缺氧缺血性脑病新生儿血清NSE、S-100B、Tau蛋白、激活素A等指标变化及诊断效能

Predictive value of serum NSE,S-100B,Tau protein and activin A expressions in neonates with hypoxic-ischemic encephalopathy

目的探讨缺氧缺血性脑病(HIE)新生儿血清生物标志物神经元特异性烯醇酶(NSE)、S-100B、Tau蛋白、激活素A等指标变化及诊断效能。方法选取2020年1月至2022年2月在温州医科大学附属台州医院出生或就诊的75例HIE足月新生儿为研究对象,按照HIE严重程度分为轻度HIE组30例,中度HIE组25例,重度HIE组20例。选取同期本院出生的75名健康足月新生儿为对照组。检测并比较4组研究对象血清生物标志物及神经发育指标[包括新生儿神经行为(NBNA)、发育商(DQ)],采用Pearson相关分析血清生物标志物与神经发育指标的相关性,ROC曲线分析各项血清生物标志物单独或联合检测对HIE的诊断效能。结果4组研究对象血清生物标志物及神经发育指标比较,差异均有统计学意义(均P<0.05),其中轻、中、重度HIE组患儿血清NSE、S-100B、Tau蛋白、激活素A水平均明显高于对照组(均P<0.05),且轻度HIE组<中度HIE组<重度HIE组(均P<0.05);生后7 d NBNA评分、生后35周DQ、生后52周DQ均明显低于对照组(均P<0.05),且轻度HIE组>中度HIE组>重度HIE组(均P<0.05)。血清NSE、S-100B、Tau蛋白、激活素A水平与生后7 d NBNA评分均呈负相关(r=-0.779、-0.788、-0.714、-0.800,均P<0.05);与生后35周DQ均呈负相关(r=-0.662、-0.700、-0.626、-0.674,均P<0.05),与生后52周DQ均呈负相关(r=-0.636、-0.684、-0.619、-0.632,均P<0.05)。血清NSE、S-100B、Tau蛋白、激活素A单独检测和4项联合检测诊断HIE的AUC分别为0.923、0.946、0.942、0.939和0.995,4项联合检测的诊断效能最佳。结论血清NSE、S-100B、Tau蛋白、激活素A与HIE新生儿神经发育有关,4项联合检测诊断HIE的效能较高。

Objective To investigate the changes of serum neuron specific enolase(NSE),S-100B,Tau protein,activin A and other biomarkers in neonates with hypoxic-ischemic encephalopathy(HIE)and their diagnostic efficacy.Methods A total of 75 HIE full-term neonates in Taizhou Hospital Affiliated to Wenzhou Medical University from January 2020 to February 2022 were enrolled.According to the HIE severity,there were 30 cases in the mild HIE group,25 cases in the moderate HIE group and 20 cases in the severe HIE group.Seventy-five healthy newborns in our hospital at the same period was selected as the control group.The levels of serum biomarkers(NSE,S-100B protein,Tau protein and activin A)in each group of neonates were detected and compared,and the neurodevelopmental indicators,including neonatal behavioral neurological assessment(NBNA)and developmental quotient(DQ)was assessed and compared.The correlation between serum biomarkers and neurodevelopmental indicators was analyzed by using Pearson correlation analysis,and the diagnostic value of NSE,S-100B,Tau protein and activin A in predicting/jointly predicting the severity and prognosis of neonatal HIE was analyzed and compared by using ROC curve analysis.Results The levels of serum NSE,S-100B protein,Tau protein and activin A,as well as neurodevelopment indicators in HIE children of four groups showed statistically significant differences(all P<0.05),among which,serum levels of NSE,S-100B protein,Tau protein and activin A in mild,moderate and severe HIE groups were significantly higher than those in control group(all P<0.05),with mild HIE group<moderate HIE group<severe HIE group(all P<0.05).The NBNA score at day 7 after birth and DQ at 35 or 52 weeks after birth in the mild,moderate and severe HIE groups were all significantly lower than those of the control group(all P<0.05),with mild HIE group>moderate HIE group>severe HIE group(all P<0.05).The levels of serum NSE,S-100B protein,Tau protein,and activin A were negatively correlated with NBNA scores at 7 days after birth(r=-0.779,-0.788,-0.714,and-0.800,all P<0.05),DQ score at 35 weeks after birth(r=-0.662,-0.700,-0.626,and-0.674,all P<0.05),and DQ score at 52 weeks after birth(r=-0.636,-0.684,-0.619,and-0.632,all P<0.05).The AUC of the single and combination of serum NSE,S-100B protein,Tau protein and activin A in detecting HIE was 0.923,0.946,0.942,0.939 and 0.995,respectively,and the combination of them showed the greatest diagnostic value in predicting the severity and prognosis of neonatal HIE.Conclusion The Tau protein,activin A,S-100B protein and NSE are correlated with neurodevelopment of newborns with HIE,and the combination of them can effectively predict the severity and prognosis of neonatal HIE.