Abstract / Summary
Abstract Antenatal corticosteroids (ACS) are widely administered to women at risk of preterm birth, yet their independent contribution to long-term cardiovascular risk remains unresolved. Using a term-born ovine model that separates ACS exposure from prematurity, we mapped cardiovascular responses from fetal life to adolescence following a clinically relevant dexamethasone regimen. ACS triggered acute fetal vasoconstriction and vascular remodelling, followed by the emergence of systolic and diastolic cardiac dysfunction by term. These effects persisted into adolescence, manifesting as impaired cardiac contractile function, restrictive ventricular filling and increased myocardial fibrosis, despite preserved resting blood pressure. By isolating the effects of ACS from those of preterm birth, here we show that fetal glucocorticoid exposure is a direct driver of adverse cardiovascular programming. These findings reveal a previously unresolved mechanism linking a global perinatal intervention to long-term cardiac remodelling, thereby having important implications for understanding cardiovascular risk in individuals exposed to ACS before birth.