Fluorides, Dental Caries Clinical Trial
Official title:
Caries Preventive Effect of Salt Fluoridation in Preschool Children in The Gambia
This was a block-randomized, controlled, open-label trial and was executed in two preschools in The Gambia. Fluoridated table salt (250 mg F/kg salt) was administered in daily communal preschool feeding. In total, 304 children in the test group and 137 children in the control group, aged 3 to 5 years were enrolled according to inclusion criteria (complete primary dentition and a parental or legal guardian informed consent). Mean difference of incidence of cavitated carious lesions (Δd3/4mft) after 12 months was the primary end point. The relative preventive dental caries effect was. Secondary end points were the difference of incidence of white spot lesions and the difference of incidence of total carious lesions.
Patients and Methods This was a block-randomized, controlled, open-label trial to evaluate
the relative caries preventive effect of fluoridated table salt in communal feeding of
preschool children after 12 months. The study protocol was approved by the Witten/Herdecke
University institutional review board (No. 106/2010) and by the Department of State for
Health and Social Welfare of the Republic of The Gambia in the form of a memorandum of
understanding. All participants and parents or legal guardians gave written informed consent
with the aid of a native speaker before study-related procedures were performed and the
study was conducted in line with the Declaration of Helsinki. Figure 1 describes the study
design in brief.
Sample Size Sample size calculation was performed with G*Power 3. Basic data for sample size
calculation was the mean dental caries experience of preschool children in urban parts of
The Gambia that was reported to be 2.09 dmft teeth (SD: 1.92). An effect measure of caries
prevention by fluoridated table salt of 35 % was assumed according to the relevant
literature. Alpha error was set with 0.05, and the study power with 80 %. A target sample of
130 subjects for each study arm (test and control group) was calculated.
Study Population
Eligible participants were children aged from 3 - 5 years living in urban Gambia with
preschool attendance at the co-operating kindergartens. The inclusion criteria for
participating in this study were:
1. a complete primary dentition
2. parental or legal guardian informed consent. The only exclusion criteria was refusal to
participate in the study. Study End Points To measure the caries preventive effect of
salt fluoridation (1) the difference of incidence of cavitated carious lesions
(Δd3/4mft) after study related intervention was chosen as the primary end point. Using
the primary study end point, the relative preventive dental caries effect was
calculated according to the following formula: 100 - (Δd3/4mft (test group) / Δd3/4mft
(control group)) x 100.
Secondary end points were:
(2) the difference of incidence of white spot lesions (ΔG2-4) with G2 denoting slight white
spot formation, G3 denoting excessive white spot formation, and G4 denoting white spot
formation with cavitation into enamel.
(3) the difference of incidence of total carious lesions (ΔTCL (= G2-4 + d3/4mft)).
Total carious lesions (TCL) were calculated as a weighted sum score according to the
following weights: G2: 1 point; G3: 2 points; G4: 3 points; d3/4t and ft: 4 points; tooth
with pulpitis, ulcera, fistula or abscess due to caries: 5 points; missing tooth (mt): 6
points.
For quality control, (4) a fluoride concentration measurement of the table salt was
performed as safety endpoint at t0, t0+6 mths, and t0+12 mths = t1. For this purpose,
packages with fluoridated salt and provided for the study were randomly selected.
Measurements were executed using an Orion Ionplus Fluoride Electrode (Thermo Electron,
Beverly, USA) after standardised calibration for low-level measurement. The analysis was
undertaken in triplicate per sample, and a mean was calculated for each measurement point.
The threshold limit value was set at 0.1 ppm F-.
Participants and Investigators Participants were screened, recruited, and included in the
study at two public preschools in Brikama, West Coast Region, The Gambia, in March 2012. The
screening and dental examinations took place during regular teaching time in an affiliated
dental station. Two investigation teams performed the study related examinations. A team
consisted of two dentists of which one was the clinical investigator and the other served as
information specialist. All were equally calibrated in clinical dental caries screening.
Inter-examiner Cohen´s reliability Ҡ was 0.82 [Cohen, 1960], indicating an almost perfect
match against the expert (RAJ).
Randomization and Allocation Concealment As the intervention procedure was bound to the
communal preschool feeding, an individual randomization of subjects to the study arms was
not feasible. Instead, one preschool was chosen for intervention and the other preschool
served as control. The assortment of intervention was performed according to a random
selection by a person who apart from this was not involved in the study (LGW). All preschool
children meeting inclusion and exclusion criteria were primarily allocated to the test group
and to the control group, respectively.
Interventions Natural fluoride availability in the Gambian West Coast Region had been
determined in advance of this interventional study to evaluate general fluoride
availability. In the study region, the fluoride concentration in drinking water was
determined to be 0.1 mg/liter. In this region, traditional oral hygiene for children does
not comprise (fluoride) toothpastes until religious maturity at the age of about 12 years.
Study related intervention of administration of fluoridated table salt (MarkenJodSalz +
Fluorid, Südsalz, Heilbronn, Germany) was organised during once-daily communal preschool
feeding. Acccording to the manufacturer's declaration, fluoride concentration of the
fluoridated table salt was 250 mg/kg. The central preschool kitchen was instructed to
flavour the meals with a calculated amount of fluoridated table salt. The amount was set
with 0.4 mg fluoride per capita and day for a period of 12 months. The study intervention
period was executed between September 2012 and August 2013. The calculation for the total
flavouring table salt amount was as follows:
- number of subjects in the intervention preschool (including subjects not included in
the study but taking part in the communal preschool feeding) n = 450
- fluoride concentration of fluoridated table salt: 25 mg F- per 100 g salt
- recommended daily age-dependent supplementary dose: 0.4 mg fluoride per capita (i. e.
0.05 - 0.07 mg F- per kg body weight)
- consequently, 720 g fluoridated table salt daily for preparation of the communal
preschool feeding, resp. 1.6 g fluoridated table salt per capita and day, which
complied with recent WHO recommendations of salt intake.
Meals of the control group were prepared without fluoridated table salt. Before starting the
intervention, all subjects received a dental examination at t0. Teeth were cleaned with an
electric toothbrush (Vitality precision clean, Oral-B, Schwalbach, Germany) before
inspection without using toothpaste. Teeth were then dried with cotton rolls (Cotton rolls
for kids, Roeko, Langenau, Germany) and hand-bellows (Delamax, Berlin, Germany). Dental
caries inspection was performed visually with the aid of dental mirrors and blunt probes in
natural light according to recent recommendation for epidemiological field studies. With
respect to available field hygiene measures, disposable dental instruments were used
(Nordenta, Hamburg, Germany). After completion of the intervention, all subjects were
dentally examined again at t1 in the exact same manner than at t0.
Study Settings According to the allocation concealment, subjects of the test group were
preschool children at the "Kindergarten Wattenscheid in Gambia", Brikama-Kabafita, West
Coast Region, The Gambia. Subjects of the control group were preschool children at the
"Kindergarten Bottrop in Gambia", Brikama, West Coast Region, The Gambia.
Study Hypothesis The investigators used a null hypothesis (H0) assuming no statistical
difference of Δd3/4mft at t1 between the test group and control group.
Statistical Analysis Demographic data were compared as inter group comparison using Wilcoxon
rank sum test with p <0.05 for statistical significance. Analyses of the study end points
were performed using 95 percent confidence intervals (95%-CI). IBM SPSS software (version
21; International Business Machines Corp, Armonk, USA) was used for computing statistical
analysis.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention