Dried Blood Spot Testing in Confirmed Congenital Cytomegalovirus Discovered by Expanded Targeted Testing.

IMPORTANCE

It is unclear whether a targeted testing or universal screening approach is preferable for identifying newborns with congenital cytomegalovirus (cCMV) infection.

OBJECTIVE

To determine whether infants with cCMV identified by an expanded targeted approach would have been identified by dried blood spot (DBS) universal screening.

DESIGN, SETTING, AND

PARTICIPANTS

This population-based cohort study included newborns from 26 birth hospitals in Utah who were diagnosed with cCMV via expanded targeted early CMV testing between 2019 and 2024. These newborns had their neonatal DBS tested for CMV DNA at the University of Minnesota laboratory in January 2025.

EXPOSURES: Detection of CMV using a polymerase chain reaction (PCR) assay.

MAIN OUTCOMES AND MEASURES: The main outcome was the diagnostic sensitivity of DBS PCR with confirmed cCMV infection and cCMV symptomatic disease severity.

RESULTS

Among 13 078 tested newborns (48.2% female and 51.8% male), 80 (0.6%) were diagnosed with cCMV following expanded targeted screening. Mean (SD) time from initial diagnosis to most recent hearing assessment was 2.3 (1.6) years. Combined results from detection of either UL83 or IE genes had a sensitivity of 86.3% (69 of 80; 95% CI, 77%-92%), specificity of 99.5% (95% CI, 97.0%-99.9%), positive predictive value of 100% (95% CI, 94.7%-100%), and negative predictive value of 94.3% (95% CI, 90.0%-96.8%). The sensitivity of DBS using either UL83 or IE genes among patients who had moderate to severe symptomatic cCMV disease was 92.7% (38 of 41; 95% CI, 80.6%-97.5%), while the sensitivity for those with mild symptomatic cCMV disease using UL83 and IE combined was 78.1% (95% CI, 61.3%-89.0%).

CONCLUSIONS AND RELEVANCE: This cohort study demonstrated a relatively high sensitivity of DBS for diagnosis of cCMV infection and differentiation of the severity of symptomatic disease in a known cCMV-positive cohort identified via expanded targeted early CMV testing. These results should be interpreted with caution given the wide confidence intervals and should not be directly extrapolated to universal DBS screening performance, particularly in asymptomatic infants.