Maternal Determinants of Human Milk Leptin and Their Associations with Neonatal Growth Parameters

<b>Introduction:</b> Human breast milk (HBM) is a critical source of nourishment for newborns, containing bioactive compounds that influence infant growth and metabolic programming. Among these compounds, leptin-a hormone primarily produced by adipocytes but also synthesized in the mammary gland-has gathered attention for its potential role in regulating energy balance and body weight. This study investigates the influence of maternal factors on HBM leptin concentrations and explores their associations with neonatal growth parameters. <b>Material and Methods:</b> 262 HBM samples were collected from healthy lactating mothers through Spanish Biobanks during the first six months postpartum. Data on maternal characteristics (body mass index (BMI), age, physical activity, parity, and delivery type) and neonatal measurements (weight, length, and head circumference) were collected. Leptin concentrations in skimmed HBM were measured using the ELISA technique (R&D Systems™, Minneapolis, MN, USA). Statistical analyses were conducted using R version 4.3.1 and MATLAB R2023a, with significance set at <i>p</i> < 0.05. <b>Results:</b> Leptin levels were highest in and declined over time, reaching a stable level after the first month of lactation. Preterm deliveries exhibited significantly higher leptin concentrations than term deliveries (0.42 vs. 0.07 ng/mL). Higher leptin levels were also observed in younger and primiparous mothers. Maternal BMI was positively associated with leptin concentration, with mothers who had elevated BMI showing higher levels than those with optimal BMI (0.36 vs. 0.05 ng/mL). Maternal physical activity was not associated with leptin concentrations in univariate analyses; although greater self-reported physical activity appeared associated with lower leptin concentrations in regression models, this finding should be interpreted cautiously and should not be considered evidence of an independent or consistent effect. Neonatal growth parameters (weight, length, and head circumference) were negatively correlated with HBM leptin concentrations. <b>Conclusions:</b> Our findings indicate that leptin levels in breast milk reflect both maternal metabolic status and neonatal characteristics and may represent a compensatory mechanism in preterm infants. HBM leptin levels are modulated by maternal BMI, age, parity, and delivery type, and are associated with neonatal growth parameters.