What is new in iron overload?

Children with severe chronic hemolytic anemia or congenital erythroblastopenia are transfusion dependent. Long-term transfusion therapy prolongs life but results in a toxic accumulation of iron in the organs. The human body cannot actively eliminate excess iron. Therefore, the use of a chelating agent is required to promote excretion of iron. So far, iron chelation has been done by subcutaneous infusion of deferoxamine given over 10 h, 5–6 days per week. Compliance is poor and chelation often insufficient. Ferritin measurements and sometimes liver biopsies are used to evaluate the iron burden in the body. At the present time, new iron chelators that can be given orally are available. Furthermore, magnetic resonance imaging (MRI) assessment of tissue iron is a noninvasive and highly reproducible method, which is able to quantitate organ iron burden. In conclusion, iron overload can be measured more accurately with noninvasive methods such as MRI. Deferasirox is a once-daily oral therapy for treating transfusional iron overload, which improves patient compliance and quality of life.     

Are ferric compounds useful in treatment of iron deficiency anemia?

The effect of ferric compounds in therapy of iron deficiency anemia is doubtful; however, the absorption of iron is not affected negatively by food or drugs. In our Well Baby Clinic, ferric polymaltose (6 mg/kg/d) was given to 59 infants (Group 1) and ferrous sulphate (same doses) was given to 64 infants (Group 2) (74 +/- 9 d, 70 +/- 7 d, respectively). These infants had iron deficiency anemia, and their therapy was continuous. Ferric polymaltose was not as effective as ferrous sulphate, although it increased hemoglobin and serum iron. Mean corpuscular volume and serum ferritin were not significantly changed after therapy. For this reason, we prefer to use only ferrous salts in therapy.     

Do cerebral blood flow velocities change in iron deficiency anemia?

Infants with iron deficiency had lower scores when tested for mental and motor development than their peers with better iron status. The aim of this study was to examine cerebral blood flow velocity in infants with iron deficiency anemia. Thirty-six infants (27 male, 9 female) with iron deficiency anemia, aged 6 to 36 months were divided into 2 groups according to the hemoglobin (Hb) values [group 1 (n=23) Hb<10 g/dL and group 2 (n=13) 11 >Hb> or =10 g/dL]. In anterior and middle cerebral arteries only end-diastolic velocity (EDV) was increased in group 1 as compared with group 2 (P=0.05 and P=0.016, respectively), whereas in posterior cerebral artery both EDV and peak-systolic velocity were different between the groups (P=0.024 and P=0.004). Both peak-systolic velocity and EDV showed significant correlation with Hb level in the posterior cerebral artery (r=-0.38, P=0.023 and r=-0.35, P=0.037) but not in the anterior and middle cerebral arteries. Increased cerebral blood flow velocities in children with lower Hb values may be due to increased cardiac output, decreased vascular resistivity caused by anemia.     

Evaluation of hepatic iron overload in Chinese children with β-thalassemia major

Patients with β-thalassemia major require long-term blood transfusions, resulting in hepatic iron overload. Thirty-five Chinese children with β-thalassemia major were recruited in the present studies. Hepatic iron overload was evaluated by histological grading. The relationships between hepatic iron overload and both serum biochemical markers and magnetic resonance imaging (MRI) examination were studied. The majority of the patients showed high degrees of hepatic iron overload by histological study. The degree of hepatic iron overload was correlated with serum ferritin (r = .70, P < .01), hyaluronic acid (r = .58, P = .011), and type III precollagen (r = .55, P = .035). Moreover, hepatic iron overload showed a negative correlation with liver to muscle signal intensity ratio (r = -.44, P = .012), and a positive correlation with red marrow area percentage (r = .52, P < .01). These results indicated that hepatic iron overload might be assessed by serum biochemical markers and MRI examination.     

Is there a relationship between childhood Helicobacter pylori infection and iron deficiency anemia?

An association between Helicobacter pylori infection and iron deficiency anemia has been reported in children, and it has been proposed that H. pylori infection needs to be eradicated to treat absolutely iron deficiency anemia (IDA). We investigated whether there was any correlation between H. pylori infection and iron deficiency (ID) and IDA in children, and whether the eradication of H. pylori infection without iron treatment would lead to the resolution of ID. Hemoglobin and ferritin levels, H. pylori stool antigen test and (14)C urea breath test were measured in 140 children aged 6--16 years (median 9.5 years). Children with H. pylori infection were divided into three groups on the basis of hemoglobin, mean corpuscular volume (MCV), and serum ferritin levels: groups of IDA, ID, and control. All the children received anti-H. pylori combination therapy consisting of amoxicillin, clarithromycin, and lansoprazole. Hemoglobin and MCV values rose significantly compared with baseline values after H. pylori eradication without iron supplementation in children with IDA (p=0.002 and p=0.003, respectively). Ferritin values increased significantly after H. pylori eradication in children with ID (p<0.001). We conclude that complete recovery of ID and IDA can be achieved with H. pylori eradication without iron supplementation in children with H. pylori infection.     

Do recombinant human erythropoietin and iron supplementation increase the risk of retinopathy of prematurity?

Comparing a group of infants treated with recombinant erythropoietin and iron supplementation to a group of control infants, no difference was observed concerning the transfusion need. The incidence of retinopathy of prematurity was significantly higher in the treated group. These data need to be confirmed in randomized controlled studies.     

Childhood anemia and iron deficiency in sub-Saharan Africa – risk factors and prevention: A review

Iron deficiency and iron deficiency anemia are public health issues recognised by the World Health Organisation, especially in sub-Saharan Africa. In some countries on this continent, the prevalence of anemia exceeds 60% in the pediatric population. Iron supplementation could prevent around one third of anemia cases in children in Africa and could decrease morbidity and mortality. A number of factors are behind this anemia, including iron deficiency caused by an inadequate diet, pica and geophagia, as well as chronic inflammation (malaria, digestive and urinary parasites, etc.). Ferritin is a good indicator of the body's iron stores, but it is not a specific reflection, with both inflammation and infection causing an increase. Ferritin could be interpreted according to C-reactive protein (CRP) or alpha-1 glycoprotein (AGP), or by adjusting the ferritin threshold to 30 μg/L. The treatment of malaria and digestive or urinary worms, the correction of factors that stimulate inflammation, the fight against geophagia, as well as more hygienic living conditions, are all prerequisites for overcoming iron deficiency. A number of campaigns using iron supplements have proven to be effective, especially in schools, to fight against iron deficiency and malnutrition. Biofortification is an innovative and promising cultivation technique that increases the content of bioavailable iron in local produce such as beans. It will become a lever in the fight against iron deficiency.     

Does inadequate maternal iron or DHA status have a negative impact on an infant's functional outcomes?

Marginal intake of iron and ω-3 long-chain fatty acids (DHA) is prevalent among pregnant women. It is not clear to what extent poor iron or DHA status during pregnancy impacts on an infant's functional outcomes. A few studies suggest that inadequate maternal iron or DHA status may be associated with suboptimal functional outcomes in infants. In addition, there is a lack of prospective studies using randomized, double-blind design or experimental studies with appropriate animal models. Although both nutrients are involved in early brain development and their metabolism is interrelated, no study has examined the interaction between iron and ω-3 fatty acids during pregnancy.

Conclusion: Long-term studies on large cohorts of pregnant women and their infants are needed to determine whether inadequate iron or DHA status during pregnancy is detrimental to infant neurodevelopment.     

Does Helicobacter pylori infection relate to iron deficiency anaemia in prepubescent children under 12 years of age?

Aim: To investigate the association between Helicobacter pylori (H. pylori) infection and iron deficiency anaemia (IDA). Methods: Haemoglobin levels, iron parameters and serum IgG antibodies to H. pylori were measured in 693 children aged 9 to 12 y. Results: No significant differences in the seroprevalence of H. pylori infection and antibody titres to H. pylori were found between the IDA group and the non-anaemic controls.

Conclusion: H. pylori infection does not seem to contribute to iron deficiency in prepubescent children.     

Indices used in differentiation of thalassemia trait from iron deficiency anemia in pediatric population: are they reliable?

Background: Iron deficiency (IDA) and beta thalassemia trait (TT) are the most common causes of hypochromia and microcytosis. Many indices have been defined to quickly discriminate these similar entities via parameters obtained from automated blood cell analyzers. However, studies in the pediatric age group are scarce and their results are controversial. Methods: We calculated eight discrimination indices [Mentzer Index (MI), England and Fraser Index (E&F), Srivastava Index (S), Green and King Index (G&K), Shine and Lal Index (S&L), red blood cell (RBC) count, RBC distribution width, and red blood cell distribution width Index (RDWI)] in 100 patients. We calculated sensitivity (SENS), specificity (SPEC), positive and negative predictive value (PPV and NPV), and Youden's Index (YI) of each discrimination index. Results: None of the discrimination indices showed a SENS and SPEC of 100%. The highest SENS was obtained with S&L (87.1%), while the highest SPEC was obtained with E&F formula (100%). The highest YI value was obtained with E&F formula (58.1%). Conclusion: In our study, none of the formulas appears reliable in discriminating between TT and IDA patients. The evaluation of iron status and measurement of hemoglobin A(2) (HbA(2)) remain the most reliable investigations to differentiate between TT and IDA patients.     

Can myocardial remodeling be a useful surrogate predictor of myocardial iron load? A 3D echocardiographic multicentric study

The relationship between myocardial iron load and eccentric myocardial remodeling remains an under‐investigated area; it was thought that remodeling is rather linked to fibrosis. This study aims to determine whether or not measures of remodeling can be used as predictors of myocardial iron. For this purpose, 60 patients with thalassemia were studied with 3D echocardiography and myocardial relaxometry (T2*) by Cardiac MRI. 3D derived sphericity index was significantly higher in patients with myocardial iron load. It was correlated with T2* with a 100% sensitivity and specificity (cut‐off value of 0.34) to discriminate between patients with and without myocardial iron overload.     

α-Thalassemia frequency and mutations in children with hypochromic microcytic anemias and relation with β-thalassemia, iron deficiency anemia

The majority of the anemias during childhood are hypochromic and microcytic. The aim of the present study was to determine the status of α-thalassemia mutations and its association with other etiologies, such as iron deficiency anemia (IDA) and β-thalassemia trait, that are frequently seen hypochromic microcytic anemias in children. Children with hypochromic microcytic anemias were included in the study. Serum iron (SI), total iron-binding capacity (TIBC), ferritin levels, and hemoglobin electrophoresis with high-performance liquid chromatography (HPLC) method were analyzed. Reverse hybridization of biotinylated polymerase chain reaction (PCR) product method was used for detection of α-globin gene mutations. Of the 46 patients involved in the study, 54.3% (n = 25) were boys, and 45.7% (n = 21) were girls. Iron deficiency anemia and β-thalassemia trait were diagnosed in 67.4% (n = 31) and 19.5% (n = 9), respectively. In 17.4% there were α-thalassemia mutations (in 10.9% 3.7 single-gene heterozygote mutation, in 4.3% 20.5-kb double-gene deletion mutation, and in 2.2% α-2 poly-A-1 heterozygote mutation was detected). In 2 patients (4.3%) no etiology was determined. In 2 patients (4.3%) association between iron deficiency anemia and α-thalassemia, in 1 patient (2.2%) association between β and α-thalassemia was detected. In conclusion, α-thalassemia carrier status and its association with other etiologies are frequently seen in Manisa. So, α-thalassemia should be considered in the differential diagnosis of hypochromic microcytic anemias, especially in cases without iron deficiency (ID) and β-thalassemia carrier state.