Impact of iron intake on growth outcomes in children with iron deficiency anemia, iron deficiency, and normal iron status: A comprehensive review

Background: Iron deficiency (ID) and iron deficiency anemia (IDA) are significant global health issues, affecting over 30% of children under five years globally, with higher prevalence in low-income countries. IDA impacts oxygen transport and energy metabolism, causing stunted growth and developmental delays. Despite the established role of iron in growth, its specific effects on height and weight outcomes remain debated.

Objectives: To review the impact of iron intake on linear growth and weight gain in children with IDA, ID, and normal iron status, synthesizing data on supplementation dose, duration, and outcomes.

Methods: A comprehensive review of studies published between 1980 and 2024 was conducted, incorporating randomized trials, observational studies, and meta-analyses. Data were extracted on study characteristics, diagnoses, sample sizes, interventions, and outcomes. Articles were categorized based on the population: children with IDA, ID, or normal iron status.

Results: This review analyzed 17 studies encompassing three categories of children: those with iron deficiency anemia (IDA) (9 studies, n=1,361), those with iron deficiency (ID) without anemia (4 studies, n=438), and those with normal iron status (4 studies, n=45,187). The findings are summarized as follows:

Children with Iron Deficiency Anemia (IDA): Iron supplementation significantly improved height standard deviation scores (SDS), growth velocity (GV), and body mass index (BMI). Serum ferritin levels strongly correlated with growth recovery, reflecting restored iron stores as a key mechanism. Studies demonstrated that daily and twice-weekly dosing regimens were equally effective, particularly in resource-limited settings. Mechanistic studies highlighted the role of improved oxygen transport, mitochondrial function, and hormonal regulation via insulin-like growth factor-I (IGF-I). Socioeconomic factors, such as low maternal income and dietary quality, were consistently associated with worse growth outcomes.

Children with Iron Deficiency (ID): The impact of iron supplementation on growth in children with ID was modest, with no significant changes in linear growth in most studies. Improvements in weight gain and hemoglobin levels were more notable when supplementation addressed co-existing micronutrient deficiencies, such as zinc. Socioeconomic and dietary factors remained critical determinants of growth outcomes, particularly in populations with high burdens of malnutrition and parasitic infections.

Children with Normal Iron Status: In iron-replete children, supplementation maintained normal growth trajectories but did not significantly enhance linear growth or weight gain. Studies emphasized the sufficiency of adequate dietary iron intake for supporting regular development. In obese children, inflammation was associated with reduced iron status, indirectly affecting growth potential. However, routine supplementation for iron-replete children in non-risk groups showed limited benefits and raised concerns about potential risks of over-supplementation.

Discussion: Iron supplementation is essential for addressing growth deficits in children with IDA, with clear improvements in height, weight, and BMI. The effect is less pronounced in non-anemic or iron-replete children, where socioeconomic and dietary factors may play a larger role. Mechanisms include improved oxygen transport, energy metabolism, and IGF-I axis modulation.

Conclusions: Iron supplementation significantly improves growth in children with IDA and is a key intervention for mitigating stunting and weight deficits in this group. In children with ID or normal iron levels, its effects are less pronounced, emphasizing the importance of tailored approaches based on iron status.