Children born very preterm (<33 weeks of gestation) are at a higher risk of developing socio-emotional difficulties compared to those born at term. In this longitudinal study, we tested the hypothesis that diffusion characteristics of white matter tracts implicated in socio-emotional processing assessed in the neonatal period are associated with socio-emotional development in 151 very preterm children previously enrolled into the Evaluation of Preterm Imaging study (Eudra: CT2009-011602-42). All children underwent diffusion tensor imaging at term-equivalent age and fractional anisotropy (FA) was quantified in the uncinate fasciculus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus and superior longitudinal fasciculus. Children's socio-emotional development was evaluated at preschool age (median=4.63 years). Exploratory factor analysis conducted on the outcome variables revealed a 3-factor structure, with latent constructs summarised as: 'emotion moderation', 'social function' and 'empathy'. Results of linear regression analyses, adjusting for full-scale IQ and clinical and socio-demographic variables, showed an association between lower FA in the right uncinate fasciculus and higher 'emotion moderation' scores (ß=-0.280; <i>p</i><0.001), which was mainly driven by negative affectivity scores (ß=-0.281; <i>p</i>=0.001). Results further showed an association between higher full-scale IQ and better social functioning (ß=-0.334, <i>p</i><0.001). Girls had higher empathy scores than boys (ß=-0.341, <i>p</i>=0.006). These findings suggest that early alterations of diffusion characteristics of the uncinate fasciculus could represent a biological substrate underlying the link between very preterm birth and emotional dysregulation in childhood and beyond.<b>Significance Statement</b>Children born very preterm are at a higher risk of developing socio-emotional difficulties compared to those born at term. Our study showed that early alterations of diffusion characteristics of the uncinate fasciculus in very preterm babies assessed at term-equivalent age were associated with emotional dysregulation in childhood. The identification of early biological substrates linked to emotional development could create opportunities for the prevention and targeting of emerging emotional problems in order to enhance children's mental health.
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