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Fetal growth and programming of the hypothalamic-pituitary-adrenal axis
1MRC Metabolic Programming Group, Southampton General Hospital, Southampton, UK. diwp@soton.ac.uk
Insights
Small size at birth increases the risk of adult heart disease and diabetes. Intrauterine factors may alter the stress response, impacting long-term health outcomes.
Area of Science:
- Developmental biology
- Endocrinology
- Epidemiology
Background:
- Epidemiological studies link low birth weight to increased risks of coronary heart disease, hypertension, and type 2 diabetes.
- This association is hypothesized to stem from fetal nutrient supply-demand imbalances during gestation.
- These imbalances trigger adaptive fetal responses that have long-term maladaptive consequences.
Purpose of the Study:
- To explore the long-term health implications of fetal growth restriction.
- To investigate the role of the hypothalamic-pituitary-adrenal axis in mediating the effects of birth size on adult disease risk.
Main Methods:
- Review of epidemiological data on birth size and adult disease.
- Analysis of experimental animal data regarding fetal development and stress response.
- Examination of human observational studies on fetal growth and endocrine adaptations.
Main Results:
- Small size at birth is a significant risk factor for cardiovascular and metabolic diseases in adulthood.
- Fetal nutrient imbalances lead to metabolic and endocrine adaptations with long-term negative health effects.
- Alterations in the hypothalamic-pituitary-adrenal axis set point are associated with reduced fetal growth.
Conclusions:
- Intrauterine factors, including nutrient availability, can permanently influence physiological set points.
- The fetal stress response programming may be established in utero, impacting adult disease susceptibility.
- Understanding these early-life influences is crucial for preventing chronic diseases later in life.
Abstract:
1. Epidemiological studies have shown that small size at birth is associated with an increased risk of coronary heart disease and its risk factors, including hypertension and type 2 diabetes. 2. It is suggested that these observed links between low birthweight with disease result from an imbalance between fetal nutrient demand and supply. This imbalance results in metabolic and endocrine adaptations that benefit the fetus in the short term by reducing fetal growth and increasing fuel availability but, in the longer term, are maladaptive, leading to an increased risk of coronary heart disease. 3. Experimental data in animals and recent human observations have suggested that an alteration in the set point of the hypothalamic-pituitary-adrenal axis is an important long-term change that occurs in association with reduced fetal growth. 4. These data raise the possibility that the nature and amplitude of the stress response may be determined by intra-uterine factors.