先天性巨细胞病毒感染儿童的临床表现、管理和结局的时间趋势。

文献信息

中文摘要

未标注： 先天性巨细胞病毒（cCMV）是最常见的先天性感染，也是感音神经性听力损失以及神经发育损害的主要原因。近年来，cCMV的认识、筛查和管理策略已经演变。本研究旨在评估诊断为cCMV感染儿童的临床表现、治疗和结局的时间变化。我们使用CCMVnet登记处（www.ccmvnet.org）的数据进行了回顾性队列分析，该登记处是一个国际多中心数据库，收集确诊cCMV感染儿童的去标识化数据。共纳入2011年至2024年间诊断的1653例患者，并分为两个队列：2011-2016年（n=566）和2017-2024年（n=1087）。选择2017年作为实用切点，对应欧洲先天性CMV专家共识声明发表之年。儿童通过产前、临床、听力相关和新生儿筛查途径被识别。出生时有症状的cCMV定义为根据既往发表标准存在至少一项预先定义的临床、实验室、听力或神经影像学发现。对两个不同时间段进行了比较分析，涵盖新生儿临床发现、神经影像学结果、治疗策略和长期结局。在较近的队列中，出生时被归类为有症状的新生儿减少，从P1的49.2%降至P2的44.2%（p=0.07）。静脉注射更昔洛韦的使用从7.3%降至2.8%（p<0.001），而单用口服缬更昔洛韦的使用从43.8%增至78.7%（p<0.001）。两个时期之间观察到长期结局差异，12个月时运动损害从16.5%降至6.2%（p<0.001），36个月时任何长期后遗症从40.0%降至31.0%（p=0.05）。
结论： 本研究强调了欧洲先天性CMV感染儿童在临床谱、管理和结局方面的时间差异。后一时期无症状和轻症儿童比例较高，可能反映了孕产妇和新生儿筛查实践的变化。观察到的时间差异为cCMV诊断和管理的不断演变的临床图景提供了见解，但其潜在原因无法从现有数据中确定。
已知内容： • 先天性巨细胞病毒（cCMV）感染是儿童感音神经性听力损失和神经发育损害的主要感染性原因。• 在过去十年中，cCMV的临床管理已发生实质性演变，尤其是在2017年欧洲专家共识声明发表之后，并伴随筛查策略的扩大。
新发现： • 在我们的队列中，2017年后诊断为cCMV的儿童比2017年前诊断的儿童临床表现更轻，长期后遗症更少。• 在两个研究时期之间观察到诊断路径、治疗实践和临床结局的时间变化。

英文摘要

UNLABELLED: Congenital cytomegalovirus (cCMV) is the most common congenital infection and a leading cause of sensorineural hearing loss as well as neurodevelopmental impairment. In recent years, awareness, screening, and management strategies for cCMV have evolved. This study aimed to assess temporal changes in the clinical presentation, treatment, and outcomes of children diagnosed with cCMV infection. We conducted a retrospective cohort analysis using data from the CCMVnet registry ( www.ccmvnet.org ), an international multicenter database collecting anonymized data on children with confirmed cCMV infection. A total of 1653 patients diagnosed between 2011 and 2024 were included and divided into two cohorts: 2011-2016 (n = 566) and 2017-2024 (n = 1087). The year 2017 was selected as a pragmatic cutoff, corresponding to the year of publication of the European expert consensus statement on congenital CMV. Children were identified through antenatal, clinical, hearing-related, and newborn screening pathways. Symptomatic cCMV at birth was defined by the presence of at least one predefined clinical, laboratory, hearing, or neuroimaging finding based on previously published criteria. A comparative analysis between two distinct time periods was conducted, encompassing neonatal clinical findings, neuroimaging results, treatment strategies, and long-term outcomes. Newborns classified as symptomatic at birth decreased in the more recent cohort, from 49.2% in P1 to 44.2% in P2 (p = 0.07). The use of intravenous ganciclovir decreased from 7.3% to 2.8% (p < 0.001), while the use of oral valganciclovir alone increased from 43.8% to 78.7% (p < 0.001). Differences in long-term outcomes were observed between the two periods, with motor impairment at 12 months decreasing from 16.5% to 6.2% (p < 0.001) and any long-term sequelae at 36 months decreasing from 40.0% to 31.0% (p = 0.05).
CONCLUSION: This study highlights temporal differences in the clinical spectrum, management, and outcomes of children with congenital CMV infection in Europe. The higher proportion of asymptomatic and mildly symptomatic children in the latter period may reflect changes in maternal and neonatal screening practices. The observed temporal differences provide insight into the evolving clinical landscape of cCMV diagnosis and management, while their underlying causes cannot be determined from the present data.
WHAT IS KNOWN: • Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of sensorineural hearing loss and neurodevelopmental impairment in children. • Clinical management of cCMV has evolved substantially over the last decade, particularly following the publication of the European expert consensus statement in 2017 and alongside expanding screening strategies.
WHAT IS NEW: • In our cohort, children diagnosed with cCMV after 2017 presented with milder clinical manifestations and experienced fewer long-term sequelae than those diagnosed before 2017. • Temporal changes in diagnostic pathways, treatment practices, and clinical outcomes were observed between the two study periods.