Antenatal Steroids and Antioxidant Enzyme Activity in Preterm Infants: Influence of Gender and Timing

Abstract

Antenatal steroids have improved the survival of preterm infants; however, the mechanism of action is not fully understood. We aimed to establish an association between antenatal steroids and antioxidant activity and postnatal oxidative stress. In a prospective cohort study, extremely preterm neonates receiving antenatal steroids (CORT) or not (NOCORT) were enrolled. An association between antenatal steroids and activities of antioxidant enzymes and glutathione cycle enzymes in cord blood was found. In addition, reduced oxidative stress (GSH/GSSG ratio, CORT vs. NOCORT, 35.68 + or - 12.20 vs. 28.38 + or - 9.92; p < 0.01) and, decreased oxidation of proteins (ortho-tyrosine/phenylalanine ratio, CORT vs. NOCORT, 8.66 + or - 2.45 vs. 12.55 + or - 4.41; p < 0.01) and DNA (8oxodG/2dG ratio, CORT vs. NOCORT, 6.73 + or - 2.18 vs. 9.53 + or - 3.83; p < 0.01) also was found. Antenatal steroids were associated with reduced oxygen supplementation, mechanical ventilation, and conditions such as bronchopulmonary dysplasia, intra-periventricular hemorrhage, or retinopathy of prematurity. The maximal effectiveness was when steroids were administered 2-4 days before delivery. Female preterm infants had less oxidative stress and increased antioxidant activity and better clinical outcomes than did male infants, independent of receiving or not antenatal steroids. Antenatal steroids are accompanied by a reduction in postnatal oxidative-stress-derived conditions and increased antioxidant enzyme activity. Both these effects seem to be influenced by specific timing and female gender.

Prenatal and postnatal risk factors for developing bronchopulmonary dysplasia

“…Male gender increases the risk for death in low birth weight populations (17). Increased incidence of BPD in males can be partly explained by higher oxidative stress and lower antioxidant activity in male preterms (18). Previously published data show that low gestational age (the stage of pulmonary development) is one of the crucial risk factors for BPD development.…”

Sex-dependent changes in the pulmonary vasoconstriction potential of newborn rats following short-term oxygen exposure

“…Prenatal exposure to corticosteroids has been shown to accelerate maturation of the lung antioxidant enzymes in rodents (31) and humans (32). Glutathione and other pulmonary antioxidant enzymes markedly increase during fetal gestation, likely as a result of the mitochondrial and microsomal-generated ROS generation prenatally (33).…”

“…In humans, sex differences in the tolerance to oxidative stress also appear to be present because following exposure to antenatal steroids, the antioxidant capacity is greater in female, as compared with male, preterm infants (13).…”

Sex-Specific Effects of Prenatal Glucocorticoids on Placental Development

“…Glucocorticoids have previously been shown to influence fetal reactive oxygen species production and antioxidant defences [100][101]. These pathways are involved in preparing the fetus for the increase in free oxygen radical generation which is experienced during the fetal to neonatal transition [102].…”