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.     

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 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.     

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.     

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 exclusively breast-fed infants.

The aim of this study is to evaluate the iron nutritional status of infants breast-fed exclusively and for a prolonged period in relation to their growth rate and dietary changes. Forty subjects (25 breast-fed; 15 formula-fed) were studied from 0 to 9 months of age. Milk (human or formula) was the only source of food during the first 6 months. From the sixth month onward mothers were instructed to use iron- and ascorbic acid-rich foods to supplement breast-feeding. At the ninth month, prevalence of anemia was 27.8% in the breast-fed group and 7.1% in the formula-fed group. Storage iron was absent in 27.8% of the breast-fed infants vs none of the formula-fed infants. These findings reinforce the recommendation that breast-fed infants be given supplemental iron from the fourth month of life.     

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.     

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.     

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.     

Exclusively breast-fed healthy infants grow slower than reference infants

We have studied the nutritional adequacy of exclusive breast-feeding by following prospectively the growth and protein nutrition of healthy infants during the 1st yr of life. The number of exclusively breast-fed infants was 116 at the age of 6 months and 36 at 9 months. These infants had slower length velocity after age 3 months than a comparison group of 32 infants who were weaned early and given formula plus solids. As a group, the exclusively breast-fed infants lagged slightly, but progressively, behind in relative length. By 9 months, 45% of them versus 18% of the comparison group showed a greater than 1 SD decrease in relative length. No such decrease was found in relative weight. Skinfolds and weight for length index showed that they were heavier for their length than the comparison infants. At 6 and 9 months the calculated protein intake (0.9 g/kg/day) was much less than the recommended amount (2.0 g/kg/day). Serum prealbumin concentration was lower than in the comparison group but this was noted as early as 4 months. No relation was found between the parameters of growth and protein nutrition either individually or in general. Whether the slower growth of the exclusively breast-fed infants represents appropriate physiological growth or whether it indicates nutritional deficiency is not known but we did not find any evidence of protein deficiency. Six infants did, however, show subsequent catch-up growth which could indicate previous malnutrition.     

Iron status in the first year of life

The iron status of babies of different race born at term to mothers in an inner city area was studied at birth and during the first year of life and related to maternal iron status. Haemoglobin and ferritin were measured in the mother at term (n = 81) and in the baby in cord blood (n = 81), at 6 months (n = 55), and at 1 year (n = 51). No relationship was found between the iron status of mothers and their babies at birth. However, iron stores at birth did affect later iron status, cord ferritin being significantly related to ferritin at 6 months (r = 0.42, p less than 0.01) and 1 year (r = 0.55, p less than 0.01) but not to haemoglobin at these ages. No relationship was found between haemoglobin iron at birth and subsequent iron status. Introduction of full cow's milk before the age of 6 months was associated with iron deficiency at this age and at 1 year. By the age of 1 year, iron deficiency was also associated with feeding greater than 900 ml whole cow's milk a day, inadequate feeding with solids, and higher weight gain. No stool parasites were found at the age of 1 year, and the presence of occult blood in stools did not significantly affect iron status at this age. At 1 year of age, 49% of these infants had low iron stores, including 20% with iron deficiency anaemia. Considerable improvement could result from simple changes in dietary practices.     

Iron status of preterm low birthweight infants and their response to oral iron

The iron status of a group of preterm low birthweight infants preventively treated with oral iron has been studied by measuring haemoglobin concentration, serum iron concentration, and total iron binding capacity (TIBC) at intervals from birth to 9 months. 47 infants born at an average gestational age of 34 weeks, with a mean birthweight of 1517 g, were investigated. They received 180 mg ferrous sulphate (= 36·3 mg Fe) daily from the fifth week and throughout the study. At 3 months of age most of the infants had low serum iron concentration and increased TIBC indicative of iron deficiency, and over half of them had iron deficiency anaemia (Hb <11 g/100 ml). At 6 and 9 months of age the mean Hb increased slightly, but mean serum iron concentrations remained low, and mean TIBC increased to over 500 μg/100 ml. It is not clear why the amount of iron, administered orally, was insufficient to prevent iron deficiency in almost all the infants, and iron deficiency anaemia in nearly half of the infants studied.     

Prevalence of iron deficiency in Saudi children from birth to 15 months of age

A cross-sectional study was carried out to determine the prevalence of iron deficiency among healthy Saudi children from birth to 15 months of age. The groups studied were: newborns, 3-4 months, 5-6 months, 7-8 months, 9-10 months and 12-15 months of age. The age groups were dictated by the vaccination schedule. Serum ferritin was measured and transferrin saturation calculated in each subject. The lower limits of normal were taken as a transferrin saturation of less than 10% and a serum ferritin of less than 12 micrograms/l. A total of 333 serum samples was adequate for analysis. None of the newborns or the 3-4-month-old infants had evidence of iron deficiency. At 5-6 months only 3.3% of subjects had iron deficiency. In the subsequent older age groups the prevalence of iron deficiency increased significantly with age from 9.3% to 12.7% and reached 14.5% in the oldest age group. Screening for iron deficiency in children attending well-baby clinics and hospitals at ages of 12-15 months is recommended.     

Predicting iron status in low birthweight infants

OBJECTIVE: To determine the iron status of a selected group of low birthweight infants at approximately 9 months of age, and examine the feasibility of predicting iron status by examining the history of supplementary iron intake. METHODS: All live low birthweight infants recorded in the Dunedin Hospital Queen Mary Maternity Unit birth register who reached 9 months of age between November 1995 and September 1996 were eligible to participate. Infants were categorized into 'high' or 'low' iron intake groups depending on their consumption of infant formula or medicinal iron for one month prior to the study, and their iron status compared. RESULTS: Eighty-one infants of 73 mothers, with an average age of 10 months (range 8-13 months), participated. Thirty-three per cent (n = 27) were iron deficient: 19% (n = 15) had latent iron deficiency and 15% (n = 12) had iron deficiency anaemia. Those with a 'low' iron intake were 13-fold more likely to be iron deficient than infants with a 'high' iron intake (95% confidence interval: 4.4-41.5). Screening for iron deficiency using categories based on supplementary iron intake had a positive predictive value of 66% and a negative predictive value of 88%. CONCLUSIONS: The risk of iron deficiency was considerably greater for infants who had not received supplementary iron daily over the course of the previous month. Current preventative methods for avoiding poor iron status in this group of high risk infants are not effective. Screening for iron deficiency in low birthweight infants on the basis of iron intake from infant formula or medicinal iron provides a useful method for identifying infants whose iron status should be investigated.     

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.     

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.     

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.     

Effect of breast feeding on the plasma cholesterol and growth of infants

The effect of breast-feeding on plasma cholesterol, body weight, and body length was studied longitudinally in a large free-living cohort of infants (n = 512) from birth until the age of 1 year. Of the cohort, 21.4% were exclusively breast-fed for at least 3 months, 39.3% received bottle-feeding, and 39.3% received a combination of breast- and bottle-feeding. At birth the plasma cholesterol was similar in the three groups. After 3 months the mean plasma cholesterol and proportion of hypercholesterolemic infants in the breast-fed group were significantly (p less than 0.001) higher than that of the other two groups. These differences had disappeared at the age of 1 year. Breast-fed infants weighed less at 3 and 12 months, but body length was similar to those of the other groups. These results suggest that breast-feeding elevates plasma cholesterol by a direct mechanism and that the effect persists only as long as the breast-feeding is continued.     

Plasma concentrations of vitamin K1 and PIVKA-II in bottle-fed and breast-fed infants with and without vitamin K prophylaxis at birth

Plasma vitamin K₁ and proteins induced by vitamin K absence (PIVKA) were assayed simultaneously 1–4 days and 29–35 days after delivery in three groups of infants: breast-fed not receiving vitamin K at birth (n=12), bottle-fed without vitamin K administration at birth (n=7) and breast-fed receiving 1 mg vitamin K₁ administered by intramuscular injection at birth (n=13). The bottle-fed infants had a significantly higher vitamin K₁ plasma level than breast-fed infants who did not receive vitamin K₁ at birth. Extremely high levels of vitamin K were obtained 1–4 days after intramuscular administration. At the age of 1 month, breast-fed infants had the same plasma vitamin K₁ concentration whether or not they had received vitamin K₁ supplements. Decarboxy prothrombin (PIVKA-II) a reliable indicator of biochemical vitamin K deficiency, was found in 5 out of 12 breast-fed and in 2 out of 6 bottle-fed infants who had not received supplemental vitamin K₁ after birth. In a separate study, we followed up to 90 days after birth a larger group if infants. PIVKA-II was found with significantly greater frequency in breast-fed infants receiving no vitamin K than in breast-fed infants receiving 1 mg vitamin K intramuscularly at birth, or in bottle-fed infants without extra vitamin K₁. These data form a strong argument for routine vitamin K prophylaxis after birth for all breast-fed infants. The optimum dose and manner of administration require further study.Abbreviations PIVKA proteins induced by vitamin K absence - PIVKA-II decarboxy prothrombin - AU arbitrary units