Leifsdottir Kristin, Jost Kerstin, Siljehav Veronica, Thelin Eric P, Lassarén Philipp, Nilsson Peter, Haraldsson Ásgeir, Eksborg Staffan, Herlenius Eric
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
Front Pediatr. 2022 Jul 19;10:921444. doi: 10.3389/fped.2022.921444. eCollection 2022.
Survival rate increases for preterm infants, but long-term neurodevelopmental outcome predictors are lacking. Our primary aim was to determine whether a specific proteomic profile in cerebrospinal fluid (CSF) of preterm infants differs from that of term infants and to identify novel biomarkers of neurodevelopmental outcome in preterm infants.
Twenty-seven preterm infants with median gestational age 27 w + 4 d and ten full-term infants were enrolled prospectively. Protein profiling of CSF were performed utilizing an antibody suspension bead array. The relative levels of 178 unique brain derived proteins and inflammatory mediators, selected from the Human Protein Atlas, were measured.
The CSF protein profile of preterm infants differed from that of term infants. Increased levels of brain specific proteins that are associated with neurodevelopment and neuroinflammatory pathways made up a distinct protein profile in the preterm infants. The most significant differences were seen in proteins involved in neurodevelopmental regulation and synaptic plasticity, as well as components of the innate immune system. Several proteins correlated with favorable outcome in preterm infants at 18-24 months corrected age. Among the proteins that provided strong predictors of outcome were vascular endothelial growth factor C, Neurocan core protein and seizure protein 6, all highly important in normal brain development.
Our data suggest a vulnerability of the preterm brain to postnatal events and that alterations in protein levels may contribute to unfavorable neurodevelopmental outcome.
早产儿的存活率有所提高，但缺乏长期神经发育结局的预测指标。我们的主要目的是确定早产儿脑脊液（CSF）中的特定蛋白质组学特征是否与足月儿不同，并识别早产儿神经发育结局的新生物标志物。
前瞻性纳入27例中位胎龄为27周+4天的早产儿和10例足月儿。利用抗体悬浮珠阵列对脑脊液进行蛋白质谱分析。测量了从人类蛋白质图谱中选出的178种独特的脑源性蛋白质和炎症介质的相对水平。
早产儿的脑脊液蛋白质谱与足月儿不同。与神经发育和神经炎症途径相关的脑特异性蛋白质水平升高，构成了早产儿独特的蛋白质谱。在参与神经发育调节和突触可塑性的蛋白质以及先天免疫系统的成分中观察到最显著的差异。几种蛋白质与18-24个月矫正年龄的早产儿良好结局相关。在对结局有强烈预测作用的蛋白质中，血管内皮生长因子C、神经黏蛋白核心蛋白和癫痫蛋白6都在正常脑发育中非常重要。
我们的数据表明早产儿脑对出生后事件具有易损性，蛋白质水平的改变可能导致不良的神经发育结局。
