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.     

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     

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 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.     

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.     

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 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.     

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.     

Red blood cell indices and iron status according to feeding practices in infants and young children

With the electronic counters routinely used, it has become practical to determine the concentration of hemoglobin, red cell indices, and RDW concurrently in association with transferrin saturation and ferritin in accordance with feeding practices. The 1028 infants and children aged 6 to 24 months, who had been mainly admitted with acute infectious or inflammatory diseases, were divided into three groups, i.e., children who were exclusively breast-fed more than 6 months (group A), those who had been given iron-fortified formula milk since birth (group B), and those who had been given breast milk for 5–6 months and then switched to the iron-fortified formula (group C). Children with anemia comprised 34.8% (104/299) of group A, significantly more than 5.6% (34/608) of group B and 6.6% (8,/121) of group C ( p < 0.001, respectively). Children with MCV < 70 fl comprised 39.5% (118/299) of group A, significantly more than 7.1% (43/608) of group B and 13.2% (16/121) of group C. Out of the total 146 patients with anemia, 82.2% ( n = 120) had laboratory evidence of iron deficiency, which was mostly suggested by a dietery history. The sensitivity of MCV values < 70 fl in IDA patients was 90.0%; specificity was 53.8%. The sensitivity of RDW values ≥ 15% was 83.3%; specificity was 57.7%. The positive predictive value could be increased to 97.8% by combining MCV < 70 fl and RDW ≥ 15%. The sensitivity of serum ferritin concentrations < 10ng/ml was 62.4% and specificity was 100%. The sensitivity of transferrin saturation < 12% was 72.3% and specificity was 81.3%. By combining the hemoglobin with MCV and RDW in screening for iron deficiency, the diagnostic accuracy of IDA can be increased. We support the use of appropriately iron-fortified weaning foods or the routine iron supplement starting at 6 months of age in exclusively breast-fed infants.     

Folate nutrition is optimal in exclusively breast-fed infants but inadequate in some of their mothers and in formula-fed infants

Plasma concentrations of folate were studied in a group of exclusively breast-fed infants and their mothers (their numbers gradually decreased from 200 at birth to 7 at 12 months) and in infants completely weaned to a cow's milk formula (containing 35 micrograms of folate/L) and solid foods. The exclusively breast-fed infants were in no danger of folate deficiency; their plasma levels were elevated after the age of 2 months and, on average, were 2.0-3.3-fold higher than maternal levels throughout the study. None of these infants had an inadequate plasma concentration, whereas up to 5% of the mothers had values less than or equal to 3 micrograms/L, despite supplementation during lactation with 0.1 mg folate/day. In the formula-fed infants, 69-94% of the plasma folate concentrations lay below the lowest concentration for the breast-fed infants. Although no infant had signs of anemia or macrocytosis in red cell indices, the infants weaned earliest had the lowest hemoglobin concentrations (p = 0.09) and the highest mean corpuscular volume (MCV) values (p = 0.06) at 9 months of age. Thus, an infant fed a formula containing the recommended amount of folate runs a risk of folate deficiency.     

Iron polymaltose versus ferrous gluconate in the prevention of iron deficiency anemia of infancy

We prospectively compared the efficacy and safety of iron deficiency anemia prophylaxis with iron gluconate (IG) or iron polymaltose complex (IPC) in healthy infants attending a community pediatric center. Participants were randomly assigned to receive one of the test drugs from age 4 to 6 months to age 12 months. Parents/guardians were given extensive information on iron-rich diets and anemia prevention. Main outcome measures were blood levels of hemoglobin, hematocrit, mean corpuscular volume, red blood cell distribution width, and serum iron, ferritin, and transferrin, in addition to adverse effects. One hundred five children completed the study: 53 in the IG group and 52 in the IPC group Mean hemoglobin levels at study end were significantly higher in the IG group (12.04±0.09 g/dL vs. 11.68±0.11, P<0.014). A hemoglobin level <11 g/dL was detected in 3 infants of the IG group, and in 10 infants of the IPC group (P<0.04). Adverse effects (spitting, vomiting, diarrhea, constipation, discolored teeth) were significantly more common in the IG group (47% vs. 25%, P>0.025). In conclusion, both oral IG and IPC prevent iron deficiency anemia in infants. Iron gluconate seems to be more effective but less tolerable.     

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.     

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.     

Relationship of maternal and newborn (cord) serum ferritin concentrations measured by immunoradiometry

Serum ferritin concentration was determined by immunoradiometry in venous blood samples of 45 pregnant women at term, in their babies' cord blood samples, and blood specimens obtained from 43 infants aged 3-12 months. The concentration of ferritin was higher in cord serum than in respective maternal samples and infant specimens. Low values were found in more than half of the maternal venous samples. Iron stores of newborns delivered by mothers with low serum ferritin concentration were lower than in newborns of mothers having normal ferritin levels. Serum ferritin measurement is a sensitive method to determine iron deficiency in pregnancy.     

Fetal iron status in maternal anemia

Hemoglobin, serum iron, transferrin saturation and ferritin were measured on paired maternal and cord blood samples in 54 anemic (hemoglobin < 110 g/L) and 22 non-anemic (hemoglobin ≥ 110 g/L) pregnant women at term gestation. The levels of hemoglobin, serum iron, transferrin saturation and ferritin were significantly low in the cord blood of anemic women, suggesting that iron supply to the fetus was reduced in maternal anemia. The linear relationships of these parameters with both maternal hemoglobin and maternal serum ferritin indicated that the fetus extracted iron in amounts proportional to the levels available in the mother. Infants of mothers with moderate and severe anemia had significantly lower cord serum ferritin levels and hence poor iron stores at birth. It is concluded that iron deficiency anemia during pregnancy adversely affects the iron endowment of the infant at birth.     

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.     

Lack of correlation between free erythrocyte porphyrin and serum ferritin values at birth and at 2 months of life in low birthweight infants

Red cell free erythrocyte porphyrin and serum ferritin determinations were performed on capillary blood specimens from 63 healthy infants weighing 2500 g or less at birth, during the first week of life, and, from 44 of them, again at 8-10 weeks. Free erythrocyte porphyrin values were high both at 3-7 days (mean 156 microgram/100 ml RBC) and at 8-10 weeks (mean 128 microgram/100 ml RBC). The respective serum ferritin values were also high (mean 226 and 107 ng/ml), excluding a depletion in iron stores. In addition, no correlation was found between free erythrocyte porphyrin and serum ferritin values either at birth or at age 2 months. These findings are consistent with an earlier hypothesis that in the presence of iron stores, the rate of iron release from the stores in low birthweight infants may not be sufficient to maintain optimal erythropoiesis if the demand is accelerated.     

Lack of correlation between free erythrocyte porphyrin and serum ferritin values at birth and at 2 months of life in low birthweight infants.

Red cell free erythrocyte porphyrin and serum ferritin determinations were performed on capillary blood specimens from 63 healthy infants weighing 2500 g or less at birth, during the first week of life, and, from 44 of them, again at 8-10 weeks. Free erythrocyte porphyrin values were high both at 3-7 days (mean 156 microgram/100 ml RBC) and at 8-10 weeks (mean 128 microgram/100 ml RBC). The respective serum ferritin values were also high (mean 226 and 107 ng/ml), excluding a depletion in iron stores. In addition, no correlation was found between free erythrocyte porphyrin and serum ferritin values either at birth or at age 2 months. These findings are consistent with an earlier hypothesis that in the presence of iron stores, the rate of iron release from the stores in low birthweight infants may not be sufficient to maintain optimal erythropoiesis if the demand is accelerated.     

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.     

Levels of serum ferritin and total body iron among infants with different feeding regimens

The levels of serum ferritin and total body iron of healthy infants were analyzed to evaluate iron status among infants with different feeding regimens. The results showed that the levels of serum ferritin and total body iron were lower in breast-fed infants than in partially breast-fed or formula-fed infants at late infancy and 18 months of age.