Prenatal and Postnatal Maternal Psychological Distress and the Metabolomic Profile of Human Milk

Human milk is the gold standard of infant nutrition, providing nutrients and bioactive metabolites that shape infant immune, cognitive, and metabolic development. Maternal psychological distress, including stress, anxiety, and depression, is prevalent during the perinatal period and may influence milk composition. Emerging evidence suggests that these alter metabolite classes, with potential long-term consequences for infant health.

This study aims to identify whether maternal stress, depressive, and anxiety symptoms are associated with differential metabolomic signatures in human milk from 2.5 to 24 mo postpartum.

Human milk samples were collected longitudinally at multiple postpartum time points from 424 mothers in the FinnBrain Birth Cohort study, yielding 718 samples. Human milk metabolite concentrations were quantified using ¹H nuclear magnetic resonance-based metabolomics. Maternal depressive, anxiety, and stress symptoms were assessed using validated self-report scales prenatally and postnatally. Simple linear regression and linear mixed models examined associations between maternal symptom scores and human milk metabolite concentrations across lactation (false discovery rate <0.05).

Human milk oligosaccharides such as Lacto-N-tetraose (LNT), lacto-N-fucopentaose I (LNFP I), and lacto-N-difucohexaose I/II (LNDFH I/II) showed negative associations with depressive and stress symptoms, whereas 3'-fucosyllactose (3'FL), 3'-sialyllactose (3'SL), and lacto-N-neotetraose (LNnT) were positively linked, particularly with prenatal symptoms.. Among amino acids, threonine concentrations declined with higher maternal symptom scores, whereas glutamate, glutamine, and taurine exhibited time-dependent associations across lactation. Succinate and hippurate showed positive associations with prenatal maternal symptom scores that shifted to negative associations later in lactation, whereas lactose and caprylate were negatively associated with postnatal symptoms.

Both prenatal and postnatal maternal distress are associated with human milk metabolites. Human milk may buffer infants from some effects of maternal psychological distress because increases in key metabolites suggest potential compensatory roles in immune modulation and healthy gut microbiota. However, reductions in metabolites with established prebiotic and immune regulatory functions reinforce the importance of interventions that support maternal mental health during the perinatal period.