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).
CONCLUSIONS: Dysregulated growth and maturation of the amygdala in preterm neonates is associated with differences in social functioning in children born preterm, with early life procedural pain moderating these associations. Examination of sensitive windows when the developing brain may be most vulnerable to the adverse effects of procedural pain may inform pain management practices. This is key in the identification of children at risk for social difficulties and can lead to targeted interventions to support social development in this population.
CONCLUSIONS: ● 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.
CONCLUSIONS: Dysregulated growth and maturation of the amygdala in preterm neonates is associated with differences in social functioning in children born preterm, with early life procedural pain moderating these associations. Examination of sensitive windows when the developing brain may be most vulnerable to the adverse effects of procedural pain may inform pain management practices. This is key in the identification of children at risk for social difficulties and can lead to targeted interventions to support social development in this population.
CONCLUSIONS: ● 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.
摘要：
早产（<32周胎龄）与后期的社交和情感障碍有关，这可能是由于在脆弱性加剧期间边缘系统的脆弱性增强所致。证据表明，早期程序性疼痛可能是早期大脑网络的关键调节因素。在一项前瞻性队列研究中，早产（<30孕周）的新生儿在足月相当年龄（TEA）时接受MRI扫描，并收集临床数据（机械通气，镇痛药,镇静剂）。手术疼痛以皮肤破裂手术的次数进行操作。自动提取杏仁核体积。使用优势和困难问卷评估5岁（平均年龄67.5个月）时的社交情感结果。一般线性模型用于检查新生儿杏仁核体积和社会情绪结果之间的关系，以及作为调节因素的程序性疼痛暴露的时间和数量（在TEA出生的最初几周内）。适应生物性别，胎龄,5年评估年龄，机械通气天数和总脑容量。共有42名早产儿参加。TEA的右杏仁核体积与5岁时的亲社会行为有关（B=-0.010，p=0.005）。发现程序性疼痛可以减轻新生儿期的右杏仁核体积与5年时的行为问题之间的关系，这样，在生命的最初几周内经历的早期皮肤破裂程序加强了右杏仁核体积与行为问题之间的关联（B=0.005，p=0.047）。晚期皮肤破裂程序，在茶附近有经验，还加强了右杏仁核体积与行为问题之间的关联（B=0.004，p=0.048）。
结论：早产儿杏仁核生长和成熟失调与早产儿社会功能的差异有关。早期生活程序性疼痛缓和了这些关联。当发育中的大脑可能最容易受到程序疼痛的不利影响时，检查敏感窗口可以告知疼痛管理实践。这是确定面临社会困难风险的儿童的关键，并可以导致有针对性的干预措施，以支持这一人群的社会发展。
结论：●早产与社会情绪挑战相关。●评估足月同等年龄的杏仁核体积与学前社会情绪结果的关系。●足月相当年龄时右杏仁核体积较大与5岁时亲社会行为受损相关。●程序性疼痛减轻了新生儿杏仁核体积与5岁时行为问题之间的关系，早期或晚期皮肤破裂手术加强了这种关联。●早产儿杏仁核生长和成熟失调与5岁时的社会功能差异相关，早期生活中的程序性疼痛起着调节作用。
结论：早产儿杏仁核生长和成熟失调与早产儿社会功能的差异有关。早期生活程序性疼痛缓和了这些关联。当发育中的大脑可能最容易受到程序疼痛的不利影响时，检查敏感窗口可以告知疼痛管理实践。这是确定面临社会困难风险的儿童的关键，并可以导致有针对性的干预措施，以支持这一人群的社会发展。
结论：●早产与社会情绪挑战相关。●评估足月同等年龄的杏仁核体积与学前社会情绪结果的关系。●足月相当年龄时右杏仁核体积较大与5岁时亲社会行为受损相关。●程序性疼痛减轻了新生儿杏仁核体积与5岁时行为问题之间的关系，早期或晚期皮肤破裂手术加强了这种关联。●早产儿杏仁核生长和成熟失调与5岁时的社会功能差异相关，早期生活中的程序性疼痛起着调节作用。
