Modelling how nutritional solutions may help alleviate paediatric iron deficiency: Application to the Indian subcontinent

Iron deficiency (ID) in children caused by dietary deprivation can be alleviated in [~]40% cases with iron-fortified nutritional solutions. Devising more effective nutritional solutions requires a quantitative understanding of iron homeostasis, which is lacking. Here, we developed a physiologically-based mathematical model of paediatric iron homeostasis that recapitulates ID due to dietary deprivation and its alleviation using nutritional solutions. The model integrates key cellular and systemic iron regulatory processes, associated anatomical sites, the gut microbiota, and nutritional solutions, and shows how their complex interplay governs iron homeostasis. The model quantitatively described the alleviation of ID with nutritional solutions in a large clinical trial in Bangladesh. In virtual Indian populations, the model predicts that over-the-counter iron-fortified nutritional solutions can restore haemoglobin level to normalcy in >85% mildly anaemic infants and young children. Our study thus elucidates individual- and population-level underpinnings of ID, describes clinical observations, and informs efforts to improve intervention strategies.