Nutritional interventions' impacts on human milk: Three trials in low-resource settings.

Human milk (HM) composition is variable to support changing infant needs and is influenced by maternal diet and health. We harmonized HM data from three randomized trials in Burkina Faso (MISAME-III), Pakistan (Mumta-LW), and Tanzania (ELICIT) within the International Milk Composition (IMiC) Consortium to test how maternal nutrition affects HM composition. Balanced energy-protein (BEP) supplements or nicotinamide given to lactating mothers increased milk B-vitamins, while macronutrients, oligosaccharides, bioactive proteins, and microbiome composition were physiologically buffered. Metabolomic and proteomic analyses revealed shifts in vitamin-related metabolites, triglyceride profiles, and intracellular protein representation. In a MISAME-III subset, maternal and infant blood showed concordant changes. Postnatal BEP improved infant growth only in the more undernourished cohort. Improved milk micronutrient quality across settings supports extending maternal supplementation into lactation.