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).


METHODS
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.


RESULTS
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<0.001) and decline in NO (P<0.001), but less decline in SOD (P=0.004). The melatonin/hypothermia group had fewer seizures on follow-up EEG and less white matter abnormalities on MRI. At 6 months, the melatonin/hypothermia group had improved survival without neurological or developmental abnormalities (P<0.001).


CONCLUSIONS
Early administration of melatonin to asphyxiated term neonates is feasible and may ameliorate brain injury.
Department of Newborn Services, George Washington University and Children's National Medical Center, Washington, DC, USA.
H
H
Aly
Department of Neonatology, Tanta University, Tanta, Egypt.
H
H
Elmahdy
Department of Newborn Services, George Washington University and Children's National Medical Center, Washington, DC, USA.
M
M
El-Dib
Department of Neonatology, Tanta University, Tanta, Egypt.
M
M
Rowisha
Department of Neonatology, Tanta University, Tanta, Egypt.
M
M
Awny
Department of Neurology, Tanta University, Tanta, Egypt.
T
T
El-Gohary
Department of Biochemistry, Tanta University, Tanta, Egypt.
M
M
Elbatch
Department of Radiology, Tanta University, Tanta, Egypt.
M
M
Hamisa
Department of Neonatology, Tanta University, Tanta, Egypt.
A-R
AR
El-Mashad
D001238:Asphyxia Neonatorum / Q000188:drug therapy*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000175:diagnosis* / Q000401:mortality; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D008550:Melatonin / Q000097:blood / Q000627:therapeutic use*; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000097:blood; D010865:Pilot Projects; D011446:Prospective Studies; D013482:Superoxide Dismutase / Q000097:blood; D047929:Term Birth
D018696:Neuroprotective Agents; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D008550:Melatonin