Are salivary NO2− / NO2− and NO3− levels biomarkers for dental caries in children? Systematic review and meta-analysis

The literature is conflicting regarding salivary nitrite (NO₂⁻)/nitrite and nitrate (NO₂⁻ and NO₃⁻) levels in children affected by dental caries. For this reason, a systematic review to provide a consensus on the subject was propose, whose objective is to verify whether these molecules could be used as biomarkers in children with caries. A comprehensive search was performed on online database and eleven articles were included in the meta-analysis. The methodological quality of studies was assessed by Newcastle-Ottawa Scale recommended for case-control studies and by AXIS tool for cross-sectional studies. Grading of Recommendations Assessment, Development and Evaluation was used for the assessment of the certainty of the evidence for each outcome. The results showed lower NO₂⁻ levels in the group of children affected by dental caries (SMD = −2.18 [-3.24, −1.13], p < 0.01). Age, saliva collection and methods of evaluation can impact the results. When evaluating the severity of the condition, an important variation was detected in relation to the different evaluation methods NO₂⁻/NO₂⁻ and NO₃⁻. In conclusion, based on the evidence presented, the results suggest that NO₂⁻ levels in saliva are a possible biomarker of dental caries. Results should be evaluated with caution due to the very low evidence from primary studies. Longitudinal studies are necessary to strengthen this hypothesis.