The purpose of this Mentored Patient-Oriented Research Career Development Award (K23) is to provide Ariel A. Salas, MD, MSPH, with the mentorship, training, and research experience needed to become an independent clinician scientist and leader in neonatal nutrition research. His long-term career goal is to reduce the burden of postnatal growth failure through novel translational studies and large scale, multi-center clinical trials of promising dietary interventions that optimize growth, reduce dysbiosis of the gut microbiome, and ultimately improve neurodevelopment. His immediate goal is to acquire the skills needed to conduct a clinical research program to study the effects of the protein intake and gut microbiome on growth and body composition of extremely preterm infants (28 weeks of gestation or less). To achieve these goals and transition to independence, Dr. Salas and his mentors have developed a comprehensive research and career development plan that includes mentorship from an exceptional team of scientists with proven track records of successful mentorship; intensive didactic training; and a research plan that is purposefully designed to provide experiential learning in advanced research methods to study postnatal growth failure and the gut microbiome of extremely preterm infants. Postnatal growth failure occurs in approximately 60% of the nearly 26,000 extremely preterm infants born every year in the United States. Postnatal growth failure is associated with a higher risk of adverse health outcomes, particularly when fat mass (FM) gains are higher than fat-free mass (FFM) gains. Recent work by Dr. Salas suggests that extremely preterm infants unable to tolerate early progression of enteral feeding volumes during the first 2 weeks after birth have an increased risk of disrupted maturation of the gut microbiome and an increased risk of postnatal growth failure. In the research plan outlined in this K23 proposal, Dr. Salas will expand upon this work by 1) investigating the effects of early postnatal life protein-enriched diets on FFM accretion in extremely preterm infants and 2) identifying maturation patterns of the gut microbiome that differentiate preterm infants with postnatal growth failure and reduced FFM accretion from preterm infants with appropriate postnatal growth and normal FFM accretion. This work will produce novel insights into the pathogenesis of postnatal growth failure in preterm infants and will serve as the foundation for Dr. Salas to inform his future R01 proposals and discover new, evidence-based approaches to prevent postnatal growth failure. His career development plan outlines a clear path to gain the knowledge, skills, and experience needed to become an independent clinician scientist, leader, and innovator in neonatal nutrition research.
Premature infants born at the limits of viability usually do not grow well during their hospital stay and have a higher risk of developing long-term nutritional complications related to extreme prematurity. Early administration of protein-enriched human milk diets could improve growth by promoting lean body mass accretion, stimulating maturation of gastrointestinal tract, and modifying the gut microbiome. We will test whether protein-enriched human milk diets during the first 2 weeks after birth in premature infants born at the limits of viability result in more lean body mass accretion and more diversity of the gut microbiome by the time of hospital discharge.
