PROJECT SUMMARY/ABSTRACT Each year, over 63,000 U.S. infants are born very preterm, below 32 weeks of gestation. With >90% now surviving to discharge from the neonatal intensive care unit (NICU), reducing the short- and long-term morbidities has become the highest priority. Neurodevelopmental impairment is a burdensome long-term morbidity that affects 50-60% of very preterm infants after NICU discharge. Nutrition is a cornerstone of clinical care in the NICU and represents a highly modifiable strategy to support healthy brain development during a critical period, thereby reducing long-term impairments. Previous studies have highlighted nutrient accretion into tissues as a key driver of healthier brain development and better neurodevelopmental outcomes. A current gap is in accurate, specific, and feasible strategies to assess and monitor nutrient accretion over time. The overall aim of this study is to investigate fat-free mass accretion as a dynamic bioindicator of nutritional status in the NICU. The specific aims involve establishing a new fetal reference for fat-free mass that covers the entire spectrum of preterm gestational ages, from 23 to 35 weeks, and using this reference to define targets for fat-free mass accretion that are based on neurodevelopmental outcomes. This study applies the innovative concept of “growth quality” to NICU nutrition research. Innovative approaches include the application of bioimpedance analysis to measure body composition in the NICU setting, and the use of quantitative brain magnetic resonance imaging (MRI) and electroencephalography (EEG) as early biomarkers of neurodevelopment in this population, in addition to standard behavioral measures. Our overarching goal is to improve long-term health and developmental outcomes of very preterm infants through pragmatic, evidence- based innovations in nutritional assessment and care during the NICU hospitalization. The results of this study will lay the foundation for fat-free mass-driven dietary interventions in the NICU setting. This study has strong potential to provide an impactful paradigm shift in the approach to the assessment and monitoring of nutritional status and ultimately the leveraging of nutritional strategies during a critical window in development to improve outcomes for this vulnerable population.