Melatonin use for neuroprotection in perinatal asphyxia: a randomized controlled pilot study

Objective: Melatonin has been shown to be neuroprotective in animal models. The objective of this study is to examine the effect of melatonin on clinical, biochemical, neurophysiological and radiological outcomes of neonates with hypoxic–ischemic encephalopathy (HIE). Study Design: We conducted a prospective trial on 45 newborns, 30 with HIE and 15 healthy controls. HIE infants were randomized into: hypothermia group ( N =15; received 72-h whole-body cooling) and melatonin/hypothermia group ( N =15; received hypothermia and five daily enteral doses of melatonin 10 mg kg −1 ). Serum melatonin, plasma superoxide dismutase (SOD) and serum nitric oxide (NO) were measured at enrollment for all infants ( N =45) and at 5 days for the HIE groups ( N =30). In addition to electroencephalography (EEG) at enrollment, all surviving HIE infants were studied with brain magnetic resonance imaging (MRI) and repeated EEG at 2 weeks of life. Neurologic evaluations and Denver Developmental Screening Test II were performed at 6 months. Result: Compared with healthy neonates, the two HIE groups had increased melatonin, SOD and NO. At enrollment, the two HIE groups did not differ in clinical, laboratory or EEG findings. At 5 days, the melatonin/hypothermia group had greater increase in melatonin ( P