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Antenatal glucocorticoids and the developing brain: mechanisms of action
1Department of Physiology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada. stephen.matthew@utoronto.ca
Insights
Prenatal synthetic glucocorticoid treatment benefits preterm infants but may cause long-term, sex-dependent physiological costs. Identifying critical developmental windows can help maximize benefits and minimize risks.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Synthetic glucocorticoids are vital for preterm infant development.
- Animal studies suggest potential long-term, sex-dependent physiological risks associated with excess prenatal glucocorticoid exposure.
- These effects may manifest later in life.
Purpose of the Study:
- To review the potential long-term physiological costs of prenatal synthetic glucocorticoid exposure.
- To identify critical developmental windows of brain sensitivity to glucocorticoids.
- To inform strategies for optimizing prenatal glucocorticoid therapy.
Main Methods:
- Review of animal studies on prenatal glucocorticoid exposure.
- Analysis of corticosteroid receptor system dynamics during late gestation.
- Examination of sex-dependent effects and later-life outcomes.
Main Results:
- Prenatal synthetic glucocorticoid exposure can have long-term physiological consequences.
- These effects appear to be sex-dependent and may emerge later in life.
- Specific developmental windows exist where brain regions are more sensitive to glucocorticoids.
Conclusions:
- Caution is advised for multiple-course prenatal glucocorticoid therapy.
- Identifying critical developmental windows is key to balancing benefits and risks.
- Further research can refine prenatal treatment strategies to mitigate long-term adverse effects.
Abstract:
Glucocorticoids are critical for normal brain development. There is no doubt that prenatal treatment with synthetic glucocorticoid affords great benefit to the preterm infant. However, animal studies, now carried out in many species, indicate that there may be some long-term physiological costs of early exposure to excess glucocorticoid, and that these appear sex-dependent. Further, the effects may not become apparent until later life. Given the dynamics of corticosteroid receptor systems in late gestation, it is likely that there are critical windows of development when specific regions of the brain are more sensitive to the influence of synthetic glucocorticoid. Once such windows have been identified it will be possible to target prenatal treatments, so as to maximize benefit and reduce risk of long-term effects. Notwithstanding, the data reviewed below indicate that caution should be exercised in the use of multiple course glucocorticoid therapy during pregnancy.