Effects of Bioactive Components in Donor Milk on Preterm Infant Growth

Suboptimal postnatal growth is common in premature infants: as many as 50% of very low birth weight (VLBW, birth weight <1500 grams) infants weigh less than the 10th percentile at the time of discharge home. The current standard for their nutritional care is to supplement maternal breast milk with pasteurized donor breast milk; compared to formula, donor milk is associated with lower rates of necrotizing enterocolitis, a devastating disease with significant risk for morbidity and mortality. However, a more pronounced growth deficit is observed in VLBW infants who receive donor milk, even with fortification, and few strategies exist to overcome this growth disparity between donor and maternal milk. Donor milk is distinct from preterm maternal milk, with reduced protein, energy, and bioactive factors that may influence growth, including hormones such as insulin, leptin, and adiponectin. There is a critical need to improve the standard of care in the human milk feeding approach for VLBW infants, especially with donor milk, in order to positively impact growth and long-term outcomes in this vulnerable population. We will address this need by investigating the role of non-nutritive bioactive components in human milk in influencing the growth differential between donor milk and preterm maternal milk, the two primary feeding choices for VLBW infants. Specifically, the aims of this proposal are: 1. Compare insulin, leptin, and adiponectin levels in pasteurized donor milk and preterm maternal milk and characterize preterm maternal milk hormone levels over time, 2. Evaluate the association between enteral insulin, leptin, and adiponectin intake via human milk and growth in very low birth weight infants, and 3. Examine the association between select maternal risk factors and levels of insulin, leptin, and adiponectin in preterm human milk. This translational prospective study leverages an existing cohort of VLBW infants with detailed enteral intake data and growth outcomes. We will perform additional hormone quantification using enzyme-linked immunosorbent assays, crossmatch with enteral intake to determine the actual hormone exposure via human milk, then evaluate their relationships with anthropometric and body composition measurements and z-scores. This study will determine whether reduced metabolic hormone content in donor milk contributes to the growth disparity compared to maternal milk in preterm infants. This will advance the field by identifying new targets in human milk to optimize nutritional support for preterm infant growth when maternal milk is unavailable. Project Number: 1K23HD118188-01A1 | Fiscal Year: 2026 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Ting Ting Fu | Institution: CINCINNATI CHILDRENS HOSP MED CTR, CINCINNATI, OH | Award Amount: $165,240 | Activity Code: K23 | Study Section: Special Emphasis Panel[ZRG1 EMS-Q (91)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11299323