Human Milk Hormones and Early-Life Programming: Effects on Growth, Body Composition, and Development in Term and Preterm Infants

Background: Human milk contains a complex and dynamic array of hormones that may influence infant growth, body composition, and metabolic development beyond the provision of nutrients alone.

Objective: To synthesize current evidence on the role of key human milk hormones—leptin, adiponectin, ghrelin, insulin, and insulin-like growth factor-1 (IGF-1)—in shaping growth and developmental outcomes in term and preterm infants.

Methods: An expanded narrative synthesis of human and relevant animal studies was conducted, focusing on hormone concentrations in human milk, proposed mechanisms of action in the infant, and associations with growth, body composition, and metabolic outcomes. Evidence was summarized across infant populations (term and preterm), lactational stages, and study designs, with risk-of-bias considerations incorporated.

Results: Leptin and adiponectin, largely derived from maternal adipose tissue and present in human milk at ng/mL concentrations, are consistently linked to infant appetite regulation, energy balance, and adiposity, although the direction and magnitude effects vary across studies. Ghrelin, an appetite-stimulatory hormone detected in human milk, may enhance feeding behavior and growth hormone secretion. Milk-borne insulin and IGF-1 appear to support gastrointestinal maturation and systemic anabolic signaling. Preterm infants, who are deprived of late-gestation placental hormone transfer, are exposed to these bioactive factors earlier ex utero; differences in hormone concentrations between preterm and term milk and their potential implications for divergent growth trajectories are highlighted. Comprehensive tables summarize hormone concentrations, mechanisms, study findings, and populations, complemented by schematic diagrams illustrating endocrine and metabolic pathways.

Conclusions: Emerging evidence supports the concept that human milk hormones function as lactocrine signals that contribute to the regulation of infant growth and metabolic programming through endocrine and epigenetic pathways. However, findings remain heterogeneous and are influenced by maternal phenotype, lactational stage, and infant characteristics. Further well-designed longitudinal and mechanistic studies are needed to clarify these effects and their long-term implications for metabolic health in both term and preterm infants.