Recent cross-sectional studies suggest that reduced ability to generate alkali via the urease pathway in dental plaque may be an important caries risk factor, but it has not been assessed prospectively. ObjectiveTo evaluate the effect of plaque and saliva urease activity on the risk for developing new caries over a three-year period in children. MethodsA panel of 80 children, three to six years of age at recruitment, was followed prospectively for three years. Plaque urease activity, saliva urease activity and dental caries were measured every six months. Survival analysis methodology was used to evaluate the effect of urease on caries development during the study period adjusted for gender, age, baseline caries levels, sugar consumption, amount of plaque, and mutans streptococci levels. ResultsThe risk for developing new caries increased in a dose-responsive manner with increasing levels of urease activity in saliva (adjusted HRQ4 vs. Q1: 4.98; 95% CI: 1.33, 18.69) and with decreasing urease activity in plaque (adjusted HRQ4 vs. Q1: 0.29; 95% CI: 0.11, 0.76). Multiple measurements of urease activity were conducted to overcome the variability of urease activity in this study. Baseline caries and mutans streptococci in saliva were also important predictors of caries risk. ConclusionsIncreased urease activity in saliva can be an indicator of increased caries risk in children, whilst increased urease activity in plaque may be associated with reduced caries risk. The reproducibility of urease measurements must be improved before these findings can be further tested and clinically applied.