Measurement of reticulocyte hemoglobin content to diagnose iron deficiency in Saudi children

Iron deficiency and iron deficiency anemia are common conditions in children, especially in developing countries. It is often difficult for the pediatrician to know which indices should be used in the diagnosis of these conditions in children. Reticulocyte hemoglobin (Hb) content (CHr) has been shown to be an accurate indicator of anemia, however whether its use suits the situation in developing countries or not is unclear. The aim of this study was to evaluate the value and effectiveness of using CHr as a method to diagnose iron deficiency and iron deficiency anemia in Saudi children. The samples for the study were collected from 305 children suspected to have anemia. Complete blood count, transferrin saturation (Tfsat), ferritin, circulating transferrin receptor (TfR) and CHr were measured. Three groups were defined, iron deficiency (Tfsat <20%, Hb >11 g/dL; n=120), iron deficiency anemia (Tfsat <20%, Hb <11 g/dL; (n=73) and controls (Tfsat >20%; n=112). The anemic group had significantly lower macrocytic anemia (MCV), mean corpuscular hemoglobin (MCH) and CHr. All of the variables in the anemia group were significantly lower than those of the control group except for the ferritin level. Compared to the control group, the iron deficiency group also showed significantly lower values except for transferrin receptor and the ferritin levels. CHr levels of <26 pg correlated well with anemic states. CHr together with a complete blood count may provide an alternative to the traditional hematologic or biochemical panel for the diagnosis of iron deficiency and iron deficiency anemia in young children and is cost-effective in developing countries. A CHr cut-off level of 26 pg is considered to be a reasonable indicator of anemic states.     

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.     

Neutrophil hypersegmentation in children with iron deficiency anemia

Neutrophil hypersegmentation (NH) is usually associated with vitamin B12 or folic acid deficiency. NH is seen in iron deficiency anemia but there are very few case studies about this. Neutrophil hypersegmentation was evaluated in 94 children with iron deficiency anemia; 23 healthy children comprised the control group with similar ages. NH was found in 76/94 (81%) in the study group and 2/23 (9%) of the control group. The difference was statistically significant (p < .01).     

UNRELATED CORD BLOOD TRANSPLANT EXPERIENCE BY THE PEDIATRIC BLOOD AND MARROW TRANSPLANT CONSORTIUM

Neutrophil hypersegmentation (NH) is usually associated with vitamin B 12 or folic acid deficiency. NH is seen in iron deficiency anemia but there are very few case studies about this. Neutrophil hypersegmentation was evaluated in 94 children with iron deficiency anemia; 23 healthy children comprised the control group with similar ages. NH was found in 76/94 (81%) in the study group and 2/23 (9%) of the control group. The difference was statistically significant ( p < .01).     

川崎病患儿外周血中红细胞和血小板参数的变化

川崎病（KD）是一种以全身血管炎为主要病理改变的急性发热、出诊性疾病：多数患儿还可以出现贫血、血小板数升高等改变。本文通过全自动血细胞计数仪对KD患儿的外周血红细胞和血小板参数的观察，发现其贫血患儿的平均红细胞体积（MCV）降低、红细胞分布宽度（RDW）增高，为小细胞不均一性贫血，符合缺铁性贫血的表现。KD患儿血小板数普遍较高，尤其病程早期的平均血小板体积（MPV）增高，提示有血小板增多的趋势和在血管炎性反应中的重要作用。因此，对KD患儿应尽早使用抗血小板药物，在治疗过程中注意对缺铁性贫血的纠正。     

Iron deficiency anemia and catecholamine metabolism

To assess the effects of iron therapy on platelet monoamine oxidase (MAO) activity and urinary excretion of total metanephrines (MN) in infants and young children with iron deficiency anemia, 24 subjects were tested before and after one month of oral iron treatment. Thirteen healthy children comprised the control group. In the control group, platelet MAO level was 0.21 +/- 0.02 U/mg protein (mean +/- SE), urinary total metanephrine was 2.51 +/- 0.47 micrograms/mg creatinine. In cases with iron deficiency, mean platelet MAO level was 47.6% lower (p less than 0.005) whereas mean urinary metanephrine plus normetanephrine (MN-NMN) was only 20.7% lower (p greater than 0.05) than the control values. After one month, the anemic patients receiving oral iron therapy showed a significant increase in hemoglobin concentration, per cent transferrin saturation and platelet MAO activity (p less than 0.05). However, urinary metanephrine excretion was found to be lower in this group when compared to the metanephrine levels in iron deficiency before the medication (p less than 0.05). Although hemoglobin and transferrin saturation did not return to normal levels, these findings suggested that platelet MAO activity increased and urinary excretion of metanephrines decreased after iron medication.     

Platelet aggregation in iron deficiency anemia

In-vitro platelet aggregation with ADP, adrenaline and collagen was studied in pediatric patients with iron deficiency before and after iron therapy, and in normal controls. Hyporeactivity of platelets to all agonists was seen in the untreated patients. This returned to normal following correction of anemia by iron therapy. There was a significant correlation between hemoglobin or serum iron and transferrin saturation on the one hand, and parameters of platelet aggregation on the other (P<0.001). Results of zero order correlation coefficient however, showed that platelet reactivity was actually dependent on the hemoglobin levels rather than the iron parameters per se. This may explain the prolonged bleeding time in patients with iron deficiency, particularly those associated with thrombocytopenia. Anemic individuals may be protected against thrombotic disorders due to this reduced platelet reactivity.     

Iron status in breast-fed full-term infants

The aim of this study was to evaluate the iron status of full-term babies breast-fed exclusively for four months and the importance of iron supplementation. One hundred sixteen term infants followed up since the newborn period by a well baby clinic were included in the study. Iron deficient and/or anemic infants were excluded from the study at four months. Some of the infants (51) were later given appropriate complementary food besides breast-feeding (Group A) and some (42) were given ferrous sulfate (1 mg/kg/d) (Group B). Blood count and serum iron and ferritin measurements were done at four and six months of age. At the 4th month, iron deficiency was found in 23 (19.8%) infants, 11 of which had iron deficiency anemia. At the 6th month, 23 (45%) infants in Group A were iron deficient and 11 (21.6%) of them had iron deficiency anemia. In Group B, three (7.1%) infants were iron deficient and one (2.4%) of them also had iron deficiency anemia (p < 0.0001). Significant iron deficiency and iron deficiency anemia have been found in four-month-old exclusively breast-fed full-term infants. It is observed that complementary food alone is insufficient; there is need for iron supplementation.     

Iron supplementation in children with Celiac Disease

Objective : To evaluate the effect of iron supplementation, in addition to gluten free diet (GFD), on hematological profile of children with Celiac Disease (CD).Methods : Children diagnosed as CD as per modified ESPGAN criteria were prospectively evaluated for their hematological profile at the time of their enrolment and after consuming GFD for at least one year. The results were compared with age and sex matched controls. Evaluation of hematological profile included hemoglobin estimation, complete blood counts, peripheral blood smear examination, serum iron, total iron binding capacity (TIBC), and serum ferritin estimation. All the enrolled cases were given iron supplementation in addition to exclusion of gluten from their diet. Repeat intestinal biopsy was performed in all the cases after completing 1 year on GFD.Results : Twenty one children (mean age 6.67 years, range 4 2–11 years) diagnosed as CD who completed at least one year of regular follow up on GFD (mean 1.5 years, range 1 2–2 years) were analysed for their hematological profile at the time of enrolment and after consuming GFD and iron supplementation. At the time of enrolment all the children had hemoglobin level <11 gm%, 78% had microcytic hypochromic anemia and 22% had dimorphic anemia, with lower mean MCV, MCH and serum ferritin levels, and a significantly higher mean TIBC as compared to controls (p <0.001). In the follow up evaluation of these cases on GFD, mean hemoglobin levels were comparable with controls but the cases continued to have lower mean MCV, MCH serum ferritin levels (p <0.05) and higher mean TIBC (p <0.05). Seven children had mild anemia. Serum ferritin levels showed a negative correlation with the grade of villous atrophy and lamina propria infiltrate.Conclusion : Our results suggest that iron deficiency anemia (IDA) is commonly associated with CD and iron deficiency state continues for a longer time even after excluding gluten from the diet and iron supplementation. Apart from offering them GFD rich in iron, early detection and treatment of IDA and prophylactic iron folic acid supplementation will go a long way to optimize their mental and psychomotor functions.     

The prevalence of anemia in adolescents: a study from Turkey

A cross-sectional method was used to study a group of 400 high school students in Kocaeli, Turkey, aged 14 to 16 years, identified among 17,812 high school students. Students from 10 high schools were selected using a random sampling method. Whole blood counts were performed as a screening test for anemia. Serum ferritin levels and, when necessary, hemoglobin electrophoresis were determined for anemic students. Iron medication was prescribed for iron deficiency and genetic counseling was given to adolescents with thalassemia trait. Out of 338 participating students (mean age, 14.72+/-0.71 y), anemia (hemoglobin <12 g/dL for girls and <13 g/dL for boys) was detected in 17/174 girls (9.7%) and 6/164 boys (3.6%). Iron deficiency anemia was detected in 20/23 (86.9%) of anemic children [15/17 (88.2%) girls and 4/6 (66.6%) boys]. Of 23 students with anemia 2 had beta-thalassemia trait and 2 had both iron deficiency, and beta-thalassemia trait. Etiology of anemia could not be defined in 1 student. The prevalence of adolescent anemia in Kocaeli is almost equal to that in developed countries.     

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.     

Reversal of iron deficiency anemia-induced peripheral neuropathy by iron treatment in children with iron deficiency anemia

The effects of iron deficiency anemia (IDA) on nerve conduction and efficiency of iron therapy were investigated by peripheral nerve-electrophysiological measurements. Eighteen children (10 boys, eight girls; mean age 31 +/- 1.3 months) with IDA and 12 healthy children (six boys, six girls; mean age 29 +/- 1.3 months) were enrolled into the study. Nerve conduction velocity was measured in the median and posterior tibial nerve. After nerve conduction values were determined in the patients and controls, 6 mg/kg/24 h ferrous sulphate was given orally to the patients for 3 months and nerve conduction velocity tests were performed again. Median/motor and sensory nerve conduction velocity and tibial/motor nerve distal-amplitute values of children with IDA were lower than for the control group (p < 0.05, p < 0.01 and p < 0.001 respectively). With iron supplementation these values increased to the normal levels and even higher than control levels for some parameters. In correlation studies between whole blood parameters and nerve conduction velocity results, there was a correlation between median/sensory nerve conduction velocity values and serum iron levels. Additionally there was a correlation between some nerve conduction velocity values and age. In conclusion, the evidence from this preliminary study suggests that peripheral neuropathy may develop in children with IDA. Peripheral neuropathy symptoms in these patients may be improved by iron therapy.     

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.     

Gastric histopathology, iron status and iron deficiency anemia in children with Helicobacter pylori infection

OBJECTIVES: Helicobacter pylori has been established as a major cause of gastritis and peptic ulcer disease in adults and children. H. pylori infection may also have a role in the development of some extra-gastrointestinal diseases, including iron deficiency anemia. The aim of this study is to investigate H. pylori-related changes in gastric physiology and histology and the relationship of these changes to iron deficiency anemia in children. METHODS: Fifty-two patients with gastrointestinal complaints were studied. Hematologic parameters, 3-day vitamin C and iron consumption, serum gastrin levels, and gastric juice ascorbic acid levels were compared in patients with and without H. pylori infection. Dietary intake of vitamin C and iron, serum gastrin, gastric juice ascorbic acid content, and gastric histology were compared in patients with H. pylori infection and anemia and in patients with H pylori infection and no anemia. The CagA status of the H. pylori organisms was evaluated. RESULTS: Twenty-eight of 52 patients had H. pylori. Thirty-one patients had iron deficiency anemia. H. pylori infection was associated with low serum iron levels. H. pylori gastritis was associated with a decrease in the gastric juice ascorbic acid level. Infection with CagA-positive strains was associated with a greater decrease in gastric juice ascorbic acid than infection with CagA-negative strains. However, the gastric juice ascorbic acid levels of patients with H. pylori and anemia were not different from those of non-anemic patients with H. pylori. Among patients with H. pylori infection, pangastritis was twice as common in those with anemia than in those without anemia. CONCLUSIONS: H. pylori infection was associated with a decrease in gastric juice ascorbic acid concentration, and this effect was more pronounced in patients with the CagA-positive strain. Pangastritis was more common in patients whose H. pylori.infection was accompanied by anemia.     

Serum transferrin receptor levels in beta-thalassemia trait

Increased levels of transferrin receptors (TfR) and soluble TfR (sTfR) are reliable indicators of iron deficiency anemia and conditions with enhanced erythropoietic activity. In this study we measured sTfR levels in the cases of beta-thalassemia trait (betaTT) and IDA to see whether it would be a diagnostic tool for the differentiation of betaTT and IDA. On the other hand STfR levels could give an idea about erythropoietic activity in betaTT. Serum transferrin receptor (sTfR) levels were measured with enzyme immune assay in 37 cases with betaTT, in 26 patients with iron deficiency anemia (IDA), in 17 patients with the coexistence of betaTT with IDA, and in 21 healthy controls. Mean sTfR in betaTT (6.54 +/- 1.88) were statistically higher than in controls (5.09 +/- 0.76) and lower than in IDA (11.46 +/- 5.03) and in IDA coexistence with betaTT (14.44 +/- 5.3, p < 0.05 in each comparison). However, in 17 cases with betaTT sTfR levels showed an overlap between the patients with IDA, and in 15 cases with betaTT it also showed an overlap with controls. The finding of higher sTfR levels in betaTT compared with controls suggested that there was a degree of ineffective hematopoiesis in betaTT. Although sTfR levels in IDA were higher than in betaTT, because of largely overlapping values in both groups, it was not satisfactory to distinguish betaTT from IDA.     

Nutritional anemia and its control

Available studies on prevalence of nutritional anemia in India show that 65% infant and toddlers, 60% 1–6 years of age, 88% adolescent girls (3.3% had hemoglobin < 7.0 g/dl; severe anemia) and 85% pregnant women (9.9% having severe anemia) were anemic. The prevalence of anemia was marginally higher in lactating women as compared to pregnancy. The commonest is iron deficiency anemia. National programmes to control and prevent anemia have not been successful. Experiences from other countries in controlling moderately-severe anemia guide to adopt long-term measures i.e. fortification of food items like milk, cereal, sugar, salt with iron. Use of iron utensils in boiling milk, cooking vegetables etc may contribute significant amount of dietary iron. Nutrition education to improve dietary intakes in family for receiving needed macro/micro nutrients as protein, iron and vitamins like folic acid, B₁₂, A and C etc. for hemoglobin synthesis is important. As an immediate measure medicinal iron is necessary to control anemia. Addition of folate with iron controls anemia and is neuroprotective. Evidence in early childhood suggests vitamin B₁₂ deficiency anemia; thus it may also be given alongwith iron and folate.     

Serum soluble transferrin receptor is a valuable diagnostic tool in iron deficiency of breath-holding spells

Iron-deficiency anemia may be a factor contributing to breath-holding spells. The serum transferrin receptor provides a useful measure of tissue iron deficiency. In this study of 50 breath-holders, while iron-deficiency anemia was detected in 28 (56%) of patients with routine tests, serum transferrin receptor levels were found increased in all patients. A positive correlation was detected between serum soluble transferrin receptor levels and frequency of attacks. It is suggested that the serum transferrin receptor level is useful as a single test for identification of iron deficiency in breath-holders. Moreover, if iron deficiency can be diagnosed earlier, then patients can be treated earlier.     

Iron deficiency anemia and iron therapy effects on infant developmental test performance

The behavioral effects of iron deficiency and its treatment were evaluated in a double-blind randomized controlled community-based study of 191 Costa Rican infants, 12 to 23 months of age, with various degrees of iron deficiency. The Bayley Scales of Infant Development were administered before and both 1 week and 3 months after IM or oral administration of iron. Appropriate placebo-treated control infants were also tested. Infants with iron deficiency anemia showed significantly lower mental and motor test scores, even after considering factors relating to birth, nutrition, family background, parental IQ, and the home environment. After 1 week, neither IM nor oral iron treatments differed from placebo treatment in effects on scores. After 3 months, lower mental and motor test scores were no longer observed among iron-deficient anemic infants whose anemia and iron deficiency were both corrected (36%). However, significantly lower mental and motor test scores persisted among the majority of initially anemic infants (64%) who had more severe or chronic iron deficiency. Although no longer anemic, they still showed biochemical evidence of iron deficiency after 3 months of treatment. These persistent lower scores suggest either that iron therapy adequate for correcting anemia is insufficient to reverse behavioral and developmental disturbances in many infants or that certain ill effects are long-lasting, depending on the timing, severity, or chronicity of iron deficiency anemia in infancy.     

Helicobacter pylori, anemia, and iron deficiency: relationships explored among Alaska native children

BACKGROUND: Attempts to understand determinants of anemia and iron deficiency have led researchers to examine the role of Helicobacter pylori infection. The current study assessed determinants of anemia and iron deficiency, including H. pylori, in Alaska Native children. METHODS: In 1999, a population-based survey was conducted among 86 children (67% response rate), mean age of 43.7 months (standard deviation = 16.8 months). Samples of breath, stool, and venous blood were obtained from children for measures of anemia, iron deficiency, H. pylori, fecal blood loss, and current inflammation. Standardized interviews with parents provided information on demographics, illness, and intake of dietary iron, iron-absorption inhibitors, and enhancers. RESULTS: Of the 86 children studied, 17.4% were anemic and 38.6% were iron deficient. Forty-one percent of the cohort had H. pylori-specific IgG antibodies, 86% tested positive by the urea breath test (UBT), and 80% tested positive by the stool antigen test. Presence of H. pylori antibodies emerged as a significant risk factor for anemia and iron deficiency in adjusted analyses controlling for demographic factors, current inflammation, and antibiotic use. In contrast, children with positive UBT or stool antigen results were significantly less likely to have anemia or iron deficiency than those with negative results. CONCLUSIONS: Results from different measures of H. pylori may reflect different stages of infection. Relationships between H. pylori and anemia/iron deficiency may depend on the phase of infection measured, with serologic tests reflecting established H. pylori infection associated with anemia/iron deficiency, and UBT and stool antigen results reflecting an earlier stage of infection.     

The incidence, treatment, and follow-up of iron deficiency in a tertiary care pediatric clinic

To assess the incidence, treatment, and follow-up of iron deficiency in children seen in a tertiary hospital, a retrospective chart review was performed in 2002 of 364 consecutive children screened for iron deficiency with free erythrocyte protoporphyrin and hemoglobin. Sixty-five of the 352 children studied (18.5%) were iron-deficient and 19 patients (5.4%) were anemic. Eighty percent of the affected children were treated with iron, and only 25% had follow-up blood testing done. Iron deficiency is common in children younger than 2 years of age. Whether or not the children had anemia, treatment and follow-up were less than optimal.