Effects of antenatal glucocorticoids on the developing brain

Abstract

Glucocorticoids (GCs) regulate distinct physiological processes in the developing fetus, in particular accelerating organ maturation that enables the fetus to survive outside the womb. In preterm birth, the developing fetus does not receive sufficient exposure to endogenous GCs in utero for proper organ development predisposing the neonate to complications including intraventricular hemorrhage, respiratory distress syndrome (RDS) and necrotizing enterocolitis (NEC). Synthetic GCs (sGCs) have proven useful in the prevention of these complications since they are able to promote the rapid maturation of underdeveloped organs present in the fetus. While these drugs have proven to be clinically effective in the prevention of IVH, RDS and NEC, they may also trigger adverse developmental side effects. This review will examine the current clinical use of antenatal sGC therapy in preterm birth, their placental metabolism, and their effects on the developing brain.

Challenges for intraventricular hemorrhage research and emerging therapeutic targets

“…Prenatal administration of glucocorticoids reduces the severity and frequency of IVH, as these can stabilize the germinal matrix vasculature 41 . However, glucocorticoids can have side effects by affecting brain development 42 . There is a growing understanding of the developmental regulation of brain angiogenesis and barriergenesis 43 .…”

The brain development of infants with intrauterine growth restriction: role of glucocorticoids

“…However, excessive exposure to GCs during pregnancy interferes with the normal development of the nervous system in the fetus [23]. Studies have shown that whether or not the offspring is exposed to a high GC environment due to stress during maternal gestation, or because treatment requires the injection of GCs during maternal gestation, this situation will lead to an increased risk of offspring behavioral and emotional disorders [24], [25], [26]. Studies have confirmed that individuals with early chronic stress will secrete more corticotropin releasing hormone (CRH) in the hippocampus, resulting in high levels of CRH causing abnormal processes such as hippocampal spines branching and synapse formation leading to hippocampal brain function defects [27].…”

The Hypothalamic-Pituitary-Adrenal Axis and the Fetus

“…A more detailed description of GC actions on fetal development is beyond the scope of this discussion but has been the subject of other thoughtful reviews [6, 17, 18]. …”