新生儿听力和基因联合筛查的临床实践研究

发布时间：2018-06-12 01:52

本文选题：新生儿 + 听力筛查　；参考：《中国人民解放军军医进修学院》2010年硕士论文

【摘要】： 自1964年,Marion Downs应用行为测听来观察和测试新生儿听力状况,并研究发现每1000个新生儿中至少有1个先天性耳聋患者。此后,新生儿听力筛查项目在全球逐步开展起来,策略不断更新,技术日益改进。新生儿先天性耳聋的发病率也不断被报道。随着新生儿聋病发生情况研究的不断深入,经流行病学资料证实,随着年龄的增长,永久性听力损失患儿也持续增加,耳聋的研究也愈发的被重视。90年代以来新生儿听力筛查在世界范围内轰轰烈烈的展开。我国学者们紧跟随国际新生儿听力筛查的主流,在90年代初就开始对新生儿听力筛查进行积极的研究,也得到了政府的大力支持,2000年,政府以中华人民共和国母婴保健法的形式肯定进行新生儿听力筛查的意义和重要性。2002年12月,我国卫生部制订了《中国提高人口素质,减少出生缺陷和残疾行动(2002-2010)》,新生儿听力筛查工作在部分有条件的省、市、自治区、县广泛开展。2009年6月1日开始实施由卫生部颁发的《新生儿疾病筛查管理办法》,新生儿听力筛查在全国范围内迅速展开。我国开展新生儿听力筛查10余年来,目前的开展状况如何?实施情况如何?本课题将进行一系统的分析研究。本研究分为三个部分：第一部分中国新生儿听力筛查文献回顾研究本部分通过PUBMED. CBMdisc数据库及互联网检索1998-2008年的有关中国新生儿听力筛查文献,系统回顾我国近10年发表的新生儿听力筛查文献,采用Meta分析方法对全部文献数据进行统计分析,在增大样本量和扩大筛查范围的基础上,初步确定中国新生儿听力筛查相关流行病学指标,并进一步探讨国内开展新生儿听力筛查工作中存在的主要问题。本研究共纳入新生儿听力筛查相关文献129篇,新生儿705 394例,分别来自全国26个省、71个地区、120家医疗机构。经统计我国各省耳聋发病率普通病房为0.06%0.57%,大部分集中在0.1%～0.4%,平均发病率为0.20%(880／447 604),NICU病房波动在0.37%～7.35%,平均发病率为2.29%(79／3 446),略高于美国和英国等西方国家。经Meta分析,正常新生儿与存在高危因素新生儿的筛查结果间差异有统计学意义(P＜0.05)；不同高危因素对耳聋的影响差异有显著性(P＜0.05)；高危因素间比较,发现各高危因素组间仅“耳聋家族史及颌面畸形”与其他高危因素组,以及“早产组”与“窒息组”间耳聋的发病率有统计学差异(P＜0.05)；新生儿聋病发病率男女间无差别(P＞0.05)。不同初筛时间筛查结果经Meta分析,其数据支持随机效应模型的假定,说明结果严重不一致(P＜0.05)。112篇文献(669230例新生儿)报道采用OAE和AABR进行联合筛查,其中15篇还采用其他方法做了进一步验证,结果一致。61篇文献报道了随访情况,失访率3.95%(10714／271069)。本研究确定了新生儿听力初筛的最佳时间,支持出生后72小时为初筛最佳时间；OAE和AABR是目前作为新生儿筛查的最佳手段；证实了不同性别新生儿听力筛查结果无明显差异；高危因素影响着新生儿听力筛查通过率,高危新生儿耳聋发病率明显高于普通病房出生新生儿。但也发现了国内新生儿听力筛查工作存在筛查手段和方法不统一、筛查样本量不足、缺乏统一筛查程序、随诊率低等不足,所以需要需求一种更为理想的筛查模式,建立比较健全的随访制度。第二部分新生儿听力与基因联合筛查结果分析及随访研究随着新生儿听力筛查工作的广泛开展和临床经验的积累,逐渐发现部分通过出生筛查的新生儿将来会发生迟发性听力损失。2006年Morton和Nance提到在新生儿中进行常见耳聋基因的检查可能会预知部分遗传相关的迟发性耳聋。同年12月,解放军总医院率先在国内提出了听力筛查中融入聋病易感基因筛查的新理念,并于2007年3月在全国开展实施新生儿听力和基因联合筛查方案。本部分针对我院出生的2716例新生儿,进行听力与耳聋易感基因(A1555G、GJB2. SLC26A4)突变的联合筛查,并确定重点随访对象进行长期随访,确定新生儿听力和联合筛查的可靠性和可行性。研究发现5例新生儿为先天性感音神经性听力损失,此5例新生儿耳聋易感基因线粒体12SrRNA基因m.A1555G、GJB2基因c.235delC、SLC26A4基因c.919-2A＞G筛查均通过；在耳聋基因筛查中发现2例为A1555G阳性者,21例GJB2c.235delC杂合携带者,23例SLC26A4的c.919-2A＞G杂合携带者,均为听力筛查通过者,被告知注意事项,随访至今听力好,言语发育好。共纳入重点随访对象289例,完成随访225人,随访率77.85%(225／289)；失访64人,失访率22.15%(64／289)。289例新生儿中未在院内进行听力筛查、听力筛查结果异常及具有高危因素新生儿共247例,随访186例,随访率75.30%(186／247),失访61例,失访率24.70%(61／247),最后确诊5例感音神经性听力损失,确诊率2.69%(5／186)；289例新生儿中基因筛查异常46例(其中1例未行听力初筛,3例有高危因素),随访43例,随访率93.48%(43／46),失访3例,失访率6.52%(3／46)。基因筛查结果异常新生儿的随访率和单纯听力筛查结果异常新生儿的随访率的统计学分析卡方检验,P＜0.05,差异有统计学意义。本研究证实听力和基因联合筛查提高了新生儿聋病或高危聋儿的检出率,增加了重点随访对象的数量,扩大了耳聋的防治与干预范围,比单纯听力筛查更能得到家长的重视和配合。第三部分新生儿听力和基因联合筛查信息化网络系统的建立新生儿听力随访问题始终是新生儿听力筛查工作中的一大难题,无论在发展中国家还是在发达国家,都亟待解决。本部分针对新生儿听力和基因联合筛查方案,研究如何将这一筛查方案快速、高效的衔接和实施?如何形成有规模有秩序有层次的管理?从而进一步加强随访。通过建立新生儿听力和基因联合筛查网络数据库,利用互联网环境下的工作平台,录入新生儿听力筛查详细资料,数据库保存和管理新生儿听力筛查、基因筛查、诊断和干预康复资料,并录入家长手机号码,自动定期完成发送和接收短信对新生儿进行跟踪随访,对新生儿听力进行动态追踪,结合遗传资料进行科学的总结分析。同时,合作单位可以通过帐号、密码使用任何一台接入互联网的电脑访问该系统的网站,查询新生儿基因筛查的相关结果,并可以将疑难问题反馈给上级单位,上级单位可以对下级单位进行帮助和监督,形成一庞大的有秩序的新生儿听力和基因联合筛查网络管理-随访系统。研究发现新生儿听力和基因筛查资料管理和随访系统,将新生儿资料详细长久保存,并具有随时随地查询功能,具有统计报表功能,实现多方面数据检索功能,并可将结果数据直接转换成EXCEL表,方便统计软件分析处理。实现上下级单位之间,单位和患者之间的互动。本研究确定了新生儿听力和基因联合筛查资料管理和随访系统能满足新生儿听力筛查-诊断-干预-康复-随访-质量控制一体化功能,实现了听力筛查数据库智能管理,解决临床听力筛查随访难题,也为新生儿聋病研究准备和保存了足够的临床和遗传资料,将新生儿聋病防治工作向前推进了一大步。
[Abstract]:Since 1964, Marion Downs applied behavior to observe and test the hearing status of newborns, and found that at least 1 congenital deafness were found in every 1000 newborns. Since then, the newborn hearing screening program has been progressively developed around the world, the strategy is constantly updated, the technical day is improved, and the incidence of congenital deafness of the newborn is also continuous. It is reported that with the deepening of the study of the occurrence of neonatal deafness, the epidemiological data have proved that with the increase of age, the children with permanent hearing loss also continue to increase, and the research of hearing loss has become more and more important in the world since the.90 age. At the beginning of 90s, the mainstream of newborn hearing screening began to make positive research on newborn hearing screening in the early 90s, and the government supported it. In 2000, the government affirmed the significance and importance of neonatal hearing screening in the form of People's Republic of China maternal and infant health care law in December. China's Ministry of health formulated < China. Improving the quality of the population, reducing the birth defect and disability action (2002-2010), the hearing screening work of newborn infants in some provinces, cities, autonomous regions and counties is widely carried out in June 1st for the implementation of "neonatal screening management methods" issued by the Ministry of health in June 1st, and new children's hearing screening is launched rapidly throughout the country. What is the current status of hearing screening for children over the past 10 years? What is the implementation of this program? A systematic analysis will be carried out. This study is divided into three parts:
The first part is a literature review of neonatal hearing screening in China.
In this part, through the PUBMED. CBMdisc database and the Internet retrieval of 1998-2008 years of Chinese newborn hearing screening literature, this paper systematically reviews the literature of newborn hearing screening published in China in the last 10 years, and uses the Meta analysis method to analyze all the literature data. On the basis of enlarging the sample size and enlarging the scope of screening, it is preliminarily confirmed. In this study, 129 articles related to hearing screening for newborns and 705394 newborns were included in this study, from 26 provinces in China, 71 regions and 120 medical institutions, respectively. The common ward of the incidence of deafness was 0.06%0.57%, mostly concentrated in 0.1% to 0.4%, the average incidence was 0.20% (880 / 447604), the NICU ward fluctuated from 0.37% to 7.35%, the average incidence was 2.29% (79 / 3446), slightly higher than the western countries such as the United States and the United Kingdom. The difference between the normal newborns and the screening results with high risk factors was different by Meta analysis. There were statistical significance (P < 0.05); there were significant differences in the effect of different risk factors on Deafness (P < 0.05). The incidence of deafness among the high-risk factors group was only "deafness family history and maxillofacial malformation", and the incidence of deafness between "preterm group" and "stifling group" was statistically different (P < 0.05). The incidence of neonatal deafness was no difference between men and women (P > 0.05). The results of screening of different initial screening time were analyzed by Meta, and the data supported the hypothesis of random effect model, which showed that the results were not consistent (P < 0.05).112 Literature (669230 cases of newborns) were screened by OAE and AABR, of which 15 were also used in other methods. According to the results, the results were consistent with the follow-up.61 literature. The loss rate was 3.95% (10714 / 271069). This study confirmed the best time for newborn hearing screening and supported the best screening time at 72 hours after birth, and OAE and AABR were the best means of newborn screening. The high risk factors affect the passing rate of newborn hearing screening, the incidence of hearing loss in high risk neonates is obviously higher than that of newborns born in the general ward. However, it is also found that there are no uniform screening methods and methods, insufficient screening samples, lack of unified screening procedures, and low follow-up rate, and so on. A more ideal screening mode is needed, and a relatively sound follow-up system should be established.
The second part of the newborn hearing and gene combined screening results analysis and follow-up study.
With the extensive development of newborn hearing screening and the accumulation of clinical experience, it is gradually found that partial hearing loss in the newborn infants will have delayed hearing loss in the future,.2006 Morton and Nance refer to the common deafness genes in newborns, which may predict partial hereditary delayed deafness. December, the same year, The General Hospital of the PLA took the lead in the new concept of hearing screening for hearing loss in hearing screening in China. In March 2007, a joint screening program for newborn hearing and gene screening was carried out throughout the country. In this part, 2716 newborns born in our hospital were combined with hearing and deafness susceptibility gene (A1555G, GJB2. SLC26A4) mutation. The reliability and feasibility of neonatal hearing and joint screening were determined by the screening, and the reliability and feasibility of neonatal hearing and joint screening were determined. The study found that 5 newborns were congenital sensorineural hearing loss, and the 5 cases of neonatal deafness susceptible gene mitochondrial 12SrRNA gene m.A1555G, GJB2 gene c.235delC, and SLC26A4 gene c.919-2A > G screening were all screened. 2 cases of A1555G positive, 21 GJB2c.235delC heterozygous carriers and 23 SLC26A4 c.919-2A > G heterozygous carriers were found in the hearing loss gene screening. All of them were heard of hearing screening, and were followed up with good hearing and speech development. A total of 289 cases were followed up, and 225 were followed up with a follow-up rate of 77.85% (225). / 289) 64 people lost their visits and the rate of loss of visits was 22.15% (64 / 289) of.289 newborns without hearing screening. Hearing screening results were abnormal and there were 247 cases with high risk factors, 186 cases were followed up, the follow-up rate was 75.30% (186 / 247), missing visits, 24.70% (61 / 247), and final diagnosis of sensorineural hearing loss. / 186): 46 cases of abnormal gene screening in 289 newborns (1 cases without hearing screening, 3 cases with high risk factors), 43 cases were followed up, the follow-up rate was 93.48% (43 / 46), 3 cases were lost, 3 and 6.52% (3 / 46). The follow-up rate of abnormal newborn and the follow-up rate of abnormal newborns with simple hearing screening results were statistically analyzed. P < 0.05, the difference was statistically significant. This study confirmed that hearing and gene combined screening improved the detection rate of neonatal deafness or high-risk deaf children, increased the number of key follow-up objects, expanded the range of prevention and intervention of deafness and had more attention and cooperation than simple hearing screening.
The third part is the establishment of an information network system for hearing and gene screening in newborns.
The problem of neonatal hearing follow-up is always a difficult problem in newborn hearing screening. It is urgent to be solved both in developing countries and in developed countries. There is a hierarchical management to further strengthen follow-up. By establishing a network database of neonatal hearing and gene screening, using the working platform in the Internet environment, recording detailed information on newborn hearing screening, database preservation and management of newborn hearing screening, gene screening, diagnosis and intervention of rehabilitation data, and entering parents' mobile phone. The number, automatic regular completion of sending and receiving SMS to follow up the newborns, tracking the hearing of the newborns dynamically, combining with the genetic data to make a scientific summary and analysis. At the same time, the cooperative unit can use the account number, the cipher to access the web site of the system by any one connected to the Internet, and inquire about the newborn gene screening. The related results can be fed back to the higher level units, and the higher units can help and supervise the lower units to form a large and orderly newborns hearing and gene joint screening network management follow-up system. It can be saved in detail for a long time. It has the function of inquiring anytime and anywhere, having statistical report function, realizing the function of multifaceted data retrieval, and converting the result data directly into the EXCEL table, which facilitates the analysis and processing of the statistical software. It can realize the interaction between the units and the patients. This study determines the joint screening of newborn hearing and gene. The data management and follow-up system can meet the integrated function of neonatal hearing screening, diagnosis intervention, rehabilitation, follow-up and quality control, realize the intelligent management of hearing screening database, solve the problems of clinical hearing screening follow-up, prepare and preserve sufficient clinical and genetic data for the study of neonatal deafness, and prevent the prevention and treatment of neonatal deafness. The work took a big step forward.
【学位授予单位】：中国人民解放军军医进修学院
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R764.43

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