铁蛋白水平越低(P＜0.05).同时VLBWI住院期间末次血清铁蛋白水平受累积输血量的影响差异有统计学意义(P＜0.05).结论 提高VLBWI基础血红蛋白水平对增加VLBWI体内铁储备是有益的,定期监测住院期间甚至出院后血清铁蛋白以指导VLBWI补铁治疗十分必要.