Date of Award


Degree Type


Degree Name

Master of Science


Physiology and Pharmacology


Dr. Bryan Richardson

Second Advisor

Dr. Victor Han

Third Advisor

Dr. Jane Rylett


While the benefits of antenatal glucocorticoids are well known for infants born preterm with enhanced lung maturation, there is increasing evidence of adverse effects on brain development, which may relate to altered metabolic activity. The primary aim of the present study was to determine the effects of a clinically-administered single-course of antenatal glucocorticoids on fetal cerebral blood flow, substrate metabolism and protein synthesis in the chronically catheterized preterm ovine fetus. Cerebral blood flow, as measured using fluorescent microspheres, was reduced by ~30% from baseline values when measured four hours after the second glucocorticoid injection and correspondingly showed a decrease in cerebral O2 delivery of ~20% (p = 0.06). In addition, the relative uptake of glucose to that of oxygen was increased at this time, indicating that an excess of glucose was being taken up by the brain exceeding the requirements for oxidative metabolism, with the likelihood that a fraction of the excess glucose was being utilized anaerobically. These metabolic changes brought on by antenatal glucocorticoids are not likely to be harmful to the pregnant patient with only threatened preterm delivery. However, a pregnancy already complicated with placental insufficiency or fetal growth restriction may limit the fetus’s ability to adapt to these additional metabolic insults, potentially contributing to developmental shortcomings, including that of the brain. Furthermore, fetal cerebral protein synthesis as studied using [13C]-leucine tracer technology in the cortex and cerebellum demonstrated high protein 111 fractional synthetic rates (FSR), indicating high rates of protein synthesis and degradation. However, we found no evidence that these FSR’s were altered by betamethasone as used clinically and thereby does not account for the reported structural alterations in the brain following a single-course of antenatal glucocorticoids. Likewise, we found no effect of maternally administered glucocorticoids on fetal leucine disposal rate values as a measure of the rate at which leucine is utilized for protein synthesis and oxidation by the whole fetal organism, as well as loss across the placenta.



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