新生儿视听功能同步监测机制及功能整合的同步诱发电位研究
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摘要
无论从神经解剖学角度、还是神经生理学范围来说,神经听觉和神经视觉的联系是十分密切的。大脑通过对视、听等感觉的空间性与时间性的整合保持认知与行为的连续性,使分散的脑功能活动在解剖上和功能上得到了平衡与协调。同时,视觉障碍和听觉障碍也是许多临床疾病和相关综合征同时伴有的症状,聋病儿童的视力问题比正常儿童更常见。听力损失和视力缺陷是新生儿和婴幼儿发育不良的重要原因,如果不能早期发现和治疗将终身影响患儿及其家庭的生活质量,加重公共资源的负担。根据世界卫生组织的估计,全世界有150万盲童,其中三分之二(100万)在发展中国家。发展中国家,30～72%的儿童盲是可以避免盲;具有严重听力损失的新生儿约占新生儿总数的1/800。所以,听力损失和视力障碍的早期检测和早期干预对认识能力、言语和语言的发育至关重要。有效的早期干预,可以使听力损伤和视力障碍儿童的发育水平和认知水平有明显的改观。
由于听觉与视觉功能的不可分割性及解剖和生理与临床密切相关性,致使探讨视听功能的相互联系及功能整合乃成为必然。然而视觉、听觉及其功能整合机制与其它智能机制一样,是十分复杂的。视听功能可以在空间和认知时间上进行不同程度的整合,有研究对空间整合的机制作出了说明;但对视听信息捆绑输入的时间整合特性尚未明确阐述。
本研究通过视听同步诱发电位技术,研究了人体视觉和听觉功能整合效应的某些神经生物学特性。同时,超越新生儿听力筛查,进行以婴幼儿听力科学为基础的、多学科交融的研究,提出“实施新生儿视听功能同步筛查”这一新的公共卫生项目,并探索婴幼儿听力损失随年龄增长而出现的动态波动状况及山东省新生儿听力损失高危因素。使我国新生儿听力筛查和眼病筛查有机结合,相互交融,更加健康有序地向前发展。
第一部分视听功能整合效应同步诱发电位的初步研究
目的:应用视听同步诱发电位技术探索正常成年人及婴幼儿视听神经功能整合的电生理特性。
方法:应用视听同步诱发电位技术和常规听性脑干反应(ABR)技术,对正常成人10名(20眼和20耳)及年龄3月至4月龄正常婴儿14名(28眼和28耳)检测,确定同步程序ABR正常值及其与常规程序ABR的差异后,检测同步程序中(1)闪光刺激信号施加前后,ABR变化特点;(2)不同强度声刺激信号下视觉诱发电位(FVEP)变化特点。
结果:(1)同步程序(不管是加用FVEP与否)与常规程序ABR比较,虽然潜伏期不同,仍具有其独自的稳定特性:同步程序ABR各波潜伏期比常规程序ABR延长,但波间期无改变;且此种特性并不受是否加用FVEP的影响。(2)应用视听同步诱发电位程序,在较强声刺激信号条件下(70 dB nHL)同时给予光刺激信号, ABR各波潜伏期和波间期的参量变化显示其Ⅲ-Ⅴ波间期有显著性差异;而在声刺激信号50 dB nHL以下,则不能引起潜伏期的显著性变化(p>0.05)。(3)听觉刺激对闪频视觉诱发电位(FVEP)的影响:测试结果表明,不同强度的声刺激对FVEP的N1、P1、和N2波潜伏期,N1-P1和P1-N2峰值均未产生显著性作用(p值均大于0.05)。采用高、中、低三种不同声刺激强度均不能改变VEP的各波潜伏期及波幅。
结论:视觉诱发电位参数的稳定性显示出视觉诱发电位耦合电场的稳定性。然而,听性脑干反应(ABR)在同步程序不同声刺激条件下,其反应参量却表现出规律性的变化。这一结果提示在视听信号整合输入过程中,视听信号进入大脑是有序性:存在视觉信号对听觉信号的时间指导性(影响潜伏期),以期达到信息内环境的稳定性。
第二部分新生儿视听同步筛查的临床模式
目的:探索新生儿听力、眼病同步筛查的可行性和临床模式;了解新生儿听力下降及新生儿眼病的发病情况。
方法:在母婴同室应用瞬态诱发耳声发射(transient otoacoustic emission,TEOAE),在NICU采用两阶段筛查技术进行新生儿听力筛查,即应用TEOAE和自动听性脑干诱发电位测试(automatic auditory brainstem response,AABR)两种筛查技术进行筛查;同步进行新生儿眼病筛查。听力复筛与部分眼病复筛同步进行。听力复筛未通过者,生后3个月进入诊断程序:①听力学评估:声导抗、ABR、40 Hz听性相关电位(40Hz auditory event related potential,40Hz-AERP)、行为测听(6个月龄以后进行);②医学评估,影像学评估,并进行跟踪随访和定期的听力学评估、眼科学评估;视力筛查疑似病例及时转诊到专业眼科进一步确诊。正常新生儿进行眼部筛查性检查;NICU新生儿于出院前进行眼部筛查性检查与诊断性检查(视听同步诱发电位检查按要求进行),眼部筛查评估疑似病例及时转诊到专业眼科进一步确诊。
结果:自2002年10月1日至2005年4月30日在济南市妇幼保健院共出生16800例新生儿,对其中的15398(917.0‰)例新生儿进行了新生儿听力、眼病同步筛查,结果显示,新生儿听力损失在同步筛查儿中的发病率:双耳3.11‰(48/15398),单耳2.27‰(35/15398);有4例单耳或双耳先天性感音神经性聋伴发眼病:1例极重度感音神经性聋(双)、听神经病伴双眼先天性完全性白内障,1例轻度感音神经性聋(双)伴发左眼永存瞳孔膜,1例轻度感音神经性聋(双)伴双眼底静脉扩张,1例右耳轻度感音神经性聋伴双眼永存玻璃体动脉。在15398例统计取样的新生儿中,共检出先天性眼病和眼部体征12种1266例。
结论:新生儿期听力损失和眼病或眼部阳性体征在临床中并不少见。新生儿视听同步筛查在听力下降以及眼病监测和防治中是可行的,亦是有效的。实践新生儿视听同步筛查工作需要两个前提:较为完善的多学科合作机制,较强的小儿听力学和小儿眼科学临床工作。二者缺一不可。新生儿视听同步筛查应是儿童眼病/视力、听力同步监测的第一步,听力评估和眼部监测应在新生儿期就开始并持续在每一个儿童保健时期,评估手段应要与发育年龄相适宜。
第三部分新生儿眼病筛查的初步研究
目的:探索新生儿眼病筛查的临床策略、了解新生儿眼病的发病情况。
方法:对母婴同室新生儿在生后2-7天进行筛查性评估(光刺激反应、外眼检查、红光反射检查),异常者进行诊断性检查;新生儿重症监护病房(NICU)新生儿于生后5-14天进行筛查,并和高危因素新生儿实行眼部全面的筛查性和诊断性检查。对疑似病例及时转诊到专业眼科进一步确诊。
结果:15398例新生儿中,检出新生儿眼病12种,共1266例,检出率为82.22‰;其中先天性眼病7种,809例(52.54‰):包括先天性上睑下垂(0.13‰),先天性角膜浑浊(0.39‰),瞳孔残膜(47.02‰),先天性白内障15例(22只眼)(0.97‰),玻璃体动脉残存(3.51‰),先天性鼻泪管闭锁(0.46‰),泪腺脱垂(0.07‰);后天获得性眼病5种,457例(29.68‰):包括新生儿结膜炎(25.39‰),玻璃体出血(0.39‰),视网膜出血(2.21‰),新生儿泪囊炎(1.49‰),在27例1500克以下的未成熟儿中检出3例(6只眼)早产儿视网膜病变。正常新生儿14306例中,检出先天性眼病7种717例,检出率为50.12‰,后天获得性眼病4种417例(29.15‰)。NICU组1092例新生儿中,检出先天性眼病5种92例,检出率为84.25‰,后天获得性眼病5种40例(36.63‰)。NICU组先天性眼病与后天获得性眼病的检出率均高于正常新生儿组(P=0.000,P=0.016)。NICU组检出率高于正常新生儿组的眼病为:先天性白内障(P=0.000)、永存玻璃体动脉(P=0.000)和视网膜出血(P=0.001),低于正常新生儿组的为瞳孔残膜(P=0.01);
结论:新生儿的视力障碍并不少见,除ROP病例均发生在NICU组外,NICU病例还是先天性白内障、玻璃体动脉残存、视网膜出血的高发人群。早期干预对预防和治疗先天性白内障,早产儿视网膜病变等新生儿眼病是极其重要的。新生儿眼病筛查在眼病监测和防治中不仅是可行的而且是有效的。
第四部分新生儿听力损失程度波动特性及其影响因素
目的:探索新生儿听力损失随年龄、疾病转归后的波动情况,为降低听力损失的整体患病率和减缓其发展进程提供依据。
方法:新生儿听力筛查未“通过”的于3月龄常规进行声导抗、耳声发射、听性脑干诱发反应、40 Hz听性相关电位(40Hz-AERP)、行为测听(6个月龄以后进行),作出听力学诊断、医学评估并制定干预方案;对初诊异常和/或具有高危因素病例,约定每3月一次的听力学和医学复评估。
结果:通过对110例新生儿听力损失病例6月-48月(17.6±3.2月)长期门诊随访及多次的听力学再评估发现,新生儿听力损失程度尽管存在好转和加重两种趋势,但仍以无变化为主(58.2%),听力损失程度改善率(29.1%)高于加重发生率(12.7%)。婴幼儿轻度和中度听力损失是较容易发生听力损失程度变化的病例,轻度、中度、重度和极重度组中,分别有79.2%、72.7%、53.3%、3.6%的病例听力程度发生了改变;传导性及感音神经性听力损失中分别有78.4%(40/51)、39.0%(23/59)的病例发生了改变(p=0.000),传导性听力损失病例的损失程度变化发生率是感音神经性听力损失的2倍。单耳及双耳听力损失中分别有55.5%(25/45)、64.6%(42/65)的病例发生了改变(p=0.448),单耳及双耳病例的听力损失程度波动发生率差异无显著性。ABR听力阈值减少(“听力”改善)的64耳中,6.3%, 28.1%, 65.6%的病例分别减少30, 20, 10 dB nHL ,79.7%耳与中耳功能改善有关;听力损失加重28耳中,75%, 21.4%, 3.6%的病例分别增大10, 20, 40 dB nHL,50%与中耳功能变化有关。
结论:婴幼儿听力损失波动在临床并不少见的,并且存在可复性和渐进性两种变化趋势,中耳功能和新生儿疾病与婴幼儿听力损失程度波动关系密切;无论是单耳或者双耳听力损失,轻度、中度听力损失皆是处于向两极转变的交界状态,也是患进行性(双和单耳)听力损失的危险状态,要加强动态监测与防治。
第五部分山东省七城市新生儿单、双耳听力损失高危因素的病例对照研究
目的:探讨单、双侧新生儿听力损失高危因素,为预防新生儿听力损失的发生和减缓其发展进程提供依据。
方法:选定山东省7市地的7个筛查中心进行多中心研究,对所有新生儿听力筛查未通过病例转诊至济南市新生儿听力筛查诊断康复中心,对确诊病例进行基本特征的统计描述,采用1:1配对病例对照研究方法,进行单因素及多元条件Logistic逐步回归分析与新生儿单、双耳听力损失有关的高危因素。选择331例(双耳177例、单耳154例)完全符合配比要求的病例为研究对象。
结果:1、新生儿双耳听力损失病例:单因素分析,发现与新生儿听力损失有关的高危因素有11个:父亲年龄、父亲文化程度、母亲文化程度、产次、出生体重、孕周、颅面畸形、NICU监护史、新生儿疾病、耳病家族史、先天性听力损失家族史;条件Logistic回归分析显示新生儿双耳听力损失有4个独立危险因素:产次( OR=16.285 , 95% CI 3.379-78.481 )、新生儿疾病( OR=34.968 , 95% CI 2.720-449.534)、先天性听力损失家族史(OR=69.488,95% CI 4.417-1093.300)、出生体重(OR=0.241,95% CI 0.090-0.648);前3个为促进因素,后1个为保护因素。2、新生儿单耳听力损失:单因素分析,发现与新生儿单耳听力损失有关的高危因素有8个:父亲职业、母亲文化程度、母亲职业、产次、颅面畸形、NICU监护史、新生儿疾病、耳病家族史;条件Logistic回归分析显示单耳新生儿听力损失有2个独立危险因素:产次(OR=9.789,95% CI 2.270-42.173)、耳病家族史产次(OR=4.234,95% CI 1.179-15.203),皆为促进因素。
结论:经过山东省多中心新生儿听力损失的病例对照研究,产次、新生儿疾病、先天性听力损失家族史是双耳新生儿听力损失的促进因素,出生体重的增加是保护因素;产次和耳病家族史是单耳新生儿听力损失的促进因素,应对其采取适当干预措施。研究特点和创新之处:
本研究超越新生儿听力筛查,基于临床工作的背景和实验技术的可行性,进行以婴幼儿听力科学为基础的,实现多学科交叉的新生儿/婴幼儿视听功能同步监测及视听功能整合的研究。
本文在国际上率先提出“实施新生儿视听功能同步筛查”这一新的公共卫生项目;它为“聋儿和听力损失儿童眼部障碍”的学术分支及“听力科学和视觉科学/听觉-视觉缺失”的临床研究带来较大的发展空间和机遇。该模式的研究国内外还未见报道,新生儿眼病听力同步筛查模式具有广泛的学术内涵和潜在的市场需求;一旦推广普及,将为全社会带来巨大社会效益和经济效益。
同时,在国际上率先开展规范化、群体化新生儿眼病筛查与防治系列工作。使眼病在新生儿期得以及时诊治,避免了新生儿视力丧失。
国内显示出的具有示范意义的是:1、在我国妇幼保健系统建立儿童耳-听力和眼-视力的保健机制和模式,使我国新生儿听力筛查和眼病筛查有机结合,相互交融,更加健康有序地向前发展;2、获取我国相关领域的第一手较为完整的资料。为儿童眼病、听力损失的三级预防措施提供依据;3、在国内率先进行多中心新生儿听力损失高危因素的研究,不但确定新生儿双耳听力损失的高危因素,还在国内首次明确了新生儿单耳听力损失的高危因素,并提出干预措施。4、应用视听同步诱发电位研究,在国内首次提出在视听信号整合输入过程中,视听信号进入大脑的有序性:存在视觉信号对听觉信号的时间指导性(影响潜伏期),以期达到信息内环境的稳定性。5、在国内率先提出无论是单耳或者双耳听力损失,轻度、中度听力损失皆是处于向两极转变的交界动态,也是患进行性(双和单耳)HL的危险状态,要加强动态监测与防治。
以上所述,将先进的听力学测试、评估及康复技术与儿童听力保健的学科范畴相融合,构建了小儿听力保健的技术规范和科学评估体系。不仅弥补了我国综合医院和专科医院耳和眼专科的工作平台,亦发展了它们的某些临床功能;它必将对我国未来儿童保健学科、小儿耳鼻咽喉科学和小儿眼科学的发展带来较大的发展空间和机遇;同时也为“听力-视力科学”与“小儿感知觉发育科学”这一新兴学科的发展开辟了广阔的发展空间;为降低听力损失和视力障碍的整体患病率和减缓其发展进程提供依据;也将对未来听觉和视觉康复的临床具有指导作用。
Both anatomically and physiologically, hearing and vision are closely related. The brain, by temporally and spatially integrating the senses of hearing and sight and other senses, maintains the continuity of cognition and behaviors, and anatomically and functionally balance and coordinate separate cerebral activities. Clinically, visual and auditory disorders are commonly seen in many diseases and syndromes and deaf children tend to have visual problems as compared with normal kids. Hearing loss and visual impairments are two important causes of developmental disabilities among infants. Hearing and ocular conditions, if undetected or untreated, can have substantial long-term implications for the quality of life of the child and the family and can be a burden on public health resources. According to an estimate of WHO, 1.5 million children worldwide are blind. Two-third of these cases (1.0 million) is in developing countries. In developing countries, 30% to 72% of childhood blindness is avoidable. Children with severe and profound hearing loss account for 1/800 of all newborns. At the mean time, deaf children are heavily reliant on the sense of vision to develop efficient communication skills and explore the world around them. Any ophthalmic disorder may thus negatively impact on this process, especially if it is not identified in the early years of their life. These disorders may be correctable (such as myopia) or curable (such as cataract), and their early identification is of the utmost importance for their development of their language (spoken or sign, or both) and social cognition.
The close relations (anatomical, physiological and clinical) between hearing and vision make it a necessity to study their functional interactions and integration. The vision and hearing processes and their integration, however, are complicated. The The vision and hearing functions can, to some degree, be temporally and spatially integrated. Some studies examined and explained the mechanism of spatial integration, but the temporal integration of auditory and visual information in brain has not been clearly elucidated.
This study, by employing the technique of synchronous auditory and visual evoked potential, examined the neuro-biological features of integration of visual and auditory senses. Meanwhile, going beyond the newborn hearing screening, a multi-discipline study on the basis of newborn audiology was conducted and a new public health program---Newborn Simultaneous Vision and Hearing Screening---was put forward. The study also examined the change in hearing loss over time among newborns and infants and the high risk factors of hearing loss in Shandong Province. The combination of vision and hearing screening in newborns will greatly contribute to the control of newborn hearing loss (NHL) in China.
PartⅠA Preliminary Study on Integration Mechanism of Auditory and Visual Neural Function by Using Synchronous Auditory and Visual Evoked Potential
Objective: To explore the electrophysiological properties of integration of auditory-visual neural functions by using the technique of synchronous auditory and visual evoked potential.
Methods: By using technique of synchronous auditory and visual evoked potential and routine auditory brain-stem response (ABR) technique, 10 normal adult subjects (20 eyes and 20 ears) and 14 infants (aged from 3 to 4 month, 28 eyes and 28 ears) were studied. First, the different properties of auditory brainstem response (ABR) in auditory -visual synchronous program and non-synchronous program were explored.
Then, under the program of auditory -visual synchronous evoked potential , unimodal (A or V) and simultaneous bimodal (A-V) stimuli were presented and we detected two aspects :( (1) the ABR changes in the synchronous procedures before and after the presentation of flash stimuli and (2) the features in flash visual evoked potential (fVEP) were examined. Results: (1) As compared with routine ABR, the synchronous procedure (with or without fVEP test) were stable. Though the latencies of ABR waves of synchronous procedure were longer than those of routine one, no changes was found between interwaves. This feature was not influenced by the addition of fVEP test. (2) With synchronous procedure, under 70 dB nHL click stimulation, when light stimuli were given, significant differences in the interwave latencies betweenⅢ-Ⅴof ABR were observed, while, the click stimuli under 30, 50 dB nHL did not cause any significant change in wave latencies and interwave latencies (P<0.05). (3) In terms of effect of sound stimuli on the fVEP, our study showed that sound stimuli of different intensities did not significantly affect the latencies of N1, P1 and N2 waves of fVEP and N1-P1 and P1-N2 amplitude (P>0.05). The sound stimuli of high, medium and low intensities did not change the length of latencies and amplitude of fVEP. Conclusion The stability of the parameters of visual evoked potential reflects the stability of electric field of the visual evoked potential. Under sound stimuli of different intensities, the changes of ABR parameters showed some patterns. Our results suggest that in the integration of visual and auditory inputs, the auditory and visual signals enter the brain in an orderly manner. There exists a temporal guidance of auditory signals by visual signals (which affects latencies), thereby maintain the homeostasis of internal milieu in terms of information processing.
PartⅡClinical Application of Simultaneous Screening for Hearing and Ocular Diseases in Newborns
Objective: In this part, we explored the feasibility of simultaneous screening for hearing and ocular diseases in newborns and its clinical application, examined the hearing impairment and eye diseases in newborns
Methods: The universal newborn hearing screening (UNHS) was performed by using transient otoacoustic emission (TEOAE) in a baby-friendly nursery, and a two-stage screening protocol (including TEOAE stage and AABR [auto auditory brainstem response] stage) was carried out in a neonatal intensive care unit (NICU). At the same time, an eye disease screening was conducted. The re-screenings for hearing diseases and eye diseases were conducted simultaneously. If a newborn failed to pass the hearing re-screening test, with in 3 months after birth, she or he will be put on a diagnostic procedure, which included: (1) TEOAE, acoustic immitance, ABR, 40 Hz auditory event related potential (40 Hz AERP), behavioral audiometry ; (2) medical and imagological evaluations, follow-up and regular audiological and ophthalmological evaluations. If suspected cases of eye diseases were referred to pediatric ophthalmologists for definite diagnosis. The normal newborns were subjected to re-screening for eye-disease. The newborns who had received treatment in NICU were examined for screening and diagnostic purposes before being discharged (technique of synchronous auditory and visual evoked potential was conducted as required). And the cases that had positive sign and/or abnormal result of the ocular disease screening were referred for further examination by pediatric ophthalmologists.
Results: A total of 16800 children were born in Jinan Maternal and Child Hospital from October 1, 2002 to April 30, 2005. Of these infants, 15398 cases (916.0‰) were subjected to simultaneous screening for hearing and eye diseases. Our results showed that the incidence of bilateral congenital sensorineural hearing loss (SNHL) among infants who received UNHS was 3.11‰(48/15398), and the incidence of unilateral SNHL was 2.27‰(35/15398). Among them, 4 cases of congenital SNHL were complicated with newborn eye diseases: including 1 case of profound SNHL (bilateral) and auditory neuropathy accompanied by congenital cataract (bilateral), 1 case of mild SNHL (bilateral) complicated with membrana pupillaris perseverans (left), 1 case of mild SNHL (bilateral) with retina vein dilatation (bilateral), and 1 case of mild SNHL (right) with accompanying bilateral persistent hyaloid artery. In all the 15398 newborns, 12 eye-related diseases and signs were detected (involving 1266 cases).
Conclusion The hearing loss and ocular diseases/visual impairment is not uncommon in neonatal time and infancy. The simultaneous screening for newborn hearing and ocular diseases is not only feasible but also effective in the control of hearing loss and/or ocular disorders. Implementation of simultaneous screening for newborn hearing and ocular diseases entails (1) a well-established mechanisms of multli-discipline co-operation and (2) intensive work in neonate audiology and ophthalmology in clinical practice. The newborn screening for visual and auditory disease is the first step towards the simultaneous monitoring of eye disease, vision and hearing; hearing evaluation and eye disease monitoring should start at neonate stage and continue at every single stage of child health care and the means of evaluation should be in line with the age of juvenile development.
PartⅢA Preliminary Study of Screening for Neonatal Ocular Diseases Objective: To explore the clinical strategies for the screening of newborn eye diseases and get information concerning the incidence of newborn ocular diseases
Methods: The newborns in a baby-friendly nursery were evaluated for screening 2 to 7 days after birth (including reaction to light sitimuli, external ocular examination and test for red reflex) and those with abnormalities were subjected to diagnostic examination. The newborns in NICU were subjected to screening 5 to 14 days after birth and they, together with those with high risk factors, received a comprehensive examination for screening and diagnostic purpose. The suspected cases were referred to department of ophthalmology for definite diagnosis.
Results: Among the 15398 (916.0‰) who were enrolled the screening program, 12 kinds of eye diseases (involving 1266 cases) were detected, with a detection rate of 82.22%. Of these eye diseases, 7 were congenital ocular diseases, involving 809 cases (52.54‰) and including congenital ptosis (0.13‰), congenital corneal opacity (0.39‰), persistent pupillary membrane (47.02‰), congenital cataract (15 cases, 22 eyes involved, accounting for 0.97‰), persistent hyaloid artery (3.51‰), obstruction of nasolacrimal duct (0.46‰), lacrimal gland prolapse (0.07‰). Five diseases (involving 457 cases) detected were acquired ones, including neonatal conjunctivitis (25.39‰), vitreous haemorrhage (0.39‰), retinal haemorrhage (2.12‰), and neonatal dacryocystitis (1.49‰). Of 27 premature babies with body weight lower than 1500 g, 3 had retinopathy of prematurity (ROP, 6 eyes involed). Of 14306 normal newborns, 7 kinds of congenital diseases were detected in 717 cases, with a detection rate of 50.12‰and 4 kinds of acquired diseases were found in 417 cases with a detection rate of (29.15‰). In 1092 newborns who had received treatment in NICU, 5 kinds of congenital diseases were found in 92 cases, with the detection rate being 84.25‰and 5 kinds of acquired eye diseases were found in 40 cases, with a detection rate of (36.63‰). The detection rate of both the congenital and acquired diseases in the NICU group were higher than those in the group of normal newborns (P=0.000; P=0.016). The eye diseases whose detection rates in NICU group were higher than those of normal newborn group included congenital cataract (P=0.000), persistent hyaloid artery (P=0.000) and retinal hemorrhage (P=0.001). The detection rate of persistent pupillary membrane in the NICU group was lower than that in normal children group (P=0.01).
Conclusion: The visual disorders were not uncommon in newborns and except for ROP that were all found in NICU group, the incidences of congenital cataract, persistent hyaloid artery, retinal hemorrhage were also high in the group. Early intervention is of great importance for the prevention and treatment of neonatal ocular diseases such as congenital cataract and ROP. The screening of newborn ocular diseases is not only feasible but also effective in the monitoring and control of the eye diseases in neonates.
PartⅣChange of the Severity of Newborn/Infant Hearing Loss and Influencing Factors
Objective: To examine the change in hearing impairment level over time (ages) and after progression of diseases in order to get information for reducing the overall morbidity and slowing the progression of hearing loss.
Methods: The newborns who failed to“pass”the hearing screening were routinely examined, with in the age of 3, by TEOAE, acoustic immitance, otoacoustic emission, ABR, 40 Hz auditory event related potential (40 Hz AERP), behavioral audiometry for audiological diagnosis and medical evaluation, and intervention plans were laid. For those with abnormalities identified and/or with high risk factors, a once-every-3-month audiological and medical evaluation was performed.
Results: A long-term (6-48 months, 17.6±3.2 months) out-patient follow-up and repeated audiological evaluations in 110 newborns with hearing impairment showed that thought the hearing impairment in newborns might improve or deteriorate over time, in most of the cases (58.2%), their conditions remained unchanged, with the improvement rate of hearing impairment (29.1%) being higher than the deterioration rate (12.7%). The cases of mild and moderate hearing loss tended to experience changes. In groups of mild, moderate, severe and profound hearing loss, 79.2% (38/48), 72.7% (16/22), 53.3% (8/15) and 3.6%(1/28)79.2%, respectively, showed changes in hearing level ; in the group of conductive hearing loss and group of sensorineural hearing loss, 78.4% (40/51) and 39.0% (23/59) had change in hearing impairment level (p=0.000), and the change rate in the conductive hearing loss group was 2 times that in sensorineural hearing loss group. The hearing level changed in 55.5% (24/45) of the cases of unilateral hearing loss group and in 64.6 % ( 42/65) of the cases of bilateral hearing loss (P=0.448). No significant difference was found in the change rate between the groups of unilateral and bilateral hearing loss. With 64 ears with decreased ABR threshold (with hearing improvement), 6.3%, 28.1%, 65.6% of them had reduction by 30, 20, 10 dB nHL respectively. In 79.7% of the ears, the function of middle ear was improved. In 28 ears with hearing deterioration, 75%, 21.4%, 3.6% of them the ABR threshold increased by 10, 20, 40 dB nHL respectively and in 50% of the ears, the deterioration concerns the functions of middle ear.
Conclusion: The change of hearing level in children with hearing loss was not uncommon in clinical practice and the change is both gradual and reversible. The functions of middle ear and neonatal diseases bear close relation with the change of hearing level in children with hearing loss. With either unilateral or bilateral hearing loss, the mild and moderate hearing loss is a border-line state which could develop toward improvement or deterioration, i.e., having high risk of developing progressive hearing loss (unilateral or bilateral), which requires dynamic monitoring and long-term preventive and therapeutic effort.
PartⅤA Case-control Study on High-risk Factors for Newborn Hearing Loss in Seven Cities of Shandong Province
Objective: To investigate the high-risk factors for newborn unilateral or bilateral hearing loss and to provide information for preventing the development of hearing loss and delaying its progression.
Methods: In 7 screening centers selected from 7 districts, a multi-center study was conducted. All the neonates who failed to pass the universal newborn hearing screening (UNHS) were referred to Jinan Newborn Hearing Screening and Rehabilitation Center. The basic features of the definitely diagnosed cases were statistically described and one-to-one pair-matched case-control method was employed. High-risk factors relating to the unilateral or bilateral hearing loss were evaluated by univariate and multivariate Logistic regression analysis. 331 cases (including 177 bilateral hearing loss cases and 154 unilateral hearing loss cases) who fully satisfied the matching requirements were included as subjects
Results: (1) With newborns with bilateral hearing loss, univariate Logistic regression identified 11 hearing loss-related risk factors: age of father, educational level of father, educational level of mother, parity, birth weight, genstation weeks, craniofacial anomalies, history of NICU care, neonatal diseases, family history of ear diseases, and family history of congenital hearing loss. Conditional Logistic regression analysis showed that neonatal bilateral hearing loss had 4 independent risk factors: parity (OR=16.285, 95% CI 3.379—78.481), neonatal diseases (OR=34.968,95% CI 2.720—449.534), family history of congenital hearing loss (OR=69.488,95% CI 4.417—1093.300) and birth weight (OR=0.241, 95% CI 0.090—0.648). The former 3 factors are promoting factors and the last one is protective factor. (2) With newborns with unilateral hearing loss, univariate Logistic regression found 8 hearing loss-related risk factors: profession of father, educational level of mother, profession of mother, parity, craniofacial anomalies, history of NICU care, neonatal diseases, family history of ear diseases. Conditional Logistic regression analysis revealed that neonatal unilateral hearing loss had 2 independent risk factors: parity (OR=9.789, 95% CI 2.270—42.173) and history of congenital hearing loss (OR=4.234, 95% CI 1.179—15.203) and they are all promoting factors.
Conclusion: The multi-center case-controlled study of neonatal hearing loss in Shandong province showed that parity, neonatal disease, congenital hearing loss are promoting factors for bilateral hearing loss in newborns, the birth weight is a protective factor. The parity and family history of ear diseases are promoting factors of unilateral hearing loss and intervening measures should be taken with these cases.
Characteristics and Innovations in the Study
The study, for the first time, put forward a new public health care program, i.e., the“simultaneous screening of vision and hearing in neonates”. It broadens the horizon of and brings opportunities for the clinical study on the branch of“ocular disorders in children with deafness and hearing loss”and the“audiovisual science/hearing loss-visual impairment”. The simultaneous screening of vision and hearing has profound academic implications and potential market demand and its extensive application will bring immense social and economic benefits.
The implementation of standardized, large-population eye disease screening and control program in newborns will lead to timely treatment of the disease at neonatal stage thereby preventing sight loss in newborns.
Domestically, the study is of great importance in that (1) establishment of ear-hearing and eye-vision health care system for children will help to integrate the hearing disease screening and eye disease screening thereby promoting their healthy development; (2) successful collection of first-hand and complete data in relevant fields can provide information of the three-tier prevention program for juvenile eye diseases and hearing loss; (3) the first-time multi-center study about the risk factors of hearing loss not only identified the high-risk factors of bilateral hearing loss but also, for the first time in China, identified the high-risk factors of unilateral hearing loss, with intervening measures proposed; (4) by employing the technique of simultaneous visual and auditory evoked potentials, the study, for the first time, suggests that the visual and auditory signals enter brain in an orderly manner and the visual signals can provide temporal guidance for auditory signal (affecting latency), thereby achieving the homeostasis of internal environment in terms of information handling; (5) the study for the first time, points out that with either unilateral or bilateral hearing loss, the mild and moderate hearing loss is a border-line state which may develop towards recovery or deterioration, i.e., a dangerous state of developing unilateral or bilateral hearing loss that requires dynamic monitoring, preventive and therapeutic measures.
To sum up, in this study, by combining advanced audiological tests, evaluation and rehabilitation techniques, hearing-care sciences, a standardized and scientific evaluation system was established. It provides information for reducing hearing loss and visual disorders and slowing their progression. It also provides clinical guidance for the future work of hearing and vision rehabilitation.
由于听觉与视觉功能的不可分割性及解剖和生理与临床密切相关性,致使探讨视听功能的相互联系及功能整合乃成为必然。然而视觉、听觉及其功能整合机制与其它智能机制一样,是十分复杂的。视听功能可以在空间和认知时间上进行不同程度的整合,有研究对空间整合的机制作出了说明;但对视听信息捆绑输入的时间整合特性尚未明确阐述。
本研究通过视听同步诱发电位技术,研究了人体视觉和听觉功能整合效应的某些神经生物学特性。同时,超越新生儿听力筛查,进行以婴幼儿听力科学为基础的、多学科交融的研究,提出“实施新生儿视听功能同步筛查”这一新的公共卫生项目,并探索婴幼儿听力损失随年龄增长而出现的动态波动状况及山东省新生儿听力损失高危因素。使我国新生儿听力筛查和眼病筛查有机结合,相互交融,更加健康有序地向前发展。
第一部分视听功能整合效应同步诱发电位的初步研究
目的:应用视听同步诱发电位技术探索正常成年人及婴幼儿视听神经功能整合的电生理特性。
方法:应用视听同步诱发电位技术和常规听性脑干反应(ABR)技术,对正常成人10名(20眼和20耳)及年龄3月至4月龄正常婴儿14名(28眼和28耳)检测,确定同步程序ABR正常值及其与常规程序ABR的差异后,检测同步程序中(1)闪光刺激信号施加前后,ABR变化特点;(2)不同强度声刺激信号下视觉诱发电位(FVEP)变化特点。
结果:(1)同步程序(不管是加用FVEP与否)与常规程序ABR比较,虽然潜伏期不同,仍具有其独自的稳定特性:同步程序ABR各波潜伏期比常规程序ABR延长,但波间期无改变;且此种特性并不受是否加用FVEP的影响。(2)应用视听同步诱发电位程序,在较强声刺激信号条件下(70 dB nHL)同时给予光刺激信号, ABR各波潜伏期和波间期的参量变化显示其Ⅲ-Ⅴ波间期有显著性差异;而在声刺激信号50 dB nHL以下,则不能引起潜伏期的显著性变化(p>0.05)。(3)听觉刺激对闪频视觉诱发电位(FVEP)的影响:测试结果表明,不同强度的声刺激对FVEP的N1、P1、和N2波潜伏期,N1-P1和P1-N2峰值均未产生显著性作用(p值均大于0.05)。采用高、中、低三种不同声刺激强度均不能改变VEP的各波潜伏期及波幅。
结论:视觉诱发电位参数的稳定性显示出视觉诱发电位耦合电场的稳定性。然而,听性脑干反应(ABR)在同步程序不同声刺激条件下,其反应参量却表现出规律性的变化。这一结果提示在视听信号整合输入过程中,视听信号进入大脑是有序性:存在视觉信号对听觉信号的时间指导性(影响潜伏期),以期达到信息内环境的稳定性。
第二部分新生儿视听同步筛查的临床模式
目的:探索新生儿听力、眼病同步筛查的可行性和临床模式;了解新生儿听力下降及新生儿眼病的发病情况。
方法:在母婴同室应用瞬态诱发耳声发射(transient otoacoustic emission,TEOAE),在NICU采用两阶段筛查技术进行新生儿听力筛查,即应用TEOAE和自动听性脑干诱发电位测试(automatic auditory brainstem response,AABR)两种筛查技术进行筛查;同步进行新生儿眼病筛查。听力复筛与部分眼病复筛同步进行。听力复筛未通过者,生后3个月进入诊断程序:①听力学评估:声导抗、ABR、40 Hz听性相关电位(40Hz auditory event related potential,40Hz-AERP)、行为测听(6个月龄以后进行);②医学评估,影像学评估,并进行跟踪随访和定期的听力学评估、眼科学评估;视力筛查疑似病例及时转诊到专业眼科进一步确诊。正常新生儿进行眼部筛查性检查;NICU新生儿于出院前进行眼部筛查性检查与诊断性检查(视听同步诱发电位检查按要求进行),眼部筛查评估疑似病例及时转诊到专业眼科进一步确诊。
结果:自2002年10月1日至2005年4月30日在济南市妇幼保健院共出生16800例新生儿,对其中的15398(917.0‰)例新生儿进行了新生儿听力、眼病同步筛查,结果显示,新生儿听力损失在同步筛查儿中的发病率:双耳3.11‰(48/15398),单耳2.27‰(35/15398);有4例单耳或双耳先天性感音神经性聋伴发眼病:1例极重度感音神经性聋(双)、听神经病伴双眼先天性完全性白内障,1例轻度感音神经性聋(双)伴发左眼永存瞳孔膜,1例轻度感音神经性聋(双)伴双眼底静脉扩张,1例右耳轻度感音神经性聋伴双眼永存玻璃体动脉。在15398例统计取样的新生儿中,共检出先天性眼病和眼部体征12种1266例。
结论:新生儿期听力损失和眼病或眼部阳性体征在临床中并不少见。新生儿视听同步筛查在听力下降以及眼病监测和防治中是可行的,亦是有效的。实践新生儿视听同步筛查工作需要两个前提:较为完善的多学科合作机制,较强的小儿听力学和小儿眼科学临床工作。二者缺一不可。新生儿视听同步筛查应是儿童眼病/视力、听力同步监测的第一步,听力评估和眼部监测应在新生儿期就开始并持续在每一个儿童保健时期,评估手段应要与发育年龄相适宜。
第三部分新生儿眼病筛查的初步研究
目的:探索新生儿眼病筛查的临床策略、了解新生儿眼病的发病情况。
方法:对母婴同室新生儿在生后2-7天进行筛查性评估(光刺激反应、外眼检查、红光反射检查),异常者进行诊断性检查;新生儿重症监护病房(NICU)新生儿于生后5-14天进行筛查,并和高危因素新生儿实行眼部全面的筛查性和诊断性检查。对疑似病例及时转诊到专业眼科进一步确诊。
结果:15398例新生儿中,检出新生儿眼病12种,共1266例,检出率为82.22‰;其中先天性眼病7种,809例(52.54‰):包括先天性上睑下垂(0.13‰),先天性角膜浑浊(0.39‰),瞳孔残膜(47.02‰),先天性白内障15例(22只眼)(0.97‰),玻璃体动脉残存(3.51‰),先天性鼻泪管闭锁(0.46‰),泪腺脱垂(0.07‰);后天获得性眼病5种,457例(29.68‰):包括新生儿结膜炎(25.39‰),玻璃体出血(0.39‰),视网膜出血(2.21‰),新生儿泪囊炎(1.49‰),在27例1500克以下的未成熟儿中检出3例(6只眼)早产儿视网膜病变。正常新生儿14306例中,检出先天性眼病7种717例,检出率为50.12‰,后天获得性眼病4种417例(29.15‰)。NICU组1092例新生儿中,检出先天性眼病5种92例,检出率为84.25‰,后天获得性眼病5种40例(36.63‰)。NICU组先天性眼病与后天获得性眼病的检出率均高于正常新生儿组(P=0.000,P=0.016)。NICU组检出率高于正常新生儿组的眼病为:先天性白内障(P=0.000)、永存玻璃体动脉(P=0.000)和视网膜出血(P=0.001),低于正常新生儿组的为瞳孔残膜(P=0.01);
结论:新生儿的视力障碍并不少见,除ROP病例均发生在NICU组外,NICU病例还是先天性白内障、玻璃体动脉残存、视网膜出血的高发人群。早期干预对预防和治疗先天性白内障,早产儿视网膜病变等新生儿眼病是极其重要的。新生儿眼病筛查在眼病监测和防治中不仅是可行的而且是有效的。
第四部分新生儿听力损失程度波动特性及其影响因素
目的:探索新生儿听力损失随年龄、疾病转归后的波动情况,为降低听力损失的整体患病率和减缓其发展进程提供依据。
方法:新生儿听力筛查未“通过”的于3月龄常规进行声导抗、耳声发射、听性脑干诱发反应、40 Hz听性相关电位(40Hz-AERP)、行为测听(6个月龄以后进行),作出听力学诊断、医学评估并制定干预方案;对初诊异常和/或具有高危因素病例,约定每3月一次的听力学和医学复评估。
结果:通过对110例新生儿听力损失病例6月-48月(17.6±3.2月)长期门诊随访及多次的听力学再评估发现,新生儿听力损失程度尽管存在好转和加重两种趋势,但仍以无变化为主(58.2%),听力损失程度改善率(29.1%)高于加重发生率(12.7%)。婴幼儿轻度和中度听力损失是较容易发生听力损失程度变化的病例,轻度、中度、重度和极重度组中,分别有79.2%、72.7%、53.3%、3.6%的病例听力程度发生了改变;传导性及感音神经性听力损失中分别有78.4%(40/51)、39.0%(23/59)的病例发生了改变(p=0.000),传导性听力损失病例的损失程度变化发生率是感音神经性听力损失的2倍。单耳及双耳听力损失中分别有55.5%(25/45)、64.6%(42/65)的病例发生了改变(p=0.448),单耳及双耳病例的听力损失程度波动发生率差异无显著性。ABR听力阈值减少(“听力”改善)的64耳中,6.3%, 28.1%, 65.6%的病例分别减少30, 20, 10 dB nHL ,79.7%耳与中耳功能改善有关;听力损失加重28耳中,75%, 21.4%, 3.6%的病例分别增大10, 20, 40 dB nHL,50%与中耳功能变化有关。
结论:婴幼儿听力损失波动在临床并不少见的,并且存在可复性和渐进性两种变化趋势,中耳功能和新生儿疾病与婴幼儿听力损失程度波动关系密切;无论是单耳或者双耳听力损失,轻度、中度听力损失皆是处于向两极转变的交界状态,也是患进行性(双和单耳)听力损失的危险状态,要加强动态监测与防治。
第五部分山东省七城市新生儿单、双耳听力损失高危因素的病例对照研究
目的:探讨单、双侧新生儿听力损失高危因素,为预防新生儿听力损失的发生和减缓其发展进程提供依据。
方法:选定山东省7市地的7个筛查中心进行多中心研究,对所有新生儿听力筛查未通过病例转诊至济南市新生儿听力筛查诊断康复中心,对确诊病例进行基本特征的统计描述,采用1:1配对病例对照研究方法,进行单因素及多元条件Logistic逐步回归分析与新生儿单、双耳听力损失有关的高危因素。选择331例(双耳177例、单耳154例)完全符合配比要求的病例为研究对象。
结果:1、新生儿双耳听力损失病例:单因素分析,发现与新生儿听力损失有关的高危因素有11个:父亲年龄、父亲文化程度、母亲文化程度、产次、出生体重、孕周、颅面畸形、NICU监护史、新生儿疾病、耳病家族史、先天性听力损失家族史;条件Logistic回归分析显示新生儿双耳听力损失有4个独立危险因素:产次( OR=16.285 , 95% CI 3.379-78.481 )、新生儿疾病( OR=34.968 , 95% CI 2.720-449.534)、先天性听力损失家族史(OR=69.488,95% CI 4.417-1093.300)、出生体重(OR=0.241,95% CI 0.090-0.648);前3个为促进因素,后1个为保护因素。2、新生儿单耳听力损失:单因素分析,发现与新生儿单耳听力损失有关的高危因素有8个:父亲职业、母亲文化程度、母亲职业、产次、颅面畸形、NICU监护史、新生儿疾病、耳病家族史;条件Logistic回归分析显示单耳新生儿听力损失有2个独立危险因素:产次(OR=9.789,95% CI 2.270-42.173)、耳病家族史产次(OR=4.234,95% CI 1.179-15.203),皆为促进因素。
结论:经过山东省多中心新生儿听力损失的病例对照研究,产次、新生儿疾病、先天性听力损失家族史是双耳新生儿听力损失的促进因素,出生体重的增加是保护因素;产次和耳病家族史是单耳新生儿听力损失的促进因素,应对其采取适当干预措施。研究特点和创新之处:
本研究超越新生儿听力筛查,基于临床工作的背景和实验技术的可行性,进行以婴幼儿听力科学为基础的,实现多学科交叉的新生儿/婴幼儿视听功能同步监测及视听功能整合的研究。
本文在国际上率先提出“实施新生儿视听功能同步筛查”这一新的公共卫生项目;它为“聋儿和听力损失儿童眼部障碍”的学术分支及“听力科学和视觉科学/听觉-视觉缺失”的临床研究带来较大的发展空间和机遇。该模式的研究国内外还未见报道,新生儿眼病听力同步筛查模式具有广泛的学术内涵和潜在的市场需求;一旦推广普及,将为全社会带来巨大社会效益和经济效益。
同时,在国际上率先开展规范化、群体化新生儿眼病筛查与防治系列工作。使眼病在新生儿期得以及时诊治,避免了新生儿视力丧失。
国内显示出的具有示范意义的是:1、在我国妇幼保健系统建立儿童耳-听力和眼-视力的保健机制和模式,使我国新生儿听力筛查和眼病筛查有机结合,相互交融,更加健康有序地向前发展;2、获取我国相关领域的第一手较为完整的资料。为儿童眼病、听力损失的三级预防措施提供依据;3、在国内率先进行多中心新生儿听力损失高危因素的研究,不但确定新生儿双耳听力损失的高危因素,还在国内首次明确了新生儿单耳听力损失的高危因素,并提出干预措施。4、应用视听同步诱发电位研究,在国内首次提出在视听信号整合输入过程中,视听信号进入大脑的有序性:存在视觉信号对听觉信号的时间指导性(影响潜伏期),以期达到信息内环境的稳定性。5、在国内率先提出无论是单耳或者双耳听力损失,轻度、中度听力损失皆是处于向两极转变的交界动态,也是患进行性(双和单耳)HL的危险状态,要加强动态监测与防治。
以上所述,将先进的听力学测试、评估及康复技术与儿童听力保健的学科范畴相融合,构建了小儿听力保健的技术规范和科学评估体系。不仅弥补了我国综合医院和专科医院耳和眼专科的工作平台,亦发展了它们的某些临床功能;它必将对我国未来儿童保健学科、小儿耳鼻咽喉科学和小儿眼科学的发展带来较大的发展空间和机遇;同时也为“听力-视力科学”与“小儿感知觉发育科学”这一新兴学科的发展开辟了广阔的发展空间;为降低听力损失和视力障碍的整体患病率和减缓其发展进程提供依据;也将对未来听觉和视觉康复的临床具有指导作用。
Both anatomically and physiologically, hearing and vision are closely related. The brain, by temporally and spatially integrating the senses of hearing and sight and other senses, maintains the continuity of cognition and behaviors, and anatomically and functionally balance and coordinate separate cerebral activities. Clinically, visual and auditory disorders are commonly seen in many diseases and syndromes and deaf children tend to have visual problems as compared with normal kids. Hearing loss and visual impairments are two important causes of developmental disabilities among infants. Hearing and ocular conditions, if undetected or untreated, can have substantial long-term implications for the quality of life of the child and the family and can be a burden on public health resources. According to an estimate of WHO, 1.5 million children worldwide are blind. Two-third of these cases (1.0 million) is in developing countries. In developing countries, 30% to 72% of childhood blindness is avoidable. Children with severe and profound hearing loss account for 1/800 of all newborns. At the mean time, deaf children are heavily reliant on the sense of vision to develop efficient communication skills and explore the world around them. Any ophthalmic disorder may thus negatively impact on this process, especially if it is not identified in the early years of their life. These disorders may be correctable (such as myopia) or curable (such as cataract), and their early identification is of the utmost importance for their development of their language (spoken or sign, or both) and social cognition.
The close relations (anatomical, physiological and clinical) between hearing and vision make it a necessity to study their functional interactions and integration. The vision and hearing processes and their integration, however, are complicated. The The vision and hearing functions can, to some degree, be temporally and spatially integrated. Some studies examined and explained the mechanism of spatial integration, but the temporal integration of auditory and visual information in brain has not been clearly elucidated.
This study, by employing the technique of synchronous auditory and visual evoked potential, examined the neuro-biological features of integration of visual and auditory senses. Meanwhile, going beyond the newborn hearing screening, a multi-discipline study on the basis of newborn audiology was conducted and a new public health program---Newborn Simultaneous Vision and Hearing Screening---was put forward. The study also examined the change in hearing loss over time among newborns and infants and the high risk factors of hearing loss in Shandong Province. The combination of vision and hearing screening in newborns will greatly contribute to the control of newborn hearing loss (NHL) in China.
PartⅠA Preliminary Study on Integration Mechanism of Auditory and Visual Neural Function by Using Synchronous Auditory and Visual Evoked Potential
Objective: To explore the electrophysiological properties of integration of auditory-visual neural functions by using the technique of synchronous auditory and visual evoked potential.
Methods: By using technique of synchronous auditory and visual evoked potential and routine auditory brain-stem response (ABR) technique, 10 normal adult subjects (20 eyes and 20 ears) and 14 infants (aged from 3 to 4 month, 28 eyes and 28 ears) were studied. First, the different properties of auditory brainstem response (ABR) in auditory -visual synchronous program and non-synchronous program were explored.
Then, under the program of auditory -visual synchronous evoked potential , unimodal (A or V) and simultaneous bimodal (A-V) stimuli were presented and we detected two aspects :( (1) the ABR changes in the synchronous procedures before and after the presentation of flash stimuli and (2) the features in flash visual evoked potential (fVEP) were examined. Results: (1) As compared with routine ABR, the synchronous procedure (with or without fVEP test) were stable. Though the latencies of ABR waves of synchronous procedure were longer than those of routine one, no changes was found between interwaves. This feature was not influenced by the addition of fVEP test. (2) With synchronous procedure, under 70 dB nHL click stimulation, when light stimuli were given, significant differences in the interwave latencies betweenⅢ-Ⅴof ABR were observed, while, the click stimuli under 30, 50 dB nHL did not cause any significant change in wave latencies and interwave latencies (P<0.05). (3) In terms of effect of sound stimuli on the fVEP, our study showed that sound stimuli of different intensities did not significantly affect the latencies of N1, P1 and N2 waves of fVEP and N1-P1 and P1-N2 amplitude (P>0.05). The sound stimuli of high, medium and low intensities did not change the length of latencies and amplitude of fVEP. Conclusion The stability of the parameters of visual evoked potential reflects the stability of electric field of the visual evoked potential. Under sound stimuli of different intensities, the changes of ABR parameters showed some patterns. Our results suggest that in the integration of visual and auditory inputs, the auditory and visual signals enter the brain in an orderly manner. There exists a temporal guidance of auditory signals by visual signals (which affects latencies), thereby maintain the homeostasis of internal milieu in terms of information processing.
PartⅡClinical Application of Simultaneous Screening for Hearing and Ocular Diseases in Newborns
Objective: In this part, we explored the feasibility of simultaneous screening for hearing and ocular diseases in newborns and its clinical application, examined the hearing impairment and eye diseases in newborns
Methods: The universal newborn hearing screening (UNHS) was performed by using transient otoacoustic emission (TEOAE) in a baby-friendly nursery, and a two-stage screening protocol (including TEOAE stage and AABR [auto auditory brainstem response] stage) was carried out in a neonatal intensive care unit (NICU). At the same time, an eye disease screening was conducted. The re-screenings for hearing diseases and eye diseases were conducted simultaneously. If a newborn failed to pass the hearing re-screening test, with in 3 months after birth, she or he will be put on a diagnostic procedure, which included: (1) TEOAE, acoustic immitance, ABR, 40 Hz auditory event related potential (40 Hz AERP), behavioral audiometry ; (2) medical and imagological evaluations, follow-up and regular audiological and ophthalmological evaluations. If suspected cases of eye diseases were referred to pediatric ophthalmologists for definite diagnosis. The normal newborns were subjected to re-screening for eye-disease. The newborns who had received treatment in NICU were examined for screening and diagnostic purposes before being discharged (technique of synchronous auditory and visual evoked potential was conducted as required). And the cases that had positive sign and/or abnormal result of the ocular disease screening were referred for further examination by pediatric ophthalmologists.
Results: A total of 16800 children were born in Jinan Maternal and Child Hospital from October 1, 2002 to April 30, 2005. Of these infants, 15398 cases (916.0‰) were subjected to simultaneous screening for hearing and eye diseases. Our results showed that the incidence of bilateral congenital sensorineural hearing loss (SNHL) among infants who received UNHS was 3.11‰(48/15398), and the incidence of unilateral SNHL was 2.27‰(35/15398). Among them, 4 cases of congenital SNHL were complicated with newborn eye diseases: including 1 case of profound SNHL (bilateral) and auditory neuropathy accompanied by congenital cataract (bilateral), 1 case of mild SNHL (bilateral) complicated with membrana pupillaris perseverans (left), 1 case of mild SNHL (bilateral) with retina vein dilatation (bilateral), and 1 case of mild SNHL (right) with accompanying bilateral persistent hyaloid artery. In all the 15398 newborns, 12 eye-related diseases and signs were detected (involving 1266 cases).
Conclusion The hearing loss and ocular diseases/visual impairment is not uncommon in neonatal time and infancy. The simultaneous screening for newborn hearing and ocular diseases is not only feasible but also effective in the control of hearing loss and/or ocular disorders. Implementation of simultaneous screening for newborn hearing and ocular diseases entails (1) a well-established mechanisms of multli-discipline co-operation and (2) intensive work in neonate audiology and ophthalmology in clinical practice. The newborn screening for visual and auditory disease is the first step towards the simultaneous monitoring of eye disease, vision and hearing; hearing evaluation and eye disease monitoring should start at neonate stage and continue at every single stage of child health care and the means of evaluation should be in line with the age of juvenile development.
PartⅢA Preliminary Study of Screening for Neonatal Ocular Diseases Objective: To explore the clinical strategies for the screening of newborn eye diseases and get information concerning the incidence of newborn ocular diseases
Methods: The newborns in a baby-friendly nursery were evaluated for screening 2 to 7 days after birth (including reaction to light sitimuli, external ocular examination and test for red reflex) and those with abnormalities were subjected to diagnostic examination. The newborns in NICU were subjected to screening 5 to 14 days after birth and they, together with those with high risk factors, received a comprehensive examination for screening and diagnostic purpose. The suspected cases were referred to department of ophthalmology for definite diagnosis.
Results: Among the 15398 (916.0‰) who were enrolled the screening program, 12 kinds of eye diseases (involving 1266 cases) were detected, with a detection rate of 82.22%. Of these eye diseases, 7 were congenital ocular diseases, involving 809 cases (52.54‰) and including congenital ptosis (0.13‰), congenital corneal opacity (0.39‰), persistent pupillary membrane (47.02‰), congenital cataract (15 cases, 22 eyes involved, accounting for 0.97‰), persistent hyaloid artery (3.51‰), obstruction of nasolacrimal duct (0.46‰), lacrimal gland prolapse (0.07‰). Five diseases (involving 457 cases) detected were acquired ones, including neonatal conjunctivitis (25.39‰), vitreous haemorrhage (0.39‰), retinal haemorrhage (2.12‰), and neonatal dacryocystitis (1.49‰). Of 27 premature babies with body weight lower than 1500 g, 3 had retinopathy of prematurity (ROP, 6 eyes involed). Of 14306 normal newborns, 7 kinds of congenital diseases were detected in 717 cases, with a detection rate of 50.12‰and 4 kinds of acquired diseases were found in 417 cases with a detection rate of (29.15‰). In 1092 newborns who had received treatment in NICU, 5 kinds of congenital diseases were found in 92 cases, with the detection rate being 84.25‰and 5 kinds of acquired eye diseases were found in 40 cases, with a detection rate of (36.63‰). The detection rate of both the congenital and acquired diseases in the NICU group were higher than those in the group of normal newborns (P=0.000; P=0.016). The eye diseases whose detection rates in NICU group were higher than those of normal newborn group included congenital cataract (P=0.000), persistent hyaloid artery (P=0.000) and retinal hemorrhage (P=0.001). The detection rate of persistent pupillary membrane in the NICU group was lower than that in normal children group (P=0.01).
Conclusion: The visual disorders were not uncommon in newborns and except for ROP that were all found in NICU group, the incidences of congenital cataract, persistent hyaloid artery, retinal hemorrhage were also high in the group. Early intervention is of great importance for the prevention and treatment of neonatal ocular diseases such as congenital cataract and ROP. The screening of newborn ocular diseases is not only feasible but also effective in the monitoring and control of the eye diseases in neonates.
PartⅣChange of the Severity of Newborn/Infant Hearing Loss and Influencing Factors
Objective: To examine the change in hearing impairment level over time (ages) and after progression of diseases in order to get information for reducing the overall morbidity and slowing the progression of hearing loss.
Methods: The newborns who failed to“pass”the hearing screening were routinely examined, with in the age of 3, by TEOAE, acoustic immitance, otoacoustic emission, ABR, 40 Hz auditory event related potential (40 Hz AERP), behavioral audiometry for audiological diagnosis and medical evaluation, and intervention plans were laid. For those with abnormalities identified and/or with high risk factors, a once-every-3-month audiological and medical evaluation was performed.
Results: A long-term (6-48 months, 17.6±3.2 months) out-patient follow-up and repeated audiological evaluations in 110 newborns with hearing impairment showed that thought the hearing impairment in newborns might improve or deteriorate over time, in most of the cases (58.2%), their conditions remained unchanged, with the improvement rate of hearing impairment (29.1%) being higher than the deterioration rate (12.7%). The cases of mild and moderate hearing loss tended to experience changes. In groups of mild, moderate, severe and profound hearing loss, 79.2% (38/48), 72.7% (16/22), 53.3% (8/15) and 3.6%(1/28)79.2%, respectively, showed changes in hearing level ; in the group of conductive hearing loss and group of sensorineural hearing loss, 78.4% (40/51) and 39.0% (23/59) had change in hearing impairment level (p=0.000), and the change rate in the conductive hearing loss group was 2 times that in sensorineural hearing loss group. The hearing level changed in 55.5% (24/45) of the cases of unilateral hearing loss group and in 64.6 % ( 42/65) of the cases of bilateral hearing loss (P=0.448). No significant difference was found in the change rate between the groups of unilateral and bilateral hearing loss. With 64 ears with decreased ABR threshold (with hearing improvement), 6.3%, 28.1%, 65.6% of them had reduction by 30, 20, 10 dB nHL respectively. In 79.7% of the ears, the function of middle ear was improved. In 28 ears with hearing deterioration, 75%, 21.4%, 3.6% of them the ABR threshold increased by 10, 20, 40 dB nHL respectively and in 50% of the ears, the deterioration concerns the functions of middle ear.
Conclusion: The change of hearing level in children with hearing loss was not uncommon in clinical practice and the change is both gradual and reversible. The functions of middle ear and neonatal diseases bear close relation with the change of hearing level in children with hearing loss. With either unilateral or bilateral hearing loss, the mild and moderate hearing loss is a border-line state which could develop toward improvement or deterioration, i.e., having high risk of developing progressive hearing loss (unilateral or bilateral), which requires dynamic monitoring and long-term preventive and therapeutic effort.
PartⅤA Case-control Study on High-risk Factors for Newborn Hearing Loss in Seven Cities of Shandong Province
Objective: To investigate the high-risk factors for newborn unilateral or bilateral hearing loss and to provide information for preventing the development of hearing loss and delaying its progression.
Methods: In 7 screening centers selected from 7 districts, a multi-center study was conducted. All the neonates who failed to pass the universal newborn hearing screening (UNHS) were referred to Jinan Newborn Hearing Screening and Rehabilitation Center. The basic features of the definitely diagnosed cases were statistically described and one-to-one pair-matched case-control method was employed. High-risk factors relating to the unilateral or bilateral hearing loss were evaluated by univariate and multivariate Logistic regression analysis. 331 cases (including 177 bilateral hearing loss cases and 154 unilateral hearing loss cases) who fully satisfied the matching requirements were included as subjects
Results: (1) With newborns with bilateral hearing loss, univariate Logistic regression identified 11 hearing loss-related risk factors: age of father, educational level of father, educational level of mother, parity, birth weight, genstation weeks, craniofacial anomalies, history of NICU care, neonatal diseases, family history of ear diseases, and family history of congenital hearing loss. Conditional Logistic regression analysis showed that neonatal bilateral hearing loss had 4 independent risk factors: parity (OR=16.285, 95% CI 3.379—78.481), neonatal diseases (OR=34.968,95% CI 2.720—449.534), family history of congenital hearing loss (OR=69.488,95% CI 4.417—1093.300) and birth weight (OR=0.241, 95% CI 0.090—0.648). The former 3 factors are promoting factors and the last one is protective factor. (2) With newborns with unilateral hearing loss, univariate Logistic regression found 8 hearing loss-related risk factors: profession of father, educational level of mother, profession of mother, parity, craniofacial anomalies, history of NICU care, neonatal diseases, family history of ear diseases. Conditional Logistic regression analysis revealed that neonatal unilateral hearing loss had 2 independent risk factors: parity (OR=9.789, 95% CI 2.270—42.173) and history of congenital hearing loss (OR=4.234, 95% CI 1.179—15.203) and they are all promoting factors.
Conclusion: The multi-center case-controlled study of neonatal hearing loss in Shandong province showed that parity, neonatal disease, congenital hearing loss are promoting factors for bilateral hearing loss in newborns, the birth weight is a protective factor. The parity and family history of ear diseases are promoting factors of unilateral hearing loss and intervening measures should be taken with these cases.
Characteristics and Innovations in the Study
The study, for the first time, put forward a new public health care program, i.e., the“simultaneous screening of vision and hearing in neonates”. It broadens the horizon of and brings opportunities for the clinical study on the branch of“ocular disorders in children with deafness and hearing loss”and the“audiovisual science/hearing loss-visual impairment”. The simultaneous screening of vision and hearing has profound academic implications and potential market demand and its extensive application will bring immense social and economic benefits.
The implementation of standardized, large-population eye disease screening and control program in newborns will lead to timely treatment of the disease at neonatal stage thereby preventing sight loss in newborns.
Domestically, the study is of great importance in that (1) establishment of ear-hearing and eye-vision health care system for children will help to integrate the hearing disease screening and eye disease screening thereby promoting their healthy development; (2) successful collection of first-hand and complete data in relevant fields can provide information of the three-tier prevention program for juvenile eye diseases and hearing loss; (3) the first-time multi-center study about the risk factors of hearing loss not only identified the high-risk factors of bilateral hearing loss but also, for the first time in China, identified the high-risk factors of unilateral hearing loss, with intervening measures proposed; (4) by employing the technique of simultaneous visual and auditory evoked potentials, the study, for the first time, suggests that the visual and auditory signals enter brain in an orderly manner and the visual signals can provide temporal guidance for auditory signal (affecting latency), thereby achieving the homeostasis of internal environment in terms of information handling; (5) the study for the first time, points out that with either unilateral or bilateral hearing loss, the mild and moderate hearing loss is a border-line state which may develop towards recovery or deterioration, i.e., a dangerous state of developing unilateral or bilateral hearing loss that requires dynamic monitoring, preventive and therapeutic measures.
To sum up, in this study, by combining advanced audiological tests, evaluation and rehabilitation techniques, hearing-care sciences, a standardized and scientific evaluation system was established. It provides information for reducing hearing loss and visual disorders and slowing their progression. It also provides clinical guidance for the future work of hearing and vision rehabilitation.
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2.张微,戚以胜.,韩德民,等.同步诱发电位在新生儿视听功能检查中的初步研究.中华医学杂志,2003,83(16).1394-1398.
3.聂文英,宫露霞,刘玉俊,等.10501例新生儿听力筛查结果.中华医学杂志,2003,83(4).274-7.
4. American Academy of Pediatrics. Eye examination in infants, children, and young adults by pediatricians. Pediatrics, 2003,111:902-7.
5. Uus K, Bamford J. Effectiveness of population-based newborn hearing screening in England: ages of interventions and profile of cases. Pediatrics, 2006, 117(5):e887-93.
6. Kile JE. Identification of hearing impairment in children :A 25-year review .Infant- Toddler Intervention, 1993,3:155.
7. Joint Committee on Infant Hearing. Year 2000 position statement: principles andguidelines for early hearing detection and intervention programs. Pediatrics, 2000,106(4):798-817.
8. Ari-Even Roth D, Hildesheimer M, Maayan-Metzger A,et al. Low prevalence of hearing impairment among very low birthweight infants as detected by universal neonatal hearing screening.Arch Dis Child Fetal Neonatal Ed,2006 ,91(4):F257-62.
9. Norris VW, Arnos KS, Hanks WD, et al. Does universal newborn hearing screening identify all children with GJB2 (Connexin 26) deafness? Penetrance of GJB2 deafness. Ear Hear,2006;27(6):732-41.
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1. Joint Committee on Infant Hearing. Year 2000 Position Statement :Principles and Guideline for Early Hearing Detection and Intervention Programs.
2. Berg AL,Spitzer JB, Towers HM,et al. Newborn hearing screening in the NICU: profile of failed auditory brainstem response/passed otoacoustic emission. Pediatrics. 2006,117:997.
3. Uus K,Bamford J. Effectiveness of population-based newborn hearing screening in England: ages of interventions and profile of cases. Pediatrics.2006,117:e887-93.
4. Kile JE. Identification of hearing impairment in children :A 25-year review .Infant- Toddler Intervention, 1993,3:155.
5. Rovet J , Walker W, Bliss B, et al .Long-team hearing impairment in congenital hypothyroidism.J Pediatr1996, 128:776.
6. Ari-Even Roth D, Hildesheimer M, Maayan-Metzger A,et al. Low prevalence of hearing impairment among very low birthweight infants as detected by universal neonatal hearing screening.Arch Dis Child Fetal Neonatal Ed.2006 ;91:F257-62.
7. Iwasaki S, Yamashita M, Maeda M, et al. Audiological Outcome of Infants with Congenital Cytomegalovirus Infection in a Prospective Study. Audiol Neurootol. 2006;12:31-36 .
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9. Weichbold V, Nekahm-Heis D, Welzl-Mueller K, et al.Universal newborn hearing screening and postnatal hearing loss. Pediatrics. 2006 ;117:e631-6.
10. Norris VW, Arnos KS, Hanks WD, et al. Does universal newborn hearing screeningidentify all children with GJB2 (Connexin 26) deafness? Penetrance of GJB2 deafness. Ear Hear.2006;27:732-41.
11. Ravecca F,Berrettini S,Forli F, et al. Cx26 gene mutations in idiopathic progressive hearing loss. J Otolaryngol. 2005;34:126-34.
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2. Steinkuller PG, Du L, Gilbert C, et al. Childhood blindness. J AAPOS,1999,3:26-32.
3. Ottar-Pfeifer W. When should children have their eyes checked? Insight, 2005, 30(2): 17-20.
4. American Academy of Pediatrics. Eye examination in infants, children, and young adults by pediatricians. Pediatrics, 2003, 111:902-7.
5. L Haines, A R Fielder, H Bake1 et al. UK population based study of severe retinopathy of prematurity: screening, treatment, and outcome. Arch Dis Child Fetal Neonatal Ed. 2005, 90(3):F240-4.
6. American Academy of Pediatrics. Red Reflex Examination in Infants. Pediatrics, 2002,109:980-981.
7. Ogut MS, Bozkurt N, Ozek E, et al. Effects and side effects of mydriatic eyedrops in neonates. Eur J Ophthalmol, 1996, 6(2):192-6.
8.张微,戚以胜,韩得民,等.同步诱发电位在新生儿视听功能检查中的初步研究.中华医学杂志,2003,83:1394-1398.
9.李建军.青光眼筛查的意义及方法评价.国外医学眼科分册,2003, 27:265-269.
10. Joint Committee on Infant Hearing, American Academy of Audiology, American Academy of Pediatrics, et al. Year 2000 position statement: principles and guidelines for early hearing detection and intervention programs. Joint Committee on Infant Hearing, American Academy of Audiology, American Academy of Pediatrics, American Speech-Language-Hearing Association, and Directors of Speech and Hearing Programs in State Health and Welfare Agencies. Pediatrics, 2000, 106(4): 798-817.
11. Castanes MS. Major review: The underutilization of vision screening (for amblyopia,optical anomalies and strabismus) among preschool age children. Binocul Vis Strabismus Q, 2003, 18(4): 217-32.
12. Williams C, Northstone K, Harrad RA, et al. Amblyopia treatment outcomes after screening before or at age 3 years: follow up from randomised trial. BMJ, 2002, 324(7353):1549.
13. Committee on Practice and Ambulatory Medicine and Section on Ophthalmology, American Academy of Pediatrics. Use of photoscreening for children's vision screening. Pediatrics, 2002, 109(3): 524-5.
14. American Academy of Pediatrics, Section on Ophthalmology. Proposed vision screening guidelines. AAP News, 1995, 11: 25.
15. American Academy of Pediatrics, Committee on Practice and Ambulatory Medicine. Recommendations for preventive pediatric health care. Pediatrics, 1995, 96:373–374.
16. Wasserman RC, Croft CA, Brotherton SE. Preschool vision screening in pediatric practice: a study from the Pediatric Research in Office Settings (PROS) Network. Pediatrics, 1992, 89 : 834–838.
17. Simons K. Preschool vision screening: rationale, methodology and outcome. Surv Ophthalmol, 1996, 41: 3–30.
18. American Academy of Ophthalmology. Amblyopia: Preferred Practice Pattern. San Francisco, CA: American Academy of Ophthalmology; 1997.
19. Hartmann EE, Dobson V, Hainline L, et al. Preschool vision screening: summary of a task force report. Pediatrics, 2000, 106: 1105–1116.
20. Ottar WI, Scott WE, Holgado SI. Photoscreening for amblyogenic factors. J Pediatr Ophthalmol Strabismus, 1995, 32: 289–295.
21. American Academy of Pediatrics, Committee on Practice and Ambulatory Medicine and Section on Ophthalmology. Use of photoscreening for children’s vision screening. Pediatrics, 2002, 109: 524–525.
22. American Academy of Pediatrics, Committee on Practice and Ambulatory Medicineand Section on Ophthalmology. Eye examination and vision screening in infants, children, and young adults. Pediatrics, 1996; 98: 153–157.
23. Van Velzen-Mol HW, Blankespoor MN, Wagenaar-Fischer MM, et al. The guideline 'Detection of visual disorders at the age of 0-19' from the Dutch Association of Child Health Care. Ned Tijdschr Geneeskd, 2003, 147(41): 2012-7.
24. Sansonetti A, Perisset J, Reinhardt M; Groupe Romand d'Etudes en Pediatrie Ambulatoire (GREPA). Screening of vision disorders in young children. Rev Med Suisse Romande, 2004, 124(8):514-6.
25. Enzenauer RW, Freedman HL, Larson MR, et al. Photoscreening for amblyogenic factors by public health personnel: the Eyecor Camera System. Ophthalmic Epidemiol, 2000, 7: 1–12.
26. Granet DB, Hoover A, Smith AR, et al. A new objective digital computerized vision screening system. J Pediatr Ophthalmol Strabismus, 1999, 36: 251–256.
27. Atkinson J, Braddick O, Robier B, et al. Two infant vision screening programmes: prediction and prevention of strabismus and amblyopia from photo- and videorefractive screening. Eye, 1996, 10: 189–198.
28. Committee on Practice and Ambulatory Medicine Section on Ophthalmology, American Association of Certified Orthoptists, American Association for Pediatric Ophthalmology and Strabismus,et al. Eye examination in infants, children, and young adults by pediatricians: organizational principles to guide and define the child health care system and/or improve the health of all children. Ophthalmology, 2003, 110(4): 860-5.
29. Bhatti TR, Dott M, Yoon PW, et al. Descriptive epidemiology of infantile cataracts in metropolitan Atlanta, GA, 1968-1998. Arch Pediatr Adolesc Med, 2003, 157(4): 341-7.
30. Lang DM, Blackledge J, Arnold RW. Is pacific race a retinopathy of prematurity risk factor?. Arch Pediatr Adolesc Med, 2005, 159 :771-3.
31. Di Bartolomeo S, Higa M, Janer M, et al. Neonatal conjunctivitis in a hospital at GranBuenos Aires. Last 5 years up-date. Rev Argent Microbiol, 2005, 37(3): 139-41.
32. Assadian O, Assadian A, Aspock C, et al. Prophylaxis of ophthalmia neonatorum-a nationwide survey of the current practice of Austria. Wien Klin Wochenschr, 2002, 114(5-6): 194-9.
33.黄洪强,陈保安,廖飞,等.新生儿结膜炎病员菌分析.邯郸医学高等专科学校学报,2005,18(1):41.
34. Chang K, Cheng VY, Kwong NS. Neonatal heamorrhagic conjunctivitis: a specific sigh of chlamydial infection. Hong Kong Med, 2006,12(3): 247.
35. Noda S, Hayasaka S, Setogawa T. Congenital nasolacrimal duct obstruction in Japanese infants: its incidence and treatment with massage. J Pediatr Ophthalmol Strabismus, 1991,28(1):20-2.
36.郑红雁,宋天勤.先天性鼻泪管阻塞的治疗.中国斜视和小儿眼科杂志, 2004, 12(4):180.
37.戚以胜,宫露霞.新生儿普遍听力筛查的网络建设,中华医学杂志, 2004, 84 :443.
38.闫洪禄,高建鲁.小儿眼科学.第1版.北京:人民卫生出版社, 2002:712-721.
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1. Centers for Disease Control and Prevention (CDC). Visual Impairment and Use of Eye-Care Services and Protective Eyewear Among Children—United States, 2002. MMWR Morb Mortal Wkly Rep,2005, 54(17): 425-9.
2. Steinkuller PG, Du L, Gilbert C, et al. Childhood blindness. J AAPOS,1999,3:26-32.
3. Ottar-Pfeifer W. When should children have their eyes checked? Insight, 2005, 30(2):17-20.
4. American Academy of Pediatrics. Eye examination in infants, children, and young adults by pediatricians. Pediatrics, 2003,111:902-7.
5. L Haines, A R Fielder, H Bake1, et al. UK population based study of severe retinopathy of prematurity: screening, treatment, and outcome. Arch Dis Child Fetal Neonatal Ed, 2005 ,90(3):F240-4.
6. American Academy of Pediatrics. Red Reflex Examination in Infants. Pediatrics, 2002,109(5):980-981.
7. Ogut MS, Bozkurt N, Ozek E, et al. Effects and side effects of mydriatic eyedrops in neonates. Eur J Ophthalmol, 1996, 6(2):192-6.
8.张微,戚以胜,韩得民,等.同步诱发电位在新生儿视听功能检查中的初步研究.中华医学杂志,2003,83(16):1394-1398.
9.李建军.青光眼筛查的意义及方法评价.国外医学眼科分册,2003, 27(5):265-269.
10. Joint Committee on Infant Hearing, American Academy of Audiology, American Academy of Pediatrics, et al. Year 2000 position statement: principles and guidelines for early hearing detection and intervention programs. Joint Committee on Infant Hearing, American Academy of Audiology, American Academy of Pediatrics, American Speech-Language-Hearing Association, and Directors of Speech and Hearing Programs in State Health and Welfare Agencies. Pediatrics, 2000, 106(4): 798-817.
11. Castanes MS. Major review: The underutilization of vision screening (for amblyopia, optical anomalies and strabismus) among preschool age children. Binocul Vis Strabismus Q, 2003, 18(4): 217-32.
12. Williams C, Northstone K, Harrad RA, et al. Amblyopia treatment outcomes after screening before or at age 3 years: follow up from randomised trial. BMJ, 2002, 324(7353):1549.
13. Committee on Practice and Ambulatory Medicine and Section on Ophthalmology, American Academy of Pediatrics. Use of photoscreening for children's vision screening. Pediatrics, 2002, 109(3): 524-5.
14. American Academy of Pediatrics, Section on Ophthalmology. Proposed vision screening guidelines. AAP News, 1995, 11: 25.
15. American Academy of Pediatrics, Committee on Practice and Ambulatory Medicine.Recommendations for preventive pediatric health care. Pediatrics, 1995, 96:373–374.
16. Wasserman RC, Croft CA, Brotherton SE. Preschool vision screening in pediatric practice: a study from the Pediatric Research in Office Settings (PROS) Network. .Pediatrics, 1992, 89: 834–838.
17. Simons K. Preschool vision screening: rationale, methodology and outcome. Surv Ophthalmol, 1996, 41: 3–30.
18. American Academy of Ophthalmology. Amblyopia: Preferred Practice Pattern. San Francisco, CA: American Academy of Ophthalmology; 1997.
19. Hartmann EE, Dobson V, Hainline L, et al. Preschool vision screening: summary of a task force report. Pediatrics, 2000, 106: 1105–1116.
20. Ottar WI, Scott WE, Holgado SI. Photoscreening for amblyogenic factors. J Pediatr Ophthalmol Strabismus, 1995, 32: 289–295.
21. American Academy of Pediatrics, Committee on Practice and Ambulatory Medicine and Section on Ophthalmology. Use of photoscreening for children’s vision screening. Pediatrics, 2002, 109: 524–525.
22. American Academy of Pediatrics, Committee on Practice and Ambulatory Medicine and Section on Ophthalmology. Eye examination and vision screening in infants, children, and young adults. Pediatrics, 1996; 98: 153–157.
23. Van Velzen-Mol HW, Blankespoor MN, Wagenaar-Fischer MM, et al. The guideline 'Detection of visual disorders at the age of 0-19' from the Dutch Association of Child Health Care. Ned Tijdschr Geneeskd, 2003, 147(41): 2012-7.
24. Sansonetti A, Perisset J, Reinhardt M; Groupe Romand d'Etudes en Pediatrie Ambulatoire (GREPA). Screening of vision disorders in young children. Rev Med Suisse Romande, 2004, 124:514-6.
25. Enzenauer RW, Freedman HL, Larson MR, et al. Photoscreening for amblyogenic factors by public health personnel: the Eyecor Camera System. Ophthalmic Epidemiol, 2000, 7: 1–12.
26. Granet DB, Hoover A, Smith AR, et al. A new objective digital computerized vision screening system. J Pediatr Ophthalmol Strabismus, 1999, 36: 251–256.
27. Atkinson J, Braddick O, Robier B, et al. Two infant vision screening programmes: prediction and prevention of strabismus and amblyopia from photo- and videorefractive screening. Eye, 1996, 10: 189–198.
28. Committee on Practice and Ambulatory Medicine Section on Ophthalmology, American Association of Certified Orthoptists, American Association for Pediatric Ophthalmology and Strabismus,et al. Eye examination in infants, children, and young adults by pediatricians: organizational principles to guide and define the child health care system and/or improve the health of all children. Ophthalmology, 2003, 110(4): 860-5.
29. Bhatti TR, Dott M, Yoon PW, et al. Descriptive epidemiology of infantile cataracts in metropolitan Atlanta, GA, 1968-1998. Arch Pediatr Adolesc Med, 2003, 157(4): 341-7.
30. Lang DM, Blackledge J, Arnold RW. Is pacific race a retinopathy of prematurity risk factor?. Arch Pediatr Adolesc Med, 2005, 159 :771-3.
31. Di Bartolomeo S, Higa M, Janer M, et al. Neonatal conjunctivitis in a hospital at Gran Buenos Aires. Last 5 years up-date. Rev Argent Microbiol, 2005, 37: 139-41.
32. Assadian O, Assadian A, Aspock C, et al. Prophylaxis of ophthalmia neonatorum-a nationwide survey of the current practice of Austria. Wien Klin Wochenschr, 2002, 114: 194-9.
33.黄洪强,陈保安,廖飞,等.新生儿结膜炎病员菌分析.邯郸医学高等专科学校学报,2005,18(1):41.
34. Chang K, Cheng VY, Kwong NS. Neonatal heamorrhagic conjunctivitis: a specific sigh of chlamydial infection. Hong Kong Med, 2006, 12: 247.
35. Noda S, Hayasaka S, Setogawa T. Congenital nasolacrimal duct obstruction in Japanese infants: its incidence and treatment with massage. J Pediatr Ophthalmol Strabismus, 1991,28:20-2.
36.郑红雁,宋天勤.先天性鼻泪管阻塞的治疗.中国斜视和小儿眼科杂志, 2004, 12(4):180.
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