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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

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McLean, Mia A

Weinberg, Joanne

Miller, Jillian V

Guo, Ting

Synnes, Anne R

Miller, Steven P

Grunau, Ruth E

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Elsevier

Abstract

BACKGROUND: Children born very preterm (≤ 32 weeks gestational age) display altered neonatal brain maturation and physiological stress regulation which 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 in toddlerhood (1.5, 3 years) may moderate the relationship between neonatal hippocampal volume, stress dysregulation across childhood and executive functions. METHOD: In a prospective longitudinal cohort study (N = 188, 100 males), infants born very preterm underwent MRI at term-equivalent age. At 1.5, 3, 4.5 years, saliva samples were collected across challenging cognitive tasks and were assayed for cortisol; area under the curve (AUCg) measured total cortisol output at each age. Parent interaction was rated from films at 1.5 & 3 years, and parents reported on child executive functions at age 4.5 years. RESULTS: Longitudinal modelling 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. CONCLUSION: In children born very preterm, smaller neonatal hippocampal volume may represent a neurophenotype of susceptibility to parent provisions of structure relating to stress regulation across early childhood. Conversely, supportive parenting may benefit development of stress regulation across early childhood and executive functions at preschool age.

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brain, Early life stress, HPA-axis, infant, MRI, parent, Brain, Early-life stress, HPA axis, Infant, MRI, Parent, 3213 Paediatrics, 32 Biomedical and Clinical Sciences, Clinical Research, Infant Mortality, Behavioral and Social Science, Basic Behavioral and Social Science, Perinatal Period - Conditions Originating in Perinatal Period, Mental Health, Neurosciences, Pediatric Research Initiative, 06 Biological Sciences, 11 Medical and Health Sciences, 17 Psychology and Cognitive Sciences, Psychiatry, 31 Biological sciences, 32 Biomedical and clinical sciences, 52 Psychology

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Biological Psychiatry, ISSN: 0006-3223 (Print); 1873-2402 (Online), Elsevier, 99(5), 398-406. doi: 10.1016/j.biopsych.2025.06.005

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© 2025 Society of Biological Psychiatry. Note: This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.

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