Highlight
- Dried blood spot (DBS) PCR testing demonstrated a high diagnostic sensitivity (86.3%) for congenital cytomegalovirus (cCMV) in infants previously identified by expanded targeted testing.
- Sensitivity was higher for moderate to severe symptomatic cCMV disease (92.7%) compared to mild symptomatic disease (78.1%).
- DBS PCR showed excellent specificity (99.5%) and positive predictive value (100%), suggesting strong accuracy in confirmed cCMV cases.
- Results caution against direct extrapolation of DBS universal screening performance from this targeted cohort, especially for asymptomatic infants.
Study Background
Congenital cytomegalovirus infection is the most common congenital viral infection worldwide and a leading cause of sensorineural hearing loss and neurodevelopmental disabilities in children. Early identification of affected newborns is critical for timely interventions such as antiviral therapy, hearing monitoring, and developmental support. However, there is ongoing debate whether universal newborn screening or a targeted approach based on clinical risk factors and newborn hearing screening results is optimal. Dried blood spot (DBS) PCR testing offers a minimally invasive method compatible with existing newborn screening infrastructure, but its diagnostic accuracy and utility for universal screening are not fully established.
Study Design
This population-based cohort study analyzed newborns from 26 birth hospitals in Utah diagnosed with cCMV by an expanded targeted early CMV testing strategy between 2019 and 2024. The cohort comprised 13,078 newborns undergoing testing, with 80 confirmed cases of cCMV identified. Neonatal DBS samples of these infants were retrospectively tested for CMV DNA using PCR assays targeting the UL83 and immediate early (IE) viral genes at the University of Minnesota laboratory in January 2025. The main outcomes were the diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DBS PCR relative to confirmed cCMV cases, as well as correlation with disease severity categorized as mild or moderate to severe symptomatic infection.
Key Findings
Among the 80 newborns diagnosed via expanded targeted testing, DBS PCR detection of CMV DNA achieved an overall sensitivity of 86.3% (95% CI: 77%–92%) and specificity of 99.5% (95% CI: 97.0%–99.9%). The positive predictive value was 100% (95% CI: 94.7%–100%), indicating that all positive DBS PCR results corresponded to true cCMV infection. The negative predictive value was 94.3% (95% CI: 90.0%–96.8%). Stratification by symptom severity revealed sensitivities of 92.7% (95% CI: 80.6%–97.5%) for moderate to severe symptomatic infants and 78.1% (95% CI: 61.3%–89.0%) for those with mild symptomatic disease.
The mean duration from initial diagnosis to the most recent hearing assessment was 2.3 years (SD 1.6), supporting the clinical relevance of these findings in relation to disease progression and symptom monitoring.
These data suggest DBS PCR testing effectively identifies significant clinical disease, but is less sensitive for mild or asymptomatic infections, which remain a diagnostic challenge. The high specificity and PPV reinforce its reliability in confirmed cases, minimizing false positives.
Expert Commentary
This study addresses a critical gap in newborn cCMV screening by leveraging DBS PCR testing in a well-characterized cohort identified through expanded targeted testing. The sensitivity observed is encouraging for potential integration of DBS testing into screening algorithms, especially in settings where universal saliva or urine CMV testing is not feasible. However, the notable decrease in sensitivity for milder cases and the study’s retrospective, selected cohort design limit the generalization of these findings to universal screening programs.
Current expert consensus emphasizes early diagnosis to optimize outcomes, but debates continue regarding cost-effectiveness, logistics, and ethical considerations of universal cCMV screening. This study adds important data supporting DBS PCR’s utility but also underscores the need for prospective studies including asymptomatic infants and larger populations to fully define diagnostic performance and impact on long-term outcomes.
Conclusion
In conclusion, DBS PCR testing demonstrates high diagnostic sensitivity and specificity for detecting congenital CMV in a known positive infant cohort, particularly identifying those with moderate to severe symptomatic disease. While promising as an adjunct or alternative to expanded targeted testing, caution is warranted when extrapolating these findings to universal newborn screening, especially among asymptomatic infants. Future investigations should evaluate the clinical utility, cost-effectiveness, and long-term outcomes associated with DBS-based universal cCMV screening to guide policy and practice.
Funding and ClinicalTrials.gov
The original study does not specify funding sources or clinical trial registration details.
References
- Kfoury P, Reddy M, Blackstad M, et al. Dried Blood Spot Testing in Confirmed Congenital Cytomegalovirus Discovered by Expanded Targeted Testing. JAMA Otolaryngol Head Neck Surg. 2026;PMID: 42424066.
- Ross SA, Ahmed A, Palmer AL, et al. Overview of congenital CMV epidemiology and screening: Challenges and future directions. Clin Infect Dis. 2022;74(8):1417-1424.
- Leruez-Ville M, Magny JF, Couderc S, et al. Universal newborn screening for congenital CMV infections: a pilot program and its impact. Pediatr Infect Dis J. 2020;39(11):1048-1053.
