Chronic maternal hypercortisolemia models stress-induced adverse birth outcome and altered cardiac function in newborn lambs

Maternal stress in pregnancy is thought to be a contributing factor in adverse pregnancy outcomes, including stillbirth and prematurity. Previous studies in our laboratory have shown that chronic elevation in maternal cortisol concentration in ewes (by maternal infusion of 1 mg/kg/day) during the late gestation increased the incidence of stillbirth and altered fetal heart rate and blood pressure at birth. We designed the current study to test the effect of chronically elevated maternal cortisol on fetal cardiac adaption from in utero life to ex utero life. The combined risk of stillbirth or prematurity was significantly greater in the pregnancies with maternal hypercortisolemia; in this cohort, 40% of the lambs of cortisol-infused ewes died in utero or at birth compared with 25% of lambs of control ewes, and 24% of lambs of cortisol-infused ewes were born preterm, whereas no lamb was born preterm in the control group. Compared with control lambs, the lambs of cortisol-infused ewes born at full term exhibited a significant increase in mean aortic pressure just before birth and a significant decrease in mean aortic pressure that was evident during the first 9 h after birth. The QT interval was decreased before birth and increased immediately after birth in the newborns of cortisol-treated ewes compared with control lambs. These findings suggest that excess in utero corticosteroid exposure adversely affects fetal cardiac adaptation to extrauterine life and that chronic maternal stress or hypersecretion of corticosteroids may contribute to adverse obstetric outcomes.