Effect of Melatonin on Neonatal Asphyxia and Hypoxic-Ischemic Encephalopathy: A Systematic Review and Meta-Analysis (2000-2024)

Document Type : systematic review

Authors

1 Neonatal Health Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Department of Cell and Molecular Biology, GO.C, Islamic Azad University, Gorgan, Iran.

Abstract

Background: Neonatal asphyxia and hypoxic-ischemic encephalopathy (HIE) affect 1–3 per 1,000 term births and are associated with severe outcomes, including cerebral palsy, epilepsy, and developmental delays. Melatonin, a hormone with antioxidant, anti-inflammatory, and anti-apoptotic properties, has shown promise in reducing brain injury. This systematic review and meta-analysis aimed to assess the neuroprotective and therapeutic effects of melatonin in neonates with HIE, focusing on mortality, neurodevelopment, and biochemical markers of brain injury, and evaluating its efficacy and safety alone or in combination with therapeutic hypothermia (HT).
Materials and Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase for studies published from January 2000 to December 2024. Search terms included “melatonin,” “neonatal asphyxia,” “hypoxic-ischemic encephalopathy,” “neuroprotection,” and “neonate.” Eligible studies included randomized controlled trials (RCTs), observational, and preclinical studies examining melatonin’s effects in neonatal HIE. Data were extracted on study design, population, dosage, timing, and outcomes. Random-effects models were used for meta-analysis, with heterogeneity assessed by I² and publication bias by funnel plots.
Results: A total of 42 studies were included (12 RCTs, 15 observational, 15 preclinical). Melatonin administered within 24 hours of birth improved neurodevelopmental outcomes and reduced oxidative stress and brain injury. The Bayley Developmental Score improved significantly (SMD = 0.65; 95% CI: 0.32–0.98; p < 0.01), and cerebral palsy risk decreased (RR = 0.72; 95% CI: 0.55–0.94; p = 0.02). No serious adverse events were reported.
Conclusion: Melatonin appears to be a safe and effective adjunct in treating neonatal HIE, improving outcomes and minimizing injury. Further large-scale trials are warranted to confirm efficacy and guide clinical use.

Keywords

References

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Journal of Pediatric Perspectives
Volume 13, Issue 9
September 2025
Pages 19686-19691

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