Fetal origins of stress-related adult disease

Abstract

During the past decade, a considerable body of evidence has emerged showing that circumstances during the fetal period may have lifelong programming effects on different body functions with a considerable impact on disease susceptibility. The purpose of this article is to provide a synopsis of these findings and their role in explaining the development of stress-related adult disease. In the context of Per Björntorp memorial symposium, stress-related disease will be interpreted broadly, including cardiovascular disease and components of the metabolic syndrome, for which the evidence of fetal origins is most abundant. It has however become evident that early-life programming has a much broader potential effect on an individual's health. For example, perinatal variables, such as low birth weight, have been associated with increased prevalence of depressive symptoms. Mechanistic studies in animals and humans have shown that lifelong programming of the hypothalamic-pituitary-adrenal axis (HPAA) function by fetal life conditions is likely to be a key factor in mediating associations with these disorders, which frequently are characterized by HPAA overactivity. Preliminary observations suggest a similar important role for early-life programming of sympathoadrenal function. Reduced HPAA activity is characteristic of a number of stress-related disorders, including posttraumatic stress disorder; chronic pain; fatigue; and atypical, melancholic depression. It is therefore highly plausible that susceptibility to these disorders originates in a similar manner during early life, although direct evidence is to a great deal lacking. Important targets for future research include distinction between the effects of different pregnancy conditions, such as maternal malnutrition, preeclampsia, and maternal infection, which may have dissimilar late-life consequences. This will be a crucial step when the associations that are currently emerging will be translated into disease prevention.