Early predictors of perinatal brain damage: the role of neurobiomarkers

Clin Chem Lab Med. 2020 Mar 26;58(4):471-486. doi: 10.1515/cclm-2019-0725.

Abstract

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.

Keywords: S100B; biomarker; brain damage; hypothermia; newborn; perinatal asphyxia.

Publication types

  • Review

MeSH terms

  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid*
  • Biomarkers / urine
  • Brain Injuries / diagnosis*
  • Female
  • Glial Fibrillary Acidic Protein / blood
  • Glial Fibrillary Acidic Protein / cerebrospinal fluid
  • Glial Fibrillary Acidic Protein / urine
  • Humans
  • Perinatal Care
  • Pregnancy
  • S100 Calcium Binding Protein beta Subunit / blood
  • S100 Calcium Binding Protein beta Subunit / cerebrospinal fluid
  • S100 Calcium Binding Protein beta Subunit / urine
  • Saliva / metabolism
  • Ubiquitin Thiolesterase / blood
  • Ubiquitin Thiolesterase / cerebrospinal fluid
  • Ubiquitin Thiolesterase / urine

Substances

  • Biomarkers
  • GFAP protein, human
  • Glial Fibrillary Acidic Protein
  • S100 Calcium Binding Protein beta Subunit
  • Ubiquitin Thiolesterase