Objective In the absence of controlled trials, treatment of neonatal seizures has changed minimally despite poor drug efficacy. We tested bumetanide added to phenobarbital to treat neonatal seizures in the first trial to include a standard‐therapy control group. Methods A randomized, double‐blind, dose‐escalation design was employed. Neonates with postmenstrual age 33 to 44 weeks at risk of or with seizures were eligible. Subjects with electroencephalography (EEG)‐confirmed seizures after ≥20 and <40mg/kg phenobarbital were randomized to receive additional phenobarbital with either placebo (control) or 0.1, 0.2, or 0.3mg/kg bumetanide (treatment). Continuous EEG monitoring data from ≥2 hours before to ≥48 hours after study drug administration (SDA) were analyzed for seizures. Results Subjects were randomized to treatment (n = 27) and control (n = 16) groups. Pharmacokinetics were highly variable among subjects and altered by hypothermia. The only statistically significant adverse event was diuresis in treated subjects (48% vs 13%, p = 0.02). One treated (4%) and 3 control subjects died (19%, p = 0.14). Among survivors, 2 of 26 treated subjects (8%) and 0 of 13 control subjects had hearing impairment, as did 1 nonrandomized subject. Total seizure burden varied widely, with much higher seizure burden in treatment versus control groups (median = 3.1 vs 1.2 min/h, p = 0.006). There was significantly greater reduction in seizure burden 0 to 4 hours and 2 to 4 hours post‐SDA (both p < 0.01) compared with 2‐hour baseline in treatment versus control groups with adjustment for seizure burden. Interpretation Although definitive proof of efficacy awaits an appropriately powered phase 3 trial, this randomized, controlled, multicenter trial demonstrated an additional reduction in seizure burden attributable to bumetanide over phenobarbital without increased serious adverse effects. Future trials of bumetanide and other drugs should include a control group and balance seizure severity. ANN NEUROL 2021;89:327–340

Objective To evaluate the efficacy and safety of passive cooling during transport of asphyxiated newborns. Study Design Retrospective medical record review of newborns with perinatal asphyxia transported for hypothermia between July 2007 and June 2010. Results Forty-three newborns were transported, 27 of whom were passively cooled. Twenty (74%) passively cooled newborns arrived with axillary temperature between 32.5 and 34.5 °C. One newborn (4%) arrived with a subtherapeutic temperature, and 6 (22%) had temperatures >34.5 °C. Time from birth to hypothermia was significantly shorter among passively cooled newborns compared with newborns not cooled (215 vs. 327 minutes, p<0.01), even though time from birth to arrival was similar (252 vs. 259 minutes, p=0.77). There were no significant adverse events related to passive cooling. Conclusions Exclusive passive cooling for hypoxic-ischemic encephalopathy results in significantly earlier achievement of effective therapeutic hypothermia without significant adverse events.

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