Shimamura Masako, Kim Juhyeong, Medoro Alexandra K, Flint Kaitlyn, Kaptsan Irina, Wang Huanyu, Pifer Traci, Harris Rachelle, Cuartas José, Leber Amy, Sánchez Pablo J
Center for Vaccines and Immunity, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Division of Pediatric Infectious Diseases, Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA.
J Med Virol. 2025 Mar;97(3):e70257. doi: 10.1002/jmv.70257.
Congenital cytomegalovirus (cCMV) infection is diagnosed by positive urine or saliva testing within 21 days after birth. Beyond this age, newborn dried blood spot (DBS) PCR can retrospectively diagnose cCMV infection but has lower sensitivity than urine or saliva PCR testing. The DBS PCR may be negative due to the absence of blood DNAemia at birth or to the technical limit of detection for DBS PCR. The objective of this study was to distinguish these two possibilities by determining agreement between DBS and plasma CMV PCR tests among cCMV-infected infants. This single center retrospective cohort study evaluated 70 cCMV-infected infants diagnosed by a positive urine CMV PCR, who had a CMV DBS at birth and a plasma PCR test within 31 days after birth. Clinical characteristics and viral loads were compared between groups according to paired DBS and plasma PCR results. Test agreement was calculated using Cohen's kappa coefficient. The DBS PCR sensitivity was 71% compared to urine PCR. Of the 70 subjects, 49 (70%) subjects were DBS+ /plasma+ , 1 (1.4%) were DBS+ /plasma-, 14 (20%) were DBS-/plasma+ , and 6 (9%) were DBS-/plasma-. Agreement between the tests was fair (κ = 0.348, 95% CI 0.115-0.581). Of the 20 subjects with DBS- tests, 6 (30%) had undetectable plasma DNAemia. Of the infants with DBS-/plasma+ PCR, plasma viral loads were significantly lower than infants with DBS+ /plasma+ PCR testing. Nearly a third of cCMV infected infants may be missed by DBS testing due to both biological and technical limitations of this method.
先天性巨细胞病毒(cCMV)感染通过出生后21天内尿液或唾液检测呈阳性来诊断。超过这个年龄,新生儿干血斑(DBS)聚合酶链反应(PCR)可回顾性诊断cCMV感染,但敏感性低于尿液或唾液PCR检测。由于出生时无血液病毒血症或DBS PCR检测的技术检测限,DBS PCR可能为阴性。本研究的目的是通过确定cCMV感染婴儿中DBS和血浆CMV PCR检测之间的一致性来区分这两种可能性。这项单中心回顾性队列研究评估了70例经尿液CMV PCR阳性诊断为cCMV感染的婴儿,这些婴儿出生时进行了CMV DBS检测,并在出生后31天内进行了血浆PCR检测。根据配对的DBS和血浆PCR结果,比较各组之间的临床特征和病毒载量。使用Cohen's kappa系数计算检测一致性。与尿液PCR相比,DBS PCR的敏感性为71%。在70名受试者中,49名(70%)受试者DBS+/血浆+,1名(1.4%)受试者DBS+/血浆-,14名(20%)受试者DBS-/血浆+,6名(9%)受试者DBS-/血浆-。检测之间的一致性为中等(κ = 0.348,95%可信区间0.115 - 0.581)。在20名DBS检测为阴性的受试者中,6名(30%)血浆病毒血症检测不到。在DBS-/血浆+ PCR的婴儿中,血浆病毒载量显著低于DBS+/血浆+ PCR检测的婴儿。由于该方法的生物学和技术限制,近三分之一的cCMV感染婴儿可能会被DBS检测遗漏。