Efficacy of natural antimicrobials derived from phenolic compounds in the control of biofilm in children and adolescents compared to synthetic antimicrobials: A systematic review and meta-analysis

Aim: To evaluate the efficacy of natural antimicrobials derived from phenolic compounds (NAPs), compared to synthetic antimicrobials (SAs), in the biofilm control and microorganisms (MOs) count among children and adolescents at different intervention times through a systematic review and meta-analysis. Methods: Electronic searches were carried out in PubMed, Scopus, Cochrane Library, Web of Science, VHL, and Grey Literature. Randomized and non-randomized clinical trials were included. Methodological quality and risk of bias were assessed using the tools ROBINS-I and RoB 2.0. Meta-analyses (MAs) were performed according to three parameters: the influence of NAPs on the plaque index (PI) mean; the period of NAPs administration (<= 15 days/>15 days) on the biofilm reduction; and the influence of NAPs on the MOs count subgrouping according to the type of MO (total MOs, S. mutans, and Streptococcus spp.). The standard mean differences were calculated (p <= 0.05) for all analyses, and the heterogeneity was tested through the I-2 index. The evidence was certaintytested using the GRADE approach. Results: Sixteen studies were selected for qualitative synthesis, and I-2 studies were included in the MAs. NAPs were less efficacious in improving the PI (p < 0.0001, I-2 > 87 %) and reducing biofilm over time (p < 0.01, I-2 > 87 %) but presented a reduction in MOs count similar to that of SAs (p = 0.3, I-2 = 0%). The quality of the evidence ranged from moderate to low. Conclusion: Although the use of NAPs is similar to the use of SAs in reducing MOs count, it is less effective than SAs in improving PI mean and for biofilm reduction over time.