血清神经调节蛋白1、叶酸在超早产儿脑损伤早期诊断、病情及预后评估中的价值研究

Clinical values of serum neuregulin-1 and folic acid for early diagnosis, evaluation of disease condition and prediction of prognosis of brain injury in extremely preterm infants

摘要

目的 探究血清神经调节蛋白1、叶酸在超早产儿脑损伤早期诊断、病情及预后评估中的价值。方法 选取2020年1月至2022年12月河北省秦皇岛市妇幼保健院收治的超早产儿128例为研究对象，其中60例超早产脑损伤患儿设为研究组，68例健康超早产儿设为对照组，采用格拉斯哥昏迷分级法（GCs）评估研究组患儿脑损伤程度，并将其分为轻度组23例、中度组19例及重度组18例；研究组患儿经治疗后根据预后情况分为预后良好组43例和预后不良组17例。酶联免疫吸附法（ELISA）检测血清中神经调节蛋白1水平；电化学发光免疫法测定血清中叶酸水平；Spearman分析神经调节蛋白1、叶酸相关性及两者与脑损伤程度的相关性；采用受试者工作特征（ROC）曲线分析血清中神经调节蛋白1、叶酸水平对早期诊断及预后的诊断价值。结果 研究组血清神经调节蛋白1、叶酸表达水平低于对照组，差异具有统计学意义（t值分别为6．894、8．947，P＜0．001）；轻度组、中度组、重度组血清中神经调节蛋白1、叶酸表达水平依次降低，差异具有统计学意义（F值分别为18．051、64．521，P＜0．001）；Spearman相关分析显示，血清神经调节蛋白1、叶酸表达水平与脑损伤程度均呈负相关性（r值分别为-0．624、-0．539，P＜0．05），血清神经调节蛋白1与叶酸表达水平呈正相关性（r＝0．567，P＜0．05）；预后良好组血清中神经调节蛋白1、叶酸表达水平高于预后不良组，差异具有统计学意义（t值分别为8．685、9．419，P＜0．001）；血清中神经调节蛋白1、叶酸及联合诊断超早产儿脑损伤发生的曲线下面积（AUC）分别为0．864、0．821、0．934，联合诊断效能更好（Z值分别为2．869、3．603，P＜0．05）；血清中神经调节蛋白1、叶酸及联合预测超早产儿脑损伤患儿预后不良的AUC分别为0．848、0．871、0．979，联合预测效能更好（Z值分别为2．616、2．688，P＜0．05）。结论 超早产儿脑损伤患者血清中神经调节蛋白1、叶酸水平降低，与脑损伤程度呈负相关，两者对超早产儿脑损伤早期诊断、不良预后发生具有一定的诊断价值。

Abstract

Objective To investigate clinical values of serum neuregulin-1 and folic acid for early diagnosis, evaluation of disease condition and prediction of prognosis of brain injury in extremely preterm infants. Methods A total of 128 extremely preterm infants who admitted to Qinhuangdao Municipal Maternal and Child Health Hospital, Hebei province from January 2020 to December 2022 were selected as study subjects. 60 extremely preterm infants with brain injury were assigned to study group, and 68 healthy extremely preterm infants were divided into control group. Glasgow coma scale (GCs) was applied to evaluate degree of brain injury of extremely preterm infants in the study group, further they were stratified into mild brain injury group (n=23), moderate brain injury group (n=19) and severe brain injury group (n=18). After treatment, these extremely preterm infants in the study group were divided into good prognosis group (n=43) and poor prognosis group (n=17) according to prognoses of the extremely preterm infants. Enzyme linked immunosorbent assay (ELISA) was applied to detect serum level of neuregulin-1, and electrochemiluminescence immunoassay (ECLIA) was applied to detect serum level of folic acid. Spearman correlation analysis was applied to analyze correlation between neuregulin-1 and folic acid, and correlations of the two indexes with severity of brain injury of the extremely preterm infants. Receiver operating characteristic (ROC) curve was applied to analyze diagnostic and predictive values of serum levels of neuregulin-1 and folic acid for early diagnosis and prognosis of the disease. Results The expression levels of serum neuregulin 1 and folic acid in the study group were lower than those in the control group, and the differences were statistically significant (t=6.894 and 8.947 respectively, both P<0.001). The expression levels of neuregulin 1 and folic acid in serum of the extremely preterm infants in the mild brain injury group, the moderate brain injury group and the severe brain injury group decreased successively, and the differences were statistically significant (F=18.051 and 64.521 respectively, both P<0.001). Spearman correlation analysis showed that the expression levels of neuregulin 1 and folic acid in serum were both negatively correlated with degree of brain injury (r=-0.624 and -0.539 respectively, both P<0.05), and neuregulin 1 and folic acid were positively correlated each other (r=0.567, P<0.05). The expression levels of neuregulin 1 and folic acid in serum of the extremely preterm infants in the good prognosis group were higher than those in the poor prognosis group, and the differences were statistically significant (t=8.685 and 9.419 respectively, both P<0.001). The areas under the curve (AUCs) of serum neuregulin 1, folic acid and combination of the two indexes for diagnosing brain injury of the extremely preterm infants were 0.864, 0.821 and 0.934 respectively, indicating that the diagnostic efficacy of the combination of the two indexes was better (Z=2.869 and 3.603 respectively, both P<0.05). The AUCs of serum neuregulin 1, folic acid and the combination of the two indexes for predicting poor prognosis of the extremely preterm infants with brain injury were 0.848, 0.871 and 0.979 respectively, indicating that the predictive efficacy of the combination of the two indexes was better (Z=2.616 and 2.688 respectively, both P<0.05). Conclusion The serum levels of neuregulin-1 and folic acid of the extremely preterm infants with brain injury descend, and the two indexes are negatively correlated with degree of brain injury. So, the two indexes have certain diagnostic values for early diagnosis and prediction of poor prognosis of these extremely preterm infants with brain injury.

关键词

神经调节蛋白1 / 叶酸 / 超早产儿 / 脑损伤 / 诊断 / 预后

Key words

neuregulin-1 / folic acid / extremely preterm infant / brain injury / diagnosis / prognosis

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基金资助

秦皇岛市科学技术研究与发展项目(202301A262)