Plasma Biomarkers of Brain Injury in Neonatal Hypoxic-Ischemic Encephalopathy

Massaro, An N.; Wu, Yvonne W.; Bammler, Theo K.; Comstock, Bryan A.; Mathur, Amit M.; McKinstry, Robert C.; Chang, Taeun; Mayock, Dennis E.; Mulkey, Sarah B.; Meurs, Krisa P. Van; Juul, Sandra E.

doi:10.1016/j.jpeds.2017.10.060

Cited by 122 publications

(122 citation statements)

References 59 publications

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“…The protein increased in infants showing pathological cerebral MRI patterns. No significant effects of erythropoietin treatment on NB levels were detectable [81].…”

Section: S100b and Hypothermiamentioning

confidence: 89%

Early predictors of perinatal brain damage: the role of neurobiomarkers

Bersani

Pluchinotta

Dotta

et al. 2019

Clinical Chemistry and Laboratory Medicine (CCLM)

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The early detection of perinatal brain damage in preterm and term newborns (i.e. intraventricular hemorrhage, periventricular leukomalacia and perinatal asphyxia) still constitute an unsolved issue. To date, despite technological improvement in standard perinatal monitoring procedures, decreasing the incidence of perinatal mortality, the perinatal morbidity pattern has a flat trend. Against this background, the measurement of brain constituents could be particularly useful in the early detection of cases at risk for short-/long-term brain injury. On this scenario, the main European and US international health-care institutions promoted perinatal clinical and experimental neuroprotection research projects aimed at validating and including a panel of biomarkers in the clinical guidelines. Although this is a promising attempt, there are several limitations that do not allow biomarkers to be included in standard monitoring procedures. The main limitations are: (i) the heterogeneity of neurological complications in the perinatal period, (ii) the small cohort sizes, (iii) the lack of multicenter investigations, (iv) the different techniques for neurobiomarkers assessment, (iv) the lack of consensus for the validation of assays in biological fluids such as urine and saliva, and (v), the lack of reference curves according to measurement technique and biological fluid. In the present review we offer an up-to-date overview of the most promising developments in the use of biomarkers in the perinatal period such as calcium binding proteins (S100B protein), vasoactive agents (adrenomedullin), brain biomarkers (activin A, neuron specific enolase, glial fibrillary acidic protein, ubiquitin carboxyl-terminal hydrolase-L1) and oxidative stress markers.

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“…The protein increased in infants showing pathological cerebral MRI patterns. No significant effects of erythropoietin treatment on NB levels were detectable [81].…”

Section: S100b and Hypothermiamentioning

confidence: 89%

Early predictors of perinatal brain damage: the role of neurobiomarkers

Bersani

Pluchinotta

Dotta

et al. 2019

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…Similarly, baseline endogenous Epo levels (pre‐Epo infusion and therapeutic hypothermia) in term infants with moderate to severe injury undergoing hypothermia were positively correlated with injury in the basal ganglia and brainstem (Massaro et al . ). Endogenous upregulation of Epo after HI is delayed but prolonged, suggesting that it likely has a role both in limiting injury in the secondary phase and promoting neurorepair in the long term.…”

Section: The Global Burden Of Hypoxic–ischaemic Brain Injurymentioning

confidence: 97%

The fetus at the tipping point: modifying the outcome of fetal asphyxia

Dhillon

Lear

Galinsky

et al. 2018

The Journal of Physiology

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Brain injury around birth is associated with nearly half of all cases of cerebral palsy. Although brain injury is multifactorial, particularly after preterm birth, acute hypoxia-ischaemia is a major contributor to injury. It is now well established that the severity of injury after hypoxia-ischaemia is determined by a dynamic balance between injurious and protective processes. In addition, mothers who are at risk of premature delivery have high rates of diabetes and antepartum infection/inflammation and are almost universally given treatments such as antenatal glucocorticoids and magnesium sulphate to reduce the risk of death and complications after preterm birth. We review evidence that these common factors affect responses to fetal asphyxia, often in unexpected ways. For example, glucocorticoid exposure dramatically increases delayed cell loss after acute hypoxia-ischaemia, largely through secondary hyperglycaemia. This critical new information is important to understand the effects of clinical treatments of women whose fetuses are at risk of perinatal asphyxia.

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“…A recent clinical study elevated umbilical cord blood levels of this protein in neonates suffering from HIE stages II-III, suggesting that this biomarker may correlate with the severity of disease and the risk of adverse neurodevelopmental outcomes and/or death [ 12 ]. Elevated S100B protein in plasma within 24 h after birth is associated with increased brain injury as evaluated by MRI in a cohort of 50 newborns with HIE [ 14 ].…”

Section: Evaluation Of Hie: Emerging Modalitiesmentioning

confidence: 99%

“…Another recent study correlated NSE levels in the early postnatal period with poor outcomes at two years of age [ 16 ]. However, other studies evaluating plasma biomarkers in HIE have found no correlation between NSE levels and brain injury outcomes [ 14 , 17 ]. Additionally, NSE is affected by any hemolytic process which is a drawback to its utility as an effective biomarker [ 18 ].…”

Section: Evaluation Of Hie: Emerging Modalitiesmentioning

confidence: 99%

Current and Emerging Therapies in the Management of Hypoxic Ischemic Encephalopathy in Neonates

2018

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Neonatal hypoxic ischemic encephalopathy (HIE) presents a significant clinical burden with its high mortality and morbidity rates globally. Therapeutic hypothermia (TH) is now standard of care for infants with moderate to severe HIE, but has not definitively changed outcomes in severe HIE. In this review, we discuss newer promising markers that may help the clinician identify severity of HIE. Therapies that are beneficial and agents that hold promise for neuroprotection are described, both for use either alone or as adjuncts to TH. These include endogenous pathway modifiers such as erythropoietin and analogues, melatonin, and remote ischemic post conditioning. Stem cells have therapeutic potential in this condition, as in many other neonatal conditions. Of the agents listed, only erythropoietin and analogues are currently being evaluated in large randomized controlled trials (RCTs). Exogenous therapies such as argon and xenon, allopurinol, monosialogangliosides, and magnesium sulfate continue to be investigated. The recognition of tertiary mechanisms of brain damage has opened up new research into therapies not only to attenuate brain damage but also to promote cell repair and regeneration in a developmentally disorganized brain long after the perinatal insult. These alternative modalities may be especially important in mild HIE and in areas of the world where there is limited access to expensive hypothermia equipment and services.

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Plasma Biomarkers of Brain Injury in Neonatal Hypoxic-Ischemic Encephalopathy

Cited by 122 publications

References 59 publications

Early predictors of perinatal brain damage: the role of neurobiomarkers

Early predictors of perinatal brain damage: the role of neurobiomarkers

The fetus at the tipping point: modifying the outcome of fetal asphyxia

Current and Emerging Therapies in the Management of Hypoxic Ischemic Encephalopathy in Neonates

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