DESCRIPTION (applicant's abstract): Although 250,000 preterm infants are reared in artificial environments of hospital nurseries in the United States each year, very little consideration is given to the lighting cycles to which infants are exposed. In neonatal intensive care units, preterm infants are typically exposed to continuous dim lighting without photic time-of-day cues. In the absence of photic entraining signals, the oscillations of the developing circadian clock will drift out of synchrony with the circadian phase of the mother and the external light-dark cycle. This desynchrony may compromise maternal-child interactions, resulting in increased infant irritability and increased newborn energy expenditure. To extend principals of circadian biology to the care of human newborns, fundamental issues, such as when the developing primate clock becomes responsive to light, need to be addressed. Thus, several years ago we initiated a series of basic studies aimed at characterizing primate circadian system development. Using baboons to model human circadian system development, we discovered that the circadian pacemaker in the hypothalamic suprachiasmatic nuclei (SCN) is functionally innervated by the retina in very premature infants. We have also discovered that low-intensity lighting (200 lux) entrains developing primate rhythmicity. Based on the above observations, we hypothesize that (1) human infants are entrained by low-intensity cycled lighting at very immature stages, (2) entrainment of the developing circadian clock leads to the earlier establishment of rest-activity cycles, and (3) neonatal entrainment improves parent-infant interactions and neonatal growth. To test these hypotheses, first we will examine influences of lighting cycles on the development of rest-activity patterns. Second, we will examine influences of cycled lighting on growth and energy expenditure. Third, we will examine the influence of cycled lighting on neonatal behavior and parent-infant interactions. These studies will involve a multidisciplinary approach combining expertise in neonatalogy, circadian biology, and child development at a single institution. Each specific aim will involve inpatient investigations, where controlling the environmental conditions is possible. We have also designed outpatient studies to test if photic entrainment before discharge is associated with long-term beneficial influences on activity, growth, infant behavior, and maternal-child interactions. In comparison with the considerable number of research initiatives aimed at examining the role of the circadian system and environmental lighting influences on human adults, circadian system-related studies of children are scant. Thus, our proposal will address recent initiatives for encouraging more child-related investigational research. We anticipate that these studies will improve new insights into the role of the circadian system and environmental lighting on the developing human infant. These studies may also lead to the development of new care practices in Neonatal Intensive Care Units and extend the field of developmental chronobiology to the bedside.