Quantifying the contribution of ¹⁸F-FDG PET to the diagnostic assessment of pediatric patients with fever of unknown origin: a systematic review and meta-analysis

Background: The value of ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) in the diagnostic assessment of pediatric fever of unknown origin is not known, and evidence from adults is not applicable.

Objective: To quantify the contribution of ¹⁸F-FDG PET to pediatric fever of unknown origin, considering its diagnostic limitations.

Materials and methods: We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials up to Feb. 18, 2021. We included studies on patients with pediatric fever of unknown origin presenting sufficient data to calculate the likelihood of achieving definite diagnosis (based on pathology or clinical follow-up) between those with abnormal PET findings versus those with normal PET findings. We assessed the risk of bias using a modified Newcastle-Ottawa quality assessment scale and quantified the value of PET by pooling the likelihood of achieving definite diagnosis using a random-effects model.

Results: We included 6 studies and found that pediatric patients with abnormal PET findings were about 17 times more likely to achieve definite diagnoses than those with normal PET findings (odds ratio [OR]: 16.75, 95% confidence interval [CI] 8.0-35, P < 0.00001). Sensitivity analyses using a fixed-effect model (OR 16.91, 95% CI 8.1-35, P < 0.0001) or removing one study at a time (OR 12-20, 95% CI lower bound 3.8-8.6, 95% CI upper bound 33-45, P < 0.0001) did not significantly alter the results. Sample size (interaction P = 0.75), imaging modality (interaction P = 0.29), length of follow-up (interaction P = 0.37), fever of unknown origin subclasses (interaction P = 0.89) and geographical areas (interaction P = 0.74) of studies showed no statistically significant influence on the results.

Conclusion: ¹⁸F-FDG PET is a promising approach in the diagnostic work-up of pediatric fever of unknown origin. Further studies are warranted to support routine use in clinical care.