From Mother–Fetus Dyad to Mother–Milk–Infant Triad: Sex Differences in Macronutrient Composition of Breast Milk

<b>Background:</b> The composition of breast milk is influenced by a variety of factors, including maternal anthropometric characteristics, dietary and lifestyle habits, and lactation and feeding parameters. Emerging evidence also suggests that an infant's sex may play a role in shaping breast milk composition. <b>Objective</b>: This study aims to investigate the macronutrient composition of early breast milk up to 3 months postpartum, with a particular focus on potential differences related to the infant's sex. <b>Methods:</b> A total of 102 breast milk samples were collected at four time points across three lactation stages, representing colostrum, transitional, and mature milk, from a cohort consisting of 51 consenting mothers of Mediterranean origin who met the inclusion criteria. The samples were analyzed using mid-infrared spectroscopy to determine their macronutrient composition. <b>Results:</b> Colostrum from mothers of male infants contained approximately 60% higher levels of nitrogenous compounds, crude protein, true protein, and non-protein nitrogen compared to colostrum from mothers of female infants. Transitional milk for female infants contained higher fat, total solids, and energy. No significant differences in macronutrient composition were observed in mature milk between the sexes. For both sexes, colostrum contained more nitrogenous compounds and fewer total solids than mature milk. Male colostrum had lower carbohydrate levels compared to the later stages of lactation, while female samples showed no significant changes. Strong positive correlations between fat and crude protein were found for both sexes during the transitional and mature milk stages. In male colostrum, all macronutrients were interrelated. <b>Conclusions:</b> The observed differences in the composition of colostrum and transitional breast milk for male and female neonates suggest potential sex-specific nutritional adaptations during early lactation. These findings may have implications for personalized infant nutrition strategies in cases where breast feeding is hampered, as well as for understanding early neonatal adaptations.