Developmental defects of enamel (DDE) represent an overarching category of enamel disturbances that occur during tooth development. Within this spectrum are specific subtypes, including enamel fluorosis and molar–incisor hypomineralization (MIH), as well as other forms such as enamel hypoplasia, amelogenesis imperfecta, and enamel defects associated with systemic or local factors. Although these defects share similar developmental origins, they differ in etiology and clinical presentation. These defects can result in abnormalities such as thin enamel, discolored spots, and pitting or grooves on the enamel surface. They can be caused by a combination of genetic, environmental, systemic, and local factors. Systemic factors associated with DDE include nutritional deficiencies, metabolic disorders, systemic infections, and exposure to medications or environmental toxins. Local factors include trauma and injury to the developing tooth that disrupts the normal formation of enamel (1, 2). Because fluorosis and MIH are the most frequently investigated forms of DDE in the literature, this review focuses primarily on these two conditions while also considering evidence related to other DDE where available to provide a comprehensive overview of the field.

Nutritional deficiencies, particularly low intake of calcium, vitamins, as well as excessive fluoride consumption during tooth development, can increase the likelihood of DDE. Inadequate maternal nutrition during pregnancy and insufficient nutrition in early childhood have also been associated with a higher risk of DDE. Furthermore, exposure to environmental toxins, such as elevated levels of heavy metals in the diet, may contribute to the development of DDE (1, 2).

MIH is a specific type of DDE that primarily affects the first permanent molars and incisors. The exact cause of MIH is still unknown, but various dietary factors, including early childhood feeding practices, have been suggested to play a role in its development. Certain studies have found an association between prolonged breastfeeding and the occurrence of MIH. Additionally, it has been suggested that low levels of vitamin D may been linked to an increased risk of MIH, however, further investigation is needed to prove such causation (3, 4).

Among the subtypes of DDE, enamel fluorosis is one of the most extensively studied. It affects the appearance and structure of dental enamel. Unlike other DDE, the etiology of enamel fluorosis has been extensively studied and is primarily attributed to the excessive consumption of fluoride during tooth development. Excessive intake of fluoride has not only been linked to an increased risk of developing enamel fluorosis but also to other developmental enamel defects such as enamel hypoplasia and MIH (5–8). Multiple studies have indicated that children may be consuming excessive amounts of fluoride through dietary sources like infant formula and certain foods and soft drinks (9, 10). Accordingly, in this review, DDE is treated as a comprehensive construct encompassing enamel fluorosis, MIH, and other developmental enamel disturbances.

While some etiological factors for DDE have been studied in more detail and their mechanisms are better understood, others are still being investigated. Certain nutritional deficiencies, such as inadequate intake of calcium, and vitamin D have been proven to affect the mineralization and formation of tooth enamel. However, the exact mechanisms by which these deficiencies cause DDE are complex and involve interactions between biological processes and nutrient availability (4).

Similarly, poor maternal nutrition during pregnancy and inadequate nutrition during early childhood have been suggested as potential causes of DDE. Nutritional deficiencies during critical periods of tooth development may impact enamel formation and result in enamel defects. However, the specific mechanisms linking poor maternal nutrition and inadequate childhood nutrition to DDE are also still being investigated (11).

The role of environmental toxicants, including high levels of heavy metals in the diet, in the development of DDE has also been studied (12). Heavy metals can disrupt enamel formation and affect the quality of tooth enamel. However, the precise mechanisms by which these environmental toxicants contribute to DDE are not fully understood and require further research.

While multiple associations between dietary factors and the development of DDE have been established, establishing definitive causality will require extensive research and the consideration of various confounding factors. Additionally, the interaction and potential synergistic effect of dietary factors and genetic and environmental influences needs to be better understood.

Given the fact that these factors and their association to DDE have been studied at varying degrees of detail, it seemed pertinent to identify what evidence is available in this area. We conducted a scoping review of available literature to summarize and evaluate the evidence on the association between dietary habits, environmental exposures, medical/health-related factors, demographic factors, and biological factors, and DDE, with a special emphasis on fluorosis and MIH. The study design, outcome measures, analytical methods, and location of the included studies were examined. This scoping review aimed to provide a comprehensive overview of the available evidence in this area.

Scoping reviews (also known as mapping reviews) are exploratory research projects that systematically map the literature on a topic by identifying key concepts, theories and sources of evidence that inform practice.

This scoping review was conducted using the Joanna Briggs Institute (JBI) methodology and guided by the Population, Concept, and Context (PCC) framework. The population of interest included individuals of any age or sex with clinically diagnosed DDE, including enamel fluorosis, MIH, and other enamel hypoplasias. The review aimed to map the range of dietary, environmental, medical, demographic, and biological factors associated with DDE as a whole, while placing particular emphasis on fluorosis and MIH due to their predominance in the published evidence (13). The population of interest included individuals of any age or sex with clinically diagnosed DDE, including enamel fluorosis, MIH, and other enamel hypoplasias. The review aimed to map the range of dietary, environmental, medical, demographic, and biological factors associated with DDE as a whole, while placing particular emphasis on fluorosis and MIH due to their predominance in the published evidence.

Research Question:

To explore the factors associated with DDE in the population.

Eligibility Criteria:

Population: Studies conducted on individuals of any age group or gender who have been diagnosed with DDE.

Concept: Various factors contribute to the development of DDE. This includes factors such as dietary habits, environmental exposures, medical/health-related factors (e.g., use of supplements, medications), demographic factors (e.g., socioeconomic status, age, gender), and biological factors (e.g., prematurity, birth weight, nutritional status).

Context: Studies conducted in any geographic location or setting, including both clinical and community-based settings.

By using the Population, Concept, and Context (PCC) framework, this scoping review aimed to gather a comprehensive understanding of the factors associated with dental fluorosis, dental enamel hypoplasia, and MIH across different populations, concepts, and contexts.

Taken together, the results of our review show that the available evidence indicates that dietary environmental, and biological factors intersect in shaping the risk of DDE. These findings are consistent with prior reviews showing that disturbances in mineral metabolism, fluoride exposure, and systemic health during the secretory and maturation stages of amelogenesis contribute to enamel abnormalities (7, 18). Across the DDE spectrum, nutritional influences, particularly vitamin D, calcium, and protein intake have been highlighted as critical modulators of ameloblast function (2, 3). Our results reinforce these mechanisms by showing overlapping risk factors for fluorosis, MIH, and other DDE, suggesting that similar biological pathways may underlie distinct clinical manifestations. Overall, dietary factors such as fluoride exposure, breastfeeding practices, and water and milk intake have been associated with the development of DDE. Additionally, previous surgical procedures and the use of antibiotics during pregnancy have also been identified as contributing factors common to all DDE.

Within the DDE spectrum, enamel fluorosis remains the most extensively studied DDE subtype. Our synthesis supports previous epidemiologic and mechanistic findings that excessive fluoride exposure from water, diet, or early-life formula feeding is the dominant determinant of fluorosis severity (18, 19). For MIH, emerging evidence points to nutritional and systemic factors—especially vitamin D deficiency, childhood illness, and perinatal complications—as key contributors (4, 8, 19). The co-occurrence of these factors in many of the included studies underscores how dietary and environmental domains are intertwined rather than mutually exclusive.

Specifically, for dental fluorosis, factors such as fluoride concentration in drinking water, use of fluoride supplements, and duration of residence in a place with high water fluoride content were found to be associated with its development. Socioeconomic status, family income, obesity, age of weaning, and exposure from birth to 4 years were also identified as demographic factors related to dental fluorosis. It is also very evident that fluorosis is the most studied of DDE. This is due to the public health significance of ensuring optimal levels of fluoride intake for caries prevention.

For MIH, certain dietary habits were identified as potential contributors. Environmental factors such as fluoridation levels of water in the residential area and fluoride levels in drinking water were also found to be associated with MIH. Medical/health-related factors such as hyperactivity/inattention symptoms and frequent use of certain antibiotics were also identified as potential factors.

Vitamin status, specifically vitamin D deficiencies, were investigated for their role in DDE development, specifically MIH. While some studies suggested a link, the evidence remains inconclusive. This disagreement is likely due to lack of standardized research methodologies, differences in vitamin D assessment methods, and the complex multifactorial etiology of DDE. Proving direct causality would require a large number of longitudinal studies evaluating maternal vitamin D and following up their offsprings.

This review revealed several key findings. Firstly, studies were conducted primarily in Asia and North America, Given the fact that environmental factors play a role, location of study seems relevant. There is also no agreement on the ideal age to study these conditions, with participants ranging from children aged 6–12 years to adolescents. Study designs could be improved, most studies have been conducted with small sample sizes, were predominantly cross-sectional and did not utilize complex statistical methods to assess complex mixtures of exposures.

In conclusion, dietary factors were found to play a significant role in the development of these conditions. Fluoride exposure from the diet, consumption of certain foods and beverages, and breastfeeding practices were identified as contributing factors. Environmental factors, such as fluoride concentration in drinking water and water fluoridation history, were reported to influence the development of dental fluorosis and MIH. Medical/health-related factors, including the use of fluoride supplements, surgical procedures, and certain medications, were also identified as contributors. Demographic factors, such as socioeconomic status, age, and gender, may also play a role. Additionally, biological factors, including prematurity, birth weight, and nutritional status, can influence the development of these conditions.

Although our review shows consistent patterns (i.e., fluoride, vitamin D, illness) across DDE types, longitudinal and mechanistic evidence remains limited. Most available studies are cross-sectional, restricting causal inference and the ability to differentiate between transient developmental disturbances and chronic exposures. Prospective cohort studies integrating dietary biomarkers, environmental monitoring, and genetic susceptibility markers would help clarify dose–response relationships for fluoride, vitamin D, and trace elements. Standardized diagnostic criteria and unified reporting of DDE subtypes are also needed to improve comparability across populations.

Overall, this review highlights that enamel fluorosis, MIH, and other DDE are interconnected outcomes within a continuum of enamel development disturbances. Dietary and environmental exposures appear to operate through shared biological pathways, altered calcium and phosphate homeostasis, oxidative stress, and impaired protein removal during enamel maturation. Recognizing these overlapping mechanisms provides a foundation for preventive strategies targeting maternal and early-childhood nutrition, as well as safe fluoride exposure. Our review suggests that while multiple factors have been studied, further research is needed to better understand the potential interactions and synergies between these factors.

The search was restricted to online sources, and only English-written papers were included in the study, which may have excluded papers from non-English-speaking nations. Additionally, the scoping review is a type of literature review that aims to map out the existing research on a particular topic. In accordance with JBI Scoping Review guidance, it is not mandatory to assess the quality of the evidence, which means that the findings may be influenced by the quality of the studies reviewed.

Another limitation of the studies reviewed is that most are small, cross-sectional studies with varying methodologies, limiting causal inference. A further limitation is that no formal review protocol was prospectively registered, which may limit reproducibility; however, this was transparently acknowledged, and the review process was conducted following JBI and PRISMA-ScR guidance to maintain methodological rigor.

This scoping review highlights the significant role of dietary and environmental factors in the development of developmental defects of enamel (DDE), encompassing enamel fluorosis, molar–incisor hypomineralization (MIH), and other related enamel anomalies. By recognizing these conditions as interrelated manifestations within the DDE spectrum, future research can better identify shared mechanisms and preventive strategies. Fluoride intake from food, beverages, water, and early feeding practices emerged as the most studied and consistently associated factor, particularly for fluorosis. Nutritional deficiencies, such as inadequate levels of vitamin D and calcium, along with environmental exposures and certain medical or biological conditions, also contribute to the risk of DDE. Despite these associations, much of the existing research relies on small, cross-sectional studies with varying methodologies, limiting causal inference. Further longitudinal and mechanistic studies are needed to clarify how these risk factors interact and to inform preventive strategies that promote optimal enamel development.