Iron status in low-birth-weight infants, small and appropriate for gestational age. A follow-up study

Iron nutrition was measured in 84 low-birth-weight infants. At birth, they were assigned to three groups: preterm infants appropriate for gestational age (n = 29); preterm infants small for gestational age (n = 17); and full-term infants small for gestational age (n = 38). A sub-sample of infants was supplemented with iron 3 mg/kg from two to four months of age. At birth, preterm appropriate-for-gestational-age infants had a lower hemoglobin concentration than full-term small-for-gestational-age infants (p < 0.01) and a higher serum ferritin than preterm small-for-gestational-age infants (p < 0.05). In the non-supplemented group, full-term small-for-gestational-age infants had significantly higher hemoglobin concentrations at four months of age. At this age, iron-supplemented preterm infants appropriate or small for gestational age had significantly higher hemoglobin levels than non-supplemented subjects, while iron supplementation did not have an effect on final hemoglobin concentration in full-term small-for-gestational-age infants. We conclude that preterm infants, irrespective of their adequacy for gestational age, show evidence of iron deficiency before four months of age. Full-term infants do not develop iron deficiency up to this age.     

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.     

Ferrous and hemoglobin-59Fe absorption from supplemented cow milk in infants with normal and depleted iron stores

Small amounts of milk do inhibit ferrous iron absorption from a 5 mg ⁵⁹Fe²⁺ dose in 1- to 18-month-old infants. Only 50 ml of 2/3 cow milk reduced the absorption from 18±3% (X_a ± S.E.) to 3.8 ± 1.2% in infants with normal iron stores (inhibition index 0.21) and from 26±3% to 8.5±1.4% in infants with depleted iron stores (inhibition index 0.33%). Milk does not inhibit the biovailability of hemoglobin iron. From a 5 mg dose of hemoglobin-⁵⁹Fe added to 50 ml of 2/3 cow milk 4.8±1.0% were absorbed by infants with normal iron stores and 8.3±0.8% by infants with depleted iron stores. The low iron content of milk (50 μg Fe/100 ml) and its poor biovailability (～5% in infants with normal iron stores) would require a daily consumption of 32 l of unfortified milk to cover infants daily iron requirement of 0.8 mg/day. The supplementation of 2–3 milk meals per day with 5 mg hemoglobin iron each meets the whole iron requirement of infants with depleted and normal iron stores respectively and can be used for iron prophylaxis in infancy during the first and second year. Prophylaxis with inorganic iron requires an empty stomach and duodenum for optimal bioavailability. A daily dose of only 5 mg ferrous sulfate iron is enough to cover the total iron requirement of infants.     

Duration of exclusive breastfeeding is a positive predictor of iron status in 6‐ to 10‐month‐old infants in rural Kenya

The prevalence of iron‐deficiency anemia (IDA) is high in infants in Sub‐Saharan Africa. Exclusive breastfeeding of infants to 6 months of age is recommended by the World Health Organization, but breast milk is low in iron. Some studies suggest exclusive breastfeeding, although beneficial for the infant, may increase risk for IDA in resource‐limited settings. The objective of this study was to determine if duration of exclusive breastfeeding is associated with anemia and iron deficiency in rural Kenyan infants. This was a cross‐sectional study of 6–10‐month‐old infants (n = 134) in southern coastal Kenya. Anthropometrics, hemoglobin (Hb), plasma ferritin (PF), soluble transferrin receptor (sTfR), and C‐reactive protein were measured. Body iron stores were calculated from the sTfR/PF ratio. Socioeconomic factors, duration of exclusive breastfeeding, nature of complementary diet, and demographic characteristics were determined using a questionnaire. Mean ± SD age of the infants was 7.7 ± 0.8 months. Prevalence of anemia, ID, and IDA were 74.6%, 82.1%, and 64.9%, respectively. Months of exclusive breastfeeding correlated positively with Hb (r = 0.187; p < .05) and negatively with sTfR (r = ?0.246; p < .05). sTfR concentrations were lower in infants exclusively breastfed at least 6 months compared with those exclusively breastfed for less than 6 months (7.6 (6.3, 9) vs. 8.9 (6.7, 13.4); p < .05). Controlling for gender, birth weight, and inflammation, months spent exclusively breastfeeding was a significant negative predictor of sTfR and a positive predictor of Hb (p < .05). The IDA prevalence in rural Kenyan infants is high, and greater duration of exclusive breastfeeding predicts better iron status and higher Hb in this age group.     

Storage iron in human foetal organs

Maternal plasma iron and storage iron (non-heme) in the foetal liver were estimated in 108 foetuses whose gestational ages ranged from 12-44 weeks. Simultaneous estimations of storage iron were also made on the spleen and kidney in 70 and 69 of these foetuses respectively. Although the concentration of iron per g wet tissue in these organs remained practically the same at all gestations, the total storage iron content increased with the increase in gestation due to growth of these organs. The liver, in particular, showed a steep rise in total iron content in the last 8 weeks of gestation. There was a significant positive correlation between the total storage iron content in the foetal organs and the birth weight and gestational age of the foetus, suggesting that the preterm infants had smaller iron stores at birth as compared to infants born at term. The direct relation of the concentration as well as the total content of storage iron in the foetal liver with the maternal plasma iron levels suggested that babies born to iron deficient mothers had poor iron stores in their livers.     

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.     

Storage Iron in Human Foetal Organs

ABSTRACT. Maternal plasma iron and storage iron (non-heme) in the foetal liver were estimated in 108 foetuses whose gestational ages ranged from 12–44 weeks. Simultaneous estimations of storage iron were also made on the spleen and kidney in 70 and 69 of these foetuses respectively. Although the concentration of iron per g wet tissue in these organs remained practically the same at all gestations, the total storage iron content increased with the increase in gestation due to growth of these organs. The liver, in particular, showed a steep rise in total iron content in the last 8 weeks of gestation. There was a significant positive correlation between the total storage iron content in the foetal organs and the birth weight and gestational age of the foetus, suggesting that the preterm infants had smaller iron stores at birth as compared to infants born at term. The direct relation of the concentration as well as the total content of storage iron in the foetal liver with the maternal plasma iron levels suggested that babies born to iron deficient mothers had poor iron stores in their livers.     

Iron supplementation of breast-fed Honduran and Swedish infants from 4 to 9 months of age

OBJECTIVE: The objective was to study the effects of iron supplementation on hemoglobin and iron status in 2 different populations. Study design: In a randomized, placebo-controlled, masked clinical trial, we assigned term Swedish (n = 101) and Honduran (n = 131) infants to 3 groups at 4 months of age: (1) iron supplements, 1 mg/kg/d, from 4 to 9 months, (2) placebo, 4 to 6 months and iron, 6 to 9 months, and (3) placebo, 4 to 9 months. All infants were breast-fed exclusively to 6 months and partially to 9 months. RESULTS: From 4 to 6 months, the effect of iron (group 1 vs 2 + 3) was significant and similar in both populations for hemoglobin, ferritin, and zinc protoporphyrin. From 6 to 9 months, the effect (group 2 vs group 3) was significant and similar at both sites for all iron status variables except hemoglobin, for which there was a significant effect only in Honduras. In Honduras, the prevalence of iron deficiency anemia at 9 months was 29% in the placebo group and 9% in the supplemented groups. In Sweden, iron supplements caused no reduction in the already low prevalence of iron deficiency anemia at 9 months (<3%). CONCLUSION: Iron supplementation from 4 to 9 months or 6 to 9 months significantly reduced iron deficiency anemia in Honduran breast-fed infants. The unexpected hemoglobin response at 4 to 6 months in both populations suggests that regulation of hemoglobin synthesis is immature at this age.     

A randomized trial of two levels of iron supplementation and developmental outcome in low birth weight infants

OBJECTIVES: To investigate the effect of increased iron intakes on hematologic status and cognition in low birth weight infants. STUDY DESIGN: We randomly assigned 58 infants to receive formula with 13.4 mg iron/L (normal iron) or 20.7 mg iron/L (high iron). At baseline, discharge, and at 3, 6, 9, and 12 months' corrected age, we assessed anthropometry; infections; red blood cell hemoglobin, catalase, glutathione peroxidase, red blood cell fragility (hydrogen peroxide test), and superoxide dismutase values; plasma malondialdehyde, ferritin, iron, transferrin, zinc and copper levels; and diet intake. Griffiths' Development Assessment was done at 3, 6, 9, and 12 months only. RESULTS: No statistical differences (P <.05) were noted for weight, catalase or malondialdehyde levels, red blood cell fragility, or Griffith's Development Assessment. Iron intakes were greater in the high iron group except at 12 months. Hemoglobin (high iron, 123 +/- 9; normal iron, 118 +/- 8) was not different at 3 months (P =.07). Plasma zinc levels (high iron, 70 +/- 14; normal iron, 89 +/- 27) and copper levels (high iron, 115 +/- 26; normal iron, 132 +/- 27; P =.06) at 12 months suggested inhibition of absorption by high iron formula. Glutathione peroxidase levels were higher in the high iron group. The total number of respiratory tract infections was greater in the high iron group (3.3 +/- 0.9) than in the normal iron group (2.5 +/- 0.9). CONCLUSION: In terms of cognitive outcome, there is no advantage associated with elevated iron intake for low birth weight 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 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.     

IRON ABSORPTION FROM INFANT MILK FORMULA AND THE OPTIMAL LEVEL OF IRON SUPPLEMENTATION

Abstract. Thirty healthy infants, aged 11–13 months, were studied with regard to the iron absorption from proprietary milk formula. The infants were divided into three groups (I-III) depending on the concentration of iron in the formula: 0.8 (I), 6.8 (II), and 12.8 (III) mg/1, respectively. The calculated amount of iron absorbed per test dose of SO ml of milk averaged 5 μg (I), 32 μg (II), and 43 μg (III). Group I differed significantly from groups II and III. No correlation was found between iron absorption and hemoglobin, MCV, serum transferrin saturation or serum ferritin within the range of normal values. Our findings suggest that at least 7 mg of iron as ferrous sulphate per litre of formula is required to prevent iron deficiency.     

Home oxygen therapy for chronic lung disease in extremely low-birth-weight infants

Chronic lung disease that requires prolonged oxygen therapy commonly complicates the recovery of extremely low-birth-weight infants (less than 1000 g). We report follow-up data through 18.5 +/- 0.9 (mean +/- SEM) months of age in 30 extremely low-birth-weight infants (birth weight, 783 +/- 24 g; gestational age, 26.0 +/- 0.3 weeks) who were discharged home receiving supplemental oxygen. Oxygen was prescribed to maintain arterial oxygen saturation at 95% or greater. At discharge, postconceptional age was 40.5 +/- 0.6 weeks, and weight was 2220 +/- 50 g. Duration of home oxygen therapy was 4.5 +/- 0.5 months. The mean weight percentile increased from less than 5 to 23 between discharge and the last follow-up. All infants survived; only 6 required hospitalization for acute medical illnesses. We conclude that carefully supervised home oxygen therapy permits the safe early discharge of selected extremely low-birth-weight infants with chronic lung disease.     

提高缺铁动物对铁补充效应的实验研究

用大鼠血红蛋白恢复试验及铁补充与整体铁存留直线回归分析研究了缺铁大鼠每３日或每日连续补铁的生物利用效率。首先，用无铁基础饲料复制大鼠的缺铁性贫血（ＩＤＡ）模型，然后分别进行两周每间隔３日或每日连续补铁（８ｍｇ）试验。以０．８ｍｇ／日铁喂饲建立铁正常大鼠为对照。结果：铁正常对照，ＩＤＡ每３日或每日补铁三组大鼠血红蛋白转换效率分别为９．２１％，６．９％及２．８％，后两组相对生物利用率（ＲＢＡ）为７４．９％及３１．６％。铁补充与动物整体铁存留直线回归分析显示整体动物的ＲＢＡ分别为４２．８％及１７．７％。两种铁补充效应的评价均表明，每３日间隔补铁的ＲＢＡ为每日连续补铁的２．４倍，血液、骨骼等组织器官的铁生物利用为１．８～１．９倍。     

Dietary fluoride intake of infants.

The fluoride content of various commercially available food items used in the preparation of the infant diet for the age groups from birth to 6 months has been analyzed and the total daily fluoride intake has been calculated on the basis of these data. The dietary fluoride intake totaled 0.32 mg/day for infants in the age group 1 to 4 weeks, increased in the subsequent months due to increasing food intake, and totaled 1.23 mg for infants 4 to 6 months of age. These fluoride intakes expressed per kilogram of body weight ranged from 0.07 mg/kg in the newborn to 0.16 mg/kg in the 6-month-old infant.     

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.     

Nutritional iron status of infants fed according to current recommendations

We examined the iron nutritional status of healthy term infants in a longitudinal study from 15 through 365 days of age. All infants were fed according to the present austrian recommendations. Serum hemoglobin (Hb) decreased from 15 through 122 days of age and remained constant thereafter. At 365 days of age, only 4.7% of the infants had hemoglobin levels below 11 g/dl, which is considered the borderline value for anemia. Mean corpuscular volume (MCV) of erythrocytes was changing during infancy. Free erythrocyte protoporphyrin (FEP) was constant from 122 days through 365 days of age. The upper normal value of 3 micrograms/gHb for infants older than 122 days of age corresponded to that for children older than one year and adults. Serum ferritin (SF) decreased from 15 through 183 days of age and remained constant thereafter. At 365 days of age, only 9.3% of the infants had SF below 10 micrograms/l, which is considered the borderline concentration for depletion of iron stores. We found no differences of iron nutritional status between infants who were breastfed longer than 122 days and infants who were breastfed shorter than 122 days or were fed formula. Our findings indicate that the prevalence of iron deficiency anemia and depletion of the iron stores is lower than in previous studies. Changes in infant nutrition during the last years resulted in higher iron intake and lower prevalence of iron deficiency.     

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.     

Iron absorption in infants: high bioavailability of breast milk iron as indicated by the extrinsic tag method of iron absorption and by the concentration of serum ferritin

Breast feeding is thought to result in a lower incidence of iron deficiency than does the use of unfortified cow milk forumalas, but there is scant documentation for this belief. The relationship of breast and cow milk feeding to absorption of iron and to iron status was investigated in a total of 45 term infants at about six months of age. Iron absorption was measured by total body counting. Laboratory assessment of iron status was based on the serum ferritin, hemoglobin, mean corpuscular volume, and transferrin saturation. The results indicated that infants fed breast milk during the entire first six to seven months of life attained greater iron stores than did those fed a cow milk formula. Breast-fed infants absorbed an average of 49% of a trace dose of extrinsic iron administered during a breast feeding in contrast to about 10% reported to be absorbed from cow milk under similar conditions. The data indicate that term infants who are breast fed may not require routine administration of supplemental iron.