Velaphi 2013.

Methods	Single‐center randomized controlled trial in South Africa
Participants	Included 94 infants ≥ 34 weeks' gestation or ≥ 2000 g weight (or both) with evidence of perinatal asphyxia (base deficit > 16 mEq/L measured within 1 hour of life and Apgar score at 5 minutes ≤ 6 or requiring resuscitation for > 5 minutes) Infants were excluded if there was evidence of congenital abnormalities, inability to randomize by 6 hours of life, or lack of spontaneous respirations within 20 minutes of life with or without bradycardia
Interventions	Phenobarbital group (n = 50) received phenobarbital loading dose (40 mg/kg IV infused over 60 minutes) within the first 6 hours of life plus conventional therapy Control group (n = 44) received placebo (normal saline 1 mL/kg IV infused over 60 minutes) within the first 6 hours of life plus conventional therapy Conventional therapy for both groups included, regular monitoring of vital signs, administration of dextrose containing IV fluids and antibiotics Clinical seizures were treated with phenytoin with or without clonazepam. If seizures persisted despite treatment, the code was broken and phenobarbital was administered for infants in the control group. For infants in the phenobarbital group, a phenobarbital level was obtained and phenobarbital was administered if the level was below the therapeutic range
Outcomes	Short‐term outcomes: seizures, death, and neurologic outcome at discharge compared to Sarnat stage at time of enrollment Neurologic exam according to Sarnat staging were performed at 12‐24 hours, 2‐3 days, 5‐7 days of life, and on discharge Adverse effects of phenobarbital administration were evaluated (including hypotension and respiratory depression)
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random number table
Allocation concealment (selection bias)	Low risk	Sealed serially numbered opaque envelopes that were opened at the time of randomization
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Blinding of the treatment team is implied but not clearly stated. A placebo was administered Neonatal consultants uninvolved the care of the study infants performed neurologic exams
Incomplete outcome data (attrition bias) All outcomes	Low risk	Outcome data was complete to 100%
Selective reporting (reporting bias)	Low risk	All outcomes were reported

aEEG: amplitude‐integrated electroencephalography; CK: creatine kinase; CSF: cerebrospinal fluid; EEG: electroencephalography; GPx: glutathione peroxidase; HIE: hypoxic‐ischemic encephalopathy; IQ: intelligence quotient; IM: intramuscular; IU: international unit; IV: intravenous; LDH: lactate dehydrogenase; LP: lumbar puncture; MDA: malondialdehyde; MRI: magnetic resonance imaging; n: number of infants; NEPSY: Developmental NEuroPSYchological; Rh: rhesus; SOD: superoxide dismutase; TAS: total serum antioxidant status; VMI: Visual‐Motor Integration; WISC‐r: Wechsler Intelligence Scale for Children ‐ revised.