Still in the dark? Cardiovascular risks of perinatal melatonin

Melatonin has attracted substantial attention as a neuroprotective therapy in the perinatal period, particularly in the context of foetal growth restriction (FGR) and birth asphyxia. Experimental and early clinical studies demonstrate that melatonin can attenuate oxidative stress, inflammation, and apoptosis in the developing brain, and improve structural and functional outcomes after hypoxic–ischaemic injury. On this basis, the perinatal field has intensely interrogated melatonin’s effects on the brain; however, far less is known about its impact on the cardiovascular system during critical windows of development. The cardiovascular system is sensitive to melatonin, given the hormone’s central role in circadian regulation of haemodynamics and its potent antioxidant and anti-inflammatory actions. Chronic exposure during late gestation and early postnatal life therefore has the potential to remodel cardiac growth, mechanics, and pulmonary vascular architecture in ways that may be beneficial or adverse. In this commentary, I highlight the study by Benãldo and colleagues within this emerging landscape, highlighting how short-term postnatal melatonin administration in newborn lambs alters the cardiopulmonary system. These findings, together with antenatal data, warrant a cautious perspective: melatonin remains a leading candidate for perinatal neuroprotection, but its wider physiological effects, particularly on the cardiovascular system, must be rigorously defined before broad clinical adoption.