Fetal growth and programming of the hypothalamic-pituitary-adrenal axis.

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.