Objectives: To investigate the effect of adding melatonin to hypothermia treatment on neurodevelopmental outcomes in asphyctic newborns.
Design: Pilot multicenter, randomized, controlled, double-blind clinical trial. Statistical comparison of results obtained in two intervention arms: hypothermia plus placebo and hypothermia plus melatonin.
Setting: Level 3 neonatal ICU.
Patients: Twenty-five newborns were recruited.
Interventions: The hypothermia plus melatonin patients received a daily dose of IV melatonin, 5 mg per kg body weight, for 3 days. General laboratory variables were measured both at neonatal ICU admission and after intervention. All infants were studied with amplitude-integrated electroencephalography and brain MRI within the first week of life. The neurodevelopmental Bayley III test, the Gross Motor Function Classification System, and the Tardieu scale were applied at the ages of 6 and 18 months.
Measurements and main results: Clinical characteristics, laboratory evaluations, MRI findings, and amplitude-integrated electroencephalography background did not differ between the treatment groups. The newborns in the hypothermia plus melatonin group achieved a significantly higher composite score for the cognitive section of the Bayley III test at 18 months old, with respect to the hypothermia plus placebo group (p = 0.05). There were no differences between the groups according to the Gross Motor Function Classification System and Tardieu motor assessment scales.
Conclusions: The early addition of IV melatonin to asphyctic neonates is feasible and may improve long-term neurodevelopment. To our knowledge, this is the first clinical trial to analyze the administration of IV melatonin as an adjuvant therapy to therapeutic hypothermia.