The aim of this 3-year longitudinal study was to analyze caries increment and the caries-preventive effect of sealants in adolescents in the setting of the German national health system. 434 pupils (193 male, 241 female) took part in compulsory school examinations at age 12 (mean 12.3 ± 0.4 years) and 15 (mean 15.6 ± 0.3 years) according to WHO criteria, including the examination of sealants. Mean DMFT increased from 1.78 (± 2.15) to 3.97 (± 3.68), mean DMFS from 2.79 (±4.07) to 6.94 DMFS (± 8.34), respectively. Logistic regression analysis showed that high caries incidence at the individual level was mostly associated with the type of school (’Gymnasium’, RR = 0.3), gender (female, RR = 2.08) and high baseline DMFS (RR = 1.2 per surface), but not with the number of sealants. In an interaction model, adolescents with high baseline DMFS values had an even higher risk of caries increment with an increasing number of sealants compared to adolescents with fewer sealants (p = 0.047). At the tooth level, this effect was detected for first permanent molars, while sealants in premolars and second permanent molars did not result in a statistically significant caries-preventive effect due to the low caries incidence on these surfaces. Thus, sealants on occlusal surfaces of first permanent molars were only protective in individuals with low or moderate caries activity (p = 0.006), which indicates the need for other measures to reduce caries activity in high risk adolescents. In addition, rates of 19% lost sealants and 18% carious or filled surfaces in 3 years suggest a discrepancy between sealant retention under real-life conditions and the results of controlled clinical trials.

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