ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Endocrinol. 2019; 242(1):T69–T79.

Maternal exposure to glucocorticoid therapy, or stress and anxiety during pregnancy, have been linked to alterations in the exposed offspring in their functioning of the hypothalamic-pituitary-adrenal (HPA) axis and stress-related behaviours. Moreover, it appears that these effects are maintained across multiple generations. There is considerable heterogeneity in the literature regarding the observed effects in the offspring. The programmed phenotype seems to be dependent on very specific factors, such as timing and dose of exposure. It is also evident that sex of the offspring and age at which assessment of outcome is undertaken are important. Mechanistic studies in animals and similar associations in humans are linking early exposures to adversity with changes in gene regulatory mechanisms, including modifications of DNA methylation and altered levels of miRNA.

These findings suggest that epigenetic mechanisms represent a fundamental link between early life adversity and developmental programming of diseases later in life. Epigenetic studies come, however, with a set of challenges that need to be addressed in order to help interpret results, and how phenotypes are transmitted between generations still needs to be explained. The new knowledge gained from studies that are addressing these issues will be very helpful in identifying individuals who are at risk of developing poor outcomes and for whom early intervention is most efficacious. These interventions can be identified and refined further by advancing our understanding of the underlying targets and factors that drive these outcomes. With time, poor outcomes associated with early life adversity can possibly be prevented, ameliorated or reversed.