Non-inflammatory Cerebrospinal Fluids Biomarkers in Neonates with Perinatal Hypoxic Brain Injury - a Systematic Review

Saihaj Deol and Dr. Sidhartha Tan, Department of Pediatrics, Wayne State University, Detroit, MI 48202

Neonatal encephalopathy that purportedly arises from a hypoxic-ischemic brain injury is labeled hypoxic-ischemic encephalopathy (HIE). Perinatal asphyxia is a clinical syndrome involving acidosis, a low Apgar score, and the need for resuscitation in the delivery room; asphyxia alerts one to the possibility of neonatal encephalopathy. The study of these diseases is important as they can have lifelong effects on the patient as well as their family. Identifying the biomarkers that may be associated with brain injury as a result of HIE or asphyxia is imperative in providing early interventions to infants. Further, due to the variation in the units of reported biomarkers and methods of measurement as well as the unfocused targets in previous studies, analysis of the current literature through a systematic review will offer more comprehensive coverage from different settings in which brain injury resulted from HIE or asphyxia. In the present systematic review, we focused on the cerebrospinal fluid (CSF) and non-inflammatory biomarkers that are involved in the development of possible brain injury in asphyxia or HIE. A literature search in PubMed and EMBASE for case-control studies was conducted and 17 studies were found suitable by a priori criteria, which is case–control studies about the correlation between hypoxic neonatal brain injury during the perinatal period. Statistical analysis used the Mantel-Haenszel model for dichotomous data. The pooled mean difference and 95% confidence intervals (CIs) were determined based on the standard deviation and sample size. We identified the best biomarkers out of hundreds in three categories: cell adhesion and proliferation, oxidants and antioxidants, and cell damage. The best biomarkers were identified as those with a difference magnitude (expressed as a percentage of the control mean) greater than 100%. The following sub-population comparisons were made: perinatal asphyxia vs. no asphyxia, asphyxia with HIE vs. asphyxia without HIE, asphyxia with HIE vs. no asphyxia, term vs. preterm HIE with asphyxia. The biological significance of the biomarkers was determined by using a modification of the estimation approach, by ranking the biomarkers according to the mean-difference confidence intervals between the comparisons. This allowed us to recommend the most promising CSF biomarkers that could be incorporated into a combined test. We found that the most promising CSF biomarkers are creatine kinase, xanthine oxidase, vascular endothelial growth factor, neuron-specific enolase, superoxide dismutase, and malondialdehyde (in order of strength with creatine kinase being the strongest). Future studies are recommended using such a combined test to prognosticate the most severely affected patients. 

Additional Abstract Information

Presenters: Saihaj Deol, Sidhartha Tan -

Institution: Wayne State University

Type: Oral

Subject: Biology

Status: Approved

Time and Location

Session: Oral 8
Date/Time: Tue 5:00pm-6:00pm
Session Number: 804
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