Otolaryngology, Audiology, and Phoniatrics Unit, University of Pisa, Pisa, Italy.
Otolaryngology, Audiology, and Phoniatrics Unit, University of Pisa, Pisa, Italy.
Int J Pediatr Otorhinolaryngol. 2024 Sep;184:112070. doi: 10.1016/j.ijporl.2024.112070. Epub 2024 Aug 13.
Congenital Cytomegalovirus (cCMV) has been associated with hearing, vision, and neurodevelopmental long-term sequelae. Despite the social burden associated with the disease, a universally accepted consensus on screening, diagnostic, therapeutic and follow-up approaches has not been reached. The present observational retrospective study aims at describing long-term sequelae and radiological abnormalities associated with cCMV in children early identified by extended hearing-targeted screening and evaluated by audiological follow-up in a single III Level Audiological Referral Center for at least 2 years.
Audiological neonatal and follow-up data were available for all subjects. Data collection included clinical neonatal and virological assessment at birth. Ophthalmological, neurodevelopmental and neuroradiological follow-up abnormalities compatible with cCMV sequelae were collected by clinical reports. Spearman's rank correlation coefficient (rho-ρ) was used to evaluate possible correlations among the considered parameters.
61 newborns were identified by extended hearing-targeted cCMV screening and diagnosed mostly (83.6 %) by PCR viral DNA extraction in urine collected within the 15° day of life. Seventeen babies were born preterm, with a mean gestational age of 33.5 weeks. Sixteen patients (26.2 %) were admitted to an Intensive or sub-Intensive Neonatal Care Unit. At birth, 35 newborns were symptomatic (57.3 %), and 19 of them received antiviral treatment by valganciclovir or ganciclovir. Overall, 20 children (32.7 %) were diagnosed with sensorineural hearing loss (SNHL), among them 17 (85 %) were refer at the newborn hearing screening while 3 (15 %) were Pass. 5/20 children (25 %) presented isolated SNHL, while in 15/20 (75 %) children SNHL was associated to other long-term sequelae. In 5 patients (25 %) a progression of the hearing threshold was observed, with a mean age of progression of 26 months of age. Risk factors for progression were a worse final hearing threshold (Spearman's ρ = 0.434; p = 0.0001) and a worse hearing threshold at birth (Spearman's ρ = 0.298; p = 0.020). Thirteen children were fitted with hearing aids, 8 of whom subsequently underwent cochlear implantation. Concerning long term impairments, 10/61 children (17 %) presented a variety of ophthalmological sequelae, while 16/40 cCMV patients (40 %) were diagnosed with neurodevelopmental abnormalities. Language delays were significantly associated with a worse hearing threshold (ρ = 0.582; p = 0.0001) and with other neurocognitive abnormalities (ρ = 0.677, p = 0.0001). 30 children underwent radiological brain evaluation by Magnetic Resonance Imaging, and 63.3 % of them presented abnormalities compatible with cCMV. Mean viral load at birth did not show significant associations with long-term sequelae.
The study highlights the diverse and significant long-term sequelae of cCMV infection detected through early screening. With a significant proportion of cCMV children developing sensorineural hearing loss, ophthalmological and neurodevelopmental issues, the results emphasize the importance of continuous, multidisciplinary follow-up. Early identification and tailored interventions are crucial for improving the long-term health and quality of life of children affected by cCMV.
先天性巨细胞病毒(cCMV)与听力、视力和神经发育的长期后遗症有关。尽管这种疾病带来了社会负担,但尚未达成关于筛查、诊断、治疗和随访方法的普遍接受的共识。本观察性回顾性研究旨在描述通过扩展的听力靶向筛查早期识别的 cCMV 患儿的长期后遗症和放射学异常,并在一个三级听力转诊中心进行至少 2 年的听力随访进行评估。
所有受试者的新生儿和随访数据均可获得。数据收集包括出生时的临床新生儿和病毒学评估。通过临床报告收集与 cCMV 后遗症相符的眼科、神经发育和神经放射学随访异常。采用 Spearman 秩相关系数(rho-ρ)评估考虑参数之间的可能相关性。
通过扩展的听力靶向 cCMV 筛查,61 名新生儿被识别出来,其中大多数(83.6%)通过出生后第 15 天内采集的尿液中病毒 DNA 提取 PCR 进行诊断。17 名婴儿早产,平均胎龄为 33.5 周。16 名患者(26.2%)入住重症监护病房或亚重症监护病房。出生时,35 名新生儿有症状(57.3%),其中 19 名接受了缬更昔洛韦或更昔洛韦的抗病毒治疗。总的来说,20 名儿童(32.7%)被诊断为感音神经性听力损失(SNHL),其中 17 名(85%)在新生儿听力筛查时被诊断,3 名(15%)通过。5/20 名儿童(25%)存在孤立性 SNHL,而在 15/20 名儿童(75%)中 SNHL 与其他长期后遗症相关。5 名儿童(25%)的听力阈值出现进展,平均进展年龄为 26 个月。进展的风险因素是更差的最终听力阈值(Spearman's ρ=0.434;p=0.0001)和出生时更差的听力阈值(Spearman's ρ=0.298;p=0.020)。13 名儿童佩戴了助听器,其中 8 名随后接受了人工耳蜗植入。关于长期损伤,61 名儿童中的 10 名(17%)出现了各种眼科后遗症,而 40 名 cCMV 患儿中的 16 名(40%)被诊断为神经发育异常。语言延迟与更差的听力阈值(ρ=0.582;p=0.0001)和其他神经认知异常(ρ=0.677,p=0.0001)显著相关。30 名儿童接受了磁共振成像脑评估,其中 63.3%的儿童存在与 cCMV 相符的异常。出生时的平均病毒载量与长期后遗症无显著相关性。
该研究强调了通过早期筛查发现的 cCMV 感染的多种显著长期后遗症。由于相当一部分 cCMV 儿童出现感音神经性听力损失、眼科和神经发育问题,研究结果强调了持续、多学科随访的重要性。早期识别和针对性干预对于改善受 cCMV 影响的儿童的长期健康和生活质量至关重要。