Comparative diagnostic performance of saliva PCR and dried blood spot PCR for congenital cytomegalovirus detection: a systematic review and meta-analysis

Abstract

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is a leading cause of non-genetic sensorineural hearing loss and neurodevelopmental impairment. This study aimed to systematically evaluate and compare the diagnostic accuracy of saliva polymerase chain reaction (PCR) and dried blood spot (DBS) PCR for detecting cCMV in newborns. METHODS: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. PubMed, Cochrane Library, ProQuest, and Google Scholar were searched for studies published between 2010 and 2025. Eligible studies reported sufficient data to construct 2 × 2 contingency tables and used urine PCR or culture as reference standards. Pooled sensitivity, specificity, likelihood ratios, diagnostic odds ratios, and summary receiver operating characteristic (SROC) curves were estimated using random-effects and bivariate models. RESULTS: Nineteen studies comprising 103,669 neonates were included. Saliva PCR demonstrated high pooled sensitivity (0.95, 95% CI: 0.91-0.97) and perfect specificity (1.00, 95% CI: 0.99-1.00). In contrast, DBS PCR showed lower pooled sensitivity (0.72, 95% CI: 0.45-0.89) while maintaining high specificity (0.99, 95% CI: 0.92-1.00). Subgroup analysis revealed significantly higher sensitivity for saliva PCR compared with DBS PCR (p = 0.004). SROC analysis indicated superior overall diagnostic performance for saliva PCR (AUC = 0.72) relative to DBS PCR (AUC = 0.56). Substantial heterogeneity was observed, particularly among DBS studies. CONCLUSION: Saliva PCR demonstrates superior sensitivity and overall diagnostic accuracy for early detection of cCMV compared with DBS PCR, while both methods show high specificity. These findings support saliva PCR as the preferred modality for newborn screening where feasible, while DBS PCR may serve as a complementary or alternative approach in large-scale or resource-limited settings. CLINICAL TRIAL: Not applicable.