Payne H, Aaltoranta M, Veikkolainen V, Kent N, Gkouleli T, Lennon A, Ramgoolam T, Adams S P
Section of Paediatric Infectious Disease, School of Medicine, Imperial College London, London, United Kingdom.
Research and Development, Revvity Inc., Turku, Finland.
Front Pediatr. 2025 Mar 18;13:1543132. doi: 10.3389/fped.2025.1543132. eCollection 2025.
Congenital cytomegalovirus (cCMV) is the leading cause of neurodevelopmental and hearing impairment resulting from infection, affecting over a million infants globally each year. Early antiviral treatment can limit sequelae; however, most newborns are diagnosed late-or not at all-due to the lack of universal screening. Ensuring the availability of appropriate screening tools is critical to facilitate accurate and timely cCMV diagnosis.
A high-sensitivity, high-throughput commercial CMV PCR kit targeting the RRP30 control gene and a conserved region of CMV DNA was provided by Revvity and tested in three population groups: (1) leftover dried blood spot (DBS) samples from the UK newborn screening programme, (2) DBS samples from children with CMV viraemia unrelated to cCMV, and (3) DBS and dried saliva samples from infants with and without cCMV.
Of 3,345 anonymised newborn DBS samples analysed, CMV was detected in 22 cases (0.66%), with a mean cycle threshold value of 36.70 (range 31.87-41.68). Assay development demonstrated a sensitivity of 2.04 CMV IU per reaction. This level of sensitivity was replicated using DBS samples prepared from infant/child blood samples with known levels of CMV, suggesting that the sensitivity reflects 2,000-3,000 CMV IU/mL blood.
We demonstrated high analytical sensitivity of the qPCR assay with an optimal extraction protocol, making it an effective strategy for cCMV screening using DBS samples. These data suggest a potential cCMV incidence rate of up to 0.66% in the United Kingdom, equivalent to 3,960 infants per year, 25% of whom may develop long-term sequelae, which could be improved through early diagnosis and treatment.
先天性巨细胞病毒（cCMV）是感染导致神经发育和听力障碍的主要原因，每年全球有超过100万婴儿受其影响。早期抗病毒治疗可限制后遗症；然而，由于缺乏普遍筛查，大多数新生儿被诊断得很晚或根本未被诊断。确保有合适的筛查工具对于促进准确、及时的cCMV诊断至关重要。
Revvity提供了一种针对RRP30对照基因和CMV DNA保守区域的高灵敏度、高通量商业CMV PCR试剂盒，并在三个群体中进行了测试：（1）来自英国新生儿筛查项目的剩余干血斑（DBS）样本，（2）来自与cCMV无关的CMV病毒血症儿童的DBS样本，以及（3）有或无cCMV的婴儿的DBS和干唾液样本。
在分析的3345份匿名新生儿DBS样本中，22例（0.66%）检测到CMV，平均循环阈值为36.70（范围31.87 - 41.68）。检测方法的开发显示每个反应的灵敏度为2.04 CMV国际单位。使用从已知CMV水平的婴儿/儿童血样制备的DBS样本重复了这种灵敏度水平，这表明该灵敏度反映的是每毫升血液中2000 - 3000 CMV国际单位。
我们证明了采用最佳提取方案的qPCR检测方法具有高分析灵敏度，使其成为使用DBS样本进行cCMV筛查的有效策略。这些数据表明，英国cCMV的潜在发病率高达0.66%，相当于每年3960名婴儿，其中25%可能会出现长期后遗症，通过早期诊断和治疗情况可能会得到改善。
