What is the preferred iron supplement, ferrous bisglycinate or ferrous sulfate, for pediatric patients with iron deficiency?

Ferrous Sulfate vs Ferrous Bisglycinate in Pediatric Iron Deficiency

Ferrous sulfate at 3 mg/kg/day should be the first-line oral iron supplement for pediatric patients with iron deficiency, as it demonstrates superior efficacy in increasing hemoglobin and achieving complete resolution of anemia compared to alternative formulations. 1, 2

Primary Recommendation

The standard therapeutic approach for treating iron deficiency in children is ferrous sulfate at 3 mg/kg per day of elemental iron, administered between meals to maximize absorption 1. This recommendation is based on the highest quality randomized controlled trial comparing iron formulations in pediatric patients, which demonstrated that ferrous sulfate resulted in a significantly greater increase in hemoglobin concentration (1.0 g/dL greater difference, 95% CI 0.4-1.6 g/dL, P<0.001) compared to alternative iron preparations 2.

Evidence Supporting Ferrous Sulfate Superiority

• Hemoglobin response: In a double-blind randomized trial of 80 children aged 9-48 months with iron deficiency anemia, ferrous sulfate increased mean hemoglobin from 7.9 to 11.9 g/dL over 12 weeks, compared to 7.7 to 11.1 g/dL with iron polysaccharide complex 2.

• Complete resolution of anemia: Ferrous sulfate achieved complete resolution of iron deficiency anemia in 29% of patients versus only 6% with alternative formulations (P=0.04) 2.

• Iron stores: Median serum ferritin increased more substantially with ferrous sulfate (from 3.0 to 15.6 ng/mL) compared to alternative preparations, with a greater difference of 10.2 ng/mL (95% CI 6.2-14.1 ng/mL, P<0.001) 2.

Ferrous Bisglycinate as an Alternative

While ferrous sulfate remains the gold standard, ferrous bisglycinate chelate offers a reasonable alternative in specific clinical scenarios:

When to consider bisglycinate:

• Gastrointestinal intolerance: Bisglycinate formulations demonstrate fewer gastrointestinal side effects (6% vs 16% with ferrous sulfate) 3.
• Compliance issues: Better treatment acceptability has been documented with bisglycinate preparations 4.
• Sustained iron stores: One study showed higher ferritin concentrations 6 months post-supplementation with bisglycinate chelate, though acute efficacy was similar 5.

Efficacy considerations for bisglycinate:

• Bisglycinate at 0.45 mg/kg/day showed good efficacy in increasing hemoglobin, though direct head-to-head comparison suggests lower doses may be less effective than standard ferrous sulfate dosing 3.
• One small study (n=40) reported 90.9% apparent bioavailability for bisglycinate versus 26.7% for ferrous sulfate, but this was not replicated in larger, higher-quality trials 6.
• The most rigorous randomized trial demonstrated clear superiority of ferrous sulfate for achieving complete resolution of anemia 2.

Practical Implementation Algorithm

Step 1: Initial treatment

• Start ferrous sulfate 3 mg/kg/day of elemental iron 1
• Administer between meals (not with food) to optimize absorption 1
• Continue for initial 4-week period 1

Step 2: Response assessment at 4 weeks

• Recheck hemoglobin 1
• If hemoglobin increases by ≥1 g/dL, continue treatment for 2 additional months 1
• Reticulocyte count should increase as early as 3 days after starting therapy 3

Step 3: Management of side effects

• If significant gastrointestinal symptoms (nausea, vomiting, diarrhea) occur and compromise compliance, switch to ferrous bisglycinate chelate 3, 4
• Mild GI symptoms should not prompt immediate discontinuation 1

Step 4: Non-responders

• If anemia does not respond after 4 weeks despite compliance, obtain further laboratory evaluation (MCV, RDW, serum ferritin) 1
• Consider parenteral iron only if enteral supplementation fails to maintain adequate iron status 7, 8

Critical Pitfalls to Avoid

• Underdosing: Do not use doses lower than 3 mg/kg/day for treatment of established iron deficiency anemia, as this is the evidence-based therapeutic dose 1, 2.
• Administering with meals: Food significantly decreases iron bioavailability; always give between meals 1.
• Premature discontinuation: Complete the full 3-month treatment course even after hemoglobin normalizes to replenish iron stores 1.
• Ignoring non-response: Failure to respond after 4 weeks warrants further investigation, not simply continuing the same regimen 1.

Monitoring Requirements

For patients on long-term iron supplementation, iron status (at minimum ferritin and hemoglobin) should be monitored regularly to prevent both iron deficiency and iron overload 7, 9. Hemoglobin and iron studies should typically be rechecked 2-4 weeks after completing iron therapy 9.