巨细胞病毒感染引起听力损害的相关因素分析

目的 探讨引起巨细胞病毒(CMV)感染患儿听力损害的相关因素分析。方法 依据脑干听觉诱发电位(BAEP)检测结果将158 例CMV 感染患儿分为听力正常组(n=117,BAEP ≤ 35)和听力异常组(n=41,BAEP>35)。收集两组患儿一般资料、血常规、肝功能、尿液及乳汁病毒拷贝数等进行回顾性分析;绘制受试者工作特征曲线(ROC)预测导致BAEP 异常的CMV-DNA 病毒载量;采用Spearman 秩相关分析对尿CMV-DNA拷贝数与听力损害程度、血小板计数间进行相关性分析。结果 听力异常组血小板异常率、肝功能异常率和尿CMV-DNA 拷贝数均高于听力正常组(P<0.01)。ROC 分析结果显示,当尿CMV-DNA 拷贝数为1.415×10⁶/mL时,预测病毒载量导致听力损伤的敏感性为46.3%,特异性为93.2%。相关性分析结果显示,听力损害的程度随着CMV-DNA 拷贝数的增加而增高(r=0.382,P<0.01);血小板计数和尿CMV-DNA 拷贝数之间存在负相关(r=-0.233,P=0.003)。结论 尿CMV-DNA 病毒载量可能与CMV 感染导致神经性听力障碍相关;当CMVDNA载量达到1.415×10⁶/mL 时,更易出现听力损害。存在血小板减少的CMV 感染患儿,应加强听力监测。     

新生儿高胆红素血症听觉诱发电位检测的临床意义

目的　 通过对新生儿高胆红素血症患儿进行脑干听觉诱发电位 (BAEP)检测 ,评估高胆红素血症在未发生核黄疸时对脑损害及听力的影响。 方法 　对新生儿高胆红素血症患儿入院后进行脑干听觉诱发电位的测定。 结果 　 49例高胆红素血症患儿中异常BAEP发生率为 3 7%( 18/ 49例 ) ,表现为各波潜伏期 (PL)及波间潜伏期 (IPL)的延长和听阈值的增高 ,听阈值随胆红素浓度的增高而增高 ,经治疗后黄疸消退 ,脑干听觉诱发电位大部分恢复正常。 结论 　高胆红素血症对新生儿可造成听力损害 ,BAEP是检测高胆红素血症患儿听力筛查的重要手段之一     

新生儿高胆红素血症听觉诱发电位检测的临床意义

目的 通过对新生儿高胆红素血症患儿进行胞干听觉诱发电位(BAEP)检测，评估高胆红素血症在未发生核黄疸时对脑损害及听力的影响。方法 对新生儿高胆红素血症患儿入院后进行脑干听觉诱发电位的测定。结果 49例高胆红素血症患儿中异常BAEP发生率为37％(18／49例)，表现为各波潜伏期(PL)及波间潜伏期(IPL)的延长和听阈值的增高，听阈值随胆红素浓度的增高而增高，经治疗后黄疸消退，脑干听觉诱发电位大部分恢复正常。结论 高胆红素血症对新生儿可造成听力损害，BAEP是检测高胆红素血症患儿听力筛查的重要手段之一。     

巨细胞病毒感染致婴儿听力受损的早期干预及随访

目的 观察婴儿期巨细胞病毒(CMV)感染后脑干听觉诱发电位(BAEP)的变化及对于早期以更昔洛韦为主综合治疗的患儿听力恢复情况.方法 选取45例听力异常的CMV感染婴儿,分析其脑干听觉诱发电位的特点,给予更昔洛韦抗病毒、营养脑细胞及听觉刺激法等早期综合干预方案,随访4 ～ 6个月,以观察治疗后听力恢复情况.结果 双耳出现异常35例(77.8%),单耳出现异常10例(22.2%);仅客观听阈轻度增高28例(62.2%),客观听阈轻度增高伴有波的异常改变5例(11.1%),仅客观听阈中重度增高1例(2.2%),客观听阈中重度增高伴有波的异常改变11例(24.5%),未发现有客观听阈正常而波有异常改变的病例.更昔洛韦等早期干预治疗后,在4 ～ 6个月随访时,除4例失访外,治愈(BAEP恢复正常)36例(87.8%),有效4例(9.8%),无效1例(2.4%),总有效率97.6%.结论 CMV感染可引起婴儿不同程度的听力受损,最常表现为客观听阈轻度增高,其次为客观听阈中重度增高伴有波的改变.更昔洛韦为主的早期综合干预,对CMV感染引起的婴儿听力损害的疗效满意、安全,值得临床推广.     

高胆红素血症新生儿总胆红素/白蛋白比值与脑干听觉诱发电位的关系

目的 探讨总胆红素/白蛋白比值与脑干听觉诱发电位(BAEP)的相关性及其预测高胆红素血症新生儿听力损害的临床价值.方法 检测113例新生儿的总胆红素(TSB)、白蛋白水平,计算总胆红素/白蛋白比值(B/A),将B/A值≥ 3.0 × 10-3的83例新生儿作为观察组,并根据B/A值分4个亚组;另30例B/A ﹤ 3.0 × 10-3的新生儿作为对照组.检测所有新生儿的BAEP,分析TSB水平、B/A值与BAEP异常的相关性.结果 观察组各亚组间新生儿的BAEP异常率差异有统计学意义(P ＜ 0.01),随B/A值增大,BAEP异常率增高;观察组各亚组间新生儿BAEP的Ⅴ波潜伏期及Ⅰ-Ⅴ、Ⅲ-Ⅴ波间期的差异有统计学意义(P均＜ 0.05);TSB水平、B/A值的工作特征曲线(ROC)下面积(AUC)差异也有统计学意义(P ＜ 0.05);BAEP异常与B/A值密切相关(χ2 ＝ 13.489,P ＜ 0.05).结论 B/A值与BAEP异常相关性高,具有预测高胆红素血症新生儿听力损害的临床价值.     

先天性症状性巨细胞病毒感染脑脊液病毒载量与听力损伤相关性

目的 探讨症状性先天性巨细胞病毒(cytomegalovirus,CMV)感染新生儿脑脊液(cerebrospinal fluid,CSF) CMV DNA载量与感音性听力损伤(sensorineural hearing loss,SNHL)的相关性.方法 36例先天性症状性CMV感染患儿,PCR法检测CSF CMV DNA载量,并于出生1个月内、生后6个月及1年左右行脑干听觉诱发电位检测.结果 (1)36例患儿,其中CSF CMV DNA阳性15例,阳性率41.2％,SNHL17例,SNHL发生率47.2％.(2) CSF CMV DNA阳性组SNHL发生率60.0％(9/15);阴性组SNHL发生率38.1％ (8/21),两组发生率比较差异无统计学意义(P =0.194).(3)CSFCMVDNA阳性组中,SNHL组与听力正常组CSF CMV DNA载量为3.35 ±0.68和3.17±0.56,两组载量比较,差异无统计学意义(P=0.36).结论 先天性症状性CMV感染患儿CSF CMV DNA是否阳性及其载量不是预测SNHL的指标.     

新生儿高胆红素血症患儿脑干听觉诱发电位及血清神经元特异性烯醇化酶变化及临床意义

目的通过对新生儿高胆红素血症患儿脑干听觉诱发电位(BAEP)及血清神经元特异性烯醇化酶(NSE)检测,评估高胆红素血症对新生儿听神经损伤。方法 56例血清胆红素大于 220．5μmol／L的新生儿为高胆红素血症组(简称高胆组),血清胆红素小于220．5μmol／L的49例足月儿为对照组,分别进行BAEP、NSE检测。结果高胆组新生儿BAEP的Ⅰ、Ⅲ、Ⅴ波绝对潜伏期(PL)、峰间潜伏期(IPL)均明显延长,与对照组比较,差异有显著性意义(P<0．01);高胆组新生儿NSE明显高于对照组,差异有显著性意义(P<0．01);NSE水平与BAEP的Ⅴ波反应阈值呈正相关(r=0．65,P<0．01)。结论高胆红素血症可导致新生儿听神经损伤;BAEP和NSE对其神经损伤有较高的敏感性,可作为监测指标。     

先天性巨细胞病毒感染对婴幼儿的影响

为探讨先天性巨细胞病毒(CMV)感染对婴幼儿的影响,采用瞬态诱发性耳声发射(TEOAE)对65例先天性CMV感染儿及82例非感染儿于新生儿期进行听力筛查,并于生后6个月至4岁进行听力及智力随访.感染组发育商落后8例,对照组仅1例,二组差异显著.感染组新生儿期、随访时分别有7例9耳、9例11耳未通过TEOAE听力测试,对照组均为1例1耳未通过,未通过率感染组明显高于对照组.新生儿期、随访时双耳反应能量感染组明显低于对照组.14例进行了脑干听觉诱发电位(ABR)检测,感染组9例17耳听力异常,对照组1例1耳听力异常.提示先天性CMV感染对听力、智力的影响应引起长期关注.     

婴儿癫(癎)与人巨细胞病毒感染的关系

目的探讨婴儿癫癎与人巨细胞病毒(HCMV)感染的关系。方法采用荧光定量聚合酶链式反应法检测婴儿癫癎52例及健康儿童20例尿HCMV-DNA,比较HCMV阳性与HCMV阴性癫癎患儿头颅CT、脑干听觉诱发电位(BAEP)异常率。结果婴儿癫癎组HCMV-DNA检出率为59.62%(31例),对照组为30%(6例),二者比较有显著差异(P<0.05)。HCMV阳性癫癎组头颅CT、BAEP异常率(54.84%、25.81%)远高于HCMV阴性癫癎组(23.81%、4.76%)(Pa<0.05)。结论HCMV感染可能是婴儿癫癎的重要致病因子之一,其感染导致的脑组织损伤在婴儿癫癎的发生发展中可能起重要作用。     

力欣奇继续医学教育园地--思考病例系列(2)答案

应完善检查:血、尿巨细胞病毒(CMV)检测,支气管镜检查,肺泡灌洗液(BALF)病原学检查,听力脑干诱发电位检测。检查结果:血CMV-IgG:>1000AU/mL、CMV-IgM:93.237 AU/m L;(尿1)CMV-DNA:9.06×102 copies/mL,(尿2)CMV-DNA:4.41×105 copies/mL,(尿3)CMV-DNA:9.42×104 copies/mL;血CMV-DNA:1.12×104 copies/mL;BALF CMV-DNA:2.98×105 copies/mL;BALF细菌培养、病毒抗原检测及偏肺病毒、鼻病毒、博卡病毒、肺炎支原体、肺炎衣原体核酸检测均阴性听力脑干诱发电位正常。     

Congenital cytomegalovirus infection: association between virus burden in infancy and hearing loss

OBJECTIVE: To determine the relationship between the virus burden in infancy and hearing loss in congenital CMV infection. STUDY DESIGN: A cohort of 76 infants with congenital cytomegalovirus (CMV) infection identified by means of newborn virologic screening was monitored for outcome. The amount of infectious CMV was analyzed in urine specimens obtained during early infancy. Peripheral blood (PB) samples obtained during early infancy were available from 75 children and CMV DNA was quantitated with a real-time quantitative polymerase chain reaction. RESULTS: Infants with clinical abnormalities at birth (symptomatic congenital CMV infection) had higher amounts of CMV in urine (P = .005) and CMV DNA in PB (P = .001) than infants with no symptoms. Eight children with and 4 children without symptoms had hearing loss. Among children without symptoms, those with hearing loss had a significantly greater amount of CMV in urine (P = .03) and PB virus burden (P = .02) during infancy than those with normal hearing. Infants with < 5 x 10(3) pfu/mL of urine CMV and infants with < 1 x 10(4) copies/mL of viral DNA in PB were at a lower risk for hearing loss. CONCLUSION: In children with asymptomatic congenital CMV infection, hearing loss was associated with increased amounts of urine CMV and PB CMV DNA during early infancy.     

Congenital cytomegalovirus infection: a cause of sensorineural hearing loss.

Prospective studies have suggested that about 108 children with congenital cytomegalovirus (CMV) infection and bilateral sensorineural hearing loss are born each year in England and Wales; this represents about 12% of all children with congenital sensorineural hearing loss. Over a nine year period 1644 children aged between 6 months and 4 years who were attending the Nuffield Hearing and Speech Centre were screened for CMV infection. The prevalence of CMV in the urine of children with sensorineural hearing loss but no immediate family history of deafness was nearly twice that (13%) found in other children with impaired hearing and those with normal hearing (7%). These findings indicate the importance of CMV as a cause of hearing loss.     

The outcome in children with congenital cytomegalovirus infection. A longitudinal follow-up study

Infants with congenital cytomegalovirus (CMV) infection were identified through urine cultures of 15,212 consecutive neonates and studied prospectively to determine whether their neurodevelopmental and audiologic status was different from that of matched uninfected control subjects. Of 64 children with congenital CMV infection, three died, 11 could not be located for follow-up, one had quadriplegic cerebral palsy, and seven had varying degrees of sensorineural hearing loss. All matched control subjects were normal neurologically, and none of them had sensorineural hearing impairment. The Stanford-Binet test revealed scores within the normal range, at 3 and 5 years of age, for both children with CMV infection and matched control subjects, as did the preschool assessment (Wide Range Achievement Test) in children older than 5 years. However, in children with CMV infection, the home environment was less stimulating, discipline and punishment were more readily implemented, and behavioral problems were significantly greater than in the matched control subjects.     

Auditory and visual defects resulting from symptomatic and subclinical congenital cytomegaloviral and toxoplasma infections.

Sensorineural hearing loss was present in ten of 59 (17%) patients with congenital cytomegalovirus (CMV) infection (three of eight born with symptomatic and seven of 51 born with subclinical infection). The defect was bilateral in eight, moderate to profound in eight, and of progressive nature in two. Hearing loss did not occur in 21 patients with natal CMV infection nor in seven of 12 patients with congenital toxoplasmosis. Histopathologic and immunofluorescent studies of the inner ear in two of three neonates who died with severe infection revealed that viral antigens were widely distributed in cochlear structures. Eye pathology was associated only with congenital Toxoplasma (nine of 12) and CMV (seven of 43) infections. Visual impairments were more prominent and severe in those born with symptomatic infections, exclusively so with CMV. However, ocular defects, in particular chorioretinitis, developed after birth in five of eight patients born with asymptomatic congenital toxoplasmosis. These data firmly establish clinically inapparent congenital CMV infection as a major public health problem and confirm the fact that congenital toxoplasmosis may be associated with late-appearing, debilitating chorioretinitis.     

Newborn hearing screening: will children with hearing loss caused by congenital cytomegalovirus infection be missed?

OBJECTIVE: To predict whether universal newborn auditory screening will identify most infants with sensorineural hearing loss (SNHL) caused by congenital cytomegalovirus (CMV) infection. STUDY DESIGN: A cohort of 388 children born between 1980 and 1996 at one hospital and identified during the newborn period as having congenital CMV infection received repeated hearing evaluations to assess whether hearing loss had occurred. RESULTS: SNHL was detected in 5.2% of all infants at birth. Late-onset SNHL occurred among the children throughout the first 6 years of life. By the age of 72 months, the cumulative incidence of SNHL was 15.4% in the cohort. Children with clinically apparent disease at birth had significantly more SNHL than children without any apparent disease (22.8% vs 4.0% at 3 months and 36.4% vs 11.3% at 72 months of age). CONCLUSIONS: Universal screening of hearing in neonates will detect less than half of all SNHL caused by congenital CMV infection. Because most infants with congenital CMV infection are without symptoms at birth, these children are unlikely to be recognized as being at risk for SNHL and will not receive further hearing evaluations to detect late-onset hearing loss. A combined approach of universal screening of neonates for hearing, as well as for detection of congenital CMV infection, needs to be considered.     

先天性巨细胞病毒感染抗病毒治疗的效果和安全性观察

目的：观察更昔洛韦（GCV）和（或）缬更昔洛韦（VGCV）治疗先天性巨细胞病毒（ CMV）感染患儿的疗效和不良反应。 方法：回顾性纳入2012年3月1日至2017年5月31日在复旦大学附属儿科医院（我院）新生儿科住院、确诊为先天性CMV感染的患儿,随访至2017年12月31日。从病史资料中提取患儿的一般资料,抗CMV治疗的药物和疗程,新生儿期及1、 3和6月龄的肝脾触诊检查结果、胆红素和肝功能检查指标、CMV抗体和DNA检测结果、颅脑MRI、眼底检查结果和听力检测结果,治疗期间药物的不良反应。根据抗病毒治疗与否以及疗程长短分组,比较各组的临床特征和治疗反应。 结果：28例先天性CMV感染患儿进入本文分析,其中早产儿11例,男17例;无症状/轻度症状9例,未予抗病毒治疗;中重度症状19例,GCV和（或）VGCV治疗≤6周组11例,治疗6个月组8例。①6月龄时,除1例胆汁酸轻度升高外27例中枢神经系统以外的症状和体征、胆红素、肝功能和血常规均恢复正常。②无症状／轻度症状组1例在6月龄时出现左侧听力中度损失。治疗≤6周组中,2例CMV相关眼底病变于1月龄时消失; 颅脑MRI异常信号和听力损失者各5例,6月龄时分别有3例和2例无改善。治疗6个月组中,4例先天性CMV感染相关视网膜病变在随访中均消失;3例头颅MRI异常信号者和7例有听力损失者,6月龄时分别有2例和1例无改善。③治疗≤6周组和治疗6个月组在6月龄时中枢神经系统病变改善情况差异无统计学意义。④治疗过程中未发现与GCV和VGCV应用相关的粒细胞减少和肝功能异常。 结论：抗病毒治疗能改善感音神经性耳聋和脉络膜视网膜炎,GCV和（或）VGCV≤6周与6个月的治疗效果相近;建议对无临床症状先天性CMV感染患儿行眼底检查、脑干诱发电位和头颅MRI检查。     

定量检测婴儿尿液巨细胞病毒DNA的临床意义

目的 探讨荧光定量聚合酶链反应(FQ-PCR)检测尿液巨细胞病毒(CMV)在儿科CMV感染诊断治疗中的意义.方法 应用FQ-PCR方法检测婴儿尿液CMV DNA量.结果 (1)280例疑似CMV感染儿有126例尿液中CMVDNA呈阳性,阳性率是45.0%,为症状性CMV感染儿;同年龄组的70例健康儿童尿液中CMV DNA阳性5例,阳性率是7.1%,为无症状性CMV感染儿.症状性感染儿尿液中CMVDNA拷贝数对数值(4.78±0.85)与无症状性感染儿(4.45±1.02)之间差异无显著性(P＞0.05).(2)90例症状性CMV感染儿应用更昔洛韦诱导治疗结束时尿液CMV DNA拷贝数对数值(3.74±0.58)较治疗前(4.64±0.90)明显减少(P＜0.01),临床症状改善.(3)45例症状性CMV感染儿在治疗后3个月CMVDNA拷贝数对数值(4.41±0.74)较治疗结束时(3.67±0.58)升高(P＜0.01).临床症状明显改善.结论 FQPCR方法检测婴儿尿液中CMVDNA量可以诊断CMV感染,但是不能区分CMV感染是症状性感染还是无症状性感染;应避免盲目反复应用更昔洛韦治疗CMV感染.     

Cytomegalovirus urinary excretion and long term outcome in children with congenital cytomegalovirus infection. Congenital CMV Longitudinal Study Group

BACKGROUND: Cytomegalovirus (CMV) is the most frequent cause of congenital infection, and both symptomatic and asymptomatic infants may have long term sequelae. Children with congenital CMV infection are chronically infected and excrete CMV in the urine for prolonged periods. However, the effect of prolonged viral replication on the long term outcome of these children is unknown. OBJECTIVE: To determine whether duration of CMV excretion is associated with outcome at 6 years of life in symptomatic and asymptomatic congenitally infected children. METHODS: Longitudinal cohort study. Children congenitally infected with CMV were identified at birth and followed prospectively in a study of long term effects of congenital CMV infection. The relationship between duration of CMV urinary excretion and growth, neurodevelopment and presence and progression of sensorineural hearing loss (SNHL) at 6 years of age was determined. RESULTS: There was no significant difference in the duration of viral urinary excretion between children born with asymptomatic (median, 4.55 years) and symptomatic (median, 2.97 years) congenital CMV infection (P = 0.11). Furthermore there was no association between long term growth or cognitive outcome and duration of viral excretion. However, a significantly greater proportion of children who excreted CMV for <4 years had SNHL and progressive SNHL compared with children with CMV excretion >4 years (P = 0.019, P = 0.009, respectively). CONCLUSIONS: Children congenitally infected with CMV are chronically infected for years, but the duration of CMV urinary excretion is not associated with abnormalities of growth, or neurodevelopmental deficits. However, SNHL and progressive SNHL were associated with a shorter duration of CMV excretion.     

GJB2 and GJB6 mutations in children with congenital cytomegalovirus infection

Congenital cytomegalovirus (CMV) infection is a leading cause of sensorineural hearing loss (SNHL) in children. Whether connexin mutations are factors in the development of CMV-related hearing loss has not been explored. We examined gap junction protein beta-2 (GJB2) and gap junction protein beta-6 (GJB6) mutations in 149 children with congenital CMV infection and 380 uninfected neonates. Mutations in GJB2 and GJB6 were assessed by nucleotide sequencing and polymerase chain reaction (PCR) methods, respectively. The study population was predominantly African American, and 4.3% of the subjects were carriers of a connexin 26 mutation. The overall frequency of GJB2 mutations was significantly higher in the group of children with CMV infection and hearing loss (21%) compared with those with CMV infection and normal hearing (3%, p = 0.017) and the group of uninfected newborns (3.9%, p = 0.016). Eight previously reported mutations (M34T, V27I, R127H, F83L, R143W, V37I, V84L, G160S), and four novel mutations (V167M, G4D, A40T, and R160Q) were detected. None of the study children had the 342-kb deletion (delGJB6-D13S1830) in GJB6, which suggests that this mutation does not play a role in hereditary deafness in the African American population. Although GJB2 mutations were detected in children with and without CMV-related hearing loss, those with hearing loss had a higher frequency of GJB2 mutations.