Regional Cerebral Development at Term Relates to School-Age Social-Emotional Development in Very Preterm Children

Objective: Preterm children are at risk for social-emotional 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 social-emotional difficulties. Method: MR images obtained at TEA from 184 very preterm infants (gestation less than 30 weeks or birth weight less than 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. Social-emotional 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 social-emotional problems at age 5 years (peer problems, p less than 0.01). In females, smaller hippocampal volume was associated with increased hyperactivity (p less than 0.01), peer problems (p less than 0.05), and SDQ total score (p less than 0.01). In males, a smaller frontal region was associated with poorer prosocial (p less than 0.05) 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 social-emotional 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 social-emotional 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. (Contains 3 figures and 2 tables.)