Antenatal Glucocorticoids and Uteroplacental Vasculature

Cornell University Ithaca, Ithaca NY

Investigators

Abstract

DESCRIPTION (provided by applicant): Antenatal glucocorticoid administration is recommended by the NIH for women at risk of premature labor to accelerate fetal lung maturation and improve survivability of the newborn. However, multiple courses of antenatal dexamethasone administration in rats and sheep reduce fetal and placental weights, induce short-term maternal and fetal hypertension, as well as result in long-term adult hypertension in the offspring. The long-term objective of this research proposal is to investigate placental vascular alterations induced by administration of multiple courses of antenatal dexamethasone. The general hypotheses are that antenatal dexamethasone reduces uterine and umbilical blood flow by increasing vascular resistance and that this is brought on by increased mRNA expression of and vascular responses to endothelin. The specific aims are to determine alterations in uterine and umbilical blood flow and vascular resistance and relate them to in vitro vascular changes. I will investigate ovine uteroplacental vascular regulation after exposure to three 48-h courses of clinically relevant doses of maternally-administered dexamethasone at 0.7, 0.75, and 0.8 of gestation. The research within this proposal relates to effects of maternal stress in pregnancy. Data obtained will provide physiologic evidence to better understand the risk:benefit analysis of a clinical therapeutic regimen that has recently been recommended by the NIH, but which carries the risk of non-pulmonary fetal effects.