Human development is a complex interplay of different factors. This thesis focuses on two of these factors: sleep and gut bacteria. Sleep takes up more than half of each day in infancy and childhood, and gut bacteria make up around half of all cells in our body. Both undergo large transitions in infancy and childhood. Sleep has been suggested to be a marker of brain maturation. Gut bacteria have been suggested to be health markers. Studies in rodents and adults have found the first evidence that sleep and gut bacteria are linked. However, no studies have examined this link in infancy - a phase with rapid developmental changes.
This thesis fulfills two aims, which are addressed in 6 research articles. The first aim is to get more precise and standardized estimates of infant sleep behavior by improving the methodology of infant actigraphy sleep research. The second is to characterize sleep across development, focusing on the link between sleep and gut bacteria.
The first aim was addressed in three articles. Article 1 systematically reviewed the existing literature that uses actigraphy to measure sleep in infants and children. We rated the methodological reporting, highlighting which information is currently underreported. Additionally, we made recommendations for future studies. Article 2 compared the estimates from two commonly used algorithms (Sadeh and Oakley/Respironics) that score sleep-wake patterns from movement. We found major differences between the sleep estimates but proposed a standardized pipeline to reduce these differences. In Article 3, we applied a principal component approach to a large array of sleep variables to find underlying sleep composites. We found 5 sleep composites, which accurately reflect sleep maturation in the first year of life: Sleep Day (measuring daytime sleep duration and regularity), Sleep Night (measuring nighttime sleep duration), Sleep Timing (measuring nighttime sleep timing), Sleep Activity (measuring awakenings and activity during the night) and Sleep Variability (measuring variability of night sleep timing and duration across measurement days).
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For the second aim, we looked at sleep development across infancy, childhood, and adolescence. Articles 3 and 4 used a large cohort of 162 infants, measured at 3, 6, and 12 months of age with behavioral follow-up at 24 months. In Article 3, we characterized infant sleep in the first year of life. We confirmed the high variability between infants but also show a high variability within infants across the first year of life. We found stable sex differences in Sleep Activity already in infancy. Furthermore, we found that Sleep Day is associated with behavioral development. In Article 4, we investigated which role gut bacteria play in these associations. We showed that alpha diversity was associated with Sleep Day, especially in early development. Additionally, Sleep Activity was associated with bacterial maturity and enterotype. Furthermore, we found exciting associations between both sleep and gut bacteria and development; most notably, we extended the finding of Sleep Day as a maturational marker by showing that daytime sleep at 12 months negatively predicts gross motor development at 24 months. Additionally, we found a positive association between alpha diversity and early behavioral development. Overall, we showed complex and dynamic associations between sleep, gut bacteria, and behavioral development.
Articles 5 and 6 examined the spatio-temporal properties of sleep slow waves. In Article 5, we investigated a dataset of 29 children and adolescents between 2 and 17 years of age. We examined how sleep slow waves travel across the cortex, how this traveling behavior changes across the night, and if the traveling behavior is different across development. We found one aspect that had age-dependent changes across the night: slow wave propagation distance. It only decreases across the night in children younger than 5 years old. In Article 6, we reviewed the relationship of intracellular slow oscillations and scalp slow waves. Additionally, we showed that the origin of sleep slow waves is less likely to be located in frontal areas in children than in adolescents. We proposed that slow waves not only mirror brain maturation but might also be driving this maturation.
This thesis shows the remarkable development of sleep from infancy to adolescence. It also provides the first evidence of a sleep-gut link in infancy and reveals interesting associations between sleep and gut bacteria and behavioral development. I propose methodological recommendations and future research directions to increase our knowledge of infant development.