Abstract:
In this two-center prospective cohort study of children on ECMO, we assessed a panel of plasma brain injury biomarkers using exploratory factor analysis (EFA) to evaluate their interplay and association with outcomes. Biomarker concentrations were measured daily for the first 3 days of ECMO support in 95 participants. Unfavorable composite outcome was defined as in-hospital mortality or discharge Pediatric Cerebral Performance Category > 2 with decline ≥ 1 point from baseline. EFA grouped 11 biomarkers into three factors. Factor 1 comprised markers of cellular brain injury (NSE, BDNF, GFAP, S100β, MCP1, VILIP-1, neurogranin); Factor 2 comprised markers related to vascular processes (vWF, PDGFRβ, NPTX1); and Factor 3 comprised the BDNF/MMP-9 cellular pathway. Multivariable logistic models demonstrated that higher Factor 1 and 2 scores were associated with higher odds of unfavorable outcome (adjusted OR 2.88 [1.61, 5.66] and 1.89 [1.12, 3.43], respectively). Conversely, higher Factor 3 scores were associated with lower odds of unfavorable outcome (adjusted OR 0.54 [0.31, 0.88]), which is biologically plausible given the role of BDNF in neuroplasticity. Application of EFA on plasma brain injury biomarkers in children on ECMO yielded grouping of biomarkers into three factors that were significantly associated with unfavorable outcome, suggesting future potential as prognostic instruments.
摘要:
在这项针对ECMO儿童的双中心前瞻性队列研究中,我们使用探索性因素分析(EFA)评估了一组血浆脑损伤生物标志物,以评估其相互作用和与结局的关联.在95名参与者的ECMO支持的前3天,每天测量生物标志物浓度。不利的复合结局定义为住院死亡率或出院小儿脑表现类别>2,从基线下降≥1点。EFA将11个生物标志物分为三个因素。因子1包含细胞脑损伤的标志物(NSE,BDNF,GFAP,S100β,MCP1,VILIP-1,神经颗粒蛋白);因子2包含与血管过程相关的标志物(vWF,PDGFRβ,NPTX1);因子3包含BDNF/MMP-9细胞途径。多变量逻辑模型表明,较高的因素1和2得分与较高的不良结局几率相关(校正OR2.88[1.61,5.66]和1.89[1.12,3.43],分别)。相反,较高的因子3得分与较低的不良结局几率相关(调整后OR0.54[0.31,0.88]),考虑到BDNF在神经可塑性中的作用,这在生物学上是合理的。EFA对儿童血浆脑损伤生物标志物的应用对ECMO产生了将生物标志物分为三个与不良结局显着相关的因素,提示未来作为预后工具的潜力。