PROJECT SUMMARY/ABSTRACT Obesity affects 1 in 5 children and adolescents in the United States and prevalence of severe obesity is worsening. Despite advances in treatment for obesity, primary prevention is essential to prevent morbidity and early death. Infants who gain weight rapidly have over 4 times higher odds of developing obesity as a child or adult, and rapid weight gain during infancy also explains a large percentage of the entrenched and worsening racial and ethnic disparities in childhood obesity and subsequent cardiometabolic disease. Infants who are predominantly bottle-fed are at higher risk for excessive infancy weight gain and childhood obesity, yet we do not have effective interventions to reduce excessive weight gain among infants who are bottle-fed. Our preliminary work suggest that two novel intervention strategies are feasible and may reduce excessive infancy weight gain: reducing bottle size; and increasing bottle opacity. Both smaller size and increased opacity attenuate the visual cues that may encourage overfeeding of bottle-fed infants and overriding infants’ hunger and satiation cues. Our past observational work shows the size of the infant bottle is positively associated with total formula fed, weight-for-age, and weight-for-length from 2 months through 12 months of life. Our past experimental work shows that smaller bottles are a feasible intervention from the primary care setting. We have also shown that caregivers using opaque bottles showed greater sensitivity to their infant’s hunger and satiation cues and fed their infants less than when using clear bottles. Opaque bottles were acceptable and feasible in a community-based intervention over 3 months. We aim to test the independent and joint efficacy of these two intervention components among exclusively bottle-fed infants in a randomized, full factorial clinical trial. We hypothesize that smaller and opaque bottles reduce conditional weight gain, decrease volume per feed, and improve caregiver sensitivity to infant hunger and satiation cues. Our objective is to understand the independent and joint efficacy of reduced bottle size and increased bottle opacity and to collect additional feasibility and acceptability data in order to facilitate rapid translation and implementation of optimized bottle feeding strategies. We plan to achieve our objectives by (1) assessing the independent and joint efficacy of reducing bottle size and increasing bottle opacity to reduce excessive weight gain from birth to four months of infant life, (2) determine the effects of reducing bottle size and increasing bottle opacity on changes in volume per feed and on caregiver-infant dyad feeding interactions through video-recorded feeding observations, and (3) quantify and describe factors associated with eligibility, enrollment, and adherence to bottle design interventions. To achieve these aims, we have assembled a team of experts in obesity, primary care-based clinical interventions, infa...