Leche fluorurada para la prevención de las caries dentales
Resumen
Antecedentes
La caries dental aún es un problema importante de salud pública en la mayoría de los países industrializados, y afecta del 60% al 90% de los niños en edad escolar y a la gran mayoría de los adultos. La leche puede ser un vehículo relativamente coste efectivo para la administración de flúor para la prevención de la caries dental. Ésta es una actualización de una revisión Cochrane publicada por primera vez en 2005.
Objetivos
Evaluar los efectos de la fluoración de la leche para prevenir la caries dental a nivel comunitario.
Métodos de búsqueda
Se hicieron búsquedas en el Registro de Ensayos del Grupo Cochrane de Salud Oral (Cochrane Oral Health Group) (hasta noviembre de 2014), en el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials, CENTRAL) (The Cochrane Library, 2014, Número 10), MEDLINE vía OVID (1946 hasta noviembre 2014) y EMBASE vía OVID (1980 hasta noviembre 2014). También se buscaron ensayos en curso en el U.S. National Institutes of Health Trials Register (https://clinicaltrials.gov) y la WHO International Clinical Trials Registry Platform (http://apps.who.int/trialsearch). No se aplicaron restricciones de idioma o fecha de publicación al buscar en las bases de datos electrónicas.
Criterios de selección
Ensayos controlados aleatorizados (ECA), con un período de intervención y seguimiento de al menos dos años, que compararon la leche fluorada con la leche no fluorada.
Obtención y análisis de los datos
Dos autores de la revisión de forma independiente evaluaron el riesgo de sesgo de los ensayos y extrajeron los datos. Se utilizaron los procedimientos metodológicos estándar previstos por Cochrane.
Resultados principales
Se incluyó un ECA no publicado que asignó al azar a 180 niños de tres años al comienzo del estudio. El contexto fue una guardería infantil en una zona con alta prevalencia de caries dental y un bajo nivel de flúor en el agua potable. Estuvieron disponibles para el análisis los datos de 166 participantes. El estudio tuvo alto riesgo de sesgo. Después de tres años, hubo una reducción de las caries en los dientes permanentes (diferencia de medias [DM] ‐0,13, intervalo de confianza [IC] del 95%: ‐0,24 a ‐0,02) y en los dientes primarios (DM ‐1,14, IC del 95%: ‐1,86 a ‐0,42), medida por el índice de dientes cariados, perdidos y obturados (DMFT para los dientes permanentes y el dmft para los dientes primarios). En el caso de los dientes primarios, se trata de una reducción sustancial equivalente a una fracción prevenida del 31%. En el caso de los dientes permanentes, el nivel de la enfermedad fue muy bajo en el estudio, lo que dio como resultado un pequeño tamaño absoluto del efecto. El estudio incluido no informó sobre otros resultado de interés para esta revisión (eventos adversos, dolor dental, uso de antibióticos o necesidad de anestesia general debido a procedimientos dentales).
Conclusiones de los autores
Hay evidencia de baja calidad que indica que la leche fluorada puede ser beneficiosa para los escolares y contribuir a una reducción sustancial de las caries dentales en los dientes primarios. En su mayoría la evidencia es de calidad baja, por lo que es probable que la realización de estudios de investigación adicionales tenga una repercusión importante sobre la confianza en la estimación del efecto y pueda cambiarla. Solo hubo un estudio relativamente pequeño, que tuvo importantes limitaciones metodológicas en los datos para la efectividad en la reducción de la caries. Además, no hubo información sobre los posibles daños de la intervención. Se necesitan ECA adicionales de alta calidad antes de poder establecer conclusiones definitivas sobre los efectos beneficiosos de la fluoración de la leche.
PICO
Resumen en términos sencillos
Leche fluorada para prevenir las caries
Pregunta de la revisión
Se comparó la evidencia sobre los efectos de la leche fluorada versus la leche no fluorada para la prevención de las caries.
Antecedentes
Las caries dentales aún son un problema importante de salud pública en la mayoría de los países industrializados, y afecta del 60% al 90% de niños en edad escolar y a la gran mayoría de los adultos. Es la causa principal del dolor oral y la pérdida de los dientes. La prevalencia de la caries dental varía entre los distintos países y dentro de ellos, pero en general las personas de los grupos socioeconómicos más bajos (medidos por los ingresos, la educación y el empleo) están más afectadas.
El flúor es un mineral que previene las caries y se puede agregar al agua potable, la sal o la leche como medida de salud pública para promover la salud oral. La leche fluorada suele estar disponible para los niños junto con la leche no fluorada, a través de los planes de distribución de leche en las escuelas o de los programas nacionales de nutrición. El uso de estos sistemas de distribución puede proporcionar un medio conveniente y económico de administrar suplementos de flúor específicos a los niños cuyos padres deseen participar en el programa.
Características de los estudios
Los autores del Grupo Cochrane de Salud Oral (Cochrane Oral Health Group) examinaron los estudios existentes para encontrar toda la evidencia disponible hasta noviembre 2014. Se buscaron en las bases de datos científicas ensayos clínicos que probaran los efectos de la leche fluorada en comparación con la leche no fluorada. El tratamiento se debía utilizar y monitorizar durante un mínimo de dos años.
Resultados clave
Se encontró un estudio no publicado que incluyó 180 niños de tres años, a los que se les dio leche fluorada o no fluorada en guarderías de una zona con alta prevalencia de caries dentales y un bajo nivel de flúor en el agua potable. Después de tres años, el 92% de los niños estaban disponibles para el análisis. La evidencia indica que la leche fluorada puede ser beneficiosa para los escolares al reducir sustancialmente la formación de caries en los dientes de leche. No hubo información disponible sobre los posibles eventos adversos.
Calidad de la evidencia
Se consideró que la evidencia fue de calidad baja debido a la falta de estudios pertinentes, el riesgo de sesgo en el estudio identificado y las preocupaciones sobre la aplicabilidad de los resultados a diferentes contextos y poblaciones. Se necesitan estudios adicionales de calidad alta antes de poder establecer conclusiones definitivas sobre los efectos beneficiosos de la fluoración de la leche.
Authors' conclusions
Summary of findings
| Fluoridated milk compared to non‐fluoridated milk for preventing dental caries | |||||
| Patient or population: general population | |||||
| Outcomes | Illustrative comparative risks* (95% CI) | No. of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | ||||
| Non‐fluoridated milk | Fluoridated milk | ||||
| Caries in permanent teeth: DMFT (3 years) | The mean caries in permanent teeth: DMFT (3 years) in the control group was 0.17 | The mean caries in permanent teeth: DMFT (3 years) in the intervention group was 0.13 lower (0.24 lower to 0.02 lower) | 166 | ⊕⊕⊝⊝ | Disease level very low; small absolute effect size |
| Caries in primary teeth: dmft (3 years) | The mean caries in primary teeth: dmft (3 years) in the control group was 3.64 | The mean caries in primary teeth: dmft (3 years) in the intervention group was 1.14 lower (1.86 lower to 0.42 lower) | 166 | ⊕⊕⊝⊝ | Substantial effect size equivalent to a 31% prevented fractionc |
| Adverse effects: dental fluorosis | No evidence found | ||||
| Dental pain due to decay | No evidence found | ||||
| Antibiotics due to dental infections | No evidence found | ||||
| Requirement for general anaesthesia due to dental procedures for caries | No evidence found | ||||
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | |||||
| GRADE Working Group grades of evidence | |||||
| aDowngraded for risk of bias: sequence generation method unclear, and participants were not blinded. bDowngraded for indirectness: applicability of evidence to different settings and populations unclear; there was not much baseline information about the population in the study. cPrevented fraction (PF), expressed as percentages = (mean increment in control group − mean increment in intervention group)/mean increment in control group) x 100%. PF values between 1% to 10% are considered to be a small effect; between 10% to 20%, a moderate effect; and above 20%, a large or substantial effect. | |||||
Background
Description of the condition
Dental caries is a disease of the hard tissues of the teeth. Over time, it forms through a complex interaction between acid‐producing bacteria, fermentable carbohydrates, and numerous host factors related to teeth and saliva. It is the primary cause of oral pain and tooth loss. In its early stages, it can be arrested and potentially reversed, but without proper care, it can progress until the tooth is destroyed, causing severe pain and suffering, especially in children (Selwitz 2007).
According to the World Oral Health Report 2003, dental caries remains a major public health problem in most industrialised countries, affecting 60% to 90% of schoolchildren and the vast majority of adults (Petersen 2003). It is also the most prevalent oral disease in several Asian and Latin American countries. Although for the moment it appears to be less common and less severe in most of Africa, the report anticipates that changing living conditions and dietary habits (particularly growing sugar consumption and low exposure to fluorides) will contribute to increasing the incidence of dental caries in many African countries.
There are profound inequalities in caries status both between and within countries, and the distribution of disease within communities fluctuates (Pitts 2011). However, a recent systematic review showed that low socioeconomic position is associated with a higher risk of having caries lesions or caries experience; this association might be stronger in developed countries (Schwendicke 2015).
Description of the intervention
The use of milk as a vehicle for providing additional fluoride in a dental public health programme is attractive for several reasons. First of all, milk is already an important part of children's diets and has long been used as a nutritional supplement for vulnerable groups. As early as 1980, a randomised controlled trial (RCT) showed a small but statistically significant benefit to growth in deprived children following the provision of free school milk over two years (Baker 1980), and the NHS Centre for Reviews and Dissemination included the provision of free school milk in a list of nine evidence‐based interventions to reduce health inequalities (Smith 1997). Another RCT confirmed that increased milk consumption significantly enhanced bone mineral acquisition and attainment of peak bone mass in adolescent girls (Cadogan 1997).
Moreover, fluoridated milk can be produced in a variety of liquid forms (pasteurised, ultra‐high temperature pasteurised (UHT) and sterilised) and in powder, each containing different fluoridating compounds. Compounds used to fluoridate milk in early clinical trials and laboratory tests included sodium fluoride, calcium fluoride, disodium monofluorophosphate (MFP) and disodium silicofluoride. However, the vast majority of current fluoridated milk schemes worldwide use sodium fluoride. The exception is the caries prevention programme in rural areas of Chile, where the powdered milk and milk derivatives provided to the participating subjects are fluoridated using MFP (Villa 2009).
The choice of fluoridation method depends on many factors, including the nature of food supplement programme itself and the availability of human resources and training. Likewise, the concentration of fluoride required will depend on the age of the children, the concentration of fluoride in the local water supply and the volume of fluoridated milk ingested daily, among other considerations (Mariño 2011).
The feasibility and sustainability of a milk fluoridation scheme depends largely on the existence and type of nutritional supplement programmes. Because any kind of milk can be fluoridated, any system that provides a regular supply of milk to children could potentially provide a vehicle for fluoride delivery. Clearly, an existing milk distribution scheme or national nutrition strategy would simplify the implementation of a milk fluoridation programme (Mariño 2011).
How the intervention might work
Elevating the concentration of the fluoride ion at the plaque‐enamel interface results in a reduction in the rate of demineralisation, an increase in the rate of remineralisation, and a reduction in the rate of acid production in plaque, all of which help to prevent caries.
The use of milk as a vehicle for fluoride delivery has raised questions concerning possible chemical reactions between milk and fluoride ions, the bioavailability of systematically administered fluoride in milk, and potential interactions involving fluoride in the oral cavity (enamel, saliva, plaque and caries). The results of basic studies on milk fluoridation have been published in more than 100 peer‐reviewed papers, with increasing frequency in the past 20 years. Based on these studies, it appears that most of the fluoride added to milk forms a soluble complex with the protein fraction of milk, from which the fluoride can be liberated in ionic (and bioavailable) form. The absorption of fluorides with simultaneous food intake is slower than for fluoride without food, and the proportion absorbed depends on the calcium content of the diet. Different types of milk are consumed around the world: whole or low‐fat; fresh, pasteurised or sterilised; liquid or powdered. The bioavailability of added fluoride has been shown to be satisfactory in all of these, both on the day of milk processing and after several days' storage (Bánóczy 2013).
The fluoride ions available from the consumption of fluoridated milk are incorporated into dental enamel, which inhibits demineralisation and promotes remineralisation. In addition, 30 to 60 minutes after ingestion of fluoridated milk, the levels of fluoride in both whole saliva and dental plaque increase as a consequence of the presence of fluoridated milk in the mouth and increased concentrations of fluoride in salivary secretions following the absorption of ingested fluoride. Thus, fluoride in milk acts both systematically and topically, in the same way as fluoride in water (Bánóczy 2013).
Why it is important to do this review
Milk fluoridation, as a possible dental caries prevention medium, was first proposed by a Swiss paediatrician in the 1950s (Ziegler 1953). Since then, the caries‐inhibiting characteristics of fluoridated milk have been investigated with a view to using it in community‐based caries prevention programmes (Bánóczy 2009). Economic evaluations have demonstrated that milk provides a relatively cost‐effective vehicle for fluoride in the prevention of dental caries (Calvert 1998; Mariño 2007; Mariño 2011).
This is an update of the Cochrane review first published in 2005 (Yeung 2005). The original review found that there were insufficient studies with good quality evidence examining the effects (benefits and harms) of fluoridated milk in preventing dental caries. The included studies, however, suggested that fluoridated milk was beneficial to schoolchildren, especially for their permanent dentition.
Objectives
To assess the effects of milk fluoridation for preventing dental caries at a community level.
Methods
Criteria for considering studies for this review
Types of studies
We included parallel RCTs, including cluster‐randomised trials (e.g. those than randomised at the level of school or class in children) and excluded quasi‐randomised trials.
We also included non‐blinded studies.
We excluded studies with an intervention or follow‐up period of less than two years. For trials designed in school settings, we included studies lasting an equivalent of two school years, even if intervention or follow‐up period fell short of 24 months.
Types of participants
General population, irrespective of age or level of risk for dental caries.
Types of interventions
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Active intervention: fluoridated milk (all concentrations/dosage were considered)
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Control: non‐fluoridated milk
The milk was provided directly to the children or their family. Any payment for milk should have been equivalent in the fluoridated and non‐fluoridated groups.
Types of outcome measures
Primary outcomes
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Changes in caries experience or caries increment, as measured by changes in decayed, missing and filled figures on permanent teeth or surfaces (DMFT or DMFS) or primary teeth or surfaces (dmft or dmfs). Caries was assessed clinically. However, if a combined clinical and radiographic assessment was used, then this was recorded and noted
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Adverse effects: dental fluorosis
Secondary outcomes
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Dental pain due to decay
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Antibiotics due to dental infections
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Requirement for general anaesthesia due to dental procedures for caries
Search methods for identification of studies
Electronic searches
To identify potential studies for inclusion in this review, we developed detailed search strategies for each database used. These were based on the search strategy developed for MEDLINE (OVID) but revised appropriately for each database. The search strategy used a combination of controlled vocabulary and free text terms and was linked with the sensitivity maximising version (2008 revision) of the Cochrane Highly Sensitive Search Strategy (CHSSS) for identifying RCTs in MEDLINE, as referenced in Section 6.4.11.1 and detailed in Box 6.4.c of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). The EMBASE search was linked to the Cochrane Oral Health Group filter for identifying RCTs.
We searched the following electronic databases.
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The Cochrane Oral Health Group's Trials Register (to November 2014) (see Appendix 1).
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CENTRAL (The Cochrane Library, 2014, Issue 10) (see Appendix 2).
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MEDLINE via OVID (1946 to November 2014) (see Appendix 3).
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EMBASE via OVID (1980 to November 2014) (see Appendix 4).
We did not place any restrictions on the language or date of publication when searching the electronic databases.
Searching other resources
We searched the following databases for ongoing trials (see Appendix 5).
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U.S. National Institutes of Health Trials Register (https://clinicaltrials.gov) (to November 2014);
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WHO International Clinical Trials Registry Platform (http://apps.who.int/trialsearch) (to November 2014).
Grey literature
In an attempt to identify unpublished or ongoing studies, we contacted the Borrow Foundation to obtain and screen the references in their database of milk fluoridation research (version 6.7, dispatched 10 December 2013) (www.borrowfoundation.org/research).
Handsearching
We handsearched the Journal of Public Health Dentistry (January 1997 to December 2003) for the original review (Yeung 2005). For the updated review, we only included handsearching done as part of the Cochrane Worldwide Handsearching Programme and uploaded to CENTRAL (see the Cochrane Master List for details of journal issues searched to date).
Reference lists
The reference lists of all included studies and relevant reviews were checked manually to identify any additional studies.
Data collection and analysis
Selection of studies
Two authors independently scanned the titles and available abstracts of all reports identified through the electronic searches.
We obtained the full text of studies that appeared to meet the inclusion criteria or for which there were insufficient data in the title and abstract to make a clear decision. Two authors then independently assessed the full reports obtained from all searches, electronic or otherwise, to establish whether the trials met the inclusion criteria or not, discussing disagreements to reach a consensus. When the two authors could not come to an agreement, we consulted a third author. We recorded all rejected studies and our reasons for excluding them in the Characteristics of excluded studies table. For all studies meeting the inclusion criteria, we extracted data and assessed the risk of bias.
Data extraction and management
Two authors independently extracted data using specially designed data extraction forms that we had previously piloted on several papers and modified as needed. We discussed disagreements, consulting a third author when necessary. We contacted study authors to clarify details or obtain missing information when necessary. We excluded data until further clarification was available if we could not reach an agreement.
For each trial, the following data were recorded.
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Citation details, including year of publication, country of origin, setting and source of funding.
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Details of participants, including demographic characteristics and criteria for inclusion.
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Details of intervention, including type and duration of intervention, duration of follow‐up and method of administration.
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Details of outcomes reported, including method of assessment and time intervals.
The following information was also noted.
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Compliance (level of supervision of participants while they drank the milk they were given).
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Comparability of control and treatment groups at entry.
We anticipated that some studies would report data at more than one time point. To minimise issues related to multiplicity of analysis, we planned to only extract and analyse the longest available data for each of the included studies.
Assessment of risk of bias in included studies
Two authors independently assessed the risk of bias of the included trial as part of the data extraction process.
We used the Cochrane Collaboration 'Risk of bias' assessment tool (Higgins 2011) available in Review Manager (RevMan). The domains we assessed included:
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sequence generation;
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allocation concealment;
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blinding of participants and personnel;
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blinding of outcomes assessment;
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incomplete outcome data;
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selective outcome reporting;
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other bias.
The review authors judged the risk of bias for each domain as 'high', 'low' or 'unclear' based on the criteria listed in Section 8.5 of the Cochrane Handbook for Systematic Reviews of Interventions, which focuses on the importance of the risk (i.e. whether the presence of the risk could have an important impact the result or the conclusion of the trial) rather than its mere presence (Higgins 2011).
If insufficient detail was reported on what happened in the study, the risk of bias would be ‘unclear' unless authors had other reasons to judge it as 'high' or 'low'. An ‘unclear’ judgement was also made if what happened in the study was adequately described, but the risk of bias was unknown or difficult to judge.
Measures of treatment effect
Prevented fraction (PF) was the measure of treatment effect presented for caries increment. PF was calculated as the mean increment in the control group minus the mean increment in the intervention group, divided by the mean increment in the control group. For an outcome such as caries increment (where discrete counts are considered to approximate to a continuous scale and are treated as continuous outcomes), this measure was considered more appropriate than the mean difference or standardised mean difference since it allowed a combination of different ways of measuring caries increment and a meaningful investigation of heterogeneity between trials. It is also simple to interpret.
For dichotomous outcomes (where the outcome of interest was either present or absent), we planned to express the estimate of treatment effect of an intervention as risk ratios (RRs) together with 95% confidence intervals (CIs) or as hazard ratios if these were available as time‐to‐event data. Where appropriate, we also planned to present the corresponding absolute reductions with risks, either as numbers needed to treat or absolute risk reduction per 1000 people. For continuous outcomes, we planned to report mean differences (MDs) and standard deviations, except for outcomes which had used difference scales, in which case we would have pooled them using the standardised mean difference.
Unit of analysis issues
Had we found cluster RCTs, we would have estimated the design effect with the appropriate methods as detailed in Chapter 16 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).
Dealing with missing data
Where data were missing from the published report of a trial, we contacted the author(s) to obtain the data and clarify any uncertainty. In case of missing data, we aimed to base the review on an available case analysis, if possible followed by a sensitivity analysis if the missing data posed a high risk of bias.
For continuous data, we planned to use the methods for estimating missing standard deviations in Section 7.7.3 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Otherwise we would not have undertaken any imputations or used any statistical methods to impute missing data.
Assessment of heterogeneity
We planned to assess clinical heterogeneity by examining the type of participants, interventions and outcomes in each study.
Had we found more than one study, we would have assessed statistical heterogeneity by inspecting the point estimates and CIs on the forest plots. We planned to assess and quantify the variation in treatment effects by means of Cochran's test for heterogeneity and the I2 statistic. We considered heterogeneity to be statistically significant if the P value was less than 0.1.
A rough guide to interpreting the values obtained from the I2 statistic, provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), is as follows:
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0% to 40%: might not be important.
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30% to 60%: may represent moderate heterogeneity.
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50% to 90%: may represent substantial heterogeneity.
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75% to 100%: considerable heterogeneity.
The importance of the observed value of the I2 statistic depends on (i) the magnitude and direction of effects and (ii) the strength of evidence for heterogeneity (e.g. P value from the Chi2 test, or a CI for the I2 statistic).
Assessment of reporting biases
Reporting bias can be assessed between studies or within studies.
If there had been sufficient numbers of trials (more than 10) in any meta‐analysis, we would have assessed publication bias according to the recommendations on testing for funnel plot asymmetry (Egger 1997) as described in Section 10.4 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We would have examined possible causes of any asymmetry identified or assessed it using a table to list the outcomes reported by each included study, to determine whether any studies did not report outcomes that had been reported by most studies.
We assessed within‐study reporting bias by comparing the outcomes presented in the published report against the original study protocol, whenever this could be obtained. If no protocol was available, we compared outcomes listed in the methods section against the results reported. If the study mentioned but did not adequately report non‐significant results, we considered it possible that bias in a meta‐analysis could occur, and we would have sought further information from the study authors. Otherwise, we would simply have noted a 'high' risk of bias. If there was insufficient information to judge the risk of bias, this was rated as 'unclear'.
Data synthesis
Outcomes may be assessed and reported at more than one time point in included studies. We planned to perform separate analyses for three different lengths of follow‐up periods: short term (two to three years of follow‐up), medium term (four to six years of follow‐up) or long term (at least seven years of follow‐up). We focused our main analysis on short‐term outcomes reported, as longer‐term data is not as reliable due to drop‐outs or the natural loss of primary teeth in the case of children.
We would have considered performing meta‐analyses had there been studies of similar comparisons reporting the same outcome measures. We would have combined RRs for dichotomous data and MDs for continuous data, using a random‐effects model if more than one study was found.
Subgroup analysis and investigation of heterogeneity
We planned to conduct subgroup analyses to compare the following possible variations in population and intervention, if data permitted.
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Indicators of background exposure to fluoride (e.g. socioeconomic status; presence of fluoride in drinking water, toothpaste, etc).
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Concentration/dosage of fluoride (low vs high).
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Frequency of consumption.
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Method of drinking (cup/straw).
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Compliance.
Sensitivity analysis
We planned to perform sensitivity analyses to examine the effect of randomisation, allocation concealment and blind outcome assessment on the overall estimates of effect. Had the data allowed it, we would have also examined the effect of including unpublished literature on the review's findings.
Summary of findings table
We used the GRADE approach to assess the quality of evidence related to each of the main outcomes. We used the GRADEprofiler to import data from RevMan to create the 'Summary of Findings' tables. To assess the overall quality of evidence for each outcome, we downgraded the evidence from 'high quality' by one level for 'serious' (or by two for 'very serious') concerns related to risk of bias, indirectness of evidence, inconsistency, imprecision of effect estimates or potential publication bias.
Results
Description of studies
Results of the search
In the 2015 review update, we revised our protocol as well as the search strategies. To take into account the changes in our protocol, we also examined earlier records to ensure no relevant studies were excluded.
The updated search identified 242 records through the electronic databases and an additional 56 records through searches of other sources. After an initial screening of the titles and abstracts, we identified 24 records requiring further examination. We obtained and assessed the full text of these where available. One unpublished trial (Maslak 2004) and two ongoing studies met our inclusion criteria. See Figure 1 for a summary of the study selection process.
Study flow diagram.
Included studies
See Characteristics of included studies table.
One RCT was included in the review (Maslak 2004). The study was carried out in Russia and published as an abstract only. However, the investigators provided unpublished trial data.
Participants
A total of 180 children aged three years old were randomised, and 166 children were available for analysis.
Intervention
The children consumed the fluoridated milk (2.5 mg per litre) using a cup.
Comparison
The children in the comparator group received milk without added fluoride.
Outcomes
Changes in caries experience, measured by the dmft and DMFT, were reported yearly (Maslak 2004).
Excluded studies
See Characteristics of excluded studies table.
We excluded 21 studies, mainly because they were not RCTs. Others did not include relevant interventions or comparison groups. We also excluded a quasi‐randomised study (Stephen 1984) included in the previous version of this review (Yeung 2005) due to lack of adequate randomisation.
Ongoing studies
See Characteristics of ongoing studies table.
We identified two RCTs that are potentially relevant to this review (Stecksén‐Blicks; Svensäter). We tried to contact the investigators to obtain further information, but at the time of writing, we had not received any response.
Risk of bias in included studies
See the 'Risk of bias' table in the Characteristics of included studies section.
Allocation
The published abstract did not contain a description of randomisation, but the author provided more information when contacted. From correspondence with Maslak 2004, we confirmed that randomisation was carried out at an individual level (i.e. it was not a cluster‐randomised trial). Trial investigators noted that "the investigators did not participate in the selection process. The district for the project was determined by the Volgograd Administration. The kindergartens [i.e. nursery schools] were selected by the District Administration. The children were recruited by the kindergarten teachers." The author also used stratification during randomisation of these children, who regularly attended the nursery school, were aged three years, were caries free, lived in one city district, and had parents who had given written consent. However, the generation of the randomisation sequence was still unclear. It was also unclear if the sequence had been concealed prior to the randomisation or recruitment of children to investigators or teachers (who were involved in recruitment). Therefore, both allocation concealment and sequence generation were considered to carry an unclear risk of bias.
Blinding
The parents knew what type of milk was given to their children in the trial.
Trialists reported blinding of outcome assessors and the statistician involved in the analyses.
Incomplete outcome data
Maslak 2004 initially randomised 180 children, of whom 14 withdrew (5 in the test group and 9 in the control group). Seventy‐five (94%) test children and 91 (91%) control children were available for follow‐up examination at the third year and included in the analysis. Some withdrawals were due to absence during the annual examination, whilst others withdrew because of their parents' decision. Correspondence with the author suggested that an intention‐to‐treat analysis had been carried out.
Selective reporting
The protocol was not available, and only an abstract was published. There was insufficient information to judge the risk of bias ('unclear' risk of bias).
Other potential sources of bias
Compliance
The included study did not report the level of compliance (Maslak 2004).
Overall risk of bias
We present the results of the risk of bias assessments graphically in Figure 2.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Effects of interventions
Primary outcomes
Changes in caries experience, caries increment
Permanent teeth
After drinking fluoridated milk for three years, there was a reduction in the DMFT between the test and control groups (MD −0.13, 95% CI −0.24 to −0.02) (Maslak 2004). The disease level was very low in the study, resulting in a small absolute effect size.
Primary teeth
After drinking fluoridated milk for three years, there was a substantial reduction in the dmft between the test and control groups (MD −1.14. 95% CI −1.86 to −0.42) (Maslak 2004), equivalent to a PF of 31%.
Adverse effects: Dental fluorosis
Correspondence with the author (Maslak 2004) confirmed that no adverse effects were reported.
Secondary outcomes
Dental pain due to decay
No information was reported.
Antibiotics use due to dental infections
No information was reported.
Requirement for general anaesthesia due to dental procedures for caries
No information was reported.
Discussion
Summary of main results
This review looked for evidence on the effectiveness of fluoridated milk as a means of preventing dental caries in people of all ages.
Overall completeness and applicability of evidence
We confined this review to studies which were designed as RCTs. The only study we found was conducted in young children (Maslak 2004).
The included study (Maslak 2004) has a high risk of bias, and its external validity should be viewed with caution. The preventive programme, however, was appropriate, as caries prevalence was high and fluoride in drinking water was low. The applicability of the findings of this study in other settings, where the baseline level of caries and exposure to fluoride through other sources (such as drinking water and toothpaste) may differ, needs to be considered on a case‐by‐case basis.
Quality of the evidence
The quality of evidence for the main outcomes was low. Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Factors that affected our confidence in effect sizes of the analysis included limitations in the study design (high risk from selection and attrition bias) and other issues in data analysis, such as not taking into account clustering effects. Although randomisation was carried out on an individual basis, analyses of programmes targeted through schools may need to take account of clustering, as children within a school may influence each other and therefore cannot be regarded as completely independent (Bland 1997). Failing to adjust for unit of analysis could lead to spurious positive findings (Altman 1997).
Intention‐to‐treat analysis is favoured in assessment of clinical effectiveness, as it mirrors the non‐compliance and treatment changes that are likely to occur when the intervention is used in practice, reducing the possibility of overestimating effectiveness due to attrition bias (when participants are excluded from the analysis) (Hollis 1999). The author of the included study reported in personal communication that intention‐to‐treat analysis had been carried out (Maslak 2004). However, this information could not be substantiated from the abstract.
Potential biases in the review process
Without a full publication of the study, it is not always possible to comprehensively assess the risk of bias in the reviews or ensure that all relevant information has been obtained. We also excluded a study that was quasi‐randomised (Stephen 1984), as this type of study design carries a high risk of selection bias.
Most analyses planned in the protocol, such as meta‐analysis, subgroup analysis, sensitivity analysis, and assessment for publication bias, could not be conducted in this review because of the lack of RCTs published on fluoridated milk.
Agreements and disagreements with other studies or reviews
Studies on the clinical effectiveness of fluoridated milk in caries prevention have been carried out in several countries using different research methods. These studies also varied with regard to the delivery of fluoridated milk, in particular, the concentration of fluoride. Reductions in caries incidence have varied from no effect (Ketley 2003; Stephen 1984) to 70% (Pakhomov 1993) in the primary dentition, and from no effect (Ketley 2003; Lopes 1984) to 97% (Pakhomov 1993) in the permanent dentition. The lack of effect shown in Ketley 2003 may be due to the lack of statistical power. On the other hand, the duration of intervention in the study by Lopes 1984 may be too short (16 months) to evaluate the effectiveness of fluoridated milk as a caries prevention method.
The findings of this updated Cochrane Review do not differ from those of the original review, which was first published in 2005 (Yeung 2005). Other systematic reviews also concluded that there is a low level of quality evidence that milk fluoridation is beneficial in preventing dental caries (Cagetti 2013; National Health and Medical Research Council 2007).
Cagetti 2013 carried out a systematic review on the caries‐prevention effect of fluoridated food. Two studies on fluoridated milk (Bian 2003; Stecksén‐Blicks 2009) fulfilled their inclusion criteria. However, as the study period for both was only 21 months, they were excluded from our review.
The systematic review by National Health and Medical Research Council 2007 identified one systematic review (Yeung 2005), no additional RCTs, no relevant cohort studies or case‐control studies. Two cross‐sectional studies (Mariño 2004; Riley 2005) met the inclusion criteria. These two studies assessed two different populations (one exposed to fluoridated milk and one not exposed to fluoridated milk) and were measured at multiple time points. As neither study was an RCT, both were excluded from the Cochrane Review.
Study flow diagram.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1 Fluoridated milk versus non‐fluoridated milk, Outcome 1 Caries in permanent teeth: DMFT (3 years).
Comparison 1 Fluoridated milk versus non‐fluoridated milk, Outcome 2 Caries in primary teeth: dmft (3 years).
| Fluoridated milk compared to non‐fluoridated milk for preventing dental caries | |||||
| Patient or population: general population | |||||
| Outcomes | Illustrative comparative risks* (95% CI) | No. of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | ||||
| Non‐fluoridated milk | Fluoridated milk | ||||
| Caries in permanent teeth: DMFT (3 years) | The mean caries in permanent teeth: DMFT (3 years) in the control group was 0.17 | The mean caries in permanent teeth: DMFT (3 years) in the intervention group was 0.13 lower (0.24 lower to 0.02 lower) | 166 | ⊕⊕⊝⊝ | Disease level very low; small absolute effect size |
| Caries in primary teeth: dmft (3 years) | The mean caries in primary teeth: dmft (3 years) in the control group was 3.64 | The mean caries in primary teeth: dmft (3 years) in the intervention group was 1.14 lower (1.86 lower to 0.42 lower) | 166 | ⊕⊕⊝⊝ | Substantial effect size equivalent to a 31% prevented fractionc |
| Adverse effects: dental fluorosis | No evidence found | ||||
| Dental pain due to decay | No evidence found | ||||
| Antibiotics due to dental infections | No evidence found | ||||
| Requirement for general anaesthesia due to dental procedures for caries | No evidence found | ||||
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | |||||
| GRADE Working Group grades of evidence | |||||
| aDowngraded for risk of bias: sequence generation method unclear, and participants were not blinded. bDowngraded for indirectness: applicability of evidence to different settings and populations unclear; there was not much baseline information about the population in the study. cPrevented fraction (PF), expressed as percentages = (mean increment in control group − mean increment in intervention group)/mean increment in control group) x 100%. PF values between 1% to 10% are considered to be a small effect; between 10% to 20%, a moderate effect; and above 20%, a large or substantial effect. | |||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Caries in permanent teeth: DMFT (3 years) Show forest plot | 1 | 166 | Mean Difference (IV, Fixed, 95% CI) | ‐0.13 [‐0.24, ‐0.02] |
| 2 Caries in primary teeth: dmft (3 years) Show forest plot | 1 | 166 | Mean Difference (IV, Fixed, 95% CI) | ‐1.14 [‐1.86, ‐0.42] |
