title: The effects of maternal betamethasone administration on the intrauterine growth-restricted fetus.
abstract: Intrauterine growth restriction (IUGR) is associated with altered fetal cardiovascular function to ensure adequate perfusion of essential organs. IUGR fetuses are at risk of preterm delivery and so are likely to receive antenatal glucocorticoids to promote lung maturation. Because glucocorticoids alter vascular tone, we questioned whether such treatment may induce fetal cardiovascular alterations. Using pregnant sheep carrying twins, we induced IUGR at approximately 0.7 gestation by single umbilical artery ligation in one twin, using the other twin as a control. In each fetus, we monitored carotid blood flow and arterial blood gases. We administered 11.4 mg betamethasone (n = 5) or vehicle (n = 4) to the ewe on d 5 (BM1) and 6 (BM2) postsurgery. On d 7, fetal brains were collected for immunohistochemistry. In control fetuses, carotid blood flow decreased 3.5 h post-BM1 by 24% (P < 0.001), returning to baseline at 5.5 h. In IUGR fetuses, carotid flow decreased 2.5 h post-BM1 by 27% and then increased by 25% over baseline, peaking at 11 h (P < 0.001). Compared to control + saline, we observed a significant increase in oxidative damage (4-hydroxynonenal-positive cells) in the fetal hippocampus and subcallosal area of all treatment groups (IUGR + BM > IUGR + saline = control + BM). There was a significant correlation between carotid blood flow reperfusion after betamethasone and the number of 4-hydroxynonenal-positive cells in the cortex and hippocampus. These data suggest that antenatal betamethasone may induce brain injury in the IUGR fetus but not in the normally grown fetus.
authors.affiliation: Department of Physiology, Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Miller
authors.forename: Mahalia
authors.initials: M
authors.lastname: Chai
authors.forename: Jan
authors.initials: J
authors.lastname: Loose
authors.forename: Margie
authors.initials: M
authors.lastname: Castillo-Meléndez
authors.forename: David W
authors.initials: DW
authors.lastname: Walker
authors.forename: Graham
authors.initials: G
authors.lastname: Jenkin
authors.forename: Euan M
authors.initials: EM
authors.lastname: Wallace
mesh_terms: D000818:Animals; D001623:Betamethasone / Q000008:administration & dosage / Q000633:toxicity*; D001783:Blood Flow Velocity / Q000187:drug effects; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D006863:Hydrogen-Ion Concentration; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D015427:Reperfusion Injury / Q000139:chemically induced; D012756:Sheep
chemical_list: D001623:Betamethasone