Project Summary / Abstract Each year, over 63,000 U.S. infants are born very preterm, prior to 32 weeks of gestation. With >90% now surviving to discharge due to better obstetrical and neonatal intensive care unit (NICU) management, the present challenge is to reduce short- and long-term morbidities experienced by survivors, including the two- to four-fold increased risk of obesity, diabetes, hypertension, and metabolic syndrome that manifest by young adulthood. The Developmental Origins of Health and Disease (DOHaD) framework posits that chronic conditions result from adverse exposures during vulnerable developmental stages known as “critical” or “sensitive” periods. Of particular importance is the first 1000 days of life, when key developmental processes set the stage for lifelong health. Very preterm infants are an especially vulnerable population, as they require NICU support for 2-4 months after birth, coinciding with the 3rd trimester – an established sensitive period for programming of obesity and cardiometabolic risk. In this context, the most highly modifiable and relevant exposure is diet during the NICU hospitalization, which may contribute to the accelerated accretion of fat mass relative to fat-free mass. Hospitalized very preterm infants typically experience impaired weight gain, stunted linear growth, and excess fat accretion relative to the typical fetus. To offset these issues and support brain development, dietary fortification of human milk is provided as standard of care. However, the consequences of dietary fortification for cardiometabolic health in this population are poorly understood. This proposal seeks to uncover the extent to which diet-based interventions that promote physical growth and brain development during a sensitive period may also contribute to cardiometabolic risk. We will study 130 infants born 24-31 weeks of gestation who are participating in the Nourish Study (R01HD097327l; PI: Belfort), an ongoing randomized controlled trial testing the effect of individually targeted human milk fortification vs. standard of care during the NICU hospitalization. By extending follow-up of this cohort and adding cardiometabolic biomarkers at 2 and 5 years of age, we have a unique opportunity to investigate how macronutrient and energy delivery during a sensitive period contributes to, or protects from, cardiometabolic risk during childhood. We are further poised to address key questions about NICU growth patterns in relation to cardiometabolic health in this population. Findings from this work have strong potential to impact clinical care by informing dietary strategies during a sensitive window in development to optimize lifelong health for a vulnerable population.

Project Narrative The public health relevance of this study relates to the persistent problem of undernutrition among very preterm infants, those born prior to 32 weeks of gestation. The proposed study will examine how the neonatal intensive care unit (NICU) diet and patterns of growth during the hospitalization contribute to, or protect against, the development of excess adiposity and cardiometabolic risk during early childhood (ages 2 and 5 years). Results from this study will inform new and more effective strategies for nutritional support, assessment, and monitoring of very preterm infants. The overall goal is for pragmatic, diet-based interventions during a sensitive period in development that support optimal long-term health for the ~63,000 very preterm infants born each year in the U.S. and many more worldwide.