A prospective randomized controlled study on mouse nerve growth factor in the treatment of global developmental delay in children YUAN Jin-Jing, WU De, WANG Wen-Wen, DUAN Jun, XU Xiao-Yan, TANG Jiu-Lai Department of Pediatric Neurology Rehabilitation Center, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China 摘要 目的 观察鼠神经生长因子（mouse nerve growth factor，mNGF）治疗儿童全面性发育迟缓的临床疗效。 方法 前瞻性选取安徽医科大学第一附属医院2016年7月至2017年7月收治的60例全面性发育迟缓患儿，随机分为常规康复组与mNGF组，每组各30例。常规康复组采用神经发育学疗法，mNGF组在此基础上，联合mNGF治疗。比较两组患儿在治疗前、治疗中和治疗结束后Gesell发育量表评分的差异。 结果 mNGF组和常规康复组治疗前、治疗1.5个月的Gesell发育量表各能区发育商（developmental quotient，DQ）差异无统计学意义（均 P >0.05）。治疗3个月后，mNGF组大运动、精细运动和应人能区的DQ高于常规康复组（均 P <0.05）。mNGF组一过性注射部位疼痛的发生率为7%（2/30），未发现癫痫等其他严重不良反应。 结论 联合应用mNGF治疗可显著改善全面性发育迟缓患儿的认知、运动和社交能力。 Abstract ：Objective To study the clinical effect of mouse nerve growth factor (mNGF) in the treatment of children with global developmental delay (GDD). Methods A prospective clinical trial was conducted in 60 children with GDD who were treated in the First Affiliated Hospital of Anhui Medical University between July 2016 and July 2017. These children were randomly divided into two groups: conventional rehabilitation treatment and mNGF treatment group (n=30 each). The children in the conventional rehabilitation treatment group were given neurodevelopmental therapy, and those in the mNGF treatment group were given mNGF treatment in addition to the treatment in the control group. The evaluation results of the Gesell Developmental Scale were compared between the two groups before and after treatment. Results Before treatment and after 1.5 months of treatment, there was no significant difference in the developmental quotient (DQ) of each functional area of the Gesell Developmental Scale between the mNGF treatment and conventional rehabilitation treatment groups (P>0.05). After 3 months of treatment, the mNGF treatment group had significantly higher DQs of gross motor, fine motor, and personal-social interaction than the conventional rehabilitation treatment group (P?0.05). The incidence rate of transient injection site pain after injection of mNGF was 7% (2/30), and there was no epilepsy or other serious adverse reactions. Conclusions In children with GDD, routine rehabilitation training combined with mNGF therapy can significantly improve their cognitive, motor, and social abilities. Key words ： Global developmental delay Mouse nerve growth factor Clinical effect Child Mithyantha R, Kneen R, McCann E, et al. Current evidence-based recommendations on investigating children with global developmental delay[J]. Arch Dis Child, 2017, 102(11): 1071-1076. DOI: 10.1136/archdischild-2016-311271. PMID: 29054862. PMCID: PMC5738593. Jeong JW, Sundaram S, Behen ME, et al. Differentiation of speech delay and global developmental delay in children using DTI tractography-based connectome[J]. AJNR Am J Neuroradiol, 2016, 37(6): 1170-1177. DOI: 10.3174/ajnr.A4662. PMID: 26797142. PMCID: PMC4907870. Dornelas LF, Duarte NM, Morales NM, et al. Functional outcome of school children with history of global developmental delay[J]. J Child Neurol, 2016, 31(8): 1041-1051. DOI: 10.1177/0883073816636224. PMID: 26936059. Bélanger SA, Caron J. Evaluation of the child with global developmental delay and intellectual disability[J]. Paediatr Child Health, 2018, 23(6): 403-419. DOI: 10.1093/pch/pxy093. PMID: 30919832. PMCID: PMC6234423. Choo YY, Agarwal P, How CH, et al. Developmental delay: identification and management at primary care level[J]. Singapore Med J, 2019, 60(3): 119-123. DOI: 10.11622/smedj.2019025. PMID: 30997518. PMCID: PMC6441684. Sone Y, Takatori S, Ochi E, et al. Nerve growth factor facilitates the innervation of perivascular nerves in tumor-derived neovasculature in the mouse cornea[J]. Pharmacology, 2017, 99(1-2): 57-66. DOI: 10.1159/000450582. PMID: 27694752. Zhao M, Li XY, Xu CY, et al. Efficacy and safety of nerve growth factor for the treatment of neurological diseases: a meta-analysis of 64 randomized controlled trials involving 6,297 patients[J]. Neural Regen Res, 2015, 10(5): 819-828. DOI: 10.4103/1673-5374.156989. PMID: 26109961. PMCID: PMC4468778. 9 许凤丽, 纪红, 宫为大, 等. 鼠神经生长因子穴位注射联合Bobath法治疗运动发育迟缓患儿临床疗效[J]. 陕西中医, 2021, 42(5): 650-653. DOI: 10.3969/j.issn.1000-7369.2021.05.027. 10 American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-5)[M]. 5th ed. Arlington VA: American Psychiatric Association, 2013: 79. 孔娟, 梁少珍, 陈海凤, 等. 出生早期体重增长速率对早产儿矫正12月龄时神经发育的影响[J]. 中国当代儿科杂志, 2021, 23(3): 236-241. DOI:10.7499/j.issn.1008-8830.2010108. PMID: 33691915. PMCID: PMC7969198. Yoshida T, Hiraiwa A, Ibuki K, et al. Neurodevelopmental outcomes at 3 years for infants with congenital heart disease and very-low birthweight[J]. Pediatr Int, 2020, 62(7): 797-803. DOI: 10.1111/ped.14160. PMID: 31957091. Li YH, Anderson LA, Ginns EI, et al. Cost effectiveness of karyotyping, chromosomal microarray analysis, and targeted next-generation sequencing of patients with unexplained global developmental delay or intellectual disability[J]. Mol Diagn Ther, 2018, 22(1): 129-138. DOI: 10.1007/s40291-017-0309-5. PMID: 29209992. 14 徐艳红, 李静, 唐久来. 儿童全面性发育落后的高危因素、临床特征和预后[J]. 中华实用儿科临床杂志, 2016, 31(10): 783-786. DOI: 10.3760/cma.j.issn.2095-428X.2016.10.015. Alamri A, Aljadhai YI, Alrashed A, et al. Identifying clinical clues in children with global developmental delay/intellectual disability with abnormal brain magnetic resonance imaging (MRI)[J]. J Child Neurol, 2021, 36(6): 432-439. DOI: 10.1177/0883073820977330. PMID: 33295251. 16 范晨雨, 谢鸿宇, 吴毅. 早期康复训练促进脑卒中神经重塑机制的研究进展[J]. 中国康复医学杂志, 2020, 35(11): 1377-1380. DOI: 10.3969/j.issn.1001-1242.2020.11.021. Rocco ML, Soligo M, Manni L, et al. Nerve growth factor: early studies and recent clinical trials[J]. Curr Neuropharmacol, 2018, 16(10): 1455-1465. DOI: 10.2174/1570159X16666180412092859. PMID: 29651949. PMCID: PMC6295934. Antonov SA, Manuilova ES, Dolotov OV, et al. Effect of nerve growth factor on neural differentiation of mouse embryonic stem cells[J]. Bull Exp Biol Med, 2017, 162(5): 679-683. DOI: 10.1007/s10517-017-3686-1. PMID: 28364186. Paoletti F, Malerba F, Ercole BB, et al. A comparative analysis of the structural, functional and biological differences between mouse and human nerve growth factor[J]. Biochim Biophys Acta, 2015, 1854(3): 187-197. DOI: 10.1016/j.bbapap.2014.12.005. PMID: 25496838. Wang QZ, Zhao HC, Zheng TH, et al. Otoprotective effects of mouse nerve growth factor in DBA/2J mice with early-onset progressive hearing loss[J]. J Neurosci Res, 2017, 95(10): 1937-1950. DOI: 10.1002/jnr.24056. PMID: 28345280. PMCID: PMC5561496. Yin XJ, Dong L, Wei W, et al. Effect of mouse nerve growth factor on the expression of glial fibrillary acidic protein in hippocampus of neonatal rats with hypoxic-ischemic brain damage[J]. Exp Ther Med, 2013, 5(2): 419-422. DOI: 10.3892/etm.2012.827. PMID: 23408790. PMCID: PMC3570183. Tuszynski MH, Yang JH, Barba D, et al. Nerve growth factor gene therapy: activation of neuronal responses in alzheimer disease[J]. JAMA Neurol, 2015, 72(10): 1139-1147. DOI: 10.1001/jamaneurol.2015.1807. PMID: 26302439. PMCID: PMC4944824. Rafii MS, Tuszynski MH, Thomas RG, et al. Adeno-associated viral vector (serotype 2)-nerve growth factor for patients with Alzheimer disease: a randomized clinical trial[J]. JAMA Neurol, 2018, 75(7): 834-841. DOI: 10.1001/jamaneurol.2018.0233. PMID: 29582053. PMCID: PMC5885277. Acosta CM, Cortes C, MacPhee H, et al. Exploring the role of nerve growth factor in multiple sclerosis: implications in myelin repair[J]. CNS Neurol Disord Drug Targets, 2013, 12(8): 1242-1256. DOI: 10.2174/18715273113129990087. PMID: 23844684. 25 李晓捷. 儿童康复学[M]. 北京: 人民卫生出版社, 2018: 159. 26 中国医师协会神经修复学分会儿童神经修复学专业委员会. 婴幼儿脑损伤神经修复治疗专家共识[J]. 中华实用儿科临床杂志, 2019, 34(1): 2-8. DOI: 10.3760/cma.j.issn.2095-428X.2019.01.002. 27 赵会玲, 冯欢欢, 李晓捷, 等. 注射用鼠神经生长因子联合康复训练治疗脑性瘫痪患儿的临床疗效[J]. 中华实用儿科临床杂志, 2019, 34(16): 1237-1240. DOI: 10.3760/cma.j.issn.2095-428X.2019.16.011. 28 邹小兵, 李咏梅. 儿童发育迟缓及发育障碍的早期干预和管理[J]. 中国实用儿科杂志, 2016, 31(10): 756-760. DOI: 10.7504/ek2016100609. 高惠琴, 管贤敏, 温贤浩, 沈亚莉, 郭玉霞, 窦颖, 孟岩, 于洁. 不同诊断标准下儿童急性不明谱系白血病的临床特点和预后分析 [J]. 中国当代儿科杂志, 2021, 23(8): 835-840. 刘桂华, 欧萍, 黄龙生, 谢娜妹, 林锦玲, 何迎霜, 胡蓉芳. 亲子绘画和创意手工疗法对学龄前期孤独症谱系障碍儿童及其母亲效果评价的前瞻性随机对照研究 [J]. 中国当代儿科杂志, 2021, 23(8): 779-785. 房海波, 王荣, 褚琳娜, 冯艳芳, 白容荣, 郭丰桐. 伴中央颞区棘波的儿童良性癫痫共患注意缺陷多动障碍患儿认知功能损害的前瞻性研究 [J]. 中国当代儿科杂志, 2021, 23(8): 791-796. 付强, 石明芳, 陈颖. 阿法骨化醇治疗儿童过敏性紫癜的前瞻性随机对照研究 [J]. 中国当代儿科杂志, 2021, 23(8): 797-801. 李东明, 何升. 30 417例儿童地中海贫血基因类型分析 [J]. 中国当代儿科杂志, 2021, 23(8): 841-847. 李敏, 汤昱, 赵二要, 陈超辉, 董利利. MTHFR 基因多态性与儿童支气管哮喘易感性及糖皮质激素疗效的相关性 [J]. 中国当代儿科杂志, 2021, 23(8): 802-808. 张如心, 张瑄, 张碧丽, 刘竹枫, 林书祥. 原发性肾病综合征患儿脂肪因子的表达及与高脂血症相关性研究 [J]. 中国当代儿科杂志, 2021, 23(8): 828-834. 高洋洋, 陈晓娟, 罗荣牡. 单倍体造血干细胞移植治疗儿童重型再生障碍性贫血的研究进展 [J]. 中国当代儿科杂志, 2021, 23(8): 854-859. 张文婷, 赵红梅, 罗艳红, 段佳琪, 李灿琳, 游洁玉. 儿童炎症性肠病艰难梭菌感染及其易感因素分析 [J]. 中国当代儿科杂志, 2021, 23(7): 718-723. 朱飒英, 彭镜, 毛蕾蕾, 邓小鹿, 张慈柳, 杨丽芬, 尹飞, 何芳. 儿童髓鞘少突胶质细胞糖蛋白抗体病复发因素及预防复发方案疗效的回顾性分析 [J]. 中国当代儿科杂志, 2021, 23(7): 724-729. 徐瑜欣, 钟建民. 热敏感相关癫痫的早期识别与诊断 [J]. 中国当代儿科杂志, 2021, 23(7): 749-754. 师琴, 汤文芳, 贺湘玲, 田鑫. 儿童EB病毒相关平滑肌肿瘤1例 [J]. 中国当代儿科杂志, 2021, 23(7): 739-742. 陈丹, 张娜丽, 张婷, 孙晓敏. 难治性肺炎支原体肺炎患儿支气管肺泡灌洗液中肺炎支原体耐药基因检测分析 [J]. 中国当代儿科杂志, 2021, 23(7): 707-712. 姜允丽, 李丹, 李田田, 吴蓓蓉, 尹冰如, 李爱求. 气道pH值监测在儿童慢性咳嗽与咽喉反流相关性判断中的价值 [J]. 中国当代儿科杂志, 2021, 23(7): 713-717. 地址：湖南省长沙市湘雅路87号　电话：0731-84327402 　传真：0731-84327922 E-mail: cjcp1999@csu.edu.cn
本系统由 北京玛格泰克科技发展有限公司 设计开发　技术支持： support@magtech.com.cn
湘ICP备17021739号-4