Oral and craniofacial research in the Generation R study: an executive summary.

OBJECTIVES: Oral conditions are of high prevalence and chronic character within the general population. Identifying the risk factors and determinants of oral disease is important, not only to reduce the burden of oral diseases, but also to improve (equal access to) oral health care systems, and to develop effective oral health promotion programs. Longitudinal population-based (birth-)cohort studies are very suitable to study risk factors on common oral diseases and have the potential to emphasize the importance of a healthy start for oral health. In this paper, we provide an overview of the comprehensive oral and craniofacial dataset that has been collected in the Generation R study: a population-based prospective birth cohort in the Netherlands that was designed to identify causes of health from fetal life until adulthood. METHODS: Within the multidisciplinary context of the Generation R study, oral and craniofacial data has been collected from the age of 3 years onwards, and continued at the age of six, nine, and thirteen. Data collection is continuing in 17-year-old participants. RESEARCH OUTCOMES: In total, the cohort population comprised 9749 children at birth, and 7405 eligible participants at the age of seventeen. Based on questionnaires, the dataset contains information on oral hygiene, dental visits, oral habits, oral health-related quality of life, orthodontic treatment, and obstructive sleep apnea. Based on direct measurements, the dataset contains information on dental caries, developmental defects of enamel, objective orthodontic treatment need, dental development, craniofacial characteristics, mandibular cortical thickness, and 3D facial measurements. CONCLUSIONS: Several research lines have been set up using the oral and craniofacial data linked with the extensive data collection that exists within the Generation R study. CLINICAL RELEVANCE: Being embedded in a multidisciplinary and longitudinal birth cohort study allows researchers to study several determinants of oral and craniofacial health, and to provide answers and insight into unknown etiologies and oral health problems in the general population.

Three-dimensional dento-skeletal effects of mandibular midline distraction and surgically assisted rapid maxillary expansion: A retrospective study.

It was the aim of the study to provide a three-dimensional evaluation of dento-skeletal effects following bone-borne vs tooth-borne mandibular midline distraction (MMD) and tooth-borne surgically assisted rapid maxillary expansion (SARME). A retrospective observational study was conducted. Cone beam computed tomography (CBCT) records were taken pre-operatively (T1), immediately post-distraction (T2) and 1 year post-operatively (T3). All included 30 patients had undergone MMD (20 bone-borne MMD; 10 tooth-borne MMD). A total of 20 bone-borne MMD and 8 tooth-borne MMD patients had simultaneously undergone tooth-borne SARME. At T1 vs T3, canine (p = 0.007; 26.0 ± 2.09 vs 29.2 ± 2.02) and first premolar (p = 0.005; 33.8 ± 2.70 vs 37.0 ± 2.43) showed significant expansion on the tip level for tooth-borne MMD. This was no significant on the apex level, indicating tipping. Bone-borne MMD showed a parallel distraction gap, whereas tooth-borne MMD showed a V-shape. There was a significant (p = 0.017; 138 ± 17.8 vs 141 ± 18.2) inter-condylar axes increase for bone-borne MMD. In conclusion, bone-borne vs tooth-borne MMD and tooth-borne SARME showed stable dento-skeletal effects at 1 year post-operatively. Bone-borne and tooth-borne MMD seemed not to be superior to each other. The choice of distractor type therefore depends more on anatomical and comfort factors.

Current Practice for Transverse Mandibular and Maxillary Discrepancies in the Netherlands: A Web-Based Survey Among Orthodontists and Oral and Maxillofacial Surgeons.

The main objective of this study was to provide an overview of the current practice for transverse mandibular and maxillary discrepancies in the Netherlands using a web-based survey. Orthodontists (ORTHO) and Oral and Maxillofacial Surgeons (OMFS) in the Netherlands were invited to the web-based survey via their professional association. Three cases were presented which could be treated non-surgically and surgically. Participants were asked what treatment they preferred: no treatment, orthodontic treatment with optional extractions or surgically assisted orthodontic treatment. The web-based survey ended with questions on various technical aspects and any experienced complication. Invitation was sent to all 303 members of professional association for ORTHO and to all 379 members of professional association for OMFS. Overall response number was 276 (response rate of 40.5%), including 127 incomplete responses. Generally, ORTHO prefer orthodontic treatment with optional extractions and OMFS lean towards surgically assisted orthodontic treatment. Mandibular Midline Distraction appears to be less preferred, possibly due to lack of clinical experience or knowledge by both professions despite being proven clinical stable surgical technique with stable long-term outcomes. There seems to be consensus on technical aspects by both professions, however, there are various thoughts on duration of consolidation period. Complications are mostly minor and manageable.

Associations Between Prenatal, Perinatal, and Early Childhood Vitamin D Status and Risk of Dental Caries at 6 Years.

BACKGROUND: Previous studies have suggested that insufficient concentrations of vitamin D are associated with dental caries in primary teeth, but evidence remains inconclusive. OBJECTIVES: We assessed the longitudinal associations between prenatal, perinatal, and early childhood serum 25-hydroxyvitamin D concentrations [25(OH)D] and the risk of dental caries in 6-year-old children. METHODS: This research was conducted within the Generation R Study, a large, multi-ethnic, prospective cohort study located in Rotterdam, the Netherlands. Dental caries were assessed in children using the decayed-missing-filled-primary teeth index at a mean age of 6.1 years (90% range, 4.8-9.1). We measured serum total 25(OH)D concentrations at 3 time points: prenatally (at 18-24 weeks of gestation), perinatally (at birth), and during early childhood (at age 6 years). We performed logistic regression analyses to determine the longitudinal association of serum 25(OH)D concentrations with caries risks in 5257 children. Additionally, we constructed a Genetic Risk Score (GRS) for the genetic predispositions to serum total 25(OH)D concentrations based on 6 vitamin D-related single nucleotide polymorphisms in a subsample of 3385 children. RESULTS: Children with severe prenatal and early childhood serum 25(OH)D deficiencies (<25 nmol/L) were more likely to be diagnosed with caries [OR, 1.56 (95% CI, 1.18-2.06) and 1.58 (95% CI, 1.10-2.25), respectively] than children with optimal concentrations (≥75 nmol/L). After adjustment for residuals of serum 25(OH)D concentrations at other time points, only the early childhood serum 25(OH)D concentration was inversely associated with the caries risk at 6 years (OR, 0.97; 95% CI, 0.95-0.98). However, our GRS analysis showed that children who are genetically predisposed to have lower serum 25(OH)D concentrations do not have a higher risk of developing caries in primary teeth. CONCLUSIONS: Our study suggests a weak association between serum 25(OH)D concentrations and risks of caries in primary teeth. Based on our results, we do not recommend vitamin D supplementation for the prevention of dental caries in children.

Caries experience among children born after a complicated pregnancy.

OBJECTIVES: Behavioural and lifestyle factors, as oral hygiene and diet, are well-established risk factors in the pathogenesis of dental caries, though displaying large differences in susceptibility across individuals. Since enamel formation already starts in utero, pregnancy course and outcome may eventually play a role in enamel strength and caries susceptibility. Therefore, we studied the association between history of pregnancy complications and the caries experience in their six-year-old children. The pregnancy complications included small for gestational age (SGA), spontaneous preterm birth (sPTB), gestational hypertension (GH), pre-eclampsia (PE), individually, and a combination of those, designated as placental syndrome. METHODS: This study was embedded in Generation R, a prospective longitudinal Dutch multiethnic pregnancy cohort study. Information about pregnancy complications was obtained from questionnaires completed by midwives and obstetricians with cross-validation in medical records. These included SGA, sPTB, GH and PE. Caries experience was assessed with the decayed, missing and filled teeth (dmft) index at a mean age of six years. The association between dental caries experience and a history of pregnancy complications was studied by using hurdle negative binomial (HNB) models. RESULTS: We were able to assess the dmft index in 5323 six-year-old children (mean age 6.2 years, SD 0.5). We did not find an association between the different pregnancy complications and dental caries experience in childhood, whether for SGA, sPTB, GH, PE, or for the combined outcome placental syndrome (HNB estimates: OR 1.02, 95%CI 0.87 - 1.19; RR 0.90, 95%CI 0.78 - 1.04). Further adjustment of the models with different confounders did not alter the outcome. CONCLUSIONS: Although it is expected that prenatal stress can be a risk factor for caries development later in life, our findings do not support this hypothesis. Therefore, we believe disparities in caries experience between children are probably not explained by early life events during a critical intrauterine period of development.

Esthetics and Patient-Reported Outcomes of Implants Placed with Guided Bone Regeneration and Complete Native Bone: A Prospective Controlled Clinical Trial.

PURPOSE: When encountering a buccal bone defect during implant placement, guided bone regeneration (GBR) is a well-accepted method for bone reconstruction. However, it is still unclear if the esthetic and patient-reported outcomes are comparable to implants placed in native bone. The purpose of this prospective trial was to compare implants placed with a GBR procedure for a small (≤ 4 mm) buccal defect with implants placed completely in native bone (control). MATERIALS AND METHODS: Patients were allocated to the GBR group or control group during implant placement in the esthetic zone. Implants were placed after at least 12 weeks of healing of the extraction sockets. A buccal bone defect of ≤ 4 mm resulted in allocation to the GBR group. Follow-up was performed until 12 months after loading. Outcome measurements were as follows: esthetic scores, patient-reported outcome measurements, implant survival and complications, clinical indices, and radiographic measurements. RESULTS: In total, 45 patients were included, of which 23 underwent a GBR procedure after implant placement, and in 22 patients no GBR was necessary. No significant differences in esthetic outcomes were seen between the two groups. At the final follow-up, a mean pink esthetic score (PES) of 7.8 (SD: 1.5) was seen for the GBR group and 8.4 (SD: 1.4) for the control group. Regarding the white esthetic score (WES), a mean of 9.1 (SD: 1.0) was found for both groups. Patients of both groups were equally satisfied with their mucosa and crown. A mean visual analog score (VAS) for the soft tissues of 8.6 (SD: 1.0) in the GBR group and 8.8 (SD: 0.9) for the control group was noted. A mean VAS of 9.2 (SD: 0.8) was noted for the crown in the GBR group and 8.6 (SD: 2.0) in the control group. Implant survival was 100%, and there were no significant differences in complications, plaque/bleeding/gingiva indices, width of attached mucosa, and marginal bone loss. CONCLUSION: Implants placed in the esthetic zone with GBR or complete native bone coverage showed successful esthetic outcomes and satisfied patients with predictable clinical and radiographic parameters after more than 1 year of loading. Within the limits of this study, GBR for a small buccal bone defect seems to be a reliable technique with good esthetics and patient-reported outcomes.

Consortium-based genome-wide meta-analysis for childhood dental caries traits.

Prior studies suggest dental caries traits in children and adolescents are partially heritable, but there has been no large-scale consortium genome-wide association study (GWAS) to date. We therefore performed GWAS for caries in participants aged 2.5-18.0 years from nine contributing centres. Phenotype definitions were created for the presence or absence of treated or untreated caries, stratified by primary and permanent dentition. All studies tested for association between caries and genotype dosage and the results were combined using fixed-effects meta-analysis. Analysis included up to 19 003 individuals (7530 affected) for primary teeth and 13 353 individuals (5875 affected) for permanent teeth. Evidence for association with caries status was observed at rs1594318-C for primary teeth [intronic within ALLC, odds ratio (OR) 0.85, effect allele frequency (EAF) 0.60, P 4.13e-8] and rs7738851-A (intronic within NEDD9, OR 1.28, EAF 0.85, P 1.63e-8) for permanent teeth. Consortium-wide estimated heritability of caries was low [h2 of 1% (95% CI: 0%: 7%) and 6% (95% CI 0%: 13%) for primary and permanent dentitions, respectively] compared with corresponding within-study estimates [h2 of 28% (95% CI: 9%: 48%) and 17% (95% CI: 2%: 31%)] or previously published estimates. This study was designed to identify common genetic variants with modest effects which are consistent across different populations. We found few single variants associated with caries status under these assumptions. Phenotypic heterogeneity between cohorts and limited statistical power will have contributed; these findings could also reflect complexity not captured by our study design, such as genetic effects which are conditional on environmental exposure.

Foetal, neonatal and child vitamin D status and enamel hypomineralization.

OBJECTIVES: Recent literature suggested that higher vitamin D concentrations in childhood are associated with a lower prevalence of molar incisor hypomineralization (MIH). As tooth development already starts in utero, we aimed to study whether vitamin D status during foetal, postnatal and childhood periods is associated with the presence of hypomineralized second primary molars (HSPMs) and/or MIH at the age of six. METHODS: Our study was embedded in the Generation R Study, a population-based, prospective cohort from foetal life onwards in Rotterdam, the Netherlands. HSPMs and MIH were scored from intraoral photographs of the children at their age of six. Serum 25(OH)D concentrations were measured at three points in time, which resulted in three different samples; mid-gestational in mothers' blood (n = 4750), in umbilical cord blood (n = 3406) and in children's blood at the age of 6 years (n = 3983). RESULTS: The children had a mean (±SD) age of 6.2 (±0.5) years at the moment of taking the intraoral photographs. After adjustment for confounders, no association was found between foetal 25(OH)D concentrations and the presence of HSPMs (OR 1.02 per 10 nmol/L higher 25(OH)D, 95% CI: 0.98-1.07) or MIH (OR 1.05 per 10 nmol/L increase, 95% CI: 0.98-1.12) in 6-year-olds. A higher 25(OH)D concentration in umbilical cord blood resulted in neither lower odds of having HSPM (OR 1.05, 95% CI: 0.98-1.13) nor lower odds of having MIH (OR 0.95, 95% CI: 0.84-1.07) by the age of six. Finally, we did not find higher 25(OH)D concentrations at the age of six to be associated with a significant change in the odds of having HSPM (OR 0.97, 95% CI: 0.92-1.02) or MIH (OR 1.07, 95% CI: 0.98-1.16). CONCLUSIONS: 25(OH)D concentrations in prenatal, early postnatal and later postnatal life are not associated with the presence of HPSMs or with MIH at the age of six. Future observational research is required to replicate our findings. Furthermore, it is encouraged to focus on identifying other modifiable risk factors, because prevention of hypomineralization is possible only if the causes are known.

The effect of resorbable membranes on one-stage ridge augmentation in anterior single-tooth replacement: A randomized, controlled clinical trial.

AIM: To evaluate the effect of resorbable membranes on one-stage ridge augmentation procedures in small (2-4 mm) buccal bony dehiscences in anterior maxillary single-tooth replacement. MATERIALS AND METHODS: Patients with a buccal bony dehiscence after implant placement in the esthetic zone were randomly allocated to one-stage ridge augmentation with (M+) or without a membrane (M-). Second-phase surgery was performed after 8 weeks, and follow-up was performed 1, 6, and ≥12 months after loading. Outcomes included implant survival and success, complications, clinical and radiographic parameters, esthetic results and patient satisfaction. RESULTS: Fifty-two patients were randomized to one-stage ridge augmentation with (n = 25) or without use of a membrane (n = 27). No significant differences in implant survival and success have been observed. The risk of having a small mucosal dehiscence was more than six times higher in the M+ group than in the M- group (RR 6.24, 95% CI 0.81 to 48.21). At the last follow-up, the bleeding index (BI) was marginally higher in the M+ group (14/9/2/0) compared to the M- group (24/2/0/0) (U = 205, Z = -2.97, p = .003, r = .42). The median change in marginal bone level was statistically lower in the M+ group (0.06 mm) than the M- group (0.60 mm) at last follow-up (U = 120, Z = -2.73 a p = .006 r = .42). Total pink esthetic index (PES) and white esthetic score (WES) and combined PES/WES were not significantly different between treatment groups at more than 12 months after loading. Only the subcategory root convexity/soft tissue color scored significantly lower in the M+ group (1.5) compared to the M- group (2.0) at the last follow-up (U = 172, Z = -2.34, p = .019 r = .34). No differences were found in patient satisfaction. CONCLUSION: The use of a resorbable membrane in small buccal bony dehiscences in anterior maxillary single-tooth replacement resulted in less marginal bone loss, but showed more mucosal dehiscences, higher bleeding scores and lower scores on root convexity and soft tissue color after at least one year of loading. No effect was seen on implant survival and success, overall esthetic results, and patient satisfaction. The research protocol was registered at the Dutch Trial Register (NTR) with ID NTR6137.

Social inequalities and dental caries in six-year-old children from the Netherlands.

OBJECTIVES: The purpose of our study was to investigate the association of different socioeconomic and sociodemographic factors with dental caries in six-year-old children. Furthermore, we applied a district based approach to explore the distribution of dental caries among districts of low and high socioeconomic position (SEP). METHODS: In our cross-sectional study 5189 six-year-olds were included. This study was embedded in a prospective population-based birth cohort study in Rotterdam, the Netherlands, the Generation R Study. Parental education level, parental employment status, net household income, single parenting, and teenage pregnancy were considered as indicators for SEP. Dental caries was scored on intraoral photographs by using the decayed, missing, and filled teeth (dmft) index. We compared children without caries (dmft=0) to children with mild caries (dmft=1-3) or severe caries (dmft >3). Multinomial logistic regression analyses and binary logistic regression analyses were performed to study the association between SEP and caries, and between district and caries, respectively. RESULTS: Only maternal education level remained significantly associated with mild caries after adjusting for all other SEP-indicators. Paternal educational level, parental employment status, and household income additionally served as independent indicators of SEP in children with severe caries. Furthermore, living in more disadvantaged districts was significantly associated with higher odds of dental caries. CONCLUSION: Dental caries is more prevalent among six-year-old children with a low SEP, which is also visible at the district level. Maternal educational level is the most important indicator of SEP in the association with caries. CLINICAL SIGNIFICANCE: Our results should raise concerns about the existing social inequalities in dental caries and should encourage development of dental caries prevention strategies. New knowledge about the distribution of oral health inequalities between districts should be used to target the right audience for these strategies.

Ethnic Disparities in Dental Caries among Six-Year-Old Children in the Netherlands.

The aim of this study was to investigate potential differences in caries prevalence of children from ethnic minority groups compared to native Dutch children and the influence of socio-economic status (SES) and parent-reported oral health behaviour on this association. The study had a cross-sectional design, embedded in a population-based prospective multi-ethnic cohort study. 4,306 children with information on caries experience, belonging to 7 different ethnic groups, participated in this study. The decayed, missing, and filled teeth (dmft) index was assessed at the age of 6 and categorized in two ways for analysis: children without caries (dmft = 0) versus any caries experience (dmft >0) and children without caries (dmft = 0) versus children with mild caries (dmft = 1-3) or severe caries (dmft >3). Compared to native Dutch children, children with a Surinamese-Hindustani, Surinamese-Creole, Turkish, Moroccan, and Cape Verdean background had significantly higher odds for dental caries. Especially the Surinamese-Hindustani, Turkish, and Moroccan group had significantly higher odds for severe dental caries. Household income and educational level of the mother explained up to 43% of the association between ethnicity and dental caries, whereas parent-reported oral health behaviour did not mediate the association. Alarming disparities in caries prevalence between different ethnic (minority) groups exist, which cannot be fully explained by social inequalities. Public health strategies can apply this new knowledge and specifically focus on the reduction of ethnic disparities in oral health. More research is needed to explain the high caries prevalence among different ethnic minority groups.

Early Caries Predicts Low Oral Health-Related Quality of Life at a Later Age.

Oral health-related quality of life (OHRQOL) is the perceived impact of one's own oral health on daily life. Oral diseases influence children's OHRQOL directly, but OHRQOL might also be related to oral health experiences from the past. We investigate the relation between dental caries at the age of 6 with OHRQOL assessed at the age of 10. This study was conducted within the Generation R Study, a population-based prospective cohort study. Caries experience was assessed with the decayed, missing, and filled teeth index (dmft) at a median age of 6.09 years (90% range: 5.73-6.80). OHRQOL was assessed with a short form of the Child Oral Health Impact Profile at the children's age of 9.79 years (9.49-10.44). In total, 2,833 children participated in this study, of whom 472 (16.6%) had mild caries (dmft 1-3) and 228 (8.0%) had severe caries (dmft >3). The higher the dmft score at the age of 6, the lower the OHRQOL at the age of 10 (p < 0.001). The children with severe caries at the age of 6 had significantly higher odds of being in the lowest OHRQOL quartile at the age of 10 (OR = 1.69; 95% CI: 1.17-2.45). Our study highlights the importance of oral health during childhood, because those who get a compromised start to oral health are much more likely to follow a trajectory which will lead to poor oral health (-related QOL) later. OHRQOL is not only related to current oral health experiences but also to oral health experiences from the past.