Efficacy of melatonin in term neonatal models of perinatal hypoxia-ischaemia

source extracted confidence: high 2026-04-09
#animals #brain-diseases #humans #hypothermia-induced #hypoxia

Efficacy of melatonin in term neonatal models of perinatal hypoxia-ischaemia

Pang et al., 2022 | Ann Clin Transl Neurol | Meta Analysis

Citation

Pang Raymand, Han Hyun Jee, ... Robertson Nicola J. Efficacy of melatonin in term neonatal models of perinatal hypoxia-ischaemia. Ann Clin Transl Neurol. 2022-Jun;9(6):795-809. doi:10.1002/acn3.51559

Abstract

OBJECTIVE: Neonatal 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. METHODS: A 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. RESULTS: We 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. INTERPRETATION: These 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.

Key Findings

We 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 ev

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size 14
Age Range See abstract
Condition See abstract

MeSH Terms

  • Animals
  • Brain Diseases
  • Humans
  • Hypothermia, Induced
  • Hypoxia
  • Infant, Newborn
  • Infant, Newborn, Diseases
  • Ischemia
  • Melatonin

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't
  • Vertical: melatonin

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09