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Altered neurobehavioral white matter integrity in preterm children: A confounding-controlled analysis using the
Hailong Li1, Yuwen Hung2, Junqi Wang3
1Imaging Research Center, Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Neurodevelopmental Disorders Prevention Center, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Introduction:
Children born preterm face elevated risks of atypical brain development and neurodevelopmental difficulties. However, little is known about childhood outcomes specifically associated with premature birth that are unconfounded by medical complications. This study takes a systematic approach to examine neural and behavioral outcomes in non-medically complex preterm children. The aim is to identify unconfounded neurobehavioral biomarkers and mechanisms that contribute to childhood vulnerability following premature birth, ultimately informing the development of effective interventions to mitigate adverse outcomes in this population.
Methods:
This study leverages the largest publicly available prospective dataset on child brain health in the U.S.-the Adolescent Brain and Cognitive Development (ABCD) Study-using a case-control design. Applying rigorous, systematic confounding control procedures, the study includes 612 children aged 9-11 who have been free of medical and developmental complications since birth. The cohort comprises 306 children born preterm and 306 full-term children matched for age, sex, and socioeconomic status. A comprehensive range of neurocognitive outcomes is examined in relation to the integrity of brain connectomes, as measured by diffusion tensor imaging (DTI).
Results:
Preterm children and full-term control children are significantly differentiated by altered microstructural and axonal integrity, in major frontal-limbic tracts in the whole brain (p < .05). In particular, the strength of structural connectivity in the anterior thalamic radiation, which connects the frontal lobe and the thalamic sensory relay circuit, shows altered brain-behavioral regulatory relationship with the performance on the attention and processing speed task (p < .05).
Conclusion:
This secondary analysis of the ABCD Study identified unconfounded neurobehavioral risk biomarkers associated with premature birth, along with underlying neurobiological and cognitive mechanisms. Children born preterm demonstrated reduced neurobehavioral white matter integrity within the frontal-limbic connectome, particularly in tasks requiring sustained attention and processing speed. This diminished adaptability places them at elevated risk for developing related neurodevelopmental difficulties. These findings highlight the urgent need for routine screening and preventive neuro-rehabilitative interventions-such as attention-focused and sensory-feedback-based training-for preterm-born populations.
