Early fluoride intake and Molar Incisor Hypomineralisation (MIH) defects: a systematic review and dose-response meta-analysis

Federica Veneri; Tommaso Filippini; Marta Cecchini; Marco Vinceti; Ugo Consolo; Luigi Generali

doi:10.23750/abm.v95i2.15477

Early fluoride intake and Molar Incisor Hypomineralisation (MIH) defects: a systematic review and dose-response meta-analysis

Authors

Federica Veneri University of Modena and Reggio Emilia https://orcid.org/0000-0002-5903-3830
Tommaso Filippini University of Modena and Reggio Emilia https://orcid.org/0000-0003-2100-0344
Marta Cecchini University of Modena and Reggio Emilia
Marco Vinceti University of Modena and Reggio Emilia https://orcid.org/0000-0002-0551-2473
Ugo Consolo University of Modena and Reggio Emilia https://orcid.org/0000-0001-5557-3285
Luigi Generali University of Modena and Reggio Emilia https://orcid.org/0000-0003-3764-7046

DOI: https://doi.org/10.23750/abm.v95i2.15477

Keywords:

Demarcated opacities; Fluoride; Hypomineralisation; MIH; Molar-Incisor; Water fluoridation.

Abstract

Background: Excessive intake of fluoride has been implicated in the complex multifactorial etiology of hypomineralisation (MIH) defects. Objective: To study the possible effect of early exposure to fluoride on the risk of molar incisor hypomineralisation, also through a dose-response approach. Methods: Observational and clinical studies investigating the relation between fluoride exposure from any source or evaluating exposure biomarkers and MIH defects. PubMed MEDLINE, Embase and Web of Science databases were consulted up to December 1, 2023, using terms related to “fluoride”, “enamel defects” and “demarcated opacities”. We performed a meta-analysis comparing the highest versus lowest fluoride exposure using a random-effects model, and we quantitively assessed this relation using piece-wise linear meta-regression. Results: Thirteen studies were included in the meta-analysis, 12 of which were eligible for the dose-response analysis, all regarding exposure from fluoride in drinking water. Three of them specifically addressed MIH, while the remaining concerned “demarcated opacities”, yet with features attributable to MIH. Comparing the highest versus lowest water fluoride exposure categories, virtually no evidence of a fluoride effect was identified, with an overall odds ratio of 0.93 [95% confidence interval 0.60; 1.45]. The dose-response meta-regression showed a decreasing risk for MIH defects exposure up to 1 mg/L, whereas an increase in risk emerged at higher exposure levels. Conclusions: This meta-analysis suggests that early systemic exposure to fluoride may affect the occurrence of MIH defects differently depending on fluoride concentration. However, these results need to be evaluated with caution due to potential methodological limitations of the studies included.

Author Biographies

Federica Veneri, University of Modena and Reggio Emilia

Unit of Dentistry & Oral-Maxillo-Facial Surgery, Department of Surgery, Medicine, Dentistry and Morphological Sciences with Transplant Surgery, Oncology and Regenerative Medicine Relevance (CHIMOMO)

Tommaso Filippini, University of Modena and Reggio Emilia

Environmental, Genetic and Nutritional Epidemiology Research Center (CREAGEN), Section of Public Health, Department of Biomedical, Metabolic and Neural Sciences

Marta Cecchini, University of Modena and Reggio Emilia

Environmental, Genetic and Nutritional Epidemiology Research Center (CREAGEN), Section of Public Health, Department of Biomedical, Metabolic and Neural Sciences

Marco Vinceti, University of Modena and Reggio Emilia

Environmental, Genetic and Nutritional Epidemiology Research Center (CREAGEN), Section of Public Health, Department of Biomedical, Metabolic and Neural Sciences

Ugo Consolo, University of Modena and Reggio Emilia

Unit of Dentistry & Oral-Maxillo-Facial Surgery, Department of Surgery, Medicine, Dentistry and Morphological Sciences with Transplant Surgery, Oncology and Regenerative Medicine Relevance (CHIMOMO)

Luigi Generali, University of Modena and Reggio Emilia

Unit of Dentistry & Oral-Maxillo-Facial Surgery, Department of Surgery, Medicine, Dentistry and Morphological Sciences with Transplant Surgery, Oncology and Regenerative Medicine Relevance (CHIMOMO)

References

Weerheijm KL, Jälevik B, Alaluusua S. Molar–Incisor Hypomineralisation. Caries Res. 2001;35(5):390–1. doi: 10.1159/000047479.

Ghanim A, Silva MJ, Elfrink MEC, et al. Molar incisor hypomineralisation (MIH) training manual for clinical field surveys and practice. Eur Arch Paediatr Dent. 2017;18(4):225–42. doi: 10.1007/s40368-017-0293-9.

Lygidakis NA, Garot E, Somani C, Taylor GD, Rouas P, Wong FSL. Best clinical practice guidance for clinicians dealing with children presenting with molar-incisor-hypomineralisation (MIH): an updated European Academy of Paediatric Dentistry policy document. Eur Arch Paediatr Dent. 2022;23(1):3–21; doi: doi: 10.1007/s40368-021-00668-5.

Lopes LB, Machado V, Mascarenhas P, Mendes JJ, Botelho J. The prevalence of molar-incisor hypomineralization: a systematic review and meta-analysis. Sci Rep. 2021;11(1):22405. doi: 10.1038/s41598-021-01541-7.

Anand T, Garg AK, Singh S. Effect of socioeconomic, nutritional status, diet, and oral habits on the prevalence of different types of malocclusion in school-children. Acta Biomed. 2022;93(3):e2022161. doi: 10.23750/abm.v93i3.13027.

Veeraboina N, Doshi D, Kulkarni S, Patanapu SK, Dantala SN, Adepu S. Association of state and trait anxiety with oral health status among adult dental patients: State and Trait Anxiety with Oral Health Status. Acta Biomed. 2020;91(3):e2020070. doi: 10.23750/abm.v91i3.8986.

Garot E, Rouas P, Somani C, Taylor GD, Wong F, Lygidakis NA. An update of the aetiological factors involved in molar incisor hypomineralisation (MIH): a systematic review and meta-analysis. Eur Arch Paediatr Dent. 2021;23(1):23–38. doi: 10.1007/s40368-021-00646-x.

Balmer R, Toumba KJ, Munyombwe T, Duggal MS. A comparison of the presentation of molar incisor hypomineralisation in two communities with different fluoride exposure. Eur Arch Paediatr Dent. 2015;16(3):257–64. doi: 10.1007/s40368-014-0170-8.

Fernandes IC, Forte FDS, Sampaio FC. Molar-incisor hypomineralization (MIH), dental fluorosis, and caries in rural areas with different fluoride levels in the drinking water. Int J Paediatr Dent. 2021;31(4):475–82. doi: 10.1111/ipd.12728.

Fiore G, Veneri F, Di Lorenzo RD, Generali L, Vinceti M, Filippini T. Fluoride Exposure and ADHD: A Systematic Review of Epidemiological Studies. Medicina. 2023;59(4):797. doi: 10.3390/medicina59040797.

Machiulskiene V, Baelum V, Fejerskov O, Nyvad B. Prevalence and extent of dental caries, dental fluorosis, and developmental enamel defects in Lithuanian teenage populations with different fluoride exposures. Eur J Oral Sci. 2009;117(2):154–60. doi: 10.1111/j.1600-0722.2008.00600.x.

Veneri F, Vinceti M, Generali L, et al. Fluoride exposure and cognitive neurodevelopment: Systematic review and dose-response meta-analysis. Environ Res. 2023;221:115239. doi: 10.1016/j.envres.2023.115239.

Balmer RC, Laskey D, Mahoney E, Toumba KJ. Prevalence of enamel defects and MIH in non-fluoridated and fluoridated communities. Eur J Paediatr Dent. 2005;6(4):209–12.

Erdal S, Buchanan SN. A quantitative look at fluorosis, fluoride exposure, and intake in children using a health risk assessment approach. Environ Health Perspect. 2005;113(1):111–7. doi: 10.1289/ehp.7077.

Ramesh G, Nagarajappa R, Raghunath V, Manohar R. Developmental defects of enamel in children of Davangere District and their relationship to fluoride levels in drinking water. Asia Pac J Public Health. 2011;23(3):341–8. doi: 10.1177/1010539509340912.

Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. J Clin Epidemiol. 2021;134:178–89. doi: 10.1016/j.jclinepi.2021.03.001.

FDI - Commission on Oral Health, Research and Epidemiology. An epidemiological index of developmental defects of dental enamel (DDE Index). Commission on Oral Health, Research and Epidemiology. Int Dent J. 1982;32(2):159–67.

Morgan RL, Thayer KA, Santesso N, et al. A risk of bias instrument for non-randomized studies of exposures: A users’ guide to its application in the context of GRADE. Environ Int. 2019;122:168–84. doi: 10.1016/j.envint.2018.11.004.

Filippini T, Wise LA, Vinceti M. Cadmium exposure and risk of diabetes and prediabetes: A systematic review and dose-response meta-analysis. Environ Int. 2022;158:106920. doi: 10.1016/j.envint.2021.106920.

WHO, Fawell J, Bailey K, et al. Fluoride in drinking-water - World Health Organization Guidelines. Geneva: World Health Organization; 2006; https://apps.who.int/iris/handle/10665/43514. Accessed November 27, 2023.

Hiller KA, Wilfart G, Schmalz G. Developmental enamel defects in children with different fluoride supplementation--a follow-up study. Caries Res. 1998;32(6):405–11. doi: 10.1159/000016479.

Angelillo IF, Romano F, Fortunato L, Montanaro D. Prevalence of dental caries and enamel defects in children living in areas with different water fluoride concentrations. Community Dent Health. 1990;7(3):229–36.

Ekanayake L, van der Hoek W. Prevalence and distribution of enamel defects and dental caries in a region with different concentrations of fluoride in drinking water in Sri Lanka. Int Dent J. 2003;53(4):243–8. doi: 10.1111/j.1875-595x.2003.tb00752.x.

Milsom K, Mitropoulos CM. Enamel defects in 8-year-old children in fluoridated and non-fluoridated parts of Cheshire. Caries Res. 1990;24(4):286–89. doi: 10.1159/000261284.

Nunn JH, Rugg-Gunn AJ, Ekanayake L, Saparamadu KD. Prevalence of developmental defects of enamel in areas with differing water fluoride levels and socio-economic groups in Sri Lanka and England. Int Dent J. 1994;44(2):165–73.

Liefde B, Herbison GP. Prevalence of developmental defects of enamel and dental caries in New Zealand children receiving differing fluoride supplementation. Commun Dent Oral Epidemiol. 1985;13(3):164–7. doi: 10.1111/j.1600-0528.1985.tb00435.x.

Cutress TW, Suckling GW, Pearce EI, Ball ME. Defects of tooth enamel in children in fluoridated and non-fluoridated water areas of the Auckland region. N Z Dent J. 1985;81(363):12–9.

Grahnén H, Lysell L, Myrberg N, Ollinen P. Fluoride, mineralisation defects of the enamel, and tooth width. Acta Paediatr Scand. 1974;63(2):188–92. doi: 10.1111/j.1651-2227.1974.tb04782.x.

European Union. Directive 2020/2184/EC. On the Quality of Water Intended for Human Consumption. Official Journal of the European Union L 435/1. 2020. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32020L2184. Accessed November 27, 2023.

U.S. Department of Health and Human Services Federal Panel on Community Water Fluoridation. U.S. Public Health Service Recommendation for Fluoride Concentration in Drinking Water for the Prevention of Dental Caries. Public Health Rep. 2015;130(4):318–31. doi: 10.1177/003335491513000408.

Crombie FA, Cochrane NJ, Manton DJ, Palamara JEA, Reynolds EC. Mineralisation of Developmentally Hypomineralised Human Enamel in vitro. Caries Res. 2013;47(3):259–63. doi: 10.1159/000346134.

Salmela E, Lukinmaa P-L, Partanen A-M, Sahlberg C, Alaluusua S. Combined effect of fluoride and 2,3,7,8-tetrachlorodibenzo-p-dioxin on mouse dental hard tissue formation in vitro. Arch Toxicol. 2011;85(8):953–63. doi: 10.1007/s00204-010-0619-4.

Vinceti SR, Veneri F, Filippini T. Water fluoridation between public health and public law: an assessment of regulations across countries and their preventive medicine implications. Ann Ig. 2024; doi: 10.7416/ai.2024.2594.

EFSA - European Food Safety Authority. Scientific Opinion on Dietary Reference Values for fluoride. EFSA J. 2013;11(8):3332. doi: 10.2903/j.efsa.2013.3332.

Veneri F, Vinceti SR, Filippini T. Fluoride and caries prevention: a scoping review of public health policies. Ann Ig. 2024; doi: 10.7416/ai.2024.2593.

Iamandii I, De Pasquale L, Giannone ME, et al. Does fluoride exposure affect thyroid function? A systematic review and dose-response meta-analysis. Environ Res. 2024;242:117759. doi: 10.1016/j.envres.2023.117759.

Veneri F, Iamandii I, Vinceti M, et al. Fluoride Exposure and Skeletal Fluorosis: a Systematic Review and Dose-response Meta-analysis. Curr Environ Health Rep. 2023;10(4):417–41 doi: 10.1007/s40572-023-00412-9.