1. A Life Course Approach to the Relationship Between Fetal Growth and Hypothalamic-Pituitary-Adrenal Axis Function.
- Author
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Martin WN, Wang CA, Lye SJ, Matthews SG, Reynolds RM, McLaughlin CE, Smith R, and Pennell CE
- Subjects
- Adolescent, Birth Weight, Female, Humans, Hydrocortisone blood, Male, Stress, Psychological physiopathology, Young Adult, Fetal Development physiology, Hypothalamo-Hypophyseal System physiology, Pituitary-Adrenal System physiology
- 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: A total of 917 participants aged 18 years from Gen2 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 birthweight 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) area under the curve with respect to ground (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 percent optimal birthweight. No consistent quadratic relationships were identified. No associations were found between measures of fetal adiposity and HPA-A function at age 18 years, 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 years. This differs from the inverse parabolic relationship (inverted U curve) reported in adults of advanced age. Altered adrenal sensitivity may underlie this relationship., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2021
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