Srinivasakumar 2015.

Study characteristics
Methods	Randomised controlled trial
Participants	Inclusion criteria: (quote:) "1. ≥ 36 weeks’ gestation at delivery; 2. Admitted to the NICU within the first 24 hours of life; and 3. Either fulfilled clinical criteria for moderate‐to‐severe HIE (Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria) or had clinical seizures (suspected or confirmed)." Exclusion criteria: (quote:) "1. Neonates < 36 weeks’ gestation; 2. > 24 hours of age (to exclude nonHIE causes of seizures); 3. Infants with congenital anomalies of the central nervous system; 4. Moribund infants for whom no further aggressive treatment is planned; 5. Infants who demonstrated electrographic SE at the beginning of the cEEG study (initial 1 hour cEEG)". Treatment of electrographic seizures group Gestational age, mean ± SD: wk 38.3 ± 2 Birth weight, mean ± SD: g 3233 ± 585 Gender, boy:girl %: 60:40 5‐min Apgar Score: 4 Cord/first pH, mean ± SD: 7.05 ± 0.1 Inborn versus outborn, %: 40:60 Severity of HIE, moderate:severe: % 67:33 Abnormality on brain MRI: % 66 Therapeutic hypothermia: % 66 Age at start of cEEG monitoring, mean ± SD: h 12.5 ± 9.5 Electrographic SE: % 33 Duration of cEEG monitoring, mean ± SD: h 72.1 ± 37 Treatment of clinical seizures group Gestational age, mean ± SD: wk 38.5 ± 2 Birth weight, mean ± SD: g 3057 ± 602 Gender, boy:girl: % 60:40 5‐min Apgar Score: 4 Cord/first pH, mean ± SD: 7.08 ± 0.2 Inborn versus outborn: % 40:60 Severity of HIE, moderate:severe: % 70:30 Abnormality on brain MRI: % 85 Therapeutic hypothermia: % 65 Age at start of cEEG monitoring, mean ± SD: h 13.3 ± 10.1 Electrographic SE: % 20 Duration of cEEG monitoring, mean ± SD: h 69.5 ± 31 The study was conducted at a single centre in the USA from 2007 to 2011.
Interventions	Treatment of electrographic seizures alone versus treatment of clinical seizures Treatment of electrographic seizures Seizures were defined as (quote:) “rhythmic spike wave activity” lasting for > 10 seconds. Any EEG event, confirmed to be a seizure, with or without a clinical correlate lasting > 30 seconds, or more than 2 confirmed events detected by the algorithm in a 24‐hour period were thresholds to commence standardised ASM treatment. Treatment consisted of a stepwise approach: PB 20 mg/kg (first‐line); PB 20 mg/kg (second‐line, if seizures continued); fosphenytoin 20 mg/kg (third‐line, if seizures continued); if seizures continued: midazolam bolus 0.05 mg/kg followed by infusion at 0.15 mg/kg per hour for 24 hours, with decrease of dose to 0.1 mg/kg per hour for 24 hours and then to 0.05 mg/kg per hour for 24 hours before stopping. Treatment of clinical seizures Seizure diagnosis and treatment was based solely on clinical observation and was based on the following protocol: PB 20 mg/kg (first‐line); PB 20 mg/kg (second‐line, if seizures continued); fosphenytoin 20 mg/kg (third‐line, if seizures continued); if seizures continued: midazolam bolus 0.05 mg/kg followed by infusion at 0.15 mg/kg per hour for 24 hours, with decrease of dose to 0.1 mg/kg per hour for 24 hours and then to 0.05 mg/kg per hour for 24 hours before stopping. (Quote:) "Neonates who developed electrographic SE, detected by the study epileptologist, in this group were unblinded and treated as in the electrographic seizures group".
Outcomes	Primary outcome: seizure burden Other outcomes: neurodevelopmental development at 18 to 24 months evaluated using the BSID III
Notes	The study was funded by the Thrasher Foundation. The authors reported not having potential conflicts of interest to disclose.