围生期脑损伤高危新生儿神经行为异常早期预测模型构建及验证

Construction and validation of an early prediction model for neurobehavioral abnormalities in high-risk neonates with perinatal brain injury

摘要

目的 基于新生儿振幅整合脑电图(aEEG)和围生期资料构建脑损伤高危新生儿神经行为异常的早期预测模型,并进行模型验证。方法 回顾性分析2021年9月至2023年6月自贡市妇幼保健院收治的246例脑损伤高危新生儿生后72 h内aEEG和围生期资料,根据12月龄时神经行为筛查是否正常分为无异常组(n=186)、异常组(n=60),比较两组围生期资料及aEEG结果,多因素Logistic回归模型分析脑损伤高危新生儿神经行为异常的相关影响因素,绘制受试者工作特征(ROC)曲线并计算曲线下面积(AUC)验证模型,绘制临床决策曲线(DCA)分析临床有效性。结果 异常组极低出生体重、产钳助产、新生儿20项行为神经测定(NBNA)评分≤35分及aEEG背景活动无连续性、无周期性、惊厥波患儿占比高于无异常组,1 min Apgar评分、aEEG宽带电压下界、窄带电压上界、窄带电压下界及总分低于无异常组,差异有统计学意义(t/χ²值介于2.874~57.970之间,P＜0.05);多因素Logistic回归结果显示早产、极低出生体重、产钳助产、NBNA评分≤35分是脑损伤高危新生儿神经行为异常的独立危险因素(OR值介于2.832~4.821之间,P＜0.05),1 min Apgar评分、aEEG总分是脑损伤高危新生儿神经行为异常的独立保护因素(OR值分别为0.446、0.722,P＜0.05);基于上述回归模型绘制脑损伤高危新生儿神经行为异常的列线图预测模型,其C-index为0.928,AUC为0.928,列线图校准度为0.876;DCA曲线显示,采用该列线图预测脑损伤高危新生儿神经行为异常能取得临床正向的净获益。结论 新生儿振幅整合脑电图结合早产、极低体重、产助产、NBNA评分、1 min Apgar评分可用于脑损伤高危新生儿神经行为异常早期预测评估中,为临床针对性制定干预方案提供参考。

Abstract

Objective To establish an early prediction model of neurobehavioral abnormalities in neonates at high risk of brain injury based on amplitude integrated electroencephalogram (aEEG) and perinatal data. Methods The aEEG and perinatal data of 246 high-risk neonates with brain injury admitted to Zigong Hospital of Woman and Child Health Care from September 2021 to June 2023 were retrospectively analyzed within 72 h after birth,and were divided into normal group (n=186) and abnormal group (n=60) according to the neurobehavioral screening at 12 months of age.Perinatal characteristics and aEEG parameters were compared between the two groups.Multivariate logistic regression analysis was performed to identify independent influencing factors for neurobehavioral abnormalities.A nomogram prediction model was constructed based on the regression results and validated using receiver operating characteristic (ROC) curves and the area under the curve (AUC).Clinical utility was evaluated by decision curve analysis (DCA). Results The proportion of very low birth weight,forceps assisted delivery,NBNA score ≤35,non-continuous,non-periodic aEEG background activity and seizure wave in abnormal group was higher than that in normal group,and the 1 min Apgar score,aEEG broadband voltage lower boundary,narrowband voltage upper boundary,narrowband voltage lower boundary and total score were lower than those in normal group (t/χ² values ranged from 2.874 to 57.970,P＜0.05).Multivariate Logistic regression analysis showed that preterm birth,very low birth weight,forceps delivery and NBNA score ≤35 were independent risk factors for neurobehavioral abnormalities in neonates at high risk of brain injury(OR values ranged from 0.446 to 0.722,P＜0.05),and 1 min Apgar score and aEEG total score were independent protective factors for neurobehavioral abnormalities in neonates at high risk of brain injury (OR values ranged from 0.446 to 0.722,P ＜0.05).Based on the above regression model,a nomogram prediction model for neurobehavioral abnormalities in neonates at high risk of brain injury was established.The model yielded a C-index of 0.928 and an AUC of 0.928,with a nomogram calibration degree of 0.876.Decision curve analysis showed that applying this nomogram to predict neurobehavioral abnormalities in neonates at high risk of brain injury could achieve a positive clinical net benefit. Conclusion Neonatal amplitude integrated EEG combined with preterm birth,very low birth weight,forceps assisted delivery,NBNA score,1 min Apgar score can be used for early prediction and evaluation of neurobehavioral abnormalities in neonates at high risk of brain injury,and provide reference for early clinical prediction and formulation of corresponding intervention programs.

关键词

新生儿 / 脑损伤 / 神经行为异常 / 振幅整合脑电图 / 预测模型

Key words

newborn / brain injury / neurobehavioral abnormality / amplitude-integrated EEG / prediction model

参考文献

[1] Shao R, Sun D, Hu Y, et al. White matter injury in the neonatal hypoxic-ischemic brain and potential therapies targeting microglia[J]. J Neurosci Res, 2021, 99(4): 991-1008.

[2] Peeples E S. MicroRNA therapeutic targets in neonatal hypoxic-ischemic brain injury:a narrative review[J]. Pediatr Res, 2023, 93(4): 780-788.

[3] Aalten M, Tataranno M L, Dudink J, et al. Brain injury and long-term outcome after neonatal surgery for non-cardiac congenital anomalies[J]. Pediatr Res, 2023, 94(4): 1265-1272.

[4] 王栋, 李盛杰, 张宁, 等. 初探MRI联合血清NSE水平评估新生儿高胆红素血症脑损伤的临床价值[J]. 中国CT和MRI杂志, 2021, 19(5): 134-136.

[5] 沈瑶, 赵国祥, 金万庆. 头颅MRI、CT和B超诊断新生儿颅脑损伤的价值观察[J]. 中国CT和MRI杂志, 2021, 19(11): 14-16.

[6] MacDonald J M, Abend N S, Topjian A A. Amplitude-integrated electroencephalography:it's not just for babies[J]. Pediatr Crit Care Med, 2020, 21(3): 292-293.

[7] Durrani N U R, Dinan M H. Amplitude-integrated electroencephalography:a primer for neonatologists and practitioners in the NICU[J]. Neoreviews, 2022, 23(2): 96-107.

[8] Wang X, Trabatti C, Weeke L, et al. Early qualitative and quantitative amplitude-integrated electroencephalogram and raw electroencephalogram for predicting long-term neurodevelopmental outcomes in extremely preterm infants in the Netherlands:a 10-year cohort study[J]. Lancet Digit Health, 2023, 5(12): e895-e904.

[9] Yates N, Gunn A J, Bennet L, et al. Preventing brain injury in the preterm infant-current controversies and potential therapies[J]. Int J Mol Sci, 2021, 22(4): 1671.

[10] Peyvandi S, Xu D, Barkovich A J, et al. Declining incidence of postoperative neonatal brain injury in congenital heart disease[J]. J Am Coll Cardiol, 2023, 81(3): 253-266.

[11] Morton S, Kua J, Mullington C J. Epidural analgesia,intrapartum hyperthermia,and neonatal brain injury:a systematic review and meta-analysis[J]. Br J Anaesth, 2021, 126(2): 500-515.

[12] Shen L, Tao M Y, Shi Y X, et al. Value of amplitude-integrated electroencephalogram combined with quantitative indices of cranial magnetic resonance imaging in predicting short-term neurodevelopment in moderately and late preterm infants:a prospective study[J]. Chinese Journal of Contemporary Pediatrics, 2021, 23(10): 987-993.

[13] Singh A, Saluja S, Kler N, et al. Amplitude integrated EEG:how much it helps in prognostication in neonatal encephalopathy[J]. J Matern Fetal Neonatal Med, 2022, 35(25): 7748-7755.

[14] Park K H, Kim Y M, Lee Y J, et al. Predictive value of an early amplitude-integrated electroencephalogram for short-term neurologic outcomes in preterm infants[J]. Turk J Pediatr, 2020, 62(3): 367-378.

[15] Tian Q, Pan Y, Zhang Z, et al. Predictive value of early amplitude integrated electroencephalogram(aEEG) in sleep related problems in children with perinatal hypoxic-ischemia(HIE)[J]. BMC Pediatr, 2021, 21(1): 410.

[16] 王书磊, 张阳阳. 血清NSE及aEEG动态变化早期预测窒息新生儿脑损伤的意义[J]. 广州医药, 2023, 54(11): 100-104.

[17] 陈健萍, 谭葵欢, 袁海超, 等. aEEG、脐血pH及新生儿Apgar评分对新生儿窒息结局的预测价值[J]. 海南医学, 2022, 33(3): 342-344.

[18] 李兆杭, 梁玉美, 孟子达, 等. 改良aEEG评分联合血清NSE对新生儿缺氧缺血性脑病早期诊断价值的研究[J]. 右江民族医学院学报, 2022, 44(5): 713-718.

[19] 阳华妹, 邓毅, 王丽, 等. NSE联合aEEG在新生儿胆红素脑病急性期诊断和预后评估中的应用分析[J]. 吉林医学, 2020, 41(3): 572-574.

[20] 姜红华, 程可然, 王月媛, 等. 血清UCH-L1、HO-1联合aEEG在早产儿脑损伤早期诊断及预后评估中的价值[J]. 徐州医科大学学报, 2023, 43(7): 517-522.

[21] 闫丽娟, 张晓丽, 翟丽娜, 等. MRI FLAIR序列联合aEEG在危重早产儿脑损伤中的早期诊断价值探究[J]. 影像科学与光化学, 2021, 39(6): 818-822.

[22] Variane G F T, Rodrigues D P, Pietrobom R F R, et al. Newborns at high risk for brain injury:the role of the amplitude-integrated electroencephalography[J]. J Pediat, 2022, 98(6): 565-571.

[23] Tandircioglu U A, Guzoglu N, Gucuyener K, et al. Influence of intensive care unit enlightenment on premature infants on functional brain maturation assessed by amplitude-integrated electroencephalograph[J]. Am J Perinatol, 2021, 38(4): 357-362.

[24] 赵凯红, 王彤, 田渤, 等. 脐动脉血气指标联合Apgar评分评估新生儿窒息的应用价值[J]. 中国妇幼健康研究, 2024, 35(1): 51-57.

基金资助

2020年四川省医学(青年创新)科研课题项目(S20174)