Human Milk and Bronchopulmonary Dysplasia in Preterm Infants: The Mediation of Inflammatory Cytokines.

OBJECTIVE

This study investigates the mediating role of inflammatory cytokines in the protective effect of human milk against bronchopulmonary dysplasia (BPD) in preterm infants.

METHODS

This prospective cohort study included 73 infants born at < 28 weeks' gestation.Infants were classified into high-dose human milk and high-dose formula groups according to feeding patterns at 36 weeks postmenstrual age (PMA). Cross-sectional group comparisons of inflammatory factors at postnatal day 7, day 28, and PMA 36 weeks were examined by Mann-Whitney U test, while longitudinal changes in plasma inflammatory cytokines were evaluated using generalized estimating equations (GEE), and mediation analysis was performed using PROCESS version 4 to assess the potential indirect effects of inflammatory cytokines on the association between human milk exposure and BPD severity.

RESULTS

Infants in the high-dose human milk group had a significantly lower incidence of grade II/III BPD and lower plasma concentrations of CXCL10, IL-1Ra, and IL-13 at 36 weeks PMA than those in the high-dose formula group. Longitudinal GEE analysis showed significant temporal changes in these cytokines but no significant group × time interactions. Mediation analysis demonstrated a significant joint indirect effect through IL-1Ra and CXCL10 (effect = -0.245, 95% CI -0.487 to -0.046), accounting for 34.9% of the total association between human milk exposure and BPD severity.

CONCLUSION

High human milk feeding was associated with lower BPD severity and a less activated inflammatory profile at 36 weeks PMA. IL-1Ra- and CXCL10-related inflammatory pathways may partially account for this association, although the observational design precludes definitive causal inference.