Early predictors of perinatal brain damage: The role of neurobiomarkers: Clinical Chemistry and Laboratory Medicine

I. Bersani, F. Pluchinotta, A. Dotta, I. Savarese, F. Campi, C. Auriti, N. Chuklantseva, F. Piersigilli, F. Gazzolo, A. Varrica, A. Satriano, D. Gazzolo

Research output: Contribution to journalArticlepeer-review


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. © 2020 Walter de Gruyter GmbH, Berlin/Boston 2020.
Original languageEnglish
Pages (from-to)471-486
Number of pages16
JournalClin. Chem. Lab. Med.
Issue number4
Publication statusPublished - 2020


  • biomarker
  • brain damage
  • hypothermia
  • newborn
  • perinatal asphyxia
  • S100B
  • 3 nitrotyrosine
  • 8 isoprostane
  • activin A
  • adrenomedullin
  • biological marker
  • glial fibrillary acidic protein
  • malonaldehyde
  • neuron specific enolase
  • nitric oxide
  • protein S100B
  • ubiquitin carboxyl terminal hydrolase L1
  • unclassified drug
  • cerebrospinal fluid
  • human
  • nonhuman
  • oxidative stress
  • predictive value
  • priority journal
  • protein cerebrospinal fluid level
  • Review
  • saliva
  • sensitivity and specificity
  • umbilical cord blood
  • urinalysis


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