振幅整合脑电图联合血清标志物对新生儿中重度缺氧缺血性脑病预后的评估价值

Prognostic value of amplitude-integrated electroencephalography combined with serum markers in neonates with moderate-to-severe hypoxic-ischemic encephalopathy

摘要:

目的 探讨振幅整合脑电图（aEEG）联合血清脑源性神经营养因子（BDNF）、低氧诱导因子-1α（HIF-1α）及中枢神经蛋白S100β对新生儿中重度缺氧缺血性脑病（HIE）预后的评估价值。方法 回顾性分析2023年1月—2024年4月徐州医科大学附属徐州儿童医院新生儿重症监护室收治的81例中重度HIE新生儿。于出生28 d后通过中国20项新生儿行为神经测定（NBNA）评分评估预后，将评分≥35分新生儿纳入预后良好组（55例），<35分新生儿纳入预后不良组（26例）。比较两组新生儿临床基线特征、aEEG指标、血清标志物（BDNF、HIF-1α、S100β）水平。采用多因素逐步Logistic回归模型分析新生儿中重度HIE的影响因素，绘制受试者工作特征（ROC）曲线，验证aEEG检测、血清标志物及联合检测对新生儿中重度HIE预后不良的预测价值。结果 预后不良组宫内窘迫发生率、出生后6～12 h亚低温治疗率、aEEG异常程度、血清HIF-1α水平和血清S100β水平均高于预后良好组（P <0.05）；预后不良组出生1 min和5 min Apgar评分、血清BDNF水平均低于预后良好组（P <0.05）。多因素逐步Logistic回归分析结果显示：aEEG异常程度高［O^R=3.462（95% CI：1.273，9.416）］、HIF-1α水平高［O^R=2.459（95% CI：1.106，5.465）］和S100β水平高［O^R=3.464（95% CI：1.162，10.330）］均为新生儿中重度HIE预后不良的危险因素，BDNF水平高［O^R=0.773（95% CI：0.634，0.944）］为新生儿中重度HIE预后不良的保护因素（均P <0.05）。ROC曲线结果显示，aEEG、血清标志物联合检测预测新生儿中重度HIE预后不良的敏感性为88.5%（95% CI：0.698，0.976）、特异性为92.7%（95% CI：0.824，0.980）。结论 aEEG异常、血清BDNF降低、HIF-1α和S100β升高与新生儿中重度HIE预后不良密切相关，联合检测可提高预后评估准确性，具有重要临床应用价值。

Abstract:

Objective To investigate the prognostic value of amplitude-integrated electroencephalography (aEEG) combined with serum brain-derived neurotrophic factor (BDNF), hypoxia-inducible factor-1α (HIF-1α) and S100 calcium-binding protein B (S100β) in neonates with moderate-to-severe hypoxic-ischaemic encephalopathy (HIE).Methods A retrospective study was conducted on 81 neonates with moderate-to-severe HIE admitted to the neonatal intensive care unit of Xuzhou Children's Hospital Affiliated to Xuzhou Medical University between January 2023 and April 2024. Prognosis was assessed 28 days after birth using the Chinese 20-item Neonatal Behavioral Neurological Assessment (NBNA). Neonates with a score of ≥ 35 were classified into the good prognosis group (55 cases), and those with a score < 35 into the poor prognosis group (26 cases). Clinical baseline characteristics, aEEG parameters, and serum biomarker levels (BDNF, HIF-1α, S100β) were compared between the two groups. A multivariable stepwise logistic regression model was employed, and receiver operating characteristic (ROC) curves were plotted to validate the predictive value of aEEG, serum biomarkers, and their combination for poor prognosis in neonates with moderate-to-severe HIE.Results In the poor prognosis group, the incidence of intrauterine asphyxia, the rate of hypothermic therapy between 6 and 12 hours after birth, the severity of aEEG abnormalities, and serum HIF-1α and S100β levels were all higher than in the good prognosis group (P < 0.05). Conversely, the 1-minute and 5-minute Apgar scores and serum BDNF levels were lower in the poor prognosis group (all P < 0.05). Multivariable stepwise logistic regression analysis showed that a high degree of aEEG abnormality [O^R = 3.462 (95% CI: 1.273, 9.416) ], high HIF-1α levels [O^R = 2.459 (95% CI: 1.106, 5.465) ] and high S100β levels [O^R = 3.464 (95% CI: 1.162, 10.330) ] were all risk factors for poor prognosis in neonates with moderate-to-severe HIE, whilst high BDNF levels [O^R = 0.773 (95% CI: 0.634, 0.944) ] were a protective factor for poor prognosis in neonates with moderate-to-severe HIE (all P < 0.05). ROC curve analysis showed that the combination of aEEG and serum biomarkers had a sensitivity of 88.5% (95% CI: 0.698, 0.976) and a specificity of 92.7% (95% CI: 0.824, 0.980) for predicting poor prognosis in neonates with moderate-to-severe HIE.Conclusion Abnormal aEEG findings, along with reduced levels of serum BDNF and elevated levels of serum HIF-1α and S100β, are closely associated with poor prognosis in neonates with moderate-to-severe HIE. The combined detection of these indicators can improve the accuracy of prognostic assessment and holds significant clinical value.