الفهرس 
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Abstract
The prevalence of obesity in children has increased dramatically. This worldwide epidemic has important consequences and lead to appearance of obesity-related comorbid disease entities at an early age. It was found that obesity is associated with iron deficiency and iron profile abnormalities, which appear to be caused by several factors such as decreased intake, insufficient bioavailability, and deficient intestinal iron uptake as well as iron release from stores because of an overexpression of hepcidin. Hepcidin is a small peptide produced by hepatocytes, secreted into plasma, and excreted in urine. Hepcidin expression in adipose tissue has been described and shown to be increased in patients with obesity. It is proposed to be a key regulator of iron metabolism. High hepcidin in obese may be associated with diminished response to oral iron therapy in childhood iron deficiency anemia. Lactoferrin is a member of the transferrin family of iron-binding glycoproteins. Using lactoferrin has been described to counteract inflammatory disorders by down regulating IL-6 and subsequently hepcidin transcription and by up-regulating ferroportin expression, to redistribute endogenous iron between tissue/secretions and blood. Lactoferrin has been proposed as an alternative to traditional therapies in iron deficiency anemia and anemia of inflammation. The aim of this work was to evaluate the role of serum hepcidin and IL-6 levels in obese children and adolescents and their association with iron deficiency anemia and to compare the efficacy of lactoferrin and oral iron therapy in treatment of obese children and adolescents with iron deficiency anemia. This study was carried out on 80 children and adolescents recruited from the pediatric nutrition outpatient clinic in gastroenterology and nutrition unit of pediatric department, Tanta university hospitals in the period between January 2019 and December 2020. They were randomized as follows: • Group1: Included 40 obese children and adolescents (BMI ≥ the 95th percentile for gender and age) with iron deficiency anemia. • Group2: Included 20 obese children and adolescents not suffering from iron deficiency anemia. • Group3: Included 20 apparently healthy non obese children and adolescents (BMI between 5th and 85th percentile for gender and age) of matched age and sex served as controls. Patients in group 1 were simply randomized into 2 subgroups: • group A: Twenty children and adolescents were given regular oral lactoferrin supplementation in a dose of 100 mg/day 15 minutes before meal for 3 months. • group B: Twenty children and adolescents received regular oral iron supplementation (Ferric hydroxide polymaltose) in a dose of 6 mg elemental iron/kg /day 2hours after meals for 3 months. All children and adolescents in the study were subjected to: A. Full history taking B. Thorough clinical examination C. Anthropometric measures: Weight, height, and body mass index (BMI). All measures were plotted on growth charts, and Z-scores calculations were done. D. Investigations included: Routine investigations (CBC, ALT, AST, blood urea, serum creatinine, CRP), investigations to exclude other causes of anemia (stool analysis, occult blood in stool, hemoglobin variants by HPLC), research investigations (iron profile, serum hepcidin and serum IL6) and abdominal ultrasound. E. Children in the therapy group had monthly follow up of CBC. Iron profile, hepcidin and IL6 were repeated after 3months of therapy. F. Informed written parental consent was obtained from every case that participated in this research. The study was approved by the Ethics committee of Faculty of Medicine, Tanta University. This study revealed the following results: Significantly higher caloric intake, vitamin C intake in obese patients (Groups 1and 2) than controls (Group3). Significantly higher total iron and heme iron intake in obese children without iron deficiency anemia (Group2) than obese children with iron deficiency anemia (Group1) and controls (Group3) with no significant difference between obese children with iron deficiency anemia (Group1) and controls (Group3). Hematological data (Hemoglobin, MCV and MCH) were significantly lower in obese children with iron deficiency anemia (Group1) than obese children without iron deficiency anemia (Group2) and controls (Group3). No significant difference was detected between obese children without iron deficiency anemia and controls. Serum ferritin, serum iron and transferrin saturation were significantly lower in obese children with iron deficiency anemia (Group1) than obese children without iron deficiency anemia (Group2) and controls (Group3). No statistically significant difference was found between obese children without iron deficiency anemia and controls. TIBC was significantly higher in obese children with iron deficiency anemia than obese children without iron deficiency anemia (Group2) and controls (Group3) with no statistically significant difference between obese children without iron deficiency anemia and controls. According to transferrin saturation parameter: Significant positive correlation between: • Transferrin saturation and serum iron in obese children with and without iron deficiency anemia. • Transferrin saturation and (hemoglobin, MCV, serum ferritin, serum iron) in obese children (Groups 1 and 2). Significant negative correlation between: • Transferrin saturation and TIBC in obese children (Groups 1 and 2). Significantly higher CRP, IL6 in obese children than controls with no significant difference between obese children with iron deficiency anemia (Group1) and obese children without iron deficiency anemia (Group2). Significant positive correlation between serum IL6 and BMI in obese children with iron deficiency anemia (Group1). Serum hepcidin was significantly higher in obese children than controls with no statistically significant difference between obese children with iron deficiency anemia (group 1) and obese children without iron deficiency anemia (group 2). Serum hepcidin on the basis of gender: • No significant difference in serum hepcidin between male and female children in each group. • Significant difference serum hepcidin between male obese children and controls. No significant difference was found between male obese children with iron deficiency anemia (group 1) & male obese children without iron deficiency anemia (group 2). • Significant difference serum hepcidin between female obese children and controls. No significant difference was found between female obese children with iron deficiency anemia (group 1) & female obese children without iron deficiency anemia (group 2). Serum hepcidin on the basis of Tanner staging: • No significant difference in serum hepcidin between pre-pubertal and pubertal children in each group. • Significant difference serum hepcidin between pre-pubertal obese children and controls with no significant difference between prepubertal obese children with iron deficiency anemia (Group1) and pre-pubertal obese children without iron deficiency anemia (Group2). • No significant difference serum hepcidin was found between pubertal obese children and controls. Serum hepcidin level at a cut off value 107.89 ng/ml or more yielded a sensitivity of 93.33% and a specificity 35% as a marker of obesity. Significant positive correlation was found between serum hepcidin and BMI in obese with iron deficiency anemia (Group1). Significant positive correlation was found between serum hepcidin and IL6 in obese children (Groups 1 and 2). Significant negative correlation was detected between serum hepcidin and hemoglobin in obese with iron deficiency anemia (Group1). The follow up study revealed: Significantly higher hematological parameters (hemoglobin, MCV and MCH) in the lactoferrin and iron therapy groups after 1,2 and 3 months with higher improvement in the lactoferrin therapy group. Significantly higher ferritin, serum iron and transferrin saturation in both lactoferrin and iron therapy groups after 3months of therapy with higher response in the lactoferrin versus the oral iron group. Significantly Lower TIBC after 3 months of lactoferrin therapy while the decrease in TIBC was not significant in the iron therapy group. Significantly lower serum hepcidin and IL6 were detected after 3months of lactoferrin therapy with no significant difference in both markers after 3months of iron therapy. As regard improvement of hemoglobin after therapy: • After 1 month of therapy: normalization of the hemoglobin was observed in 25% of anemic obese children who received lactoferrin therapy compared to 5% of the children treated with oral iron. • After 3 months of therapy: normalization of the hemoglobin was observed in 95% of anemic obese children who received lactoferrin therapy compared to 65% of the iron therapy group. The difference was statistically significant. As regard improvement of transferrin saturation after therapy: • 90% of anemic children treated with lactoferrin had transferrin saturation >16% after 3months compared to 55% of participants in the oral iron therapy group and the difference was statistically significant. As regard adverse effects of therapy • In the iron therapy group, 30% of the children had gastric irritation, 35% had nausea, 40% had abdominal pain, 55% had constipation and 75% experienced dark stools. • Children in the lactoferrin therapy group experienced fewer side effects. Only 5% had gastric irritation, 5% had nausea, 15% had constipation. No dark stools or abdominal pain were observed in the lactoferrin therapy group.