Oral Feeding Difficulty in Large for Gestational Age Infants: Defining Interrelationships between Body Composition, Oral Feeding Ability, and Appetite-Regulating Hormones - Project Summary/Abstract Prevalence of oral feeding difficulty in infants admitted to a neonatal intensive care unit (NICU) is increasing. This not only leads to prolonged NICU stay, but an escalation of healthcare costs as well. A major contributor is the increase in large for gestational age (LGA) infant birth rate because of rising maternal obesity and diabetes during pregnancy. LGA infants are considered poor oral feeders. Significant knowledge gaps exist in understanding the complex mechanisms implicated in LGA infants with oral feeding difficulty. LGA infants are exposed to excess energy in utero and body composition studies have shown that they have higher fat mass (FM) and lower fat-free mass (FFM) proportion. Oral feeding ability can be influenced by hunger and satiety, which may have a feedback mechanism with the state of the body's energy stores (FM as proxy) and resting metabolic rate (RMR, FFM as proxy), and these effects may be mediated through the appetite-regulating hormone (ARH) levels. Our preliminary data suggest that infants with a higher FM and lower FFM proportion (disproportionate body composition) took longer to reach independent oral feeds, required longer hospitalization, and required higher g-tube placement. FFM is better associated with oral (energy) intake than FM, suggesting that FFM is major determinant of energy intake and appetite in infants. The standard NICU feeding strategy is focused on promoting weight gain irrespective of birth weight or body composition, which is inappropriate in LGA infants as LGA infants who demonstrated ‘catch-down’ growth in early infancy had better long-term outcomes. These infants had a greater proportion of FM loss compared to FFM during the catch-down period. LGA infants with oral feeding difficulty in the NICU are dependent on tube-feeding and the feeding intake is regulated by the care team rather than being infant-driven. The lower FFM% in these infants may reduce their ability to meet the standard oral intake volumes indexed to total mass (150 ml/kg/day). The continued provision of excess calories above the metabolic needs from tube-feeding may increase their body adiposity, prevent natural catch-down growth, and exacerbate their oral feeding difficulty. The proposed research will evaluate the interrelationship between body composition, oral feeding ability, and ARH levels in LGA infants. Further, we will evaluate the effects of a short-term FFM-indexed feeding (target feeding volume indexed to FFM) versus the standard approach to feeding (target feeding volume indexed to total mass) on oral feeding outcomes, catch-down weight, and body composition in LGA infants with oral feeding difficulty. Knowledge gained from this proposal will provide a rationale for future studies designed to evaluate precision nutritional therapies for LGA infants. This may ultimately shorten the length of hospital stay and enhance the quality of life for these infants.