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A three-decade-long retrospective study of iron status in a cohort of 1250 children aged 8-36 months was carried out at the Pediatric Department at the Second University Naples. Iron status was evaluated with independent variables such as family income, weight for height, introduction of cow's milk (CM), iron supplementation and weaning. Iron deficiency (ID) is prevalent in children with low income, early introduction of CM, delayed weaning, over-weight, and in those not receiving iron supplementation (P

Effects of iron supplementation (IS) on haematological and anthropometric parameters in a cohort of 121 healthy children, followed from 6 to 24 months of life, in the Paediatric Department, Second University of Naples, were evaluated. Children were randomly segregated in four groups: (1) exclusively breast feeding (BF) weaned with non-iron fortified (NIF) foods, (2) BF and iron fortified formulas (IFF) and foods, (3) exclusively IFF and foods, (4) BF and oral iron supplementation (OIS). Haematological parameters (Hb, MCV, Serum ferritin and transferrin saturation) in addition to anthropometric measurements (length and weight) were obtained. Results from the study at 6, 12, 18 and 24 months showed significantly lower values of haematological parameters in BF infants than other groups and in IFF infants than in those with OIS. In contrast children with OIS showed significant lower length. It appears that IS may be of limited or no benefit for growth in non-iron deficient children.

In an observational cohort of 385 infants, we have investigated the relationship between hemoglobin (Hb) levels and iron stores and the type of milk feeding [breast milk (BM), formula milk (FM), cow's milk (CM), age and type of weaning, and socioeconomic status] at 8 and 12 months of age. Levels of Hb11 g/dl and iron stores15 ng/ml were significantly more frequent in BM and CM groups than in FM group (P0·05). Significant differences of Hb mean were observed among the three groups, while ferritin mean were lower in BM and CM groups than in FM group (P0·05). Socioeconomic factors also influenced Hb levels and iron stores through differences in diet. Deprived infants were 23·1% of cohort and many of them received BM (43·5% at 8 months versus 38·5% at 12 months) or CM (42·6% at 8 months versus 47% at 12 months), while50% were weaned before 6th month of age. FM feeding and weaning6 months of age are related with better Hb levels and iron stores. Analysis of the impact of weaning on Hb levels and iron stores showed that infants weaned6 months of life had, regardless of milk feeding, higher Hb and ferritin levels than weaned6 months.

Iron deficiency (ID) and beta thalassemia trait (betaTT) are the most common causes of hypochromia and microcytosis. This study evaluates the reliability of some of the red blood cell (RBC) indices and the formulas used in the differentiation between betaTT and ID in a cohort of 458 children aged between 1.8 and 7.5 years (mean age 5.6+/-1.7 years) with mild hypochromic microcytic anemia. Within this group, 243 were confirmed with ID and 215 with betaTT. Red cell indices derived from automated red cell analyzers were used to evaluate the following discriminant indices and formulas: Mentzer Index (MI), Green and King Index (GK), England and Fraser Index (EF), RBC Distribution Width Index (RDWI), RBC distribution width (RDW) and RBC count. Sensitivity (SENS), specificity (SPEC), positive and negative prognostic value, efficiency (EFF) and Youden's Index (YI) were evaluated. For each index or formula Gauss curves were constructed. The highest SENS was obtained with RDWI (78.9%), while the highest SPEC and YI with EF (99.1 and 64.2% respectively), the highest EFF (80.2%) with GK. Gauss curves obtained from betaTT and ID children showed a different degree of overlap for each formula or index. In conclusion, none of RBC indices or formulas appears reliable to discriminate between betaTT and ID subjects.

In 102 children of both genders aged between 10 and 12 years affected by iron deficiency anaemia (IDA) from various causes, a retrospective study from 1999 to 2007 has been performed to investigate possible relationships between IDA and physical growth. Patients were divided into two groups according to gender. Hb, MCV, ferritin levels, HSDS and body mass index (BMI) were recorded to confirm the diagnosis and the height standard deviation scores were also evaluated. The causes of IDA were investigated. At study entry, both groups of patients, regardless of IDA etiology, had microcytic hypochromic anaemia with low ferritin level. Anthropometric parameters were also reduced. Significant differences of anthropometric parameters were found in both groups in relationship to various causes of IDA (p

The impact of ER XbaI and PvuII α gene polymorphisms on overweight and obesity were studied in 77 subjects with Down Syndrome (DS), of which 32 were children (18 boys, 14 girls), mean age 8.7 ± 2.3 years, and 45 adolescents (28 boys, 17 girls) mean age 14 ± 2.5 years. Their lifestyle was compared to 40 healthy age-matched controls. DS subjects had significant lesser physical activity than controls (p0.05). The frequency of ER genotypes in DS subjects was compared with the healthy controls, finding that there was a high prevalence of XXER genotype in DS subjects. Children and adolescents with DS, lacking ER XbaI site, showed significantly higher BMI and body fat distribution than other XbaI genotypes. The lack of ER XbaI site can indicate added risk of obesity in DS. No differences in metabolic and cardiovascular parameters were observed among ER genotypes. However, childhood obesity is associated with increased cardiovascular risk.

The forms and severity of cardiac complications were investigated in patients with asymptomatic thalassemia intermedia and thalassemia major by M‐mode, bi‐dimensional echocardiography (ECHO) and echo‐Doppler. Twenty‐eight patients of both sexes with β‐thalassemia intermedia (β‐TI), mean age 23.2 ± 6.3 years, untransfused or minimally transfused, were compared to 42 age‐ and sex‐matched subjects with thalassemia major, who were regularly treated with hemotransfusive therapy [pre‐transfusion hemoglobin (Hb) values 9.5 ± 0.9 g/dL] and iron chelation. All patients were splenectomized. Age and sex matched healthy control subjects were randomly selected. β‐Thalassemia major (β‐TM) patients showed a marked reduction in contractile state and a milder left ventricular (LV) enlargement than β‐TI patients. Cardiac output (CO) and cardiac index (CI) were increased in both groups of patients but appeared significantly higher in β‐TI patients with consequent altered LV diastolic function indices. In addition, β‐TI pati...

Sixty‐seven homozygous male and female thalassemic patients with different phenotypes, aged between 8 and 33 years, were divided into three groups, according to the severity of their β‐thalassemia (thal) mutations. We investigated whether some co‐inherited genetic factors could influence the phenotype. Patients with milder β‐thal defects, homozygotes or compound heterozygotes for the IVS‐I‐6 (T→C) or −87 (C→G) mutations had a milder disease. In addition, determination of the co‐inheritance of the −158 (C→T) Gγ polymorphism and the (AT)9T5 repeat motif in the region −540 to −525, 5′ to the β‐globin gene, showed that in some patients with severe or mild/severe β‐thal mutations, linked to haplotype III, there was higher Hb F expression. We conclude that in homozygous β‐thal patients, the severity of the mutations is the most important factor influencing the phenotype, but some polymorphisms such as the −158 (C→T) Gγ and (AT)9T5 repeat motif, increasing the Hb F expression and ameliorate the clinical course o...

In 35 patients of both sexes (18 boys and 17 girls), mean age 8.9 ± 4.5 years, affected by migraine both with (45.2%) and without an aura (54.9%) (P0.05) who had no alteration of brain computerized tomography and/or magnetic resonance imaging, we evaluated possible thrombotic events in the pathogenesis of the disease. In all cases and in 50 random healthy controls clotting tests (prothrombin time, activated partial thromboplastin time, protein C activity (PC), antithrombin III (ATIII), protein S (PS), antiphospholipid antibodies (aPL), and Lupus anticoagulant (LA) were normal. FVIII and FIX activities were increased in seven and five migraine sufferers, respectively. Genetic thrombophilic risk factors - factor V Leiden (FVL) and MTHFR677T - resulted in a significantly increased prevalence in migraine patients when compared with controls but without significant differences for the F2 polymorphism. The examined polymorphisms were associated with an increased risk of developing migraine (odds ratio (OR)1). These findings could confirm the key role of a reduced cerebral flow in the pathogenesis of migraine and possible risk of ischaemic stroke (IS) but we feel that these observations need to be confirmed in larger multi-centre studies.

We examined the effect of vitamin D receptor (VDR) polymorphisms at exon 2 (FokI) and intron 8 (BsmI) on the stature and bone mineral density at femoral neck (FBMD) and lumbar spine (LBMD) in 108 prepubertal and pubertal homozygous beta thalassaemic patients, regularly treated. We found significantly shorter stature and lower LBMD and FBMD in all patients with CC VDR genotype, and significant shorter height and lower LBMD in prepubertal and pubertal female patients with BB VDR genotype. Because homozygous CC and BB VDR genotypes influence Vitamin D activity, they can be considered additional risk factors for bone disease in beta thalassaemia.

Objective and Importance: We have evaluated retrospectively in splenectomized hematologic patients by 10 year follow-up the incidence of thromboembolic events (VTE) in relationship not only with thrombocytosis but also with other possible risk factors, particularly anemia and some genetic mutations. Clinical presentation: Fifty children of both sexes with Hereditary Spherocytosis (HS), Piruvate Kinase Deficit (PK), Congenital Dyserythropoiesis II (CDII), Chronic Idiopathic Thrombocytopenic Purpura (cITP), β thalassemia intermedia (TI), splenectomized at 12.8 ± 6.2 years and untransfused or not transfused in the last 5 years were followed. Four patients with iron deficiency anemia had, on follow-up, deep venous thrombosis (DVT) during pregnancy (1 HS and 1 cITP) or after blood losses (2 PK deficits). Two patients with mild chronic anemia affected by CDII and TI respectively showed cerebrovascular thrombosis (CVT). None patient with VTE had genetic mutations. Intervention (& technique): Platelet count (PLT), Hb levels, clotting tests were performed once a year and compared with healthy controls. Genetic mutations of Methylentetrahydrofolate reductase (MTHFR) C677T, Factor V Leiden G1691A and Prothrombin G20210A were studied. VTE was diagnosed by Doppler Ultrasonography and Magnetic Resonance. Conclusion: CDII, TI and PK deficit subjects had altered Anti-thrombin III, Protein S, Protein C, activated partial thromboplastin time, thrombocytosis and lower Hb levels than other pat ients (p

In 29 symptomatic children of both sexes with chronic idiopathic thrombocytopenic purpura (CITP) with platelet counts < or = 30,000/mm3, of mean age 7.2 +/- 1.3 years, the side effects of long-term glucocorticoid therapy were evaluated. Patients were divided into three groups based on the different glucocorticoid protocols they were receiving. Baseline measurements (t0) of height (H) as standard deviation score (SDS), body mass index (BMI) as kg/m2 and bone mineral density (BMD) at the femoral neck (FBMD) and lumbar spine L2-L4 (LBMD) by a dual energy X-ray absorption technique, expressed as Z score, with follow-up measurements at 1 (t1) and 2 (t2) years were assessed. Group I patients (10 pts) treated with oral prednisone (2 mg/kg/die-for one month for 2 cycles) showed significantly different HSDS, BMI, FBMD and LBMD at t1 and t2 (P < 0.005) than other groups treated respectively with pulsed high doses of dexamethasone (24 mg/m2 over 4 days/months for 6 cycles) and methylprednisolone (9 mg/kg/die for 5 days for 3-4 months). These findings suggest that pulsed high doses of glucocorticoid lead to fewer side effects than oral prednisone therapy.

From 2005 to 2011, 25 children of both sexes (13 boys and 12 girls, mean age 7.8 ± 2.5 years, 5-12.4 years) with acute varicella zoster virus (VZV) infection were selected. Five patients showed venous thromboembolism characterized by deep venous thrombosis (DVT). Comparison of activated partial thromboplastin time, antithrombin III, D-dimer, lupus anticoagulant, free S protein (PS), C protein, and antiphospholipid and PS antibodies was performed on children with acute VZV and DVT (group I), acute uncomplicated VZV (group II), and 30 healthy controls of both sexes (15 boys and 15 girls, mean age 7.5 ± 2.6 years, group III). Genetic thrombophilic mutations (Factor V Leiden, MTHFR C677T, and Prothrombin G20210A) were evaluated. Coagulation disorders and PS antibody were found in children with acute VZV (groups I and II). Significant differences were shown among the three groups (P0.05). Acute VZV infection could be associated with coagulation disorders and production of inhibitory PS antibodies in many uncomplicated cases.

A population of 26 children of both sexes mean age 8.5 ± 5.8 years with thrombocytopaenic purpura, disease duration at least 7 months (2.5 ± 1.8 years), platelet count 22 000 ± 12 000/mm(3) was studied. Patients were divided into three age groups; I: 2-6 years (8 children); II: 7-10 years (10 children); III: 11-16 years (8 patients). Careful history, physical examination, complete blood count with blood smear, platelet autoantibodies, bone marrow aspirate, and response to intravenous immunoglobulins (IV Igs) were evaluated. Statistical analysis was performed by χ(2) test. Platelet count, duration of disease, megakaryocytic reduction, need of splenectomy were significantly lower in younger children than older children of III group (P0.05). All patients were responsive to IV Ig. No significant differences of presence of platelet autoantibodies, were found among the groups. Relapse after splenectomy was observed in four older patients among whom three had Evans syndrome: complete remission was obtained with rituximab. Disease duration appears to be associated to megakaryocytic alterations and patient age.

Recent reports have suggested, particularly in adults, an association between Helicobacter pylori infection (HPI) and chronic idiopatic thrombocytopenic purpura (cITP) with improvement of platelet count after eradication therapy. We investigated the association of HPI and cITP and the effect of HP eradication therapy on thrombocytopenia in a population of 24 children of both sexes mean age 8.0+/-0.28 years (range 5.4-10.7 years), affected by cITP (PLTor=50 x 10(9)/l) lasting more than 6 months. HPI was investigated by Helicobacter pylori stool antigens (HpSA). In eight out 24 patients (33.3%) HP infection was identified positive and bacterial eradication was successful following 7 days of triple therapy (amoxicillin, clarithromicin and proton pump inibitors). A follow-up of platelet count was performed for 1 year after HpSA detection. Six out eight patients (75%) had total recovery of platelet count during the first year after bacterial eradication (PLT before therapy 32.5+/-3.5 x 10(9)/l; after 1 year 275+/-106.06 x 10(9)/l) (P0.05), two patients (25%) had partial recovery (PLT before therapy 30 x 10(9)/l, after 1 year 103.5 x 10(9)/l) although not reaching statistical significance (P0.05). Non-significant differences were found in platelet count between infected and uninfected patients before eradication treatment (PLT 33.0+/-2.8 x 10(9)/l versus 34.0+/-5.75 x 10(9)/l) (P0.05), while significant differences were observed after eradication therapy (PLT 315.0+/-7.07 x 10(9)/l versus 43.5+/-2.12 x 10(9)/l) (P0.05). HP assessment should be performed in all cITP patients and eradication therapy should be attempted in positive cases.

Methylentetrahydrofolate reductase C677T genotype was assessed in 35 patients of both sexes aged between 3.2 and 5.4 years affected by Wilms tumor (WT) and in 70 random controls. Statistical analysis was performed comparing frequency of WT methylentetrahydrofolate reductase genotypes with 70 controls and a larger Italian population. The homozygous TT and heterozygous CT genotypes were associated with a significantly higher frequency of WT than CC genotype. By reducing tissue folate concentrations and inducing hypomethylation both TT and CT genotypes could be risk factors for WT (odds ratio >1).

The safety of low platelet thresholds for prophylactic transfusions was retrospectively evaluated in 673 children with various thrombocytopenic disorders. In patients with idiopathic thrombocytopenic purpura and X linked thrombocytopenia the threshold for the use of platelet transfusion was based on bleeding events rather than platelet count. In children with hypoproliferative thrombocytopenia and Wiskott–Aldrich syndrome, prophylactic platelet transfusions were used when the platelet count was ≤ 5000/μl in stable patients and > 10,000/μl in cases of bleeding or infections. The restrictive policy of platelet transfusions was shown to be proved safe in many thrombocytopenic disorders.

Two hundred and thirty-eight subjects of both sexes, age range 7.5 months-16 years, with iron deficiency (ID), were included in a retrospective review of ID causes, to determine the best treatment. Inadequate iron intake was the cause of ID or iron deficiency anemia (IDA) in 59 subjects from the first months of life to adolescence. Blood loss linked to cow's milk intolerance was the cause of ID or IDA in 37 younger children. Meckel's diverticulum (MD) (6 cases), reflux esophagitis (RE) (10 cases), some drugs such as acetyl salicylic acid (11 cases) induced bleeding with ID or IDA in children and adolescents. In pubertal females with ID or IDA, polymenorrhea was observed in 16 cases. Coelic disease (CD) (37 cases), Helicobacter pylori infection (HPI) (39 cases), association of HPI and CD (8 cases), enteromonas infection (15 cases), determining particularly malabsorption, were causes of ID or IDA in patients of a wide age range, unresponsive to iron therapy. Our findings show that iron replacement therapy was not always required and should not be prescribed until the diagnosis is certain.

The forms and severity of cardiac complications were investigated in patients with asymptomatic thalassemia intermedia and thalassemia major by M-mode, bi-dimensional echocardiography (ECHO) and echo-Doppler. Twenty-eight patients of both sexes with beta-thalassemia intermedia (beta-TI), mean age 23.2 +/- 6.3 years, untransfused or minimally transfused, were compared to 42 age- and sex-matched subjects with thalassemia major, who were regularly treated with hemotransfusive therapy [pre-transfusion hemoglobin (Hb) values 9.5 +/- 0.9 g/dL] and iron chelation. All patients were splenectomized. Age and sex matched healthy control subjects were randomly selected. beta-Thalassemia major (beta-TM) patients showed a marked reduction in contractile state and a milder left ventricular (LV) enlargement than beta-TI patients. Cardiac output (CO) and cardiac index (CI) were increased in both groups of patients but appeared significantly higher in beta-TI patients with consequent altered LV diastolic function indices. In addition, beta-TI patients had reduced indices of pulmonary artery flow related to long-term chronic anemia rather than iron overload. The progressive rise in CO and CI casts doubts on the current management of beta-TI syndromes.

Sixty-seven homozygous male and female thalassemic patients with different phenotypes, aged between 8 and 33 years, were divided into three groups, according to the severity of their beta-thalassemia (thal) mutations. We investigated whether some co-inherited genetic factors could influence the phenotype. Patients with milder beta-thal defects, homozygotes or compound heterozygotes for the IVS-I-6 (T--C) or -87 (C--G) mutations had a milder disease. In addition, determination of the co-inheritance of the -158 (C--T) G(gamma) polymorphism and the (AT)9T5 repeat motif in the region -540 to -525, 5' to the beta-globin gene, showed that in some patients with severe or mild/severe beta-thal mutations, linked to haplotype III, there was higher Hb F expression. We conclude that in homozygous beta-thal patients, the severity of the mutations is the most important factor influencing the phenotype, but some polymorphisms such as the -158 (C--T) G(gamma) and (AT)9T5 repeat motif, increasing the Hb F expression and ameliorate the clinical course of the disease.

Few studies are available on left ventricular diastolic function in beta-thalassemia major, and these have conflicting results. Our aim in this study was to analyze myocardial systolic and diastolic functions in patients with beta-thalassemia major using, for the first time, pulsed Doppler tissue imaging (DTI), and compare data with standard Doppler echocardiography. We studied 30 young patients with beta-thalassemia major (age

We examined the effect of vitamin D receptor (VDR) polymorphisms at exon 2 (FokI) and intron 8 (BsmI) on the stature and bone mineral density at femoral neck (FBMD) and lumbar spine (LBMD) in 108 prepubertal and pubertal homozygous beta thalassaemic patients, regularly treated. We found significantly shorter stature and lower LBMD and FBMD in all patients with CC VDR genotype, and significant shorter height and lower LBMD in prepubertal and pubertal female patients with BB VDR genotype. Because homozygous CC and BB VDR genotypes influence Vitamin D activity, they can be considered additional risk factors for bone disease in beta thalassaemia.

This epidemiological study was based on a hematological and a molecular analysis of 310 heterozygous beta thalassemic and 75 carriers of Hb Lepore out of 3,000 microcythemic subjects from the Campania region of Italy. The molecular analysis of beta chains and the deltabeta hybrid gene has shown different beta chain defects, but only the Hb Lepore-Boston-Washington type in association with haplotypes I and V. The prevalence and distribution of these molecular defects in Campania show that they are linked to historical events and to the geographical characteristics of this region.

The idiopathic hypereosinophilic syndrome (HSE) is a new heterogeneus disorder characterized by persistent unxplained hypereosinophilia (eosinophil count > 1.5 x 10 9 /L) persisting at least 6 months with possibile organ involvment. The diagnosis of HSE is based on exclusion criteria of other causes of eosinophilia. We reporte a case of an atopic 3 year-old male child with a history of eczema since first years of life and hypereosinophilia. At admission he showed severe generalized eczema with pruritus pain in the jonts, fever, several athsma, mild hepatosplenomegaly and lymphoadenomegaly. Biological findings included mild hypochromic microcytic anemia (Hb 10.5 g/dl, MCV 65 μ3, MCH 23 pg) due to heterozygous α thalassemia -delection (α) −37-, hyperleukocitosis (WBC 45.5 x 10 3 / μL) and hypereosynophilia (20.9 x 10 3 / μL). Bone marrow aspiration revealed absence of blast cells, mild reduction of myeloid (40%) and erythroid cells (10%) with increased M/E ratio 6/1. The eosynophilic cells represented 35%. Some of these cells presented cytoplasmatic atypia. Blood lymphocyte immunophenotypical analysis showed increased values of T lymphocytes CD3+, B lymphocytes CD19+ and T helper lymphocytes CD3+CD4+ Serum IgE levels were increased. Cytokines serum levels were undectable. Karyotype was 46XY. Non cytogenetic abnormalities were found in myeloid cells. Specific viral antibodies as well as autoantibodies and parasitologic assessements were negative. Corticosteroids were used with mild clinical improvement, followed by worsenings when the drug was stopped. The absence of blast cells or cytogenetic abnormality favor the diagnosis of HSE. However some patients in whom a diagnosis of idiopathic HSE appears appropiate may subsequently develope malignancies. A systematic survey of a large group of patients with otherwise unexplained eosinophilia is needed as well as a prolonged follow up of patients to early evaluate in each case neoplastic risk.