What is the approach to diagnosing and managing pediatric anemia?

Diagnosis and Management of Pediatric Anemia

The diagnosis of pediatric anemia requires a systematic approach using morphologic and kinetic evaluations, with treatment focused on addressing the underlying cause, most commonly iron deficiency which should be treated with 3 mg/kg/day of oral iron for a total of 3 months. 1, 2

Diagnostic Approach

Initial Assessment

• Complete blood count (CBC) with indices is the first step to characterize anemia and identify other potential cytopenias 3
• Visual review of peripheral blood smear is critical to confirm red blood cell size, shape, and color 3
• Age-specific hemoglobin cutoffs should be used to diagnose anemia (defined as hemoglobin level less than the 5th percentile for age) 4

Morphologic Classification

• Microcytic anemia (MCV < 80 fL): Most commonly caused by iron deficiency; other causes include thalassemia, anemia of chronic disease, and sideroblastic anemia 3
• Normocytic anemia (MCV 80-100 fL): May be caused by hemorrhage, hemolysis, bone marrow failure, anemia of chronic inflammation, or renal insufficiency 3
• Macrocytic anemia (MCV > 100 fL): Usually megaloblastic, indicating vitamin B12 or folate deficiency; less commonly caused by medications, alcoholism, or liver disease 3, 5

Kinetic Evaluation

• Reticulocyte count corrected against the degree of anemia (reticulocyte index [RI]) is essential to determine bone marrow production capacity 3
• Low RI: Indicates decreased RBC production (iron deficiency, vitamin B12/folate deficiency, aplastic anemia, bone marrow dysfunction) 3, 1
• High RI: Indicates normal/increased RBC production (blood loss or hemolysis) 3

Additional Testing Based on Classification

• For microcytic anemia: Serum iron, total iron binding capacity (TIBC), transferrin saturation, serum ferritin, lead levels, and hemoglobin electrophoresis 1, 4
  • Transferrin saturation < 15% and ferritin < 30 ng/mL indicate iron deficiency 3
  • Reticulocyte hemoglobin content (CHr) < 26 pg is a strong predictor of iron deficiency 6
• For normocytic anemia: Reticulocyte count to determine bone marrow function; if elevated, evaluate for blood loss or hemolysis; if low, consider bone marrow disorders 4
• For macrocytic anemia: Vitamin B12 and folate levels, thyroid function tests 4, 5

Screening Recommendations

High-Risk Populations

• Screen all children from high-risk populations (low-income families, WIC-eligible, migrants, refugees) for anemia between 9-12 months, 6 months later, and annually from ages 2-5 years 3

Selective Screening

• For children not at high risk, screen only those with risk factors 3:
  • Preterm or low-birthweight infants not fed iron-fortified formula 3
  • Infants fed non-iron-fortified formula for >2 months 3
  • Infants introduced to cow's milk before 12 months 3
  • Breastfed infants with insufficient iron from supplementary foods after 6 months 3
  • Children consuming >24 oz daily of cow's milk 3
  • Children with special healthcare needs (medications interfering with iron absorption, chronic infection, inflammatory disorders, restricted diets, or extensive blood loss) 3

Treatment Algorithm

Iron Deficiency Anemia (Most Common)

• First-line treatment: Oral iron supplementation at 3 mg/kg/day of elemental iron administered between meals 1, 2
• Check response with repeat hemoglobin/hematocrit in 4 weeks 2
• An increase in hemoglobin ≥1 g/dL or hematocrit ≥3% confirms diagnosis and adequate response 2
• Continue iron treatment for 2 additional months after hemoglobin normalizes (total treatment duration approximately 3 months) 1, 2

Dietary Modifications

• Limit cow's milk consumption to no more than 24 oz daily 3, 1
• For infants <12 months who are not breastfed, recommend only iron-fortified infant formula 3
• For breastfed infants with insufficient iron from supplementary foods by 6 months, suggest 1 mg/kg/day of iron drops 3
• For preterm or low birthweight breastfed infants, recommend 2-4 mg/kg/day of iron drops (maximum 15 mg/day) starting at 1 month until 12 months 3
• Introduce iron-fortified infant cereal at 4-6 months 3
• Encourage foods rich in vitamin C with meals to improve iron absorption 3, 1

Management of Refractory Cases

• If anemia persists after 4 weeks of iron supplementation despite compliance, perform additional testing 1:
  • Mean cell volume (MCV) and red blood cell distribution width (RDW) to differentiate iron deficiency from thalassemia 3
  • Check for other deficiencies (copper, ceruloplasmin, vitamin B12) 1
• Consider hematology referral for patients who do not respond to treatment or for any diagnosed bone marrow suppression 5

Follow-up and Monitoring

• Reassess hemoglobin/hematocrit approximately 6 months after successful treatment 1, 2
• Consider routine screening at regular intervals for children at high risk for recurrent iron deficiency anemia 1

Common Pitfalls and Caveats

• Inadequate duration of treatment can fail to replenish iron stores 1, 2
• Poor compliance due to gastrointestinal side effects can be improved by adjusting administration timing 1, 2
• Failure to address underlying dietary issues can lead to recurrence of iron deficiency anemia 1, 2
• Anemia screening alone has limited usefulness as an indicator of iron deficiency; additional measurements of iron status may be necessary 3
• Less than 50% of children with anemia (defined by low hemoglobin) are actually iron deficient; other causes include nutritional deficiencies, hereditary defects, infections, and chronic inflammation 3, 7