Effects of prenatal betamethasone administration

Description

Between 7--10% of pregnant women are at risk of preterm labour. These women are routinely treated with synthetic glucocorticoids (sGCs), betamethasone (2 x 12 mg i.m., 24 hrs apart) or dexamethasone (4 x 6 mg i.m., 12 hrs apart), to mature the fetal lungs. However, the longitudinal effects of prenatal sGC administration are still unknown in human populations as evaluation of the children and adults exposed in utero is currently ongoing. The current thesis investigates the long term effects of repeated prenatal betamethasone exposure on the development of the hypothalamic-pituitary adrenal (HPA) axis, the N-methyl-D-aspartate (NMDA) receptor system, and anxiety and cognitive behaviours. The guinea pig was used as a model in these studies as its intrauterine brain development and relative neuroendocrine maturity at birth more closely parallel events in human development. In the perinatal guinea pig, the hippocampus was the putative driver of HPA function as the fetal hypothalamus and pituitary remained vulnerable to the negative feedback effects of rising plasma cortisol levels. Although prenatal betamethasone administration markedly suppressed HPA function, it did not acutely affect the expression of corticosteroid or NMDA receptors in the fetal hippocampus. In juvenile life, prenatal betamethasone treatment was associated with significant changes in anxiety behaviour in an open field. However, these young guinea pigs (postnatal day 10) appeared to experience a stress hyporesponsive period as HPA activity was not correlated with behavioural stress. In pre-pubertal and adult life, the same antenatal betamethasone regimen did not grossly affect acquisition ability in the Morris Water Maze, a test of hippocampal-dependent spatial learning, yet there were significant differences in retrieval strategies to solve the spatial task. Our data suggest that the HPA and the NMDA receptor systems are dynamic during the lifespan and that prenatal exposure to glucocorticoids can affect multiple aspects of endocrine and behavioural function.

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