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


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.
To determine the relationship between fetal growth and HPA-A stress response to a psychosocial stressor in young adults.
Multigenerational, prospective cohort study (The Raine Study) conducted between 1989 and 1991.
King Edward Memorial Hospital, Perth, Western Australia, Australia.
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.
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
Publication statusPublished - 17 May 2021


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