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Title: Biomarkers of hypoxic-ischemic encephalopathy: a systematic review
Authors: Caramelo, Inês 
Coelho, Margarida 
Rosado, Miguel 
Cardoso, Carla M P
Dinis, Alexandra
Duarte, Carlos B. 
Grãos, Mário 
Manadas, Bruno 
Keywords: Biomarker; Hypoxic–ischemic encephalopathy; Neonatal brain injury; Newborn; Neuron-specific enolase; S100-calcium-binding protein-B
Issue Date: Jun-2023
Publisher: Institute of Pediatrics of Zhejiang University
Project: This work was financed by the European Regional Development Fund (ERDF), through the COMPETE 2020—Operational Programme for Competitiveness and Internationalization and Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia, under projects POCI-01–0145-FEDER-029311, POCI-01–0247- FEDER-045311, UIDB/04539/2020 and UIDP/04539/2020, and individual Ph.D. fellowships PD/BD/135178/2017 (Margarida Coelho), SFRH/BD/143442/2019 (Inês Caramelo), and 2020.07749.BD (Miguel Rosado). 
Serial title, monograph or event: World Journal of Pediatrics
Volume: 19
Issue: 6
Abstract: Background Current diagnostic criteria for hypoxic–ischemic encephalopathy in the early hours lack objective measurement tools. Therefore, this systematic review aims to identify putative molecules that can be used in diagnosis in daily clinical practice (PROSPERO ID: CRD42021272610). Data sources Searches were performed in PubMed, Web of Science, and Science Direct databases until November 2020. English original papers analyzing samples from newborns > 36 weeks that met at least two American College of Obstetricians and Gynecologists diagnostic criteria and/or imaging evidence of cerebral damage were included. Bias was assessed by the Newcastle–Ottawa Scale. The search and data extraction were verified by two authors separately. Results From 373 papers, 30 met the inclusion criteria. Data from samples collected in the first 72 hours were extracted, and increased serum levels of neuron-specific enolase and S100-calcium-binding protein-B were associated with a worse prognosis in newborns that suffered an episode of perinatal asphyxia. In addition, the levels of glial fibrillary acidic protein, ubiquitin carboxyl terminal hydrolase isozyme-L1, glutamic pyruvic transaminase-2, lactate, and glucose were elevated in newborns diagnosed with hypoxic–ischemic encephalopathy. Moreover, pathway analysis revealed insulin-like growth factor signaling and alanine, aspartate and glutamate metabolism to be involved in the early molecular response to insult. Conclusions Neuron-specific enolase and S100-calcium-binding protein-B are potential biomarkers, since they are correlated with an unfavorable outcome of hypoxic–ischemic encephalopathy newborns. However, more studies are required to determine the sensitivity and specificity of this approach to be validated for clinical practice.
ISSN: 1708-8569
DOI: 10.1007/s12519-023-00698-7
Rights: openAccess
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais
FCTUC Química - Artigos em Revistas Internacionais
IIIUC - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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