Neonatal amygdala volumes, procedural pain and the association with social-emotional development in children born very preterm.

ABSTRACT

Very preterm birth (< 32 weeks' gestational age) is associated with later social and emotional impairments, which may result from enhanced vulnerability of the limbic system during this period of heightened vulnerability. Evidence suggests that early procedural pain may be a key moderator of early brain networks. In a prospective cohort study, neonates born very preterm (< 30 weeks' gestation) underwent MRI scanning at term-equivalent age (TEA) and clinical data were collected (mechanical ventilation, analgesics, sedatives). Procedural pain was operationalized as the number of skin breaking procedures. Amygdala volumes were automatically extracted. The Strengths and Difficulties questionnaire was used to assess social-emotional outcomes at 5 years of age (mean age 67.5 months). General linear models were employed to examine the association between neonatal amygdala volumes and social-emotional outcomes and the timing and amount of procedural pain exposure (early within the first weeks of life to TEA) as a moderator, adjusting for biological sex, gestational age, 5-year assessment age, days of mechanical ventilation and total cerebral volumes. A total of 42 preterm infants participated. Right amygdala volumes at TEA were associated with prosocial behaviour at age 5 (B = -0.010, p = 0.005). Procedural pain was found to moderate the relationship between right amygdala volumes in the neonatal period and conduct problems at 5 years, such that early skin breaking procedures experienced within the first few weeks of life strengthened the association between right amygdala volumes and conduct problems (B = 0.005, p = 0.047). Late skin breaking procedures, experienced near TEA, also strengthened the association between right amygdala volumes and conduct problems (B = 0.004, p = 0.048).

HIGHLIGHTS ● Preterm birth is associated with social-emotional challenges.● Amygdala volumes at term equivalent age were assessed in relation to preschool social-emotional outcomes.● Larger right amygdala volumes at term-equivalent age were associated with impaired prosocial behaviour at age 5.● Procedural pain moderated the relationship between neonatal amygdala volumes and conduct problems at age 5, with early or late skin breaking procedures strengthening this association.● Dysregulated growth and maturation of the amygdala in preterm neonates were associated with differences in social functioning at 5 years old, with early life procedural pain playing a moderating role.