Effects of antenatal glucocorticoids on cerebral substrate metabolism in the preterm ovine fetus.
OBJECTIVE
Although the benefits of antenatal glucocorticoids are well known for infants who are born preterm, there is increasing evidence of adverse effects on brain development, which may relate to altered metabolic activity. We have determined the effect of maternal glucocorticoid administration at doses that are used clinically on cerebral substrate metabolism in the preterm ovine fetus.


METHODS
Chronically instrumented pregnant sheep at 0.85 gestation received 2 intramuscular injections of betamethasone at 170 microg/kg maternal weight (n = 13) or saline (n = 10) 24 hours apart together with a continuous infusion of L-[1-(13)C] leucine to the fetus. Fetal cerebral substrate arteriovenous differences (O2, glucose, leucine, leucine enrichment) and blood flow (fluorescent microspheres) were measured at baseline, 24 hours after the first betamethasone/saline injection (late beta/saline 1), and 4 hours after the second betamethasone/saline injection (early beta/saline 2) to obtain substrate deliveries and fractional extractions.


RESULTS
Fetal pH, blood gases, and metabolites were little changed in either group over the course of the study, except for glucose values in the betamethasone animals, which increased 1.4- and 1.9-fold, measured late beta 1 and early beta 2, respectively (both P < .01). Cerebral blood flow, although little changed in the control group or at late beta 1, was decreased at early beta 2 by approximately 30% (P < .05). As such, early beta 2 animals showed a decrease in cerebral O2 delivery of approximately 20% (P = .06) and conversely an increase in cerebral glucose delivery of 1.4- and 1.3-fold at late beta 1 (P < .05) and early beta 2 (P = .08), respectively. Fractional extraction values for these substrates were not changed significantly, which resulted in corresponding decreases in estimated O2 uptake and increases in estimated glucose uptake, such that the glucose/oxygen quotient (as an index of glucose oxidative metabolism) measured 1.6 at early beta 2, which was considerably greater than baseline values at 1.1 (P < .05). Fractional extraction values for leucine and leucine enrichment averaged 2%-3%; although somewhat higher in the betamethasone animals, none of the between or within group differences were significant.


CONCLUSIONS
Fetal cerebral metabolism in the preterm ovine fetus is altered by antenatal glucocorticoid administration, which is comparable with that used in human pregnancy, and includes an acute decrease in cerebral blood flow and a probable increase in anaerobic glucose metabolism. Although likely of short duration in conjunction with peak glucocorticoid levels, these metabolic effects may place the developing brain at added risk for superimposed hypoxic injury.
McCallum
Jeremy
J
Department of Obstetrics and Gynecology, Faculty of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
Smith
Norman
N
Schwab
Matthias
M
Coksaygan
Turhan
T
Reinhardt
Bettina
B
Nathanielsz
Peter
P
Richardson
Bryan S
BS
D000818:Animals; D001623:Betamethasone / Q000633:toxicity*; D001921:Brain / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D005865:Gestational Age; D005938:Glucocorticoids / Q000633:toxicity*; D007273:Injections, Intramuscular; D007930:Leucine / Q000097:blood; D018811:Maternal Exposure; D010101:Oxygen Consumption / Q000502:physiology; D011247:Pregnancy; D011897:Random Allocation; D012016:Reference Values; D034561:Sheep, Domestic
D005938:Glucocorticoids; D001623:Betamethasone; D007930:Leucine