High-energy human milk diets in the first two weeks after birth to reduce the severity of respiratory morbidity in extremely preterm infants

This hypothesis-driven, patient-oriented pilot randomized clinical trial will evaluate whether providing a high- energy human milk diet during the first two weeks after birth reduces respiratory morbidity in extremely preterm (EPT) infants. EPT infants, born at 28 weeks of gestation or earlier, have immature lungs and a high risk of developing bronchopulmonary dysplasia (BPD)—a chronic lung disease that increases mortality and long-term developmental complications. Early enteral nutrition is critical for lung development, yet most EPT infants receive insufficient energy during the first 14 days after birth. Docosahexaenoic acid (DHA) and arachidonic acid (ARA) supplementation is a promising strategy to increase energy intake through human milk, but there is no consensus on whether fat- enriched or protein-enriched diets are more beneficial for improving lung function. Building on findings from our recent NIH-funded trial, which demonstrated that protein-enriched diets improved growth and potentially reduced BPD severity, we will now assess whether a DHA/ARA-enriched exclusive human milk diet can achieve superior benefits. In this trial, we will randomize 150 EPT infants to receive either an exclusive human milk diet enriched with a commercially available DHA/ARA supplement or a standard, exclusive human milk diet during the first 14 days after birth. The primary outcome is the severity of respiratory morbidity at term equivalent age. We will also evaluate the feasibility of using non-invasive oscillometry to measure lung function in this population. This study will inform the design of a larger clinical trial and may establish that early enteral energy provision— unlike parenteral nutrition—provides measurable respiratory benefits. The findings could reshape neonatal nutrition strategies and optimize care for preterm infants at risk of BPD. Project Number: 1R34HL183268-01 | Fiscal Year: 2026 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Ariel Salas | Institution: UNIVERSITY OF ALABAMA AT BIRMINGHAM, BIRMINGHAM, AL | Award Amount: $180,860 | Activity Code: R34 | Study Section: Special Emphasis Panel[ZRG1 RCCS-P (92)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R34HL18326801