Basics
Description
A reduction in hemoglobin production due to an insufficient supply of iron that results in a microcytic, hypochromic anemia
Epidemiology
- Iron deficiency is the most common nutritional deficiency of children.
- Leading cause of anemia among infants and children in the United States
- Most commonly seen in children ages 9 months-3 years and in teenage girls
Prevalence
- Prevalence is variable depending on socioeconomic status, availability of iron-fortified formulas, and prevalence and duration of breastfeeding.
- Prevalence of iron deficiency anemia in United States is generally between 1% and 5% of children.
Risk Factors
- Low socioeconomic status
- Certain ethnic groups (e.g., Southeast Asian) may be at increased risk due to dietary practices.
- History of prematurity
General Prevention
- Maintain breastfeeding for the first 5-6 months of life if possible.
- Breast milk has lower iron concentration than formula, but iron in breast milk is more bioavailable (50% vs. 10%).
- Iron supplementation
- 1 mg/kg/day for infants who are exclusively breastfed beyond 4 months
- 2 mg/kg/day by 1 month of life for low-birth-weight and premature infants who are breastfed because of poor iron stores and increased growth rate
- Iron-fortified formula for the first 12 months of life for infants who are not breastfed
- Encourage iron-enriched cereal when infants are started on solid food.
- Avoid whole cow's milk during the 1st year of life to prevent occult GI bleeding.
- Screen hemoglobin level at periodic intervals.
- The American Academy of Pediatrics recommends screening at 12 months, 1-3 years old, and adolescents as well as annually in menstruating females.
- CDC recommends screening high-risk groups annually between ages 2 and 5 years and all menstruating women every 5-10 years.
Pathophysiology
- Iron is required for oxygen transport by hemoglobin.
- Iron absorption and distribution is regulated by hepcidin, a peptide hormone secreted by liver, macrophages, and adipocytes.
- Iron is absorbed primarily in the duodenum.
- Iron deficiency develops because of an inadequate supply or increased demand for iron or a combination of these.
- Sequential stages of iron deficiency
- Depletion of iron stores: reflected by low serum ferritin and absent bone marrow stores
- Iron-deficient erythropoiesis: Near-normal number of red blood cells (RBCs) produced, but they have abnormal hemoglobin synthesis with wide distribution in RBC size.
- Iron deficiency anemia: microcytosis evident
Etiology
- Causes of inadequate supply include dietary deficiency and malabsorption.
- Dietary deficiency in infants and young children results from introduction of cow's milk prior to age 12 months, exclusive breastfeeding beyond age 6 months without iron supplementation, and excessive cow's milk intake (>24 oz/day).
- Malabsorption results from surgical resection of intestine or celiac disease.
- Certain foods impair iron absorption (tannins in tea and coffee, phytates).
- Causes of increased demand include rapid growth and blood loss.
- Periods of rapid growth include infancy (especially low-birth-weight and premature infants) and adolescence.
- GI blood loss is most common and includes cow's milk enteropathy (seen in infants), inflammatory bowel disease (IBD), and bleeding from Meckel diverticulum.
- Other etiologies of blood loss include perinatal loss, menorrhagia, pulmonary hemosiderosis, and hematuria.
Diagnosis
History
- Evaluate dietary intake of iron, including breast- or formula feeding and type of formula (iron fortified or low iron).
- Age at introduction of cow's milk
- Daily intake of cow's milk
- Birth history for prematurity or blood loss
- Lead exposure
- Blood loss from urine, stool, menorrhagia
- Iron deficiency anemia often develops slowly, and no symptoms may be present. When present, signs and symptoms include the following:
- Irritability and behavioral disturbances
- Fatigue, exercise intolerance
- Pallor
- Headache
- Pica or pagophagia (chewing ice)
Physical Exam
- Often normal
- Pallor, irritability
- Tachycardia, flow murmur if anemia is more severe
- Koilonychia (spoon nails)
- Glossitis or stomatitis
Diagnostic Tests & Interpretation
Lab
- Hemoglobin level <2 standard deviations below the age-specific mean defines anemia.
- Low MCV (red cell volume) and MCH (hemoglobin concentration) for age
- High RDW (red cell distribution width)
- Measures the variation in red cell size
- Normal is <14.5%.
- Often increased before anemia is present
- Low serum ferritin (≤12 ng/mL) reflects reduced tissue iron stores.
- Earliest laboratory abnormality
- May be normal or increased with concurrent infection or inflammation
- Higher cutoff improves sensitivity of the test.
- Ferritin ≤30 ng/mL has sensitivity of 92% and PPV of 83% for iron deficiency anemia versus sensitivity of 25% for ferritin ≤12 ng/mL.
- Low serum iron
- Increased total iron-binding capacity
- Low transferrin saturation; measures the iron available for hemoglobin synthesis
- Increased soluble transferrin receptor (sTfR)
- Indicator of increased tissue iron demand
- Also increased in thalassemia syndromes but not in anemia of chronic inflammation
- sTfR/log(ferritin) <1 suggests anemia of chronic inflammation.
- sTfR/log(ferritin) >2 suggests iron deficiency anemia.
- Decreased reticulocyte hemoglobin content: This test is an early indicator of iron deficiency because reticulocytes have a short (1-2-day) lifespan before becoming mature red cells.
- Increased free erythrocyte protoporphyrin, a precursor molecule in hemoglobin synthesis; also high in lead poisoning and chronic inflammation
- Thrombocytosis (can approach 1 million/dL)
- Peripheral blood smear with microcytosis, hypochromia, poikilocytosis (varying shapes), pencil forms, and anisocytosis (varying sizes)
- Test for occult blood in stool often positive with GI blood loss
- However, the test can be positive with oral iron supplementation.
- Iron absorption test can assess adequacy of PO iron supplementation. 3 mg/kg elemental iron should increase serum iron more than 100 mcg/dL within 4 hours of ingestion.
Diagnostic Procedures/Other
Bone marrow examination: shows decreased iron stores by Prussian blue staining; it is the gold standard to determine iron stores but rarely needed to establish diagnosis.
Differential Diagnosis
- Recent infection
- Lead poisoning
- Thalassemia trait
- Anemia of chronic inflammation (e.g., juvenile rheumatoid arthritis, IBD)
- Sideroblastic anemias
Treatment
- Iron supplementation
- Family education regarding age-appropriate diet and iron-containing foods
- Specific treatment if underlying condition causing blood loss is found (e.g., hormonal therapy for menorrhagia, medications for IBD)
- May require initial inpatient observation in cases of severe anemia
- Red cell transfusion only if evidence of cardiovascular compromise (rarely indicated)
Medication
First Line
Oral replacement with ferrous iron, 3-6 mg/kg/24 h of elemental iron divided into 2 or 3 doses
- Iron should be given on an empty stomach or with a vitamin C-containing juice to increase absorption. Ascorbic acid increases oral absorption of iron by ~30%.
- Side effects (in 10-20%) include nausea, constipation, GI upset, and vomiting. Iron suspensions can stain teeth temporarily.
Second Line
Parenteral iron formulations are indicated for severe noncompliance or malabsorption or if ongoing loss exceeds absorption capacity. Administration may be associated with pain at injection site or anaphylaxis, less common with newer preparations such as ferric gluconate and iron sucrose.
Issues for Referral
- Evaluation for source of GI blood loss
- Unexplained recurrence after treatment
- Failure to improve with iron supplementation
Inpatient Considerations
Admission Criteria
- Active bleeding
- Severe anemia (hemoglobin level <6 g/dL) especially if symptoms or ongoing blood loss
- Tachycardia, S3 gallop, or other signs of CHF
Nursing
Family education: teaching administration of iron and dietary counseling
Discharge Criteria
- No signs of CHF
- If blood loss, bleeding is controlled
- Stable hemoglobin level
- Parent demonstrates ability to administer oral iron therapy to young children and demonstrates adequate knowledge about dietary modifications.
- Adequate follow-up ensured
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Reticulocyte count increases in 3-4 days.
- Hemoglobin concentration should rise by at least 1 g/dL in 2-3 weeks.
- Continue iron for 2 months beyond correction of anemia to replenish body stores.
- Causes of poor response to oral iron supplementation include the following:
- Nonadherence (most common)
- Ongoing blood loss
- Insufficient duration of therapy
- High gastric pH
- Concurrent lead intoxication
- Other diagnosis: Thalassemia trait and anemia of chronic disease are not iron responsive.
Diet
- Milk should be restricted to <24 oz daily or eliminated in those with milk protein enteropathy.
- Bottle should be discontinued after 12 months.
- Diet should include foods rich in iron: meats, beans, iron-fortified cereal, strawberries, spinach.
Patient Education
- Activity: Usually, no activity restriction is needed. Those with severe anemia resulting in CHF should have limited activity until the anemia is corrected.
- Diet: A diet containing iron-rich foods should be encouraged. Limit milk intake to <24 oz daily.
- Prevention: Prevention of iron deficiency is preferable. Anticipatory guidance about diet, prolonged bottle use, etc., should be given.
Prognosis
- Anemia is readily corrected with iron replacement.
- Developmental delay may be long lasting or irreversible.
Complications
- Impaired cognitive and motor development as well as behavioral changes in infants and toddlers
- Short-term memory impairment and poor exercise performance in adolescents
Additional Reading
- Baker RD, Greer FR, Committee on Nutrition American Academy of Pediatrics. Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age). Pediatrics. 2010;126(5):1040-1050. [View Abstract]
- Centers for Disease Control and Prevention. Iron deficiency-United States 1999-2000. MMWR Morb Mortal Wkly Rep. 2002;51(40):897-899.
- Goodnough LT, Nemeth E, Ganz T. Detection, evaluation, and management of iron-restricted erythropoiesis. Blood. 2010;116(23):4754-4761. [View Abstract]
- Konofal E, Lecendreux M, Deron J, et al. Effects of iron supplementation on attention deficit hyperactivity disorder in children. Pediatr Neurol. 2008;38(1):20-26. [View Abstract]
- Centers for Disease Control and Prevention
- McCann JC, Ames BN. An overview of evidence for a causal relation between iron deficiency during development and deficits in cognitive or behavioral function. Am J Clin Nutr. 2007;85(4):931-945. [View Abstract]
- Wu AC, Lesperance L, Bernstein H. Screening for iron deficiency. Pediatr Rev. 2002;23(5):171-177. [View Abstract]
Codes
ICD09
- 280.9 Iron deficiency anemia, unspecified
- 280.1 Iron deficiency anemia secondary to inadequate dietary iron intake
- 280.0 Iron deficiency anemia secondary to blood loss (chronic)
- 280.8 Other specified iron deficiency anemias
- 280 Iron deficiency anemias
ICD10
- D50.9 Iron deficiency anemia, unspecified
- D50.8 Other iron deficiency anemias
- D50.0 Iron deficiency anemia secondary to blood loss (chronic)
SNOMED
- 87522002 Iron deficiency anemia (disorder)
- 371315009 Iron deficiency anemia secondary to inadequate dietary iron intake (disorder)
- 413532003 Anemia due to blood loss (disorder)
- 191128004 Iron deficiency anemia due to dietary causes (disorder)
FAQ
- Q: What dietary changes can help prevent the recurrence of iron deficiency?
- A: Limit milk to 24 oz/day to improve appetite for iron-containing foods. Heme iron, found in meats, fish, and poultry, is absorbed better than nonheme iron and enhances absorption of nonheme iron. Other foods that have iron are raisins, dried fruit, sweet potatoes, lima beans, chili beans, green peas, peanut butter, and enriched foods. Give iron on an empty stomach along with an ascorbic acid-containing juice to increase absorption. Foods that decrease absorption include bran, vegetable fiber, tannins found in tea, and phosphates. Antacids may also decrease iron absorption.
- Q: What are the side effects of iron therapy?
- A: Iron may cause temporary staining of the teeth, which can be decreased by diluting the iron with a small amount of juice. Iron will also change the color of bowel movements to greenish black. Constipation may occur.
- Q: What are the most important tests to do to establish the diagnosis of iron deficiency?
- A: For patients with a history of dietary deficiency or known blood loss, a CBC that shows a low hemoglobin and MCV and an elevated RDW is very suggestive of iron deficiency. A therapeutic trial of iron without further laboratory testing is an appropriate next step. A rise in the hemoglobin concentration of ≥1 g/dL after 1 month of therapy confirms the diagnosis. Otherwise, further laboratory testing is necessary and other diagnoses should be considered.
- Q: How does a concurrent infection affect the diagnosis of iron deficiency?
- A: Common childhood infections may be associated with a mild microcytic anemia that resembles iron deficiency. Laboratory tests to diagnose iron deficiency may be misleading while a child is acutely ill. Acute infection is associated with a shift of iron from serum to storage sites, causing a decrease in serum iron and an increase in ferritin. It is more helpful to test a child for iron deficiency 3-4 weeks after an acute infection.