1 Volume 24 2025 e255975 Critical Review Braz J Oral Sci. 2025;24:e255975http://dx.doi.org/10.20396/bjos.v24i00.8675975 1 DDS, Post Graduate Student, School of Dentistry, Universidade Federal de Alfenas, Alfenas, Minas Gerais, Brazil. 2 DDS, MSc, School of Dentistry, Faculdade de Odontologia São Leopoldo Mandic, Campinas, São Paulo, Brazil. 3 DDS, MSc, PhD, Professor, School of Dentistry, Universidade Federal de Alfenas, Alfenas, Minas Gerais, Brazil. 4 DDS, MSc, PhD, Post Doctorate Student, School of Dentistry, Universidade Federal de Alfenas, Alfenas, Minas Gerais, Brazil. Corresponding author: Heloisa de Sousa Gomes Rua Gabriel Monteiro da Silva, 700, Centro CEP: 37137-001; Alfenas/Minas Gerais, Brasil. Telephone: +55 (35) 98829-5958 E-mail: hsousagomes@yahoo.com.br Editor: Dr. Altair A. Del Bel Cury Received: March 06, 2024 Accepted: November 19, 2024 The intersection of stress, childhood adversities, and oral health: implications for pediatric care Maria Eugênia Domingueti Rabelo Ribeiro1 , Lara Evangelista Orlandi1 , Rodrigo Rodrigues2 , Leandro Araújo Fernandes3 , Daniela Coelho de Lima3 , Heloisa de Sousa Gomes4* Aim: The physiological stress response is shaped in childhood and the intensity, frequency, and duration of stressful stimuli determine it. Adverse emotions experienced in early childhood can have profound and lasting physiological and psychological consequences. Therefore, it is important to understand how dental treatment can be a significant stressful in a child’s life and recognize the potential lifelong impact. It is also crucial to comprehend how chronic stress can negatively affect oral health over time. Methods: In the present study, a critical review was conducted by analyzing scientific articles related to stress, salivary cortisol levels, child neurodevelopment, and the association of these factors during pediatric dental care, from 1981 to 2024, in databases such as PubMed and SciElo. Results: Across 69 studies, the review emphasizes the connections between adverse childhood experiences (ACEs), dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, and their cumulative effect on pediatric oral health. The findings illustrate how ACEs can disrupt normal brain functioning, leading to chronic stress, poor oral health outcomes, and altered behavior during dental care. Conclusion: Dental professionals must approach pediatric care with a deep understanding of the child’s emotional and psychological state. By doing so, they can contribute to healthier oral outcomes and help mitigate the long-term impact of childhood adversities on oral health. Keywords: Adverse childhood experience. Dentists. Stress, physiological. https://orcid.org/0000-0003-1182-2002 https://orcid.org/0000-0003-3926-0750 https://orcid.org/0000-0002-4218-2303 https://orcid.org/0000-0003-2227-5366 https://orcid.org/0000-0002-7945-435X https://orcid.org/0000-0002-0065-9556 2 Ribeiro et al. Braz J Oral Sci. 2025;24:e255975 Introduction Understanding the biological, physical, and social events of children’s neuropsycho- motor and social development is crucial for their integral care. Dental professionals should recognize that their role extends beyond physical, clinical, and complementary examination, they must be aware of the possible adversities that surround that child. After all, the adversities present in childhood are responsible for delineating the future adults they will become. The first 1000 days of the baby encompass the 270 days of the gestational period and the first two years of the baby’s life. During these moments, children are vulnerable to genetic, epigenetic, and environmental factors which is a decisive period, that has a great influence and can be determining factors in their future life, regarding their per- sonality, behavior, and general health1-2. Given that many children undergo dental care during this period, it is essential to understand how these experiences can impact their lives, as they can be significant stressors. Furthermore, it is crucial to consider the potential long-term consequences for the child, particularly on oral health and stress response, underscoring the impor- tance of professional expertise in this area. Materials and Methods In the present study, a critical review was conducted to evaluate studies that relate stress in childhood and its effect throughout life, and the relation with dental treat- ment, using the PubMed and SciELO databases, employing the keywords “Pediatric Dentistry”, “Dental Care”, “Child Development,” “Adverse Childhood Experiences,” “Toxic Stress,” “Hypothalamus-Pituitary System,” and “Brain Development,” in both Portu- guese and English languages, from 1981 to 2024. Sixty-five duplicate studies were excluded from the articles retrieved. The search results were reviewed, the titles and abstracts were screened to remove studies out- side the scope of this review, and three hundred ninety-seven articles were excluded. Then, the full text of all potentially eligible studies was obtained and further examined to exclude those that did not fulfill the inclusion criteria. In this step, 85 citations were removed. Ultimately, sixty-nine scientific articles were analyzed and included in this review, focusing on toxic stress, salivary cortisol levels, brain development, and the association of these changes with dental care. A flow diagram of the literature is pre- sented in Figure 1. The inclusion criteria for the selection of articles were clinical case studies, review articles, and original articles with experimental studies. Papers on perspectives and opinions, commentary articles, and book reviews were excluded. 3 Ribeiro et al. Braz J Oral Sci. 2025;24:e255975 Identification of studies via database Id en tif ic at io n Sc re en in g In cl ud ed Studies included in review (n = 69) Studies selected for full reading (n = 154) Studies found on each database (n = 616) Pubmed (n = 429) Scielo (n = 187) Selected studies after excluding duplicates (n = 551) Records removed before screening: Duplicate records removed (n = 65) Excluded studies after reading of title, abstract, and keywords (n = 397) Excluded studies after full reading for not matching the elegibility criteria (n = 85) Figure 1. Flow diagram of the literature search and included studies. Results Children’s Neurodevelopment Children’s neurodevelopment, spanning birth to early school age, involves physical, emotional, social, and cognitive aspects. The study of neurodevelopment reveals that experiences in various environments and relationships shape the brain’s architecture from an early age1-3. In early childhood, children develop across three dimensions: biological, psychi- cal, and social. Biologically, ensuring proper nutrition and a hygienic environment is essential for fostering healthy physical growth. Physiologically, tactile experi- ences, affectionate interactions, and exposure to visual, olfactory, and auditory stimuli from caregivers play a pivotal in shaping motor, cognitive, emotional, and sensory skills. Lastly, the social dimension emphasizes the significance of a nur- turing environment that supports appropriate social interventions for the overall well-being of the child1-3. During the first years of life, the various stimuli that the child is exposed sees enable and increase dendrites and synaptic connections, as well as cerebral myelinization, crucial for efficient nerve conduction. This period and adolescence are critical for brain development, starting from the third week of pregnancy, where the development of neural structures begins, starting with the formation of the neural tube4, as well as the stress response, occurring from the 20th week of the intrauterine life of the baby5. 4 Ribeiro et al. Braz J Oral Sci. 2025;24:e255975 Some of these stimuli may come from adverse childhood situations, by external stim- uli performed by parents, caregivers, and prepared professionals, which are related to negative experiences in a short or long time, impacting physiological, cognitive, behavioral, and psychological functions throughout life6-7. Neuroscience studies confirm that events during pregnancy and childhood influence a lifetime1,7-11. Analyses the function, structure, and brain development of pre-term babies compared to term-born babies, especially those births between the 27th and 32nd weeks, show functional disorganization and heightened stress response, com- pared to term-born children, from the 38th week birth12. Stressful factors in neonatal intensive care, like exposure to strong lights, loud noises, and frequent invasive inter- ventions, may be associated with this outcome13. Corroborating these results12-13, another research revealed that perinatal stress induces behavioral changes, including heightened and prolonged stress response, increased anxiety, difficulties in learning and memory, and an intensified desire and preference for alcoholic beverages14. On the other hand, in childhood, a period of active brain development and highly responsive to lived experiences, there is a remarkable capac- ity for plastic changes, which influences behavioral, epigenetic, and neural outcomes throughout life14. Research suggests14-16 a stress response mechanism, known as resilience, that enables the body to adapt to adversity. This capacity varies among individuals, influ- enced by factors such as the presence of a support network to overcome adversi- ties and early coping mechanisms developed since childhood, because of brain plasticity16. Also known as neural plasticity, the brain’s constant remodeling capac- ity, extends throughout life, peaking during childhood, allowing for adaptation to new stimuli and events14. Stress Response and Childhood Stressors A study involving rodents, where offspring separated from their mothers shortly after birth for a prolonged period displayed increased vulnerability to stressors in adult- hood. This supports the idea that adversities faced in childhood and adolescence can significantly influence later life17-18. These stress-inducing situations potentially activate two interconnected systems, the hypothalamic-pituitary-adrenal axis (HPA) and the sympathetic nervous system (SNS), triggering responses in the body6,19-21. These responses are linked to an activa- tion of the sympathetic nervous system (SNS) stimulates the adrenal medulla, leading to the release of adrenaline and noradrenaline into the bloodstream. This influences the functioning of peripheral organs, resulting in changes in hepatic, cardiovascular, respiratory, and other systems6,16-21. Activation of the HPA axis in response to stress involves the hypothalamus produc- ing and realizing corticotropin-releasing hormone (CRH), and the pituitary gland gen- erating adrenocorticotropin hormone (ACTH). This stimulates the adrenal cortex to release cortisol into the blood plasma15-22. The peak in blood occurs 15 to 20 minutes post-release, and after 2-3 minutes, there is a peak of cortisol in saliva. This cortisol 5 Ribeiro et al. Braz J Oral Sci. 2025;24:e255975 diffuses across salivary gland membranes, reflecting concentrations of free cortisol in plasma23. The stressor stimulus can trigger two mechanisms: allostasis or allostatic load. Allostasis, which aims to adapt the body and achieve homeostasis, is considered a normal reactive response to stress known as resilience. Homeostasis functions as negative feedback through catecholamines’ secretion and action, controlling the release of these substances and preventing a harmful response24,25. When this activation and release of hormones become persistent over the long term, the response to adverse situations can be compromised [25], so, the mechanisms of allostatic load are triggered, resulting from cumulative adaptations and the fail- ure to control these systems. Allostatic load occurs when the individual inadequately responds to stress, leading to stressor overload16,24,25. Stress can be classified into three forms based on the analysis of intensity, fre- quency, and duration, along with the individual’s reaction: positive, tolerable, and toxic stress6,24. Positive stress involves low-intensity and short-duration stress, modulated by protective mechanisms that swiftly restore homeostasis. It fosters resilience skills, stimulates neural synapses, and contributes to adaptive responses24. Tolerable stress arises when it persists over a period that could potentially impact brain architecture. However, the presence of a supportive network and strong relation- ships creates a welcoming environment for the child, helping maintain physiological homeostasis and preventing stress from reaching toxic levels24. On the other hand, toxic stress is characterized by chronic, intense adverse experi- ences that exceed the child’s coping abilities, lacking a support network to navigate through them. In such cases, disturbances in neuropsychomotor development and an increased risk of organic diseases throughout life, such as diabetes mellitus, systemic arterial hypertension, pulmonary, cardiovascular, and autoimmune diseases, in addi- tion to poor oral health, can be observed as consequences20,21,24. These risks include issues, such as cigarette use, alcohol and drug abuse and obesity6. Stress Response in Dental Setting Dental treatment is widely recognized as a stressor for individuals who undergo it. Among children and adolescents, approximately 9% of them experience fear, anxiety, and behavior management challenges in dental settings, a negative experience they had26. Studies27,28 reveal that anxious patients, in retrospect, perceive the procedure as more distressing and painful weeks after the treatment, contrary to the opinion of non-anxious patients who report reduced pain over time29. A study supporting this idea observed that patients with fear, anxiety, and dentist phobia had previous negative experiences, reliving these emotions. However, the study, involving adults aged 44 to 51, focused on experiences in adulthood around 25 years old, excluding childhood and adolescent memories, requiring additional research validation30. During dental appointments, stress can be measured through cortisol levels in saliva31, with its collection and analysis regarded as a non-invasive, simple, and pain- 6 Ribeiro et al. Braz J Oral Sci. 2025;24:e255975 less method. Many studies are conducted to identify which dental procedures and situations are considered more stressful in the dental environment23,32-44. Some studies indicate that even in simple procedures like dental prophylaxis, changes in cortisol levels can be observed, with increased reports23,32-35. Even before the first consultation, during the examination, non-cooperative patients exhibited elevated cor- tisol levels36. Slightly more invasive treatments involving anesthesia have also been studied, revealing higher cortisol levels after extraction procedures37,38 and post-anes- thesia for restoration procedures39. Moreover, studies have found a correlation between higher stress levels in children with cavities40,41. Another study showed that less cooperative children presented higher cortisol levels than cooperative ones42, enabling professionals to identify moments and children more sensitive to stress through behavior. Furthermore, additional research has been conducted on dental care and stress. It was possible to identify that procedures incorporating aromatherapy as a means to manage anxiety and stress yielded positive results, with lower levels of salivary cortisol reported43,44. Discussion Dental care in children, even a less invasive procedure, can be a stressor, especially for those who have experienced more frequent adversities during childhood23. The ability to cope with stressful situations is mediated by interconnected brain and hormonal systems, promoting adaptability to life circumstances. The proper and balanced func- tioning of these systems is essential for healthy development45. The response to stress occurs from intrauterine life, around the 20th week5, but the stability of the stress regulatory system (HPA) takes place only after a few months or years46. Thus, adversities experienced during childhood may alter the functioning of this system, leading to pathological responses to stress throughout life47. Continuous, intense, and uncontrollable stress, known as toxic stress, has the poten- tial to affect the brain structure48. With this, the response of the stress regulatory sys- tem is likely to be altered in the presence of adverse situations, resulting in a lowered stress threshold. This makes even simple stimuli capable of activating this system, and stress becomes more common and frequent, which reduces resilience and increases impulsivity in the face of these events24. Adults who reported experiencing adversities during childhood exhibited higher cortisol levels49. These findings support the arguments that changes occurring in childhood can affect the functioning of the stress regulatory system throughout life. Research suggests that psychosocial interventions during childhood espe- cially in vulnerable groups can be effective. This reinforces that the nervous sys- tem responsible for stress (HPA) is more malleable during this period, offering the potential for resilience50-52. Dysregulation of the HPA system significantly affects neural function, leading to changes in brain regions responsible for learning and memory, as well as alterations in the immune system53,54. Specifically, high cortisol levels can suppress the immune 7 Ribeiro et al. Braz J Oral Sci. 2025;24:e255975 system, affecting the inflammatory response and increasing susceptibility to infec- tions21. Additionally, some studies have indicated that exposure to stress during child- hood is associated with delays in cognitive development, increased susceptibility to infections, somatic diseases, alterations in sleep patterns, and poor oral health10,55. Studies56-58 have also sought to explain the relationship between adverse childhood experiences (ACEs) and poor oral health. These studies demonstrate that chronic stress results in allostatic load, which is the hyperactivation of the stressor response system. This cumulative physiological impact of stress directly affects oral health by promoting inflammatory responses and contributing to poor oral health maintenance, thereby increasing the risk of periodontal disease and caries. This is consistent with other research showing that children who experience stressful situations are more likely to have poor oral health, with ACEs acting as a predictor55,59. Furthermore, the presence of childhood adversities often means that children receive less preventive care, which can lead to greater development of caries dis- ease and other oral health deficiencies60. Other studies have observed that children whose parents were more careful from pregnancy through the early years of life demonstrated better development and lower rates of caries due to less exposure to adverse events and the provision of necessary care by the mother61. In this context, premature and low birth weight children also had a higher prevalence of caries in early childhood62, and are more prone to stressful experiences compared to those born at term12,13. Moreover, children with untreated decayed teeth are more likely to be bullied com- pared to those who have had caries treated or those who are caries-free55,63,64, indicat- ing a stressful and often chronic situation in a child’s life. This association may help explain the link between caries and ACEs24. Additionally, it has been observed that children born to parents who smoke are at greater risk of developing caries65, which may further explain the connection between stress and poor oral health, as stressful situations can lead to increased tobacco and drug use14. Lastly, the long-term effects of parents who experienced chronic adversity during childhood can manifest in the oral health condition of their children, increasing the likelihood of caries disease in early childhood62,66. These findings support the argument that adversities in childhood can impact brain development and various bodily systems, giving rise to consequences that persist throughout life9. Among these factors associated with the oral health and adverse situations is dental care itself, which can also function as a stressful moment in a person’s life, where higher levels of cortisol, the stress hormone, can be observed after care33,34,67. Stress can be measured quantitatively through salivary collection and analysis, using salivary biomarkers, specifically cortisol68. Although dental treatment reduced cortisol levels in children with early childhood caries after the end of treat- ment, the presence of cortisol was higher in children requiring dental treatment and who had caries compared to those without the disease41. A previous negative experience related to dental treatment can be significantly associ- ated with uncooperative behavior29,69. Corroborating this, studies indicate that patients with fear, anxiety, and dentist phobia, who had previously undergone negative experi- 8 Ribeiro et al. Braz J Oral Sci. 2025;24:e255975 ences, often report feeling as if they are reliving those past situations30. However, one of these studies involved adult patients, aged between 45 and 51 years old, and the reported negative experiences occurred in adulthood, around 25 years old, which does not encompass memories from childhood and adolescence, requiring further studies to substantiate it30. Taking into consideration all of that, mental disorders mostly develop in childhood and negative dental experiences in this period of life trigger the development of dental fear and anxiety. Furthermore, the reaction and behavior of children during dental treatment do not necessarily correspond to the psychological stress of chil- dren once uncooperative behavior does not always reflect the anxiety state. So, it is essential to understand the emotional changes and mental stress in children who underwent dental procedures as well as to be apt to evaluate the exact level of a child’s development, attitudes, and temperament to predict their reaction in front of a stressful stimulus. So, professional who deals with children as dentists must be aware of making good memories on children for them become healthy and free of traumas adults. In conclusion: 1. Awareness of Risk Factors: pediatric dentists should be aware of the risk factors contributing to stress in young patients; 2. Understanding the Impact of Dental Care: recognize how dental care can influen- ce their stress response for mitigating these effects; 3. Knowledge of Children’s Neurodevelopment: health professionals must know children’s neurodevelopment to apply behavior management techniques accor- ding to individual cognitive development stages; 4. Understanding the Impact of Stress on Oral Health: it is crucial to comprehend how chronic stress can negatively affect oral health, leading to long-term conse- quences if not properly managed. By incorporating these considerations into their practice, they can create a more pos- itive and supportive dental experience for children, potentially reducing stress, and fostering long-term oral health habits. Acknowledgments We wish to thank the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), for providing the scholarship. Data Availability Datasets related to this article will be available upon request to the corresponding author. Conflicts of interest None. 9 Ribeiro et al. Braz J Oral Sci. 2025;24:e255975 Author Contribution Maria Eugênia Domingueti Rabelo Ribeiro actively participated in the construction of the manuscript, her responsibility was to conceptualize, investigate, and find the data curation, writing-original draft preparation, and after the supervision, review, edit, and approve the final version of the manuscript. Lara Evangelista Orlandi actively participated in the construction of the manuscript, her responsibility was to conceptualize, investigate and find the data curation, review, edit, and approve the final version of the manuscript. Rodrigo Rodrigues and Leandro Araújo Fernandes actively participated in the construction of the manuscript, their responsibility was to do the formal analysis, make the data curation, review, edit, and approve the final version of the manuscript. Daniela Coelho de Lima and Heloisa de Sousa Gomes actively participated in the construction of the manuscript, their responsibility was to do the formal analysis and review, editing, supervision, and approve the final ver- sion of the manuscript. References 1. Brines J, Rigourd V, Billeaud C. The first 1000 days of infant. Healthcare (Basel). 2022 Jan;10(1):106. doi: 10.3390/healthcare10010106. 2. Mobarek NH, Khalil AM, Talaat DM. Exposure to electronic screens and children’s anxiety and behavior during dental treatment. J Dent Child (Chic). 2019 Sep 15;86(3):139-44. 3. de Mendonça FS, Scalamandré de Mendonça TF, Rêgo ICQ, Motta RHL, Oliveira LB. Children’s perceptions of the dentist and dental office through drawings. J Dent Child (Chic). 2021 Jan;88(1):35-9. 4. Osawa M, Konishi Y. [Developing the brain--proposal to child neurologists: how to nurture and stimulate brain development]. No To Hattatsu. 2003 Mar;35(2):113-6. Japanese. 5. Gitau R, Fisk NM, Teixeira JM, Cameron A, Glover V. Fetal hypothalamic-pituitary-adrenal stress responses to invasive procedures are independent of maternal responses. J Clin Endocrinol Metab. 2001 Jan;86(1):104-9. doi: 10.1210/jcem.86.1.7090. 6. Oral R, Ramirez M, Coohey C, Nakada S, Walz A, Kuntz A, et al. Adverse childhood experiences and trauma informed care: the future of health care. Pediatr Res. 2016 Jan;79(1-2):227-33. doi: 10.1038/pr.2015.197. Epub 2015 Oct 13. 7. Felitti VJ. Adverse childhood experiences and adult health. Acad Pediatr. 2009 May-Jun;9(3):131-2. doi: 10.1016/j.acap.2009.03.001. 8. Flaherty EG, Thompson R, Litrownik AJ, Zolotor AJ, Dubowitz H, Runyan DK, et al. Adverse childhood exposures and reported child health at age 12. Acad Pediatr. 2009 May-Jun;9(3):150-6. doi: 10.1016/j.acap.2008.11.003. 9. Bunea IM, Szentágotai-Tătar A, Miu AC. Early-life adversity and cortisol response to social stress: a meta-analysis. Transl Psychiatry. 2017 Dec;7(12):1274. doi: 10.1038/s41398-017-0032-3. 10. Oh DL, Jerman P, Silvério Marques S, Koita K, Purewal Boparai SK, Burke Harris N, et al. Systematic review of pediatric health outcomes associated with childhood adversity. BMC Pediatr. 2018 Feb;18(1):83. doi: 10.1186/s12887-018-1037-7. 11. Scher MS. “The First Thousand Days” Define a Fetal/Neonatal Neurology Program. Front Pediatr. 2021 Aug;9:683138. doi: 10.3389/fped.2021.683138. 10 Ribeiro et al. Braz J Oral Sci. 2025;24:e255975 12. Als H, Duffy FH, McAnulty GB. Behavioral differences between pre- term and full term newborns as measured with the API system scores: I. Infant Behav Dev. 1988;11:305-18 13. Als H, Duffy FH, McAnulty GB, Rivkin MJ, Vajapeyam S, Mulkern RV, et al. Early experience alters brain function and structure. Pediatrics. 2004 Apr;113(4):846-57. doi: 10.1542/peds.113.4.846. 14. Kolb B, Harker A, Gibb R. Principles of plasticity in the developing brain. Dev Med Child Neurol. 2017 Dec;59(12):1218-23. doi: 10.1111/dmcn.13546. 15. Timmermans W, Xiong H, Hoogenraad CC, Krugers HJ. Stress and excitatory synapses: from health to disease. Neuroscience. 2013 Sep;248:626-36. doi: 10.1016/j.neuroscience.2013.05.043. 16. Cathomas F, Murrough JW, Nestler EJ, Han MH, Russo SJ. Neurobiology of Resilience: Interface Between Mind and Body. Biol Psychiatry. 2019 Sep;86(6):410-20. doi: 10.1016/j.biopsych.2019.04.011. 17. Tractenberg SG, Levandowski ML, de Azeredo LA, Orso R, Roithmann LG, Hoffmann ES, et al. An overview of maternal separation effects on behavioural outcomes in mice: Evidence from a four-stage methodological systematic review. Neurosci Biobehav Rev. 2016 Sep;68:489-503. doi: 10.1016/j.neubiorev.2016.06.021. 18. Kolb B, Harker A, Mychasiuk R, de Melo SR, Gibb R. Stress and prefrontal cortical plasticity in the developing brain. Cognitive Dev. 2017 Apr;42:15-26. doi: 10.1016/j.cogdev.2017.01.001. 19. Garner AS, Shonkoff JP; Committee on Psychosocial Aspects of Child and Family Health; Committee on Early Childhood, Adoption, and Dependent Care; Section on Developmental and Behavioral Pediatrics. Early childhood adversity, toxic stress, and the role of the pediatrician: translating developmental science into lifelong health. Pediatrics. 2012 Jan;129(1):e224-31. doi: 10.1542/peds.2011-2662. Epub 2011 Dec 26. 20. Shonkoff JP, Garner AS; Committee on Psychosocial Aspects of Child and Family Health; Committee on Early Childhood, Adoption, and Dependent Care; Section on Developmental and Behavioral Pediatrics. The lifelong effects of early childhood adversity and toxic stress. Pediatrics. 2012 Jan;129(1):e232-46. doi: 10.1542/peds.2011-2663. Epub 2011 Dec 26. 21. Johnson SB, Riley AW, Granger DA, Riis J. The science of early life toxic stress for pediatric practice and advocacy. Pediatrics. 2013 Feb;131(2):319-27. doi: 10.1542/peds.2012-0469. 22. Barbosa TS, Castelo PM, Leme MS, Gavião MB. Associations between oral health-related quality of life and emotional statuses in children and preadolescents. Oral Dis. 2012 Oct;18(7):639-47. doi: 10.1111/j.1601-0825.2012.01914.x. 23. Gomes HS, Vieira LA, Costa PS, Batista AC, Costa LR. Professional dental prophylaxis increases salivary cortisol in children with dental behavioural management problems: a longitudinal study. BMC Oral Health. 2016 Aug 18;16(1):74. doi: 10.1186/s12903-016-0273-1. 24. National Scientific Council on the Developing Child. , Center on the Developing Child at Harvard University. Excessive Stress Disrupts the Architecture of the Developing Brain. Working Paper 3. 2005 [cited 2023 Oct 10]. Available from: https://developingchild.harvard.edu/ resources/working-paper/wp3. 25. Gunn BG, Cunningham L, Mitchell SG, Swinny JD, Lambert JJ, Belelli D. GABAA receptor-acting neurosteroids: a role in the development and regulation of the stress response. Front Neuroendocrinol. 2015 Jan;36:28-48. doi: 10.1016/j.yfrne.2014.06.001. Epub 2014 Jun 12. 26. Klingberg G, Broberg AG. Dental fear/anxiety and dental behaviour management problems in children and adolescents: a review of prevalence and concomitant psychological factors. Int J Paediatr Dent. 2007 Nov;17(6):391-406. doi: 10.1111/j.1365-263X.2007.00872.x. 27. Kyle BN, McNeil DW, Weaver B, Wilson T. Recall of Dental Pain and Anxiety in a Cohort of Oral Surgery Patients. J Dent Res. 2016 Jun;95(6):629-34. doi: 10.1177/0022034516631977. 11 Ribeiro et al. Braz J Oral Sci. 2025;24:e255975 28. Gedney JJ, Logan H, Baron RS. Predictors of short-term and long-term memory of sensory and affective dimensions of pain. J Pain. 2003 Mar;4(2):47-55. doi: 10.1054/jpai.2003.3. 29. Risløv Staugaard S, Jøssing M, Krohn C. The role of negative and positive memories in fear of dental treatment. J Public Health Dent. 2017 Dec;77(1):39-46. doi: 10.1111/jphd.12169. Epub 2016 Aug 16. 30. Van Houtem CMHH, van Wijk AJ, de Jongh A. Presence, content, and characteristics of memories of individuals with dental phobia. Appl Cognit Psychol. 2015;29:515-23. doi: 10.1002/acp.3127. 31. Blomqvist M, Holmberg K, Lindblad F, Fernell E, Ek U, Dahllöf G. Salivary cortisol levels and dental anxiety in children with attention deficit hyperactivity disorder. Eur J Oral Sci. 2007 Feb;115(1):1-6. doi: 10.1111/j.1600-0722.2007.00423.x. 32. Kambalimath HV, Dixit UB, Thyagi PS. Salivary cortisol response to psychological stress in children with early childhood caries. Indian J Dent Res. 2010 Apr-Jun;21(2):231-7. doi: 10.4103/0970-9290.66642. 33. Furlan NF, Gavião MB, Barbosa TS, Nicolau J, Castelo PM. Salivary cortisol, alpha-amylase and heart rate variation in response to dental treatment in children. J Clin Pediatr Dent. 2012 Fall;37(1):83-7. doi: 10.17796/jcpd.37.1.n32m21n08417v363. 34. Rodrigues Gomes SS, Barretobezerra AC, Maia Prado AC. Salivary biomarkers, vital signs and behaviour of pre-school children during their first dental visit. Eur J Paediatr Dent. 2013;14(4):279-83. 35. Yfanti K, Kitraki E, Emmanouil D, Pandis N, Papagiannoulis L. Psychometric and biohormonal indices of dental anxiety in children. A prospective cohort study. Stress. 2014 Jul;17(4):296-304. doi: 10.3109/10253890.2014.918602. 36. Curcio WB, Abreu LG, Carrada CF, Ribeiro Scalioni FA, Ribeiro RA. Relationship between salivary cortisol levels and children’s behavior during a dental examination. J Dent Child (Chic). 2017 May;84(2):80-5. 37. Patil SJ, Shah PP, Patil JA, Shigli A, Patil AT, Tamagond SB. Assessment of the changes in the stress- related salivary cortisol levels to the various dental procedures in children. J Indian Soc Pedod Prev Dent. 2015 Apr-Jun;33(2):94-9. doi: 10.4103/0970-4388.155116. 38. Chaturvedi Y, Chaturvedy S, Marwah N, Chaturvedi S, Agarwal S, Agarwal N. Salivary cortisol and alpha-amylase-biomarkers of stress in children undergoing extraction: an in vivo study. Int J Clin Pediatr Dent. 2018; 11(3):214-8. doi: 10.5005/jp-journals-10005-1514. 39. Queiroz AM, Carvalho AB, Censi LL, Cardoso CL, Leite-Panissi CR, da Silva RA, et al. Stress and anxiety in children after the use of computerized dental anesthesia. Braz Dent J. 2015; 26(3):303-7. doi: 10.1590/0103-6440201300211. 40. Kandemir S, Okşan T, Alpöz AR, Ergezer G, Kabalak T. Salivary cortisol levels in children during dental treatment. J Marmara Univ Dent Fac. 1997 Sep;2(4):639-42. PMID: 9569792. 41. Pani SC, Al Odhaib M. The impact of dental treatment on the salivary cortisol levels of children with severe early childhood caries. Eur Arch Paediatr Dent. 2013. doi: 10.1007/s40368-013-0083-y. 42. dos Santos MJ, Bernabé DG, Nakamune AC, Perri SH, de Aguiar SM, de Oliveira SH. Salivary alpha amylase and cortisol levels in children with global developmental delay and their relation with the expectation of dental care and behavior during the intervention. Res Dev Disabil. 2012;33(2):499-505. doi: 10.1016/j.ridd.2011.10.015. 43. Jafarzadeh M, Arman S, Pour FF. Effect of aromatherapy with orange essential oil on salivary cortisol and pulse rate in children during dental treatment: A randomized controlled clinical trial. Adv Biomed Res. 2013 Mar;2:10. doi: 10.4103/2277-9175.107968. 44. Ghaderi F, Solhjou N. The effects of lavender aromatherapy on stress and pain perception in children during dental treatment: a randomized clinical trial. Complement Ther Clin Pract. 2020 Aug;40:101182. doi: 10.1016/j.ctcp.2020.101182. 12 Ribeiro et al. Braz J Oral Sci. 2025;24:e255975 45. McEwen BS. Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. Eur J Pharmacol. 2008; 583(2-3):174-85. doi: 10.1016/j.ejphar.2007.11.071. 46. Jessop DS, Turner-Cobb JM. Measurement and meaning of salivary cortisol: a focus on health and disease in children. Stress. 2008 Jan;11(1):1-14. doi: 10.1080/10253890701365527. 47. Hunter AL, Minnis H, Wilson P. Altered stress responses in children exposed to early adversity: a systematic review of salivary cortisol studies. Stress. 2011;14(6):614-26. doi: 10.3109/10253890.2011.577848. 48. Shonkoff JP, Boyce WT, McEwen BS. Neuroscience, molecular biology, and the childhood roots of health disparities: building a new framework for health promotion and disease prevention. JAMA. 2009 Jun;301(21):2252-9. doi: 10.1001/jama.2009.754. 49. Heim C, Newport DJ, Bonsall R, Miller AH, Nemeroff CB. Altered pituitary-adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. Am J Psychiatry. 2001;158(4):575-81. doi: 10.1176/appi.ajp.158.4.575. 50. Brotman LM, Gouley KK, Huang KY, Kamboukos D, Fratto C, Pine DS. Effects of a psychosocial family-based preventive intervention on cortisol response to a social challenge in preschoolers at high risk for antisocial behavior. Arch Gen Psychiatry. 2007 Oct; 64(10):1172-9. doi: 10.1001/archpsyc.64.10.1172. 51. Dozier M, Peloso E, Lewis E, Laurenceau JP, Levine S. Effects of an attachment-based intervention on the cortisol production of infants and toddlers in foster care. Dev Psychopathol. 2008 Summer;20(3):845-59. doi: 10.1017/S0954579408000400. 52. Fernald LC, Gunnar MR. Poverty-alleviation program participation and salivary cortisol in very low-income children. Soc Sci Med. 2009 Jun;68(12):2180-9. doi: 10.1016/j.socscimed.2009.03.032. 53. Lupien SJ, de Leon M, de Santi S, Convit A, Tarshish C, Nair NP, et al. Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nat Neurosci. 1998 May;1(1):69-73. doi: 10.1038/271. 54. Lupien SJ, McEwen BS, Gunnar MR, Heim C. Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci. 2009;10(6):434-45. doi: 10.1038/nrn2639. 55. Folayan MO, Oginni O, Arowolo O, El Tantawi M. Association between adverse childhood experiences, bullying, self-esteem, resilience, social support, caries and oral hygiene in children and adolescents in sub-urban Nigeria. BMC Oral Health. 2020 Jul;20(1):202. doi: 10.1186/s12903-020-01160-0 56. Pearlin LI, Lieberman MA, Menaghan EG, Mullan JT. The stress process. J Health Soc Behav. 1981 Dec;22(4):337-56. 57. Shankardass K. Place-based stress and chronic disease: a systems view of environmental determinants. In: O’Campo P, Dunn JR, editors. Rethinking social epidemiology: towards a science of change. New York: Springer Publishing Company; 2012. p.117-8. 58. Vasiliou A, Shankardass K, Nisenbaum R, Quiñonez C. Current stress and poor oral health. BMC Oral Health. 2016 Sep 2;16(1):88. doi: 10.1186/s12903-016-0284-y. 59. Ford K, Brocklehurst P, Hughes K, Sharp CA, Bellis MA. Understanding the association between self-reported poor oral health and exposure to adverse childhood experiences: a retrospective study. BMC Oral Health. 2020 Feb;20(1):51. doi: 10.1186/s12903-020-1028-6. 60. Crouch E, Radcliff E, Nelson J, Strompolis M, Martin A. The experience of adverse childhood experiences and dental care in childhood. Community Dent Oral Epidemiol. 2018 Oct;46(5):442-8. doi:10.1111/cdoe.12389 13 Ribeiro et al. Braz J Oral Sci. 2025;24:e255975 61. Gomersall JC, Slack-Smith L, Kilpatrick N, Muthu MS, Riggs E. Interventions with pregnant women, new mothers and other primary caregivers for preventing early childhood caries. Cochrane Database Syst Rev. 2024 May;5(5):CD012155. doi: 10.1002/14651858.CD012155.pub3. 62. Selen MB, Demir P, Inceoglu F. Evaluation of possible associated factors for early childhood caries: are preterm birth and birth weight related?.BMC Oral Health. 2024 Feb;24(1):218. doi: 10.1186/s12903-024-04004-3. 63. Barasuol JC, Soares JP, Castro RG, Giacomin A, Gonçalves BM, Klein D, et al. Untreated dental caries is associated with reports of verbal bullying in children 8-10 years old. Caries Res. 2017;51(5):482-8. doi: 10.1159/000479043. 64. Santos PS, Evangelista ME, Brancher GP, da Silva Moro J, Borgatto AF, Santana CM, et al. Pathways between verbal bullying and oral conditions among school children. Eur Arch Paediatr Dent. 2023 Aug;24(4):499-505. doi: 10.1007/s40368-023-00818-x.. 65. Clementino LC, Freire-Maia J, Pereira TS, Martins-Júnior PA. Passive smoking and early childhood caries: when adult addiction affects children’s oral health. Evid Based Dent. 2024;25(1):49-50. doi: 10.1038/s41432-024-00980-1. 66. Bilmez Selen M, Demir P, Eden E, Inceoğlu F. Relationship between parental adverse childhood experiences and the prevalence of early childhood caries. Clin Oral Investig. 2024 Apr;28(5):243. doi: 10.1007/s00784-024-05635-0 67. Gomes HS, Corrêa-Faria P, Silva TA, Paiva SM, Costa PS, Batista AC, et al. Oral midazolam reduces cortisol levels during local anaesthesia in children: a randomized controlled trial. Braz Oral Res. 2015;29(1):S1806-83242015000100305. doi: 10.1590/1807-3107BOR-2015. 68. Golden SH, Wand GS, Malhotra S, Kamel I, Horton K. Reliability of hypothalamic-pituitary-adrenal axis assessment methods for use in population-based studies. Eur J Epidemiol. 2011 Jul;26(7):511-25. doi: 10.1007/s10654-011-9585-2. 69. Mitchual S, da Fonseca MA, Raja S, Weatherspoon D, Koerber A. Association between childhood traumatic stress and behavior in the pediatric dental clinic. Pediatr Dent. 2017 May;39(3):203-8.