The hypothalamic pituitary axis in the fetus and newborn

Glucocorticoid receptor activation in the fetal lung triggers maturation necessary for extra-uterine life. Antenatal treatment with betamethasone and dexamethasone has lowered severity of respiratory distress in very low birth weight infants, and dexamethasone given postnatally has resulted in short-term improvement in chronic lung disease. Recently, however, surfactant therapy has diminished the differential benefit of antenatal glucocorticoid treatment, and it has been difficult to show that postnatal dexamethasone therapy improves survival. Treated infants may have reduced weight gain, adrenal suppression, increased incidence of intestinal perforation and infection, and long-term developmental and metabolic problems. Recent data suggest that the fetal hypothalamic/pituitary/adrenal axis is active early and is precisely structured for an intricate sequence of specifically fetal developmental events, which may be deranged by dexamethasone therapy. We consider data suggesting that persistence of the fetal pattern in some premature infants constitutes adrenal insufficiency, and that therapy at stress replacement doses with less potent glucocorticoids might avoid side effects seen with traditional regimens.