Effectiveness of nutrition education, iron supplementation or both on iron status in children

OBJECTIVE: A community-based, randomized trial was designed to compare the effect of nutrition education and/or iron supplementation (weekly) on iron status of children in an urban slum in Delhi. METHODS: Four hundred and fifty one children, 9-36 months of age and their caretakers (mothers), assigned to one of the following groups were included in the cohort. Group 1, nutrition education. Group 2, supplementation (with 20 mg elemental iron). Group 3, nutrition education with supplementation (with 20 mg elemental iron) and Group 4, control given placebo. The intervention program was of four months duration, with a treatment phase of 8 wk followed by 8 wk of no treatment. RESULTS: Post intervention, at 8 wk and at 16 wk, the hemoglobin change in the nutrition education, supplementation, nutrition education with supplementation and control groups was 2.9, 1.9, 3.8 and -5.9%, respectively and 2.1, -1.9, 0 and -9.3%, respectively (as compared to initial values). There was no significant effect of any of the intervention at 8 weeks. At 16 wk, there was significant positive effect of nutrition education group (p less than 0.05). The percent change in serum ferritin value at 16 wk in the nutrition education, supplementation, nutrition education with supplementation and control groups was 5.7, -2.3, -3.4 and -40%, respectively. Serum ferritin values were significantly higher for the nutrition education group (p < 0.001) as compared to the control. At 16 wk, the nutrition education group mothers showed significantly higher nutrition knowledge and the dietary iron intake of children was significantly higher than their control group counterparts (p < 0.0001). CONCLUSION: The study suggests that nutrition education did have a positive effect on the iron status possibly by improving the dietary iron intake.     

Serum iron,serum transferrin and transferrin saturation in healthy children without iron deficiency

Serum iron, serum transferrin and transferrin saturation were studied in 253 healthy, non-anaemic children 4, 8 and 13 years old, and in 60 healthy, non-anaemic adults having serum ferritin values 15 g/l. One hundred and ninety-six children had serum ferritin values 15 g/l (i.e. replete iron stores), 35 had intermediate ferritin values from 10–14 g/l and 22 had ferritin values <10 g/l (i.e. depleted iron stores). Iron replete children showed a gradual rise in serum iron and transferrin saturation values with age. Serum iron and transferrin saturation values were lower (P<0.001, P<0.0001) and transferrin values high (P<0.0001) in iron replete children compared to adults. Iron replete children had a 2.5 centile transferrin saturation value of 5%; 19.9% of these children had saturation values <15% and 8.2% had values <10%. In iron depleted children a transferrin saturation value <7% yielded the highest diagnostic efficiency as regards exhausted iron stores, although with a low predictive value of a positive test. The transferrin saturation is unsuitable as a single diagnostic criterion in the evaluation of iron deficiency in children and should always be combined with other indicators of iron status.     

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.     

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.     

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.     

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).     

THE ANEMIA OF FAMILIAL MEDITERRANEAN FEVER DISEASE

The aim of this study was to evaluate the incidence of anemia detected in familial Mediterranean fever (FMF) and the effect of disease activity and colchicine therapy along with inteleukins to laboratory tests, including serum transferrin receptor (TfR), in the diagnosis of anemia seen in FMF in children. After detecting anemia in 63.4% of 172 FMF patients followed up by our rhematology outpatient polyclinics, it was decided to study 3 groups of patients: group 1, 17 newly diagnosed FMF patients; group 2, 36 FMF patients on colchicine therapy; and group 3, 17 healthy children as control for the symptom of anemia. All 3 groups of patients were investigated for their hematological parameters, iron status, including soluble transferrin receptor (sTFR) concentrations and sTFR index, and IL-6 levels. Anemia ratio was 9/17, 53%; 11/36, 31%; and 1/17, 5% in the groups 1, 2 and 3, respectively. There was a significant difference between hemoglobin (Hb) values in the first group and the second (patients who were on colchicine therapy). Furthermore, in the second group there was a significant difference between the Hb concentrations at the time of diagnosis and after colchicine therapy (p =. 003). There was a positive correlation between Hb and plasma iron and transferrin saturation in group 1 and disease beginning age, iron, transferrin saturation, and erythrocyte sedimentation rate (ESR) in the second group. In the first group the anemic patients' iron and transferrin saturation were significantly lower than normal, while ferritin levels were higher. In the second group, a good correlation was found with ESR and Hb levels; the higher ESR values were detected in patients with lower Hb values. Of the anemic and nonanemic patients of the first and second groups, values for interleukin 6 and iron parameters, including sTFR, were found similar. Anemia detected in FMF patients was found related to iron status more than interleukins. Colchicine therapy had a positive effect on anemia as well as on disease activity. Resolution of symptoms of FMF occurred with correction of the anemia, if the patient ESR values also decreased on colchicine therapy.     

Antenatal micronutrient supplementation and third trimester cortisol and erythropoietin concentrations

Antenatal iron and multiple micronutrient supplementation has been shown in randomized trials to improve birthweight, although mechanisms are unknown. We examined late pregnancy serum erythropoietin (EPO) and cortisol concentrations in relation to maternal micronutrient supplementation and iron status indicators (haemoglobin, serum ferritin, soluble transferrin receptor) in 737 rural Nepalese women to explore evidence of stress or anaemia‐associated hypoxia. A double‐masked randomized control trial was conducted from December 1998 to April 2001 in Sarlahi, Nepal, in which women received vitamin A alone (as control), or with folic acid (FA), FA + iron, FA + iron + zinc and a multiple micronutrient supplement. In a substudy, we collected maternal blood in the first and third trimester for biochemical assessments. Generalized estimating equations linear regression analysis was used to examine treatment group differences. EPO was ～14–17 mIU mL^?1 lower (P < 0.0001) in late pregnancy in groups receiving iron vs. the control group, with no difference in the FA‐only group. Cortisol was 1.3 μg dL^?1 lower (P = 0.04) only in the micronutrient supplement group compared with the control group. EPO was most strongly associated with iron status indicators in groups that did not receive iron, and in the non‐iron groups cortisol was positively correlated with EPO (r = 0.15, P < 0.01) and soluble transferrin receptor (sTfR, r = 0.19, P < 0.001). In adjusted analyses, third trimester EPO was associated with a reduction in low birthweight, whereas cortisol was negatively associated with length of gestation and higher risk of preterm birth. Iron and multiple micronutrient supplementation may enhance birth outcomes by reducing mediators of maternal stress and impaired erythropoiesis.     

T2* MRI in Regularly Transfused Children with Thalassemia Intermedia: Serum Ferritin Does Not Reflect Liver Iron Stores

Nontransfused patients with thalassemia intermedia (TI) accumulate iron due to increased gastrointestinal absorption of iron. Recent studies using T2* MRI revealed that serum ferritin does not reflect the severity of iron overload in nontransfused TI patients. We evaluated the iron overload status in TI children on monthly transfusion. Based on serum ferritin levels, 11 such patients (mean age 13.18 ± 4.09 years), were classified into two groups, group 1 (six patients) and group 2 (five patients) with serum ferritin levels below and above 1000 ng/mL, respectively. T2* MRI assessments were done for evaluation of hepatic and cardiac iron status. Group 1 and group 2 had mean serum ferritin levels of 817.300 ± 244.690 ng/mL and 1983.80 ± 662.862 ng/mL, respectively (P = .003). T2* MRI showed comparable moderate to severe hepatic iron overload status in both. None of the patients had myocardial iron deposition. We conclude that serum ferritin does not reflect the hepatic iron overload status in our patients with TI on regular transfusion.     

Undernutrition in Nepalese children: a biochemical and haematological study

Aim: This study was undertaken to assess the nutritional status of 6–10 years old Nepalese children by measuring some haematological and biochemical parameters. Methods: Nutritional status was assessed by height‐for‐age z‐score. Total count of red blood corpuscles (TC of RBC), packed cell volume, haemoglobin concentration, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration were measured. Biochemical parameters such as serum iron, total iron‐binding capacity (TIBC), serum ferritin, serum transferrin, transferrin saturation (TS) and serum albumin were also measured. Serum folate and vitamin B₁₂ were measured in well‐nourished and undernourished children. Results: TC of RBC, serum iron, serum ferritin, TS and serum albumin of stunted children were significantly lower (p < 0.05) than that of well‐nourished children. MCV, MCH, TIBC and serum transferrin of stunted children were significantly higher (p < 0.05) than that of well‐nourished children. Serum folate and vitamin B₁₂ values of stunted children were significantly lower (p < 0.001) than that of well‐nourished children. Conclusion: A mild iron deficiency was found in stunted Nepalese children. The serum ferritin has been identified as a sensitive marker for measurement of iron status in surveyed children. A deficiency of serum protein, serum folate and vitamin B₁₂ was also found in the undernourished Nepalese children.     

Haematologic consequences of viral infections including serum iron status

Twenty-seven children with mumps or chickenpox were taken as a model to evaluate the haematological consequences of viral infections including serum iron status. Blood samples were obtained from all patients at presentation and on the 21 st day of the disease. While haemoglobin, haematocrit, and meam corpuscular volume levels were similar in two measurements (P>0.05), the mean leucocyte, absolute lymphocyte and thrombocyte counts, mean serum iron, serum iron binding capacity and transferrin saturation levels were lower at presentation than on the 21 st day of the disease. The serum iron levels were below 30 g/dl in 16 (59.2%) patients at presentation while only 4 (14.8%) had low values on 21 st day. Twenty-four (88.9%) patients had an increment in the serum iron binding capacity levels and 2 (7.6%) reached values above the normal range on the 21 st day. Int 21 (77.8%) patients, the transferrin saturation levels were below the expected ranges at presentation but 26 (96.3%) showed an increment on the 21 st day. However, the mean ferritin level was higher at presentation. Therefore, during the evaluation of patients for anaemia, the presence of a recent acute viral infection should be documented so as to avoid unnecessary iron medication.     

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 effect of diet on total antioxidant status,ceruloplasmin, transferrin and ferritin serum levels in phenylketonuric children

Objectives: To investigate the effect of diet on total antioxidative status (TAS), transferrin, ferritin and ceruloplasmin serum levels in phenylketonuric (PKU) children. Patients and methods: Seventeen poorly controlled PKU children underwent clinical and laboratory examinations before, ‘off diet’, and 60 days after adhering to their special diet ‘on diet’, whereas controls (N = 24) were examined once. Blood chemistry was performed with the appropriate methodologies. Results: Phenylalanine levels differed significantly among the examined groups. Lipids and lipoproteins were higher in ‘off diet’ than in ‘on diet’ group, except of high density lipoprotein and apolipoprotein AI that remained unaffected. Total antioxidative status (386 ± 30 vs 204 ± 23 μmol/L, p < 0.001), ferritin (48.2 ± 2.3 vs 33.0 ± 2.8 μg/L, p < 0.001) and ceruloplasmin (40.02 ± 2.5 vs 25.5 ± 2.8 mg/dL, p < 0.001) levels were significantly higher in ‘on diet’ patients’ group compared to ‘off diet’ one. The low lipoprotein and the high TAS and ferritin levels in patients with PKU ‘on diet’ may be related to the vegetarian diet and the rich in iron formula supplementation. Conclusions: The low ferritin levels found in ‘off diet’ patients with PKU may be attributed to a decreased liver production of ceruloplasmin, which evaluation may be a useful tool for the follow‐up of patients with PKU.     

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.     

The anemia of familial Mediterranean fever disease

The aim of this study was to evaluate the incidence of anemia detected in familial Mediterranean fever (FMF) and the effect of disease activity and colchicine therapy along with inteleukins to laboratory tests, including serum transferrin receptor (TfR), in the diagnosis of anemia seen in FMF in children. After detecting anemia in 63.4% of 172 FMF patients followed up by our rhematology outpatient polyclinics, it was decided to study 3 groups of patients: group 1, 17 newly diagnosed FMF patients; group 2, 36 FMF patients on colchicine therapy; and group 3, 17 healthy children as control for the symptom of anemia. All 3 groups of patients were investigated for their hematological parameters, iron status, including soluble transferrin receptor (sTFR) concentrations and sTFR index, and IL-6 levels. Anemia ratio was 9/17, 53%; 11/36, 31%; and 1/17, 5% in the groups 1, 2 and 3, respectively. There was a significant difference between hemoglobin (Hb) values in the first group and the second (patients who were on colchicine therapy). Furthermore, in the second group there was a significant difference between the Hb concentrations at the time of diagnosis and after colchicine therapy (p = .003). There was a positive correlation between Hb and plasma iron and transferrin saturation in group 1 and disease beginning age, iron, transferrin saturation, and erythrocyte sedimentation rate (ESR) in the second group. In the first group the anemic patients' iron and transferrin saturation were significantly lower than normal, while ferritin levels were higher. In the second group, a good correlation was found with ESR and Hb levels; the higher ESR values were detected in patients with lower Hb values. Of the anemic and nonanemic patients of the first and second groups, values for interleukin 6 and iron parameters, including sTFR, were found similar. Anemia detected in FMF patients was found related to iron status more than interleukins. Colchicine therapy had a positive effect on anemia as well as on disease activity. Resolution of symptoms of FMF occurred with correction of the anemia, if the patient ESR values also decreased on colchicine therapy.     

Iron’s role in paediatric restless legs syndrome – a review

Paediatric restless legs syndrome (RLS) treatment is important because RLS’s associated sleep disturbance causes significant developmental-behavioural morbidity and impacts family well-being. RLS is associated with brain iron insufficiency and dopaminergic dysfunction. Diagnosis requires fulfillment of diagnostic criteria, which for children are currently in evolution, and have limitations, especially in preschoolers. The community physician needs to recognize the possibility of RLS to refer to a sleep specialist for diagnostic confirmation and management recommendations, which include oral iron therapy, even though there is currently no definitive research evidence for iron efficacy in most children with RLS. A 3 mg to 6 mg elemental iron/kg/day dose for three months could be tried if the ferritin level is <50 ug/L. Sleep hygiene and behavioural strategies are also recommended. Iron supplementation should be safe in the absence of iron metabolism disorders, provided that transferrin saturation and ferritin levels are monitored pre-and post-treatment.     

Soluble transferrin receptor levels and soluble transferrin receptor/log ferritin index in the evaluation of erythropoietic status in childhood infections and malignancy

Soluble transferrin receptor (sTfR) is a new diagnostic tool for determining iron status and erythropoietic activity. The increased concentrations of sTfR in patients with iron deficiency reflect the hyperplasia of erythroid precursors. The objective of this study was to evaluate sTfR and sTfR/log ferritin index (sTfR-F) values in healthy children (n = 64), full-term neonates (n = 18), children with iron deficiency (n = 16), hemolytic anemia (n = 7), beta-thalassemia traits (n = 18), respiratory infections (n = 41) and malignancies (n = 13), and to compare these parameters for the different subgroups with those of healthy children. The sTfR levels were increased in children with iron deficiency in the same way as in adults (p < 0.0001) and in cases of increased erythropoietic activity, such as during the neonatal period (p < 0.0001), and of hemolytic anemias (p = 0.006). The index was significantly increased in iron deficiency (p < 0.0001) and decreased in neonates (p = 0.011). Children carriers of beta-thalassemia were found to have increased sTfR values (p = 0.015), but not sTfR/log ferritin index (p = 0.491), a finding suggesting that use of both parameters is necessary for distinguishing between those with and those without iron deficiency. In children with upper respiratory infection, the sTfR levels were close to normal, while the index was found to be low. In order to evaluate the iron status in infections, we further subdivided the children into two groups according to the value of ferritin, with the cut-off point at 35 microg/L. Children with ferritin level above 35 microg/L experienced normal sTfR levels but very low index, a finding which could enable the use of these two parameters for distinguishing patients with infection without concomitant iron deficiency. In the group of malignancies under chemotherapy both indices were low (p = 0.005, p < 0.0001) mainly due to myelosuppression. CONCLUSION: The interpretation of both sTfR and sTfR/log ferritin index is useful in the evaluation of iron status and erythropoietic activity, especially in children with heterozygous beta-thalassemia, infection and malignancies.     

Effects of three different iron supplementations in term healthy infants after 5 months of life

The aim of this study was to investigate the effects of different doses of iron on haematological status of breastfed infants. One hundred and thirteen infants were randomized into four groups at 5 months of age. Iron supplementation was given at doses of 1 mg/kg/day, 2 mg/kg/day, and 2 mg/kg/every other day in the first three study groups, respectively, and the last group received placebo. The hematological values, except hemoglobin, were higher in the group supplemented with iron at a dose of 2 mg/kg/day, and ferritin values were statistically higher in the group supplemented with iron at a dose of 2 mg/kg/every other day than in the group supplemented with iron at a dose of 1 mg/kg/day. We suggest that intermittent iron supplementation is more effective than a daily regimen in equal dosages.     

Value of serum ferritin estimation in sickle cell anaemia.

In a group of 35 children with sickle cell anaemia serum ferritin concentration ranged from 70 to 2460 microgram/l (mean 367, median 180 microgram/l). This was significantly higher than the ferritin levels (range 8-101, mean 34, median 30 microgram/l) in a group of 63 normal control children of the same age group. 30 (86%) of the sickle cell children showed serum ferritin levels greater than 101 microgram/l, and 2 (6%) levels greater than 1000 microgram/l. 7 of the patients had not been transfused before this study. Their serum ferritin levels were all raised and showed a significant correlation with age but not with haemoglobin level. In the remainder of the patients the serum ferritin bore no significant correlation with age, haemoglobin level, or number of units of blood transfused. 2 children with HbSC disease had levels within the control range. Since patients with sickle cell anaemia have an increasing chance of long survival, we suggest that serial estimations of their iron status be made by means of serum ferritin assay in order to determine which patients are accumulating excessive iron.