(Adapted from the applicant's abstract): The CAP candidate is a pediatrician with medical subspecialty training in nutrition, training in clinical epidemiology, and a long-standing interest in clinical research. The complementary and interdisciplinary nature of the training component of the proposed CAP program will enable him to become an independent and productive, patient-oriented researcher. The CAP candidate will be mentored for this clinical research training by Dr. Virginia A. Stallings, Chief of the Nutrition Section at the Children's CHOP, and will acquire proficiency with the techniques for the assessment of body composition, growth and energy balance. Drs. Babette S. Zemel at CHOP, and Michael I. Goran at the University of Southern California will serve as co-mentors for some aspects of this training. The candidate will also continue his advanced training in the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania, leading to a Ph.D. in clinical epidemiology. The research component of the program proposes a three-year prospective cohort study aimed at investigating the components of energy balance in children with DS, to identify the causes of their increased risk for obesity. As the life expectancy of people with DS has increased, chronic diseases and the psychosocial burden associated with obesity have a significant impact on their quality of life. The primary hypothesis is that the resting energy expenditure (REE) of children with DS, measured by indirect calorimetry, is lower than the REE of healthy control subjects sharing the same family background, their siblings. The association between REE and the accretion of fat mass over a three-year follow-up period, as well as the impact of physical activity will also be investigated. REE, growth, and body composition will be measured by state of the art technologies available at the GCRC Nutrition Assessment Core Laboratory, and physical activity will be derived from measurement of total energy expenditure measured by doubly labeled water. This study will contribute to the understanding of the development of obesity in DS, and lead to clinical trials for its prevention and treatment. Furthermore, this study of children with DS is likely to provide a model of the development of obesity applicable to other children at risk, and may lead to the assessment of gene expression in DS responsible for changes in energy balance and the development of obesity.