Short- and long-term effects of exposure to natural and synthetic glucocorticoids during development

Abstract

1.Glucocorticoids (GCs) are necessary for fetal development, but clinical and experimental studies suggest that excess exposure may be detrimental to health in both the short and longer term. 2.Exposure of the fetus to synthetic GCs can occur if the mother has a medical condition requiring GC therapy (e.g. asthma) or if she threatens to deliver her baby prematurely. Synthetic GCs can readily cross the placenta and treatment is beneficial, at least in the short term, for maternal health and fetal survival. 3.Maternal stress during pregnancy can raise endogenous levels of the natural GC cortisol. A significant proportion of the cortisol is inactivated by the placental 'GC barrier'. However, exposure to severe stress during pregnancy can result in increased risk of miscarriage, low birth weight and behavioural deficits in children. 4.Animal studies have shown that excess exposure to both synthetic and natural GCs can alter normal organ development, including that of the heart, brain and kidney. The nature and severity of the organ impairment is dependent upon the timing of exposure and, in some cases, the type of GC used and the sex of the fetus. 5.In animal models, exposure to elevated GCs during pregnancy has been associated with adult-onset diseases, including elevated blood pressure, impaired cardiac and vascular function and altered metabolic function.