Chronic maternal hypercortisolemia in late gestation alters fetal cardiac function at birth

Abstract

Studies in our laboratory have shown that modest chronic increases in maternal cortisol concentrations over the last 0.20 of gestation impair maternal glucose metabolism and increase the incidence of perinatal stillbirth. Previous studies had found that an increase in maternal cortisol concentrations from 115 to 130 days of gestation in sheep increased both proliferation in fetal cardiomyocytes and apoptosis in the fetal cardiac Purkinje fibers. We hypothesized that the adverse effects of excess cortisol may result in defects in cardiac conduction during labor and delivery. In the present study, we infused cortisol (1 mg·kg·day) into late gestation pregnant ewes and continuously monitored fetal aortic pressure and ECG through labor and delivery. We found that, although the fetuses of cortisol infused ewes had normal late gestation patterns of arterial pressure and heart rate, there was a significant decrease in fetal aortic pressure and heart rate on the day of birth, specifically in the final hour before delivery. Significant changes in the fetal ECG were also apparent on the day of birth, including prolongation of the P wave and P-R interval. We speculate that chronic exposure to glucocorticoids alters cardiac metabolism or ion homeostasis, contributing to cardiac dysfunction, precipitated by active labor and delivery.

Chronic maternal cortisol excess during late gestation leads to metabolic alterations in the newborn heart

“…Future targeted studies, including flux with stable isotopes, would better determine altered metabolism in the newborn cardiac tissue due to chronic maternal cortisol exposure during late gestation. Our results suggest that excess maternal cortisol alters the normal cardiac metabolic maturation that occurs; this perturbation may contribute to the peripartum cardiac arrhythmias and stillbirth observed previously in our laboratory (1,42). Therefore, metabolic alterations in the mother, either from high stress or disease, may lead to metabolic changes in the fetal heart before birth.…”

“…If the chronic maternal infusion of cortisol was maintained from 115 days of gestation until birth, we observed an increased incidence of stillbirth during the peripartum period (22). This incidence of stillbirth was associated with fetal bradycardia and increased incidence of arrhythmias in the heart during the late stages of labor and delivery (1). Transcriptomic analysis of the term fetal heart suggested alterations in lipid and small molecule metabolism due to excess maternal cortisol exposure in a similarly treated cohort of sheep (42).…”

“…Ewes were assigned to one of two groups at gestational day 115: a control group (n ϭ 9) with no treatment and a cortisol group (CORT; n ϭ 6) with infusion of 1 mg•kg Ϫ1 •day Ϫ1 of hydrocortisone sodium succinate in sodium phosphate (Solu-Cortef; Pfizer, New York, NY). This amount of cortisol is enough to roughly double maternal plasma cortisol levels (1). Cortisol infusion and surgery were conducted at gestational day 118 (Ϯ1 day) to insert maternal and fetal catheters, fetal telemetry device, and a flow probe as previously described (1).…”

“…This amount of cortisol is enough to roughly double maternal plasma cortisol levels (1). Cortisol infusion and surgery were conducted at gestational day 118 (Ϯ1 day) to insert maternal and fetal catheters, fetal telemetry device, and a flow probe as previously described (1). Blood pressure, heart rate, ECG, and plasma cortisol concentrations from these ewes and fetuses have been previously reported (1).…”

Glucocorticoids, antenatal corticosteroid therapy and fetal heart maturation

“…2014 ). Chronic maternal hypercortisolaemia also altered the fetal ECG and depressed aortic pressure and heart rate immediately prior to delivery ( Antolic et al . 2018 ).…”