SynthesisAnnals of clinical and translational neurology2022
Efficacy of melatonin in term neonatal models of perinatal hypoxia-ischaemia.
Synthesis in Annals of clinical and translational neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Hypoxic-Ischemic Encephalopathy: Pathogenesis and Promising Therapies.Molecular neurobiology · 2025Pooled it
- Melatonin in Pregnancy-Related Disorders: A Review of Protective Mechanisms and Therapeutic Potential.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Review
- Melatonin treatment alters cardiopulmonary structure, function, and acute hypoxic response in the newborn lamb.Pediatric research · 2026Article
- What are the implications of sex differences in cell death for treatment after neonatal hypoxia-ischemia, if any?Pediatric research · 2025Article
- Article
- Melatonin: a positive influencer of inflammation in neonatal encephalopathy.Pediatric research · 2025Article
- Neuroprotection for neonatal hypoxic-ischemic encephalopathy: A review of novel therapies evaluated in clinical studies.Developmental medicine and child neurology · 2025Review
- Therapeutic hypothermia for neonates: a bibliometric analysis and visualization research.Frontiers in neurology · 2025Article
- Neuroprotective Effect of Melatonin in a Neonatal Hypoxia-Ischemia Rat Model Is Regulated by the AMPK/mTOR Pathway.Journal of the American Heart Association · 2024Article
- Neuroprotective effects of maternal melatonin administration in early-onset placental insufficiency and fetal growth restriction.Pediatric research · 2024Article
- Melatonin as a Therapy for Preterm Brain Injury: What Is the Evidence?Antioxidants (Basel, Switzerland) · 2023Review
- [Research research on the use of melatonin in combination with therapeutic hypothermia for the treatment of neonatal hypoxic-ischemic encephalopathy].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2023Review
- Melatonin: A Potential Candidate for the Treatment of Experimental and Clinical Perinatal Asphyxia.Molecules (Basel, Switzerland) · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveNeonatal encephalopathy (NE) is an important cause of mortality and disability worldwide. Therapeutic hypothermia (HT) is an effective therapy, however not all babies benefit. Novel agents are urgently needed to improve outcomes. Melatonin in preclinical studies has promising neuroprotective properties. This meta-analysis assessed the efficacy of melatonin in term animal models of NE on cerebral infarct size, neurobehavioural tests and cell death.
methodsA literature search was carried out using Embase, MEDLINE and Web of Science (31 May 2021). We identified 14 studies and performed a meta-analysis with a random effects model using standardised mean difference (SMD) as the effect size. The risk of bias was assessed using the Systematic Review Centre for Laboratory animal Experimentation tool and publication bias was assessed with funnel plots, and adjusted using trim and fill analysis. Subgroup and meta-regression analyses were performed to assess the effects of study design variables.
resultsWe observed significant reduction in brain infarct size (SMD -2.05, 95% CI [-2.93, -1.16]), improved neurobehavioural outcomes (SMD -0.86, 95% CI [-1.23, -0.53]) and reduction in cell death (SMD -0.60, 95% CI [-1.06, -0.14]) favouring treatment with melatonin. Neuroprotection was evident as a single therapy and combined with HT. Subgroup analysis showed greater efficacy with melatonin given before or immediately after injury and with ethanol excipients. The overall effect size remained robust even after adjustment for publication bias.
interpretationThese studies demonstrate a significant neuroprotective efficacy of melatonin in term neonatal models of hypoxia-ischaemia, and suggest melatonin is a strong candidate for translation to clinical trials in babies with moderate-severe NE.
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Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.