1. Iron deficient anemia in children Department of pediatrics

2. Definition: Iron deficient anemia is an anemia determined by insufficient assimilation of iron and is characterized by reducing of Hb quantity, reducing of serum iron and increasing of general iron binding capacity of blood plasma.

3. Epidemiologic data Iron deficient anemia (IDA) represents a major problem of public health both in developing countries, and in industrialized countries also, affecting individually and economically the population. The consequences of IDA have a major importance for children and adolescents, including disorders of immune function, retention in physical and psychomotor development, potential irreversible deficit in system of coagulation and motor function. The latent deficiency of iron is registering in 30% of earth globe population and in children from developing countries more than 50%.

4. IDA represents maximal prevalence in 6-20 months old infants (earlier in premature term babies) and in the puberty period. In developing countries IDA constitutes 36% in children until 5 years age, and in industrialized countries – 20%.

5. Classification of IDA Prelatent iron deficiency (Phase 1) Exhaustion of iron storages in tissues, the level of transport iron and hemoglobin are normal Latent iron deficiency (Phase 2) Exhaustion of iron storages and of transport iron fraction. The first clinical signs of anemia appear. Iron deficient anemia (Phase 3) Insufficiency of iron in organism and reducing of Hb concentration. The clinical manifestations include anemic + sideropenic syndrome + other manifestations with trophic disorders

6. Classification conformable to degree of severity Soft IDA Hb – 120-91 g/l (child > 5 years) Hb – 110-91 g/l (child < 5 years) Medium IDA Hb – 90-71 g/l Severe IDA Hb – 70-51 g/l

7. The risk factors of IDA appearance: The insufficient level of iron in organism (disorder of blood feto-placental circulation, syndrome of fetal transfusion in the case of multiple pregnancy, intrauterine melena, prematurity, long-term severe anemia in pregnant woman, tardy or precocious ligature of umbilical cord, intranatal hemorrhage as a result of traumatism due to obstetrical intervention or some developmental anomaly of placenta or umbilical vessels. Increased needs of organism in iron (prematurity, baby with big body mass at birth, babies in the second half of first year of life, adolescents.

8. Insufficiency of iron in foods (early introducing of bottle feeding, feeding preponderantly with cow’s or goat’s milk, with non-adapted formulas, flour products, milk products or lacto-vegetarian diet, non- equilibrated diet). Losses of iron after hemorrhages by diverse etiology, disorders of intestinal absorption (chronic bowel inflammatory diseases, malabsorption syndrome) also marked and long-term metrorrhagies in girls. Disturbance of iron metabolism (hormonal prepuberty and puberty period disequilibrium)

9. Disturbance of iron transport and utilization in organism (hypo- and atransferrinemia, enzymopathies, autoimmune processes) Insufficient reabsorption of iron in GIT (agastral and postresection states) Parasite diseases

10. High risk groups Premature babies Babies from multiple pregnancy or associated with gestoses, feto-placentar insufficiency, complications of chronic pathologies in pregnant women Children with disturbance of intestinal flora or food allergy Bottle fed babies Babies with hypotrophy Children with accelerated growing Children with rickets Frequently ill children

11. Procedures of IDA diagnosis Anamnesis Complex physical examination Obligatory laboratory investigations: - General peripheral blood analysis - Determination of Hb concentration and content in one erythrocyte - Serum iron level - Iron binding capacity (general and latent) of plasma (as possible) - Coefficient of transferrin saturation (as possible) - Serum ferritin (as possible) · Recommendable paraclinical investigations.

12. Anamnesis Recommendations for anamnesis collection:  Evidence of risk factors  Collection of antenatal, postnatal anamnesis  Sudden onset of disease

13. Physical examination The rules of physical examination in IDA:  Complete physical examination  Appreciation of general state  Evidence of IDA clinical signs: - Anemic syndrome: pallor of teguments and mucosae, dyspnea, tachycardia, low cardiac beats, functional systolic murmur at apex, neuroastenic phenomena. - Sideropenic syndrome (in little age infants it is not significant): epithelial changes (trophic changes of skin, nails, hair, mucosae), perversity of taste (pica cholotica) and smell, vegeto-vascular reactions, disorders of intestinal absorption, dysphagia, dyspepsia, decreasing of local immunity.

14. Paraclinical investigations Obligatory investigations: General analysis of peripheral blood, including reticulocytes, thrombocytes Serum iron level Iron binding capacity (general and latent) of plasma (if possible) Coefficient of transferrin saturation (if possible) Serum ferritin (if possible)

15. Recommendable investigations for the evaluation of etiology and differential diagnosis: Biochemical blood analysis: total bilirubin and its fractions, urea, creatinine, ALAT, ASAT, general LDH, K, Na, Ca ions General analysis of urine ECG EchoCG Abdominal ultrasonography X-ray chest Medullar (bone marrow) punction

16. 1. General blood analysis: decreasing of Hb level, hypochromia, microcytosis, anizocytosis, poikilocytosis 2. Reduced level of serum iron: < 14 µmol/l 3. Increased iron binding capacity (general and latent) of plasma: > 63 µmol/l (general), < 47 µmol/l (latent) 4. Decreased percent of transferrin saturation: < 17% (latent phase), < 15-16% (IDA) 5. Decreased serum ferritin: < 12 µg/l

17. Differential diagnosis Deficient anemias (deficiency of proteins, vitamins) Sideroblastic (protoporphirin synthesis deficit) anemias Hemolytic, aplastic anemias Anemias in chronic diseases

18. Sideroblastic anemias are characterized by: Hypochromia of erythrocytes High level of serum iron Increasing of transferrin saturation Increasing of sideroblasts count in bone marrow

19. Hemolytic anemias are characterized by: Erythrocytary hypochromia Erythrocytary microcytosis Presence of erythrocytes in the form of “target” Presence in erythrocytes of basophilic dotting Normal or increased serum iron Reduced general iron binding capacity of plasma Reticulocytosis Moderate increasing of indirect bilirubin Splenomegaly (not obligatory) Absent efficacy of treatment with iron preparations

20. Anemias in chronic diseases are characterized by: Moderated hypochromia Normal or slight reduced serum iron Normal or decreased iron binding capacity of plasma Increased level of serum ferritin Increased count of sideroblasts in bone marrow Clinical and laboratory signs characteristic for some active process (inflammatory, tumoral) – fever, pathology of corresponding organ Absent effect after iron preparations administration

21. The basic principles of treatment with Fe preparations: The recovery of iron deficit is impossible without medicamental treatment Thermic and mechanical processing of aliments doesn’t increase the iron absorption The therapy of IDA must be performed preferentially with peroral iron preparations The therapy of IDA will be not interruped after Hb level and RBCs count restoring The hemotransfusions in IDA will be performed only at vital indications

22. The treatment of IDA with peroral preparations: The advantages of peroral therapy: - It increases the level of Hb 2-4 days later than in the case of parenteral administration - The peroral preparations rarely induce substantial adverse reactions, in contrast with parenteral preparations - They don’t lead to development of hemosiderosis in the case of incorrect establishment of diagnosis The indicated iron preparations: · Monopreparations: - Complex of Fe +++ hydroxide with polimaltose: sirup, solution, pills - Iron chloride: solution, pills - Iron sulfate: pills · Combined preparations (Fe, Mn, Cu): solution, pills

23. The doses: AgeDoses of elementary iron (active) < 5 years4 – 6 mg/kg/24 hours 5 – 12 years75 – 100 mg/24 hours 12 – 18 years150 – 200 mg/24 hours

24. The mode of administration: The therapy of IDA with drugs containing iron sulfate will begin with doses equal to ¼-1/2 from therapeutic dose during 7 – 14 days (taking into account the individual tolerance of patients) The daily dose is divided and administered in 2 – 3 times per day The bivalent preparations are recommended to be administered 1 hour before meal The administering of iron preparations must be done without tea, milk because they decrease the drug absorption The concomitant administration with calcium preparations, tetracyclines, penicilamine is not recommended. The following forms of drugs will be administered in dependence of age: Sirup, drops – little age infants Pills, capsules – in older children and adolescents

25. Duration of treatment: Stages I degree of IDA II degree of IDAIII degree of IDA Restoring of Hb level 1 month2 months3 months Restoring of iron storage 1 month2 months3 months

26. The treatment of IDA with parenteral preparations: Indications: Stages after stomach, small intestine resection Malabsorption syndrome Non-specific ulcerative colitis Chronic enterocolitis Anomalies of gastro-intestinal tract Chronic esophagitis Intolerance of peroral preparations

27. Contraindications: Aplastic anemia Hemolytic anemia Hemosiderosis, hemochromatosis Sideroblastic anemias Thalassemia Other anemias not caused by iron deficiency

28. Hemotransfusions in IDA: Hemotransfusions of erythrocytary mass are performed rarely and strictly at vital indications. The criteria for hemotransfusion are: - decreasing of Hb under critical level and symptoms of central hemodynamics disorders - hemorrhagic shock, preanemic comas, hypoxic syndrome In the case of massive hemorrhages the hemotransfusions can be performed if the level of Hb and Ht is more than that critical.

29. Additional therapy Eubiotics for children with disorders of intestinal microflora spectrum Vitamin C 250 – 500 mg 2 times per day, administered together with iron preparations – in the case if it is not included in iron-containing preparation

30. Control of therapy effectiveness Indices of administered therapy effectiveness: Improvement of patient’s state Reticulocytosis at the 10 – 14 th day from the treatment beginning Restoring of Hb level in 3 – 4 weeks Monthly increasing of Hb with 10 – 20 g/week in the first 2 – 3 weeks, ulterior slower Normalizing of clinical and laboratory indices at the end of treatment

31. Prognosis Evolution and prognosis of IDA are favorable, with condition of generator cause removing. The soft forms have tendency to itself correction through increasing of iron absorption and storages restoring, realizable in conditions of some adequate intake of iron. Absence of response to the treatment with iron preparation can mean: - correctitude of etiologic diagnosis (association of inflammatory infections, hepatic or renal disease etc.); - righteousness of therapeutic prescribing (dose, way of administration, duration); - respecting of therapeutic indications; - existence of some associated diseases or not resolved complications (bleeding, exudative and/or hemorrhagic enteropathy, malabsorption, deficiency associated with folic acid).

32. The follow-up of patients with IDA: The follows will be performed at each 10 – 14 days during the treatment: - Clinical examination; - General blood analysis (Hb, RBCs, RBCs’ morphology, leucogram) After Hb level normalizing in each month during 1 year the follows will be done: - Clinical examination - Laboratory tests (Hb, RBCs – count and morphologic peculiarities After that in each trimester in the next three years the follows will be done: - Hb, RBCs, color index, reticulocytes, leucogram, ferritin.

33. The children are putted out from evidence and are transferring from the II group of health in the I group after 1 year of clinical and laboratory indices normalizing. All premature children are followed-up during the first year of life. Immunization of patients with IDA will be performed after Hb level normalizing.

34. The emergency states and complications: The emergency states: In the department of emergency therapy the children with anemic shock, babies of first year of age and children with Hb < 60 g/l will be admitted. The complications of IDA: - growing disorders - accelerated or irregular cardiac rhythm - physical and mental retardation - increased rate of led intoxication (saturnism) - increased susceptibility to infections

35. Primary prophylaxis of IDA: Primary non-specific prophylaxis Antenatal (pregnant women): Equilibrated (quantitatively and qualitatively) alimentation Walking on fresh air Postnatal: Natural alimentation with introducing of complement, of produces containing iron (especially for infants from risk group); Using of adapted milk formulas supplemented with iron (in bottle fed infants); Respecting of daily regime, walking on fresh air; Prophylaxis and treatment of rickets, hypotrophy and other associated pathologies in infants; Monthly performing of general blood analysis.

36. Primary specific prophylaxis Antenatal: Treatment of IDA in pregnant women Supplementation of iron intake with long-term acting or combined drugs (Fe + polivitamins) for pregnant women in the first pregnancy from the second half of pregnancy, for pregnant women with multiple or second (and more) pregnancy during the II and III trimester.

37. Postnatal: The peroral iron preparations (iron sulfate) to premature babies in dependence of prematurity degree are administering in the dose of 3-5 mg/kg from the 4 th week of life. The iron enriched adapted formulas for bottle fed infants and these from risk group will be recommended from the age of 3-5 months of life, and for premature babies from 1.5-2 months of life. the content of iron in artificial milk formulas will be 3-5-8 mg/l in the first half of I year of life and 10-14 mg/l in the second half. The prophylactic administration of iron preparations is recommended for infants from risk group (breast fed premature babies or which didn’t receive iron enriched adapted formulas, babies from multiple pregnancy, with big birth weight, with accelerated growing). The daily dose of active iron will constitute 2-3 mg/kg during 1 month with verifying of blood indices. Note: the prophylaxis of IDA will be done with peroral preparations that will be given daily

38. Secondary prophylaxis Rational alimentation - breast feeding - avoidance of precocious introducing (before 4-5 months) of solid aliments, with unfavorable effect on iron absorption - when breast feeding is not available - bottle feeding with iron enriched powder milk formulas - diversifying with meat products (the rate of iron assimilation is 20 times better than from vegetal products), cereals, iron enriched mash vegetables and fruits - avoidance of phytates, phosphates and calcium salts excess, because they have inhibitor effect on iron absorption More time at fresh air Follow-up by family doctor

39. Thank you for attention.