Fetal programming of stress responses.

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.It is suggested that these observations linking low birthweight with disease result from an imbalance between fetal nutrient demand and supply. This imbalance results in metabolic and endocrine adaptations, which benefit the fetus in the short term by reducing fetal growth and increasing fuel availability, but in the longer term they are maladaptive leading to an increased risk of coronary heart disease. Experimental data in animals and recent human observations have suggested that alterations in the set point of the hypothalamic-pituitary-adrenal axis and sympathoadrenal system are important long-term changes that occur in association with reduced fetal growth. These data suggest that the nature and amplitude of the stress response may be determined by intrauterine factors.