A life course approach to the relationship between fetal growth and hypothalamic-pituitary-adrenal axis function

Wrivu N Martin, Carol A Wang, Stephen J Lye, Stephen G Matthews, Rebecca M Reynolds, Carly E Mclaughlin, Roger Smith, Craig E Pennell

Research output: Contribution to journalArticlepeer-review

Abstract

Context:
Human and animal studies suggest that hypothalamic-pituitary-adrenal axis (HPA-A) function may be programmed in utero; however, these findings are inconsistent. Given the powerful metabolic actions of cortisol, it is important to clarify the influence of early life on adult HPA-A function.
Objective:
To determine the relationship between fetal growth and HPA-A stress response to a psychosocial stressor in young adults.
Design:
Multigenerational, prospective cohort study (The Raine Study) conducted between 1989 and 1991.
Setting:
King Edward Memorial Hospital, Perth, Western Australia, Australia.
Participants:
917 participants aged 18 from Gen 2 of the Raine Study.
Main Outcome Measures:
Measures of Hypothalamic-Pituitary-Adrenal-Axis function before and after exposure to the Trier Social Stress Test.
Results:
In fully adjusted models, an inverse linear relationship was observed between birth weight and and plasma measures of 1) baseline cortisol (β = -0.90%, 95% CI: -1.73 to -0.07; p = 0.03); 2) peak cortisol (β = -0.78%, 95% CI -1.51 to -0.06; p=0.03); 3) AUCg (β = -0.89%, 95% CI -1.60 to -0.18; p=0.01); and 4) adrenal sensitivity (β = -1.02, 95% CI: -1.85 to -0.18; p=0.02). Similar results were demonstrated for per cent optimal birth weight. No consistent quadratic relationships were identified. No associations were found between measures of fetal adiposity and HPA-A function at age 18, or fetal growth and HPA-A response pattern.Removal of anticipatory responders from the models substantially attenuated the observed relationships.
Conclusion: We observed an inverse linear relationship between fetal growth and HPA-A function at age 18. This differs from the inverse parabolic relationship (inverted U curve) reported in adults of advanced age. Altered adrenal sensitivity may underlie this relationship.
Original languageEnglish
JournalJournal of Clinical Endocrinology & Metabolism
DOIs
Publication statusPublished - 17 May 2021

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