儿童甲型H1N1流行性感冒相关性脑病死亡危险因素分析

doi:10.12372/jcp.2025.24e0881

Abstract

Abstract:

Objective To explore the risk factors of death from influenza A (H1N1)-associated encephalopathy (IAE) in children, and to provide evidence for early clinical diagnosis and intervention. Methods The clinical data of children with H1N1 IAE admitted to the hospital from January 2014 to December 2020 were retrospectively analyzed, and they were divided into the survival group and the death group according to prognosis. The risk factors associated with death in children with H1N1 IAE were analyzed by binary logistic regression. Results A total of 59 children (39 boys and 20 girls) with H1N1 IAE were included. The median age was 42 (21-73) months, and 66.1% (39/59) of the children were <5 years old. The median time between the onset of neurological symptoms and fever was 1 (0.5-2) days. Thirty-three patients (55.9%) had severe pneumonia and respiratory failure, and 1 of them had plastic bronchitis. Fifty-eight children were treated with oseltamivir. The median time from onset to use of anti-influenza drugs was 2 (1-4) days. Forty-eight patients were discharged from hospital with improvement and 11 died (18.6%). The median time from admission to death was 3 (1-5) days. Compared with the survival group, the death group presented higher incidences of consciousness disorder, respiratory failure, and brain herniation, a greater proportion of cases requiring mechanical ventilation treatment, a higher neutrophil count, elevated levels of procalcitonin, blood glucose, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, a longer prothrombin time, a higher ratio of abnormal head CT findings, and a lower monocyte count. All the differences were statistically significant (P<0.05). The results of binary logistic regression analysis revealed that elevated neutrophil count and lactate dehydrogenase levels might be associated with the occurrence of death in children with H1N1 IAE (P<0.05). Conclusions For children with H1N1 IAE, the risk of death may increase with elevated neutrophil counts and lactate dehydrogenase levels.

Key words: influenza A (H1N1), encephalopathy, death, risk factor, child

LI Shanshan, HU Dandan. Analysis of risk factors for death from influenza A (H1N1)-associated encephalopathy in children[J].Journal of Clinical Pediatrics, 2025, 43(3): 177-183.

Figures/Tables 5

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References 33

[1]	国家呼吸系统疾病临床医学研究中心, 中华医学会儿科学分会呼吸学组. 儿童流感诊断与治疗专家共识(2020年版)[J]. 中华实用儿科临床杂志, 2020, 35(17): 1281-1288.
	China National Clinical Research Center for Respiratory Diseases, Group of Respirology, Chinese Pediatric Society, Chinese Medical Association. Expert consensus on diagnosis and treatment of influenza in children (2020 Edition)[J]. Zhonghua Shiyong Erke Linchuang Zazhi, 2020, 35(17): 1281-1288.
[2]	Shi Y, Chen W, Zeng M, et al. Clinical features and risk factors for severe influenza in children: a study from multiple hospitals in Shanghai[J]. Pediatr Neonatol, 2021, 62(4): 428-436. doi: 10.1016/j.pedneo.2021.05.002 pmid: 34103261
[3]	Song YL, Qiu TX, Xiao WQ, et al. Characteristics and mortality risk factors of influenza-associated encephalopathy/encephalitis in children in a tertiary pediatric hospital in China, 2016-2019[J]. Austin J Infect Dis, 2021, 8(3): 1053.
[4]	Yu MKL, Leung CPP, Wong WHS, et al. Clinical spectrum and burden of influenza-associated neurological complications in hospitalised paediatric patients[J]. Front Pediatr, 2022, 9: 752816.
[5]	Bi J, Wu X, Deng J. Mortality risk factors in children with influenza-associated encephalopathy admitted to the paediatric intensive care unit between 2009 and 2021[J]. J Paediatr Child Health, 2024, 60(9): 456-461.
[6]	Nguyen LV, Nguyen DS, Pham QT, et al. Clinical features and treatment outcomes of influenza-associated encephalitis and encephalopathy: a study on 16 children in Vietnam[J]. Glob Pediatr Health, 2024, 11: 2333794X241286549.
[7]	Centers for Disease Control and Prevention (CDC). Neurologic complications associated with novel influenza A (H1N1) virus infection in children - Dallas, Texas, May 2009[J]. MMWR Morb Mortal Wkly Rep, 2009, 58(28): 773-778.
[8]	Muhammad Ismail HI, Teh CM, Lee YL, et al. Neurologic manifestations and complications of pandemic influenza A H1N1 in Malaysian children: what have we learnt from the ordeal?[J]. Brain Dev, 2015, 37(1): 120-129.
[9]	Tsuji M, Yoshida T, Miyakoshi C, et al. Is a reversible splenial lesion a sign of encephalopathy?[J]. Pediatr Neurol, 2009, 41(2): 143-145. doi: 10.1016/j.pediatrneurol.2009.02.019 pmid: 19589466
[10]	中华人民共和国国家卫生健康委员会, 国家中医药管理局. 流行性感冒诊疗方案 (2020年版)[J]. 中华临床感染病杂志, 2020, 13(6): 401-405.
	National Health Commission of the People’s Republic of China, State Administration of Traditional Chinese Medicine. Protocol for diagnosis and treatment of influenza (2020 version)[J]. Zhonghua Linchuang Ganranbing Zazhi, 2020, 13(6): 401-405.
[11]	Song Y, Li S, Xiao W, et al. Influenza-associated encephalopathy and acute necrotizing encephalopathy in children: a retrospective single-center study[J]. Med Sci Monit, 2021, 27: e928374.
[12]	Okuno H, Yahata Y, Tanaka-Taya K, et al. Characteristics and outcomes of influenza-associated encephalopathy cases among children and adults in Japan, 2010-2015[J]. Clin Infect Dis, 2018, 66(12): 1831-1837. doi: 10.1093/cid/cix1126 pmid: 29293894
[13]	卓秀伟, 丁昌红, 刘明, 等. 儿童流感相关脑病40例临床影像学特征及预后分析[J]. 中华实用儿科临床杂志, 2021, 36(24): 1876-1881.
	Zhuo XW, Ding CH, Liu M, et al. Clinical imaging features and prognosis of 40 children with influenza associated encephalopathy[J]. Zhonghua Shiyong Erke Linchuang Zazhi, 2021, 36(24): 1876-1881.
[14]	Li S, Hu D, Li P, et al. Parameters indicating development of influenza-associated acute necrotizing encephalopathy: experiences from a single center[J]. Med Sci Monit, 2021, 27: e930688.
[15]	罗意, 庄义江, 范绮梦, 等. 儿童流感相关性脑病15例死亡病例临床及影像分析[J]. 临床放射学杂志, 2022, 41(7): 1336-1341.
	Luo Y, Zhuang YJ, Fan QM, et al. Clinical and imaging analysis of 15 death cases of influenza associated encephalopathy in children[J]. Linchuang Fangshexue Zazhi, 2022, 41(7): 1336-1341.
[16]	Yang M, Yi L, Jia F, et al. Characteristics and outcome of influenza-associated encephalopathy/encephalitis among children in China[J]. Clinics (Sao Paulo), 2024, 79: 100475.
[17]	Li XF, Ai B, Ye JW, et al. Clinical analysis of seven cases of H1N1 influenza-associated encephalopathy in children[J]. Zhonghua Erke Zazhi, 2019, 57(7): 538-542.
[18]	李甜, 陈希文, 张剑珲, 等. 儿童重症流感相关性脑病17例诊治分析[J]. 广州医药, 2021, 52(4): 14-19. doi: 10.3969/j.issn.1000-8535.2021.04.004
	Li T, Chen XW, Zhang JH, et al. Analysis on diagnosis and treatment of 17 cases of severe influenza-associated encephalopathy of childhood[J]. Guangzhou Yiyao, 2021, 52(4): 14-19.
[19]	Vilensky JA, Foley P, Gilman S. Children and encephalitis lethargica: a historical review[J]. Pediatr Neurol, 2007, 37(2): 79-84. pmid: 17675021
[20]	Togashi T, Matsuzono Y, Narita M, et al. Influenza-associated acute encephalopathy in Japanese children in 1994-2002[J]. Virus Res, 2004, 103(1-2): 75-78. doi: 10.1016/j.virusres.2004.02.016 pmid: 15163492
[21]	Takahashi M, Yamada T, Nakashita Y, et al. Influenza virus-induced encephalopathy: clinicopathologic study of an autopsied case[J]. Pediatr Int, 2000, 42(2): 204-214. pmid: 10804743
[22]	Hui DS, Lee N, Chan PK, et al. The role of adjuvant immunomodulatory agents for treatment of severe influenza[J]. Antiviral Res, 2018, 150: 202-216.
[23]	Zhu HM, Zhang SM, Yao C, et al. The clinical and imaging characteristics associated with neurological sequelae of pediatric patients with acute necrotizing encephalopathy[J]. Front Pediatr, 2021, 9: 655074.
[24]	Okajima K, Hayakawa I, Tsuboi N, et al. Early therapeutic plasma exchange may lead to complete neurological recovery in moderate to severe influenza-associated acute necrotizing encephalopathy[J]. Brain Dev, 2022, 44(7): 492-497.
[25]	刘珺, 钱素云, 高恒妙, 等. 儿童甲型H1N1流感八例死亡病例临床特征及死因分析[J]. 中国小儿急救医学, 2019, 26(1): 32-36.
	Liu J, Qian SY, Gao HM, et al. Analysis of eight fatal cases of severe influenza A (H1N1) in children[J]. Zhongguo Xiaoer Jijiu Yixue, 2019, 26(1): 32-36.
[26]	Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, et al. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico[J]. N Engl J Med, 2009, 361(7): 680-689.
[27]	Chen Q, Liu J, Liang W, et al. Clinical features, replication competence, and innate immune responses of human adenovirus type 7 infection[J]. J Infect Dis, 2021, 223(8): 1390-1399. doi: 10.1093/infdis/jiaa524 pmid: 32840612
[28]	Sun J, Ma X, Zhang M, et al. Comparisons of lymphocytes profiles and inflammatory cytokines levels in blood of patients with differed severity of infection by human adenovirus type 7[J]. BMC Infect Dis, 2023, 23(1): 174.
[29]	Lefrançais E, Mallavia B, Zhuo H, et al. Maladaptive role of neutrophil extracellular traps in pathogen-induced lung injury[J]. JCI Insight, 2018, 3(3): e98178.
[30]	Keir HR, Chalmers JD. Neutrophil extracellular traps in chronic lung disease: implications for pathogenesis and therapy[J]. Eur Respir Rev, 2022, 31(163): 210241.
[31]	Pan T, Lee JW. A crucial role of neutrophil extracellular traps in pulmonary infectious diseases[J]. Chin Med J Pulm Crit Care Med, 2024, 2(1): 34-41. doi: 10.1016/j.pccm.2023.10.004 pmid: 39170960
[32]	王亚坤, 侯伟, 贾美轩, 等. 儿童重症流感的临床特征及发生危重症的危险因素分析[J]. 中国全科医学, 2021, 24(11): 1339-1343. doi: 10.12114/j.issn.1007-9572.2021.00.415
	Wang YK, Hou W, Jia MX, et al. Clinical characteristics and risk factors for critical-ill events in children with severe influenza[J]. Zhongguo Quanke Yixue, 2021, 24(11): 1339-1343.
[33]	Lin F, Chen MT, Zhang L, et al. Resurgence of influenza A after SARS-CoV-2 omicron wave and comparative analysis of hospitalized children with COVID-19 and influenza A virus infection[J]. Front Med (Lausanne), 2024, 10: 1289487.

项目	存活组(n=48)	死亡组(n=11)	统计量	P
男性[n(%)]	34(70.8)	5(45.5)	χ²=1.56	0.211
年龄( x±s)/月	46.2±32.5	62.7±29.1	t=1.36	0.180
热峰( x±s)/℃	39.8±0.8	39.9±0.7	t=0.73	0.466
热程[M(P₂₅~P₇₅)]/d	5.0(4.0~7.5)	3.0(1.8~6.0)	Z=1.85	0.064
季节[n(%)]			－	0.328¹⁾
冬春	41(85.4)	11(100.0)
夏秋	7(14.6)	0(0.0)
发病前接种流感疫苗²⁾	13(28.9)	4(36.4)	χ²=0.01	0.906
癫痫发作[n(%)]	32(66.8)	9(81.8)	－	0.534¹⁾
意识障碍[n(%)]	30(62.5)	11(100)	－	0.038¹⁾
呼吸衰竭[n(%)]	22(45.8)	11(100)	－	0.003¹⁾
电解质紊乱[n(%)]	5(10.4)	1(9.1)	χ²=0.00	1.000
脑疝[n(%)]	0(0)	10(90.9)	－	<0.001¹⁾
神经系统症状距发热时间[M(P₂₅~P₇₅)]/d	1.0(0.5~2.0)	0.3(0~2.0)	Z=1.30	0.194
治疗[n(%)]
奥司他韦	48(100.0)	10(90.9)	－	0.186¹⁾
激素	24(50.0)	7(63.6)	χ²=0.67	0.414
丙种球蛋白	29(60.4)	6(54.4)	χ²=0.00	0.986
激素联合丙种球蛋白	19(39.6)	4(36.4)	χ²=0.00	1.000
机械通气	12(25.0)	11(100.0)	－	<0.001¹⁾
降颅压	33(68.8)	7(63.6)	χ²=0.00	1.000
发病至使用奥司他韦时间[M(P₂₅~P₇₅)]/d	2.0(1.0~3.8)	1.5(1.0~4.5)	Z=0.27	0.785

项目	存活组(n=48)	死亡组(n=11)	统计量	P
血液检查
WBC( x±s)/×10⁹·L^-1	9.9±5.2	11.2±4.4	t=1.75	0.086
PLT( x±s)/×10⁹·L^-1	243.6±92.4	195.1±106.5	t=1.31	0.195
中性粒细胞计数[M(P₂₅~P₇₅)]/×10⁹·L^-1	6.8(2.0~11.1)	10.2(5.5~13.5)	Z=2.17	0.030
淋巴细胞计数[M(P₂₅~P₇₅)]/×10⁹·L^-1	1.4(0.6~3.3)	0.9(0.6~3.1)	Z=0.58	0.953
单核细胞计数[M(P₂₅~P₇₅)]/×10⁹·L^-1	0.4(0.2~0.8)	0.2(0.2~0.4)	Z=2.34	0.019
HB[M(P₂₅~P₇₅)]/g·L^-1	117.0(111.0~122.0)	111.0(103.0~121.3)	Z=0.81	0.419
超敏CRP[M(P₂₅~P₇₅)]/mg·L^-1	2.4(1.0~18.4)	11.4(1.2~18.4)	Z=0.25	0.800
PCT[M(P₂₅~P₇₅)]/ng·mL^-1	0.6(0.1~5.1)	8.6(1.6~26.0)	Z=2.58	0.010
血糖[M(P₂₅~P₇₅)]/mmol·L^-1	6.2(5.3~7.8)	8.5(5.8~12.6)	Z=2.01	0.045
乳酸[M(P₂₅~P₇₅)]/mmol·L^-1	1.5(1.1~2.3)	1.7(1.4~4.0)	Z=1.76	0.079
血氨[M(P₂₅~P₇₅)]/μmol·L^-1	46.6(21.8~78.6)	51.3(28.9~72.3)	Z=0.48	0.633
AST[M(P₂₅~P₇₅)]/U·L^-1	43.0(35.0~105.0)	144.5(43.3~537.0)	Z=2.63	0.009
ALT[M(P₂₅~P₇₅)]/U·L^-1	16.0(13.0~38.0)	55.50(17.8~176.3)	Z=2.57	0.010
LDH[M(P₂₅~P₇₅)]/U·L^-1	396.0(291.5~731.5)	626.5(453.3~1 706.5)	Z=2.96	0.003
CK[M(P₂₅~P₇₅)]/U·L^-1	171.0(69.8~486.3)	167.0(90.1~679.5)	Z=0.69	0.488
APTT[M(P₂₅~P₇₅)]/s	34.7(30.3~41.2)	35.9(28.7~45.5)	Z=0.53	0.599
PT[M(P₂₅~P₇₅)]/s	13.2(12.4~15.1)	14.7(12.7~18.2)	Z=2.13	0.034
脑脊液检查¹⁾[n(%)]
白细胞升高	2(5.4)	1(25.0)	－	0.271⁴⁾
脑脊液蛋白阳性	5(13.5)	1(25.0)	－	0.483⁴⁾
潘氏蛋白阳性	3(8.1)	2(50.0)	－	0.066⁴⁾
头颅CT异常²⁾[n(%)]	7(18.4)	8(80.0)	χ²=11.25	<0.001
头颅MRI异常³⁾[n(%)]	20(50.0)	1(100.0)	－	1.000⁴⁾

项目	偏回归系数	标准误	χ²值	P	OR(95%CI)
中性粒细胞计数	0.174	0.085	4.26	0.039	1.190(1.009~1.405)
LDH	0.002	0.001	6.80	0.009	1.002(1.001~1.004)

Analysis of risk factors for death from influenza A (H1N1)-associated encephalopathy in children

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