Congenital cytomegalovirus screening by dried blood spot: a systematic review

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: Sensitivity range: 28.3% to 79.3%; Specificity range: 99.9% to 100%

• Primary Outcome: Diagnostic accuracy of DBS PCR for congenital CMV detection in newborns

• Nnt Or Sensitivity: Sensitivity: 28.3%–79.3% (highly variable); Specificity: 99.9%–100%; PPV: 39%–100%; NPV: 99.6%–99.9%. The wide sensitivity range indicates DBS PCR would miss 20%–72% of cCMV-infected newborns depending on the method employed.

• Confidence Interval: Not reported (ranges only provided across nine studies)

Clinical Application

DBS samples are already collected universally in most high-income countries as part of routine newborn metabolic screening, making DBS-based cCMV testing logistically attractive and cost-effective. However, the low and variable sensitivity means that DBS PCR alone is insufficient as a standalone screening tool without significant methodological standardisation. Paired or reflex testing strategies (e.g., DBS followed by confirmatory saliva/urine PCR) may improve clinical utility. In Australia, the National Newborn Bloodspot Screening Program (NNBSP) collects DBS from virtually all newborns, administered through state and territory health departments. Congenital CMV is not currently included in the Australian newborn screening panel. The RACGP and RACP have not issued specific guidelines on universal cCMV screening. Antiviral therapy with valganciclovir is available in Australia (TGA-registered) and has demonstrated benefit in symptomatic cCMV with CNS involvement. PBS listing for valganciclovir in cCMV is limited to specific indications. Given the high sensitivity required for population screening and the current evidence gaps, incorporation of DBS cCMV PCR into the NNBSP would require further Australian-specific feasibility and cost-effectiveness data, as well as MSAC (Medical Services Advisory Committee) evaluation. The variable sensitivity reported in this review would be a significant barrier to MSAC approval in its current form. All newborns undergoing routine neonatal metabolic screening (Guthrie card/DBS collection), particularly in settings where universal saliva or urine PCR screening is not yet feasible. Most applicable to high-resource settings with established newborn screening infrastructure.

Abstract

UNLABELLED: Congenital human cytomegalovirus (cCMV) infection is a leading cause of sensorineural hearing loss and neurological sequelae in children. Although newborn screening strategies remain controversial, dried blood spots (DBS) collected for routine metabolic screening have been proposed as a low-cost method for large-scale detection. This systematic review assessed studies that evaluated the accuracy of DBS testing for screening newborns for cCMV infection. A systematic review was conducted following the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy and reported in accordance with PRISMA-DTA. The PIRT strategy included the following: Population (newborns undergoing screening for cCMV), Index test (detection of cCMV using DBS samples), Reference standard (confirmatory testing using saliva or urine PCR collected within 21 days of life), Target condition (cCMV infection). Searches were performed in PubMed/MEDLINE, Scopus, Bireme, Embase, LILACS, SciELO, and CENTRAL. The search identified 365 articles; after removing 210 duplicates, 155 were screened by title and abstract, and 9 studies were included. The included studies tested between 1174 and 551,034 DBS samples each. Confirmatory testing used PCR in urine (seven studies) or saliva (two studies). Three studies used paired samples for screening; sensitivity ranged from 28.3% to 79.3%, specificity from 99.9% to 100%. Positive predictive value (PPV) ranged from 39 to 100%, and negative predictive value (NPV) from 99.6% to 99.9%. CONCLUSION: Neonatal screening for congenital cytomegalovirus using DBS samples is promising, since it would allow early identification for timely interventions to reduce sequelae. WHAT IS KNOWN: • Congenital CMV is a leading cause of sensorineural hearing loss and neurodevelopmental sequelae, with many cases asymptomatic at birth. Diagnosis relies on early viral detection, and while saliva/urine PCR is sensitive, newborn screening lacks consensus and feasibility is unknown in many settings. WHAT IS NEW: • DBS PCR emerges as a scalable, feasible low-cost screening alternative for cCMV screening. A few states in the USA and provinces in Canada have implemented newborn cCMV screening programs using DBS, but the sensitivity appears lower than in research studies. Improving DNA extraction and PCR methods are required as well as assessing feasibility of using other specimens (e.g., urine or saliva) for screening.

References

1. 1.Machado, R. A., Bicalho Garcia, I. S., de Albuquerque, G. S., de Araújo, J. L. P., Coelho Gonçalves, R., Rodrigues de Almeida, N. M., Dos Santos Borges, R., Machado Carellos, E. V., & de Castro Romanelli, R. M. (2026). Congenital cytomegalovirus screening by dried blood spot: a systematic review. European Journal of Pediatrics. https://doi.org/10.1002/rmv.70132