Purpose: To assess the diagnostic accuracy and safety of contrast-enhanced voiding urosonogram using second-generation contrast with harmonic imaging (CEVUS-HI) in detecting vesicoureteral reflux (VUR) among children.
Methods: A systematic literature search was performed in March 2018. Relevant comparative studies from Medline, EMBASE, World of Science, Scopus, CENTRAL, WHO trial registry and Clinicaltrials.gov were identified and appraised using QUADAS-2. Diagnostic accuracy parameters were determined using VCUG as the reference standard. Adverse effects related to ultrasound contrast were summarized. The heterogeneity and inter-study variability were determined. After appropriate subgroup diagnostic accuracy parameters were investigated, summarizing receiver operator characteristics was constructed using the bivariate model meta-regression to determine the area under the curve (AUC).
Results: A total of 12 studies with low-high risk of bias, including 1917 ureteral units from 953 patients were assessed for this meta-analysis. The included studies reported no serious adverse events associated with the ultrasound contrast. The pooled diagnostic accuracy parameters of CEVUS-HI in detecting VUR amongst children were: sensitivity 90.43 (95% CI 90.36-90.50), specificity 92.82 (95% CI 92.76-92.87), the calculated (+) likelihood-ratio 12.59 (95% CI 12.49-12.68), (-) likelihood-ratio of 0.103 (95% CI 0.102-0.104) and extrapolated pooled diagnostic odds-ratio was 122.12 (95% CI 120.75-123.49). Heterogeneity with interstudy variability was noted (p < 0.0001, I-squared > 70%). The AUC was determined to be 0.965 for VUR detection.
Conclusions: The pooled diagnostic accuracy parameters from low-moderate quality of evidence have illustrated that the CEVUS-HI study has an excellent safety profile and acceptable diagnostic accuracy. It may be considered as an alternative diagnostic modality for assessment of VUR among children.
Keywords: Contrast-enhanced voiding urosonogram; Diagnostic accuracy; Vesicoureteral reflux; Voiding cystourethrogram.