血清HIF-1α、NSE、GFAP及相关临床特征与新生儿缺氧缺血性脑病发生风险的关系分析

Relationship analysis between serum HIF-1α, NSE, GFAP and related clinical features with the risk of neonatal hypoxic-ischemic encephalopathy

摘要:

目的 探讨血清低氧诱导因子-1α（HIF-1α）、神经元特异性烯醇化酶（NSE）、胶质纤维酸性蛋白（GFAP）及相关临床特征与新生儿缺氧缺血性脑病（HIE）发生风险的关系。方法 选取2020年1月—2023年1月苏州大学附属儿童医院收治的85例HIE患儿作为HIE组，另选取同期在该院出生的120例健康新生儿作为对照组，分析两组的临床资料并检测新生儿出生后3 d血清HIF-1α、NSE、GFAP水平。绘制受试者工作特征（ROC）曲线分析血清HIF-1α、NSE、GFAP水平预测新生儿HIE发病的价值；多因素逐步Logistic回归模型分析新生儿HIE发病的影响因素。结果 与对照组相比，HIE组宫内窘迫、脐带异常、羊水污染、1 min Apgar评分 ≤ 7分的患儿比例较高（P <0.05），并且血清HIF-1α、NSE、GFAP水平较高（P <0.05）；两组孕妇年龄、孕妇文化程度、胎龄、新生儿性别、出生体重、产次、剖宫产、胎膜早破比较，差异均无统计学意义（P >0.05）。ROC曲线分析结果显示，HIF-1α、NSE、GFAP及三者联合预测新生儿HIE发病的敏感性分别为82.7%（95% CI：0.795，0.862）、78.7%（95% CI：0.705，0.849）、84.0%（95% CI：0.803，0.891）、85.3%（95% CI：0.788，0.922），特异性分别为85.3%（95% CI：0.816，0.907）、74.7%（95% CI：0.715，0.796）、72.0%（95% CI：0.692，0.771）、90.5%（95% CI：0.825，0.956），AUC分别为0.907（95% CI：0.884，0.930）、0.850（95% CI：0.816，0.884）、0.893（95% CI：0.827，0.959）、0.936（95% CI：0.905，0.967）；多因素逐步Logistic回归分析显示，宫内窘迫［O^R =3.592（95% CI：2.017，6.397）］、脐带异常［O^R =4.905（95% CI：2.862，8.406）］、羊水污染［O^R =7.262（95% CI：3.603，14.637）］、1 min Apgar评分≤ 7分［O^R =3.139（95% CI：1.954，5.043）］、HIF-1α ≥ 0.463 ng/mL［O^R =2.916（95% CI：1.422，5.980）］、NSE ≥ 12.395 μg/L［O^R =3.714（95% CI：1.955，7.056）］、GFAP ≥ 3.962 ng/mL［O^R =3.556（95% CI：2.039，6.202）］均是新生儿HIE发病的危险因素（P <0.05）。结论 宫内窘迫、脐带异常、羊水污染、出生后1 min Apgar评分低及血清HIF-1α、NSE、GFAP水平高是新生儿HIE发病的危险因素，临床通过检测血清HIF-1α、NSE、GFAP水平可为临床筛查HIE提供帮助，3项指标联合检测可进一步提高诊断价值。

Abstract:

Objective To investigate the relationship between serum hypoxia-inducible factor-1α (HIF-1α), neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP) levels, and related clinical features with the risk of neonatal hypoxic-ischemic encephalopathy (HIE).Methods Eighty-five cases of HIE children treated at the Children's Hospital Affiliated to Soochow University from January 2020 to January 2023 were selected as the HIE group, and 120 healthy newborns born in the same period were selected as the control group. Clinical data of the two groups were analyzed, and serum HIF-1α, NSE, and GFAP levels were measured in the newborns within 3 days after birth. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of serum HIF-1α, NSE, and GFAP levels in predicting the occurrence of neonatal HIE, and multivariate stepwise logistic regression analysis was used to analyze the influencing factors of neonatal HIE.Results Compared with the control group, the proportion of infants with intrauterine distress, umbilical cord abnormalities, amniotic fluid pollution, and 1-minute Apgar score ≤ 7 in the HIE group was higher (P < 0.05), and serum HIF-1α, NSE, and GFAP levels were higher (P < 0.05). There was no statistically significant difference in maternal age, maternal education level, gestational age, newborn gender, birth weight, parity, cesarean section, and premature rupture of membranes between the two groups (P > 0.05). ROC curve analysis showed that the sensitivity of HIF-1α, NSE, GFAP, and their combination in predicting the occurrence of neonatal HIE was 82.7% (95% CI: 0.795, 0.862), 78.7% (95% CI: 0.705, 0.849), 84.0% (95% CI: 0.803, 0.891), and 85.3% (95% CI: 0.788, 0.922), respectively, and the specificity was 85.3% (95% CI: 0.816, 0.907), 74.7% (95% CI: 0.715, 0.796), 72.0% (95% CI: 0.692, 0.771), and 90.5% (95% CI: 0.825, 0.956), respectively. The area under the ROC curve (AUC) was 0.907 (95% CI: 0.884, 0.930), 0.850 (95% CI: 0.816, 0.884), 0.893 (95% CI: 0.827, 0.959), and 0.936 (95% CI: 0.905, 0.967), respectively. Multivariate stepwise logistic regression analysis showed that intrauterine distress [O^R = 3.592 (95% CI: 2.017, 6.397)], umbilical cord abnormalities [O^R = 4.905 (95% CI: 2.862, 8.406)], amniotic fluid pollution [O^R = 7.262 (95% CI: 3.603, 14.637)], 1-minute Apgar score ≤ 7 [O^R = 3.139 (95% CI: 1.954, 5.043)], HIF-1α ≥ 0.463 ng/mL [O^R = 2.916 (95% CI: 1.422, 5.980)], NSE ≥ 12.395 μg/L [O^R = 3.714 (95% CI: 1.955, 7.056)], and GFAP ≥ 3.962 ng/mL [O^R = 3.556 (95% CI: 2.039, 6.202)] were risk factors for neonatal HIE (P < 0.05).Conclusion Intrauterine distress, umbilical cord abnormalities, amniotic fluid pollution, low 1-minute Apgar score after birth, and high serum HIF-1α, NSE, and GFAP levels are risk factors for neonatal HIE. Clinical detection of serum HIF-1α, NSE, and GFAP levels can assist in the screening of HIE. The combination of these three indicators for detection can further improve the diagnostic value.