Significant mortality and morbidity result from premature birth, due largely to immaturity of the lung, kidney and vascular systems. this proposal requests support for three clinical protocols examining strategies for maturing organ systems in preterm newborns by means of prenatally administered drugs given to the mother at risk for preterm delivery. The prenatal drugs to be tested will be corticosteroids (betamethasone, 12 mg I.M. q 24 hr for a maximum of 2 doses), corticosteroids with thyrotropin releasing hormone (TRH), (400 ug as a 20 minute infusion of 8 hr for a total of 4 doses) or no agent. The neuroendocrine, renal and vascular maturational hormone effects of each of these treatments will be examined. In the study of neuroendocrine effects, fetal catecholamine secretory responses, beta adrenergic receptor density and receptor mediated adenyl cyclase activity will be compared. The renal maturational study will examine effects on glomerular filtration rate and urinary sodium and water excretion. The study of vasoactive substances will evaluate circulating levels of endothelial derived factors, as well as endothelin receptor numbers and function in umbilical cord blood. Contractile behavior of cord vessels also will be evaluated. Subsequent clinical trials will be developed based on the results from the animal experiments, and the infants will be evaluated similarly for organ maturational effects. These studies will be important in defining any potential benefit or harm to various organ systems associated with these agents before they achieve widespread clinical use. If an effect on maturation can be demonstrated, maternal prenatal therapies in threatened preterm deliveries could provide a safe, relatively easy to administer therapy to minimize the significant problems of organ immaturity.
Showing the most recent 10 out of 34 publications
