Melatonin for Neuroprotection Following Perinatal Asphyxia

This is a prospective study on 30 neonates with moderate to moderately to severe hypoxic ischemic encephalopathy (HIE) . HIE infants are randomized into two groups: Whole body cooling group (N = 15; receive 72 hours of whole body hypothermia) and melatonin/ hypothermia group (N = 15; receive hypothermia and 5 daily enteral doses of melatonin 10 mg/kg). Serum melatonin, plasma superoxide dismutase (SOD),and serum nitric oxide (NO) are measured at enrollment and after 2 weeks for the two HIE groups. The HIE groups underwent electroencephalography at enrollment and at 2 to 3 weeks. Brain MRI was performed after 2 weeks of life. Neurologic evaluations and Denver Developmental Screening Test II assessments were performed at 6 months. A group of healthy newborns will be used as a control for baseline labs.

Inclusion criteria

• Inborn infants at term gestation (38-42 weeks)
• Apgar scores ≤ 3 at 5 minutes and/or delayed first breath (>5 minutes after birth)
• Profound metabolic or mixed acidosis with serum bicarbonate levels of <12 mmol/L in initial blood gas analyses
• Evidence of moderate or moderate to severe encephalopathy, such as lethargy, seizures, abnormal reflexes, or hypotonia, in the immediate neonatal period

Exclusion criteria

• Twin gestation
• Maternal neuro-endocrinal disturbances including diabetes mellitus
• Chorioamnionitis or congenital infections
• Low birth weight less than 2.5 kg
• Congenital malformations of the central nervous system or gastrointestinal anomalies
• Chromosomal abnormalities
• After 6 hours of birth.
• Patients in extremis such as: (1) hypoxemia requiring supplemental oxygen 100% FiO2, (2) life threatening coagulopathy, or (3) deep coma.