Regional cerebral development at term relates to school-age social-emotional development in very preterm children

Objective: Preterm children are at risk for socialemotional difficulties, including autism and attention-deficit/hyperactivity disorder. We assessed the relationship of regional brain development in preterm children, evaluated via magnetic resonance imaging (MRI) at term-equivalent postmenstrual age (TEA), to later socialemotional difficulties. Method: MR images obtained at TEA from 184 very preterm infants (gestation <30 weeks or birth weight <1,250 g) were analyzed for white matter abnormalities, hippocampal volume, and brain metrics. A total of 111 infants underwent diffusion tensor imaging, which provided values for fractional anisotropy and apparent diffusion coefficient. Socialemotional development was assessed with the Infant Toddler Social and Emotional Assessment (ITSEA) at age 2 and the Strengths and Difficulties Questionnaire (SDQ) at age 5 years. Results: Higher apparent diffusion coefficient in the right orbitofrontal cortex was associated with socialemotional problems at age 5 years (peer problems, p <.01). In females, smaller hippocampal volume was associated with increased hyperactivity (p <.01), peer problems (p <.05), and SDQ total score (p <.01). In males, a smaller frontal region was associated with poorer prosocial (p <.05) scores. Many of the hippocampal findings remained significant after adjusting for birthweight z score, intelligence, social risk, immaturity at birth, and parental mental health. These associations were present in children who had socialemotional problems in similar domains at age 2 and those who did not. Conclusions: Early alterations in regional cerebral development in very preterm infants relate to specific deficits in socialemotional performance by school-age. These results vary by gender. Our results provide further evidence for a neuroanatomical basis for behavioral challenges found in very preterm children.