Developmental changes in red blood cell counts and indices of infants after exclusion of iron deficiency by laboratory criteria and continuous iron supplementation

The developmental changes in red blood cell counts and indices were determined in infants after mild iron deficiency was excluded. The normal values were obtained from a selected group of healthy, term infants who were receiving continuous iron supplementation during a period of one year while normal values for transferrin saturation and serum ferritin were being maintained. The data indicated marked developmental changes in red blood cell counts and indices during the first year of life that are independent of iron intake. Serial analysis of individual infant's values indicated that the red cell measurement at 4 months of age are, to some extent, predictive of the level of subsequent values within the normal range.     

Iron status of the preterm infant during the first year of life

The iron status of 49 preterm infants (mean gestational age 33.1 weeks) was assessed serially during the 1st year of life. Haemoglobin concentration, serum ferritin, serum transferrin, serum iron, and transferrin saturation were measured on nine occasions in each infant. In 16 infants of gestational age 28-32 weeks the haemoglobin concentration was significantly lower at 3, 6, and 9 weeks when compared to 33 infants of gestational age 33-36 weeks. For all other measures of iron status there were no significant differences between these gestational age groups. For the entire group of 49 infants the mean haemoglobin concentration reached a nadir of 11.2 g/dl at 9 weeks. Mean serum iron and transferrin saturation reached peaks of 24 mumol/l and 65%, respectively, at 3 weeks. The mean serum ferritin remained over 100 micrograms/l until after 18 weeks. 13 infants (26%) had iron deficiency defined as either serum ferritin less than 10 micrograms/1 (n = 10) or transferrin saturation less than 10% (n = 5) or both (n = 3).     

Impact on iron status of introducing cow's milk in the second six months of life

To determine the impact on iron status of introducing cow's milk (CM) into the diet during the second 6 months of life, nutrient intake was assessed and iron status measured in 100 infants. Nutrient intake for 40 of the 45 infants, age 8 to 13 months, fed CM as the primary beverage for at least 3 months prior to the study and for 45 of 55 infants the same age fed a milk-based infant formula (FF) as the primary beverage for at least 3 months were assessed. All infants in the study were healthy, and the majority were taking no medications or supplements other than vitamins or fluoride for 3 weeks prior to the assessment. Blood drawn by peripheral venipuncture was analyzed by Coulter Counter for complete blood count; plasma albumin, iron, ferritin, transferrin saturation, and total iron-binding capacity were measured in all infants. CM-fed infants had significantly lower mean iron and vitamin C intakes, plasma albumin, transferrin saturation, and ferritin than did FF infants. The frequency of low plasma iron, low transferrin saturation, and low plasma ferritin was significantly greater in CM-fed than in FF infants. The percentage of subjects with three or more abnormal iron indices was more than twice as great in CM-fed infants (58%) as in FF infants (23%). Feeding infants iron-fortified formula to 12 months of age appears to deter iron deficiency.     

PLASMA FERRITIN CONCENTRATIONS IN PRETERM INFANTS IN CORD BLOOD AND DURING THE EARLY ANAEMIA OF PREMATURITY

Abstract. Hågå, P. (Department of Paediatrics and Paediatric Research Institute, National Hospital of Norway, and Department of Paediatrics, Oslo City Hospital, Ullevål, Oslo, Norway). Plasma ferritin concentrations in preterm infants in cord blood and during the early anaemia of prematurity. Acta Paediatr Scand, 69: 637, 1980.—Ferritin concentrations in cord blood were determined in 22 normal term and 32 preterm infants (birth weights 600–2000 g). Eight of the preterms were SGA infants. AGA preterm infants had significantly lower concentrations than term infants, and the SGA preterm newborn had even lower levels. Plasma ferritin in cord blood of the term and AGA preterm infants correlated positively with plasma iron and transferrin saturations, but not with the transferrin level, while plasma iron and transferrin concentrations correlated positively. In a longitudinal study, 17 AGA preterm infants (birth wights 850–1500 g) were followed during the early anaemia of prematurity. Iron was supplemented from 4 weeks of age. Plasma ferritin rose rapidly during the first days after birth, peak levels being reached at 1–4 weeks. Thereafter linear falls (semilog) occurred with similar slopes in different infants. Transferrin concentrations showed a slow progressive increase from 0–8 weeks. Plasma ferritin, after reaching the peak value, correlated negatively with weight gain. No infant had low ferritin values indicating iron deficiency during the early anaemia.     

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.     

Evaluation of iron status in women with pregnancy complicated by tobacco smoking

Relatively common iron deficiency in pregnant women is assumed to be enhanced by cigarette smoking. In the presented studies we determined cotinine in serum and urine of 75 pregnant women in order to select groups of smoking women and tobacco abstinence. In the smoking group, a mean concentration of cotinine 1039 +/- 560 mg/L in serum and 1025 +/- 540 mg/L in urine were observed. For assessment of iron status we determined in serum: iron, iron-binding capacity (TIBC), transferrin, transferrin saturation, soluble transferrin receptor and ferritin. In serum of smoking woman in comparison to non smoking, the level of ferritin and transferrin was higher but non significantly. Significant increase of TIBC (p < 0.05) and decrease of transferrin saturation (p < 0.05) was observed. Therefore iron deficiency in transport compartment can not be excluded. The concentration of soluble transferrin receptor was the same in both groups studied. However, in late pregnancy (above 27 week of gestation) ferritin concentration less than 20 mg/L of serum was observed in 70% of smoking and only in 39% of non smoking women (p < 0.05). We concluded that cigarette smoking during pregnancy did not have any effect on the entry of iron-bearing transferrin to cells mediated by soluble transferrin receptor, but affected the level of iron-storage ferritin, which leads to iron deficiency in the storage compartment (ID I).     

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.     

Iron deficiency in an Eskimo village. The value of serum ferritin in assessing iron nutrition before and after a three-month period of iron supplementation.

The serum ferritin concentration, a new means of assessing iron nutrition, was utilized in conjunction with the hematocrit value, serum iron concentration, and total iron binding capacity to determine the effect of a three-month period of iron supplementation in a group of 146 Eskimo children in Chevak, Alaska. Before treatment, 41% of the children had concentrations of serum ferritin below normal, 18% had a subnormal serum transferrin saturation, and 26% were anemic. After supplementation, only 6% had a subnormal serum ferritin concentration. Despite this evidence of improved iron stores in the group as a whole, the prevalence of low serum transferrin saturation and of anemia remained high, 15% and 17%, respectively. These results could be explained by a high incidence of infection, which, like iron deficiency, is associated with anemia and a low serum transferrin saturation. We conclude that the serum ferritin determination reflected an improvement in iron nutrition that was not as readily apparent by other measurements, and that factors other than iron deficiency also played an important role in the mild anemia that was prevalent in Chevak.     

Need for iron supplementation in infants on prolonged breast feeding

Iron status, as measured by blood counts and indices, serum iron, transferrin saturation, and serum ferritin values, was studied longitudinally in 56 infants on prolonged breast feeding, and compared to that of 29 infants receiving cow milk formula prepared at home and of 47 infants receiving a proprietary infant formula. The first two groups received no iron supplementation, whereas the proprietary formula was supplemented with iron. Although breast feeding was found to be sufficient to meet iron needs during the first 6 months of life, supplemental iron would be necessary during the second half of infancy in order to guarantee the optimal iron status.     

Prevalence of iron deficiency in 12-mo-old infants from 11 European areas and influence of dietary factors on iron status (Euro-Growth study)

A prospective longitudinal cohort study was performed to assess the prevalence of iron deficiency in European infants at 12 mo of age, and to study the influence of socio-economic status, dietary factors, growth and morbidity on iron status. The cohort consisted of 488 normal term infants from primary healthcare centres in 11 European areas. Assessed were socio-economic variables, dietary intake, anthropometry and morbidity at regular intervals from birth to 12 mo, and haemoglobin, serum ferritin, mean corpuscular volume, transferrin saturation and serum transferrin receptor concentrations at age 12 mo. The prevalence of anaemia was 9.4%, of iron deficiency 7.2%, and of iron deficiency anaemia 2.3%. More than 40% of anaemia was associated with normal iron status and associated with an increased frequency of recent infections. Iron deficiency anaemia was significantly more frequent with low (5.1%) than high socio-economic status (0%). Dietary factors accounted for most of this variation in multiple regression analysis. Early introduction of cows' milk was the strongest negative determinant of iron status. Feeding of iron-fortified formula was the main factor positively influencing iron status. Other dietary factors, including breastfeeding, did not play a significant role as determinants of iron status at age 12 mo. Conclusion. Iron deficiency anaemia is present in 2.3% of 12-mo-old European infants. The prevalence of iron deficiency anaemia varies strongly with socio-economic status. Avoidance of cows' milk feeding during the first year of life is the key measure in the prevention of iron deficiency.     

CORD BLOOD HAEMOGLOBIN, IRON AND FERRITIN STATUS IN MATERNAL ANAEMIA

ABSTRACT. Maternal and cord blood haemoglobin, serum iron, transferrin saturation and ferritin were studied in sets of 30 anaemic (haemoglobin <110 g/l) and 21 nonanaemic (haemoglobin ≧110 g/l) mothers. The cord serum iron, transferrin saturation and ferritin concentrations had significant correlation with maternal haemoglobin. The significant low levels of these parameters suggested that maternal anaemia adversely affected the iron status including iron stores of the newborns. The cord serum iron of 15.2±4.35 μmol/l and ferritin of 29.7±10.93 ng/ml seem to be effective to maintain cord haemoglobin levels. Thus, anaemic mothers with reasonably maintained ferritin and trasferrin saturation levels provide sufficient iron for maintenance of cord haemoglobin, although foetal iron stores are likely to be depleted.     

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.     

Comparison of indirect and direct measurement of transferrin in healthy and sick children (author's transl)

In 207 children chemical measurement of total iron binding capacity (TIBC) and direct immunological evaluation of transferrin by radial immunodiffusion were compared. In addition, serum ferritin was measured in nearly all cases, to exclude iron deficiency. In 14 newborns, 20 infants and 35 older children TIBC and transferrin values correlated significantly (p < 0.001), as well as in various disorders (infections, hyporegenerative anemia, beta-thalassemia, acute blood loss) and in prelatent, latent and manifest iron deficiency. Standard deviations of both methods were comparable. Anemia and hyposideremia due to infection could be clearly distinguished from iron deficiency of all stages. The diagnosis of prelatent iron deficiency, however, can be definitely established only by measurement of serum ferritin or other more complicated procedures (59Fe2+-whole body retention test, estimation of diffuse iron in bone marrow macrophages). An interesting finding was the negative significant correlation (r = 0.69) between the two iron binding proteins in serum, transferrin and ferritin. In summary, the simple radial immunodiffusion technique for transferrin with its minimal requirement of serum can be recommended for pediatric routine laboratories in the differential diagnosis of anemia and hyposideremia, before unnecessary iron medication is institued.     

Serum transferrin receptor levels in the evaluation of iron deficiency in the neonate

Iron deficiency anemia (IDA) is a major global problem. Early onset of iron deficiency in developing countries makes it imperative to identify iron deficiency in neonates. Most conventional laboratory parameters of iron status fail to distinguish neonates with iron deficient erythropoiesis. Serum transferrin receptor (STFR) levels are a recent sensitive measure of iron deficiency and the present study was carried out to evaluate the usefulness of cord serum transferrin receptors in identifying iron deficient erythropoiesis in neonates. A complete hemogram, red cell indices, iron profile: serum iron (SI), percent transferrin saturation (TS%) and serum ferritin (SF) was carried out in 100 full-term neonates and their mothers at parturition. Cord and maternal STFR levels were estimated using a sensitive enzyme-linked immunosorbent assay (ELISA) technique. Anemic women had a significantly lower SI, their TS% and high STFR levels suggesting that iron deficiency was responsible for the anemia. In the neonates of iron deficient mothers, cord SI, TS% and cord ferritin were not significantly different from those of neonates born to non-anemic mothers. Cord STFR level correlated well with hemoglobin (Hb) and laboratory parameters of iron status, and its level was significantly higher in neonates born to anemic mothers than in those bom to non-anemic mothers. It was the only laboratory parameter to differentiate between neonates bom to anemic and non-anemic mothers. Therefore, STFR is a sensitive index of iron status in neonates and identifies neonates with iron deficient erythropoiesis.     

Blood transfusion and chronic lung disease in preterm infants

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

The diagnosis of iron deficiency by erythrocyte protoporphyrin and serum ferritin analyses

Free erythrocyte protoporphyrin (FEP) and serum ferritin have been determined in 57 healthy children and in 25 children with varying degrees of iron deficiency. FEP was found to be inversely correlated to the concentration of hemoglobin (r = -0.80) as well as to serum ferritin (r=-0.64). Elevated FEP was found in children with hemoglobin less than 12.5 g/dl, or serum ferritin less than 8 microgram/l. In a group of apparently hematologically normal children between the age of 10--14 years (hemoglobin greater than 12.5 g/dl), a 2-month-trial of iron medication resulted in an increase in hemoglobin and ferritin, and a decrease in FEP, indicating suboptimal supply of iron for hemoglobin synthesis before iron medication. In a patient with iron deficiency (FEP 15.3 mumole/l, hemoglobin 5.2 g/dl), iron therapy was followed by a rapid fall in FEP before any changes in hemoglobin, serum iron transferrin saturation and ferritin could be detected. The rapid fall in FEP during start of treatment in iron deficiency makes FEP a sensitive biochemical parameter on iron homeostasis in iron deficiency anemia.     

Iron deficiency and Pseudomonas aeruginosa colonization in cystic fibrosis

The incidence of iron deficiency and its relationship with the concentration or iron in sputum and the number of Pseudomonas aeruginosa (PA) colonies was studied in an unselected group of 53 cystic fibrosis (CF) patients with an age range of 3 months to 21 years. Parameters used to assess the iron status included serum iron, the % saturation of transferrin (n = 53). The number of subjects with depletion of iron stores was estimated by levels of ferritin (n = 50). The concentration of iron and of PA was measured in a subgroup (n = 24) and compared to a control group (n = 8) with pulmonary infections of varying etiology. A close correlation was found between serum iron and the % saturation of transferrin (r = 0.952; p less than 0.001). Between 22.6 to 28.3% of patients were found to be iron deficient. An abnormally low ferritin (less than 12 ng/ml) was noted in 28% of cases but no correlation could be established between changes of serum iron and ferritin levels as a function of the degree of infection and/or of inflammation. In 62% of cases (n = 15) the concentration of iron in sputum was found to be within the range of control values (12-27 mumols/l). In 38% of cases (n = 9), ferritin values were above 27 mumols/l. No correlation was found between the concentration of iron and the number of PA colonies in sputum. We can therefore conclude the following: 1) iron deficiency is more common in CF than previously reported; 2) ferritin levels constitute a poor index of iron deficiency; 3) colonisation with PA is not associated with iron content of bronchial secretions.     

THE DIAGNOSIS OF IRON DEFICIENCY BY ERYTHROCYTE PROTOPORPHYRIN AND SERUM FERRITIN ANALYSES

ABSTRACT. Free erythrocyte protoporphyrin (FEP) and serum ferritin have been determined in 57 healthy children and in 25 children with varying degrees of iron deficiency. FEP was found to be inversely correlated to the concentration of hemoglobin (r=-0.80) as well as to serum ferritin (r=-0.64). Elevated FEP was found in children with hemoglobin less than 12.5 g/dl, or serum ferritin less than 8 μg/l. In a group of apparently hematologically normal children between the age of 10–14 years (hemoglobin≥ 12.5 g/dl), a 2-month-trial of iron medication resulted in an increase in hemoglobin and ferritin, and a decrease in FEP, indicating suboptimal supply of iron for hemoglobin synthesis before iron medication. In a patient with iron deficiency (FEP 15.3 μmole/l, hemoglobin 5.2 g/dl), iron therapy was followed by a rapid fall in FEP before any changes in hemoglobin, serum iron transferrin saturation and ferritin could be detected. The rapid fall in FEP during start of treatment in iron deficiency makes FEP a sensitive biochemical parameter on iron homeostasis in iron deficiency anemia.     

Blood transfusion and chronic lung disease in preterm infants

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

Anemia of a mild viral infection: the measles vaccine as a model

To define the hematologic changes during a mild viral infection, 93 infants were immunized with live attenuated measles virus and studied prospectively at 0, 4, 9, 14, 21, and 30 days. Hemoglobin concentration decreased significantly by days 9 and 14. The decrease was greater than 1.0 g/dL in 8.6% and greater than 0.6 in 24.3% of the infants. Of the nonanemic infants, 22% became anemic. Serum iron and percentage saturation of transferrin decreased, whereas serum ferritin increased significantly. Mean cell volume, iron-binding capacity, protoporphyrin, and haptoglobin did not show changes. Reticulocyte index and erythropoietin increased significantly at 30 days. Leukocyte counts, Zetacrit, and C-reactive protein did not help to predict the hemoglobin decrease. These results suggest that a mild viral infection in infants induces a significant decrease in hemoglobin that may persist for 14 to 30 days and may be difficult to distinguish from iron deficiency.