AbstractBackgroundPostnatal corticosteroids are used in the critical care of preterm infants for the prevention and treatment of bronchopulmonary dysplasia. We aimed to investigate the effects of early postnatal dexamethasone therapy and dose on cardiac maturation and morphology in preterm lambs.MethodsLambs were delivered prematurely at ~128 days of gestational age and managed postnatally according to best clinical practice. Preterm lambs were administered dexamethasone daily at either a low‐dose (n = 9) or a high‐dose (n = 7), or were naïve to steroid treatment and administered saline (n = 9), over a 7‐day time‐course. Hearts were studied at postnatal Day 7 for gene expression and assessment of myocardial structure.ResultsHigh‐dose dexamethasone treatment in the early postnatal period led to marked differences in cardiac gene expression, altered cardiomyocyte maturation and reduced cardiomyocyte endowment in the right ventricle, as well as increased inflammatory infiltrates into the left ventricle. Low‐dose exposure had minimal effects on the preterm heart.ConclusionNeonatal dexamethasone treatment led to adverse effects in the preterm heart in a dose‐dependent manner within the first week of life. The observed cardiac changes associated with high‐dose postnatal dexamethasone treatment may influence postnatal growth and remodeling of the preterm heart and subsequent long‐term cardiac function.