Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age)

This clinical report covers diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants (both breastfed and formula fed) and toddlers from birth through 3 years of age. Results of recent basic research support the concerns that iron-deficiency anemia and iron deficiency without anemia during infancy and childhood can have long-lasting detrimental effects on neurodevelopment. Therefore, pediatricians and other health care providers should strive to eliminate iron deficiency and iron-deficiency anemia. Appropriate iron intakes for infants and toddlers as well as methods for screening for iron deficiency and iron-deficiency anemia are presented.     

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 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.     

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.     

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

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

Iron and breastfeeding

Given the importance of iron nutrition during the first year of life, there are surprisingly few true, randomized, controlled studies addressing this issue; however, it seems that iron deficiency is unlikely in full-term, breastfed infants during the first 6 months of life because these infants' body iron stores are sufficient to meet requirements. After this time, many infants exhaust their iron stores and become dependent on a secondary dietary iron supply. Although iron deficiency is a significant nutritional problem worldwide, most of the adverse effects of iron deficiency in this age group are hypothetical and rely on extrapolation from animal studies or studies at different ages. This, however, also is true of most of the adverse effects of iron excess in this age group. Given this uncertainty, it seems prudent to use the lowest dose of iron that prevents iron-deficiency anemia. Currently, the best evidence is that this is achieved by prolonged breastfeeding, avoidance of unfortified formulas and cow's milk, and the introduction of iron-fortified and vitamin C-fortified weaning foods at approximately 6 months of age. Despite much research, there are many areas of uncertainty regarding iron supplementation of infants, including that: 1. The optimal age for introducing iron-fortified supplemental foods is poorly defined and should be further evaluated. 2. The natural history of iron deficiency and iron-deficiency anemia during the first year of life is unclear, as are the possible long-term effects of this, especially on developmental outcome. 3. The biologic variability among infants and among their mothers that allows many infants who do not receive iron-fortified foods to prevent iron deficiency while receiving only human milk throughout the first year of life is intriguing and warrants additional study. 4. The iron requirements of small-for-gestational-age, term infants are unknown. Their iron requirements are likely to be higher than those of average term infants, but whether iron supplements are required is unclear. 5. The optimum amount of dietary iron in the weaning diet needs to be further defined. Similarly, the optimal source and amount of iron in infant formulas given to infants who receive a mixture of human milk and formula is unclear.     

Iron deficiency anemia: adverse effects on infant psychomotor development

In a double-blind, placebo-control prospective cohort study of 196 infants from birth to 15 months of age, assessment was made at 12 months of age of the relationship between iron status and psychomotor development, the effect of a short-term (10-day) trial of oral iron vs placebo, and the effect of long-term (3 months) oral iron therapy. Development was assessed with the mental and psychomotor indices and the infant behavior record of the Bayley Scales of Infant Development in 39 anemic, 30 control, and 127 nonanemic iron-deficient children. Anemic infants had significantly lower Mental and Psychomotor Developmental Index scores than control infants or nonanemic iron-deficient infants (one-way analysis of variance, P less than .0001). Control infants and nonanemic iron-deficient infants performed comparably. No difference was noted between the effect of oral administration of iron or placebo after 10 days or after 3 months of iron therapy. Among anemic infants a hemoglobin concentration less than 10.5 g/dL and duration of anemia of greater than 3 months were correlated with significantly lower motor and mental scores (P less than .05). Anemic infants failed specifically in language capabilities and body balance-coordination skills when compared with controls. These results, in a design in which intervening variables were closely controlled, suggest that when iron deficiency progresses to anemia, but not before, adverse influences in the performance of developmental tests appear and persist for at least 3 months despite correction of anemia with iron therapy. If these impairments prove to be long standing, prevention of iron deficiency anemia in early infancy becomes the only way to avoid them.     

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.     

Cow milk feeding in infancy: further observations on blood loss from the gastrointestinal tract

Because feeding of cow milk causes normal infants to lose increased amounts of occult blood from the gastrointestinal tract, we conducted a prospective trial to measure intestinal blood loss quantitatively and to monitor iron nutritional status. Fifty-two infants entered the trial at 168 days of age and were assigned at random to receive either cow milk or a milk-based formula. Initially, 31 infants had been breast-fed and 21 had been fed formulas. With the feeding of cow milk, the proportion of guaiac-positive stools increased from 3.0% at baseline to 30.3% during the first 28 days of the trial (p less than 0.01), whereas the proportion of positive stools remained low (5.0%) with the feeding of formula. The proportion of guaiac-positive stools among cow milk-fed infants declined later, but for the entire trial it remained significantly (p less than 0.01) elevated. Stool hemoglobin concentration increased markedly with the introduction of cow milk, rising from a mean (+/- SD) of 622 +/- 527 micrograms/gm dry stool at baseline to 3598 +/- 10,479 micrograms/gm dry stool during the first 28 days of ingestion of cow milk. Among infants fed formula, stool hemoglobin did not increase and was significantly (p less than 0.01) less than in the cow milk group. Among infants fed cow milk, the increase in hemoglobin concentration tended to be greater for those who had initially been fed human milk than for those who had initially been fed formulas. Iron nutritional status was not significantly different between the two feeding groups. However, one infant became iron deficient after 4 weeks of ingesting cow milk. We conclude that cow milk feeding leads to increased intestinal tract blood loss in a large proportion of normal infants and that the amount of iron lost is nutritionally important.     

Anemia and iron deficiency among schoolchildren in the Aral Sea region,Kazakhstan

The objectives of this study were to estimate the prevalence of anemia and iron deficiency among schoolchildren in the Aral Sea region of Kazakhstan and to determine the various factors associated with anemia in this population. We conducted a cross-sectional study of randomly selected schoolchildren. Blood samples were collected for measuring hemoglobin (Hb), serum ferritin (SF), total iron binding capacity (TIBC), and other hematological indices, and subjects were screened for anemia and iron deficiency. Associations between Hb concentration and SF, TIBC, anthropometric, and socioeconomic data were evaluated using regression analysis. The prevalence of anemia was 49.8 per cent although levels were mostly mild. Twenty-two per cent of the children were iron depleted (SF < 12 microg/l). Of the anemic children, 32.4 per cent were found to have iron deficiency anemia (anemia with SF < 12 microg/l). There were significant positive correlations between the levels of Hb and SF, but a negative correlation with serum TIBC. Age, mean corpuscular volume (MCV) and SF were found to be significantly related to Hb by stepwise multiple regression analysis. Multiple logistic regression analysis revealed that anemia was independently related to living district, education of father, and child's age. The results suggest that iron deficiency is an important determinant of anemia in this population; however, whole anemia cannot be solely explained by iron deficiency. Further studies are needed for consideration of micronutrients status, parasite infestation, hereditary disorders, and exposure to environmental pollutants.     

IRON RELEASE FROM THE STORES: A MECHANISM IN MAINTENANCE OF CONCENTRATION OF HEMOGLOBIN IN LOW-BIRTH-WEIGHT INFANTS

Abstract. Lundström, U. (Pediatric Hematology, Children's Hospital, University of Helsinki, Findland). Iron release from the stores: A mechanism in maintenance of concentration of hemoglobin in low-birth-weight infants. Acta Paediatr Scand, 69: 249, 1980.—After the resuming of the postnatal red cell production at two months of age infants are dependant on storage iron due to the great need for iron at a time when the iron content of the diet is low. This is even further accentuated in low-birth-weight infants. In this study the release of storage iron in the hemoglobin pool. During the two month period from two to four months of age at least 20 mg of iron per month was transferred from the storage sites for hemoglobin production. This amount represents 5 mg per kg of body weight and exceeds the rate iron was mobilized from storage sites in an adult male under experimental conditions. Rapid weight gain was associated with early depletion of iron stores. However, residual iron stores in infants with the slowest growth rate could not maintain the level of hemoglobin achieved in iron-supplemented low-birth-weight infants. These findings suggest that in rapidly growing low-birth-weight infants the need of iron for erythropoiesis is so great that iron deficient erythropoiesis may develop in the presence of iron stores if the diet is not supplemented with iron.     

Iron status and infant feeding practices in an urban ambulatory center

The relationship of infant feeding practices to iron status was examined in a group of 280 infants, 9 to 12 months of age, attending a "well-baby" clinic. Of this group, 7.6% were found to be iron depleted, 19.7% were iron deficient without anemia, and 8.2% were iron deficient with anemia. The incidence of iron-deficiency anemia was significantly greater in the black infants than the white infants (14.3% v 2.7%). The introduction of whole cow's milk into the diet had occurred prior to 6 months of age in 29.2% of the infants, and 62.1% of these infants had laboratory evidence of nutritional iron inadequacy, as contrasted with only 21.8% of those with iron deficiencies fed cow's milk after 6 months of age. Of the 21 infants with iron-deficiency anemia, 19 (90.5%) had been fed whole cow's milk prior to 6 months of age. Iron deficiency remains a nutritional problem for infants in an urban setting and is largely a result of the early introduction of whole cow's milk into the diet.     

福建省儿童铁缺乏症流行病学调查报告

目的 　了解我省儿童铁营养的现状 ,为使儿童缺铁性贫血的患病率在 2 0 0 0年的基础上下降 1 / 3掌握基数。方法 　在全省范围分三个层次九个流调点对 2 584名儿童作Hb(血红蛋白 )、ZPP(锌原卟啉 )及SF(血清铁蛋白 )的测定。结果 　我省儿童总的铁缺乏症发生率 37 2 3% ;铁减少发生率 2 2 87% ;缺铁性贫血发生率 1 4 36 %。结论 　铁缺乏、铁减少及缺铁性贫血的发生率 ,与饮食的合理性有密切关系。     

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.     

Interaction of iron deficiency and lead and the hematologic findings in children with severe lead poisoning

Microcytic anemia, long considered an effect of lead poisoning, may in fact result from coexisting iron deficiency. In this study, how RBC size, hemoglobin, and zinc protoporphyrin vary as a function of iron status in a group of children with high lead levels was examined. Charts of all children (N = 51) admitted to Cook County Hospital for treatment of lead poisoning in 1981 to 1983 were reviewed for data on age, blood lead level, hemoglobin concentration, MCV, transferrin saturation and zinc protoporphyrin level. The mean lead level was 86 micrograms/dL and the range was 63 to 190 micrograms/dL. Children with transferrin saturation values less than 7% had a mean MCV of 56 microL, hemoglobin of 8.9 g/dL, and zinc protoporphyrin of 693 micrograms/dL; for those with saturations of 7% to 16%, the values were 61 microL, 10.1 g/dL, and 581 micrograms/dL, respectively; the children with saturations greater than 16% had normal mean MCVs and hemoglobin concentrations (74 microL and 11.4 g/dL) and a mean zinc protoporphyrin value of 240 micrograms/dL (P less than .0005). Multiple linear regression was used to correct for effect of age, and transferrin saturation remained the most important predictor of MCV, hemoglobin, and zinc protoporphyrin levels; the addition of lead did not improve the models. Results of this study suggest that iron deficiency is strongly associated with some of the observed toxicities of lead. Also, lead poisoning can exist without producing microcytosis or anemia, and zinc protoporphyrin concentration may not be a sensitive indicator of lead level in the absence of iron deficiency.     

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 of adolescent females in three schools in an urban area of Sri Lanka

Ninety-three females in the age group 14-18 years were randomly selected from three schools in Colombo. Their iron and nutritional status was assessed using clinical, anthropometric, haematological, and biochemical parameters. Haemoglobin levels less than 12 g/dl were seen in 3.7 per cent of adolescent females. Free erythrocyte protoporphyrin levels greater than 70 micrograms/dl and serum percentage transferrin saturation values less than 16 per cent indicate iron deficiency and were seen in 10 per cent and 14 per cent of the subjects, respectively. Serum ferritin levels less than 12 micrograms/l indicate depleted iron stores and were seen in 59 per cent of the subjects studied. Our results suggest that although overt anaemia was not common among the subjects studied, a large number of subjects belonging to the lower socio-economic groups were in the early stages of iron deficiency and had depleted iron stores. These subjects are, therefore, at risk of developing clinical manifestations of iron deficiency when the demand for iron is increased, as in pregnancy.     

��֯��ϸ��ƽ��Ѫ�쵰�����������С��ȱ����ƶѪ�е���ϼ�ֵ

目的探讨网织红细胞平均血红蛋白质量在小儿缺铁性贫血中的诊断价值。方法采用拜耳ADVIA120全自动血液分析仪检测50名健康儿童和59例临床诊断为缺铁性贫血患儿的外周血细胞和网织红细胞血红蛋白质量,同时用BeckmanCx9测定血清铁蛋白质量浓度,将所得数据进行统计学分析。结果血红蛋白(Hb)、平均红细胞体积(MCV)、单个网织红细胞平均血红蛋白(CHr)质量、血清铁蛋白(SF)在缺铁性贫血患儿明显低于健康儿童,而平均红细胞体积分布宽度(RDW)在缺铁性贫血患儿明显高于健康儿童。结论CHr质量作为诊断儿童缺铁性贫血的指标,具有重要的临床价值。     

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.     

Perinatal aspects of iron metabolism

Iron sufficiency is critical for rapidly developing fetal and neonatal organ systems. The majority of iron in the third trimester fetus and the neonate is found in the red cell mass (as hemoglobin), with lesser amounts in the tissues as storage iron (e.g. ferritin) or functional iron (e.g. myoglobin, cytochromes). Iron is prioritized to hemoglobin synthesis in red cells when iron supply does not meet iron demand. Thus, non-heme tissues such as the skeletal muscle, heart and brain will become iron deficient before signs of iron-deficiency anemia. Gestational conditions that result in lower newborn iron stores include severe maternal iron deficiency, maternal hypertension with intrauterine growth retardation and maternal diabetes mellitus. Stable, very low birthweight premature infants are also at risk for early postnatal iron deficiency because they accrete less iron during gestation, grow more rapidly postnatally, are typically undertreated with enteral iron and receive fewer red cell transfusions. Conversely, iron overload remains a significant concern in multiply transfused sick preterm infants because they have low levels of iron-binding proteins and immature antioxidant systems. CONCLUSION: The highly variable iron status of preterm infants combined with their risk for iron deficiency and toxicity warrants careful monitoring and support in the newborn and postdischarge periods.