The effects of intrauterine growth restriction and antenatal glucocorticoids on ovine fetal lung development

Abstract

Intrauterine growth restriction (IUGR) is associated with high rates of neonatal morbidity. IUGR babies are often born preterm and are, therefore, exposed to antenatal glucocorticoids. Antenatal glucocorticoids significantly improve overall survival rates of preterm infants, but there is a paucity of information about their effects on IUGR Infants. We induced IUGR in sheep by single umbilical artery ligation (SUAL), or sham in control fetuses. To half the ewes, we administered betamethasone (BM) on d 5 (BM1) and 6 (BM2) following surgery, and collected fetal lung tissue on d 7. SUAL alone was associated with higher circulating fetal cortisol levels (2.8 ± 0.4 vs. 1.0 ± 0.4, P = 0.001) as compared with controls but not with changes in lung morphology or surfactant protein (SP) gene expression. BM was associated with a significant reduction in lung tissue density (P = 0.048). There were no significant differences between groups in lung DNA concentration or septal crest density. SP-A, SP-B, and SP-C gene expressions were significantly increased in control and SUAL fetuses that were administered BM. These results show that in SUAL fetuses, maternal BM is associated with acceleration of fetal lung structure, as occurs in normally grown fetuses, and that BM induces SP production, an effect not observed in SUAL-induced IUGR fetuses alone.