• neonatology
• neuropathology
• child development

The human fetal hypothalamic–pituitary axis (HPA) becomes activated as pregnancy advances towards term. This critical developmental trigger occurs in most mammalian species and results in a fetal adrenal glucocorticoid (GC) surge essential for lung maturation.1 In addition, HPA activation also contributes to parturition and the maturation of other fetal organs. Precocious activation of GC receptors (GRs) can be induced by endogenous cortisol release in response to fetal exposure to an adverse intrauterine environment, or when synthetic GCs are administered to the mother during pregnancy (antenatal maternal GC, AMGC).

There is no doubt that AMGC therapy significantly reduces neonatal morbidity and mortality in preterm deliveries. First described in sheep and then trialled in human pregnancies, GCs primarily act to increase surfactant production in fetal lungs thereby reducing the likelihood of several life-threatening conditions at birth. Indeed, repeated meta-analyses support this conclusion and have shown that AMGC administration prior to anticipated preterm delivery is associated with a reduction in perinatal death, neonatal death, acute respiratory distress syndrome (RDS) and probably intraventricular haemorrhage. For AMGC therapy, the number needed to treat (NNT) to prevent neonatal death increases with gestational age at the time of delivery, likely reflecting the natural increase in fetal adrenal GC production and the reduced absolute risk of severe complications approaching term. One large-scale study showed that at 23 and 24 weeks’ gestation, the NNT is 6 women to prevent one death before discharge, where it increased to 798 women at 34 weeks’ gestation.2

Synthetic corticosteroids are known to be potent activators of GRs when compared with the lower affinity binding that occurs with endogenous cortisol, known to bind more strongly to mineralocorticoid receptors. AMGC therapy …