The fetal and neonatal hypothalamic–pituitary–adrenal axis

The hypothalamus, pituitary, and adrenal glands are dynamic endocrine organs during fetal development.1-3 The adrenal glands, in particular, exhibit remarkable transformation in size, morphology, and function during the prenatal and neonatal periods.2 3 It is now recognised that normal development of the hypothalamic–pituitary–adrenal (HPA) axis is essential for: (1) the regulation of intrauterine homeostasis; and (2) the timely differentiation and maturation of vital organ systems including the lungs, liver, and central nervous system necessary for immediate neonatal survival after birth. In addition, acting together with the placenta, the HPA axis might indirectly control the normal timing of parturition in primates.1-3 The liberal use of exogenous antenatal and postnatal corticosteroids during pregnancy and early neonatal life have also raised concerns about potential adverse effects on the HPA axis and subsequent neurodevelopment.4 Thus, an understanding of the physiology and function of the HPA axis in intrauterine and extrauterine life is important for neonatologists. This article aims to provide an overview on the physiology of the glucocorticoid axis and the effects that exogenous corticosteroids have on this system.