Neonatal Hippocampal Volume and Parent Structuring at 18 Months in Relation to Cortisol Stress Regulation Across Early Childhood and Executive Functions at Age 4 Years in Children Born Very Preterm

Abstract

Background: Children born very preterm (≤32 weeks gestational age) display altered neonatal brain maturation and physiological stress regulation that may be related to executive function difficulties. Supportive parent behaviors are related to better neurodevelopment, but children may vary in their susceptibility to such behaviors. We investigated whether supportive parenting during toddlerhood (1.5, 3 years) moderated the relationship between neonatal hippocampal volume, stress dysregulation across childhood, and executive functions.

Methods: In a prospective longitudinal cohort study (N = 188, 100 male), infants born very preterm underwent magnetic resonance imaging at term-equivalent age. At 1.5, 3, and 4.5 years, saliva samples were collected during challenging cognitive tasks and assayed for cortisol; area under the curve with respect to ground (AUCg) measured total cortisol output at each age. Parent interaction was rated from films at 1.5 and 3 years, and parents reported on child executive functions at age 4.5 years.

Results: Longitudinal modeling revealed no direct relationship between hippocampal volume and cortisol trajectories. Children with smaller neonatal hippocampal volume showed greater susceptibility to poorer parent structuring at 1.5 years, associated with altered AUCg trajectories across age, and displayed fewer executive functions in the face of optimal structuring. Lower AUCg across age was related to more positive parenting (sensitivity, nonhostility, nonintrusiveness) at 3 years and better child executive function at 4.5 years.

Conclusions: In children born very preterm, smaller neonatal hippocampal volume may represent a neurophenotype of susceptibility to parent provisions of structure related to stress regulation across early childhood. Conversely, supportive parenting may benefit the development of stress regulation across early childhood and executive functions at preschool age.

Keywords: Brain; Early-life stress; HPA axis; Infant; MRI; Parent.