A Life Course Approach to the Relationship Between Fetal Growth and Hypothalamic-Pituitary-Adrenal Axis Function
Bibliographic record
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.008 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".