This PERC application is directed toward developing and testing new strategies for achieving fetal maturation when preterm delivery is imminent. The goal is to improve outcome for preterm infants by minimizing postnatal complications related to organ functional immaturity. The emphasis is on global fetal maturation rather than the more traditional focus on lung maturation only. The research projects focus on testing only hormone treatment strategies that could be used clinically. Preterm fetal sheep will be treated by the Core Unit with hormones and combinations of hormones followed by delivery for the study of postnatal adaptation and organ function. Fetal treatments will be by direct fetal administration by ultrasound guided injections to permit us to assess maturational effects on unstressed fetuses. The dosage schedules will emphasize single doses of agents and combinations of agents such as corticosteroid, T3, TRH, and EGF. Effects will be evaluated by organ specific Research Projects during a 5 hr postnatal study period by evaluating lung performance, kidney function, vascular tone regulation and neuroendocrine adaptive responses. tissue will then be used by the Research Projects to measure maturational effects in the lungs, kidneys, vascular and neuroendocrine systems. In the initial 3 years, the clinical studies will evaluate kidney, neuroendocrine and vascular effects resulting from maternal treatments with betamethasone or betamethasone plus TRH in comparison to an untreated comparison group. The maternal treatment protocol is ongoing at Harbor-UCLA and King-Drew Medical Center and will provide subjects for the focused clinical evaluations proposed for the PERC. A clinical trial will be designed in the final years of the proposal that incorporate the concepts developed in the preterm lambs.
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