Iron Therapy in Pediatric Iron Deficiency and Iron-Deficiency Anemia: Efficacy, Safety, and Formulation-Specific Trade-Offs—A Narrative Review

Background/Objectives: Iron deficiency (ID) is the most common nutritional disorder in childhood worldwide. It has profound consequences for growth, neurodevelopment, behaviour, and overall health. Despite the long-standing efficacy of oral ferrous salts, their poor gastrointestinal tolerability and adherence challenges have spurred the development of alternative formulations and innovative dosing strategies. Methods: We conducted a narrative review of national and international guidelines, pediatric randomized controlled trials, observational and cohort studies, cost-effectiveness analyses, diagnostic method papers, and reviews, with emphasis on diagnostic innovations, therapeutic outcomes, tolerability, and formulation-specific efficacy. Results: Ferrous salts remain the gold standard for efficacy, low cost, and guideline endorsement, but up to 40% of children experience GI intolerance. Therefore, a lower dosage of ferrous salts has been proposed for IDA as still being an efficacious and better-tolerated schedule. Also, alternate-day dosing improves absorption and tolerability and is supported by a recent pediatric RCT. Newer formulations—ferric polymaltose, ferrous bisglycinate, co-processed bisglycinate with alginate (Feralgine™), and vesicular encapsulated forms such as sucrosomial and liposomal ferric pyrophosphate—showed improved tolerability and palatability, supporting adherence with hematologic outcomes comparable to ferrous salts, particularly in children with intolerance, malabsorption, or inflammatory comorbidities. Intravenous iron is effective and safe with modern preparations and is reserved for severe anemia, malabsorption, or oral therapy failure. Conclusions: Oral ferrous salts should remain the first-line therapy in pediatric ID/IDA. Future pediatric trials should prioritize head-to-head comparisons of formulations, hepcidin-guided dosing, and patient-centred outcomes, including neurocognitive trajectories and quality of life.