Project Summary / Abstract Despite marked improvement in survival in the past 3 decades, very preterm infants continue to experience high rates (50-60%) of neurodevelopmental impairment after discharge from the neonatal intensive care unit (NICU). These impairments burden children and families and incur large societal costs for early intervention and special educational services. An important contributing factor to neurodevelopmental impairment is extrauterine growth restriction, which is common (50%) and reflects undernutrition during the NICU hospitalization. Normal brain development depends on the availability of key nutrients during specific sensitive or critical periods, and preterm infants are entirely dependent on the nutrition they receive in the NICU during the “brain growth spurt” of the third trimester. Nutritional strategies in the NICU that reduce undernutrition during this critical period for brain development are likely to result in better long-term neurodevelopmental outcomes. The American Academy of Pediatrics recommends a fortified human milk diet for all preterm infants, and human milk use is rising in NICUs across the U.S. However, because human milk is highly variable in its macronutrient content, consistently meeting nutrient requirements for human milk-fed infants is a challenge. Evidence of slower weight gain and head growth in fortified human milk- vs. formula-fed very preterm infants suggests that current human milk fortification strategies are inadequate to fully support their growth. The aim of this study is to investigate a new, individualized approach to human milk fortification, leveraging technology from the dairy industry to analyze human milk composition at the point of care and target fortification to ensure that protein and energy intakes consistently meet recommendations. We are proposing to study this new approach by conducting a randomized, controlled trial of individually targeted vs. standard fortification among preterm infants receiving human milk (maternal milk plus donor milk if needed, no formula). Outcomes will include physical growth and body composition (fat and fat-free mass), quantitative MRI to assess brain size and microstructure, and neurodevelopment assessed across a range of domains (cognition, executive function, attention, behavior) at 2 years’ corrected age. Our overarching goal is to improve long-term health and developmental outcomes of very preterm infants through pragmatic, evidence-based innovations in nutritional care during the NICU hospitalization. The impact of the current study will be to determine the benefits of individually targeted human milk fortification not just to physical growth, but also to the structure and function of the developing brain. These answers are needed to inform larger-scale clinical trials and for the translation of this and other promising nutritional strategies into clinical practice. This work has the potential to benefit over 63,000 very preterm infants born each year in the U.S. and many more worldwide.

Project Narrative This study will test an innovative strategy to individually target human milk fortification and eliminate macronutrient intake deficits during the neonatal intensive care unit hospitalization, which is a critical period for brain development in the very preterm infant. We will test the effects of this intervention on physical growth and body composition, early brain development assessed by MRI, and a range of neurodevelopmental outcomes at 2 years corrected age. The overall goal is to identify pragmatic nutrition-based clinical strategies for neonatal intensive care that improve long-term health and neurodevelopmental outcomes for the ~63,000 very preterm infants born each year in the U.S. and many more worldwide.