Background: Donor human milk (DHM) is recommended when the mother’s own milk (MOM) is unavailable for extremely low birth weight (ELBW) infants. However, the impact of DHM implementation on NICUs with already high human milk utilization remains incompletely characterized. Objective: We aimed to evaluate the association between DHM implementation and feeding practices, feeding progression, parenteral nutrition (PN) exposure, and major neonatal morbidities in ELBW infants. Methods: We conducted a retrospective before–after cohort study in a single tertiary NICU including 116 ELBW infants with feeding data through day 28 (58 pre-DHM; 58 post-DHM). Exploratory multivariable models evaluated factors associated with NEC and PN duration. Results: In the post-DHM epoch, enteral feeding was initiated earlier (2 vs. 2.5 days, p < 0.001) and full enteral feeding was achieved sooner (14 vs. 24.5 days, p < 0.001). PN duration was numerically shorter (17.5 vs. 27 days, p = 0.088). Feeding shifted from predominantly exclusive MOM to mixed MOM + DHM regimens, eliminating formula-only feeding. NEC, feeding intolerance, bloodstream infection, and mortality did not differ between epochs. Feeding intolerance was associated with NEC, whereas lower gestational age predicted longer PN duration; epoch was not independently associated with either outcome. Conclusions: In this high-MOM NICU, DHM implementation was associated mainly with earlier feeding progression and reduced formula reliance, without a measurable reduction in NEC.

Background/Objectives: Mother’s own milk (MOM) is widely recognized as the best source of nutrition for premature infants, with donor human milk (DHM) as the next recommended option. However, it remains controversial whether DHM confers the same benefits as MOM. We aimed to compare growth and clinical outcomes in very-low-birth-weight (VLBW) infants before and after the introduction of DHM in our Neonatal Intensive Care Unit (NICU). Methods: This is a retrospective cohort of VLBW and/or very-low-birth-weight infants born between January 2018 and June 2023. Infants were divided based on birth date into Epoch-1 (pre-DHM, N = 98) and Epoch-2 (post-DHM, N = 138). Feeding groups included exclusive MOM (N = 112), MOM + DHM (N = 71), and MOM + Formula (N = 39). Baseline characteristics were compared between groups. The primary outcome was weight gain; secondary outcomes included incidence of necrotizing enterocolitis (NEC), time to full enteral feeding, and length of hospitalization. Multivariable regression models were used to assess these outcomes while adjusting for relevant confounders. Results: Infants in Epoch-2 were born at a significantly higher gestational age (29.3 vs. 28.2 weeks, p < 0.001) and had a higher median birth weight (1350 g vs. 1080 g, p < 0.001) compared to Epoch-1. In this before-and-after cohort, the post-DHM implementation epoch was not independently associated with differences in growth or complication rates after adjustment. Time to reach full enteral feeding was significantly shorter in the post-DHM epoch (B = −0.255, p < 0.001). Conclusions: DHM had no independent effect on growth or complication rates but was associated with earlier achievement of full enteral feeding. Further studies are needed to evaluate its contribution to neonatal clinical outcomes.