- Title
- A Life Course Approach to the Relationship Between Fetal Growth and Hypothalamic-Pituitary-Adrenal Axis Function
- Creator
- Martin, Wrivu N.; Wang, Carol A.; Lye, Stephen J.; Matthews, Stephen G.; Reynolds, Rebecca M.; McLaughlin, Carly E.; Smith, Roger; Pennell, Craig E.
- Relation
- The Journal of Clinical Endocrinology & Metabolism Vol. 106, Issue 9, p. 2646-2659
- Publisher Link
- http://dx.doi.org/10.1210/clinem/dgab341
- Publisher
- Oxford University Press
- Resource Type
- journal article
- Date
- 2021
- Description
- 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. Supplementary data: Martin, University of Newcastle, Wang, et al. Fetal growth and adult HPA-Axis function. Supplementary data. 2020. Available at: http://hdl.handle.net/1959.13/1411461
- Subject
- DOHaD; HPA; hypothalamic-pituitary-adrenal axis; trier social stress test; fetal growth; developmental origins
- Identifier
- http://hdl.handle.net/1959.13/1468924
- Identifier
- uon:48123
- Identifier
- ISSN:0021-972X
- Language
- eng
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