Exposure to high levels of the body's primary stress hormone - cortisol - in preterm fetuses can disrupt normal heart development, potentially increasing the risk of cardiovascular disease in later life.
That's the finding from a new study led by the University of South Australia (UniSA), showing that elevated cortisol levels in preterm lambs significantly alters molecules that control proper heart development.
The findings, published in Experimental Physiology, offer vital insights into how early life stress may influence heart health in later life and could help inform how corticosteroids are used in pregnancy.
Lead author Professor Janna Morrison, Head of the Early Origins of Adult Health Research Group at UniSA, says preterm birth is a leading cause of neonatal mortality and is associated with an increased risk of cardiovascular disease in adulthood.
"Our research sought to understand how cortisol - whether naturally elevated or via synthetic versions of cortisol to promote lung development - affects the developing cardiovascular system in preterm fetuses," Prof Morrison says.
"We know that cortisol rises naturally in late pregnancy and plays a critical role in maturing fetal organs in preparation for birth, but we did not know how crucial molecules involved in heart development were impacted by cortisol in the preterm period.
"When cortisol levels rise too early - either due to maternal stress or medical intervention - it may accelerate heart development in ways that aren't entirely beneficial, increasing the risk of cardiovascular disease many years later."
Pregnancy complications such as gestational diabetes, preeclampsia, obesity and placental insufficiency can lead to a premature increase in cortisol concentrations earlier in gestation that impacts the developing fetus.
To mimic the cortisol levels that are normal in late gestation, researchers administered cortisol to preterm sheep fetuses over seven days and then studied the impact on signalling molecules in the heart.
The results showed significant changes in the heart's molecular structure.
"We found that elevated levels of cortisol during early heart development disrupt key cardiac pathways by suppressing glucocorticoid receptors and altering molecular signals involved in growth, energy metabolism, and cardio-protection," says co-author UniSA researcher Dr Reza Amanollahi.
"These disruptions may leave the premature heart more susceptible to cardiovascular instability. Given the close similarities between sheep and human heart development, our findings raise important concerns that prenatal stress could also compromise heart health in preterm human infants."
Co-lead on the project, Dr Mitchell Lock, says that while antenatal corticosteroids remain critical for improving survival, our research highlights the importance of closely monitoring their use in pregnancy.
"We hope these findings will also help refine the clinical care of preterm babies to support better long-term outcomes."
"Elevated cortisol concentration in preterm sheep fetuses impacts heart development" was authored by researchers from the University of South Australia, the University of Queensland and Oregon Health & Science University. DOI: 10.1113/EP092506
A video discussing the findings is available here.
Notes for editors
Cardiovascular disease is the number one cause of death worldwide and several risk factors such as age, pre-existing conditions and lifestyle contribute to its disease burden. This study explores the causes from a different angle: the influence of stress hormones when the heart is developing in the fetus.
