Oxidative stress after antenatal betamethasone: acute downregulation of glutathione peroxidase-3.
BACKGROUND
Human and experimental data show that antenatal exposure to glucocorticoids (GC) temporarily reduces fetal well-being and impairs the fetal response to hypoxemia.


OBJECTIVE
We tested the hypothesis that antenatal betamethasone provokes transient oxidative stress, which may be triggered directly by the GC or indirectly by metabolic signals such as increased glucose and free fatty acid (FFA) concentrations.


METHODS
Prospective (single center, 18 months) cohort study in newborns <34 weeks gestational age at birth.


METHODS
We studied 105 newborns and measured oxidative damage to lipids [malondialdehyde (MDA)] and proteins (protein carbonyls), as well as glutathione peroxidase-3 (GPx3), an important antioxidant enzyme, in umbilical vein (UV) plasma. In addition, we measured umbilical artery and UV blood gases, and metabolic indices (plasma glucose, FFA and insulin) in UV.


RESULTS
MDA but not protein carbonyl concentrations was inversely related to time elapsed since the first or last betamethasone administration (p=0.006); MDA remained elevated by 69-96% for at least 72 h after the last betamethasone. By contrast, GPx3 concentrations were repressed in newborns who received betamethasone < or =24h before birth. GPx3 and MDA concentrations were correlated (r=-0.38, p<0.001). Labor, GA, sex, size at birth, blood gases or metabolic indices did not explain the effects of betamethasone on MDA and GPx3.


CONCLUSIONS
Antenatal GC elicit a rapid suppression of the GPx3 antioxidant defense system which may contribute to a longer-lasting but also transient rise in lipid oxidative damage.
Verhaeghe
Johan
J
Department of Obstetrics and Gynecology, Health Campus Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium. johan.verhaeghe@uz.kuleuven.be
van Bree
Rita
R
Van Herck
Erik
E
D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000494:pharmacology; D001623:Betamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001774:Blood Chemical Analysis; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005312:Fetal Blood / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood* / Q000139:chemically induced / Q000201:enzymology; D013997:Time Factors; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D001623:Betamethasone; C486484:GPX3 protein, human; D005979:Glutathione Peroxidase