Hematology / Oncology

Iron Deficiency Anemia

Background

Iron deficiency is the most common nutritional disturbance in pediatrics and the number one cause of anemia in the pediatric age range, affecting 2-3% of toddlers and 3% of adolescent girls. In the United States, the prevalence of iron deficiency is higher among children living at or below the poverty level, and in Black and Hispanic children. Other risk factors for iron deficiency include childhood obesity and a history of prematurity or low-birth-weight.  The incidence of anemia secondary to iron deficiency has decreased with the increased incidence of breast feeding, the addition of iron to formula (12 mg/L), and the development of WIC programs. 

Iron is an essential nutrient absorbed in the proximal small intestine.  Iron in foods comes in two forms: heme iron bound within hemoglobin and myoglobin, found in meat and fish, and non-heme iron such as iron salts, found in plant products.  Heme iron is better absorbed (30% vs 10%), and thus iron deficiency may be a problem in vegetarian children.  Absorption of non-heme iron can be improved by addition of other factors such as ascorbic acid. Inhibitors of iron absorption include bran, vegetable fiber, tannic acid found in tea, and phosphates.

Etiology

  1. Poor dietary intake
    1. Infants must absorb 0.5-0.8 mg/day; breast milk contains 0.3 to 1.0 mg/L iron but has a high bioavailability (50 percent); formulas with 12 mg/L iron have 4 to 6 percent bioavailability
    2. Recommended daily allowances: 1 mg/kg/day for FT infants, 2-4 mg/kg/day for premature infants; 7-10 mg/day for children 1-13 years old
  2. Low birth weight
    1. Blood loss at birth
    2. Increased requirement due to rapid catch-up growth.
    3. Without supplementation, SGA infants may demonstrate iron deficiency at 2 months of age; the normal newborn has enough iron stores to last 4 months without supplementation.
  3. Early introduction of whole cow's milk (at less than 12 mos)
  4. Blood loss- more common in older children
    1. Meckel's diverticulum
    2. malabsorption and inflammatory bowel disease
    3. milk protein intolerance with blood loss
    4. polyps and hemangiomas of the GI tract . 
    5. Heavy menses with poor diet in adolescents associated with increased growth rate
  5. Increased demands associated with chronic hypoxia
  6. Urine loss with intravascular hemolysis
  7. Lung losses with pulmonary hemosiderosis and Gooodpasture's syndrome.

Clinical manifestations

  1. Irritability
  2. Pica- may have concurent lead poisoning
  3. Exercise intolerance
  4. Inattentive, cognitive delays, impaired psychomotor development
  5. Pallor (often more severe)

Screening recommendations

  1. Focused history for all patients to identify risk factors
  2. AAP: universal screening with at least H/H at 12 mos (Hgb < 11 g/dL is abnormal); repeat at 15-18 months if high-risk
  3. AAP: Annual H/H for menstruating girls; H/H once for boys during peak growth phase

Diagnosis

  1. Usually clinical, with empiric trial of iron supplementation
    1. Provide 3 mg/kg of elemental Fe BID (see Treatment, below)
    2. If Hgb rises 1 g/dL over 4 weeks, Dx is confirmed
  2. Consider further laboratory evaluation if empiric trial fails or anemia is severe (e.g. <7 g/dL). Abnormalities in iron deficiency include:
    1. Serum ferritin, an iron storage protein, is low
    2. Decreased serum iron, increased iron binding capacity, < 16% Fe saturation
    3. Microcytosis, hypochromia, anisocytosis, poikilocytosis
    4. Increased red cell distribution width (RDW)
    5. Decreased absolute reticulocyte count with inadequate response to anemia.
    6. Normal WBCs 
    7. Thrombocytosis
    8. Decreased iron staining in the bone marrow

Differential Diagnosis

  1. Lead levels above 100ug may be associated with microcytosis.
  2. Alpha thal trait and Beta thal trait may be associated with low MCV, but RDW is WNL
  3. Chronic disease often have normochromic and normocytic anemia, but may be microcytic. The ferritin is usually normal to elevated.

Treatment

  1. 6 mg/kg/day of elemental iron. Ferrous sulfate contains 20% elemental iron. Fer-in-sol, contains 25 mg of elemental iron/cc.  Major side effects are GI (e.g. diarrhea, stool changes, cramps).
  2. Diet adjustments- increase amount of Fe in the diet and eliminate whole cow's milk if under 12 months
  3. In 3-4 days will see a reticulocyte response and after 2 months of therapy, bone marrow stores replenished.
  4. Blood transfusions rarely necessary
  5. Can consider parenteral therapy (iron dextran) in older patients with intolerance of or noncompliance with oral therapy
  6. Reasons for treatment failure
    1. Wrong diagnosis
    2. Failure to take the medicine or wrong dosage
    3. Associated folate deficiency(B6)
    4. Malabsorption of Fe (e.g. IBD)
    5. Ongoing blood/iron loss

Prevention of Iron Deficiency

  1. Encourage breast feeding for 6 months; consider adding another source of iron such as a supplement or iron-fortified cereal at 4-6 mos.
  2. If not breastfed, use iron fortified formulas for 12 months
  3. At 6-12 months, encourage foods rich in vitamin C
  4. Use iron fortified cereals
  5. Avoid whole cow's milk until after 12 mos
  6. Once eating solids, parents should provide diet high in Fe- cereals, green vegetables, meat, and chicken.

References

  1. Brotanek, Jane M., et al. Iron deficiency in early childhood in the United States: risk factors and racial/ethnic disparities. Pediatrics 120.3 (2007): 568-575.
  2. Wu, Ann Chen, Leann Lesperance, and Henry Bernstein. Screening for iron deficiency. Pediatrics in Review 23.5 (2002): 171-178.
  3. Zlotkin S. Single Vervus Three-Times-Daily Iron Drops to Treat Anemia Pediatrics September 2001
  4. Richardson M,  Microcytic Anemia. Pediatrics in Review Jan 2007
  5. AAP. Diagnosis and Prevention of Iron Deficiency and Iron Deficiency Anemia in Infants and Young Children (0-3 Years of Age) Pediatics November 2010
  6. Zimmermann, Michael B., and Richard F. Hurrell. Nutritional iron deficiency. The Lancet 370.9586 (2007): 511-520.
  7. Maguire, Jonathon L., et al. Association Between Total Duration of Breastfeeding and Iron Deficiency. Pediatrics 131.5 (2013): e1530-e1537.