MODULATION OF CIRCADIAN RHYTHMICITY IN PRETERM INFANTS

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The environment in which many premature infants reside for weeks or months after birth differs markedly from the surroundings encountered in utero. Thermal, hormonal, and other rhythmic and patterned maternal inputs which are normally conferred on the developing fetus are replaced by the constantly lit, noisy milieu of the neonatal intensive care unit (NICU). Very little is known about the development of circadian rhythmicity of physiological variables such as temperature, cardiorespiratory control, activity, and sleep in preterm infants. Similarly, it is unclear how the NICU environment influences rhythmic activity. In addition, the longer- term effects of nursery environments on sleep quality, feeding, growth, and other aspects of the physiology and behavior of preterm infants are poorly understood. In addressing these questions, a multidisciplinary approach is proposed which examines neuroanatomical, environmental, physiologic, and behavior aspects of the infant circadian system. First, the development of the neuronal pathway mediating the effects of light on the hypothalamic suprachiasmatic nucleus (SCN), the putative "biological clock" will be examined, providing the first data on the maturation of the neuronal components of the human infant circadian system. Second, the NICU light environment will be quantified from a chronobiological perspective, permitting comparison with a vast literature on the influences of light on biological rhythms. Third, the development of overt rhythmicity of temperature, heart rate, and activity will be described across a spectrum of gestational and postnatal ages using a powerful battery of analytical techniques. Apnea and periodic breathing, which have been linked with increased risk for Sudden Infant Death Syndrome (SIDS) and increased morbidity, will also be measured over multiday periods to provide new data on possible cyclic alterations in the characteristics of respiratory control. Finally, using Stanford Medical Center's Premature Research Center as a controlled environment, the immediate and longer-term effects of light-dark cycling on the appearance of rhythmic events and sleep will be tested. Awareness of the ontogeny of circadian rhythmicity in infants will be helpful in neonatal assessment, intervention, management, and in optimizing the physical environment and caregiving procedures in the NICU. Results from these studies will provide a scientific basis for the refinement of the NICU environment and facilitate the recovery, development, and improved outcome in this significant infant population.