Diagnostic and Therapeutic Roles of the “Omics” in Hypoxic–Ischemic Encephalopathy in Neonates

Abstract

Perinatal asphyxia and neonatal encephalopathy remain major causes of neonatal mortality, despite the improved availability of diagnostic and therapeutic tools, contributing to neurological and intellectual disabilities worldwide. An approach using a combination of clinical data, neuroimaging, and biochemical parameters is the current strategy towards the improved diagnosis and prognosis of the outcome in neonatal hypoxic–ischemic encephalopathy (HIE) using bioengineering methods. Traditional biomarkers are of little use in this multifactorial and variable phenotype-presenting clinical condition. Novel systems of biology-based “omics” approaches (genomics, transcriptome proteomics, and metabolomics) may help to identify biomarkers associated with brain and other tissue injuries, predicting the disease severity in HIE. Biomarker studies using omics technologies will likely be a key feature of future neuroprotective treatment methods and will help to assess the successful treatment and long-term efficacy of the intervention. This article reviews the roles of different omics as biomarkers of HIE and outlines the existing knowledge of our current understanding of the clinical use of different omics molecules as novel neonatal brain injury biomarkers, which may lead to improved interventions related to the diagnostic and therapeutic aspects of HIE.

The association between plasma IgG N-glycosylation and neonatal hypoxic–ischemic encephalopathy: a case-control study

“…HIE accounts for about 15–35% of all cases of brain damage in late-preterm neonates and disorders in late-preterm and term neonates and is associated with the potential for long-term complications, including epilepsy, motor impairment, and cognitive impairment ( Wang et al, 2022 ). The pathological process of HIE includes three stages: early injury, intermediate stage, and reperfusion injury ( Rasineni et al, 2022 ). A cascade of pathophysiological changes occurs during the reperfusion phase, and the inflammatory response induced by hypoxic stress plays a critical role in this process ( Savman et al, 2013 ; Okazaki et al, 2023 ; Teo et al, 2023 ).…”

Biomarkers of hypoxic–ischemic encephalopathy: a systematic review

“…There are no accurate and objective tools with high sensitivity and specificity to diagnose newborns suffering from HIE. Some complementary blood tests have been proposed to evaluate liver and renal function and support the diagnosis, but they lack neuronal specificity [ 5 ]. According to the American College of Obstetricians and Gynecologists (ACOG) [ 6 ], if more than one of the following criteria is met, the newborn is more likely to suffer from a peripartum hypoxic–ischemic event: (1) appearance, pulse, grimace, activity, respiration (APGAR) score below 5 at 5 and 10 minutes; (2) fetal umbilical artery pH less than 7.0 and/or base deficit equal to or greater than 12 mmol/L; (3) neuroimaging evidence of acute brain injury seen on magnetic resonance imaging (MRI) or magnetic resonance spectroscopy (MRS), and (4) presence of multiorgan failure.…”

“…According to the American College of Obstetricians and Gynecologists (ACOG) [ 6 ], if more than one of the following criteria is met, the newborn is more likely to suffer from a peripartum hypoxic–ischemic event: (1) appearance, pulse, grimace, activity, respiration (APGAR) score below 5 at 5 and 10 minutes; (2) fetal umbilical artery pH less than 7.0 and/or base deficit equal to or greater than 12 mmol/L; (3) neuroimaging evidence of acute brain injury seen on magnetic resonance imaging (MRI) or magnetic resonance spectroscopy (MRS), and (4) presence of multiorgan failure. However, imaging is usually performed in the first two weeks of life and is not suitable for a rapid diagnosis [ 5 ].…”

“…Several studies have been published in recent decades proposing hypothetical biomarkers for HIE [ 5 , 9 ]. Nevertheless, to our knowledge, there is no review on the literature that collects all these data.…”