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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 …
Contributors NS and GCS both wrote the editorial.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests GCS has received research support from Roche Diagnostics, GSK, Illumina and Sera Prognostics (fetal growth restriction, pre-eclampsia and preterm birth). GCS’s department has received payment from Roche for a talk given by GCS (fetal growth restriction). GCS has been a paid consultant to GSK (preterm birth) and is a member of a Data Monitoring Committee for GSK trials of RSV vaccination in pregnancy. GCS is one of three named inventors on a patent application (PCT/GB2020/053312) filed by Cambridge Enterprise for novel predictive test for fetal growth disorder.
Provenance and peer review Commissioned; externally peer reviewed.