Abstract
BACKGROUND: To investigate the neurodevelopmental associations of moderate to late preterm (MLP) birth during late childhood. METHODS: We examined the relationship between MLP birth and neuroimaging markers of brain health, as well as neurocognitive performance, in a large cohort from the Adolescent Brain Cognitive Development study. Our analysis included 3323 children (mean age of 10.0 years), with 2710 full-term (mean gestational age of 40.0 weeks) and 613 preterm children (mean gestational age of 34.72 weeks). RESULTS: MLP birth was associated with significant brain neurodevelopmental alterations primarily in the frontal lobes, as evidenced by reductions in white matter integrity, widespread frontal lobe cortical morphology alterations, and reduced functional connectivity in regions and networks subserving executive functions. Compared to full-term children, MLP-born children also showed small, but significantly lower scores on neurocognitive tests of executive functions. Mediation analysis revealed that the relationship between gestational age and neurocognitive performance was positively mediated by the same neuroimaging metrics which were altered by MLP-birth. CONCLUSION: These findings suggest that alterations in brain development due to lower gestational age contribute to poorer cognitive outcomes in MLP-born children. As the frontal lobes continue developing through adolescence, ongoing monitoring will be crucial to address potential long-term challenges. IMPACT: While MLP births make up the largest proportion of preterm births, they remain understudied compared to very preterm births. In our multimodal neuroimaging analysis, we found that MLP-born children exhibit whole brain neurodevelopmental alterations, predominantly in the frontal lobes and in regions subserving executive functions. In addition, our mediation analysis showed that the same brain networks and regions altered in MLP-born children partially mediate the relationship between gestational age and cognitive outcomes, suggesting that these brain alterations directly contribute to poorer cognitive outcomes. Our findings emphasize the need for continued monitoring of MLP-born children into adolescence.