Proteomic profiles in cerebrospinal fluid predicted death and disability in term infants with perinatal asphyxia: A pilot study

• Published in: Acta Paediatrica 2022-05, Vol.111 (5), p.961-970
• Main Authors: Leifsdottir, Kristin, Thelin, Eric P, Lassarén, Philipp, Siljehav, Veronica, Nilsson, Peter, Eksborg, Staffan, Herlenius, Eric
• Format: Article
• Language: English
• Subjects: adverse outcome; alpha2 spectrin; Asphyxia; Asphyxia Neonatorum - complications; biomarkers; brain protein; Cerebrospinal fluid; child death; clinical article; clinical outcome; controlled study; disability; Encephalopathy; Female; human; Humans; Hypoxia; Hypoxia-Ischemia, Brain - complications; hypoxic ischemic encephalopathy; hypoxic-ischaemic encephalopathy; Infant; Infant, Newborn; Infants; Inflammation; Ischemia; male; Medicin och hälsovetenskap; Myelin; Myelin basic protein; Neurodevelopmental disorders; neuron specific enolase; Original; pathway analysis; perinatal asphyxia; Phosphopyruvate hydratase; Pilot Projects; pilot study; Pregnancy; principal component analysis; prospective study; protein cerebrospinal fluid level; protein fingerprinting; protein microarray; protein profile; Proteins; proteome; Proteomes; Proteomics; regulator protein; Regulatory proteins; Spectrin; structural protein; Structural proteins; Suffocation; synaptic regulatory protein; unclassified drug; upregulation
• ISSN: 0803-5253; 1651-2227; 1651-2227
• DOI: 10.1111/apa.16277

Aim Perinatal asphyxia, resulting in hypoxic‐ischaemic encephalopathy (HIE), has been associated with high mortality rates and severe lifelong neurodevelopmental disabilities. Our aim was to study the association between the proteomic profile in cerebrospinal fluid (CSF) and the degree of HIE and long‐term outcomes. Methods We prospectively enrolled 18‐term born infants with HIE and 10‐term born controls between 2000 and 2004 from the Karolinska University Hospital. An antibody suspension bead array and FlexMap3D analysis was used to characterise 178 unique brain‐derived and inflammation associated proteins in their CSF. Results Increased CSF concentrations of several brain‐specific proteins were observed in the proteome of HIE patients compared with the controls. An upregulation of neuroinflammatory pathways was also noted and this was confirmed by pathway analysis. Principal component analysis revealed a gradient from favourable to unfavourable HIE grades and outcomes. The proteins that provided strong predictors were structural proteins, including myelin basic protein and alpha‐II spectrin. The functional proteins included energy‐related proteins like neuron‐specific enolase and synaptic regulatory proteins. Increased CSF levels of 51 proteins correlated with adverse outcomes in infants with HIE. Conclusion Brain‐specific proteins and neuroinflammatory mediators in CSF may predict HIE degrees and outcomes after perinatal asphyxia.