Background Experimental studies suggest that melatonin is neuroprotective. Preterm infants are deprived of thenormal intrauterine exposure to maternal melatonin and may benefit from supplementation to adult physiological levels.
Aim To prove that melatonin supplementation to adult concentrations decreases prematurity associated white matter injury assessed by tract based spatial statistics at term equivalent age.
Methods The study was a phase 2 exploratory; multi-centre double-blinded randomised placebo-controlled 2-arm trial, evaluating the neuroprotective effect of melatonin in preterm infants less than 31 weeks gestation. The 2 study drugs, melatonin (active) and normal saline (placebo) were given as an intravenous infusion once a day for 7 days starting by 48 h after birth. The dose of melatonin (0.1 mcg/kg/hr for 2 h) was derived from our previous pharmacokinetic study. Analysis was by intention to treat. Magnetic resonance imaging (MRI) was done at term corrected age. A 5% difference in the fractional anisotropy (FA) on MRI was taken as the primary endpoint.
Results Fifty-eight preterm infants participated in the study; 30 received melatonin and 28 received saline. Four babies died in each group. The 2 groups did not show any differences inthe demographic data or in the short term adverse events. Seventeen infants from the melatonin group and 19 from the placebo group had MR images which were analysed. There was no difference in the FA in the 2 groups.
Conclusions Melatonin supplementation to adult physiological levels during the first week after birth did not alter FA in the preterm white matter at term equivalent age.