ABSTRACTBackgroundRecent work has challenged the long-held assumption that appetite functions to maintain stable body mass and fat mass (FM), suggesting instead that appetite matches food intake to energy expenditure and its correlate, fat-free mass (FFM). Whether this scenario applies to young infants, in chronic positive energy balance, remains unknown.ObjectivesTo test associations of components of energy expenditure and body composition with milk intake (MI) and energy intake (EI) in 12-week infants, by reanalyzing published cross-sectional data.MethodsData were available for 48 infants. In addition to anthropometric measurements, we assessed MI and EI by test-weighing, sleeping metabolic rate (SMR) by indirect calorimetry, and FFM, FM, and total energy expenditure (TEE) by doubly labeled water. Mean parental height was calculated as a marker of infant growth drive. Correlation and multiple regression analyses were applied.ResultsMI and EI correlated with FFM (r = 0.47 and 0.57, respectively; P < 0.01), but not FM (P > 0.6). MI and EI correlated with SMR (r = 0.42 and 0.53, respectively; P < 0.01) and TEE (r = 0.50 and 0.49, respectively; P < 0.01). SMR and TEE correlated with FFM (r = 0.41 and 0.42, respectively; P < 0.01), but not FM (P > 0.2). In a multiple regression analysis, MI was independently associated with TEE (partial r = 0.39) and FFM (partial r = 0.35). EI showed similar associations. Mean parental height was correlated with weight gain, MI, and EI.ConclusionsAs in adults, MI and EI in young infants were strongly associated with FFM and with total and sleeping components of energy expenditure, but not with fatness. The infant's growth drive contributed to these associations. This suggests that appetite is regulated by the rate of energy expenditure, the size of energy-using tissues, and tissue deposition rate, and that the high levels of body fat characteristic of infants may not constrain weight gain.