Neuroprotectors in hypoxic ischemic encephalopathy in neonates: a systematic review

Abstract

Objective The aim was to discuss the neuroprotectors in hypoxic ischemic encephalopathy (HIE) in neonates.Materials and methodsA systematic review of MEDLINE (PubMed, Medscape, Science Direct, and EMF-Portal) and internet was conducted on all articles published from 2002 to 2018. English-language reports of the neuroprotectors in HIE in neonates were searched. The initial search presented 117 articles, where 29 had inclusion criteria. Articles not reporting on the neuroprotectors in HIE in the title or abstract were not included. A total of five independent investigators extracted data on methods. Comparisons were made by a structured review, with the results tabulated. A total of seven studies were about hypoxic ischemic encephalopathy in neonates, nine about experimental translational studies, and 13 about current clinical trial studies for neuroprotectors in HIE.Results HIE is still a serious condition that is unresolved and causes significant mortality and long-term morbidity. Approximately 20–25% of term newborn infants die during the neonatal period and ∼25% of those who survive develop permanent neurological disabilities. Several studies showed that there were neuroprotective molecules that bring hope to future treatments such as melatonin, topiramate, xenon, interferon-β, and stem cell transplantation. Owing to the lack of imaging diagnostic difficulties to detect HIE in premature newborns and insufficient data, present stem cell therapy trials are restricted to full-term infants. Besides stem cell transplantation, there is research ongoing in the field of stem cell factors.ConclusionSome gaps in the knowledge concerning the pathophysiology and the timing of important endogenous neuroprotective and neuroregenerative mechanisms still exist. To make basic science results more clinically relevant and translational, combinational therapies with hypothermia should be considered and studied. There is also a need for more biomarker studies that can be used along with the brain imaging, and long-term neuroassessments.