Current dilemmas in perinatal corticosteroid therapy: insight into adrenocortical function in newborns

Corticosteroids are powerful and often prescribed medicaments although the exact mechanism of their action and potential long-term adverse effects are not fully known. They have been widely used in perinatal medicine since it was shown, more than 30 years ago, that they induce fetal lung maturation and reduce the incidence of respiratory distress syndrome in premature infants. Post-natally administered corticosteroids also exert some short-term beneficial effects on neonatal ventilation, facilitating extubation, and preventing to some extent the occurrence of chronic lung disease. However, recent reports have raised concerns that corticosteroid therapy in the perinatal period compromises growth and may cause permanent neurodevelopmental impairment in children. The differences in outcome regarding the gestational period and postnatal age, the choice of corticosteroid, the doses and duration of therapy are reported. Fetal adrenocortical development is affected by complex hormonal maternal, placental and fetal interactions. Low levels of fetal cortisol promote growth and proliferation of fetal tissues until late in gestation, when fetal hypothalamic- pituitary-adrenal axis is stimulated. Elevated corticosteroid levels in the fetus, especially during the critical periods of organ development, reduce the rate of cell hyperplasia and may cause reduction in organ size and whole body weight. Sustained increases in fetal cortisol may adversely program the fetal hypothalamic-pituitary-adrenal axis and result in the development of some diseases in adult life like hypertension, type II diabetes, depression, and renal diseases. In premature and critically ill newborns, developmental immaturity and the effects of illness may result in relative adrenal insufficiency with cardiovascular instability and shock. Low-dose corticosteroid treatment may improve the outcome in such patients. Further studies are needed to define justifiable indications for antenatal and postnatal corticosteroid therapy as well as the right treatment protocols to ensure that the benefits outweigh the overall risks of such treatment.