The Development of Circadian Rhythms in Human Infants

Introduction: The first four postnatal months, for a newborn infant, is a period of rapid adaptation and change. Infants undergo a series of integrated physiological changes that culminate in mature physiological diurnal rhythms by which they establish equilibrium with the new environment, all of which are under the genetic control of the biological clock. This is a longitudinal study of 35 infants in which the age related changes in physiology, are assessed during night time sleep and related to circadian genes, melatonin and cortisol. Aim: The aim of the study is to monitor the physiological development of normal full-term human infants concomitantly assessing the expression of circadian genes. Method: Full term healthy infants were selected. Infants were recruited into the study from 6 weeks until 18 weeks of age. Fortnightly home visits were conducted in which the overnight deep body temperature of infants was monitored. On each night of study, actigraphy was used to study infant and maternal sleep. Longitudinal measurements of melatonin and cortisol secretion by paired day-night urine collection and peripheral gene expression using buccal swabs were taken by mothers. Results: There is evidence of a sequential and ordered development of circadian rhythms in human infant physiology. There was a temporal relationship demonstrated in the maturation of the infant circadian rhythms. Core body temperature demonstrated a robust rhythm, characterised by an abrupt change, the timing of which varied from infant to infant. Night time melatonin secretion increased with age. Cortisol played a key role. Infant sleep improved with physiological maturation. A number of complex relationships between aspects of the physiology and circadian gene expression were elucidated. Conclusion: There is a demonstrable integration of genetic and physiological changes, during the immediate postnatal period when infants are most vulnerable to illnesses and particularly to sudden and unexpected death.