Human Milk Melatonin Across Early Lactation in Preterm Birth: Maternal, Pregnancy, and Neonatal Correlates

Melatonin is a multipotent neuroendocrine transducer. Human-milk melatonin is the sole source of exogenous melatonin in the neonatal period, this being especially true for premature infants. This study aimed to examine maternal, pregnancy, and neonatal correlates of human-milk melatonin concentrations measured at three predefined lactational stages-colostrum, transitional, and mature milk-in mothers of preterm infants, as well as the variation of melatonin concentration in human milk during the first postnatal month, possibly shedding light on an understudied area of neonatal nutrition.

This longitudinal observational cohort enrolled 101 mothers who delivered 128 infants before 35 completed weeks of gestation. Melatonin was quantified by ELISA in daytime milk samples obtained at T1 (postnatal days 2-5), T2 (days 10-14), and T3 (days 20-28).

Human-milk melatonin declined across early lactation, with significantly lower concentrations in mature milk than in colostrum (T3 versus T1: geometric mean ratio [GMR]: 0.74, 95% confidence interval [CI]: 0.62-0.88, p < 0.001). Fetal growth restriction (FGR) was associated with lower melatonin concentrations after adjustment for the predefined maternal and pregnancy covariates (GMR: 0.76, 95% CI: 0.58-1.00, p = 0.046). No significant correlation was found with any of the other maternal, obstetric, or neonatal demographic characteristics.

This longitudinal study indicates that daytime human-milk melatonin decreases from colostrum to mature milk during the first postnatal month in mothers of preterm infants. Among the maternal, pregnancy, and neonatal factors examined, FGR was the only factor independently associated with lower milk melatonin concentrations. These findings support the need for larger longitudinal studies combining maternal, placental, and milk melatonin measurements in order to clarify the biological basis of this association and its possible clinical relevance for infants born preterm.