Neuroprotection for neonatal hypoxic-ischemic encephalopathy: A review of novel therapies evaluated in clinical studies.
Natalie H Chan, Cheryl C Hawkins, Benjamin V Rodrigues and 3 others
PMID 39563426WHAT IT FOUND
Most neuroprotective drugs added to cooling for neonatal hypoxic-ischemic encephalopathy have failed in trials, including magnesium, xenon, topiramate, and erythropoietin.
Some showed signal in small studies without cooling, but evidence remains uncertain and definitive trials are still needed.
Key findings
01Magnesium sulfate monotherapy showed conflicting results in meta-analyses, with one finding no effect on death or abnormal neurological examination at discharge and another associating it with lower mortality, while combination with therapeutic hypothermia showed no evidence of reduced mortality.
02Xenon, topiramate, and melatonin added to therapeutic hypothermia did not demonstrate significant benefit in clinical trials for neuroimaging biomarkers, death or severe neurological impairment, or mortality, respectively.
03A definitive phase III trial found that adding erythropoietin to therapeutic hypothermia did not reduce the risk of death or neurodevelopmental impairment at 2 years and was associated with a higher rate of serious adverse events.
STILL TO COME
How it was doneWhat they found
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What it does not show
As a narrative review, it does not systematically search or appraise all evidence, so selection of studies may introduce bias. Many cited studies are small, underpowered, or still ongoing, limiting conclusions about efficacy. Results from studies without therapeutic hypothermia may not translate to current standard-of-care settings where cooling is used. The review includes preclinical data which often does not replicate in human clinical trials.
The easy way to misread this
Do not interpret positive findings from small studies of agents like allopurinol or combination therapies as evidence they work in current practice. Most of these promising results were seen in infants who did not receive therapeutic hypothermia, and larger trials with cooling have generally failed to show benefit or have shown harm.