Maternal glucocorticoids

Barbazanges, A. et al., Maternal glucocorticoid secretion mediates long-term effects of prenatal stress, J. Neurosci., 16, 3943, 1996. 

Owen, D., Andrews, M.H., and Matthews, S.G., Maternal adversity, glucocorticoids and programming of neuroendocrine function and behaviour, Neurosci.Biobehav. Rev., 29, 209, 2005. 

Mulay, S., Varma, D.R. and Solomon, S. (1982). Influence of protein deficiency in rats on hormonal status and cytoplasmic glucocorticoid receptors in maternal and fetal tissues. J. Endocrinol. 95 49-58. 

Liu, D., Diorio, J., Tannenbaum, B., Caldji, C., Francis, D., Freedman, A., et al. (1997) Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science 12277 1659-1662. 

Lung maturation in the fetus is regulated by the fetal secretion of cortisol. Treatment of the mother with large doses of glucocorticoid reduces the incidence of respiratory distress syndrome in infants delivered prematurely. When delivery is anticipated before 34 weeks of gestation, intramuscular betamethasone, 12 mg, followed by an additional dose of 12 mg 18-24 hours later, is commonly used. Betamethasone is chosen because maternal protein binding and placental metabolism of this corticosteroid is less than that of cortisol, allowing increased transfer across the placenta to the fetus. 

In an analysis of 595 preterm infants born at 26-32 weeks gestation during a randomized controlled trial for the prevention of lung disease, glucocorticoids given to women at risk of preterm delivery promoted fetal lung maturation, reduced the incidence of respiratory distress syndrome, and reduced neonatal morbidity and mortality (370). Dexamethasone was given as either two doses of 12 mg 24 hours apart or four doses of 6 mg every 6 hours. Mortality was 9.2% after three or more courses, compared with 4.8% after one or two courses. This association was not explained by other factors (maternal or other common preterm morbidities). 

Subsequently, the addition of protirelin to glucocorticoid therapy was the subject of a meta-analysis (7). In 1134 premature infants the serum TSH concentration was increased for the first 6 hours after the last maternal dose of protirelin, then suppressed for 36 hours before returning to control values (8). The largest controlled trial (in 1368 infants) reported a small delay in development at 12 months (5). However, developmental assessment was by questionnaire, with incomplete ascertainment, and these findings have been questioned (6). In the mothers, there was a three-fold increase in nausea, vomiting, or flushing and a two-fold increase in hypertension compared with glucocorticoid therapy alone. 

Fig. 2. Specificity determined by availability of steroid. A. Even though glucocorticoid ( i>) and progesterone (2) receptors are present, in the absence of plasma progesterone, only glucocorticoid (G) effects are seen. B. Both oestradiol (E) and testosterone (T) may be present in the plasma but E is not available to the hypothalamic cell due to sequestration by neonatal oestradiol binding protein ([ ]). Therefore maternal oestrogen will not affect the cell whereas, in male foetuses, testosterone can be aro-matised to oestradiol within the cell.

Glucocorticoids. Glucocorticoids can be mediators of the action of stress on PG and in turn on other PG-dependent reproductive events. Stress induces an increase in glucocorticoid formation in maternal and embryonal tissues. The glucocorticoids (mainly corticosterone) in turn activate PGF production by both embryonal membranes and the uterus, and promote the PGF-induced labor in different animal species and humans (2,19). 

Teratogenicity Acute adrenal insufficiency in a neonate followed maternal exposure to moderate doses of glucocorticoids during pregnancy [24 ]. 

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