水通道蛋白-4与缺氧缺血性脑病患儿严重程度的相关性及对预后的评估价值

Correlation between aquaporin-4 and the severity of hypoxic-ischemic encephalopathy in children and its prognostic value

摘要:

目的 探讨水通道蛋白-4（AQP4）与缺氧缺血性脑病（HIE）患儿严重程度的相关性及对预后的评估价值。方法 选取2019年6月—2021年5月武汉市第一医院收治的137例HIE患儿为研究对象。依据影像学检查结果，将HIE患儿分为轻度组、中度组和重度组，分别有75例、37例和25例。比较不同严重程度HIE患儿脑脊液AQP4水平。统计HIE患儿28 d生存情况，依据患儿是否存活分为死亡组和生存组，分别有34例和103例。比较死亡组和存活组HIE患儿的临床资料。多因素Logistic回归分析影响HIE患儿预后的危险因素。绘制受试者工作特征（ROC）曲线分析脑脊液AQP4水平对HIE患儿预后的评估价值。结果 重度组脑脊液AQP4水平较中度组、轻度组高，中度组较轻度组高（P <0.05）。死亡组与存活组患儿性别、分娩孕周、日龄、分娩方式、出生时体重、胆固醇、白蛋白、血尿素、脐带异常、母体贫血比较，差异无统计学意义（P >0.05），死亡组Apgar评分低于存活组，开始治疗日龄长于存活组，重度病情程度占比、C反应蛋白、白细胞介素-8、肿瘤坏死因子-α及AQP4水平高于存活组（P <0.05）。多因素Logistic回归分析结果显示：开始治疗日龄［OR=2.907（95% CI：1.049，3.758）］、病情程度为重度［OR=3.843（95% CI：1.853，8.027）］、AQP4［OR=4.175（95% CI：2.146，10.482）］是导致HIE患儿死亡的影响因素（P <0.05）。ROC曲线分析结果显示，脑脊液AQP4水平对HIE患儿预后评估的最佳截断值为21.07 g/L，敏感性、特异性及AUC分别为76.47%（95% CI：58.43，88.62）、58.44%（95% CI：76.80，91.35）、0.821（95% CI：0.747，0.881）。结论 脑脊液AQP4水平与HIE患儿的病情严重程度及预后有关，且脑脊液AQP4水平对HIE患儿预后的评估效能良好。

Abstract:

Objective To investigate the correlation between aquaporin-4 (AQP4) and the severity of hypoxic-ischemic encephalopathy (HIE) in children and its prognostic value.Methods A total of 137 children with HIE who were admitted to Wuhan No.1 Hospital from June 2019 to May 2021 were selected. According to imaging findings, children with HIE were divided into mild (75 cases), moderate (37 cases) and severe (25 cases) groups. The levels of AQP4 in the cerebrospinal fluid of children with different severity of HIE were compared. The 28-day survival of children with HIE was observed, and the children were divided into death group (34 cases) and survival group (103 cases) according to the survival status. The clinical data of HIE children in the death group and the survival group were compared. Multivariable Logistic regression analysis was performed to determine the risk factors for the prognosis of children with HIE. The receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUC) was used to assess the value of the level of AQP4 in the cerebrospinal fluid for the prognosis of children with HIE.Results The levels of AQP4 in the cerebrospinal fluid of children with HIE in the severe group were higher than those in the mild and moderate groups (P < 0.05). There was no difference in the sex composition, the gestational age, the age in days, the delivery mode, birth weight, the levels of cholesterol, albumin and blood urea nitrogen, the proportion of children with abnormality of umbilical cord, and the frequency of maternal anemia between the death group and the survival group (P >0.05). Compared with the survival group, the Apgar score was lower, the age in days at the time of initial treatment was older, and the proportion of severe cases and the levels of C-reactive protein (CRP), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) and AQP4 were higher in the death group (P < 0.05). The multivariable Logistic regression analysis demonstrated that the age in days at the time of initial treatment [O^R = 2.907 (95% CI: 1.049, 3.758) ], the severe disease [O^R = 3.843 (95% CI: 1.853, 8.027) ] and the level of AQP4 [O^R = 4.175 (95% CI: 2.146, 10.482) ] were factors affecting the death of children with HIE (P < 0.05). The results of ROC curve analysis showed that the optimal cutoff value of the level of AQP4 in the cerebrospinal fluid for predicting the prognosis of HIE children was 21.07 g/L, with the sensitivity, specificity and AUC being 76.47% (95% CI: 58.43, 88.62), 58.44% (95% CI: 76.80, 91.35), and 0.821 (95% CI: 0.747, 0.881), respectively.Conclusions The level of AQP4 in the cerebrospinal fluid is related to the disease severity and prognosis of children with HIE, and is effective in predicting the prognosis of children with HIE.