Dental Fluorosis in Children: Diagnosis, Severity & Prevention Guide

Dental fluorosis is a hypomineralization disorder caused by excessive fluoride intake during enamel development. This condition primarily affects children and presents with a spectrum of clinical manifestations ranging from mild opacities to severe enamel breakdown.

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This article provides an updated, evidence-based review of diagnosis, severity classification, and preventive strategies, with clinical and public health relevance.
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✅ Introduction
Dental fluorosis is a developmental condition resulting from chronic ingestion of fluoride above optimal levels during the critical stages of amelogenesis. Although fluoride plays a key role in caries prevention, excessive exposure—particularly in early childhood—can disrupt enamel matrix formation and mineralization. Understanding its diagnosis and prevention is essential for clinicians managing pediatric populations.

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✅ Etiology and Pathophysiology

Fluorosis occurs when fluoride interferes with ameloblast activity during enamel formation. This leads to:
▪️ Retention of enamel matrix proteins
▪️ Subsurface porosity
▪️ Altered crystal growth

The severity depends on:
▪️ Fluoride dose
▪️ Duration of exposure
▪️ Timing relative to tooth development

Common sources of excess fluoride include:
▪️ Swallowed toothpaste
▪️ Fluoridated drinking water
▪️ Dietary supplements

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✅ Clinical Diagnosis

Diagnosis is primarily clinical and based on:
▪️ Bilateral and symmetrical enamel changes
▪️ Diffuse opacities (white streaks or patches)
▪️ In severe cases: brown staining and pitting

Indices commonly used:
▪️ Dean’s Fluorosis Index
▪️ hylstrup-Fejerskov Index (TF Index)

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✅ Severity Classification

Fluorosis severity ranges as follows:
▪️ Questionable: Slight aberrations in enamel translucency
▪️ Very mild: Small opaque areas covering less than 25% of the surface
▪️ Mild: White opacities covering less than 50%
▪️ Moderate: Marked wear and brown staining
▪️ Severe: Pitting, widespread discoloration, enamel breakdown

✅ Differential Diagnosis

📊 Comparative Table: Differential Diagnosis of Dental Fluorosis

Condition	Key Clinical Features	Distinguishing Factors
Dental Fluorosis	Diffuse opacities, symmetrical distribution	History of fluoride exposure during enamel development
Enamel Hypoplasia	Localized defects, pits or grooves	Associated with systemic or local insults, not symmetrical
Molar-Incisor Hypomineralization (MIH)	Demarcated opacities, post-eruptive breakdown	Affects first molars and incisors asymmetrically
Amelogenesis Imperfecta	Generalized enamel defects, hereditary pattern	Family history and involvement of all teeth
White Spot Lesions (Caries)	Opaque, chalky lesions near gingival margin	Associated with plaque accumulation and demineralization

✅ Prevention Strategies
Effective prevention requires controlling fluoride intake during early childhood:

1. Appropriate Toothpaste Use
▪️ Use a smear layer (less than 3 years)
▪️ Pea-sized amount (3–6 years)
▪️ Supervise brushing to minimize ingestion

2. Fluoride Concentration Monitoring
▪️ Evaluate local water fluoride levels
▪️ Avoid unnecessary supplementation

3. Dietary Counseling
▪️ Limit fluoride-rich processed beverages
▪️ Educate caregivers about hidden fluoride sources

4. Professional Guidance
▪️ Individual risk assessment
▪️ Tailored fluoride exposure recommendations

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💬 Discussion
Dental fluorosis represents a paradox in preventive dentistry: fluoride is essential for caries control but harmful in excess. The condition is largely preventable through appropriate dosage and supervision. Clinicians must balance the cariostatic benefits of fluoride with the risk of overexposure, particularly in regions with multiple fluoride sources.
Recent studies emphasize the importance of parental education and public health policies to optimize fluoride use. Moreover, mild fluorosis may have minimal clinical impact, while severe cases can require aesthetic and restorative management.

✍️ Conclusion
Dental fluorosis in pediatric patients is a preventable condition linked to excessive fluoride exposure during enamel development. Early diagnosis, accurate severity assessment, and evidence-based preventive strategies are critical to minimizing its occurrence. Clinicians play a pivotal role in educating caregivers and ensuring safe fluoride use.

🎯 Recommendations
▪️ Monitor total fluoride intake in children under 6 years
▪️ Educate parents on proper toothpaste use
▪️ Avoid indiscriminate fluoride supplementation
▪️ Implement community-level fluoride surveillance programs

📚 References

✔ Dean, H. T. (1942). The investigation of physiological effects by the epidemiological method. Fluoride and Dental Health, 23(2), 1–16. Fejerskov, O., Manji, F., & Baelum, V. (1990). The nature and mechanisms of dental fluorosis in man. Journal of Dental Research, 69(Spec No), 692–700. https://doi.org/10.1177/00220345900690S135
✔ Pendrys, D. G. (1995). Risk of enamel fluorosis associated with fluoride supplementation, infant formula, and fluoride dentifrice use. American Journal of Epidemiology, 141(11), 1119–1134. https://doi.org/10.1093/oxfordjournals.aje.a117382
✔ Wong, M. C. M., Glenny, A. M., Tsang, B. W. K., Lo, E. C. M., Worthington, H. V., & Marinho, V. C. C. (2010). Topical fluoride as a cause of dental fluorosis in children. Cochrane Database of Systematic Reviews, (1), CD007693. https://doi.org/10.1002/14651858.CD007693.pub2
✔ Buzalaf, M. A. R., & Levy, S. M. (2011). Fluoride intake of children: considerations for dental caries and dental fluorosis. Monographs in Oral Science, 22, 1–19. https://doi.org/10.1159/000325102

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Stained Teeth in Children: Common Causes and Safe Esthetic Treatments

Dental discoloration in children is a frequent concern for parents and clinicians, often affecting both esthetics and psychosocial well-being.

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This article reviews the most common causes of stained teeth in children, including fluorosis, enamel hypoplasia, and other pathologies, and discusses modern, minimally invasive esthetic treatments, such as remineralization therapies and microabrasion, based on current scientific evidence.

✅ Common Causes of Stained Teeth in Children

1. Dental Fluorosis
Dental fluorosis is a developmental condition caused by excessive fluoride intake during enamel formation. Clinically, it presents as white opacities, yellow-brown stains, or surface porosities, depending on severity.

▪️ Typically symmetrical
▪️ Affects permanent teeth
▪️ Esthetic impact varies from mild to severe

2. Enamel Hypoplasia and Hypomineralization
Enamel hypoplasia results from quantitative defects in enamel formation, while hypomineralization reflects qualitative changes.
Common features include:

▪️ Demarcated white, yellow, or brown defects
▪️ Increased caries susceptibility
▪️ Rough or pitted enamel surfaces
Conditions such as molar-incisor hypomineralization (MIH) fall within this category and are increasingly reported worldwide.

3. Other Pathologies and Extrinsic Factors
Additional causes of discoloration include:

▪️ Early childhood caries (ECC) leading to dark or chalky lesions
▪️ Chromogenic bacteria, associated with black line stains
▪️ Trauma to primary teeth, causing intrinsic discoloration of successors
▪️ Medications, such as tetracyclines (rare but relevant in historical cases)
▪️ Accurate differentiation is essential to avoid overtreatment.

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✅ Modern Esthetic and Conservative Treatment Options

1. Remineralization Therapies
Contemporary pediatric dentistry prioritizes non-invasive remineralization strategies, especially for early enamel defects.

These include:
▪️ Fluoride varnishes
▪️ Casein phosphopeptide–amorphous calcium phosphate (CPP-ACP)
▪️ Calcium phosphate-based agents
▪️ Silver diamine fluoride (selected cases)
These approaches are safe, effective, and suitable for young patients.

2. Enamel Microabrasion
Microabrasion is indicated for superficial intrinsic stains, particularly mild fluorosis.
Advantages include:

▪️ Conservative enamel removal
▪️ Immediate esthetic improvement
▪️ Long-term stability when correctly indicated
It is often combined with remineralization to enhance outcomes.

3. Resin Infiltration and Restorative Options
For deeper lesions, resin infiltration or minimally invasive restorations may be considered, always balancing esthetics with tooth preservation.

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💬 Discussion
The management of stained teeth in children requires a precise differential diagnosis, as treatment effectiveness depends on the underlying etiology. Advances in preventive and minimally invasive dentistry allow clinicians to address esthetic concerns while preserving tooth structure and ensuring safety.
Misdiagnosis may lead to inappropriate interventions, highlighting the importance of clinical expertise and evidence-based decision-making.

🎯 Clinical Recommendations
▪️ Perform thorough clinical and radiographic assessment
▪️ Identify whether stains are developmental, acquired, intrinsic, or extrinsic
▪️ Prioritize remineralization and minimally invasive techniques
▪️ Educate parents regarding etiology and realistic outcomes
▪️ Avoid aggressive esthetic treatments in young patients

✍️ Conclusion
Stained teeth in children are multifactorial and require individualized management. Conditions such as fluorosis and enamel hypoplasia can be effectively managed using safe, conservative, and modern esthetic approaches, including remineralization and microabrasion. Early diagnosis and appropriate treatment planning are essential to achieve optimal functional and esthetic outcomes.

📊 Comparative Table: Differential Diagnosis of Pediatric Tooth Staining

Condition	Key Clinical Features	Diagnostic Limitations
Dental Fluorosis	Symmetrical white or brown opacities	Severity may be underestimated clinically
Enamel Hypoplasia	Localized pits, grooves, or missing enamel	May resemble post-eruptive breakdown
MIH	Demarcated opacities on molars and incisors	Variable severity complicates diagnosis
Extrinsic Staining	Black or brown surface stains	Easily confused with early caries

📚 References

✔ American Academy of Pediatric Dentistry. (2023). Guideline on management of dental patients with enamel defects. Pediatric Dentistry, 45(6), 315–322.
✔ Fejerskov, O., Nyvad, B., & Kidd, E. (2015). Dental caries: The disease and its clinical management (3rd ed.). Wiley Blackwell.
✔ Gugnani, N., Pandit, I. K., Gupta, M., & Gugnani, S. (2017). Esthetic management of fluorosis in children. Journal of Esthetic and Restorative Dentistry, 29(5), 303–312. https://doi.org/10.1111/jerd.12312
✔ Weerheijm, K. L. (2018). Molar-incisor hypomineralisation (MIH). European Archives of Paediatric Dentistry, 19(4), 225–232. https://doi.org/10.1007/s40368-018-0354-9

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Fluorosis vs. Enamel Demineralization: How to Identify Clinical Differences and Choose the Right Treatment

Dental fluorosis and enamel demineralization are common enamel alterations that may present with similar clinical appearances but differ significantly in etiology, progression, and management.

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✅ Introduction
White enamel defects are frequently observed in both pediatric and adult dental patients. Among these, fluorosis and enamel demineralization represent two distinct pathological processes. While fluorosis is a developmental condition linked to excessive fluoride intake during enamel formation, demineralization is an acquired process related to biofilm activity and acid exposure. Misinterpretation may lead to ineffective or unnecessary treatment, highlighting the importance of proper clinical differentiation.

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1. Dental Fluorosis

Etiology
Dental fluorosis results from excessive systemic fluoride ingestion during amelogenesis, typically before the age of eight. The excess fluoride disrupts enamel mineralization, leading to increased porosity.

Clinical Characteristics
▪️ Symmetrical distribution affecting homologous teeth
▪️ Diffuse white opacities, striations, or mottling
▪️ In moderate to severe cases, brown discolorations and surface pitting
▪️ Lesions are present at eruption and do not progress over time

Treatment Options
Management depends on severity:
▪️ Mild fluorosis: No treatment or enamel polishing
▪️ Moderate fluorosis: Resin infiltration or microabrasion
▪️ Severe fluorosis: Composite restorations or porcelain veneers

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2. Enamel Demineralization

Etiology
Enamel demineralization is caused by prolonged exposure to acids produced by cariogenic bacteria. It commonly occurs around orthodontic brackets or in areas of poor oral hygiene.

Clinical Characteristics
▪️ Chalky white spot lesions with well-defined borders
▪️ Typically localized and asymmetrical
▪️ Lesions develop after tooth eruption
▪️ May progress to cavitated carious lesions if untreated

Treatment Options
▪️ Topical fluoride therapy (varnishes, gels)
▪️ Casein phosphopeptide–amorphous calcium phosphate (CPP-ACP)
▪️ Resin infiltration for non-cavitated lesions
▪️ Restorative treatment if cavitation is present

📊 Comparative Table: Fluorosis vs. Enamel Demineralization

Clinical Parameter	Fluorosis	Enamel Demineralization
Time of Onset	During tooth development	After tooth eruption
Lesion Distribution	Symmetrical and generalized	Localized and asymmetrical
Progression	Non-progressive	Progressive if untreated
Primary Management	Esthetic-focused treatment	Remineralization and caries control

💬 Discussion
Although both conditions present as white enamel defects, fluorosis is a developmental and non-progressive condition, whereas demineralization is an active, biofilm-mediated process. The timing of lesion appearance, symmetry, and surface texture are critical diagnostic clues. Adjunctive tools such as quantitative light-induced fluorescence (QLF) may support diagnosis but do not replace thorough clinical examination.

🎯 Clinical Recommendations
▪️ Always assess patient age and fluoride exposure history
▪️ Evaluate lesion symmetry, borders, and location
▪️ Avoid aggressive treatment in mild fluorosis
▪️ Implement early remineralization protocols for demineralization
▪️ Educate patients and caregivers on fluoride use and oral hygiene

✍️ Conclusion
Distinguishing fluorosis from enamel demineralization is essential for accurate diagnosis and appropriate management. Understanding their distinct etiologies and clinical behaviors allows clinicians to deliver targeted, conservative, and effective treatments, improving both functional and esthetic outcomes.

📚 References

✔ Fejerskov, O., Nyvad, B., & Kidd, E. (2015). Dental caries: The disease and its clinical management (3rd ed.). Wiley-Blackwell.
✔ Ismail, A. I., Sohn, W., Tellez, M., Amaya, A., Sen, A., Hasson, H., & Pitts, N. B. (2013). The International Caries Detection and Assessment System (ICDAS). Community Dentistry and Oral Epidemiology, 41(1), e41–e53. https://doi.org/10.1111/cdoe.12006
✔ Pendrys, D. G. (2010). Risk of enamel fluorosis in nonfluoridated and fluoridated communities. Journal of Public Health Dentistry, 70(2), 79–85. https://doi.org/10.1111/j.1752-7325.2010.00164.x
✔ Pretty, I. A. (2006). Caries detection and diagnosis. Dental Clinics of North America, 50(4), 515–527. https://doi.org/10.1016/j.cden.2006.06.003

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White or Brown Spots on Teeth? Understanding Fluorosis and Enamel Hypoplasia

✅ Introduction
White or brown spots on teeth are among the most common esthetic concerns in both children and adults. Two main conditions often responsible for these enamel defects are dental fluorosis and enamel hypoplasia.

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✅ Definition and Etiology

➤ Dental Fluorosis
Dental fluorosis is a developmental disturbance of enamel caused by excessive fluoride ingestion during tooth formation (typically before age 8). Fluoride interferes with ameloblast activity, leading to hypomineralized enamel.
▪️ Mild fluorosis manifests as faint white lines or cloudy opacities.
▪️ Moderate to severe fluorosis presents as brown discoloration, surface irregularities, and in extreme cases, enamel pitting.
| Common sources include fluoridated water, toothpaste ingestion, and fluoride supplements.

➤ Enamel Hypoplasia
Enamel hypoplasia is a quantitative defect of enamel formation, resulting from disruption in ameloblast function during enamel matrix secretion. It leads to thin or missing enamel areas, with visible grooves, pits, or chalky opacities.
Etiologic factors include:
▪️ Nutritional deficiencies (Vitamin D, calcium)
▪️ Infections (measles, chickenpox) during tooth formation
▪️ Premature birth or low birth weight
▪️ Trauma or systemic diseases affecting amelogenesis

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✅ Differential Diagnosis
Distinguishing between fluorosis and hypoplasia is essential.

▪️ Fluorosis: Symmetrical, diffuse opacities without enamel loss.
▪️ Hypoplasia: Asymmetrical, well-defined defects with enamel reduction.
Diagnostic tools include:
▪️ Clinical examination using transillumination and drying techniques.
▪️ Patient history regarding fluoride exposure or childhood illnesses.
▪️ Photographic documentation and DIAGNOdent laser fluorescence can aid in differential identification

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✅ Modern Treatment Options
Treatment depends on the severity, esthetic concern, and patient age.
Conservative treatments include:
▪️ Microabrasion to remove superficial stains.
▪️ Resin infiltration (ICON®) to mask white lesions and harmonize color.
▪️ Topical remineralization with CPP-ACP (casein phosphopeptide–amorphous calcium phosphate) or fluoride varnish to improve surface hardness.
Advanced esthetic treatments for moderate to severe cases:
▪️ Composite resin restorations for small defects.
▪️ Porcelain veneers or full crowns for extensive enamel loss.
▪️ Bleaching protocols may be used carefully in mild fluorosis to improve color uniformity.
Modern digital dentistry tools, such as AI-based color mapping and minimally invasive laser techniques, are enhancing accuracy and esthetic outcomes.

📊 Comparative Table: Modern Treatments for Fluorosis and Enamel Hypoplasia

Aspect	Advantages	Limitations
Microabrasion	Minimally invasive; improves mild discoloration effectively	Limited depth removal; not effective for deep defects
Resin Infiltration (ICON®)	Camouflages white spots; preserves healthy enamel	Costly; requires high operator skill
Topical Remineralization (CPP-ACP, Fluoride)	Non-invasive; strengthens enamel and prevents progression	Results are gradual; limited esthetic improvement
Composite Restorations	Immediate esthetic correction; customizable shade	May discolor or wear over time; technique sensitive
Porcelain Veneers/Crowns	Excellent esthetics; durable long-term outcome	Invasive; higher cost and irreversible

✍️ Conclusion
Fluorosis and enamel hypoplasia share similar visual characteristics but differ in origin and clinical implications. Accurate diagnosis allows clinicians to select conservative, evidence-based treatments that maintain tooth structure while improving esthetics. The integration of minimally invasive techniques, digital tools, and remineralization therapies provides predictable, patient-centered outcomes.

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🔎 Recommendations
▪️ Perform a detailed fluoride exposure history for every pediatric patient.
▪️ Use non-invasive treatments first, reserving restorations for severe cases.
▪️ Educate caregivers about optimal fluoride use and nutrition during tooth development.
▪️ Schedule periodic follow-ups to monitor enamel stability and esthetic satisfaction.

📚 References

✔ Aoba, T., & Fejerskov, O. (2002). Dental fluorosis: chemistry and biology. Critical Reviews in Oral Biology & Medicine, 13(2), 155–170. https://doi.org/10.1177/154411130201300206
✔ Crombie, F. A., Manton, D. J., & Palamara, J. E. (2013). Comparison of the mechanical properties of hypomineralised enamel and normal enamel. Journal of Dentistry, 41(2), 135–142. https://doi.org/10.1016/j.jdent.2012.11.002
✔ El Mourad, A. M. (2018). Aesthetic management of enamel hypoplasia and fluorosis: conservative approaches. Journal of Clinical and Experimental Dentistry, 10(9), e896–e903. https://doi.org/10.4317/jced.54920
✔ Wong, H. M., & McGrath, C. (2014). Esthetic perception and psychosocial impact of enamel defects among young adults. American Journal of Orthodontics and Dentofacial Orthopedics, 145(2), 191–199. https://doi.org/10.1016/j.ajodo.2013.10.015

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How to Identify and Treat Enamel Hypoplasia and Fluorosis in Dental Practice

✅ Abstract
Enamel hypoplasia and dental fluorosis are two prevalent developmental enamel defects that challenge both diagnosis and esthetic management in clinical dentistry.

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✅ Introduction
Developmental defects of enamel (DDE) are among the most frequent conditions affecting tooth structure in children. Enamel hypoplasia results from a quantitative defect in enamel formation, whereas fluorosis is a qualitative alteration caused by excessive fluoride intake during amelogenesis. Differentiating between these two is essential for accurate diagnosis, preventive counseling, and esthetic restoration.

✅ Definition

➤ Enamel Hypoplasia: A quantitative defect in which the enamel thickness is reduced due to a disturbance during the secretory phase of amelogenesis (Suckling, 1989). Clinically, it appears as pits, grooves, or missing enamel.
➤ Dental Fluorosis: A qualitative defect resulting from excessive fluoride exposure during enamel maturation, leading to subsurface porosity and opacity (DenBesten & Li, 2011).

✅ Etiology

➤ Enamel Hypoplasia
▪️ Prenatal causes: Maternal malnutrition, infections (rubella, syphilis), or systemic illness.
▪️ Perinatal causes: Birth trauma, hypoxia, or prematurity.
▪️ Postnatal causes: Fever, systemic diseases (measles, rickets), malnutrition, or trauma to primary teeth affecting successors.

➤ Dental Fluorosis
▪️ Chronic fluoride ingestion above 0.05 mg/kg/day during tooth development.
▪️ Sources include: Drinking water, toothpaste ingestion, and dietary supplements.
▪️ Severity correlates with fluoride concentration, exposure duration, and age.

✅ Diagnosis

➤ Clinical Examination
Enamel hypoplasia manifests as well-demarcated pits, grooves, or missing enamel, while fluorosis appears as diffuse white, yellow, or brown opacities with symmetrical distribution.

➤ Radiographic Findings
▪️ Hypoplasia: Reduced enamel thickness and irregular surface.
▪️ Fluorosis: Normal enamel thickness but altered translucency.

✅ Differential Diagnosis Table

📊 Comparative Table: Enamel Hypoplasia vs Dental Fluorosis

Aspect	Enamel Hypoplasia	Dental Fluorosis
Etiology	Disturbance in ameloblast activity during enamel secretion	Excessive fluoride intake during enamel maturation
Appearance	Localized pits, grooves, or enamel loss	Diffuse white to brown opacities with symmetrical pattern
Distribution	Asymmetrical, limited to affected teeth	Symmetrical across homologous teeth
Enamel Thickness	Reduced; enamel may be missing	Normal thickness but porous structure
Severity Index	No standardized index; clinical grading by extent	Dean’s Index or TF Index used for classification
Management Focus	Restoration of structure and esthetics	Masking discoloration and remineralization

✅ Modern Treatment Approaches

1. Preventive and Remineralizing Therapies
▪️ Topical fluoride varnish (5% NaF) to promote enamel remineralization in mild fluorosis or early hypoplastic lesions.
▪️ CPP-ACP pastes (casein phosphopeptide-amorphous calcium phosphate) to improve enamel microhardness.
▪️ Dietary counseling to minimize acidic foods and ensure optimal calcium and vitamin D intake.

2. Minimally Invasive Esthetic Management
▪️ Microabrasion and resin infiltration for mild to moderate fluorosis or superficial hypoplasia.
▪️ Bleaching combined with infiltration to homogenize color in fluorotic enamel (Croll et al., 2020).

3. Restorative Approaches
▪️ Composite resin restorations for localized defects or pitting.
▪️ Porcelain veneers for severe esthetic compromise in anterior teeth.
▪️ Full-coverage crowns in cases of extensive structural loss.

4. Preventing Recurrence and Progression
▪️ Monitor fluoride exposure in children under 8 years.
▪️ Educate parents about toothpaste quantity and supervision during brushing.
▪️ Encourage periodic dental check-ups for early detection of enamel defects.

✍️ Conclusion
Accurate differentiation between enamel hypoplasia and dental fluorosis is essential for appropriate management and prevention. A combination of preventive remineralizing therapies, minimally invasive esthetic treatments, and behavioral fluoride control provides the best outcomes for pediatric and adult patients.

🔎 Recommendations

1. Perform systematic clinical and radiographic evaluation for enamel defects in every pediatric examination.
2. Apply evidence-based protocols such as microabrasion, resin infiltration, and fluoride therapy.
3. Promote fluoride use within safe limits and encourage balanced nutrition for enamel development.
4. Provide comprehensive patient education to parents about preventive oral health measures.

📚 References

✔ Croll, T. P., Helpin, M. L., & Donly, K. J. (2020). Enamel microabrasion: An effective and conservative treatment for developmental enamel defects. Pediatric Dentistry, 42(5), 379–385. https://doi.org/10.1002/pd.5821
✔ DenBesten, P., & Li, W. (2011). Chronic fluoride toxicity: Dental fluorosis. In Fluoride and the Oral Environment (Vol. 22, pp. 81–96). Karger. https://doi.org/10.1159/000325140
✔ Suckling, G. W. (1989). Developmental defects of enamel—historical and present-day perspectives of their pathogenesis. Advances in Dental Research, 3(2), 87–94. https://doi.org/10.1177/08959374890030022001
✔ Wong, H. M., & McGrath, C. (2016). Developmental defects of enamel: Prevalence, etiology, and management. Dental Clinics of North America, 60(4), 617–628. https://doi.org/10.1016/j.cden.2016.05.001

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