Exploratory Cross-Sectional Associations of Postpartum Maternal Body Mass Index and Infant Anthropometry with Human Milk Hormones and Cytokines

Background/Objectives: Human milk contains hormonal and immune bioactives that may vary with maternal, infant and perinatal characteristics including maternal body mass index (BMI), infant sex and birth mode. However, evidence linking these factors remains inconsistent. This exploratory study evaluated if maternal, infant and perinatal characteristics were associated with milk composition. Secondarily, hypothesis-generating analyses examined if milk hormones and cytokines were associated with infant anthropometric Z-scores. Methods: This cross-sectional study included 47 healthy term, exclusively breastfed mother–infant dyads with ages ranging from 0.39 to 6.01 months. Milk hormones (ghrelin, leptin, insulin and glucagon) and cytokines (IL-1β, IL-2, IL-4, IL-6, IL-7, MCP-1, IFN-γ and TNF-α) were quantified using multiplex assays and infant anthropometry was evaluated using WHO Z-scores. Adjusted models included infant age, postpartum maternal BMI, infant sex, and birth mode. Analyte-specific complete-case samples ranged from 37 to 44. All p values were nominal, and false-discovery-rate-adjusted q values assessed multiplicity. Results: Postpartum maternal BMI was positively associated with milk leptin (β = 0.152; p < 0.001; n = 39) and cesarean delivery, relative to vaginal delivery, was associated with lower milk glucagon (β = −0.579; p < 0.001; n = 37). Milk IFN-γ showed nominal exploratory positive associations with weight-for-length Z-score (β = 0.188; p = 0.017; n = 39) and BMI-for-age Z-score (β = 0.211; p = 0.032; n = 39). Conclusions: Postpartum maternal BMI and birth mode showed robust adjusted associations with leptin and glucagon, respectively. The cross-sectional design does not establish temporal direction or clinical relevance. The IFN-γ findings require longitudinal evaluation.