UITNODIGING Advances in Epidemiological Research of Dental in Epidemiological Research and Dental Enamel Hypomineralization CariesAdvances Advances in Epidemiological Research of Dental Enamel Hypomineralization J.T. van der Tas and Dental Caries Voor het bijwonen van de verdediging van het proefschrift Advances in Epidemiological Research of Dental Enamel Hypomineralization and Dental Caries door Justin van der Tas op woensdag 4 november 2020 om 11:30 uur in de Prof. Andries Querido­ zaal van het Onderwijs centrum van het Erasmus Medisch Centrum te Rotterdam. Vanwege COVID­19 is de promotieplechtigheid uitsluitend op specifieke uitnodiging fysiek bij te wonen. Zonder uitnodiging bent u welkom de plechtigheid via een livestream te volgen. De link voor de livestream volgt te zijner tijd op uwer verzoek. Na afloop is er beperkt ruimte voor de receptie tot maximaal 50 personen. Justin van der Tas Nicolaas Ruyschstraat 8­02L 3039 WR Rotterdam 0629293542 [email protected] J.T. van der Tas van J.T. Paranimfen Jeffrey Hoek [email protected] Bart van Dijk [email protected] boekenlegger_justin_van_der_tas.indd 1 21-9-2020 08:43:00 Advances in Epidemiological Research of Dental Enamel Hypomineralization and Dental Caries Justin van der Tas Acknowledgements The general design of the Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands. Organization for Health Research and Development (ZonMw), the Nether- lands Organisation for Scientific Research (NWO), the Ministry of Health, Welfare and Sport and the Ministry of Youth and Families. The work presented in this thesis was conducted in the Generation R Study Group, in close collaboration with the Departments of Epidemiology and the Department of Oral and Maxillofacial Surgery, Special Dental Care and Orthodontics, Erasmus University Medical Centre Rotterdam, The Netherlands. Printing and distribution of this thesis was kindly supported by the Generation R Study, ChipSoft B.V., Nederlandse Vereniging voor Mondziekten, Kaak- en Aangezichtschirurgie and Materialise NV. Cover Paul Stoutjesdijk Layout Renate Siebes | Proefschrift.nu Printing Proefschriftmaken.nl ISBN 978-94-6380-948-1 © 2020 Justin van der Tas, Rotterdam, the Netherlands For all articles published or accepted the copyright has been transferred to the respective publisher. No part of this thesis may be reproduced, stored in a retrieval system, or transmitted in any form or by any means without prior permission of the author or when appropriate, of the publisher of the manuscript. Advances in Epidemiological Research of Dental Enamel Hypomineralization and Dental Caries Vorderingen in epidemiologisch onderzoek van tandglazuur hypomineralisatie en tandcariës Proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof.dr. R.C.M.E. Engels en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op woensdag 4 november 2020 om 11:30 uur door Justin Thomas van der Tas geboren te Rotterdam Promotiecommissie Promotoren: Prof.dr. E.B. Wolvius Prof. dr. F. Rivadeneira Ramírez Overige leden: Prof.dr. J.M. ten Cate Prof.dr. V.W.V. Jaddoe Prof.dr. H. Raat Copromotor: Dr. L. Kragt Paranimfen: Bart van Dijk Jeffrey Hoek Contents Chapter 1 General introduction 7 Chapter 2 Dental enamel hypomineralization 25 2.1 Association between bone mass and dental 27 hypomineralization 2.2 Foetal, neonatal and child vitamin D status and enamel 43 hypomineralization Chapter 3 Dental caries 65 3.1 Ethnic disparities in dental caries among six-year-old 67 children in the Netherlands 3.2 Consortium-based genome-wide meta-analysis for 87 childhood dental caries traits 3.3 Social inequalities and dental caries in six-year-old 117 children from the Netherlands 3.4 Caries experience among children born after a 137 complicated pregnancy Chapter 4 Validation of using quantitative light-induced fluorescence 155 photographs for assessing dental caries and enamel hypomineralization Chapter 5 General discussion 173 Chapter 6 Summary 197 Samenvatting 201 Chapter 7 Appendices 207 7.1 Curriculum Vitae 209 7.2 Portfolio 215 7.3 Dankwoord 221 1 General introduction General introduction Oral health is determined by multiple factors and biological processes, initiating from embryonic development and extending throughout the life course. Teeth already start to develop in an embryo of approximately 45 days old [1]. Before eruption of the first 1 teeth at the age of six months, the teeth undergo several stages in which dental enamel is formed [2]. Dental enamel is a calcified tissue consisting of hydroxyapatite crystals and is the hardest tissue in the human body [1]. Despite its hardness, however, dental enamel may be affected by several entities. Molar Incisor Hypomineralization (MIH) and Hypomineralized Second Primary Molars (HSPM) for example, are two diseases in which the dental enamel shows mineralization defects after eruption. To date, there is limited knowledge about the etiology of MIH and HSPM. They both lead to more vulnerable dental enamel which leads to a higher risk of caries development [3, 4]. Dental caries is the other, much more common, disease of the enamel in which demineralization by external influences is the problem. Unlike MIH and HSPM, the etiology of dental caries has been well established, which have led to the development of effective preventive strategies such as fluoridation of toothpastes or the Nexø-method in which the focus lies on the patient’s responsibility for self-care and the interval between periodic visits is based on the patient’s level of self-care, the eruption period of the permanent teeth and the caries progression within the dentition and especially in the permanent first molars [5, 6]. However, up to now the prevalence of caries remains relatively high, with approximately 24% of all five-year-old children in the Netherlands [7]. Identification of risk groups and new risk factors may be a promising approach to facilitate more effective prevention. This thesis will focus on MIH, HSPM, and dental caries, tooth disorders in which the dental enamel plays a central role. MIH and HSPM Generally, MIH can be seen as enamel hypomineralization of the first permanent molars and/or incisors and HSPM as enamel hypomineralization of the second primary molars [8-10]. In some cases, the tips of permanent canine cusps and/or permanent premolars are affected as well. Enamel hypomineralization of these other sites, however, is little studied. Therefore, MIH is still defined as “enamel hypomineralization from systemic origin of one to four first permanent molars and is frequently associated with affected incisors as well” [10]. Clinically, MIH and HSPM affected teeth can be recognized by demarcated opacities with a white, yellow or brown aspect (Figure 1.1). Among oral healthcare professionals in the Netherlands, MIH and HSPM are often referred to as “cheese molars”, because of their visual resemblance to cheese. The diagnosis of enamel 9 Chapter 1 hypomineralization in most research is based on the European Academy of Pediatric Dentistry (EAPD)-criteria for MIH (Table 1.1) [10, 11]. Elfrink et al. made an adaptation to these criteria with regard to HSPM [12]. Furthermore, many researchers added a distinction between mild and severe hypomineralization [11]. The mild form only shows opacities and severe hypomineralization includes posteruptive enamel loss, atypical caries lesions, atypical restorations and/or atypical extractions [12]. Figure 1.1. A: MIH of the first permanent molar in the right upper jaw showing yellow opacities over the entire occlusal surface. B: HSPM of the second primary molar in the right upper jaw showing a big occlusal restoration and a brown/yellow opacity on the mesiopalatal cusp. Table 1.1. EAPD criteria for scoring HSPM and MIH on intra-oral photographs (Elfrink et al. 2009; Weerheijm et al. 2003) Mild: Opacity: A defect that changes the translucency of the enamel, variable in degree. The defective enamel is of normal thickness with a smooth surface and can be white, yellow or brown in color. The demarcated opacity is not caused by caries, ingestion of excess fluoride during tooth development or amelogenesis imperfect etc. Severe: Posteruptive enamel loss: A defect that indicates surface enamel loss after eruption of the tooth, e.g., hypomineralization related attrition. Enamel loss due to erosion was excluded, and/or Atypical caries: The size and form of the caries lesion do not match the present caries distribution in the child’s mouth, and/or Atypical restoration: The size and form of the restoration do not match the present caries distribution in the child’s mouth, and/or Atypical extraction: Absence of a molar that does not fit in the dental development and caries pattern of the child. The burden of MIH is high with a calculated estimate of 878 million affected people worldwide, roughly 11% of the complete world population [13]. Within the Netherlands the reported prevalence of MIH is comparable and is somewhere around 10 General introduction 10% [14-16]. The prevalence of HSPM in Dutch children is calculated between 5% and 10% [17, 18]. As a result of the weaker enamel, they are more susceptible to dental caries, dental pulp inflammation, pain and/or hypersensitivity [4, 8, 13, 19, 20]. This 1 leads to extra usage of healthcare, probable extra healthcare costs and a decreased oral health-related quality of life [13, 21, 22]. Therefore, accurate management of MIH and HSPM in patients is important and prevention is desirable, but not possible yet. Dental caries Dental caries is defined as “localized destruction of susceptible dental hard tissues by acidic by-products from bacterial fermentation of dietary carbohydrates” [23]. Hence, caries is not caused by intrinsic factors, but the biofilm in which these bacteria fermentate carbohydrates. The global burden of dental caries in both the primary and permanent dentition is tremendously high with almost three billion affected people [24].