Developmental Trajectories and Differences in Functional Brain Network Properties of Preterm and At-Term Neonates

Premature infants, born before 37 weeks of gestation can have alterations in neurodevelopment and cognition, even when no anatomical lesions are evident. Resting-state functional neuroimaging of naturally sleeping babies has shown altered connectivity patterns, but there is limited evidence on the developmental trajectories of functional organization in preterm neonates. By using a large dataset from the developing Human Connectome Project, we explored the differences in graph theory properties between at-term (n = 332) and preterm (n = 115) neonates at term-equivalent age, considering the age subgroups proposed by the World Health Organization for premature birth. Leveraging the longitudinal follow-up for some preterm participants, we characterized the developmental trajectories for preterm and at-term neonates, for this purpose linear, quadratic, and log-linear mixed models were constructed with gestational age at scan as an independent fixed-effect variable and random effects were added for the intercept and subject ID. Significance was defined at p < 0.05, and the model with the lowest Akaike Information Criterion (AIC) was selected as the best model. We found significant differences between groups in connectivity strength, clustering coefficient, characteristic path length and global efficiency. Specifically, at term-equivalent ages, higher connectivity, clustering coefficient and efficiency are identified for neonates born at later postmenstrual ages. Similarly, the characteristic path length showed the inverse pattern. These results were consistent for a variety of connectivity thresholds at both the global (whole brain) and local level (brain regions). The brain regions with the greatest differences between groups include primary sensory and motor regions and the precuneus which may relate to the risk factors for sensorimotor and behavioral deficits associated with premature birth. Our results also show non-linear developmental trajectories for premature neonates, but decreased integration and segregation even at term-equivalent age. Overall, our results confirm altered functional connectivity, integration and segregation properties of the premature brain despite showing rapid maturation after birth.