Project Summary/Abstract Preterm infants (≤ 37 weeks gestational age at birth) only represent 10% of live births in the United States, yet account for 43% of the total cost of infant care in hospitals. Delays in the development of oral feeding skills in preterm infants are one of the main reasons for prolonged hospitalization, which increases the cost of care and delays unification with family. Preterm infants often experience oral feeding difficulties due to immaturity of their neurologic, cardiorespiratory, gastrointestinal, and oral-motor systems. Recurrent distress during feeding alters sensory-motor pathways in the developing brain, leading to long-term, maladapted feeding behaviors. Up to 41% of preterm infants experience feeding difficulties that continue into childhood, which has implications for long- term growth and neurodevelopment. Traditionally, the semi-elevated supine position (hereafter referred to as supine position) has been used in neonatal intensive care units when preterm infants are bottle-fed. Over the past decade, the semi-elevated side-lying position (hereafter referred to as side-lying position) has been proposed as a potential strategy to improve preterm infants’ oral feeding skills and to reduce adverse events during feeding, but the quality of the evidence to support the side-lying position as a feeding intervention is in an early, emergent stage. Due to limited evidence, clinicians are inconsistent in their use of the side-lying position, exposing infants already experiencing feeding challenges to unpredictable and variable feeding positions, which can further complicate their feeding skill development. Additional research is necessary to provide more definitive knowledge on whether the side-lying position improves preterm infants’ feeding skills and to generate needed information to enhance precision to the application of this intervention. To address this gap, we propose a single- center randomized cross-over trial to gain a thorough understanding of the biobehavioral efficacy of the side- lying vs. the supine position on physiologic and behavioral responses of preterm infants while transitioning from tube to full oral feeding, and to identify infant characteristics associated with the intervention response. The specific aims are to: 1) compare physiologic responses in preterm infants while bottle feeding in the side-lying vs. supine position; 2) compare behavioral responses in preterm infants while bottle feeding in the side-lying vs. supine position; and 3) identify moderators of intervention response, evaluating infant sex, maturity level, and co-morbid conditions. Physiologic responses will include continuous measures of heart rate, respiratory rate, oxygen saturation, and autonomic nervous system regulation (heart rate variability and splanchnic-cerebral oxygen ratio) prior to, during and after feeding. Behavioral responses will include observations of the infant’s feeding behavior through microanalysis of the...