Table 3.
Randomised clinical trials using melatonin for neonatal encephalopathy in infants and relevant clinical outcomes.
| Study | Population | Intervention | Comparison | Clinical Outcomes |
|---|---|---|---|---|
| Fulia et al. (2001) [154] | Single centre, Italy Diagnosis of perinatal asphyxia within 6 h, criteria not listed |
N = 10 Melatonin alone Dose: 80 mg (10 mg 2 hourly) Route: Enteral Excipient: 1:90 ethanol:0.9% saline |
N = 10 Supportive care, no HT |
Mortality: RR 0.14 (95% CI 0.01–2.45) Imaging: Not reported Neurodevelopment: Not reported |
| Aly et al. (2015) [155] | Single centre, Egypt HIE: Inborn, Apgar score ≤ 3 at 5 min, BE < 12, moderate-severe NE |
N = 15 HT + Melatonin Dose: 10 mg/kg daily for 5 days Route: Enteral Excipient: Distilled water |
N = 15 HT Manual cooling with ice packs |
Mortality: RR 0.25 (95% CI 0.03, 1.98) EEG: melatonin had fewer seizures (3/14 in HT + melatonin vs. 7/11 in HT) Imaging: MRI–less white matter abnormalities (0/14 in HT + melatonin vs. 4/11 in HT) Neurodevelopment: Improved survival without abnormalities at 6 months (10/14 in HT + melatonin vs. 3/11 in HT) |
| Ahmad et al. (2018) [156] | Single centre, Pakistan Any HIE *: >34 weeks gestation, based on clinical features alone * includes 12.5% mild cases |
N = 40 Melatonin alone Dose: 10mg single dose Route: Enteral Excipient: Not reported |
N = 40 Supportive care, no HT |
Mortality: RR 0.35 (95% CI 0.14, 0.90) all cases Imaging: Not reported Neurodevelopment: Not reported |
| El Farargy et al. (2019) [157] | Single centre, Egypt HIE: Apgar score < 5 at 5 min, Cord pH < 7 and/or BE ≥ 12 mmol/L), and moderate NE |
N = 30 Melatonin + Magnesium Sulphate Dose: 10 mg/kg daily for 5 days Route: Enteral Excipient: Not reported |
N = 30 Melatonin alone |
Mortality: Not reported Imaging: Not reported Neurodevelopment: Not reported |
| Jerez-Calero et al. (2020) [164] | Two centres, Spain HIE: ≥36 weeks gestation, severe perinatal asphyxia (Apgar < 5 at 5 min, Cord pH < 7 and/or BE ≤ −16, Moderate-severe NE (Sarnat score ≥ 6) |
N = 12 HT + Melatonin Dose: 5 mg/kg within 6 h of birth, over 2 h, daily for 3 days Route: IV Excipient: propylene glycol + macrogol |
N = 13 HT, servo-controlled, Tecotherm cooling device |
Mortality: RR 1.0 (95% CI 0.07, 14.21) aEEG: No difference in background activity or seizure burden Imaging: No difference in MRI outcomes Neurodevelopment: Improved cognitive composite score (p = 0.05) at 18 months on Bayley III Test, no other significant differences |