The impact of melatonin on intrauterine growth restriction

OBJECTIVES: The aim of this study is to review the current state of knowledge on the role of melatonin in the pathophysiology and treatment of intrauterine growth restriction (IUGR) based on recent clinical and experimental studies. MATERIAL AND METHODS: A systematic review of scientific literature published between 2012-2025 in PubMed, Cochrane Library and Web of Science databases was conducted. Studies on melatonin mechanisms of action, their levels in IUGR, and results of experimental and clinical studies were analyzed. RESULTS: Melatonin is synthesized not only by the pineal gland but also by the placenta, where it plays a crucial role as an antioxidant and modulator of inflammatory processes. Women with IUGR showed significantly lower melatonin levels in umbilical cord blood. The MT2 melatonin receptor regulates placental angiogenesis through the STAT3/VEGFR2/PI3K/AKT pathway. Experimental studies demonstrated that melatonin improves fetal oxygenation, reduces oxidative stress, and protects the brain and heart from damage. CONCLUSIONS: Melatonin shows promising neuroprotective and cardioprotective properties in IUGR fetuses. The PROTECT Me trial, which completed recruitment in 2025, will provide crucial data on melatonin's clinical efficacy. Until then, melatonin use in IUGR should be limited to controlled clinical trials.